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Overview and Recommendations
Background
- •Septic shock accounts for ~10% of ICU admissions globally and carries a hospital mortality of 37-51%, depending on severity and setting. The Sepsis-3 definition operationalizes the diagnosis as a vasopressor requirement to maintain MAP ≥65 mm Hg and serum lactate >2 mmol/L after adequate fluid resuscitation, a combination that selects a cohort with mortality >40%.
- •The pathophysiology centers on infection-triggered vasoplegia, capillary leak, and maladaptive immune activation. Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) drive widespread endothelial injury, nitric oxide-mediated vasodilation, and relative hypovolemia, resulting in distributive shock.
- •Septic shock represents the most severe end of the sepsis continuum, with pooled ICU mortality of 37.3% in recent meta-analyses. Mortality has declined from ~47% in the early 1990s to ~29% by the late 2000s, attributed to improved recognition, protocolized care, and the adoption of Surviving Sepsis Campaign (SSC) bundles.
- •The lung is the dominant source of infection (~68%), followed by the abdomen (~27%) and bloodstream (~8%). Source is a powerful independent predictor of outcome: ischemic bowel carries 75% hospital mortality, whereas obstructive uropathy carries only 26%.
- •The four pillars of early management, antibiotics within 1 hour, 30 mL/kg crystalloid, norepinephrine to MAP 65-70 mm Hg, and source control within 12 hours, are supported by landmark trials: ARISE, ProCESS, ProMISe, SEPSISPAM, OPTPRESS, and ANDROMEDA-SHOCK.
Evaluation
- •Suspect septic shock in any patient with suspected infection who presents with hypotension (MAP <65 mm Hg) or serum lactate ≥2 mmol/L. Altered mental status, tachypnea, and unexplained organ dysfunction are red flags, especially in the elderly or immunocompromised, who may present with hypothermia or confusion.
- •Ask about fever, chills, dyspnea, cough, abdominal pain, dysuria, and recent antibiotic or healthcare exposure. In immunocompromised patients, infection may be afebrile; elicit symptoms of opportunistic infections.
- •Examine vital signs and peripheral perfusion. Measure capillary refill time (CRT) by pressing the pulp of the index finger for 5 seconds; a CRT >3 seconds indicates tissue hypoperfusion and is a strong predictor of 24-hour mortality (AUC 0.829). Assess skin mottling (score 0-5 from knees to periphery); a score ≥2 at 6 hours carries a 16-fold higher odds of 14-day mortality, and score ≥4 carries a 74-fold increase.
- •Order a serum lactate immediately. A lactate >2 mmol/L (≥4 mmol/L indicates severe tissue hypoperfusion) is required for the Sepsis-3 shock definition and must be repeated within 2-4 hours to assess clearance. Obtain blood cultures (aerobic and anaerobic) before antibiotics if this does not delay therapy beyond 1 hour.
- •Perform point-of-care ultrasound (POCUS) to exclude obstructive shock (tamponade, tension pneumothorax, massive PE), assess left and right ventricular function (LV systolic dysfunction in up to 63%, RV dysfunction in 48%, associated with 3-fold higher mortality), and evaluate fluid responsiveness using passive leg raise or IVC collapsibility.
- •Use the Sepsis-3 criteria to confirm the diagnosis: vasopressor requirement to maintain MAP ≥65 mm Hg and serum lactate >2 mmol/L after at least 30 mL/kg of crystalloid. This distinguishes septic shock from sepsis alone and from other forms of shock.
- •In non-ICU settings, screen with qSOFA: ≥2 of altered mentation, respiratory rate ≥22/min, systolic BP ≤100 mm Hg. qSOFA has lower sensitivity (65%) but high specificity (92%) for predicting in-hospital mortality, outperforming SIRS criteria.
- •Order additional laboratory studies: complete blood count (leukocytosis or leukopenia, thrombocytopenia), coagulation profile (PT, aPTT, fibrinogen, D-dimers for DIC screening), procalcitonin (moderate diagnostic accuracy; not diagnostic alone but supportive when >10 ng/mL strongly predicts need for invasive support), and basic metabolic panel (renal function, electrolytes, glucose).
- •Obtain imaging to identify the source of infection: chest X-ray or CT for pneumonia, abdominal CT or ultrasound for intra-abdominal infection, and consider dedicated imaging based on clinical suspicion.
- •Serial lactate measurement, CRT reassessment, and trending of the mottling score guide the response to resuscitation. The ANDROMEDA-SHOCK-2 trial (2025) confirmed that a personalized protocol targeting CRT (≤3 seconds) is superior to usual care for a composite outcome (win ratio 1.16).
Management
- •Initiate the 1-hour bundle immediately upon recognition: draw blood cultures, measure lactate, start broad-spectrum antibiotics (within 1 hour of recognition), and begin IV crystalloid at 30 mL/kg. Each hour delay in antibiotics increases mortality (OR 1.04 per hour).
- •Administer balanced crystalloids (lactated Ringer’s or PlasmaLyte) over 0.9% saline. The SMART trial showed balanced solutions reduce 30-day mortality in sepsis (26.3% vs 31.2%; aOR 0.74; NNT=20) and major adverse kidney events. In pediatric patients, PlasmaLyte lowers new/progressive AKI (RR 0.62; NNT=8).
- •Start norepinephrine as the first-line vasopressor, titrated to a MAP target of 65-70 mm Hg. Initiate early (within 90 minutes of ED arrival) to improve shock control (76.1% vs 48.4% at 6 hours; NNT=3.6). Compared with dopamine, norepinephrine causes fewer arrhythmias (12.4% vs 24.1%; NNH=8.6).
- •Avoid targeting a high MAP (80-85 mm Hg) in patients aged ≥65 years: the OPTPRESS trial found significantly increased 90-day mortality (39.3% vs 28.6%; NNH=9.3), regardless of chronic hypertension status.
- •Add vasopressin (0.01-0.06 U/min) as a second-line agent when the norepinephrine dose exceeds 0.25-0.5 μg/kg/min. The VANISH trial showed vasopressin reduces renal replacement therapy (RRT) use (25.4% vs 35.3%; NNT=10.1).
- •For refractory shock requiring high-dose norepinephrine, add epinephrine (0.05-0.5 μg/kg/min) or start hydrocortisone 50 mg IV every 6 hours plus fludrocortisone 50 μg daily (APROCCHSS regimen). Hydrocortisone alone (ADRENAL) did not reduce 90-day mortality, but the combination reduced it from 49.1% to 43.0% (NNT=16.4).
- •Achieve source control within 12 hours of diagnosis, drain abscesses, remove infected catheters, debride necrotic tissue, and surgically repair perforated viscera. Every hour of delay to surgical source control increases the odds of death (adjusted OR 1.013 per hour).
- •De-escalate antibiotics daily based on culture results and procalcitonin kinetics. Stop antibiotics when procalcitonin falls by ≥90% from peak. Procalcitonin-guided algorithms safely reduce antibiotic duration by a mean of 1.28 days without increasing mortality.
- •Use capillary refill time (CRT) as a resuscitation target. The ANDROMEDA-SHOCK-2 trial (2025) demonstrated superiority of CRT-targeted resuscitation (goal ≤3 seconds) over usual care (win ratio 1.16; driven by shorter vital-support duration). Do not routinely target ScvO₂ ≥70%, the PRISM meta-analysis showed no benefit.
- •Apply lung-protective ventilation: tidal volume 6 mL/kg predicted body weight, plateau pressure <30 cm H₂O. Target SpO₂ 90-97% (conservative oxygen did not improve outcomes and may harm). Consider prone positioning if PaO₂/FiO₂ <150 mm Hg with ARDS.
- •Delay renal replacement therapy (RRT) in septic shock with acute kidney injury unless life-threatening indications (severe hyperkalemia, acidosis, volume overload). The IDEAL-ICU trial showed no mortality benefit with early RRT; 38% of the delayed group never required RRT. Early RRT may harm patients meeting AKI by creatinine alone (58% vs 42% mortality).
- •Provide stress ulcer prophylaxis with a proton pump inhibitor (e.g., pantoprazole 40 mg IV once daily) for mechanically ventilated patients. Administer VTE prophylaxis with low-molecular-weight heparin (e.g., enoxaparin 40 mg daily) in the absence of contraindications; maintain throughout the ICU stay.
- •Implement the ABCDEF bundle daily: Assess-Prevent-Manage pain, Both SAT and SBT, Choice of sedation (light, non-benzodiazepine), Delirium monitoring (CAM-ICU), Early mobility (within 48 hours even on vasopressors), and Family engagement. Higher bundle adherence reduces mechanical ventilation duration and post-intensive care syndrome.
- •Avoid harmful interventions: do not use hydroxyethyl starch (increases AKI and mortality), drotrecogin alfa (PROWESS-SHOCK: no benefit, increased bleeding), high-dose corticosteroids (>400 mg/day), tight glycemic control (80-110 mg/dL, increased hypoglycemia), or routine vitamin C (two large RCTs showed no benefit, possible harm).
- •Refer to a high-volume ICU (≥13 septic shock cases per year) when possible; such centers have lower mortality (adjusted OR 0.63 for cancer patients). Escalate to a tertiary center when source control cannot be achieved locally, shock is refractory, or advanced organ support (e.g., ECMO) is considered.
Board Review — High Yield
- •Sepsis-3 definition, Septic shock requires vasopressor dependence (MAP ≥65) and lactate >2 mmol/L after adequate fluid resuscitation; mortality >40%.
- •SOFA vs qSOFA, SOFA (ICU) AUROC 0.74; qSOFA (non-ICU) AUROC 0.81 with sensitivity 65%, specificity 92%.
- •ANDROMEDA-SHOCK-2, CRT-targeted resuscitation (goal ≤3 s) superior to usual care (win ratio 1.16); CRT is the best bedside perfusion monitor.
- •SMART trial, Balanced crystalloids (lactated Ringer’s/PlasmaLyte) reduce 30-day mortality vs saline in sepsis (aOR 0.74; NNT=20).
- •OPTPRESS trial, High MAP target (80-85 mm Hg) in elderly increases 90-day mortality (39.3% vs 28.6%; NNH=9); target MAP 65-70.
- •VANISH trial, Early vasopressin reduces RRT use vs norepinephrine alone (25.4% vs 35.3%; NNT=10).
- •APROCCHSS trial, Hydrocortisone + fludrocortisone reduces 90-day mortality in refractory shock (43% vs 49.1%; NNT=16); hydrocortisone alone (ADRENAL) does not.
- •Source control timing, Each hour delay to surgical source control increases odds of death (aOR 1.013/h); achieve within 12 hours.
- •IDEAL-ICU, Delayed RRT in septic AKI does not increase mortality; 38% avoid RRT entirely; early RRT may harm those with creatinine-only AKI.
- •Abandoned therapies, Drotrecogin alfa (PROWESS-SHOCK, no benefit), HES (AKI risk), tight glycemic control (hypoglycemia), vitamin C (two negative RCTs).
Deep Dive — Evidence Details
Definition, Classification & Shock-Physiology Spine
- ▸Septic shock is defined by Sepsis-3 as vasopressor requirement to maintain MAP ≥65 mm Hg plus lactate >2 mmol/L after fluid resuscitation, with hospital mortality >40%.
- ▸Septic shock is a distributive shock but frequently coexists with hypovolemic, cardiogenic, or obstructive components, the four-shock classification guides initial resuscitation.
- ▸Organ dysfunction is quantified by the SOFA score (≥2-point increase defines sepsis); qSOFA is a bedside screening tool for non-ICU settings.
Septic shock is a subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a substantially greater risk of mortality than sepsis alone [44]A1c. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) operationalizes the diagnosis as a vasopressor requirement to maintain a mean arterial pressure (MAP) ≥65 mm Hg and a serum lactate >2 mmol/L (>18 mg/dL) in the absence of hypovolemia, a combination that carries hospital mortality rates exceeding 40% [20]A1c[44]A1c.
Also Called / Synonyms
- Septic shock (standard term)
- Distributive shock due to infection
- Vasodilatory shock (when emphasizing the hemodynamic phenotype)
- Refractory septic shock (when vasopressor requirements exceed 0.5 µg/kg/min norepinephrine equivalents)
- Warm shock (early, hyperdynamic phase) / Cold shock (late, hypodynamic phase)
Classification of Shock Types
Septic shock is the prototypical distributive shock, but it frequently coexists with other shock forms. The four-shock classification governs initial resuscitation strategy:
| Shock Type | Primary Mechanism | Key Hemodynamic Profile | Septic Shock Relevance |
|---|---|---|---|
| Distributive | Vasoplegia, capillary leak, relative hypovolemia | Low SVR, normal/high CO, low CVP | Dominant mechanism; triggered by pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) [44]A1c |
| Hypovolemic | Absolute intravascular volume depletion | Low CVP, low CO, high SVR | Often coexists due to vomiting, diarrhea, or insensible losses |
| Cardiogenic | Myocardial depression (sepsis-induced cardiomyopathy) | Low CO, high CVP, high SVR | Occurs in up to 40% of septic shock; LVEF <25% or >70% both independently increase mortality (OR 2.75 and 1.70, respectively) [39]B2b |
| Obstructive | Mechanical impediment to flow (e.g., , pericardial tamponade) | Variable | Must be excluded when shock is refractory to fluids and vasopressors |
Organ Dysfunction Spine
The Sepsis-3 framework anchors organ dysfunction to the Sequential Organ Failure Assessment ( ) score. An acute increase of ≥2 SOFA points in the setting of infection defines sepsis and predicts in-hospital mortality >10% [44]A1c[46]B2b. For non-ICU settings, the quick SOFA ( ), ≥2 of altered mentation, respiratory rate ≥22/min, systolic BP ≤100 mm Hg, identifies patients at high risk of poor outcomes [46]B2b. Septic shock represents the most severe end of this spectrum, with pooled ICU mortality of 37.3% and hospital mortality of 39.0% [24]B2a. Mortality has declined from 46.9% in 1991-1995 to 29% in 2006-2009, attributed to improved recognition and protocolized care [14]A1a.
Clinical Significance
Septic shock is the leading cause of death in non-cardiac ICUs worldwide, affecting approximately 10% of ICU admissions [24]B2a. In Japan, in-hospital mortality among 649,082 patients with septic shock was 36.5% from 2010-2020, decreasing from 46.7% to 33.2% over the decade [29]B2b. The condition imposes a massive burden on healthcare systems, with median hospital length of stay of 38 days and ICU admission rates of 50.7% [29]B2b.
Pearl: The Sepsis-3 definition of septic shock requires both vasopressor dependence (MAP ≥65 mm Hg) and lactate >2 mmol/L after adequate fluid resuscitation, do not diagnose septic shock based on hypotension alone, as hypovolemic or may mimic it [20]A1c[44]A1c.
| Shock Type | Primary Mechanism | Key Hemodynamic Profile | Septic Shock Relevance |
|---|---|---|---|
| Distributive | Vasoplegia, capillary leak, relative hypovolemia | Low SVR, normal/high CO, low CVP | Dominant mechanism; triggered by PAMPs and DAMPs [44]A1c |
| Hypovolemic | Absolute intravascular volume depletion | Low CVP, low CO, high SVR | Often coexists due to vomiting, diarrhea, or insensible losses |
| Cardiogenic | Myocardial depression (sepsis-induced cardiomyopathy) | Low CO, high CVP, high SVR | Occurs in up to 40% of septic shock; LVEF <25% or >70% both independently increase mortality (OR 2.75 and 1.70, respectively) [39]B2b |
| Obstructive | Mechanical impediment to flow (e.g., tension pneumothorax, pericardial tamponade) | Variable | Must be excluded when shock is refractory to fluids and vasopressors |
Pathophysiology & Mechanism
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Epidemiology, Etiology & Risk Factors
- ▸Septic shock affects 15-19 million people globally annually, with ICU mortality exceeding 50% in low-income settings.
- ▸The lung is the most common infection source, but ischemic bowel carries the highest mortality (75%), highlighting the prognostic importance of anatomic source.
- ▸Key risk factors include metastatic disease (OR 3.17), elevated lactate (OR 3.19), acute gastrointestinal injury, and hypernatremia; 86% of RCT patients have diabetes.
The transition from systemic inflammation to end-organ hypoperfusion described above drives a condition that affects an estimated 15 to 19 million people globally each year, with mortality approaching 60% in low-income countries [130]C4. In mainland Chinese ICUs, the frequency of sepsis is 20.6 cases per 100 ICU admissions, and among those, septic shock accounts for 53.3% of cases, carrying a 90-day mortality of 51.94% [123]C4. Septic shock thus constitutes the most lethal tier of the sepsis continuum, with overall ICU mortality for septic shock ranging from 30% to 50% across international cohorts [114]B2b[123]C4.
Anatomic Sources and Microbiology
The lung is the dominant source of infection, implicated in 68.2% of sepsis cases in Chinese ICUs, followed by the abdomen (26.6%) and bloodstream (7.8%) [123]C4. Anatomic source is a powerful independent predictor of outcome: ischemic bowel carries a standardized hospital mortality of 75%, whereas obstructive uropathy-associated urinary tract infection carries only 26% [124]B2b. Among nosocomial lower respiratory tract infections, (VAP) is the most frequent diagnosis (52.5%), and is the leading pathogen, detected in 14.5% of samples with multidrug-resistant strains in 19.6% of those [135]B2b. Gram-negative bacteria, particularly Enterobacterales, cause 64% of VAP episodes [134]B2b.
| Source of Infection | Standardized Hospital Mortality [124]B2b |
|---|---|
| Ischemic bowel | 75% |
| Community-acquired peritonitis | ~52% |
| Pneumonia | ~45% |
| Urinary tract (obstructive uropathy) | 26% |
Risk Factors for Development and Mortality
Baseline comorbidities are highly prevalent in septic shock populations: diabetes (86.1% of RCT enrollees), (65.1%), chronic kidney disease (56%), and cancer (53.1%) [35]A1a. Among patients with solid tumors, independent predictors of 28-day mortality include metastatic disease (OR 3.17), elevated lactate (OR 3.19), respiratory failure (OR 2.34), and poor performance status ( 3-4; OR 2.72) [36]B2b. In sepsis complicated by pulmonary infection, sepsis-associated encephalopathy occurs in 68% of patients, with independent risk factors including acute injury grade II (OR 1.86), hypernatremia (OR 1.93), elevated serum lactate (OR 1.25), and higher blood urea nitrogen (OR 1.03; 95% CI 1.00-1.05) [137]B2b. New-onset is a frequent complication, with cumulative risk of 40% in septic shock, and it independently increased mortality (subdistribution HR 2.10) [115]B2b.
Temporal Trends
Mortality from severe sepsis and septic shock has declined substantially over the past two decades, from 21.2% in 2004 to 8.7% in 2010 in a multicenter U.S. quality improvement initiative, paralleling increased bundle compliance [125]B2b. Reporting of baseline comorbidities in sepsis RCTs has also improved, increasing approximately 8% per year (OR 1.08) [35]A1a.
Pearl: The source of infection is a powerful, independent predictor of outcome - ischemic bowel carries three times the mortality of urosepsis - yet this variable is rarely used to stratify patients in clinical trials [124]B2b.
| Source of Infection | Standardized Hospital Mortality [124]B2b |
|---|---|
| Ischemic bowel | 75% |
| Community-acquired peritonitis | ~52% |
| Pneumonia | ~45% |
| Urinary tract (obstructive uropathy) | 26% |
Clinical Presentation
- ▸Septic shock presents along a spectrum from classic fever/hypotension to subtle syndromes in the elderly (hypothermia, altered mental status) and immunocompromised (afebrile neutropenic sepsis).
- ▸Lactate ≥4.0 mmol/L, bandemia ≥10%, and nonpersistent hypotension within 4 hours of presentation are the strongest predictors of progression to shock.
- ▸Bedside hemodynamic assessment (capillary refill time, mottling, warm vs cold extremities) distinguishes vasoplegic from hypodynamic phenotypes, guiding initial vasopressor/inotrope choice.
From the preceding and risk factors, the clinician must now translate population-level vulnerability into bedside recognition. The presentation of septic shock spans a spectrum from the classic febrile hypotensive patient to subtle, easily missed syndromes in the elderly or immunocompromised.
Presenting Symptoms
The onset is typically acute, evolving over hours to days. High fever and cough predominate in influenza-associated septic shock [150]B2b, while fatigue, myalgias, and symptoms (nausea, vomiting, diarrhea) characterize [172]D5. In bacterial sepsis, chills, dyspnea, and altered mental status are common [176]D5. A case series of candidemia in cirrhosis found fever in only 60.6% of episodes, with septic shock present in 34.9% at presentation [157]B3b. Leg cramps and hematochezia, attributed to hypoperfusion and coagulopathy, can be initial complaints [148]C4. Importantly, elderly patients may present with hypothermia, confusion, or relative bradycardia rather than fever and tachycardia, delaying recognition [155]D5.
Physical Examination and Hemodynamic Assessment
Vital signs are the cornerstone. Septic shock is defined by persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥65 mm Hg and serum lactate >2 mmol/L despite adequate volume resuscitation [162]D5. Bedside signs of hypoperfusion include prolonged capillary refill time (CRT) >3 seconds, skin mottling (especially over knees), and oliguria [167]B2b. CRT is the strongest predictor of 24-hour mortality among noninvasive tools (area under the curve 0.829) [167]B2b. Purpura fulminans, sudden, extensive purpuric lesions with vasopressor requirement, carries a hospital mortality of 41.2%; in adults, it is most often meningococcal (63.7%) or pneumococcal (21.9%) [147]B2b. The mottling score correlates with mid-term outcomes (28-day mortality AUC 0.749) [167]B2b.
Phenotypic Variants
Two classic hemodynamic phenotypes inform initial :
| Variant | Key Features | Frequency & Context |
|---|---|---|
| Warm (vasoplegic) shock | Bounding pulses, warm extremities, low systemic vascular resistance index (SVRI <800 dyne·s/cm⁵/m²) | Predominates in hospital-acquired infections; responds to vasopressors [156]B2b |
| Cold (hypodynamic) shock | Cold extremities, delayed CRT, low cardiac index (<3.3 L/min/m²), narrow pulse pressure | More common in community-acquired pediatric septic shock; requires inotropes [156]B2b |
| Purpura fulminans | Rapidly spreading purpura, necrosis, DIC | Meningococcus > pneumococcus; high amputation risk [147]B2b |
| Neutropenic sepsis | May lack fever, focal signs; often presents with rigors and hypotension | Chemotherapy-induced neutropenia; high mortality [148]C4 |
| Pediatric septic shock | Cold shock in community-acquired cases; warm shock in hospital-acquired | Central venous oxygen saturation lower in community-acquired (mean 51.7% vs 58.7%) [156]B2b |
Sex differences are increasingly recognized: women may exhibit less febrile response and different vasopressor requirements, though data remain inconsistent [155]D5.
Time Course and Progression
Approximately 8-12% of emergency department patients with sepsis without initial shock progress to septic shock within 48 hours [153]B3b. Lactate ≥4.0 mmol/L (odds ratio 5.30), bandemia ≥10% (OR 2.60), and nonpersistent hypotension in the first 4 hours (OR 6.24) are the strongest predictors of progression [153]B3b. Each hour delay in antibiotic administration is associated with a 4.0% increased risk of progression to shock (adjusted OR 1.03 per hour) [159]B3b. Patients with a positive score in triage progress to shock faster (median 11.2 hours) than those with positive SIRS criteria (median 26 hours) [159]B3b. In community-acquired pneumonia, half develop severe sepsis, usually early in hospitalization [160]B3b.
Red Flags and Atypical Presentations
A high index of suspicion is required when any of the following are present: altered mental status, tachypnea, unexplained hypotension (SBP ≤90 mm Hg), lactate ≥4 mmol/L, purpura, or new organ dysfunction (oliguria, hypoxemia, coagulopathy) [176]D5. In the immunocompromised, infection may be afebrile; in the elderly, hypothermia and delirium may be the only clues. Relative bradycardia (inappropriate for fever) can signal severe infection or . Elevated urinary neutrophil gelatinase-associated lipocalin (NGAL) may identify subclinical acute kidney injury despite normal creatinine, portending fewer hospital-free days [164]B2b. Procalcitonin >10 ng/mL strongly predicts the need for invasive respiratory or vasopressor support (risk 22.4%) [161]B2b.
Pearl: In any patient with suspected infection, a lactate ≥4.0 mmol/L or nonpersistent hypotension in the first 4 hours heralds imminent progression to shock, start resuscitation and immediately, even if the blood pressure normalizes transiently.
Diagnosis & Workup (Hemodynamic & Bedside-First)
- ▸Septic shock is diagnosed clinically by the Sepsis-3 triad: vasopressor requirement, lactate >2 mmol/L, and MAP <65 mm Hg after adequate fluid resuscitation; no single laboratory test confirms the diagnosis.
- ▸Bedside assessment of peripheral perfusion (capillary refill time, mottling score, skin temperature) provides powerful prognostic and therapeutic information and can be integrated into resuscitation algorithms.
- ▸Point-of-care ultrasound (POCUS) is the consensus-recommended first-line imaging tool to exclude alternative shock etiologies, assess ventricular function, and guide fluid and vasopressor therapy.
The transition from clinical suspicion to diagnostic confirmation occurs during the first hour of resuscitation, and the diagnosis of septic shock is made at the bedside using a combination of clinical and physiologic criteria. The Sepsis-3 definition operationalizes this: septic shock is identified by a vasopressor requirement to maintain mean arterial pressure ≥65 mm Hg and a serum lactate >2 mmol/L after adequate fluid resuscitation [20]A1c[44]A1c. This triad defines a cohort with hospital mortality >40% [44]A1c. No single laboratory or imaging test alone establishes the diagnosis; rather, the diagnosis is a resuscitation-paced clinical decision that triggers simultaneous therapy.
