Adult Septic Shock Research Articles

Immunometabolic Chaos in Septic Shock.

Septic shock is associated with over 40% mortality. The immune response in septic shock is tightly regulated by cellular metabolism and transitions from early hyper-inflammation to later hypo-inflammation. Patients are susceptible to secondary infections during hypo-inflammation. The magnitude of the metabolic dysregulation and the effect of plasma metabolites on the circulating immune cells in septic shock are not reported. We hypothesized that the accumulated plasma metabolites affect the immune response in septic shock during hypo-inflammation. Our study took a unique approach. Using peripheral blood from adult septic shock patients and healthy controls, we studied: 1. Whole blood stimulation ± E. Coli lipopolysaccharide (LPS: endotoxin) to analyze plasma TNF protein, and 2. Plasma metabolomic profile by Metabolon. Inc. 3. We exposed peripheral blood mononuclear cells (PBMCs) from healthy controls to commercially available carbohydrate, amino acid, and fatty acid metabolites and studied the response to LPS. We report that: 1. The whole blood stimulation of the healthy control group showed a significantly upregulated TNF protein, while the septic shock group remained endotoxin tolerant, a biomarker for hypo-inflammation. 2. A significant accumulation of carbohydrate, amino acid, fatty acid, ceramide, sphingomyelin, and TCA cycle pathway metabolites in septic shock plasma. 3. In vitro exposure to five metabolites repressed while two metabolites upregulated the inflammatory response of PBMCs to LPS. We conclude that the endotoxin-tolerant phenotype of septic shock is associated with a simultaneous accumulation of plasma metabolites from multiple metabolic pathways, and these metabolites fundamentally influence the immune response profile of circulating cells.

Temperature trajectories and mortality in hypothermic sepsis patients

ObjectivesHypothermia is associated with poor outcomes in sepsis patients, and hypothermic sepsis patients exhibit temperature alterations during initial treatment. The objective of this study was to classify hypothermic sepsis patients based on body temperature trajectories and investigate the associations of these patients with 28-day mortality. MethodsThis was a retrospective analysis of prospectively collected data from adult sepsis or septic shock patients who visited three emergency departments between August 2014 and December 2019. Hypothermic sepsis was defined as an initial body temperature <36 °C. delta temperature was calculated by subtracting the 0 h body temperature from the 6 h body temperature. We divided the patients into three groups according to delta temperature: Group A (delta temperature ≤ 0), Group B (0 < delta temperature ≤ 1) and Group C (delta temperature > 1). The primary outcome was 28-day mortality, and a multivariable Cox proportional hazards regression model was generated. ResultsAmong 7344 patients with sepsis or septic shock, 325 hypothermic patients were included in the analysis, and the overall mortality rate was 36%. While initial body temperature was not different between survivors and nonsurvivors, survivors exhibited a higher body temperature at 6 h. The 28-day mortality rates for Groups A, B and C were 53.1%, 36.0%, and 30.0%, respectively, and Group A had significantly higher mortality than Group C did (p < 0.05). Group C demonstrated a 44.2% decrease in 28-day mortality compared to Group A (adjusted hazard ratio of 0.558; 95% confidence interval of 0.330–0.941). ConclusionsIn hypothermic sepsis patients, an increase of 1 °C or more in body temperature after the initial 6 h is associated with a reduced risk of 28-day mortality.

Ischemia-Modified Albumin, Lactate, and Combination for Predicting Mortality in Patients with Septic Shock in the Emergency Department.

Ischemia-modified albumin (IMA) is produced during ischemia and reactive oxygen species production. This study aimed to evaluate the association between IMA and mortality in a larger population and the prognostic value of the combination of IMA and lactate for predicting mortality in septic shock patients in the emergency department. This retrospective observational study included adult septic shock patients between October 2019 and December 2021. A multivariable Cox proportional hazards model was performed. IMA was significantly higher in the non-surviving group than in the surviving group (89.1 ± 7.2 vs. 83.8 ± 6.2 U/mL, p < 0.001). IMA was independently associated with 28-day mortality after adjustments (adjusted hazard ratio [aHR]: 1.075, 95% confidence interval [CI]: 1.016-1.138, p = 0.012). The area under the ROC curve (AUROC) of IMA was 0.712 (95% CI: 0.648-0.775, p < 0.001) and was comparable to that of lactate. The AUROC of the combination of IMA and lactate was 0.838 (95% CI: 0.786-0.889, p < 0.001). The group with both high lactate and high IMA levels showed an extremely high risk of mortality than other groups (86.1%; aHR 8.956, 95% CI 4.071-19.70, p < 0.001). The elevation of IMA was associated with mortality in septic shock patients. The combination of IMA and lactate can be a helpful tool for early risk stratification of septic shock patients.