Bedside Hemodynamic Assessment
Physical examination provides the earliest and most dynamic diagnostic information. Capillary refill time (CRT), measured by pressing the pulp of the index finger for 5 seconds and timing return to normal color, is a validated marker of peripheral perfusion. In the ANDROMEDA-SHOCK trial, a CRT-targeted resuscitation strategy (goal ≤3 seconds) was compared with lactate-targeted resuscitation; 28-day mortality was 34.9% vs 43.4% (HR 0.75, 95% CI 0.55-1.02; P=0.06), with a Bayesian reanalysis showing >90% posterior probability of benefit [108]A1b[196]B2b. Mottling, graded from 0 to 5 based on extension from the knees to the periphery, also carries strong prognostic power: a score of 4-5 at 6 hours had an OR for 14-day mortality of **74 ** compared with score 0-1 [67]B2b. Skin temperature, toe-to-room temperature gradient, and diastolic blood pressure (DBP) complement the assessment. A low DBP (≤40 mm Hg) or a high diastolic shock index (heart rate/DBP ≥3) identifies patients who may benefit from early vasopressor initiation [213]D5.
Point-of-Care Ultrasound (POCUS)
Critical care ultrasound is the single diagnostic modality that reached consensus agreement in the SCCM/ESICM Delphi definition of refractory septic shock [194]D5. POCUS rapidly excludes obstructive shock (e.g., pericardial tamponade, massive pulmonary embolism), identifies left ventricular systolic dysfunction (present in 63% of septic patients) and right ventricular dysfunction (48%, associated with a threefold higher mortality) [129]B2b, and assesses fluid responsiveness using dynamic measures such as inferior vena cava collapsibility or passive leg raise [200]D5[210]D5. The FALLS protocol (Fluid Administration Limited by Lung Sonography) sequentially rules out obstructive, cardiogenic, and hypovolemic shock before concluding distributive (septic) shock, using the transition from A-lines to B-lines as a marker of pulmonary congestion at a pulmonary artery occlusion pressure ≈18 mm Hg [200]D5.
Laboratory Studies
| Test | Key Finding | Timing | Pooled Sensitivity | Pooled Specificity |
|---|---|---|---|---|
| Serum lactate | >2 mmol/L (≥4 mmol/L indicates tissue hypoperfusion) | Within 1 hour | Not applicable for diagnosis | Not applicable for diagnosis |
| Blood cultures (aerobic + anaerobic) | Positive in ~40% | Before (within 1 hour) | , | , |
| Leukocytosis or leukopenia, thrombocytopenia | At presentation | , | , | |
| Coagulation studies (PT, aPTT, fibrinogen, D-dimer) | DIC hallmark: low fibrinogen, elevated D-dimers | At presentation | , | , |
Procalcitonin has moderate diagnostic accuracy: a 2025 meta-analysis of 10 studies using Sepsis-3 criteria reported a pooled diagnostic odds ratio of **7.08 ** and an area under the SROC curve of 0.79 [205]A1a. PCT should not be used in isolation to rule sepsis in or out, but it can support the diagnosis when combined with clinical assessment. Lactate is not diagnostic of infection but is a critical marker of tissue hypoperfusion and is required for the Sepsis-3 shock definition; a lactate >2 mmol/L plus vasopressor dependence identifies septic shock [20]A1c[44]A1c. Blood cultures should be drawn before antibiotics when this does not delay therapy beyond 1 hour [5]A1c.
Diagnostic Algorithm
The diagnosis of septic shock proceeds simultaneously with initial resuscitation:
- Recognize the clinical presentation: suspected infection + hypotension (MAP <65 mm Hg) or lactate ≥2 mmol/L.
- Initiate the 3-hour bundle immediately: measure lactate, obtain blood cultures, begin broad-spectrum antibiotics, administer ≥30 mL/kg crystalloid [5]A1c[203]B3b.
- After initial fluid bolus, reassess: if MAP remains <65 mm Hg or lactate >2 mmol/L, start vasopressors (norepinephrine) without further delay [180]A1b[213]D5.
- Confirm septic shock criteria: vasopressor requirement + lactate >2 mmol/L after adequate fluid resuscitation (≥30 mL/kg). This fulfills the Sepsis-3 definition [20]A1c[44]A1c.
- Use POCUS and peripheral perfusion assessment (CRT, mottling) to refine the diagnosis and guide further therapy [108]A1b[210]D5.
Pearl: In suspected septic shock, the diagnosis is made at the bedside using the Sepsis-3 criteria; do not wait for procalcitonin or culture results to initiate treatment, the first hour defines the trajectory of organ dysfunction and survival [203]B3b.
| Test | Pooled Sensitivity (95% CI) | Pooled Specificity (95% CI) | Pooled Diagnostic Odds Ratio (95% CI) |
|---|---|---|---|
| Procalcitonin (PCT) | 0.72 (0.68-0.75) [205]A1a | 0.65 (0.61-0.69) [205]A1a | 7.08 (3.69-13.58) [205]A1a |
| Lactate (>2 mmol/L) | , | , | Threshold for septic shock definition [20]A1c[44]A1c |
| Blood cultures | , | , | Not for diagnosis; identifies pathogen |
Severity Scoring & Risk Stratification (ICU Scores)
- ▸SOFA score (AUROC 0.74 in ICU) and qSOFA (AUROC 0.81 in non-ICU) are the Sepsis-3 standard severity tools; static scores miss trajectory, so dynamic assessment and biomarkers (presepsin, PSP, mottling score, BPRI) improve risk stratification.
- ▸Transcriptomic subtypes (CTS1-3) identify distinct biology; CTS2 patients may be harmed by corticosteroids, a precision-medicine signal from VANISH reanalysis.
- ▸Special populations require tailored interpretation: sex-based differences in SOFA components (women score lower without mortality difference), pediatric Phoenix Sepsis Score outperforms SOFA in certain age groups, and high-volume centers improve survival in cancer patients with septic shock.
Having identified septic shock through clinical and biochemical criteria, the clinician must next quantify the severity of organ dysfunction and the risk of death. Validated scoring tools stratify prognosis, guide triage decisions, and provide a framework for enrollment in clinical trials.
Core Prognostic Tools
The Sequential Organ Failure Assessment ( ) score is the accepted Sepsis-3 standard for quantifying organ dysfunction in the ICU. In the primary validation cohort, SOFA had an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI 0.73-0.76) for predicting in-hospital mortality among ICU patients with suspected infection [46]B2b. The quick SOFA ( ), assigning 1 point each for systolic hypotension ≤100 mm Hg, tachypnea ≥22/min, and altered mentation, was designed for non-ICU settings, where it achieved an AUROC of 0.81 (95% CI 0.80-0.82), outperforming both SOFA (0.79) and SIRS criteria (0.76) [46]B2b. Among hospitalized patients assessed by a rapid response team, those meeting Sepsis-3 septic shock criteria had 40.9% in-hospital mortality vs 33.5% for patients meeting SIRS-based criteria [236]B3b. The qSOFA demonstrated sensitivity 64.9% and specificity 92.2% for predicting in-hospital mortality, while SIRS had sensitivity 91.6% but specificity only 23.6% [236]B3b. Other commonly used scores include (mean 25.7 in culture-negative septic shock [223]B3b; OR 1.09 per point for 30-day mortality in CDAD [237]B3b), SAPS II, and LODS (AUROC 0.75 vs SOFA and LODS not different [46]B2b).
| Score | Components | Setting | AUROC (in-hospital mortality) | Key Reference |
|---|---|---|---|---|
| SOFA | 6 organ systems (0-24) | ICU | 0.74 | [46]B2b |
| qSOFA | 3 clinical variables (0-3) | Non-ICU | 0.81 | [46]B2b |
| APACHE II | 12 physiologic + age + chronic health | ICU | ~0.64-0.72 (varies) | [223]B3b[237]B3b |
| SAPS II | 17 variables | ICU | 0.60 (mortality) | [235]B2b |
| LODS | 6 organ systems (0-22) | ICU | 0.75 | [46]B2b |
Dynamic and Biomarker-Enhanced Risk Stratification
Static scores miss the trajectory of organ failure. The mottling score (0-5) at 6 h predicts 14-day mortality: score 2-3 (OR 16), score 4-5 (OR 74); decreasing mottling during resuscitation is associated with lower mortality (12% vs 77%, p=0.0005) [67]B2b. The Blood Pressure Response Index (BPRI) trajectory identified 6 hemodynamic phenotypes, with ICU mortality ranging from 21.9% (C3 responders) to 54.5% (C2 non-responders); adding BPRI trajectory to severity scores improved AUC by +0.020 (p<0.001) [28]B2b.
Biomarkers augment prediction. Baseline presepsin (median 946 ng/L in the ALBIOS trial) independently predicted ICU and 90-day mortality [222]B3b. Combining APACHE II + procalcitonin + pancreatic stone protein (PSP) yielded an AUC of 0.721 vs APACHE II alone (0.638) [235]B2b. A multibiomarker model (5 plasma proteins + lactate + age + chronic disease) in adults with septic shock had sensitivity 85% and specificity 60% for 28-day mortality in validation [228]B3b. Procalcitonin-guided antibiotic reduced mortality (21.1% vs 23.7%; adjusted OR 0.89, 95% CI 0.8-0.99) [23]A1a.
Consensus transcriptomic subtypes (CTS) classify sepsis into three groups: CTS1 (inflammatory, immature neutrophil theme), CTS2 (hemoglobin metabolism, fibrinolytic), CTS3 (interferon, lymphocyte features). In a pseudo-randomized reanalysis of the VANISH trial, CTS2 patients assigned to corticosteroids had a harmful signal [34]B2b.
Special Populations
Pediatric: In children with septic shock, SOFA and Phoenix Sepsis Score (PSS) both showed moderate mortality correlation (r=0.57 and 0.56); SOFA was slightly more accurate overall, but PSS performed better in children aged 3-6 years [241]B3b. A prediction model for septic shock in pediatric RSV bronchiolitis (incorporating fungal co-infection, admission glucose, antithrombin III, IL-6) achieved an AUC of 0.892 [163]B3b. Children with prearrest sepsis had worse survival to hospital discharge with favorable neurologic outcome (28.3% vs 58.4%; adjusted RR 0.54) [226]B2b.
Cancer and case volume: In patients with malignancies and septic shock, ICU mortality declined from 70.4% (1997) to 52.5% (2008); admission to a high-volume unit (≥13 cases/yr) was associated with lower mortality (adjusted OR 0.63, 95% CI 0.46-0.87) [230]B3b. Sex differences: Women had slightly lower total SOFA at admission (7.5 vs 7.8, p<0.001), driven by coagulation, liver, and renal components, yet ICU mortality did not differ (14% vs 15%) [243]B3b.
Prognostic Use in Clinical Decision-Making
Severity scores inform triage and escalation. Implementation of the Surviving Sepsis Campaign bundles (with all-or-none compliance rising from 4.9% to ****) was associated with a decline in hospital mortality from 21.7% to 9.7% [125]B2b. In the CORTICUS trial, accelerated SOFA improvement (p=0.0027) without reducing mortality [221]A1b. In ICU-acquired pneumonia, higher SOFA and APACHE II predicted mortality but not the presence of multidrug-resistant pathogens [227]B2b. In patients with liver abscess requiring ICU, SOFA score (HR 3.45, 95% CI 1.95-6.09) and portal vein thrombosis were independent mortality risk factors [244]B3b. Right ventricular dysfunction (present in 48% of septic patients) tripled 28-day mortality (OR 3.4), while left ventricular diastolic dysfunction, though prevalent (76%), was not associated with mortality [129]B2b[232]B2b.
Pearl: The SOFA score is the accepted standard for quantifying organ dysfunction in septic shock, but dynamic assessment (trend over 48-72 h) and incorporation of biomarkers (presepsin, PSP) improve prognostic accuracy beyond a single static value.
| Score | Setting | AUROC (95% CI) | Key Reference |
|---|---|---|---|
| SOFA | ICU | 0.74 (0.73-0.76) | [46]B2b |
| qSOFA | Non-ICU | 0.81 (0.80-0.82) | [46]B2b |
| SIRS | Non-ICU | 0.76 (0.75-0.77) | [46]B2b |
| LODS | ICU | 0.75 (0.73-0.76) | [46]B2b |
| APACHE II | ICU | ~0.64-0.72 (varies) | [223]B3b[237]B3b |
| SAPS II | ICU | 0.60 | [235]B2b |
Acute Resuscitation & Time-Critical Management
- ▸First-hour bundle: 30 mL/kg balanced crystalloid, antibiotics within 1 hour, norepinephrine to MAP 65-70 mm Hg.
- ▸Balanced crystalloids reduce mortality and acute kidney injury compared with 0.9% saline (SMART, MES trial).
- ▸Early norepinephrine improves shock control and reduces pulmonary edema; vasopressin added at NE >0.25 µg/kg/min reduces RRT need.
- ▸High MAP targets (80-85 mm Hg) increase mortality in older patients (OPTPRESS).
- ▸Capillary refill time is a valid resuscitation target (ANDROMEDA-SHOCK).
- ▸Avoid starch, dexmedetomidine, landiolol, drotrecogin alfa, vitamin C/thiamine/iloprost.
With septic shock confirmed by the Sepsis‑3 clinical criteria (vasopressor requirement to maintain MAP ≥65 mm Hg and serum lactate >2 mmol/L despite initial fluid) and severity graded (Section 6), the first hour is a time‑critical bundle. The Surviving Sepsis Campaign (SSC) 2016 recommends beginning resuscitation immediately [2]A1c.
Step 1: Immediate Actions (First 30 min)
- Draw blood cultures before (strong recommendation, low quality) [1]A1c[2]A1c.
- Measure lactate; repeat within 2-4 h to assess clearance [44]A1c.
- Initiate broad‑spectrum antibiotics within 1 hour of recognition (strong recommendation, moderate quality) [1]A1c[2]A1c. Each hour of delay increases risk‑adjusted in‑hospital mortality (OR 1.04 per hour; P < 0.001) [203]B3b[272]B2b.
- Obtain imaging to identify source control needs.
Step 2: Fluid Resuscitation
- Infuse 30 mL/kg of isotonic crystalloid over the first 3 h [1]A1c[2]A1c[245]A1c. Failure to achieve this volume was associated with increased odds of death (OR 1.52, 95% CI 1.03‑2.24) [273]B3b.
- Balanced crystalloids (lactated Ringer’s, PlasmaLyte) are preferred over 0.9% saline. In the SMART trial, balanced solutions reduced 30‑day in‑hospital mortality (26.3% vs 31.2%; aOR 0.74, 95% CI 0.59‑0.93; NNT = 20) and major adverse kidney events (35.4% vs 40.1%; aOR 0.78) [10]B2b. In pediatric septic shock, PlasmaLyte lowered new/progressive AKI (RR 0.62, 95% CI 0.49‑0.80; NNT = 8) [246]A1b.
- After the initial 30 mL/kg, assess fluid responsiveness using dynamic measures (passive leg raise, stroke volume change) to guide further boluses. The FRESH trial found that passive leg raise‑guided reduced net fluid balance at 72 h by -1.37 L, renal replacement therapy (5.1% vs 17.5%; NNT = 8.1), and mechanical ventilation (17.7% vs 34.1%; NNT = 6.1) [253]A1b.
Step 3: Vasopressor Therapy
- First‑line: , titrated to a MAP target of 65-70 mm Hg (strong recommendation, moderate quality) [2]A1c[3]A1c. Compared with dopamine, norepinephrine causes fewer arrhythmias (12.4% vs 24.1%; absolute difference 11.7%; NNH = 8.6) [257]A1b.
- High‑target MAP (80-85 mm Hg) is harmful in older patients: the OPTPRESS trial showed higher 90‑day mortality (39.3% vs 28.6%; risk difference 10.7%; NNH = 9.3) [100]A1b. The SEPSISPAM trial found no benefit in younger patients [261]A1b.
- Early norepinephrine (median time 93 min vs 192 min from ED arrival) improves shock control at 6 h (76.1% vs 48.4%; absolute difference 27.7%; NNT = 3.6) and reduces pulmonary edema (14.4% vs 27.7%; NNT = 7.5) [180]A1b. A meta‑analysis of RCTs reported a mortality benefit with early initiation (OR 0.49, 95% CI 0.25‑0.96) [122]B2a.
- Second‑line: add when the norepinephrine dose exceeds 0.25-0.50 µg/kg/min (SSC weak recommendation) [2]A1c[3]A1c[49]D5. In the VANISH trial, vasopressin reduced renal replacement therapy use (25.4% vs 35.3%; NNT = 10.1) [109]A1b. The OVISS reinforcement learning study associated earlier vasopressin initiation (at lower norepinephrine doses) with lower in‑hospital mortality (OR 0.81, 95% CI 0.73‑0.91) [138]B2b.
- Third‑line: 0.05-0.5 µg/kg/min or add 50 mg IV every 6 h (with 50 µg daily in the APROCCHSS regimen) if shock persists [256]A1b. Hydrocortisone alone (CORTICUS) did not improve survival [260]A1b, but the combination reduced 90‑day mortality (43.0% vs 49.1%; RR 0.88, 95% CI 0.78‑0.99; NNT = 16.4) [256]A1b.
Step 4: Resuscitation Targets and Monitoring
- Use capillary refill time (CRT) as an adjunct target. The ANDROMEDA‑SHOCK trial showed a 28‑day mortality of 34.9% with CRT‑guided care vs 43.4% with lactate‑guided care (HR 0.75, 95% CI 0.55‑1.02; Bayesian posterior probability of benefit >90%) [108]A1b[196]B2b. ANDROMEDA‑SHOCK‑2 confirmed a win ratio of 1.16 (95% CI 1.02‑1.33) favoring CRT‑targeted resuscitation [186]A1b.
- Assess perfusion using skin mottling score (scored 0-5) [67]B2b and urine output. Do not routinely target ScvO₂ ≥ 70% or use early goal‑directed therapy bundles (PRISM meta‑analysis, N=3723, 90‑day mortality 24.9% vs 25.4%) [189]A1a.
Step 5: Avoid Harmful Interventions
- Avoid (strong recommendation against, high quality) [1]A1c.
- Avoid high MAP targets in elderly [100]A1b.
- Avoid routine (possible harm in ADRESS) [8]A1b and (STRESS‑L, stopped early for harm) [283]A1b.
- Do not use (PROWESS‑SHOCK, RR 1.09; P = 0.31) [262]A1b.
- Routine vitamin C, thiamine, and iloprost are not supported [19]A1b[52]A1b.
Pearl: The first‑hour bundle, balanced crystalloid 30 mL/kg, early norepinephrine targeting MAP 65-70 mm Hg, broad‑spectrum antibiotics within 1 hour, reduces mortality and organ failure; later fluid restriction guided by dynamic assessments avoids harm (SMART, CENSER, SEPSISPAM, OPTPRESS, CLASSIC) [10]B2b[100]A1b[122]B2a[180]A1b[259]A1b.
| Agent | Starting Dose | Key Evidence | Comment |
|---|---|---|---|
| Norepinephrine (first‑line) | Titrated to MAP 65-70 mmHg | Reduced arrhythmias vs dopamine [257]A1b; early use improves shock control [180]A1b | Preferred first‑line (SSC 2016) [2]A1c |
| Vasopressin (second‑line) | 0.01-0.06 U/min (fixed dose) | Less RRT vs norepinephrine (VANISH; NNT = 10) [109]A1b; no mortality reduction in VASST [258]A1b | Add when NE >0.25 µg/kg/min [2]A1c[49]D5 |
| Epinephrine (third‑line) | 0.05-0.5 µg/kg/min | Equivalent to NE+DOB in 28‑d mortality (40% vs 34%) [264]A1b | Reserve for refractory shock |
| Hydrocortisone + fludrocortisone | HC 50 mg q6h + FC 50 µg daily | 90‑d mortality 43% vs 49.1%; NNT = 16.4 (APROCCHSS) [256]A1b | Consider in NE‑refractory shock |
Definitive Therapy & Source Control of the Inciting Insult
- ▸Source control must be achieved within 12 hours of diagnosis (grade 1C); each hour of delay increases mortality in patients with septic shock.
- ▸Broad-spectrum antibiotics should be started within the first hour; combination therapy benefits patients with a pre-treatment mortality risk >25%.
- ▸Procalcitonin-guided de-escalation safely shortens antibiotic duration, but does not reduce mortality; routine vitamin C, HES, and high-volume hemofiltration are not recommended.
Once the initial resuscitation is underway, fluids and vasopressors titrated to a MAP ≥65 mm Hg, the clinician must pivot to eradicating the source of infection. This is the only intervention that directly addresses the cause of septic shock; without it, no amount of organ support will reverse the course.
Source Control: Principle and Timing
Source control, drainage of an abscess, removal of an infected catheter, debridement of necrotic tissue, or definitive surgical repair of a perforated viscus, must be achieved within 12 hours of diagnosis (grade 1C) [1]A1c. Every hour of delay to surgical source control increases the odds of death in patients with septic shock (adjusted OR 1.013 per hour, 95% CI 1.001-1.026) [300]B2b. The method chosen should balance the risks and benefits of the intervention; percutaneous drainage is preferred when feasible [1]A1c. Source-control failure, defined by the need for surgical revision or persistent inflammation, strongly predicts mortality (OR 2.5-3.0) in intra-abdominal sepsis [113]B2b.
Antimicrobial Therapy: Timing, Regimen, and De-escalation
Administer broad-spectrum within the first hour of recognizing septic shock (grade 1B) [1]A1c. Hospital mortality increases by 0.42% per hour of delay (OR 1.019, 95% CI 1.01-1.028) [272]B2b. The initial regimen must cover all likely pathogens based on source, local , immune status, and prior antibiotic exposure [304]D5. In patients with septic shock whose risk of death exceeds 25%, combination therapy (two agents of different classes) reduces mortality (OR 0.49) [298]B2a. For hospital-acquired pneumonia with septic shock, European guideline-driven empiric therapy (e.g., anti-pseudomonal beta-lactam plus an agent active against MRSA) did not improve mortality in the shock subgroup [306]B3b. During outbreaks of carbapenem-resistant , a polymyxin should be part of the empiric regimen [292]D5.
De-escalation, narrowing or stopping antibiotics once culture results return, should be performed daily (grade 1B) [1]A1c. -guided algorithms safely reduce antibiotic duration by a mean of 1.28 days (95% CI -1.95 to -0.61) without increasing mortality [47]A1a. A practical algorithm suggests stopping antibiotics when procalcitonin falls by ≥90% from the peak [104]A1b.
Treatment Escalation and When to Reassess
If shock persists beyond 48-72 hours, reassess for: (1) an undrained source (repeat imaging or surgical consultation); (2) a resistant pathogen (e.g., , , or carbapenemase-producing Enterobacteriaceae [114]B2b[135]B2b); (3) an alternative diagnosis (e.g., stress cardiomyopathy, pulmonary embolism). Broaden empiric coverage to include these threats, and consider adding a second Gram-negative agent if the patient is deteriorating. In refractory septic shock, adjunctive (0.01-0.06 U/min) reduces the need for renal replacement therapy compared with norepinephrine alone (25.4% vs. 35.3%; difference -9.9%, 95% CI -19.3% to -0.6%) [109]A1b.
What NOT to Do
- Do not delay antibiotics beyond 1 hour [1]A1c[272]B2b.
- Do not use hydroxyethyl starch (HES) solutions; they increase acute kidney injury and mortality [185]A1b.
- Do not administer high-volume hemofiltration or coupled plasma filtration-adsorption as routine adjuncts; CPFA was associated with harm (90‑day survival curves diverged early in favor of controls, p = 0.100) [143]A1a[297]A1b.
- Do not add routinely; two large RCTs showed no reduction in organ dysfunction or mortality [118]A1b[308]A1b.
- Do not start for its anti-inflammatory effect; it increased major bleeding (8.5% vs. 1.2%, p = 0.02) without reducing organ dysfunction [179]A1b.
Controversies and Guideline Disagreement
| Question | Position A | Position B | Strength | Implication for practice |
|---|---|---|---|---|
| Procalcitonin to guide antibiotic duration | SSC/IDSA, algorithm recommended to shorten exposure [1]A1c | Cochrane review, no mortality benefit, duration reduction modest (1.28 days) [47]A1a | Moderate (different emphasis on benefit vs. harm) | PCT-guided cessation is safe but does not reduce mortality; use as part of daily stewardship. |
| Combination therapy for septic shock | Kumar meta‑analysis, benefit only when mortality risk >25% [298]B2a | Surviving Sepsis, weak recommendation for initial combination in neutropenia or difficult-to-treat pathogens [1]A1c | Mild (target population disagreement) | In high-risk patients (shock, high early lactate, multi-organ failure), start two agents; de-escalate when sensitivities return. |
| Vitamin C as adjunct | LOVIT, no benefit, possible harm (trend toward increased 90‑day mortality) [307]B2b | VITACiPS (pediatric), no difference [308]A1b | Strong (overall evidence shows no benefit) | Do not use vitamin C in septic shock. |
Pearl: In septic shock, source control within 12 hours and appropriate antimicrobials within the first hour are the only interventions proven to independently reduce mortality; no adjunctive therapy compensates for a missed or uncontrolled source [1]A1c[300]B2b.
| Infection source | Typical pathogens | Example empiric regimen | Evidence level |
|---|---|---|---|
| Community-acquired pneumonia | S. pneumoniae, Legionella, H. influenzae | Beta-lactam + macrolide (e.g., ceftriaxone 2 g IV + azithromycin 500 mg IV) | [22]B3b (3b) |
| Hospital-acquired / ventilator-associated pneumonia | MRSA, Pseudomonas aeruginosa, Acinetobacter | Anti-pseudomonal beta-lactam (e.g., cefepime 2 g IV q8h) + anti-MRSA agent (e.g., vancomycin 15-20 mg/kg IV q12h) | [114]B2b[135]B2b (2b) |
| Intra-abdominal infection | Enterobacteriaceae, anaerobes, Enterococcus | Piperacillin-tazobactam 4.5 g IV q6h or carbapenem (e.g., meropenem 1 g IV q8h) ± antifungal (e.g., fluconazole 800 mg load) | [113]B2b (2b) |
History and Evolution of Treatment
- ▸EGDT, which reduced mortality from 46.5% to 30.5% in the landmark 2001 Rivers trial, was later found non-superior to usual care in three large multicenter RCTs (ProCESS, ARISE, ProMISe), shifting focus to rapid antibiotics and bedside dynamic assessment.
- ▸Drotrecogin alfa (activated protein C) was withdrawn from the market after the confirmatory PROWESS-SHOCK trial showed no mortality benefit (26.4% vs 24.2%), a cautionary tale of post-marketing requirement.
- ▸Corticosteroid therapy in septic shock shows benefit only in the sickest patients: hydrocortisone plus fludrocortisone reduced 90-day mortality from 49.1% to 43.0% in APROCCHSS, while hydrocortisone alone in ADRENAL showed no effect (27.9% vs 28.8%).
Source control has been a pillar of sepsis since the germ theory of disease, but the pharmacologic and hemodynamic approach to septic shock has undergone three distinct revolutions. Tracing this timeline grounds every current recommendation in the evidence, and in the therapies that were abandoned when trials failed to confirm promise.
The empiric era (pre-2001)
Before 2001, septic shock resuscitation relied on clinical gestalt: fluid boluses titrated to urine output, dopamine as first-line vasopressor, and supranormal targets. A 1992 trial randomizing patients to cardiac index goals of 3.0 L/min/m² (normal therapy) versus 6.0 L/min/m² (optimal therapy) found paradoxically higher mortality in the high-target group (72% vs 50%), though the difference was not statistically significant [326]A1b. The practice of pushing fluids without regard to dynamic response was inherited from hypovolemic shock, a model that does not account for the vasoplegia and endothelial injury of sepsis [352]D5. Dopamine was the default vasopressor despite a 1993 randomized trial showing norepinephrine reversed hyperdynamic shock in 93% of patients versus 31% for dopamine [323]A1b.
The goal-directed revolution (2001-2014)
The watershed arrived with Rivers et al. in 2001, who randomized 263 patients presenting to an urban emergency department with severe sepsis or septic shock to 6 hours of early goal-directed therapy (EGDT) or standard care. EGDT titrated CVP, mean arterial pressure, and central venous oxygen saturation (ScvO₂) >70% using fluids, vasopressors, dobutamine, and packed red cells. In-hospital mortality dropped from 46.5% to 30.5% (P = 0.009) [329]A1b. The Surviving Sepsis Campaign (SSC), launched in 2002, codified this approach into a sepsis bundle, and a 2010 meta-analysis of eight unblinded trials found bundle use was associated with a consistent survival increase (OR 1.91) [312]B2a. The first SSC guidelines (2004) recommended EGDT, early broad-spectrum within 1 hour of recognition, and equivalence of crystalloid and colloid resuscitation [310]D5.
This era also saw trial successes and failures. The 2002 Annane trial showed low-dose plus fludrocortisone reduced 28-day mortality in nonresponders to corticotropin testing from 63% to 53% (HR 0.67; 95% CI 0.47-0.95) [342]A1b. Recombinant human activated protein C (drotrecogin alfa) was approved after the 2001 PROWESS trial, but the confirmatory PROWESS-SHOCK trial (2012) found no mortality benefit (26.4% vs 24.2%; RR 1.09; 95% CI 0.92-1.28), leading to market withdrawal [262]A1b[320]A1b. The CORTICUS trial (2008) failed to show a survival advantage for hydrocortisone in septic shock, though shock reversed more quickly [260]A1b.
The deconstruction era (2014-present)
Three large multicenter trials, ProCESS (2014), ARISE (2014), and ProMISe (2015), tested EGDT against usual care and each found no mortality difference. In ARISE, 90-day mortality was 18.6% with EGDT versus 18.8% with usual care [106]A1b. The 2016 SSC guidelines downgraded EGDT from a strong recommendation to a suggestion, emphasizing instead rapid antibiotic administration, 30 mL/kg crystalloid as an initial bolus, and frequent reassessment using dynamic measures [2]A1c[3]A1c. The CLASSIC trial (2022) then demonstrated that restricting intravenous fluids to a median of 1798 mL versus standard 3811 mL during ICU stay did not reduce 90-day mortality (42.3% vs 42.1%) [259]A1b.
For vasopressors, SOAP II (2010) showed norepinephrine was non-inferior to dopamine but with significantly fewer arrhythmic events (12.4% vs 24.1%; P < 0.001) [257]A1b. SEPSISPAM (2014) found no mortality difference between a MAP target of 65-70 mm Hg versus 80-85 mm Hg, though the higher target increased new [261]A1b. A 2025 post-hoc analysis confirmed that targeting higher MAP was associated with harm when high norepinephrine doses were required or mottled skin persisted [7]B2b. The ANDROMEDA-SHOCK trial (2019) found that targeting normalization of capillary refill time rather than lactate clearance did not significantly reduce 28-day mortality (34.9% vs 43.4%; P = 0.06) [108]A1b, but the follow-up ANDROMEDA-SHOCK-2 trial (2025) showed a personalized hemodynamic protocol centered on capillary refill time was superior to usual care for a composite endpoint (win ratio 1.16; 95%) [186]A1b.
Corticosteroid therapy underwent a similar pendulum swing. ADRENAL (2018) randomized 3800 mechanically ventilated patients to hydrocortisone 200 mg/day versus placebo and found no 90-day mortality benefit (27.9% vs 28.8%) [330]A1b. In contrast, APROCCHSS (2018) demonstrated that hydrocortisone plus fludrocortisone lowered 90-day mortality from 49.1% to 43.0% (RR 0.88; 95% CI 0.78-0.99) in a sicker population [256]A1b. The 2017 SCCM/ESICM guidelines now recommend using IV hydrocortisone <400 mg/day for ≥3 days in septic shock unresponsive to fluid and vasopressors (conditional, low quality evidence) [6]A1c.
Controversies and Guideline Disagreement
| Question | Position A | Position B | Strength | Implication |
|---|---|---|---|---|
| First-line vasopressor | Norepinephrine (SSC 2016, strong recommendation) [2]A1c | Vasopressin as early adjunct in patients at risk for renal failure (VANISH) [109]A1b | Conditional, moderate | Norepinephrine remains first-line; vasopressin added when escalating doses needed |
| Corticosteroids in septic shock | 200 mg/day hydrocortisone for shock unresponsive to fluids/pressors (SCCM/ESICM 2017) [6]A1c | No routine steroids (ADRENAL) [330]A1b | Conditional, low | ADRENAL vs APROCCHSS enrolled different severity; use in high-dose-pressor-dependent patients |
| Fluid resuscitation volume | 30 mL/kg crystalloid initially (SSC 2016, best practice) [2]A1c | Restrictive strategy to avoid fluid overload (CLASSIC) [259]A1b | Conditional, very low | ESICM 2025 suggests up to 30 mL/kg initially then individualize [245]A1c |
| Balanced vs saline crystalloid | Balanced crystalloids preferred (SMART sepsis subgroup) [10]B2b | Saline acceptable if balanced solutions unavailable | Conditional, moderate | Balanced solutions reduce AKI and hyperchloremia [10]B2b[246]A1b |
Abandoned therapies
Several promising interventions failed in adequately powered trials. Drotrecogin alfa was withdrawn after PROWESS-SHOCK demonstrated no benefit and increased bleeding risk [262]A1b. Tight glycemic control (target glucose 80-110 mg/dL) increased severe hypoglycemia without mortality benefit [345]A1b. High-dose corticosteroids (>400 mg/day) caused immunosuppression and superinfection [260]A1b. Methylene blue, though showing promise in vasopressor reduction in a 2001 pilot [313]A1b and a 2023 RCT [268]A1b, remains investigational. Polymyxin B hemoperfusion failed to reduce 28-day mortality in the EUPHRATES trial (37.7% vs 34.5%) [343]A1b. The combination of vitamin C, thiamine, and hydrocortisone, popularized after retrospective studies, showed no benefit in the VITAMINS [19]A1b and ACTS [346]A1b trials.
Pearl: Every current recommendation in septic shock is supported by at least one negative trial that disproved a prior dogma, EGDT was de-escalated after ProCESS/ARISE/ProMISe, hydrocortisone alone failed in ADRENAL but succeeded with fludrocortisone in APROCCHSS, and fluid restriction was safe but not superior in CLASSIC. Evidence evolves; therapy should too.
| Trial (Year) | Population | Intervention | Key Finding | Impact |
|---|---|---|---|---|
| Rivers EGDT (2001) [329]A1b | 263 ED patients, severe sepsis/septic shock | 6h protocol targeting ScvO₂ >70% | In-hospital mortality 30.5% vs 46.5% (P=0.009) | Established goal-directed resuscitation |
| SOAP II (2010) [257]A1b | 1679 patients with shock | Dopamine vs norepinephrine as first-line | 28-day mortality: 52.5% vs 48.5% (P=0.10); arrhythmias 24.1% vs 12.4% (P<0.001) | Established norepinephrine as first-line vasopressor |
| PROWESS-SHOCK (2012) [262]A1b | 1697 patients with septic shock | Drotrecogin alfa vs placebo | 28-day mortality 26.4% vs 24.2% (RR 1.09; 95% CI 0.92-1.28) | Led to market withdrawal of drotrecogin alfa |
| SEPSISPAM (2014) [261]A1b | 776 patients with septic shock | MAP target 80-85 vs 65-70 mmHg | 28-day mortality 36.6% vs 34.0% (P=0.57); more AF with high target | Established 65 mmHg as default MAP target |
| ARISE (2014) [106]A1b | 1600 ED patients with early septic shock | EGDT vs usual care | 90-day mortality 18.6% vs 18.8% | De-escalated EGDT from standard of care |
| ANDROMEDA-SHOCK (2019) [108]A1b | 424 patients with septic shock | Capillary refill time vs lactate-guided resuscitation | 28-day mortality 34.9% vs 43.4% (HR 0.75; 95% CI 0.55-1.02) | Demonstrated feasibility of peripheral perfusion targets |
| ADRENAL (2018) [330]A1b | 3800 mechanically ventilated patients with septic shock | Hydrocortisone 200 mg/day vs placebo | 90-day mortality 27.9% vs 28.8% (OR 0.95; 95% CI 0.82-1.10) | Corticosteroids alone do not improve survival |
| APROCCHSS (2018) [256]A1b | 1241 patients with septic shock | Hydrocortisone + fludrocortisone vs placebo | 90-day mortality 43.0% vs 49.1% (RR 0.88; 95% CI 0.78-0.99) | Combination corticosteroid regimen reduces mortality |
| CLASSIC (2022) [259]A1b | 1554 ICU patients with septic shock | Restrictive vs standard IV fluids | 90-day mortality 42.3% vs 42.1% | Fluid restriction safe but not superior |
Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets
- ▸MAP target 65-70 mm Hg is standard; higher targets requiring high norepinephrine doses or failing to resolve mottled skin are associated with increased mortality.
- ▸Vasopressin added early reduces RRT use; hydrocortisone accelerates shock reversal but only combined with fludrocortisone reduces 90-day mortality (APROCCHSS).
- ▸Delayed RRT strategy in septic AKI allows 38-45% of patients to avoid RRT without increasing mortality; early RRT may be harmful when AKI is diagnosed by creatinine elevation alone.
From the historical lessons of crystalloid wars, early goal-directed therapy trials, and corticosteroid controversies, contemporary organ support integrates evidence-based targets across every failing system simultaneously, not merely the lung and the pressor.
Ventilatory Support
Lung-protective ventilation (tidal volumes 6 mL/kg predicted body weight, plateau pressure <30 cm H₂O) is standard. Conservative oxygen therapy targeting SpO₂ 90-97% did not improve outcomes in sepsis: in the ICU-ROX post hoc analysis, 90-day mortality was 36.2% (47/130) with conservative oxygen vs 29.2% (35/120) with usual care (absolute difference 7 percentage points; 95% CI -4.6 to 18.6; P = 0.24), raising harm concerns [379]B2b. control via external cooling to normothermia (36.5-37°C) for 48 hours decreased vasopressor requirements and reduced day-14 mortality from 34% to 19% (absolute difference -16%; 95% CI -28 to -4; P = 0.013) [251]A1b. Prone positioning is indicated when PaO₂/FiO₂ <150 mm Hg with ARDS.
Hemodynamic Targets
The target mean arterial pressure (MAP) is 65-70 mm Hg. SEPSISPAM randomized 776 patients to MAP 65-70 vs 80-85 mm Hg; 28-day mortality did not differ (34.0% vs 36.6%; HR 1.07; 95% CI 0.84-1.38; P = 0.57) [261]A1b. A higher target requiring high norepinephrine doses or failing to resolve mottled skin at 24 hours was associated with increased mortality (risk difference 0.027; 95%) [7]B2b. TARTARE-2S tested a tissue-perfusion protocol permitting MAP 50-65 mm Hg with capillary refill time monitoring; 30-day mortality was 24.7% vs 27.8%, with similar vasopressor-free days (23 vs 22; difference 0.59; 95% CI -3 to 4) [97]A1b. ANDROMEDA-SHOCK-2 (1467 patients) demonstrated superiority of a personalized protocol targeting capillary refill time over usual care (win ratio 1.16; 95%; P = 0.04), driven by shorter vital-support duration [186]A1b.
First-line vasopressor is . Early addition of (up to 0.06 U/min) in the VANISH trial did not improve kidney-failure-free days but reduced renal replacement therapy (RRT) use (25.4% vs 35.3%; difference -9.9%; 95% CI -19.3 to -0.6) [109]A1b. as adjunctive therapy (norepinephrine >0.2 mcg/kg/min) achieved target MAP with lower catecholamine doses in 22.7% vs 9.4% (RR 1.53; 95% CI 1.09-2.14; P = 0.039), without altering 28-day mortality (60.6% vs 64.1%) [299]A1b. In pediatric septic shock, targeting the 5th vs 50th centile MAP showed no mortality difference (16.9% vs 23.2%; P = 0.41) and reduced vasoactive use and ARDS (16.9% vs 32.8%; P = 0.02) [99]A1b.
, 200 mg/day, do not reduce 90-day mortality (27.9% vs 28.8%; OR 0.95; 95% CI 0.82-1.10) but accelerate shock reversal (median 3 vs 4 days) [330]A1b. Hydrocortisone plus 50 mcg/day reduced 90-day mortality from 49.1% to 43.0% (RR 0.88; 95% CI 0.78-0.99) [256]A1b. A post hoc ADRENAL analysis found hydrocortisone associated with reduced KRT initiation (21% vs 24%; OR 0.84; 95% CI 0.70-0.99) [393]B2b.
titrated to heart rate 80-94/min in patients with persistent tachycardia (HR ≥95) reduced norepinephrine requirements (AUC difference -0.11 mcg/kg/min), fluid requirements, and lactate [110]A1b; very early administration is feasible and safe [81]A1b. for decatecholaminization reduced epinephrine rescue (RR 0.6; 95% CI 0.06-0.93) and new-onset (RR 0.47; 95% CI 0.21-0.99) [254]A1b.
Renal Replacement Therapy
RRT timing does not affect mortality in septic shock with acute kidney injury. IDEAL-ICU (488 patients, RIFLE-Failure stage) reported 90-day mortality 58% with early vs 54% with delayed RRT (P = 0.38); 38% of delayed-group patients never received RRT [18]A1b. A substudy found early RRT harmful in patients meeting AKI by creatinine alone (mortality 58% vs 42%; adjusted interaction P = 0.021) but trending protective with oliguria [389]B2b. Fluid resuscitation with vs 0.9% saline is associated with lower 30-day mortality in sepsis (26.3% vs 31.2%; aOR 0.74; 95% CI 0.59-0.93) [10]B2b.
Extracorporeal Therapies
hemoperfusion in abdominal septic shock from gram-negative infection improved MAP and reduced 28-day mortality from 53% to 32% (HR 0.43; 95% CI 0.20-0.94) in EUPHAS [265]A1b. Coupled plasma filtration-adsorption (COMPACT-2) was stopped for possible harm: last-hospital mortality 55.6% vs 46.2% (P = 0.35) [297]A1b. High-volume hemofiltration (65 mL/kg/h) decreased vasopressor requirements vs 35 mL/kg/h [381]A1b but did not improve catecholamine-free days or mortality [380]A1b.
Nutrition and Metabolic Support
Enteral nutrition should begin within 48 hours. Early enteral nutrition was associated with more ICU-free days (9.3 vs 5.7; P = 0.0002) [117]B2b. A diet enriched with , , and antioxidants reduced mortality by an absolute 19.4% (P = 0.037) and increased ventilator-free days (13.4 vs 5.8; P < 0.001) [376]C4. Total parenteral nutrition supplemented with alanine-glutamine dipeptide reduced nosocomial pneumonia (8.04 vs 29.25 episodes per 1000 ventilator-days; P = 0.02) and improved glycemic control [372]A1b.
Sedation and
Sedation goals target light sedation (Richmond Agitation-Sedation Scale 0 to -2) using non-benzodiazepine agents ( , dexmedetomidine). In a SPICE III substudy, dexmedetomidine did not reduce vasopressor requirements in septic shock (median NEq 0.03 vs 0.04 mcg/kg/min; P = 0.17) but was associated with a lower norepinephrine-equivalent-to-MAP ratio on adjusted analysis [391]B2b.
Pearl: Start with MAP 65-70 mm Hg using norepinephrine; add vasopressin early to reduce RRT risk, but avoid high norepinephrine doses chasing a higher MAP when mottled skin persists, this signals harm rather than benefit [7]B2b[261]A1b[393]B2b.
Controversies and Guideline Disagreement
| Question | Position A | Position B | Strength | Implication |
|---|---|---|---|---|
| Corticosteroid regimen | Hydrocortisone alone (SSC/ADRENAL) [330]A1b | Hydrocortisone + fludrocortisone (APROCCHSS) [256]A1b | ADRENAL: no mortality benefit; APROCCHSS: RR 0.88, 95% CI 0.78-0.99 | Consider fludrocortisone addition in patients with refractory shock, though ADRENAL’s null result limits enthusiasm |
| RRT timing in septic AKI | Early (within 12 h of RIFLE-Failure) [18]A1b | Delayed (48 h, await recovery) [11]B2b[18]A1b | No mortality difference; 38-45% escape RRT with delay | Delay RRT unless life-threatening complications; early RRT may harm creatinine-only AKI [389]B2b |
| System | Target | Evidence |
|---|---|---|
| Ventilatory | Tidal volume 6 mL/kg PBW, plateau <30 cm H₂O, SpO₂ 90-97% | ICU-ROX post hoc [379]B2b; fever control [251]A1b |
| Hemodynamic MAP | 65-70 mm Hg | SEPSISPAM [261]A1b |
| Vasopressor first-line | Norepinephrine | SSC guidelines |
| Vasopressor adjunct | Vasopressin (0.06 U/min) | VANISH [109]A1b |
| Corticosteroids | Hydrocortisone 200 mg/day +/ fludrocortisone 50 mcg/day | ADRENAL [330]A1b, APROCCHSS [256]A1b |
| Renal replacement | Delayed unless life-threatening | IDEAL-ICU [18]A1b, AKIKI [11]B2b |
| Nutrition | Early enteral (≤48 h); consider EPA/GLA/antioxidants | [117]B2b, [376]C4 |
| Sedation | Light (RASS 0 to -2); non-benzodiazepine | SPICE III substudy [391]B2b |
De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS)
- ▸Early rehabilitation within 48 hours of ICU admission for septic shock improves mobilization (sitting/standing) without increasing 90-day mortality (28% vs 23%, P=0.51) [400].
- ▸Anticholinergic drug exposure at ICU admission increases delirium risk (subdistribution HR 1.35 for ADS ≥2); minimizing anticholinergic burden is a modifiable prevention target [401].
- ▸SBT success alone does not guarantee timely extubation: same-day extubation occurs in only 77% of patients who pass, and septic shock independently predicts delay (OR 0.77) [398].
Once the immediate threats of septic shock, hypoperfusion, organ failure, and ongoing infection, are stabilized through the coordinated application of ventilatory, hemodynamic, and renal support, the clinical focus pivots to liberation: freeing the patient from life support without precipitating decompensation or long-term disability. The multicomponent ABCDEF bundle (Assess-Prevent-Manage pain, Both SAT and SBT, Choice of sedation, Delirium assess/manage, Early mobility, Family engagement) directly targets these goals; higher bundle adherence is associated with shorter mechanical ventilation and reduced post-intensive care syndrome (PICS) [399]D5.
Spontaneous Awakening and Breathing Trials
Daily interruption of sedation (SAT) paired with a spontaneous breathing trial (SBT) reduces ventilator days. Among mechanically ventilated patients who pass an SAT/SBT, 77% are extubated the same day. Independent predictors of same-day extubation include a higher Richmond Agitation-Sedation Scale (RASS) score (OR 1.83 for RASS -2 vs -4, 95% CI 1.56-2.14) and receipt of sedation the prior day (OR 2.12, 95% CI 1.63-2.74), while a diagnosis of sepsis or septic shock (OR 0.77, 95% CI 0.59-1.00) and hemodynamic instability (OR 0.67, 95% CI 0.47-0.95) reduce the odds [398]B3b. Septic shock before awakening is a powerful contributor to respiratory muscle weakness (OR 3.17), and maximal inspiratory pressures are frequently low (median 30 cm H₂O), independently predicting delayed extubation (HR 1.86) [396]B2b. Acute kidney injury further prolongs weaning: a ≥85% rise in baseline creatinine increases weaning duration (HR 2.30), and oliguria confers an adjusted OR for mortality of 30.8 [397]B3b.
Delirium: Detection, Prevention, and
Sepsis-associated delirium is present in the majority of septic ICU patients and is linked to disturbed cerebrovascular autoregulation (P = 0.015) [395]B2b. Elevated C-reactive protein, S-100β, and cortisol are associated with delirium, while interleukin-6 is not [395]B2b. Screening with the Confusion Assessment Method for the ICU (CAM-ICU) is mandatory. Anticholinergic drug exposure at ICU admission increases delirium risk (subdistribution HR 1.35, 95% CI 1.09-1.68 for Anticholinergic Drug Scale score ≥2), especially in patients >65 years without severe sepsis (SHR 2.15) [401]B2b. Standardized multiprofessional delirium guidelines incorporating risk identification, preventive measures, screening, and treatment reduce ICU length of stay (time ratio 0.94, 95% CI 0.89-1.00) and ventilator days (TR 0.84, 95% CI 0.77-0.92) [402]B2b. The choice of sedation influences delirium burden: -first, light sedation protocols minimize exposure. A randomized trial of in severe sepsis without shock showed no protection against shock development and a trend toward more muscle weakness (30.7% vs 23.8%) and hyperglycemia (90.9% vs 81.5%) [111]A1b, reinforcing the need to limit corticosteroids to refractory shock.
Early Rehabilitation in Septic Shock
Concerns that mobilizing a vasopressor-dependent patient might worsen outcomes have been addressed. In the multicenter BEAT-SHOCK registry of patients with septic shock requiring high-dose norepinephrine (≥0.2 µg/kg/min), early rehabilitation started within 48 hours of ICU admission was associated with a significantly higher likelihood of sitting on the edge of the bed (adjusted HR 1.66) and standing (aHR 2.20) within 14 days, without increasing 90-day mortality (28% vs 23%; aHR 1.27, 95%; P = 0.51) [400]B2b. No evidence of harm, and a clear functional benefit, supports making early mobilization the default strategy for septic shock.
Post-Intensive Care Syndrome (PICS) and ICU Recovery
Survivors of septic shock face a complex triad of physical impairment, cognitive decline, and mental health disorders, collectively PICS [399]D5. Family members also experience psychological distress (PICS-F). Qualitative analyses of telemedicine multidisciplinary ICU recovery clinic dialogues identify five problem domains: health status, mental health and cognition, medication management, health-care access and navigation, and quality of life [394]C4. Sex and gender differences influence PICS risk and recovery trajectories; women may report different symptom burdens and require tailored rehabilitation strategies [155]D5. ICU recovery clinics that integrate pharmacy, psychology, and physician input address these heterogeneous needs. The ABCDEF bundle is the bedside tool that prevents or mitigates PICS: daily SAT/SBT, light sedation, delirium monitoring, early mobility, and family engagement should be woven into every septic shock patient's daily care plan. The next section explores complications and iatrogenesis that can arise during this liberation phase.
Pearl: The same early-mobilization principles proven safe in mixed ICU populations apply to septic shock within 48 hours of resuscitation; the default should be to sit the patient up, not to keep them flat, vasopressors alone are not a contraindication to rehabilitation.
| Element | Intervention | Key Evidence |
|---|---|---|
| Assess, Prevent, Manage pain | Analgesia-first sedation, protocolized pain assessment | Reduces sedation exposure and delirium [399]D5 |
| Both SAT and SBT | Daily sedation interruption + spontaneous breathing trial | Shortens ventilator days; sepsis-specific delayed extubation predictors identified [398]B3b |
| Choice of sedation | Propofol or dexmedetomidine over benzodiazepines | Benzodiazepines increase delirium risk; CAM-ICU monitoring guides choice |
| Delirium monitor/manage | CAM-ICU screening, nonpharmacologic bundle, minimize anticholinergics | Standardized management reduces ICU LOS and ventilator days (TR 0.84-0.94) [402]B2b |
| Early mobility | Within 48 h of resuscitation (including vasopressor-dependent patients) | Safe in septic shock: aHR 1.66 for sitting, no mortality increase [400]B2b |
| Family engagement | Family presence, communication, PICS-F support | ICU recovery clinics improve problem identification [394]C4 |
Complications & Iatrogenesis
- ▸ICU-acquired infections are the most common iatrogenic complication, occurring in 30-40% of 48-hour survivors and accounting for the highest sepsis-attributable mortality.
- ▸Platelet and fresh frozen plasma transfusions independently increase the risk of subsequent ICU-acquired infections (cause-specific HR 1.55 and 1.38).
- ▸Multidrug-resistant pathogen VAP is predicted by prior exposure to >2 antibiotic classes and prolonged carbapenem-colistin use; VAP duration should be 7-8 days.
Despite protocolized care, iatrogenic complications dominate ICU morbidity in septic shock, with ICU-acquired infections driving the highest sepsis-attributable mortality (23.7% in ICU-acquired sepsis vs 12.9% community-acquired) [404]B2b.
ICU-Acquired Infections
(VAP) occurs in 26.0 per 1000 intubation-days; bloodstream infections in 11.7 per 1000 ICU patient-days [134]B2b. Gram-negative pathogens predominate ( 18.4%, Klebsiella spp. 14.4%), and multidrug-resistance is identified in 36% of cases [114]B2b. Invasive candidiasis complicates 7.07 per 1000 ICU admissions; crude 30-day mortality is 42% [422]B2b.
| Complication | Frequency | Prevention | |
|---|---|---|---|
| VAP | 26/1000 intubation-days [134]B2b | -of-bed elevation, daily sedation interruption, oral chlorhexidine | Empiric therapy per local antibiogram; duration 7-8 days [416]A1c |
| BSI | 11.7/1000 ICU-days [134]B2b | Hand hygiene, catheter check & removal | Targeted ; remove infected lines |
| Candidemia | 7.07/1000 ICU admissions [422]B2b | Avoid prolonged broad-spectrum antibiotics | first-line |
Multidrug-resistant pathogens are predicted by prior exposure to >2 antibiotic classes (OR 5.11) and comorbidity burden [421]B2b. The combination of carbapenem use >20 days and colistin >13 days predisposes to pandrug-resistant P. aeruginosa VAP (OR 76.0) [412]B3b.
Transfusion-Related Immunomodulation
Platelet and fresh frozen plasma transfusions independently increase the risk of subsequent ICU-acquired infection (cause-specific HR 1.55 and 1.38, respectively) [410]B2b. A restrictive RBC transfusion strategy (threshold 7 g/dL) is recommended for most critically ill patients, including those with septic shock, as it does not increase mortality and reduces transfusion exposure [9]A1c.
Venous Thromboembolism Prophylaxis
Septic shock patients carry high VTE risk. Low-molecular-weight (e.g., 40 mg daily) is preferred over unfractionated heparin based on lower rates of heparin-induced thrombocytopenia and comparable efficacy [418]D5. Sequential compression devices should be added if pharmacologic prophylaxis is contraindicated.
Other Iatrogenic Injuries
Severe ischemic events occur in 11.8% of septic shock patients; hemorrhagic complications in 8.7%, with hematologic malignancy conferring a 3.17-fold higher risk of hemorrhage [409]B2b. Pressure injuries develop in up to 30% of prolonged ICU stays, protocolized turning and specialty mattresses are essential. Persistent autonomic dysfunction (ileus requiring nasogastric decompression, sinus tachycardia, urinary retention) often prolongs ICU stay but resolves with shock resolution.
Pearl: ICU-acquired infections affect one in three survivors beyond day 3, and their occurrence, not the identity of the pathogen, drives excess mortality; prevention through bundle adherence reduces VAP rates by more than 50% [224]B3b[231]B3b.
Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation)
- ▸Hospital mortality in septic shock is 51%, rising to 69% in solid-tumor patients with metastatic disease
- ▸Bedside mottling score (4-5: OR 74) and BPRI <7.1 (OR 1.32 per unit decrease) outperform traditional severity scores for real-time prognostication
- ▸End-of-life decisions occur in 29% of septic shock deaths; early structured goals-of-care discussions are essential in high-risk patients
Complications and iatrogenesis directly shape short- and long-term prognosis in septic shock. Prognostication in the ICU is therefore an ongoing process that should guide goals-of-care discussions from the first hours of resuscitation.
Mortality and Prognostic Factors
Hospital mortality across Sepsis-3 categories tracks severity: 13% for infection alone, 20% for sepsis, 39% for cardiovascular dysfunction, and 51% for septic shock [425]B2b. In patients with solid tumors and septic shock, 28-day mortality reaches 69.4%, with only 14% discharged home without assistance; metastatic disease (OR 3.17), respiratory failure (OR 2.34), lactate >4 mmol/L (OR 3.19), and performance score 3-4 (OR 2.72) independently predict death [36]B2b. Among cancer patients overall, pooled mortality is 58% (95% CI 54-63%), with little change between 2000 and 2024 [441]A1a. Cirrhosis confers an ICU mortality of 70.1% (adjusted OR 2.52) [431]B3b, and end-stage kidney disease carries ICU mortality of 41.4% and one-year mortality of 63% [424]B2b. Culture-negativity in septic shock independently predicts mortality despite paradoxically higher appropriateness of empirical [438]B2b.
| Prognostic Factor | Good Prognosis | Poor Prognosis |
|---|---|---|
| Mottling score | 0-1 (OR 1) | 4-5 (OR 74 for 14-day mortality) [67]B2b |
| Lactate | <1.5 mmol/L | >3 mmol/L (OR 9.6) [67]B2b |
| BPRI (MAP/vasoactive-inotropic score) | >7.1 | <7.1 (OR 1.32 per unit decrease) [443]B3b |
| Renin trajectory | Decreasing over time | Rising (AUC 0.80 for ICU mortality) [430]B2b |
| Thrombocytopenia | Absent | Severe (<50 × 10⁹/L; OR 3.38 for ICU mortality) [442]A1a |
| Sepsis-associated encephalopathy | Absent | Present (HR 1.61 for 28-day mortality) [137]B2b |
Biomarkers augment risk stratification. Presepsin >700 pg/mL defines septic shock, and patients in the 4th quartile have 5-7 times higher six-month mortality [428]B2b. NT-proBNP and hs-cTnT are elevated in >80% of patients and independently predict 90-day mortality, with early changes adding prognostic value [423]A1b. Serum angiotensinogen outperforms both lactate and renin in 30-day mortality prediction [121]B2b.
Goals of Care and End-of-Life Decisions
End-of-life decisions (EOLDs) occur in 29% of patients who die in surgical ICUs, and severe sepsis/septic shock is associated with a 16-fold increased likelihood of an EOLD [433]B2b. The decision to withdraw life support in septic shock is most often initiated by medical staff, in contrast to long-term acute care hospitals where families lead the process [440]B3b. Early structured goals-of-care discussions are recommended for patients with advanced malignancy, poor performance status, or high illness severity scores, without denying ICU admission [36]B2b.
Brain-Death Determination and Organ Donation
Sepsis-associated encephalopathy (SAE) complicates 68% of sepsis with pulmonary infection and is independently linked to higher mortality [137]B2b. In patients with catastrophic neurologic injury (e.g., hypoxic-ischemic injury from refractory shock), brain-death determination follows standard protocols (clinical exam, apnea testing, ancillary testing as needed). Once brain death is confirmed, organ donation referral is mandatory in jurisdictions with opt-out or mandated referral laws. No specific evidence from the retrieved literature addresses organ donation outcomes in septic shock, but the general principles of donor (hemodynamic optimization, lung-protective ventilation, hormonal resuscitation) apply.
Pearl: At the bedside, a rising mottling score or a falling BPRI (MAP/vasoactive-inotropic ratio <7.1) identifies patients with septic shock who are failing resuscitation and should prompt an immediate goals-of-care discussion with surrogates [67]B2b[443]B3b.
Special Populations
- ▸Elderly patients with septic shock have increased mortality with high-target MAP (80-85 mm Hg); a 65-70 mm Hg target is safer (NNT = 9) [100].
- ▸Immunodeficiency is an independent risk factor for 28-day mortality (sHR 1.37), with AIDS, neutropenia, and solid tumors conferring the highest risk [449].
- ▸Pediatric and pregnant populations lack randomized trial evidence; management extrapolates from adult data with weight-based dosing and multidisciplinary planning.
The prognostic models and treatment algorithms discussed thus far apply to general adult populations, but several groups, pediatric, pregnant, elderly, and immunocompromised patients, require tailored approaches due to unique physiology, altered pharmacokinetics, and distinct disease courses.
Elderly
Older patients with septic shock are particularly vulnerable to iatrogenic harm from aggressive resuscitation targets. The OPTPRESS trial, conducted in Japan where the prevalence of chronic among older individuals is 66.9%, randomized patients aged ≥65 years to either a high-target MAP of 80-85 mm Hg or a standard target of 65-70 mm Hg. The trial was stopped early because high-target MAP significantly increased 90-day mortality from 28.6% to 39.3% (risk difference 10.7%, 95%) [100]A1b. No subgroup, including those with known chronic hypertension, derived benefit from the higher pressure target. A nationwide Japanese claims database confirmed persistently high mortality among patients aged ≥85 years, with in-hospital mortality of 36.5% for septic shock overall [29]B2b. These data support adopting a conservative MAP goal (65-70 mm Hg) in elderly patients, consistent with the Surviving Sepsis Campaign recommendations. Comorbidities that accumulate with age, heart failure, chronic kidney disease, frailty, modify risk: older age, low body weight, and comorbid heart failure were independently associated with 90-day mortality in a Chinese ICU cohort [123]C4.
Immunocompromised
Immunocompromised patients constitute a substantial fraction of septic shock admissions (31% in a multicenter prospective database) and carry an increased risk of short-term death after adjustment for confounders (subdistribution hazard ratio [sHR] 1.37) [449]B2b. Among the immunodeficiency profiles independently associated with mortality are AIDS (sHR 1.9), non-neutropenic solid tumor (sHR 1.8), hematologic malignancies without neutropenia (sHR 1.4), and all-cause neutropenia (sHR 1.7) [449]B2b. These patients often present with fewer signs of shock (lower lactate, less hypotension) yet progress rapidly, and standard severity scores may underestimate risk. Empiric antibiotic regimens must cover opportunistic pathogens (e.g., , , ) and account for prior antimicrobial exposure. Fungal colonization is an independent predictor of septic shock in postoperative intra-abdominal infections (OR 4.37) [454]B3b, and early initiation of active therapy (within 48-72 hours of culture collection) is critical when carbapenem-resistant Gram-negative infections are suspected [455]C4.
Pediatrics
Pediatric septic shock differs from adult disease in hemodynamic profile (predominantly hypovolemic and low-cardiac-output states), age-dependent drug clearance, and developmental vulnerability of the immune and cardiovascular systems. Weight-based dosing is mandatory: norepinephrine starting at 0.05-0.3 μg/kg/min, titrated to age-appropriate MAP targets (e.g., 5th percentile for age). The evidence base for pediatric-specific interventions remains limited; most landmark trials (ARISE, ProCESS, ProMISe) excluded children. A 0.1 ng/mL procalcitonin cut-off used in adults did not achieve a 25% reduction in antibiotic duration among critically ill adults [103]A1b; pediatric data are even scarcer.
Pregnancy
Septic shock in pregnancy is rare but carries high maternal and fetal mortality. Physiologic changes (increased plasma volume, decreased systemic vascular resistance, elevated cardiac output) alter vasopressor response and drug distribution. is the first-line vasopressor despite limited prospective pregnancy data; should be used cautiously because of potential uterine contraction. Delivery planning must be multidisciplinary: early delivery may improve maternal oxygenation but poses risks to the preterm fetus. No randomized trials guide fluid volume or transfusion thresholds in this population, so extrapolation from adult data (e.g., a restrictive transfusion threshold of 7 g/dL [107]A1b) is reasonable.
Pearl: In elderly patients with septic shock, targeting a MAP of 65-70 mm Hg rather than 80-85 mm Hg reduces 90-day mortality by 11% (NNT = 9), even in those with chronic hypertension [100]A1b.
Prevention, Screening and Post-ICU Surveillance
- ▸Universal pharmacologic VTE prophylaxis (UFH or LMWH) is indicated in septic shock; discontinuation during critical illness increases VTE risk [458].
- ▸Multidisciplinary ICU recovery clinics within 12 weeks of discharge address the heterogeneous recovery needs of septic shock survivors [134].
- ▸Stress ulcer prophylaxis with pantoprazole is being evaluated specifically in septic shock; routine SUP with a PPI remains standard pending results [209].
Surviving septic shock is only the first step; the ICU prophylaxis bundle and structured post-discharge surveillance close the loop on critical illness.
ICU Prophylaxis Bundle
Venous thromboembolism (VTE) prophylaxis is underused in septic shock. In the XPRESS trial, approximately half of subjects received no prophylaxis before enrollment, and by day 6, 5% had developed VTE, the vast majority clinically silent [458]A1b. A history of VTE was the strongest predictor (odds ratio 3.66; 95% CI 1.77‑7.56), and discontinuation of increased VTE risk compared to continued prophylaxis [458]A1b. Therefore, universal pharmacologic VTE prophylaxis with or is indicated in the absence of contraindications. No heparin type showed superiority [458]A1b.
Stress ulcer prophylaxis (SUP) is routinely administered to mechanically ventilated patients, but randomized evidence specific to septic shock is limited. The REVISE trial subgroup analysis will evaluate intravenous 40 mg once daily versus placebo in invasively ventilated septic shock patients, with primary outcomes of clinically important upper GI bleeding and 90‑day mortality [209]D5. Until these results, SUP with a remains standard, guided by bleeding risk assessment.
Probiotic therapy as prevention has shown promise in selected populations, though data specifically in septic shock are lacking. The PROACT trial examines a probiotic formulation ( LA‑5, , BB12, ) twice daily via nasogastric tube in acute brain injury patients [461]D5. For septic shock, standard VAP prevention bundles ( ‑of‑bed elevation, oral care, daily sedation interruption) remain the cornerstone.
Minimizing -associated bloodstream infections is another prevention priority. In a retrospective cohort, administered via midline catheters in intermediary care units had a major complication rate of only 2.5% (1 suspected extravasation, 7 thromboembolic events, 4 catheter‑related BSIs), suggesting midline catheters can safely reduce central line use in selected patients [460]C4.
Post-ICU Surveillance and Patient Education
Survivors of septic shock face a heterogeneous recovery marked by physical, cognitive, and psychological challenges. A telemedicine multidisciplinary ICU recovery clinic (ICU‑RC) within 12 weeks of discharge addresses these through visits with an ICU pharmacist, physician, and psychologist [134]B2b. Problem identification in these visits clustered around five subthemes: health status, mental health and cognition, medication , healthcare access and navigation, and quality of life [134]B2b. Problem‑solving strategies included care coordination, education, and constructive feedback [134]B2b. This model provides a framework for detecting and managing (PICS).
Sex and gender differences influence post-ICU outcomes. Women may experience differential burdens, and care should be personalized to ensure equitable recovery [155]D5.
Patient education should emphasize recognition of recurrent infection symptoms, adherence to prophylactic medications (e.g., anticoagulation), and the importance of follow‑up visits. Caregiver involvement is critical, as they often navigate transitions and provide ongoing support [134]B2b[155]D5.
Pearl: The presence of a prior VTE (odds ratio 3.66) and discontinuation of heparin during critical illness each independently increase VTE risk in septic shock; maintain prophylaxis throughout the ICU stay unless contraindicated [458]A1b.
References
- [1]
Dellinger RP, Levy MM, Rhodes A et al.. “Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.” Critical care medicine (2013). PMID: 23353941 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation), Prevention, Screening and Post-ICU Surveillance - [2]
Rhodes A, Evans LE, Alhazzani W et al.. “Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.” Critical care medicine (2017). PMID: 28098591 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [3]
Rhodes A, Evans LE, Alhazzani W et al.. “Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.” Intensive care medicine (2017). PMID: 28101605 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [4]
Weiss SL, Peters MJ, Alhazzani W et al.. “Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.” Intensive care medicine (2020). PMID: 32030529 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [5]
Dellinger RP, Levy MM, Rhodes A et al.. “Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.” Intensive care medicine (2013). PMID: 23361625 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, Clinical Presentation, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [6]
Annane D, Pastores SM, Rochwerg B et al.. “Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017.” Intensive care medicine (2017). PMID: 28940011 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First), History and Evolution of Treatment - [7]
Pirracchio R, Fong N, Legrand M. “Heterogeneity in the response to a high vs low mean arterial pressure target in patients with septic shock a post hoc analysis of a randomized controlled trial.” Intensive care medicine (2025). PMID: 40960603 ↗
L2RCTCited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First), History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [8]
Dargent A, Bourredjem A, Jacquier M et al.. “Dexmedetomidine to Reduce Vasopressor Resistance in Refractory Septic Shock: α2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS): A Double-Blind Randomized Controlled Pilot Trial.” Critical care medicine (2025). PMID: 40019329 ↗
L1RCTCited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [9]
Coz Yataco AO, Soghier I, Hébert PC et al.. “Red Blood Cell Transfusion in Critically Ill Adults: An American College of Chest Physicians Clinical Practice Guideline.” Chest (2024). PMID: 39341492 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, History and Evolution of Treatment, Complications & Iatrogenesis - [10]
Brown RM, Wang L, Coston TD et al.. “Balanced Crystalloids versus Saline in Sepsis. A Secondary Analysis of the SMART Clinical Trial.” American journal of respiratory and critical care medicine (2019). PMID: 31454263 ↗
L2RCTCited in: Definition, Classification & Shock-Physiology Spine, Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [11]
Gaudry S, Hajage D, Schortgen F et al.. “Timing of Renal Support and Outcome of Septic Shock and Acute Respiratory Distress Syndrome. A Post Hoc Analysis of the AKIKI Randomized Clinical Trial.” American journal of respiratory and critical care medicine (2018). PMID: 29351007 ↗
L2RCTCited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [12]
Mueller MM, Van Remoortel H, Meybohm P et al.. “Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference.” JAMA (2019). PMID: 30860564 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, History and Evolution of Treatment - [13]
Menon K, Schlapbach LJ, Akech S et al.. “Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce.” Critical care medicine (2022). PMID: 34612847 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First) - [14]
Stevenson EK, Rubenstein AR, Radin GT et al.. “Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*.” Critical care medicine (2014). PMID: 24201173 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine - [15]
Sato R, Kuriyama A. “Venoarterial Extracorporeal Membranous Oxygenation: Treatment Option for Sepsis-Induced Cardiogenic Shock? A Systematic Review.” Critical care medicine (2020). PMID: 32697514 ↗
L2SR_OBSCited in: Definition, Classification & Shock-Physiology Spine - [16]
Weiss SL, Peters MJ, Oczkowski SJW et al.. “Surviving Sepsis Campaign International Guidelines for the Management of Sepsis and Septic Shock in Children 2026.” Intensive care medicine (2026). PMID: 41870559 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine, Acute Resuscitation & Time-Critical Management - [17]
Pettilä V, Hjortrup PB, Jakob SM et al.. “Control groups in recent septic shock trials: a systematic review.” Intensive care medicine (2016). PMID: 27448676 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First) - [18]
Barbar SD, Clere-Jehl R, Bourredjem A et al.. “Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.” The New England journal of medicine (2018). PMID: 30304656 ↗
L1RCTCited in: Definition, Classification & Shock-Physiology Spine, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [19]
Fujii T, Luethi N, Young PJ et al.. “Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial.” JAMA (2020). PMID: 31950979 ↗
L1RCTCited in: Definition, Classification & Shock-Physiology Spine, Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [20]
Shankar-Hari M, Phillips GS, Levy ML et al.. “Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).” JAMA (2016). PMID: 26903336 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [21]
Annane D, Bellissant E, Bollaert PE et al.. “Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review.” JAMA (2009). PMID: 19509383 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine - [22]
Reyes LF, Garcia E, Ibáñez-Prada ED et al.. “Impact of macrolide treatment on long-term mortality in patients admitted to the ICU due to CAP: a targeted maximum likelihood estimation and survival analysis.” Critical care (London, England) (2023). PMID: 37259125 ↗
L3RCTCited in: Definition, Classification & Shock-Physiology Spine, Definitive Therapy & Source Control of the Inciting Insult, Special Populations - [23]
Wirz Y, Meier MA, Bouadma L et al.. “Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials.” Critical care (London, England) (2018). PMID: 30111341 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores) - [24]
Vincent JL, Jones G, David S et al.. “Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis.” Critical care (London, England) (2019). PMID: 31151462 ↗
L2SR_OBSCited in: Definition, Classification & Shock-Physiology Spine - [25]
Xu JY, Chen QH, Xie JF et al.. “Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.” Critical care (London, England) (2014). PMID: 25499187 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine - [26]
Raschke RA, Garcia-Orr R. “Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults.” Chest (2011). PMID: 21737492 ↗
L4CASE_REPORTCited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First) - [27]
Woolum JA, Abner EL, Kelly A et al.. “Effect of Thiamine Administration on Lactate Clearance and Mortality in Patients With Septic Shock.” Critical care medicine (2018). PMID: 30028362 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First) - [28]
Shen Y, Zhang W, Lin K et al.. “Blood pressure response index trajectories identify distinct hemodynamic phenotypes and predict mortality in septic shock: a two-database retrospective cohort study.” Critical care (London, England) (2026). PMID: 42057084 ↗
L2COHORTCited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores), Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Special Populations - [29]
Imaeda T, Oami T, Yokoyama T et al.. “Epidemiology and outcomes of septic shock in Japan: a nationwide retrospective cohort study from a medical claims database by the Japan Sepsis Alliance (JaSA) study group.” Critical care (London, England) (2025). PMID: 40671140 ↗
L2COHORTCited in: Definition, Classification & Shock-Physiology Spine, Special Populations - [30]
Wong HR, Cvijanovich NZ, Anas N et al.. “Developing a clinically feasible personalized medicine approach to pediatric septic shock.” American journal of respiratory and critical care medicine (2015). PMID: 25489881 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine - [31]
Wong HR, Cvijanovich NZ, Anas N et al.. “Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP.” American journal of respiratory and critical care medicine (2017). PMID: 28324661 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine, Pathophysiology & Mechanism - [32]
Muszynski JA, Nofziger R, Moore-Clingenpeel M et al.. “Early Immune Function and Duration of Organ Dysfunction in Critically III Children with Sepsis.” American journal of respiratory and critical care medicine (2018). PMID: 29470918 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine - [33]
Weiss SL, Peters MJ, Oczkowski SJW et al.. “Surviving Sepsis Campaign International Guidelines for the Management of Sepsis and Septic Shock in Children 2026.” Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies (2026). PMID: 41869844 ↗
L1GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, Acute Resuscitation & Time-Critical Management - [34]
Scicluna BP, Cano-Gamez K, Burnham KL et al.. “A consensus blood transcriptomic framework for sepsis.” Nature medicine (2025). PMID: 41028542 ↗
L2GUIDELINECited in: Definition, Classification & Shock-Physiology Spine, Severity Scoring & Risk Stratification (ICU Scores) - [35]
Radulescu SM, Prizeman-Green S, Seth S et al.. “Prevalence and representation of comorbidities and multimorbidity in randomised controlled trials in sepsis or septic shock: a systematic review.” Critical care (London, England) (2026). PMID: 42092974 ↗
L1SR_MA_RCTCited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors - [36]
Cuenca JA, Manjappachar NK, Ramírez CM et al.. “Outcomes and Predictors of 28-Day Mortality in Patients With Solid Tumors and Septic Shock Defined by Third International Consensus Definitions for Sepsis and Septic Shock Criteria.” Chest (2022). PMID: 35644244 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [37]
Murphy CV, Schramm GE, Doherty JA et al.. “The importance of fluid management in acute lung injury secondary to septic shock.” Chest (2009). PMID: 19318675 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine - [38]
Otero RM, Nguyen HB, Huang DT et al.. “Early goal-directed therapy in severe sepsis and septic shock revisited: concepts, controversies, and contemporary findings.” Chest (2006). PMID: 17099041 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Shock-Physiology Spine, Clinical Presentation, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [39]
Dugar S, Sato R, Chawla S et al.. “Is Left Ventricular Systolic Dysfunction Associated With Increased Mortality Among Patients With Sepsis and Septic Shock?” Chest (2023). PMID: 36646415 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine - [40]
Hammond NE, Kumar A, Kaur P et al.. “Estimates of Sepsis Prevalence and Outcomes in Adult Patients in the ICU in India: A Cross-sectional Study.” Chest (2022). PMID: 35092747 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine, Definitive Therapy & Source Control of the Inciting Insult - [41]
Singh G, Bhaskar V, Batra P et al.. “Dopamine versus epinephrine for neonatal septic shock: an open labeled, randomized controlled trial.” Journal of perinatology : official journal of the California Perinatal Association (2025). PMID: 40877444 ↗
L1RCTCited in: Definition, Classification & Shock-Physiology Spine - [42]
Eaton TL, Danesh V, Jones AC et al.. “Clinician and Patient Responses to US Health Insurers' Policies: A Qualitative Study of Higher Risk Patients.” Health services research (2025). PMID: 40275640 ↗
L5RCTCited in: Definition, Classification & Shock-Physiology Spine - [43]
Cecconi M, Evans L, Levy M et al.. “Sepsis and septic shock.” Lancet (London, England) (2018). PMID: 29937192 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First) - [44]
Singer M, Deutschman CS, Seymour CW et al.. “The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).” JAMA (2016). PMID: 26903338 ↗
L1OTHERCited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [45]
Schlapbach LJ, Watson RS, Sorce LR et al.. “International Consensus Criteria for Pediatric Sepsis and Septic Shock.” JAMA (2024). PMID: 38245889 ↗
L1OTHERCited in: Definition, Classification & Shock-Physiology Spine, Diagnosis & Workup (Hemodynamic & Bedside-First) - [46]
Seymour CW, Liu VX, Iwashyna TJ et al.. “Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).” JAMA (2016). PMID: 26903335 ↗
L2OTHERCited in: Definition, Classification & Shock-Physiology Spine, Severity Scoring & Risk Stratification (ICU Scores) - [47]
Andriolo BN, Andriolo RB, Salomão R et al.. “Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock.” The Cochrane database of systematic reviews (2017). PMID: 28099689 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine, Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Definitive Therapy & Source Control of the Inciting Insult - [48]
Corley A, Rickard CM, Aitken LM et al.. “High-flow nasal cannulae for respiratory support in adult intensive care patients.” The Cochrane database of systematic reviews (2017). PMID: 28555461 ↗
L1SR_OBSCited in: Definition, Classification & Shock-Physiology Spine, Complications & Iatrogenesis - [49]
Lajoye Q, Orieux A, Boyer A et al.. “Vasopressin and its analogues in patients with septic shock: holy Grail or unfulfilled promise?” Critical care (London, England) (2025). PMID: 40731360 ↗
L5REVIEW_NARRATIVECited in: Definition, Classification & Shock-Physiology Spine, Acute Resuscitation & Time-Critical Management - [50]
Bruno RR, Wollborn J, Fengler K et al.. “Direct assessment of microcirculation in shock: a randomized-controlled multicenter study.” Intensive care medicine (2023). PMID: 37278760 ↗
L1RCTCited in: Pathophysiology & Mechanism, Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment - [51]
Cohen J, Blumenthal A, Cuellar-Partida G et al.. “The relationship between adrenocortical candidate gene expression and clinical response to hydrocortisone in patients with septic shock.” Intensive care medicine (2021). PMID: 34185116 ↗
L2RCTCited in: Pathophysiology & Mechanism - [52]
Legrand M, Jullien E, Kimmoun A et al.. “Iloprost for the Treatment of Severe Septic Shock with Persistent Hypoperfusion: A Double-Blind, Randomized Controlled Trial.” American journal of respiratory and critical care medicine (2025). PMID: 40387381 ↗
L1RCTCited in: Pathophysiology & Mechanism, Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [53]
Meyer NJ, Ferguson JF, Feng R et al.. “A functional synonymous coding variant in the IL1RN gene is associated with survival in septic shock.” American journal of respiratory and critical care medicine (2014). PMID: 25089931 ↗
L2RCTCited in: Pathophysiology & Mechanism - [54]
Boerma EC, Kuiper MA, Kingma WP et al.. “Disparity between skin perfusion and sublingual microcirculatory alterations in severe sepsis and septic shock: a prospective observational study.” Intensive care medicine (2008). PMID: 18317733 ↗
L2TRIAL_NONRANDOMCited in: Pathophysiology & Mechanism - [55]
Patel JJ, Willoughby R, Peterson J et al.. “High-Dose IV Hydroxocobalamin (Vitamin B12) in Septic Shock: A Double-Blind, Allocation-Concealed, Placebo-Controlled Single-Center Pilot Randomized Controlled Trial (The Intravenous Hydroxocobalamin in Septic Shock Trial).” Chest (2022). PMID: 36174744 ↗
L1RCTCited in: Pathophysiology & Mechanism, Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [56]
Biesalski HK, McGregor GP. “Antioxidant therapy in critical care--is the microcirculation the primary target?” Critical care medicine (2007). PMID: 17713412 ↗
L5SR_OBSCited in: Pathophysiology & Mechanism - [57]
Jacquet-Lagrèze M, Pernollet A, Kattan E et al.. “Prognostic value of capillary refill time in adult patients: a systematic review with meta-analysis.” Critical care (London, England) (2023). PMID: 38042855 ↗
L2SR_OBSCited in: Pathophysiology & Mechanism - [58]
De Backer D, Deutschman CS, Hellman J et al.. “Surviving Sepsis Campaign Research Priorities 2023.” Critical care medicine (2024). PMID: 38240508 ↗
L5OTHERCited in: Pathophysiology & Mechanism, Acute Resuscitation & Time-Critical Management - [59]
Rudiger A. “Beta-block the septic heart.” Critical care medicine (2010). PMID: 21164404 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [60]
Sathianathan S, Sachar S, Berro J et al.. “Vasoactive Medications and the Microcirculation in Septic Shock: A Scoping Review.” Critical care medicine (2026). PMID: 41528192 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [61]
Barrett LK, Singer M, Clapp LH. “Vasopressin: mechanisms of action on the vasculature in health and in septic shock.” Critical care medicine (2007). PMID: 17133186 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [62]
Funk DJ, Jacobsohn E, Kumar A. “Role of the venous return in critical illness and shock: part II-shock and mechanical ventilation.” Critical care medicine (2013). PMID: 23263572 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [63]
Takahashi N, Campbell KR, Nakada TA et al.. “Decreased Clearance of Low-Density Lipoprotein Cholesterol is Causally Associated With Increased Mortality of Septic Shock.” Critical care medicine (2025). PMID: 40758386 ↗
L2OTHERCited in: Pathophysiology & Mechanism - [64]
Tachon G, Harrois A, Tanaka S et al.. “Microcirculatory alterations in traumatic hemorrhagic shock.” Critical care medicine (2014). PMID: 24561562 ↗
L2OTHERCited in: Pathophysiology & Mechanism - [65]
Fang X, Tang W, Sun S et al.. “Comparison of buccal microcirculation between septic and hemorrhagic shock.” Critical care medicine (2006). PMID: 17114976 ↗
L5OTHERCited in: Pathophysiology & Mechanism - [66]
Russell JA. “Vasopressor therapy in critically ill patients with shock.” Intensive care medicine (2019). PMID: 31646370 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management - [67]
Ait-Oufella H, Lemoinne S, Boelle PY et al.. “Mottling score predicts survival in septic shock.” Intensive care medicine (2011). PMID: 21373821 ↗
L2OTHERCited in: Pathophysiology & Mechanism, Diagnosis & Workup (Hemodynamic & Bedside-First), Severity Scoring & Risk Stratification (ICU Scores), Acute Resuscitation & Time-Critical Management, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation), Special Populations - [68]
De Backer D, Cecconi M, Lipman J et al.. “Challenges in the management of septic shock: a narrative review.” Intensive care medicine (2019). PMID: 30741328 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [69]
Karvunidis T, Chvojka J, Lysak D et al.. “Septic shock and chemotherapy-induced cytopenia: effects on microcirculation.” Intensive care medicine (2012). PMID: 22584795 ↗
L2OTHERCited in: Pathophysiology & Mechanism - [70]
Lange M, Ertmer C, Westphal M. “Vasopressin vs. terlipressin in the treatment of cardiovascular failure in sepsis.” Intensive care medicine (2007). PMID: 18066524 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [71]
Polito A, Lorin de la Grandmaison G, Mansart A et al.. “Human and experimental septic shock are characterized by depletion of lipid droplets in the adrenals.” Intensive care medicine (2010). PMID: 20665002 ↗
L3OTHERCited in: Pathophysiology & Mechanism - [72]
Cartwright N, Murch O, McMaster SK et al.. “Selective NOD1 agonists cause shock and organ injury/dysfunction in vivo.” American journal of respiratory and critical care medicine (2007). PMID: 17234906 ↗
L5OTHERCited in: Pathophysiology & Mechanism - [73]
Sherer K, Li Y, Cui X et al.. “Lethal and edema toxins in the pathogenesis of Bacillus anthracis septic shock: implications for therapy.” American journal of respiratory and critical care medicine (2006). PMID: 17095744 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [74]
Stolk RF, van der Poll T, Angus DC et al.. “Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis.” American journal of respiratory and critical care medicine (2016). PMID: 27398737 ↗
L5OTHERCited in: Pathophysiology & Mechanism, Acute Resuscitation & Time-Critical Management - [75]
Maiden MJ, Otto S, Brealey JK et al.. “Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study.” American journal of respiratory and critical care medicine (2016). PMID: 26967568 ↗
L5OTHERCited in: Pathophysiology & Mechanism, Diagnosis & Workup (Hemodynamic & Bedside-First) - [76]
Kapoor A, Shintani Y, Collino M et al.. “Protective role of peroxisome proliferator-activated receptor-β/δ in septic shock.” American journal of respiratory and critical care medicine (2010). PMID: 20693380 ↗
L5OTHERCited in: Pathophysiology & Mechanism - [77]
Wang Z, Su F, Bruhn A et al.. “Acute hypercapnia improves indices of tissue oxygenation more than dobutamine in septic shock.” American journal of respiratory and critical care medicine (2007). PMID: 17947612 ↗
L5OTHERCited in: Pathophysiology & Mechanism, Diagnosis & Workup (Hemodynamic & Bedside-First) - [78]
Chaudhuri D, Herritt B, Lewis K et al.. “Dosing Fluids in Early Septic Shock.” Chest (2020). PMID: 33058814 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [79]
Hollenberg SM. “Vasopressor support in septic shock.” Chest (2007). PMID: 17998371 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Acute Resuscitation & Time-Critical Management - [80]
Ferhat Y, Serkan Y, Ulaş Öİ et al.. “Peripheral Perfusion vs Standard Management in Sepsis/Septic Shock: A Prospective Randomized ED Study.” The American journal of emergency medicine (2025). PMID: 41033063 ↗
L1RCTCited in: Pathophysiology & Mechanism, Definitive Therapy & Source Control of the Inciting Insult - [81]
Lu S, Kattan E, Pan C et al.. “VERY EARLY USE OF ESMOLOL IN HYPERKINETIC SEPTIC SHOCK PATIENTS WITH PERSISTENT TACHYCARDIA: A RANDOMIZED CONTROLLED PILOT STUDY.” Shock (Augusta, Ga.) (2025). PMID: 40101954 ↗
L1RCTCited in: Pathophysiology & Mechanism, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [82]
Cusack RAF, Rodríguez A, Cantan B et al.. “Microcirculation properties of 20 % albumin in sepsis; a randomised controlled trial.” Journal of critical care (2025). PMID: 40020556 ↗
L1RCTCited in: Pathophysiology & Mechanism - [83]
Luo JC, Ma L, Luo MH et al.. “Early Methylene Blue for Mortality Reduction in High-Dose VasoPREssor-Dependent Septic Shock (EMPRESS): protocol for a multicenter randomized controlled trial.” Scandinavian journal of trauma, resuscitation and emergency medicine (2026). PMID: 41580807 ↗
L5TRIAL_NONRANDOMCited in: Pathophysiology & Mechanism, Acute Resuscitation & Time-Critical Management - [84]
Vignon P, Léger J, Evrard B et al.. “Adjunctive dobutamine in patients with septic cardiomyopathy and tissue hypoperfusion: a blinded randomised controlled multicentre trial study protocol of the ADAPT-dobutamine trial.” BMJ open (2025). PMID: 40588393 ↗
L5TRIAL_NONRANDOMCited in: Pathophysiology & Mechanism - [85]
Christensen J, Sivapalan P, Meyhoff TS et al.. “Restrictive Versus Standard Intravenous Fluid Therapy and Endothelial Glycocalyx Shedding in ICU Patients With Septic Shock-A Preplanned Sub-Study of the Randomized CLASSIC Trial.” Acta anaesthesiologica Scandinavica (2026). PMID: 41321198 ↗
L1RCTCited in: Pathophysiology & Mechanism - [86]
Calabrò LA, Pasetto M, Scolletta S et al.. “Ivabradine use in critical care: a systematic review and metanalysis of cardiogenic and septic shock patients.” BMC anesthesiology (2025). PMID: 40448257 ↗
L5SR_OBSCited in: Pathophysiology & Mechanism - [87]
Zhang X, Zhang H, Jin R et al.. “Assessment of Sublingual Microcirculation to Evaluate the Efficacy of Resuscitation Therapy in Septic Shock Patients: A Cohort Study.” Shock (Augusta, Ga.) (2025). PMID: 41031817 ↗
L2COHORTCited in: Pathophysiology & Mechanism - [88]
Lambden S, Creagh-Brown BC, Hunt J et al.. “Definitions and pathophysiology of vasoplegic shock.” Critical care (London, England) (2018). PMID: 29980217 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [89]
Kellum JA, Ronco C. “The role of endotoxin in septic shock.” Critical care (London, England) (2023). PMID: 37858258 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Diagnosis & Workup (Hemodynamic & Bedside-First) - [90]
Levy B, Fritz C, Tahon E et al.. “Vasoplegia treatments: the past, the present, and the future.” Critical care (London, England) (2018). PMID: 29486781 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Acute Resuscitation & Time-Critical Management - [91]
Atreya MR, Huang M, Moore AR et al.. “Identification and transcriptomic assessment of latent profile pediatric septic shock phenotypes.” Critical care (London, England) (2024). PMID: 39014377 ↗
L2OTHERCited in: Pathophysiology & Mechanism - [92]
Atreya MR, Cvijanovich NZ, Fitzgerald JC et al.. “Prognostic and predictive value of endothelial dysfunction biomarkers in sepsis-associated acute kidney injury: risk-stratified analysis from a prospective observational cohort of pediatric septic shock.” Critical care (London, England) (2023). PMID: 37400882 ↗
L2OTHERCited in: Pathophysiology & Mechanism - [93]
Garcia B, Su F, Manicone F et al.. “Angiotensin 1-7 in an experimental septic shock model.” Critical care (London, England) (2023). PMID: 36915144 ↗
L5OTHERCited in: Pathophysiology & Mechanism - [94]
Ronco C, Klein DJ. “Polymyxin B hemoperfusion: a mechanistic perspective.” Critical care (London, England) (2014). PMID: 25043934 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism - [95]
Picod A, Azibani F, Harjola VP et al.. “Targeting high circulating dipeptidyl peptidase 3 in circulatory failure.” Critical care (London, England) (2025). PMID: 40745610 ↗
L5REVIEW_NARRATIVECited in: Pathophysiology & Mechanism, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [96]
Chen JJ, Lai PC, Lee TH et al.. “Blood Purification for Adult Patients With Severe Infection or Sepsis/Septic Shock: A Network Meta-Analysis of Randomized Controlled Trials.” Critical care medicine (2023). PMID: 37470680 ↗
L1SR_MA_RCTCited in: Epidemiology, Etiology & Risk Factors, Special Populations - [97]
Pettilä V, Pfortmüller CA, Perner A et al.. “Targeted Tissue Perfusion Versus Macrocirculatory-Guided Standard Care in Patients With Septic Shock: A Randomized Clinical Trial-The TARTARE-2S Trial.” Critical care medicine (2025). PMID: 41105050 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [98]
Monti G, Carta S, Kotani Y et al.. “A Multinational Randomized Trial of Mega-Dose Esomeprazole as Anti-Inflammatory Agent in Sepsis.” Critical care medicine (2025). PMID: 40439536 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Special Populations - [99]
Shah S, Kaul A, Shiwarkar G et al.. “Fifth Centile Versus 50th Centile Mean Blood Pressure Targets in Pediatric Septic Shock: A Randomized Controlled Trial.” Critical care medicine (2025). PMID: 40511998 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [100]
Endo A, Yamakawa K, Tagami T et al.. “Efficacy of targeting high mean arterial pressure for older patients with septic shock (OPTPRESS): a multicentre, pragmatic, open-label, randomised controlled trial.” Intensive care medicine (2025). PMID: 40358717 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management, Special Populations - [101]
Myburgh JA, Higgins A, Jovanovska A et al.. “A comparison of epinephrine and norepinephrine in critically ill patients.” Intensive care medicine (2008). PMID: 18654759 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [102]
Walsham J, Hammond N, Blumenthal A et al.. “Fludrocortisone dose-response relationship in septic shock: a randomised phase II trial.” Intensive care medicine (2024). PMID: 39235623 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Special Populations - [103]
Shehabi Y, Sterba M, Garrett PM et al.. “Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. A randomized controlled trial.” American journal of respiratory and critical care medicine (2014). PMID: 25295709 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Special Populations - [104]
Nobre V, Harbarth S, Graf JD et al.. “Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial.” American journal of respiratory and critical care medicine (2007). PMID: 18096708 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Special Populations - [105]
Schmidt EP, Overdier KH, Sun X et al.. “Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome.” American journal of respiratory and critical care medicine (2016). PMID: 26926297 ↗
L2TRIAL_NONRANDOMCited in: Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores), Special Populations - [106]
Peake SL, Delaney A, Bailey M et al.. “Goal-directed resuscitation for patients with early septic shock.” The New England journal of medicine (2014). PMID: 25272316 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Special Populations - [107]
Holst LB, Haase N, Wetterslev J et al.. “Lower versus higher hemoglobin threshold for transfusion in septic shock.” The New England journal of medicine (2014). PMID: 25270275 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Special Populations - [108]
Hernández G, Ospina-Tascón GA, Damiani LP et al.. “Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial.” JAMA (2019). PMID: 30772908 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Severity Scoring & Risk Stratification (ICU Scores), Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [109]
Gordon AC, Mason AJ, Thirunavukkarasu N et al.. “Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial.” JAMA (2016). PMID: 27483065 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Complications & Iatrogenesis, Special Populations - [110]
Morelli A, Ertmer C, Westphal M et al.. “Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial.” JAMA (2013). PMID: 24108526 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [111]
Keh D, Trips E, Marx G et al.. “Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.” JAMA (2016). PMID: 27695824 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS), Special Populations - [112]
Schmidt K, Worrack S, Von Korff M et al.. “Effect of a Primary Care Management Intervention on Mental Health-Related Quality of Life Among Survivors of Sepsis: A Randomized Clinical Trial.” JAMA (2016). PMID: 27367877 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [113]
Blot S, Antonelli M, Arvaniti K et al.. “Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project.” Intensive care medicine (2019). PMID: 31664501 ↗
L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Special Populations - [114]
Martin-Loeches I, Reyes LF, Nseir S et al.. “European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.” Intensive care medicine (2023). PMID: 37812242 ↗
L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Complications & Iatrogenesis - [115]
Klein Klouwenberg PM, Frencken JF, Kuipers S et al.. “Incidence, Predictors, and Outcomes of New-Onset Atrial Fibrillation in Critically Ill Patients with Sepsis. A Cohort Study.” American journal of respiratory and critical care medicine (2017). PMID: 27467907 ↗
L2COHORTCited in: Epidemiology, Etiology & Risk Factors, Special Populations - [116]
Abdul-Aziz MH, Hammond NE, Brett SJ et al.. “Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis.” JAMA (2024). PMID: 38864162 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors - [117]
Ortiz-Reyes L, Patel JJ, Jiang X et al.. “Early versus delayed enteral nutrition in mechanically ventilated patients with circulatory shock: a nested cohort analysis of an international multicenter, pragmatic clinical trial.” Critical care (London, England) (2022). PMID: 35681220 ↗
L2RCTCited in: Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [118]
Vandervelden S, Cortens B, Fieuws S et al.. “Early administration of vitamin C in patients with sepsis or septic shock in emergency departments: a multicenter, double-blind, randomized controlled trial: the C-EASIE trial.” Critical care (London, England) (2025). PMID: 40269974 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [119]
Boulet N, Quenot JP, Serrand C et al.. “Impact on fluid balance of an optimized restrictive strategy targeting non-resuscitative fluids in intensive care patients with septic shock: a single-blind, multicenter, randomized, controlled, pilot study.” Critical care (London, England) (2024). PMID: 39709493 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [120]
Roggeveen LF, Guo T, Fleuren LM et al.. “Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock-a two-centre randomised clinical trial.” Critical care (London, England) (2022). PMID: 36064438 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment - [121]
Chappell MC, Schaich CL, Busse LW et al.. “Stronger association of intact angiotensinogen with mortality than lactate or renin in critical illness: post-hoc analysis from the VICTAS trial.” Critical care (London, England) (2024). PMID: 39402593 ↗
L2RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation), Special Populations - [122]
Shi R, Braïk R, Monnet X et al.. “Early norepinephrine for patients with septic shock: an updated systematic review and meta-analysis with trial sequential analysis.” Critical care (London, England) (2025). PMID: 40329359 ↗
L2SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [123]
Xie J, Wang H, Kang Y et al.. “The Epidemiology of Sepsis in Chinese ICUs: A National Cross-Sectional Survey.” Critical care medicine (2020). PMID: 31804299 ↗
L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Special Populations - [124]
Leligdowicz A, Dodek PM, Norena M et al.. “Association between source of infection and hospital mortality in patients who have septic shock.” American journal of respiratory and critical care medicine (2014). PMID: 24635548 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Special Populations - [125]
Miller RR, Dong L, Nelson NC et al.. “Multicenter implementation of a severe sepsis and septic shock treatment bundle.” American journal of respiratory and critical care medicine (2013). PMID: 23631750 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores), Special Populations - [126]
Mickiewicz B, Vogel HJ, Wong HR et al.. “Metabolomics as a novel approach for early diagnosis of pediatric septic shock and its mortality.” American journal of respiratory and critical care medicine (2013). PMID: 23471468 ↗
L3OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [127]
Lac J, Han S, Ahmad M et al.. “Low-dose corticosteroids in severe pulmonary infection: a meta-analysis of randomised controlled trials.” BMJ open respiratory research (2026). PMID: 42425738 ↗
L1SR_MA_RCTCited in: Epidemiology, Etiology & Risk Factors - [128]
Nguyen N, Tran NB, de Barros E Lyra NA et al.. “Conservative Oxygen Targets in Mechanically Ventilated Patients (OXY-BREATHES): A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Critical care medicine (2026). PMID: 41661051 ↗
L1SR_MA_RCTCited in: Epidemiology, Etiology & Risk Factors - [129]
Lanspa MJ, Cirulis MM, Wiley BM et al.. “Right Ventricular Dysfunction in Early Sepsis and Septic Shock.” Chest (2020). PMID: 33068615 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Severity Scoring & Risk Stratification (ICU Scores), Acute Resuscitation & Time-Critical Management - [130]
Marik PE, Khangoora V, Rivera R et al.. “Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study.” Chest (2016). PMID: 27940189 ↗
L4OTHERCited in: Epidemiology, Etiology & Risk Factors, Acute Resuscitation & Time-Critical Management, Special Populations - [131]
John S, Eckardt KU. “Renal replacement strategies in the ICU.” Chest (2007). PMID: 17934125 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Special Populations - [132]
Canet E, Zafrani L, Azoulay É. “The Critically Ill Kidney Transplant Recipient: A Narrative Review.” Chest (2016). PMID: 26836919 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors - [133]
Chockalingam A, Mehra A, Dorairajan S et al.. “Acute left ventricular dysfunction in the critically ill.” Chest (2010). PMID: 20605820 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Definitive Therapy & Source Control of the Inciting Insult, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [134]
Grasselli G, Scaravilli V, Mangioni D et al.. “Hospital-Acquired Infections in Critically Ill Patients With COVID-19.” Chest (2021). PMID: 33857475 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Complications & Iatrogenesis, Special Populations - [135]
Serrano-Mayorga CC, Olivella-Gomez J, Sanabria-Herrera N et al.. “Pseudomonas aeruginosa in Patients With Nosocomial Respiratory Infections: A Secondary Analysis of the European Network for ICU-Related Respiratory Infections.” Chest (2026). PMID: 41520818 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Complications & Iatrogenesis, Special Populations - [136]
Sakr Y, Nierhaus A, Schumacher U et al.. “Albumin Replacement Therapy in Septic Shock: A Randomized Clinical Trial.” JAMA network open (2026). PMID: 41712212 ↗
L1RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Special Populations - [137]
Meng L, Liu J, Wang P et al.. “Risk factors of sepsis-associated encephalopathy in sepsis patients with pulmonary infection: from the secondary analysis of a cluster-randomized controlled trial.” Respiratory medicine (2026). PMID: 41570945 ↗
L2RCTCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation), Special Populations - [138]
Kalimouttou A, Kennedy JN, Feng J et al.. “Optimal Vasopressin Initiation in Septic Shock: The OVISS Reinforcement Learning Study.” JAMA (2025). PMID: 40098600 ↗
L2OTHERCited in: Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores), Acute Resuscitation & Time-Critical Management, Special Populations - [139]
Zampieri FG, Bagshaw SM, Semler MW. “Fluid Therapy for Critically Ill Adults With Sepsis: A Review.” JAMA (2023). PMID: 37314271 ↗
L5REVIEW_NARRATIVECited in: Epidemiology, Etiology & Risk Factors, Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [140]
Fu Y, Wang T, Lu R et al.. “Red blood cell transfusion in neurocritical patients: an updated systematic review and meta-analysis.” BMC anesthesiology (2026). PMID: 41918075 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [141]
Guvenc KB, Sahin EG, Yılmaz IA et al.. “Early hematologic cellular effects of IgM-enriched intravenous immunoglobulin in pediatric sepsis: a retrospective cohort study.” European journal of pediatrics (2026). PMID: 41984212 ↗
L4COHORTCited in: Epidemiology, Etiology & Risk Factors - [142]
Borthwick EM, Hill CJ, Rabindranath KS et al.. “High-volume haemofiltration for sepsis in adults.” The Cochrane database of systematic reviews (2017). PMID: 28141912 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors - [143]
Borthwick EM, Hill CJ, Rabindranath KS et al.. “High-volume haemofiltration for sepsis.” The Cochrane database of systematic reviews (2013). PMID: 23440825 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Definitive Therapy & Source Control of the Inciting Insult - [144]
Bruder EA, Ball IM, Ridi S et al.. “Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients.” The Cochrane database of systematic reviews (2015). PMID: 25568981 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors, Severity Scoring & Risk Stratification (ICU Scores) - [145]
Delgado Moya FP, Antequera A, Muriel A et al.. “Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children.” The Cochrane database of systematic reviews (2026). PMID: 42011817 ↗
L1SR_OBSCited in: Epidemiology, Etiology & Risk Factors - [146]
Rivers EP, Kruse JA, Jacobsen G et al.. “The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock.” Critical care medicine (2007). PMID: 17855815 ↗
L1RCTCited in: Clinical Presentation - [147]
Contou D, Sonneville R, Canoui-Poitrine F et al.. “Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study.” Intensive care medicine (2018). PMID: 30128591 ↗
L2COHORTCited in: Clinical Presentation - [148]
Saiyed A, Datta D. “A Middle-Aged Woman With Hematochezia, Hypotension, and Leg Cramps.” Chest (2020). PMID: 32654734 ↗
L4CASE_REPORTCited in: Clinical Presentation - [149]
Dellinger RP, Levy MM, Carlet JM et al.. “Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.” Critical care medicine (2008). PMID: 18158437 ↗
L1OTHERCited in: Clinical Presentation - [150]
Yang Y, Guo F, Zhao W et al.. “Novel avian-origin influenza A (H7N9) in critically ill patients in China*.” Critical care medicine (2015). PMID: 25365721 ↗
L2OTHERCited in: Clinical Presentation - [151]
Wong HR, Cvijanovich N, Allen GL et al.. “Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum.” Critical care medicine (2009). PMID: 19325468 ↗
L2OTHERCited in: Clinical Presentation - [152]
Boyd JH, Forbes J, Nakada TA et al.. “Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality.” Critical care medicine (2011). PMID: 20975548 ↗
L3OTHERCited in: Clinical Presentation - [153]
Capp R, Horton CL, Takhar SS et al.. “Predictors of patients who present to the emergency department with sepsis and progress to septic shock between 4 and 48 hours of emergency department arrival.” Critical care medicine (2015). PMID: 25668750 ↗
L3OTHERCited in: Clinical Presentation - [154]
Deep A, Sagar H, Goonasekera C et al.. “Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.” Critical care medicine (2018). PMID: 29677008 ↗
L2OTHERCited in: Clinical Presentation - [155]
Merdji H, Long MT, Ostermann M et al.. “Sex and gender differences in intensive care medicine.” Intensive care medicine (2023). PMID: 37676504 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS), Prevention, Screening and Post-ICU Surveillance - [156]
Deep A, Goonasekera CD, Wang Y et al.. “Evolution of haemodynamics and outcome of fluid-refractory septic shock in children.” Intensive care medicine (2013). PMID: 23812341 ↗
L2OTHERCited in: Clinical Presentation - [157]
Bassetti M, Peghin M, Carnelutti A et al.. “Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study.” Intensive care medicine (2017). PMID: 28271321 ↗
L3OTHERCited in: Clinical Presentation, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [158]
Dellinger RP, Levy MM, Carlet JM et al.. “Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.” Intensive care medicine (2007). PMID: 18058085 ↗
L1OTHERCited in: Clinical Presentation - [159]
Bisarya R, Song X, Salle J et al.. “Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection.” Chest (2021). PMID: 34186038 ↗
L3OTHERCited in: Clinical Presentation - [160]
Dremsizov T, Clermont G, Kellum JA et al.. “Severe sepsis in community-acquired pneumonia: when does it happen, and do systemic inflammatory response syndrome criteria help predict course?” Chest (2006). PMID: 16608946 ↗
L3OTHERCited in: Clinical Presentation - [161]
Self WH, Grijalva CG, Williams DJ et al.. “Procalcitonin as an Early Marker of the Need for Invasive Respiratory or Vasopressor Support in Adults With Community-Acquired Pneumonia.” Chest (2016). PMID: 27107491 ↗
L2OTHERCited in: Clinical Presentation - [162]
Seymour CW, Rosengart MR. “Septic Shock: Advances in Diagnosis and Treatment.” JAMA (2015). PMID: 26284722 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation, Diagnosis & Workup (Hemodynamic & Bedside-First) - [163]
Dong J, Ouyang Y, Ni J et al.. “Development and internal validation of a clinical prediction model for septic shock in pediatric respiratory syncytial virus bronchiolitis based on routine blood biomarkers and concomitant fungal infection.” Frontiers in cellular and infection microbiology (2026). PMID: 42221582 ↗
L3TRIAL_NONRANDOMCited in: Clinical Presentation, Severity Scoring & Risk Stratification (ICU Scores) - [164]
Weiss SL, Fitzgerald JC, Laskin BL et al.. “Time Course of Kidney Injury Biomarkers in Children With Septic Shock: Nested Cohort Study Within the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis Trial.” Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies (2025). PMID: 40172287 ↗
L2TRIAL_NONRANDOMCited in: Clinical Presentation - [165]
Imamura M, Duggan SN, Vadiveloo T et al.. “Clinical utility of biomarkers for outcomes prediction in adults with suspected sepsis presenting to the emergency department: a synthesis of current evidence.” Health technology assessment (Winchester, England) (2026). PMID: 41912331 ↗
L5SR_OBSCited in: Clinical Presentation - [166]
Jung RG, Gupta A, Stotts C et al.. “Prognostic factors associated with mortality in septic shock: a systematic review and meta-analysis.” The Lancet. Respiratory medicine (2026). PMID: 41619747 ↗
L1SR_OBSCited in: Clinical Presentation, Diagnosis & Workup (Hemodynamic & Bedside-First) - [167]
Guarino M, Maroncelli G, Perna B et al.. “Comparison of four noninvasive tools for predicting sepsis and septic shock mortality: a prospective cohort study.” Clinical and experimental emergency medicine (2025). PMID: 41327979 ↗
L2COHORTCited in: Clinical Presentation - [168]
Coston TD, Wright SW, Hantrakun V et al.. “Pre-Referral Antibiotics and Mortality Among Adults With Sepsis in Southeast Asia: A Secondary Analysis of a Prospective Cohort Study.” Critical care medicine (2025). PMID: 41196125 ↗
L2COHORTCited in: Clinical Presentation - [169]
Bavaro DF, Diella L, De Angelis A et al.. “Why do echinocandins fail? Identifying key predictors to improve clinical outcomes of candida bloodstream infections: a retrospective multicenter cohort study.” International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (2025). PMID: 40912531 ↗
L3COHORTCited in: Clinical Presentation - [170]
Siddiqui S, Razzak J. “Early versus late pre-intensive care unit admission broad spectrum antibiotics for severe sepsis in adults.” The Cochrane database of systematic reviews (2010). PMID: 20927754 ↗
L1SR_OBSCited in: Clinical Presentation - [171]
. “36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.” Critical care (London, England) (2016). PMID: 27885969 ↗
L5OTHERCited in: Clinical Presentation - [172]
Leligdowicz A, Fischer WA, Uyeki TM et al.. “Ebola virus disease and critical illness.” Critical care (London, England) (2016). PMID: 27468829 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation - [173]
Ho BC, Bellomo R, McGain F et al.. “The incidence and outcome of septic shock patients in the absence of early-goal directed therapy.” Critical care (London, England) (2006). PMID: 16704743 ↗
L3OTHERCited in: Clinical Presentation - [174]
Rivers E. “The outcome of patients presenting to the emergency department with severe sepsis or septic shock.” Critical care (London, England) (2006). PMID: 16887012 ↗
L5REVIEW_NARRATIVECited in: Clinical Presentation - [175]
Yang JO, Zinter MS, Pellegrini M et al.. “Whole blood transcriptomics identifies subclasses of pediatric septic shock.” Critical care (London, England) (2023). PMID: 38066613 ↗
L2OTHERCited in: Clinical Presentation - [176]
Marik PE. “Don't miss the diagnosis of sepsis!” Critical care (London, England) (2014). PMID: 25675360 ↗
L5OTHERCited in: Clinical Presentation - [177]
Giamarellos-Bourboulis EJ, Routsi C, Plachouras D et al.. “Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?” Critical care (London, England) (2006). PMID: 16696867 ↗
L2OTHERCited in: Clinical Presentation - [178]
Nagendran M, Russell JA, Walley KR et al.. “Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials.” Intensive care medicine (2019). PMID: 31062052 ↗
L1SR_MA_RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [179]
Almeida TML, Freitas FGR, Figueiredo RC et al.. “Acetylsalicylic Acid Treatment in Patients With Sepsis and Septic Shock: A Phase 2, Placebo-Controlled, Randomized Clinical Trial.” Critical care medicine (2025). PMID: 39982179 ↗
L1RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult, Special Populations - [180]
Permpikul C, Tongyoo S, Viarasilpa T et al.. “Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial.” American journal of respiratory and critical care medicine (2019). PMID: 30704260 ↗
L1RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [181]
Delabranche X, Boisramé-Helms J, Asfar P et al.. “Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy.” Intensive care medicine (2013). PMID: 23793890 ↗
L2TRIAL_NONRANDOMCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [182]
Hou PC, Filbin MR, Wang H et al.. “Endothelial Permeability and Hemostasis in Septic Shock: Results From the ProCESS Trial.” Chest (2017). PMID: 28109962 ↗
L2RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), History and Evolution of Treatment - [183]
Uzzan B, Cohen R, Nicolas P et al.. “Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis.” Critical care medicine (2006). PMID: 16715031 ↗
L1SR_OBSCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [184]
Shankar-Hari M, Culshaw N, Post B et al.. “Endogenous IgG hypogammaglobulinaemia in critically ill adults with sepsis: systematic review and meta-analysis.” Intensive care medicine (2015). PMID: 25971390 ↗
L1SR_OBSCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [185]
Brunkhorst FM, Engel C, Bloos F et al.. “Intensive insulin therapy and pentastarch resuscitation in severe sepsis.” The New England journal of medicine (2008). PMID: 18184958 ↗
L1RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Definitive Therapy & Source Control of the Inciting Insult, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [186]
Hernandez G, Ospina-Tascón GA, Kattan E et al.. “Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.” JAMA (2025). PMID: 41159835 ↗
L1RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [187]
Jones AE, Shapiro NI, Trzeciak S et al.. “Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.” JAMA (2010). PMID: 20179283 ↗
L1RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [188]
Fernando SM, Rochwerg B, Soliman K et al.. “Methylene Blue Administration in Septic Shock: A Retrospective Cohort Study.” Critical care medicine (2025). PMID: 41171046 ↗
L2COHORTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [189]
Rowan KM, Angus DC, Bailey M et al.. “Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.” The New England journal of medicine (2017). PMID: 28320242 ↗
L1SR_OBSCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [190]
Bréchot N, Hajage D, Kimmoun A et al.. “Venoarterial extracorporeal membrane oxygenation to rescue sepsis-induced cardiogenic shock: a retrospective, multicentre, international cohort study.” Lancet (London, England) (2020). PMID: 32828186 ↗
L2COHORTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [191]
Yanase F, Spano S, Maeda A et al.. “Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial.” Critical care (London, England) (2023). PMID: 37828547 ↗
L1RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), History and Evolution of Treatment - [192]
Lamarche-Fontaneto R, Oud L, Howell KD et al.. “Cardiac output monitors in septic shock: do they deliver what matters? A systematic review and meta-analysis.” Critical care (London, England) (2025). PMID: 40652247 ↗
L1SR_OBSCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [193]
Sacha GL, Lam SW, Wang L et al.. “Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock.” Critical care medicine (2022). PMID: 34582425 ↗
L2OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [194]
Leone M, Myatra SN, Dugar S et al.. “Clinical Criteria for the Definition of Refractory Septic Shock: A Joint Delphi Consensus from the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM).” Critical care medicine (2026). PMID: 41873857 ↗
L5OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [195]
Delaney A, Borges-Sa M, Chew MS et al.. “Current standard of care for septic shock.” Intensive care medicine (2025). PMID: 41359028 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [196]
Zampieri FG, Damiani LP, Bakker J et al.. “Effects of a Resuscitation Strategy Targeting Peripheral Perfusion Status versus Serum Lactate Levels among Patients with Septic Shock. A Bayesian Reanalysis of the ANDROMEDA-SHOCK Trial.” American journal of respiratory and critical care medicine (2020). PMID: 31574228 ↗
L2OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [197]
Annane D, Maxime V, Ibrahim F et al.. “Diagnosis of adrenal insufficiency in severe sepsis and septic shock.” American journal of respiratory and critical care medicine (2006). PMID: 16973979 ↗
L2OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [198]
Dépret F, Hollinger A, Cariou A et al.. “Incidence and Outcome of Subclinical Acute Kidney Injury Using penKid in Critically Ill Patients.” American journal of respiratory and critical care medicine (2020). PMID: 32516543 ↗
L2OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [199]
Wong HR, Cvijanovich N, Wheeler DS et al.. “Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shock.” American journal of respiratory and critical care medicine (2008). PMID: 18511707 ↗
L2OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [200]
Lichtenstein DA. “BLUE-protocol and FALLS-protocol: two applications of lung ultrasound in the critically ill.” Chest (2015). PMID: 26033127 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [201]
Sacha GL, Bauer SR. “Optimizing Vasopressin Use and Initiation Timing in Septic Shock: A Narrative Review.” Chest (2023). PMID: 37479058 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [202]
Kethireddy S, Light RB, Mirzanejad Y et al.. “Mycobacterium tuberculosis septic shock.” Chest (2013). PMID: 23429859 ↗
L3OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [203]
Seymour CW, Gesten F, Prescott HC et al.. “Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.” The New England journal of medicine (2017). PMID: 28528569 ↗
L3OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management - [204]
Sanchez-Pinto LN, Bennett TD, DeWitt PE et al.. “Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.” JAMA (2024). PMID: 38245897 ↗
L3OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [205]
Ghatak T, Pal A, Rochwerg B et al.. “The diagnostic accuracy of serum procalcitonin for sepsis in critically ill adults. A systematic review and diagnostic meta-analysis.” Journal of critical care (2025). PMID: 41421176 ↗
L1SR_OBSCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [206]
Wang Y, Chen G, Zhai N et al.. “Risk factors for 28-day mortality and pathogen characteristics of septic shock in children: a 10-year retrospective cohort study.” Frontiers in cellular and infection microbiology (2026). PMID: 42256218 ↗
L3COHORTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Complications & Iatrogenesis - [207]
Choi JW, Shin TG, Maeng SJ et al.. “Effect of norepinephrine initiation timing on mortality in septic shock: a multicenter cohort study.” BMC anesthesiology (2026). PMID: 41549241 ↗
L3COHORTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [208]
Liao D, Zhang S, Zhang J et al.. “Association of the Lactate-to-Albumin Ratio With All-Cause Mortality in Trauma and Surgical Intensive Care Patients: A Retrospective Study.” The Journal of surgical research (2025). PMID: 41411770 ↗
L3COHORTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [209]
Kuriyama A, Heels-Ansdell D, Fernando SM et al.. “Pantoprazole Use in Invasively Ventilated Patients With Septic Shock: A Protocol and Statistical Analysis Plan.” Acta anaesthesiologica Scandinavica (2026). PMID: 42186360 ↗
L5TRIAL_NONRANDOMCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Prevention, Screening and Post-ICU Surveillance - [210]
De Backer D, Cecconi M, Chew MS et al.. “A plea for personalization of the hemodynamic management of septic shock.” Critical care (London, England) (2022). PMID: 36457089 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [211]
Barichello T, Generoso JS, Singer M et al.. “Biomarkers for sepsis: more than just fever and leukocytosis-a narrative review.” Critical care (London, England) (2022). PMID: 34991675 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [212]
Nates JL, Pène F, Darmon M et al.. “Septic shock in the immunocompromised cancer patient: a narrative review.” Critical care (London, England) (2024). PMID: 39215292 ↗
L5REVIEW_NARRATIVECited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [213]
Monnet X, Lai C, Ospina-Tascon G et al.. “Evidence for a personalized early start of norepinephrine in septic shock.” Critical care (London, England) (2023). PMID: 37608327 ↗
L5OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [214]
White KC, Costa-Pinto R, Blank S et al.. “Effect of early adjunctive vasopressin initiation for septic shock patients: a target trial emulation.” Critical care (London, England) (2025). PMID: 40355911 ↗
L3OTHERCited in: Diagnosis & Workup (Hemodynamic & Bedside-First), Severity Scoring & Risk Stratification (ICU Scores), Acute Resuscitation & Time-Critical Management - [215]
Jiang H, Xie Z, Xiang J et al.. “Diagnostic Value of End-Tidal Carbon Dioxide Combined With Lactate for Early Detection of Sepsis in Prehospital Patients: A Prospective Cohort Study.” Medical science monitor : international medical journal of experimental and clinical research (2026). PMID: 41973647 ↗
L2COHORTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [216]
Jacq E, Maire F, Cucherousset J et al.. “From Cutaneous Necrosis to Septic Shock: An ICU Case of Pancreatico portal Fistula Complicating Necrotizing Acute Pancreatitis.” Critical care explorations (2026). PMID: 42390290 ↗
L4CASE_REPORTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [217]
Huang P, He SS, Feng S et al.. “Efficacy and Safety of Shenfu Injection in Patients with Septic Shock: A Randomized Controlled Open-Label Trial with Network Pharmacology-Based Mechanistic Insights.” Chinese journal of integrative medicine (2026). PMID: 41870792 ↗
L1RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [218]
Li BH, Liang ZY, Chen LL et al.. “[Application and comparative study of critical care ultrasound and noninvasive cardiac output monitoring in fluid resuscitation of neonatal septic shock: a randomized controlled trial].” Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics (2026). PMID: 41766144 ↗
L1RCTCited in: Diagnosis & Workup (Hemodynamic & Bedside-First) - [219]
Antcliffe DB, Santhakumaran S, Orme RML et al.. “Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial.” Intensive care medicine (2019). PMID: 31428804 ↗
L3RCTCited in: Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult - [220]
Pappalardo F, Crivellari M, Di Prima AL et al.. “Protein C zymogen in severe sepsis: a double-blinded, placebo-controlled, randomized study.” Intensive care medicine (2016). PMID: 27344436 ↗
L1RCTCited in: Severity Scoring & Risk Stratification (ICU Scores), Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [221]
Moreno R, Sprung CL, Annane D et al.. “Time course of organ failure in patients with septic shock treated with hydrocortisone: results of the Corticus study.” Intensive care medicine (2011). PMID: 21847649 ↗
L1RCTCited in: Severity Scoring & Risk Stratification (ICU Scores) - [222]
Masson S, Caironi P, Fanizza C et al.. “Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial.” Intensive care medicine (2014). PMID: 25319385 ↗
L3RCTCited in: Severity Scoring & Risk Stratification (ICU Scores) - [223]
Kethireddy S, Bilgili B, Sees A et al.. “Culture-Negative Septic Shock Compared With Culture-Positive Septic Shock: A Retrospective Cohort Study.” Critical care medicine (2018). PMID: 29293143 ↗
L3COHORTCited in: Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult - [224]
Barbier F, Buetti N, Dupuis C et al.. “Prognostic Impact of Early Appropriate Antimicrobial Therapy in Critically Ill Patients With Nosocomial Pneumonia Due to Gram-Negative Pathogens: A Multicenter Cohort Study.” Critical care medicine (2025). PMID: 40009040 ↗
L3COHORTCited in: Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult, Complications & Iatrogenesis - [225]
Kuipers S, Klein Klouwenberg PM, Cremer OL. “Incidence, risk factors and outcomes of new-onset atrial fibrillation in patients with sepsis: a systematic review.” Critical care (London, England) (2014). PMID: 25498795 ↗
L3SR_OBSCited in: Severity Scoring & Risk Stratification (ICU Scores) - [226]
Morgan RW, Reeder RW, Carcillo JA et al.. “Outcomes, Characteristics, and Physiology of In-Hospital Cardiac Arrest in Children With Sepsis.” Critical care medicine (2025). PMID: 40558671 ↗
L2OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [227]
Di Pasquale M, Ferrer M, Esperatti M et al.. “Assessment of severity of ICU-acquired pneumonia and association with etiology.” Critical care medicine (2014). PMID: 23989176 ↗
L2OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores), Complications & Iatrogenesis - [228]
Wong HR, Lindsell CJ, Pettilä V et al.. “A multibiomarker-based outcome risk stratification model for adult septic shock*.” Critical care medicine (2014). PMID: 24335447 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [229]
van Zanten AR, Brinkman S, Arbous MS et al.. “Guideline bundles adherence and mortality in severe sepsis and septic shock.” Critical care medicine (2014). PMID: 24670937 ↗
L2OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [230]
Zuber B, Tran TC, Aegerter P et al.. “Impact of case volume on survival of septic shock in patients with malignancies.” Critical care medicine (2012). PMID: 21926606 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [231]
Damas P, Ledoux D, Nys M et al.. “Intensive care unit acquired infection and organ failure.” Intensive care medicine (2008). PMID: 18259728 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores), Complications & Iatrogenesis - [232]
Vignon P, Charron C, Legras A et al.. “Left ventricular diastolic dysfunction is prevalent but not associated with mortality in patients with septic shock.” Intensive care medicine (2025). PMID: 39774865 ↗
L2OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores), Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [233]
Vassiliou AG, Maniatis NA, Kotanidou A et al.. “Endothelial protein C receptor polymorphisms and risk of severe sepsis in critically ill patients.” Intensive care medicine (2013). PMID: 23881209 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [234]
Azoulay E, Lemiale V, Mokart D et al.. “Acute respiratory distress syndrome in patients with malignancies.” Intensive care medicine (2014). PMID: 24898895 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [235]
Que YA, Guessous I, Dupuis-Lozeron E et al.. “Prognostication of Mortality in Critically Ill Patients With Severe Infections.” Chest (2015). PMID: 26065577 ↗
L2OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [236]
Fernando SM, Reardon PM, Rochwerg B et al.. “Sepsis-3 Septic Shock Criteria and Associated Mortality Among Infected Hospitalized Patients Assessed by a Rapid Response Team.” Chest (2018). PMID: 29778659 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores), Special Populations - [237]
Kenneally C, Rosini JM, Skrupky LP et al.. “Analysis of 30-day mortality for clostridium difficile-associated disease in the ICU setting.” Chest (2007). PMID: 17573523 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [238]
Farzanegan B, Shafigh N, Hasheminik M et al.. “The combined effect of statin and vitamin C in patients with pulmonary septic shock: a single-center, double-blind clinical trial.” BMC infectious diseases (2025). PMID: 41136950 ↗
L1RCTCited in: Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult - [239]
Saraiva LT, da Silva Costa WN, Grams ST et al.. “Discriminatory Characteristics of Responders and Nonresponders of Patients With Sepsis to Neuromuscular Electrical Stimulation: A Subanalysis of a Randomized Controlled Double-Blinded Trial.” Archives of physical medicine and rehabilitation (2025). PMID: 41083041 ↗
L2RCTCited in: Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult - [240]
Safabakhsh M, Shab-Bidar S, Rohani P et al.. “Effect of probiotics on intestinal permeability in critically ill children with sepsis: preliminary results from a double-blind, placebo-controlled trial.” European journal of nutrition (2025). PMID: 40986080 ↗
L1RCTCited in: Severity Scoring & Risk Stratification (ICU Scores), Definitive Therapy & Source Control of the Inciting Insult, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [241]
Du C, Li X. “Comparative prognostic evaluation of SOFA and PSS scores in pediatric septic shock: A retrospective study.” Advances in clinical and experimental medicine : official organ Wroclaw Medical University (2026). PMID: 41524716 ↗
L3COHORTCited in: Severity Scoring & Risk Stratification (ICU Scores) - [242]
Duan J, Chen L, Liu X et al.. “An updated HACOR score for predicting the failure of noninvasive ventilation: a multicenter prospective observational study.” Critical care (London, England) (2022). PMID: 35786223 ↗
L2OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [243]
Zimmermann T, Kaufmann P, Amacher SA et al.. “Sex differences in the SOFA score of ICU patients with sepsis or septic shock: a nationwide analysis.” Critical care (London, England) (2024). PMID: 38937819 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores) - [244]
Le Goff M, Martino F, Rossi G et al.. “Prognosis of liver abscess in the intensive care unit (POLAIR), a multicentre observational study.” Critical care (London, England) (2025). PMID: 40197508 ↗
L3OTHERCited in: Severity Scoring & Risk Stratification (ICU Scores), Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [245]
Mekontso Dessap A, AlShamsi F, Belletti A et al.. “European Society of Intensive Care Medicine (ESICM) 2025 clinical practice guideline on fluid therapy in adult critically ill patients: part 2-the volume of resuscitation fluids.” Intensive care medicine (2025). PMID: 40163133 ↗
L1GUIDELINECited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [246]
Sankar J, Muralidharan J, Lalitha AV et al.. “Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial.” Critical care medicine (2023). PMID: 37294145 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [247]
Hajjar LA, Zambolim C, Belletti A et al.. “Vasopressin Versus Norepinephrine for the Management of Septic Shock in Cancer Patients: The VANCS II Randomized Clinical Trial.” Critical care medicine (2019). PMID: 31609774 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [248]
Rehberg S, Frank S, Černý V et al.. “Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial (Landi-SEP).” Intensive care medicine (2024). PMID: 39297945 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [249]
Antcliffe DB, Burnham KL, Al-Beidh F et al.. “Transcriptomic Signatures in Sepsis and a Differential Response to Steroids. From the VANISH Randomized Trial.” American journal of respiratory and critical care medicine (2019). PMID: 30365341 ↗
L3RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [250]
Moskowitz A, Berg KM, Grossestreuer AV et al.. “Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial.” American journal of respiratory and critical care medicine (2023). PMID: 37364280 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [251]
Schortgen F, Clabault K, Katsahian S et al.. “Fever control using external cooling in septic shock: a randomized controlled trial.” American journal of respiratory and critical care medicine (2012). PMID: 22366046 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [252]
Kellum JA, Chawla LS, Keener C et al.. “The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock.” American journal of respiratory and critical care medicine (2016). PMID: 26398704 ↗
L2RCTCited in: Acute Resuscitation & Time-Critical Management, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [253]
Douglas IS, Alapat PM, Corl KA et al.. “Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial.” Chest (2020). PMID: 32353418 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [254]
Ezz Al-Regal AR, Ramzy EA, Atia AAA et al.. “Dexmedetomidine for Reducing Mortality in Patients With Septic Shock: A Randomized Controlled Trial (DecatSepsis).” Chest (2024). PMID: 39004217 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [255]
Sehgal IS, Basumatary NM, Dhooria S et al.. “A Randomized Trial of Mycobacterium w in Severe Presumed Gram-Negative Sepsis.” Chest (2021). PMID: 33852919 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [256]
Annane D, Renault A, Brun-Buisson C et al.. “Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.” The New England journal of medicine (2018). PMID: 29490185 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [257]
De Backer D, Biston P, Devriendt J et al.. “Comparison of dopamine and norepinephrine in the treatment of shock.” The New England journal of medicine (2010). PMID: 20200382 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [258]
Russell JA, Walley KR, Singer J et al.. “Vasopressin versus norepinephrine infusion in patients with septic shock.” The New England journal of medicine (2008). PMID: 18305265 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [259]
Meyhoff TS, Hjortrup PB, Wetterslev J et al.. “Restriction of Intravenous Fluid in ICU Patients with Septic Shock.” The New England journal of medicine (2022). PMID: 35709019 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Complications & Iatrogenesis - [260]
Sprung CL, Annane D, Keh D et al.. “Hydrocortisone therapy for patients with septic shock.” The New England journal of medicine (2008). PMID: 18184957 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [261]
Asfar P, Meziani F, Hamel JF et al.. “High versus low blood-pressure target in patients with septic shock.” The New England journal of medicine (2014). PMID: 24635770 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [262]
Ranieri VM, Thompson BT, Barie PS et al.. “Drotrecogin alfa (activated) in adults with septic shock.” The New England journal of medicine (2012). PMID: 22616830 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [263]
Gendreau S, Frapard T, Carteaux G et al.. “Geo-economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis.” American journal of respiratory and critical care medicine (2024). PMID: 38259196 ↗
L1SR_OBSCited in: Acute Resuscitation & Time-Critical Management - [264]
Annane D, Vignon P, Renault A et al.. “Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial.” Lancet (London, England) (2007). PMID: 17720019 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [265]
Cruz DN, Antonelli M, Fumagalli R et al.. “Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial.” JAMA (2009). PMID: 19531784 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [266]
Ahn C, Yu G, Shin TG et al.. “Comparison of Early and Late Norepinephrine Administration in Patients With Septic Shock: A Systematic Review and Meta-Analysis.” Chest (2024). PMID: 38972348 ↗
L1SR_OBSCited in: Acute Resuscitation & Time-Critical Management - [267]
Kotani Y, Belletti A, D'Amico F et al.. “Non-adrenergic vasopressors for vasodilatory shock or perioperative vasoplegia: a meta-analysis of randomized controlled trials.” Critical care (London, England) (2024). PMID: 39736782 ↗
L1SR_MA_RCTCited in: Acute Resuscitation & Time-Critical Management - [268]
Ibarra-Estrada M, Kattan E, Aguilera-González P et al.. “Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.” Critical care (London, England) (2023). PMID: 36915146 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [269]
Jorda A, Douglas IS, Staudinger T et al.. “Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial.” Critical care (London, England) (2024). PMID: 38992663 ↗
L2RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [270]
Davis AL, Carcillo JA, Aneja RK et al.. “American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock.” Critical care medicine (2017). PMID: 28509730 ↗
L1OTHERCited in: Acute Resuscitation & Time-Critical Management - [271]
Sanchez E C, Taha A, Tolba Y et al.. “Assessment of Tissue Perfusion Pressure in Patients With Septic Shock: Beyond Mean Arterial Pressure.” Critical care medicine (2025). PMID: 40668153 ↗
L5REVIEW_NARRATIVECited in: Acute Resuscitation & Time-Critical Management - [272]
Ferrer R, Martin-Loeches I, Phillips G et al.. “Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program.” Critical care medicine (2014). PMID: 24717459 ↗
L2OTHERCited in: Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult - [273]
Kuttab HI, Lykins JD, Hughes MD et al.. “Evaluation and Predictors of Fluid Resuscitation in Patients With Severe Sepsis and Septic Shock.” Critical care medicine (2019). PMID: 31393324 ↗
L3OTHERCited in: Acute Resuscitation & Time-Critical Management - [274]
Im Y, Kang D, Ko RE et al.. “Time-to-antibiotics and clinical outcomes in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study.” Critical care (London, England) (2022). PMID: 35027073 ↗
L2COHORTCited in: Acute Resuscitation & Time-Critical Management - [275]
Munroe ES, Hyzy RC, Semler MW et al.. “Evolving Management Practices for Early Sepsis-induced Hypoperfusion: A Narrative Review.” American journal of respiratory and critical care medicine (2023). PMID: 36812500 ↗
L5REVIEW_NARRATIVECited in: Acute Resuscitation & Time-Critical Management - [276]
Byrne L, Obonyo NG, Diab SD et al.. “Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia.” American journal of respiratory and critical care medicine (2018). PMID: 29882682 ↗
L5OTHERCited in: Acute Resuscitation & Time-Critical Management - [277]
Teja B, Bosch NA, Walkey AJ. “How We Escalate Vasopressor and Corticosteroid Therapy in Patients With Septic Shock.” Chest (2022). PMID: 36162481 ↗
L5REVIEW_NARRATIVECited in: Acute Resuscitation & Time-Critical Management - [278]
Yealy DM, Kellum JA, Huang DT et al.. “A randomized trial of protocol-based care for early septic shock.” The New England journal of medicine (2014). PMID: 24635773 ↗
L1OTHERCited in: Acute Resuscitation & Time-Critical Management - [279]
Boussina A, Allison C, Quintero K et al.. “Medical Record Abstraction for Quality Improvement in Sepsis Care Using Artificial Intelligence: A Cluster Randomized Trial.” JAMA network open (2026). PMID: 42348212 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [280]
Christensen J, Sivapalan P, Meyhoff TS et al.. “Restrictive versus standard intravenous fluid therapy and NTproBNP in ICU patients with septic shock - a sub-study of the randomised CLASSIC trial.” BMC anesthesiology (2026). PMID: 41987014 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management, Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Special Populations - [281]
Neyra JA, Legrand M, Tidswell MA et al.. “Polymyxin B haemoadsorption in endotoxic septic shock (Tigris): a multicentre, open-label, Bayesian, randomised, controlled, phase 3 trial.” The Lancet. Respiratory medicine (2026). PMID: 41887242 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management - [282]
Lotz C, Heckelmann J, Lendzian C et al.. “Clinical and Immunologic Effects of Extracorporeal Cytokine Removal in Patients with Septic Shock: A Randomized Controlled Trial.” Shock (Augusta, Ga.) (2026). PMID: 41670614 ↗
L1RCTCited in: Acute Resuscitation & Time-Critical Management - [283]
Whitehouse T, Hossain A, Perkins GD et al.. “Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.” JAMA (2023). PMID: 37877587 ↗
L1OTHERCited in: Acute Resuscitation & Time-Critical Management - [284]
Luo JC, Mou T, Li M et al.. “Recombinant human brain natriuretic peptide for the recovery stage of septic shock: an interventional study protocol.” BMJ open (2026). PMID: 42192636 ↗
L5TRIAL_NONRANDOMCited in: Acute Resuscitation & Time-Critical Management - [285]
Tekin A, Halpern G, Gowda D et al.. “Midodrine for Sepsis Treatment and Early Vasopressor Weaning (MID-STEP): protocol for a pragmatic randomised clinical trial.” BMJ open (2026). PMID: 42020133 ↗
L5TRIAL_NONRANDOMCited in: Acute Resuscitation & Time-Critical Management, History and Evolution of Treatment - [286]
Menon K, Agus MSD, O'Hearn K et al.. “Stress Hydrocortisone in Pediatric Septic Shock: Protocol for a Pragmatic, Multicenter, International, Randomized, Double-Blinded, Placebo-Controlled Interventional Trial.” Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies (2025). PMID: 41504575 ↗
L5TRIAL_NONRANDOMCited in: Acute Resuscitation & Time-Critical Management - [287]
Desfosses M, Røislien J. “An overview of reviews of Angiotensin II in distributive shock.” BMC anesthesiology (2026). PMID: 41942842 ↗
L2SR_OBSCited in: Acute Resuscitation & Time-Critical Management - [288]
Süffert LC, Pergher EAB, de Abreu HS et al.. “Low-dose corticosteroids in cirrhotic patients with septic shock or vasopressor-dependent shock: A systematic review and meta-analysis.” Journal of critical care (2025). PMID: 41412001 ↗
L2SR_OBSCited in: Acute Resuscitation & Time-Critical Management - [289]
Li D, Li X, Cui W et al.. “Liberal versus conservative fluid therapy in adults and children with sepsis or septic shock.” The Cochrane database of systematic reviews (2018). PMID: 30536956 ↗
L1SR_OBSCited in: Acute Resuscitation & Time-Critical Management - [290]
Monnet X, Lai C, Teboul JL. “How I personalize fluid therapy in septic shock?” Critical care (London, England) (2023). PMID: 36964573 ↗
L5REVIEW_NARRATIVECited in: Acute Resuscitation & Time-Critical Management - [291]
Arias-Ortiz J, Vincent JL. “Administration of methylene blue in septic shock: pros and cons.” Critical care (London, England) (2024). PMID: 38365828 ↗
L5REVIEW_NARRATIVECited in: Acute Resuscitation & Time-Critical Management - [292]
Garnacho-Montero J, Dimopoulos G, Poulakou G et al.. “Task force on management and prevention of Acinetobacter baumannii infections in the ICU.” Intensive care medicine (2015). PMID: 26438224 ↗
L5GUIDELINECited in: Definitive Therapy & Source Control of the Inciting Insult - [293]
Iapichino G, Albicini M, Umbrello M et al.. “Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients.” Intensive care medicine (2008). PMID: 18504551 ↗
L1SR_MA_RCTCited in: Definitive Therapy & Source Control of the Inciting Insult, Special Populations - [294]
Sivapalan P, Kaas-Hansen BS, Meyhoff TS et al.. “Effects of IV Fluid Restriction According to Standard Fluid Treatment Intensity Across Conservative Versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care (CLASSIC) Trial Sites.” Critical care medicine (2025). PMID: 40272936 ↗
L2RCTCited in: Definitive Therapy & Source Control of the Inciting Insult, Complications & Iatrogenesis, Special Populations - [295]
Ahlstedt C, Sivapalan P, Kriz M et al.. “Effects of restrictive fluid therapy on the time to resolution of hyperlactatemia in ICU patients with septic shock. A secondary post hoc analysis of the CLASSIC randomized trial.” Intensive care medicine (2024). PMID: 38598125 ↗
L2RCTCited in: Definitive Therapy & Source Control of the Inciting Insult - [296]
Yildizdas D, Yapicioglu H, Celik U et al.. “Terlipressin as a rescue therapy for catecholamine-resistant septic shock in children.” Intensive care medicine (2007). PMID: 18092150 ↗
L1RCTCited in: Definitive Therapy & Source Control of the Inciting Insult, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [297]
Garbero E, Livigni S, Ferrari F et al.. “High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial.” Intensive care medicine (2021). PMID: 34601619 ↗
L1RCTCited in: Definitive Therapy & Source Control of the Inciting Insult, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [298]
Kumar A, Safdar N, Kethireddy S et al.. “A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study.” Critical care medicine (2010). PMID: 20562695 ↗
L2SR_OBSCited in: Definitive Therapy & Source Control of the Inciting Insult - [299]
Tongyoo S, Chayakul C, Aritajati T et al.. “Adjunctive terlipressin versus placebo in the treatment of refractory septic shock: a randomized, placebo-controlled trial.” Critical care (London, England) (2025). PMID: 41121365 ↗
L1RCTCited in: Definitive Therapy & Source Control of the Inciting Insult, History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Special Populations - [300]
Rüddel H, Thomas-Rüddel DO, Reinhart K et al.. “Adverse effects of delayed antimicrobial treatment and surgical source control in adults with sepsis: results of a planned secondary analysis of a cluster-randomized controlled trial.” Critical care (London, England) (2022). PMID: 35227308 ↗
L2RCTCited in: Definitive Therapy & Source Control of the Inciting Insult - [301]
Yu Y, Zhu C, Hong Y et al.. “Effectiveness of anisodamine for the treatment of critically ill patients with septic shock: a multicentre randomized controlled trial.” Critical care (London, England) (2021). PMID: 34579741 ↗
L1RCTCited in: Definitive Therapy & Source Control of the Inciting Insult, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [302]
Prkno A, Wacker C, Brunkhorst FM et al.. “Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock--a systematic review and meta-analysis.” Critical care (London, England) (2013). PMID: 24330744 ↗
L1SR_OBSCited in: Definitive Therapy & Source Control of the Inciting Insult - [303]
Song MJ, Seo WI, Jang Y et al.. “RBC Transfusion Practices in Critically Ill Patients With Sepsis.” Critical care medicine (2025). PMID: 41090988 ↗
L2OTHERCited in: Definitive Therapy & Source Control of the Inciting Insult - [304]
Timsit JF, Ruppé E, Barbier F et al.. “Bloodstream infections in critically ill patients: an expert statement.” Intensive care medicine (2020). PMID: 32047941 ↗
L5OTHERCited in: Definitive Therapy & Source Control of the Inciting Insult - [305]
Barbier F, Dupuis C, Buetti N et al.. “Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study.” Critical care (London, England) (2024). PMID: 38172969 ↗
L3COHORTCited in: Definitive Therapy & Source Control of the Inciting Insult, Complications & Iatrogenesis - [306]
Calabretta D, Cilloniz C, Gabarrus A et al.. “Impact of Empirical Treatment Recommendations From 2017 European Guidelines for Nosocomial Pneumonia.” Chest (2024). PMID: 39461555 ↗
L3OTHERCited in: Definitive Therapy & Source Control of the Inciting Insult, Complications & Iatrogenesis - [307]
Müller MM, Pinto R, Lamontagne F et al.. “Vitamin C Does Not Affect Platelet Counts in Patients With Sepsis: A Post hoc Analysis of the Lessening Organ Dysfunction With Vitamin C Randomized Trial.” Critical care explorations (2025). PMID: 40927646 ↗
L2RCTCited in: Definitive Therapy & Source Control of the Inciting Insult - [308]
Sankar J, Manoharan A, Lodha R et al.. “Vitamin C Versus Placebo in Pediatric Septic Shock (VITACiPS) - A Randomised Controlled Trial.” Journal of intensive care medicine (2025). PMID: 40708328 ↗
L1RCTCited in: Definitive Therapy & Source Control of the Inciting Insult - [309]
Kollef MH, Shorr AF, Bassetti M et al.. “Timing of antibiotic therapy in the ICU.” Critical care (London, England) (2021). PMID: 34654462 ↗
L5REVIEW_NARRATIVECited in: Definitive Therapy & Source Control of the Inciting Insult - [310]
Dellinger RP, Carlet JM, Masur H et al.. “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.” Critical care medicine (2004). PMID: 15090974 ↗
L5GUIDELINECited in: History and Evolution of Treatment - [311]
Díaz-Gómez JL, Sharif S, Ablordeppey E et al.. “Society of Critical Care Medicine Guidelines on Adult Critical Care Ultrasonography: Focused Update 2024.” Critical care medicine (2025). PMID: 39982182 ↗
L1GUIDELINECited in: History and Evolution of Treatment - [312]
Barochia AV, Cui X, Vitberg D et al.. “Bundled care for septic shock: an analysis of clinical trials.” Critical care medicine (2010). PMID: 20029343 ↗
L2TRIAL_NONRANDOMCited in: History and Evolution of Treatment - [313]
Kirov MY, Evgenov OV, Evgenov NV et al.. “Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study.” Critical care medicine (2001). PMID: 11588440 ↗
L1RCTCited in: History and Evolution of Treatment - [314]
Hagel S, Bach F, Brenner T et al.. “Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial.” Intensive care medicine (2022). PMID: 35106617 ↗
L1RCTCited in: History and Evolution of Treatment - [315]
Liu ZM, Chen J, Kou Q et al.. “Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial.” Intensive care medicine (2018). PMID: 29971593 ↗
L1RCTCited in: History and Evolution of Treatment, Complications & Iatrogenesis - [316]
Leaf DE, Raed A, Donnino MW et al.. “Randomized controlled trial of calcitriol in severe sepsis.” American journal of respiratory and critical care medicine (2014). PMID: 25029202 ↗
L1RCTCited in: History and Evolution of Treatment - [317]
Ferrer M, Esquinas A, Arancibia F et al.. “Noninvasive ventilation during persistent weaning failure: a randomized controlled trial.” American journal of respiratory and critical care medicine (2003). PMID: 12689847 ↗
L1RCTCited in: History and Evolution of Treatment - [318]
Ortolani O, Conti A, De Gaudio AR et al.. “The effect of glutathione and N-acetylcysteine on lipoperoxidative damage in patients with early septic shock.” American journal of respiratory and critical care medicine (2000). PMID: 10852765 ↗
L1RCTCited in: History and Evolution of Treatment - [319]
Cohen J, Bellomo R, Billot L et al.. “Plasma Cortisol, Aldosterone, and Ascorbic Acid Concentrations in Patients with Septic Shock Do Not Predict Treatment Effect of Hydrocortisone on Mortality. A Nested Cohort Study.” American journal of respiratory and critical care medicine (2020). PMID: 32396775 ↗
L2RCTCited in: History and Evolution of Treatment - [320]
Annane D, Timsit JF, Megarbane B et al.. “Recombinant human activated protein C for adults with septic shock: a randomized controlled trial.” American journal of respiratory and critical care medicine (2013). PMID: 23525934 ↗
L1RCTCited in: History and Evolution of Treatment - [321]
Meisel C, Schefold JC, Pschowski R et al.. “Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial.” American journal of respiratory and critical care medicine (2009). PMID: 19590022 ↗
L1RCTCited in: History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [322]
Simou E, Leonardi-Bee J, Britton J. “The Effect of Alcohol Consumption on the Risk of ARDS: A Systematic Review and Meta-Analysis.” Chest (2017). PMID: 29288645 ↗
L2SR_OBSCited in: History and Evolution of Treatment - [323]
Martin C, Papazian L, Perrin G et al.. “Norepinephrine or dopamine for the treatment of hyperdynamic septic shock?” Chest (1993). PMID: 8404107 ↗
L1RCTCited in: History and Evolution of Treatment - [324]
Wunderink R, Leeper K, Schein R et al.. “Filgrastim in patients with pneumonia and severe sepsis or septic shock.” Chest (2001). PMID: 11171733 ↗
L1RCTCited in: History and Evolution of Treatment - [325]
Fourrier F, Chopin C, Huart JJ et al.. “Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation.” Chest (1993). PMID: 8365305 ↗
L1RCTCited in: History and Evolution of Treatment - [326]
Tuchschmidt J, Fried J, Astiz M et al.. “Elevation of cardiac output and oxygen delivery improves outcome in septic shock.” Chest (1992). PMID: 1623756 ↗
L1RCTCited in: History and Evolution of Treatment - [327]
Puskarich MA, Trzeciak S, Shapiro NI et al.. “Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock.” Chest (2013). PMID: 23740148 ↗
L2RCTCited in: History and Evolution of Treatment - [328]
Attard G, Murphy L, Clarke NW et al.. “Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.” Lancet (London, England) (2021). PMID: 34953525 ↗
L1SR_OBSCited in: History and Evolution of Treatment - [329]
Rivers E, Nguyen B, Havstad S et al.. “Early goal-directed therapy in the treatment of severe sepsis and septic shock.” The New England journal of medicine (2001). PMID: 11794169 ↗
L1RCTCited in: History and Evolution of Treatment - [330]
Venkatesh B, Finfer S, Cohen J et al.. “Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.” The New England journal of medicine (2018). PMID: 29347874 ↗
L1RCTCited in: History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [331]
Caironi P, Tognoni G, Masson S et al.. “Albumin replacement in patients with severe sepsis or septic shock.” The New England journal of medicine (2014). PMID: 24635772 ↗
L1RCTCited in: History and Evolution of Treatment, Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [332]
Rugo HS, Bardia A, Marmé F et al.. “Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial.” Lancet (London, England) (2023). PMID: 37633306 ↗
L1RCTCited in: History and Evolution of Treatment - [333]
Thompson GR, Soriano A, Cornely OA et al.. “Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial.” Lancet (London, England) (2022). PMID: 36442484 ↗
L1RCTCited in: History and Evolution of Treatment - [334]
Baudin E, Goichot B, Berruti A et al.. “Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial.” Lancet (London, England) (2024). PMID: 38402886 ↗
L1RCTCited in: History and Evolution of Treatment - [335]
DeMaria A, Carven DE, Heffernan JJ et al.. “Naloxone versus placebo in treatment of septic shock.” Lancet (London, England) (1985). PMID: 2861315 ↗
L1RCTCited in: History and Evolution of Treatment - [336]
Roberts DE, Dobson KE, Hall KW et al.. “Effects of prolonged naloxone infusion in septic shock.” Lancet (London, England) (1988). PMID: 2901565 ↗
L1RCTCited in: History and Evolution of Treatment - [337]
Abraham E, Anzueto A, Gutierrez G et al.. “Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group.” Lancet (London, England) (1998). PMID: 9734938 ↗
L1RCTCited in: History and Evolution of Treatment - [338]
Baumgartner JD, Glauser MP, McCutchan JA et al.. “Prevention of gram-negative shock and death in surgical patients by antibody to endotoxin core glycolipid.” Lancet (London, England) (1985). PMID: 2861523 ↗
L1RCTCited in: History and Evolution of Treatment - [339]
Schortgen F, Lacherade JC, Bruneel F et al.. “Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study.” Lancet (London, England) (2001). PMID: 11289347 ↗
L1RCTCited in: History and Evolution of Treatment - [340]
Lachman E, Pitsoe SB, Gaffin SL. “Anti-lipopolysaccharide immunotherapy in management of septic shock of obstetric and gynaecological origin.” Lancet (London, England) (1984). PMID: 6143965 ↗
L2RCTCited in: History and Evolution of Treatment - [341]
Day NP, Phu NH, Bethell DP et al.. “The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection.” Lancet (London, England) (1996). PMID: 8684198 ↗
L1RCTCited in: History and Evolution of Treatment - [342]
Annane D, Sébille V, Charpentier C et al.. “Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.” JAMA (2002). PMID: 12186604 ↗
L1RCTCited in: History and Evolution of Treatment - [343]
Dellinger RP, Bagshaw SM, Antonelli M et al.. “Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial.” JAMA (2018). PMID: 30304428 ↗
L1RCTCited in: History and Evolution of Treatment - [344]
Quezado ZM, Natanson C, Alling DW et al.. “A controlled trial of HA-1A in a canine model of gram-negative septic shock.” JAMA (1993). PMID: 8474201 ↗
L5RCTCited in: History and Evolution of Treatment - [345]
Annane D, Cariou A, Maxime V et al.. “Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.” JAMA (2010). PMID: 20103758 ↗
L1RCTCited in: History and Evolution of Treatment - [346]
Moskowitz A, Huang DT, Hou PC et al.. “Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial.” JAMA (2020). PMID: 32809003 ↗
L1RCTCited in: History and Evolution of Treatment, Complications & Iatrogenesis - [347]
Roux D, Benichou N, Hajage D et al.. “Impact of renal replacement therapy strategy on beta-lactam plasma concentrations: the BETAKIKI study-an ancillary study of a randomized controlled trial.” Annals of intensive care (2023). PMID: 36840825 ↗
L2RCTCited in: History and Evolution of Treatment - [348]
Vallabhajosyula S, Kumar M, Pandompatam G et al.. “Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.” Annals of intensive care (2017). PMID: 28884343 ↗
L2COHORTCited in: History and Evolution of Treatment - [349]
Llitjos JF, Bredin S, Lascarrou JB et al.. “Increased susceptibility to intensive care unit-acquired pneumonia in severe COVID-19 patients: a multicentre retrospective cohort study.” Annals of intensive care (2021). PMID: 33512602 ↗
L2COHORTCited in: History and Evolution of Treatment - [350]
Viswanathan M, Kahwati L, Jahn B et al.. “Universal screening for SARS-CoV-2 infection: a rapid review.” The Cochrane database of systematic reviews (2020). PMID: 33502003 ↗
L2SR_OBSCited in: History and Evolution of Treatment - [351]
Moutinho A, Martins F, Fontes J et al.. “[Management of the Patient with Suspected Sepsis or Septic Shock: Clinical Recommendations for the Portuguese Prehospital Setting].” Acta medica portuguesa (2026). PMID: 42044523 ↗
L1GUIDELINECited in: History and Evolution of Treatment - [352]
Byrne L, Van Haren F. “Fluid resuscitation in human sepsis: Time to rewrite history?” Annals of intensive care (2017). PMID: 28050897 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment - [353]
Crosignani A, Spina S, Marrazzo F et al.. “Intravenous fluid therapy in patients with severe acute pancreatitis admitted to the intensive care unit: a narrative review.” Annals of intensive care (2022). PMID: 36251136 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment - [354]
Ronco C, Bellomo R. “Hemoperfusion: technical aspects and state of the art.” Critical care (London, England) (2022). PMID: 35549999 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment - [355]
Bottari G, Ranieri VM, Ince C et al.. “Use of extracorporeal blood purification therapies in sepsis: the current paradigm, available evidence, and future perspectives.” Critical care (London, England) (2024). PMID: 39722012 ↗
L5REVIEW_NARRATIVECited in: History and Evolution of Treatment - [356]
Wongtirawit N, Inyu W, Prajantasen U et al.. “HA-330 hemoadsorption in septic shock requiring high-dose norepinephrine: a multicenter randomized controlled trial (CLEANSE).” Critical care (London, England) (2026). PMID: 42277846 ↗
L1RCTCited in: History and Evolution of Treatment - [357]
Thanasai J, Chanthot C, Chittamma A et al.. “Serum Procalcitonin in Culture-Confirmed Melioidosis: A Systematic Review and Meta-Analysis with Narrative Evaluation of Clinical and Prognostic Implications.” Diseases (Basel, Switzerland) (2026). PMID: 42041611 ↗
L1SR_OBSCited in: History and Evolution of Treatment - [358]
Mowafy HL, Garin N, Katsounas A et al.. “Sex-related disparities in sepsis in western Europe: A systematic review and meta-analysis.” European journal of internal medicine (2026). PMID: 42115064 ↗
L1SR_OBSCited in: History and Evolution of Treatment - [359]
Anton GI, Radu R, Ceban E et al.. “Efficacy and Safety of Meropenem in Pregnant Women with Upper Urinary Tract Infections: A Retrospective Cohort Study in Romania.” Antibiotics (Basel, Switzerland) (2026). PMID: 42353734 ↗
L2COHORTCited in: History and Evolution of Treatment - [360]
Zhou L, Li S, Ding Q et al.. “A comparison of pediatric sepsis definitions based on systemic inflammatory response syndrome and Phoenix criteria: a single-center PICU retrospective study.” Italian journal of pediatrics (2026). PMID: 42321878 ↗
L2COHORTCited in: History and Evolution of Treatment - [361]
Lyu X, Chen S, Shi H et al.. “Development and validation of a predictive model for septic shock in maternal sepsis: a retrospective cohort study in a single referral center.” BMC pregnancy and childbirth (2026). PMID: 42252422 ↗
L2COHORTCited in: History and Evolution of Treatment - [362]
Çelik FH, Eren EE, Baykan N et al.. “Elderly patients with healthcare-associated infections in the emergency department: clinical characteristics and risk factors for septic shock: a retrospective study.” BMC geriatrics (2026). PMID: 42026516 ↗
L2COHORTCited in: History and Evolution of Treatment - [363]
Fage N, Demiselle J, Seegers V et al.. “Effects of mean arterial pressure target on mottling and arterial lactate normalization in patients with septic shock: a post hoc analysis of the SEPSISPAM randomized trial.” Annals of intensive care (2022). PMID: 35984574 ↗
L2OTHERCited in: History and Evolution of Treatment - [364]
Gonzalez FA, Bacariza J, Varudo AR et al.. “Sepsis-induced myocardial dysfunction diagnosed with strain versus non-strain echocardiography parameters: incidence, evolution and association with prognosis.” Annals of intensive care (2025). PMID: 40999250 ↗
L2OTHERCited in: History and Evolution of Treatment - [365]
Hohn A, Balfer N, Heising B et al.. “Adherence to a procalcitonin-guided antibiotic treatment protocol in patients with severe sepsis and septic shock.” Annals of intensive care (2018). PMID: 29869120 ↗
L2OTHERCited in: History and Evolution of Treatment - [366]
Helms J, Merdji H, Loewert S et al.. “Disseminated intravascular coagulation is strongly associated with severe acute kidney injury in patients with septic shock.” Annals of intensive care (2023). PMID: 38038826 ↗
L2OTHERCited in: History and Evolution of Treatment - [367]
Peschanski N, Chenevier-Gobeaux C, Mzabi L et al.. “Prognostic value of PCT in septic emergency patients.” Annals of intensive care (2016). PMID: 27207179 ↗
L2OTHERCited in: History and Evolution of Treatment - [368]
Panitchote A, Mehkri O, Hastings A et al.. “Factors associated with acute kidney injury in acute respiratory distress syndrome.” Annals of intensive care (2019). PMID: 31264042 ↗
L2OTHERCited in: History and Evolution of Treatment - [369]
Jouan Y, Grammatico-Guillon L, Teixera N et al.. “Healthcare trajectories before and after critical illness: population-based insight on diverse patients clusters.” Annals of intensive care (2019). PMID: 31707487 ↗
L2OTHERCited in: History and Evolution of Treatment - [370]
Brierley J, Carcillo JA, Choong K et al.. “Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine.” Critical care medicine (2009). PMID: 19325359 ↗
L1GUIDELINECited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [371]
Wacker DA, Burton SL, Berger JP et al.. “Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy.” Critical care medicine (2022). PMID: 34982738 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [372]
Grau T, Bonet A, Miñambres E et al.. “The effect of L-alanyl-L-glutamine dipeptide supplemented total parenteral nutrition on infectious morbidity and insulin sensitivity in critically ill patients.” Critical care medicine (2011). PMID: 21336131 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Complications & Iatrogenesis - [373]
Trof RJ, Beishuizen A, Cornet AD et al.. “Volume-limited versus pressure-limited hemodynamic management in septic and nonseptic shock.” Critical care medicine (2012). PMID: 22202713 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [374]
Payen JF, Dupuis C, Trouve-Buisson T et al.. “Corticosteroid after etomidate in critically ill patients: a randomized controlled trial.” Critical care medicine (2012). PMID: 21926601 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [375]
Warrillow S, Egi M, Bellomo R. “Randomized, double-blind, placebo-controlled crossover pilot study of a potassium channel blocker in patients with septic shock.” Critical care medicine (2006). PMID: 16484892 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [376]
Pontes-Arruda A, Aragão AM, Albuquerque JD. “Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock.” Critical care medicine (2006). PMID: 16850002 ↗
L4RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [377]
Park CHL, de Almeida JP, de Oliveira GQ et al.. “Lactated Ringer's Versus 4% Albumin on Lactated Ringer's in Early Sepsis Therapy in Cancer Patients: A Pilot Single-Center Randomized Trial.” Critical care medicine (2019). PMID: 31356475 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [378]
Lauzier F, Lévy B, Lamarre P et al.. “Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial.” Intensive care medicine (2006). PMID: 17019548 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [379]
Young P, Mackle D, Bellomo R et al.. “Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX).” Intensive care medicine (2019). PMID: 31748836 ↗
L2RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [380]
Quenot JP, Binquet C, Vinsonneau C et al.. “Very high volume hemofiltration with the Cascade system in septic shock patients.” Intensive care medicine (2015). PMID: 26431720 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [381]
Boussekey N, Chiche A, Faure K et al.. “A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock.” Intensive care medicine (2008). PMID: 18542921 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [382]
Zhang Z, Ni H, Qian Z. “Effectiveness of treatment based on PiCCO parameters in critically ill patients with septic shock and/or acute respiratory distress syndrome: a randomized controlled trial.” Intensive care medicine (2015). PMID: 25605469 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Complications & Iatrogenesis - [383]
Radrizzani D, Bertolini G, Facchini R et al.. “Early enteral immunonutrition vs. parenteral nutrition in critically ill patients without severe sepsis: a randomized clinical trial.” Intensive care medicine (2006). PMID: 16788808 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [384]
Chen C, Kollef MH. “Targeted Fluid Minimization Following Initial Resuscitation in Septic Shock: A Pilot Study.” Chest (2015). PMID: 26291900 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets, Complications & Iatrogenesis - [385]
Munch MW, Myatra SN, Vijayaraghavan BKT et al.. “Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.” JAMA (2021). PMID: 34673895 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [386]
Tadié JM, Locher C, Maamar A et al.. “Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial.” Critical care (London, England) (2023). PMID: 37784110 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [387]
Piotti A, Novelli D, Meessen JMTA et al.. “Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS.” Critical care (London, England) (2021). PMID: 33741039 ↗
L3RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [388]
Rehberg S, Ertmer C, Lange M et al.. “Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study.” Critical care (London, England) (2010). PMID: 21054850 ↗
L5RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [389]
Barbar SD, Bourredjem A, Trusson R et al.. “Differential effect on mortality of the timing of initiation of renal replacement therapy according to the criteria used to diagnose acute kidney injury: an IDEAL-ICU substudy.” Critical care (London, England) (2023). PMID: 37592355 ↗
L2RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [390]
Morelli A, Ertmer C, Rehberg S et al.. “Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study.” Critical care (London, England) (2009). PMID: 19664253 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [391]
Cioccari L, Luethi N, Bailey M et al.. “The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial.” Critical care (London, England) (2020). PMID: 32678054 ↗
L2RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [392]
Adlbrecht C, Wurm R, Depuydt P et al.. “Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients-a randomized clinical trial.” Critical care (London, England) (2020). PMID: 32131866 ↗
L1RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [393]
Donaldson LH, Devaux A, White KC et al.. “Hydrocortisone and Risk Factors for Kidney Replacement Therapy in Septic Shock.” JAMA network open (2025). PMID: 40423970 ↗
L2RCTCited in: Organ Support: Ventilatory, Hemodynamic, Renal & Extracorporeal Targets - [394]
Boehm LM, Danesh V, Eaton TL et al.. “Multidisciplinary ICU Recovery Clinic Visits: A Qualitative Analysis of Patient-Provider Dialogues.” Chest (2022). PMID: 36243061 ↗
L4TRIAL_NONRANDOMCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS), Prevention, Screening and Post-ICU Surveillance - [395]
Pfister D, Siegemund M, Dell-Kuster S et al.. “Cerebral perfusion in sepsis-associated delirium.” Critical care (London, England) (2008). PMID: 18457586 ↗
L2TRIAL_NONRANDOMCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS), Special Populations - [396]
De Jonghe B, Bastuji-Garin S, Durand MC et al.. “Respiratory weakness is associated with limb weakness and delayed weaning in critical illness.” Critical care medicine (2007). PMID: 17855814 ↗
L2OTHERCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS) - [397]
Vieira JM, Castro I, Curvello-Neto A et al.. “Effect of acute kidney injury on weaning from mechanical ventilation in critically ill patients.” Critical care medicine (2007). PMID: 17080002 ↗
L3OTHERCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS) - [398]
Patel S, Stollings JL, Casey JD et al.. “Identifying Predictors of Extubation on the day of Passing an SBT in Critically ill Adults.” Journal of intensive care medicine (2023). PMID: 36648173 ↗
L3TRIAL_NONRANDOMCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS) - [399]
Liu K, Kotani T, Nakamura K et al.. “Effects of evidence-based ICU care on long-term outcomes of patients with sepsis or septic shock (ILOSS): protocol for a multicentre prospective observational cohort study in Japan.” BMJ open (2022). PMID: 35351710 ↗
L5TRIAL_NONRANDOMCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS) - [400]
Hanajima T, Kawazoe Y, Morimoto T et al.. “Early Rehabilitation for Patients with Septic Shock Associated with Mobilization During Their Intensive Care Unit Stay Without Worsening Mortality: A Multicenter, Prospective, Cohort Study.” Journal of intensive care medicine (2025). PMID: 40611676 ↗
L2COHORTCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS) - [401]
Vondeling AM, Knol W, Egberts TCG et al.. “Anticholinergic drug exposure at intensive care unit admission affects the occurrence of delirium. A prospective cohort study.” European journal of internal medicine (2020). PMID: 32487370 ↗
L2COHORTCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS) - [402]
Schubert M, Bettex D, Steiger P et al.. “Implementation of a multiprofessional, multicomponent delirium management guideline in two intensive care units, and its effect on patient outcomes and nurse workload: a pre-post design retrospective cohort study.” Swiss medical weekly (2020). PMID: 31986217 ↗
L2COHORTCited in: De-escalation, Ventilator Liberation, Sedation-Delirium Control & Early Rehabilitation (ABCDEF Bundle & PICS) - [403]
Chang P, Liao Y, Guan J et al.. “Combined Treatment With Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock: A Randomized Controlled Trial.” Chest (2020). PMID: 32243943 ↗
L1RCTCited in: Complications & Iatrogenesis - [404]
Shah AD, MacCallum NS, Harris S et al.. “Descriptors of Sepsis Using the Sepsis-3 Criteria: A Cohort Study in Critical Care Units Within the U.K. National Institute for Health Research Critical Care Health Informatics Collaborative.” Critical care medicine (2021). PMID: 34259454 ↗
L2COHORTCited in: Complications & Iatrogenesis - [405]
Frencken JF, van Vught LA, Peelen LM et al.. “An Unbalanced Inflammatory Cytokine Response Is Not Associated With Mortality Following Sepsis: A Prospective Cohort Study.” Critical care medicine (2017). PMID: 28257334 ↗
L2COHORTCited in: Complications & Iatrogenesis - [406]
Seligman R, Papassotiriou J, Morgenthaler NG et al.. “Copeptin, a novel prognostic biomarker in ventilator-associated pneumonia.” Critical care (London, England) (2008). PMID: 18252006 ↗
L2TRIAL_NONRANDOMCited in: Complications & Iatrogenesis - [407]
Pichon N, Amiel JB, François B et al.. “Efficacy of and tolerance to mild induced hypothermia after out-of-hospital cardiac arrest using an endovascular cooling system.” Critical care (London, England) (2007). PMID: 17598898 ↗
L4TRIAL_NONRANDOMCited in: Complications & Iatrogenesis - [408]
Ramanathan K, Yeo N, Alexander P et al.. “Role of extracorporeal membrane oxygenation in children with sepsis: a systematic review and meta-analysis.” Critical care (London, England) (2020). PMID: 33287861 ↗
L1SR_OBSCited in: Complications & Iatrogenesis - [409]
Jamme M, Daviaud F, Charpentier J et al.. “Time Course of Septic Shock in Immunocompromised and Nonimmunocompromised Patients.” Critical care medicine (2017). PMID: 28937407 ↗
L2OTHERCited in: Complications & Iatrogenesis - [410]
Péju E, Llitjos JF, Charpentier J et al.. “Impact of Blood Product Transfusions on the Risk of ICU-Acquired Infections in Septic Shock.” Critical care medicine (2021). PMID: 33591005 ↗
L2OTHERCited in: Complications & Iatrogenesis - [411]
Monneret G, Lafon T, Gossez M et al.. “Monocyte HLA-DR expression in septic shock patients: insights from a 20-year real-world cohort of 1023 cases.” Intensive care medicine (2025). PMID: 40986015 ↗
L2OTHERCited in: Complications & Iatrogenesis - [412]
Mentzelopoulos SD, Pratikaki M, Platsouka E et al.. “Prolonged use of carbapenems and colistin predisposes to ventilator-associated pneumonia by pandrug-resistant Pseudomonas aeruginosa.” Intensive care medicine (2007). PMID: 17549457 ↗
L3OTHERCited in: Complications & Iatrogenesis - [413]
Damas P, Layios N, Seidel L et al.. “Severity of ICU-acquired pneumonia according to infectious microorganisms.” Intensive care medicine (2011). PMID: 21614638 ↗
L2OTHERCited in: Complications & Iatrogenesis - [414]
Grimaldi D, Louis S, Pène F et al.. “Profound and persistent decrease of circulating dendritic cells is associated with ICU-acquired infection in patients with septic shock.” Intensive care medicine (2011). PMID: 21805160 ↗
L2OTHERCited in: Complications & Iatrogenesis - [415]
Morel J, Casoetto J, Jospé R et al.. “De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit.” Critical care (London, England) (2010). PMID: 21167047 ↗
L2COHORTCited in: Complications & Iatrogenesis - [416]
Rademacher J, Ewig S, Grabein B et al.. “Key summary of German national guideline for adult patients with nosocomial pneumonia- Update 2024 Funding number at the Federal Joint Committee (G-BA): 01VSF22007.” Infection (2024). PMID: 39115698 ↗
L1GUIDELINECited in: Complications & Iatrogenesis - [417]
Tumbarello M, De Pascale G, Trecarichi EM et al.. “Effect of aerosolized colistin as adjunctive treatment on the outcomes of microbiologically documented ventilator-associated pneumonia caused by colistin-only susceptible gram-negative bacteria.” Chest (2013). PMID: 23989805 ↗
L3OTHERCited in: Complications & Iatrogenesis - [418]
Gurnani PK, Barlow B, Boling B et al.. “Major Publications in the Critical Care Pharmacotherapy Literature: 2022.” Critical care explorations (2023). PMID: 37753239 ↗
L5SR_OBSCited in: Complications & Iatrogenesis, Prevention, Screening and Post-ICU Surveillance - [419]
Kubo K, Kondo Y, Yoshimura J et al.. “Short- versus prolonged-course antibiotic therapy for sepsis or infectious diseases in critically ill adults: a systematic review and meta-analysis.” Infectious diseases (London, England) (2021). PMID: 34772325 ↗
L1SR_OBSCited in: Complications & Iatrogenesis - [420]
Nair GB, Niederman MS. “Year in review 2013: Critical Care--respiratory infections.” Critical care (London, England) (2014). PMID: 25672674 ↗
L5REVIEW_NARRATIVECited in: Complications & Iatrogenesis, Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [421]
Depuydt PO, Vandijck DM, Bekaert MA et al.. “Determinants and impact of multidrug antibiotic resistance in pathogens causing ventilator-associated-pneumonia.” Critical care (London, England) (2008). PMID: 19014695 ↗
L2OTHERCited in: Complications & Iatrogenesis - [422]
Bassetti M, Giacobbe DR, Vena A et al.. “Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project.” Critical care (London, England) (2019). PMID: 31200780 ↗
L2OTHERCited in: Complications & Iatrogenesis - [423]
Masson S, Caironi P, Fanizza C et al.. “Sequential N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin Measurements During Albumin Replacement in Patients With Severe Sepsis or Septic Shock.” Critical care medicine (2016). PMID: 26571184 ↗
L1RCTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [424]
Trusson R, Brunot V, Larcher R et al.. “Short- and Long-Term Outcome of Chronic Dialyzed Patients Admitted to the ICU and Assessment of Prognosis Factors: Results of a 6-Year Cohort Study.” Critical care medicine (2020). PMID: 32697507 ↗
L2COHORTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [425]
Estenssoro E, Kanoore Edul VS, Loudet CI et al.. “Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina.” Critical care medicine (2018). PMID: 29742584 ↗
L2COHORTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [426]
Palizas F, Dubin A, Regueira T et al.. “Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial.” Critical care (London, England) (2009). PMID: 19335912 ↗
L1RCTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [427]
Merouani M, Guignard B, Vincent F et al.. “Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic.” Critical care (London, England) (2008). PMID: 19068113 ↗
L1RCTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [428]
Behnes M, Bertsch T, Lepiorz D et al.. “Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment.” Critical care (London, England) (2014). PMID: 25190134 ↗
L2TRIAL_NONRANDOMCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [429]
Dong X, Liu Q, Zheng Q et al.. “Alterations of B Cells in Immunosuppressive Phase of Septic Shock Patients.” Critical care medicine (2020). PMID: 32304414 ↗
L2OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [430]
Gleeson PJ, Crippa IA, Mongkolpun W et al.. “Renin as a Marker of Tissue-Perfusion and Prognosis in Critically Ill Patients.” Critical care medicine (2019). PMID: 30653055 ↗
L2OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [431]
Galbois A, Aegerter P, Martel-Samb P et al.. “Improved prognosis of septic shock in patients with cirrhosis: a multicenter study*.” Critical care medicine (2014). PMID: 24732239 ↗
L3OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [432]
Lemiale V, Pons S, Mirouse A et al.. “Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.” Critical care medicine (2020). PMID: 32317596 ↗
L3OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [433]
Meissner A, Genga KR, Studart FS et al.. “Epidemiology of and factors associated with end-of-life decisions in a surgical intensive care unit.” Critical care medicine (2010). PMID: 20068464 ↗
L2OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [434]
Orlikowski D, Sharshar T, Porcher R et al.. “Prognosis and risk factors of early onset pneumonia in ventilated patients with Guillain-Barré syndrome.” Intensive care medicine (2006). PMID: 17019557 ↗
L2OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [435]
Bedos JP, Varon E, Porcher R et al.. “Host-pathogen interactions and prognosis of critically ill immunocompetent patients with pneumococcal pneumonia: the nationwide prospective observational STREPTOGENE study.” Intensive care medicine (2018). PMID: 30456466 ↗
L2OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [436]
Vandijck DM, Benoit DD, Depuydt PO et al.. “Impact of recent intravenous chemotherapy on outcome in severe sepsis and septic shock patients with hematological malignancies.” Intensive care medicine (2008). PMID: 18214437 ↗
L3OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [437]
Coslovsky M, Takala J, Exadaktylos AK et al.. “A clinical prediction model to identify patients at high risk of death in the emergency department.” Intensive care medicine (2015). PMID: 25792208 ↗
L2OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [438]
Chang Y, Oh JH, Oh DK et al.. “Culture-negative sepsis may be a different entity from culture-positive sepsis: a prospective nationwide multicenter cohort study.” Critical care (London, England) (2024). PMID: 39587586 ↗
L2COHORTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [439]
Montravers P, Kantor E, Constantin JM et al.. “Epidemiology and prognosis of anti-infective therapy in the ICU setting during acute pancreatitis: a cohort study.” Critical care (London, England) (2019). PMID: 31805988 ↗
L3COHORTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [440]
White AC, Joseph B, Gireesh A et al.. “Terminal withdrawal of mechanical ventilation at a long-term acute care hospital: comparison with a medical ICU.” Chest (2009). PMID: 19429725 ↗
L3OTHERCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [441]
García-Aguilera MF, Yu-Liu Y, Alexander-León H et al.. “Mortality in Cancer Patients with Septic Shock in Intensive Care: Systematic Review and Meta-Analysis.” Journal of intensive care medicine (2025). PMID: 40953035 ↗
L1SR_OBSCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [442]
Alqeeq BF, Ayyad M, Albandak M et al.. “The clinical significance of thrombocytopenia in sepsis and septic shock: a systematic review and meta-analysis.” BMC anesthesiology (2025). PMID: 40597659 ↗
L1SR_OBSCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [443]
Chen Y, Jiang H, Wei Y et al.. “Blood pressure response index and clinical outcomes in patients with septic shock: a multicenter cohort study.” EBioMedicine (2024). PMID: 39059317 ↗
L3COHORTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [444]
Tao X, Ye S. “Risk factors for invasive mechanical ventilation, extracorporeal membrane oxygenation, and mortality in children with severe adenovirus infection in the pediatric intensive care unit: a retrospective study.” BMC pediatrics (2025). PMID: 40296021 ↗
L3COHORTCited in: Prognostication, Goals of Care & End-of-Life (incl. Brain-Death Determination & Organ Donation) - [445]
Fujii T, Ganeko R, Kataoka Y et al.. “Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult patients with sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis.” Intensive care medicine (2017). PMID: 29204670 ↗
L1SR_OBSCited in: Special Populations - [446]
Vincent JL, Sakr Y, Sprung CL et al.. “Sepsis in European intensive care units: results of the SOAP study.” Critical care medicine (2006). PMID: 16424713 ↗
L2OTHERCited in: Special Populations - [447]
Geri G, Vignon P, Aubry A et al.. “Cardiovascular clusters in septic shock combining clinical and echocardiographic parameters: a post hoc analysis.” Intensive care medicine (2019). PMID: 30888443 ↗
L2OTHERCited in: Special Populations - [448]
Tissot F, Lamoth F, Hauser PM et al.. “β-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis.” American journal of respiratory and critical care medicine (2013). PMID: 23782027 ↗
L2OTHERCited in: Special Populations - [449]
Tolsma V, Schwebel C, Azoulay E et al.. “Sepsis severe or septic shock: outcome according to immune status and immunodeficiency profile.” Chest (2014). PMID: 25033349 ↗
L2OTHERCited in: Special Populations - [450]
Dmello D, Taylor S, O'Brien J et al.. “Outcomes of etomidate in severe sepsis and septic shock.” Chest (2010). PMID: 20651024 ↗
L3OTHERCited in: Special Populations - [451]
Whitson MR, Mo E, Nabi T et al.. “Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock.” Chest (2016). PMID: 26953217 ↗
L3OTHERCited in: Special Populations - [452]
Kaukonen KM, Bailey M, Suzuki S et al.. “Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012.” JAMA (2014). PMID: 24638143 ↗
L2OTHERCited in: Special Populations - [453]
Ferrer R, Artigas A, Levy MM et al.. “Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain.” JAMA (2008). PMID: 18492971 ↗
L2OTHERCited in: Special Populations - [454]
Mokart D, Bianchi A, Ronflé R et al.. “Determinants of Septic Shock and 90-Day Mortality After Postoperative Healthcare-Associated Intra-Abdominal Infection: The Sepsi-Pop Study, a Multicenter Retrospective Study.” Shock (Augusta, Ga.) (2026). PMID: 41949841 ↗
L3COHORTCited in: Special Populations - [455]
Şahinoğlu MS, Kökkızıl SÖ, Tarakçı A et al.. “Prognostic factors for mortality in critically ill patients with infections caused by carbapenem-resistant gram-negative pathogens treated with ceftazidime-avibactam: a multicenter retrospective study.” BMC infectious diseases (2026). PMID: 41882581 ↗
L4COHORTCited in: Special Populations - [456]
Chen Q, Zeng J, Zhong L et al.. “From proteomics to colloidal gold tests for urinary thrombomodulin: a prospective cohort study on accurate sepsis screening.” Frontiers in cellular and infection microbiology (2026). PMID: 41878263 ↗
L3COHORTCited in: Special Populations - [457]
Wattanarat B, Foocharoen C, Panitchote A. “Clinical predictors of mortality in critically ill systemic sclerosis patients: a 6-year retrospective cohort study.” Rheumatology (Oxford, England) (2026). PMID: 41507092 ↗
L4COHORTCited in: Special Populations - [458]
Shorr AF, Williams MD. “Venous thromboembolism in critically ill patients. Observations from a randomized trial in sepsis.” Thrombosis and haemostasis (2009). PMID: 19132200 ↗
L1RCTCited in: Prevention, Screening and Post-ICU Surveillance - [459]
Monti G, Konkayev A, Carta S et al.. “High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.” Contemporary clinical trials (2023). PMID: 37625587 ↗
L5TRIAL_NONRANDOMCited in: Prevention, Screening and Post-ICU Surveillance - [460]
Karlsson H, Afrasiabi A, Ohlsson M et al.. “Treating shock with norepinephrine administered in midline catheters in an intermediary care unit: a retrospective cohort study.” BMJ open (2024). PMID: 39806688 ↗
L4COHORTCited in: Prevention, Screening and Post-ICU Surveillance - [461]
Corriero A, Soloperto R, Giglio M et al.. “Probiotics to reduce ventilator-associated pneumonia in adults with acute non‑anoxic brain injury: Study Protocol for a Double-Blind Multicenter Randomized International Clinical Trial (PROACT).” Trials (2025). PMID: 41214813 ↗
L5TRIAL_NONRANDOMCited in: Prevention, Screening and Post-ICU Surveillance - [462]
Kofoed A, Perner A, Marker S et al.. “Effects of simulated sample sizes on mortality estimates-Protocol for a study in 3 randomised ICU trials.” Acta anaesthesiologica Scandinavica (2019). PMID: 31032881 ↗
L5TRIAL_NONRANDOMCited in: Prevention, Screening and Post-ICU Surveillance