An observational prospective cross-sectional study on extravascular lung water by lung ultrasound as a guide to fluid resuscitation therapy in adult septic shock in tertiary care hospital in central India

Background Septic shock is a life-threatening condition characterized by systemic inflammation and organ dysfunction, with fluid resuscitation being a cornerstone of management. However, indiscriminate fluid administration can lead to fluid overload and worsen outcomes. Extravascular lung water (EVLW) estimation by lung ultrasound has emerged as a promising tool for guiding fluid therapy in septic shock, allowing clinicians to assess pulmonary edema and tailor resuscitation strategies accordingly. Methods This prospective observational study aims to evaluate the utility of EVLW estimation by lung ultrasound in guiding fluid resuscitation therapy in adult patients with septic shock admitted to a rural tertiary care teaching hospital. Eligible patients admitted to the intensive care unit (ICU) will undergo baseline demographic and clinical assessments, including lung ultrasound, to quantify EVLW using B-line analysis. Fluid resuscitation therapy will be initiated based on EVLW findings, with subsequent adjustments guided by repeat lung ultrasound examinations at 6, 12, 24, and 48 hours post-initiation. Outcome measures include changes in mean PaO2/FiO2 ratios, respiratory parameters, renal function, fluid balance, and mortality rates. Expected Outcome We anticipate that EVLW-guided fluid resuscitation therapy will lead to more precise and tailored management of septic shock, potentially reducing the incidence of fluid overload, ARDS, and renal dysfunction. By optimizing fluid management strategies based on individual patient characteristics and responses, we aim to improve clinical outcomes and enhance the delivery of care for patients with septic shock.

Septic shock in adults: guidelines of the All-Russian public organization “Federation of Anesthesiologists and Reanimatologists”

The paper represents the clinical guidelines for septic shock in adults, approved by the All-Russian public organization “Federation of anesthesiologists and reanimatologists” in 2023. Septic shock is a widespread condition with a high mortality rate. The recommendations cover the issues of etiology, pathogenesis, clinical signs and symptoms, methods of laboratory and instrumental diagnosis of septic shock. The clinical guidelines present initial therapy for septic shock, including approaches to vasopressor and inotropic therapy, recommendations for choosing antibacterial drugs, fluid and adjuvant therapy. The issues of surgical treatment of the infection are discussed. The article contains the criteria for the quality of medical care for the adult patients with septic shock and algorithms for the decision making in the diagnosis and intensive care of patients with septic shock.

Extracorporeal Membrane Oxygenation for Septic Shock in Adults and Children: A Narrative Review.

Refractory septic shock is associated with a high risk of death. Circulatory support in the form of veno-arterial extracorporeal membrane oxygenation (VA ECMO) may function as a bridge to recovery, allowing for the treatment of the source of the sepsis. Whilst VA ECMO has been accepted as the means of hemodynamic support for children, in adults, single center observational studies show survival rates of only 70-90% for hypodynamic septic shock. The use of VA ECMO for circulatory support in hyperdynamic septic shock with preserved cardiac output or when applied late during cardio-pulmonary resuscitation is not recommended. With unresolving septic shock and a loss of ventriculo-arterial coupling, stress cardiomyopathy often develops. If the cardiac index (CI) approaches subnormal levels (CI < 2.5 L/min m-2) that do not match low systemic vascular resistance with a resulting loss of vital systemic perfusion pressure, VA ECMO support should be considered. A further decrease to the level of cardiogenic shock (CI < 1.8 L/min m-2) should be regarded as an indication for VA ECMO insertion. For patients who maintain a normal-to-high CI as part of their refractory vasoparalysis, VA ECMO support is justified in children and possibly in patients with a low body mass index. Extracorporeal support for septic shock should be limited to high-volume ECMO centers.

Impact of Vasodilator Administration on Survival in Patients with Sepsis: A Systematic Review and Meta-Analysis.

Rationale: Sepsis and septic shock are associated with microcirculatory dysfunction, which is believed to contribute to sepsis-induced organ failure. Vasodilators have been proposed to improve tissue perfusion in sepsis, but the overall survival impact of this strategy is unclear. Objectives: To evaluate the impact of systemic vasodilator administration in patients with sepsis and septic shock on mortality. Methods: We conducted a meta-analysis using a random effects model. Published and unpublished randomized trials in adult patients with sepsis and septic shock were included when comparing the use of systemic vasodilators against no vasodilators. The primary outcome was 28-30-day mortality, and secondary outcomes were organ function and resource use measures. Results: We included eight randomized trials (1,076 patients). In patients randomized to vasodilator arms compared with those randomized to treatment without vasodilators, the 28-30-day mortality risk ratio was 0.74 (95% confidence interval, 0.54-1.01). In a chronological cumulative meta-analysis, the association between vasodilators and survival improved over time. In a prespecified subgroup analysis in 104 patients in two randomized trials, prostacyclin analogues were associated with a decreased rate of 28-30-day mortality among patients with sepsis and septic shock (risk ratio, 0.46; 95% confidence interval, 0.25-0.85). Conclusions: In patients with sepsis and septic shock, administration of vasodilators is not associated with decreased 28-30-day mortality, but the confidence interval suggests potential benefit, and the meta-analysis might lack power. Prostacyclin appears the most promising. The results of this meta-analysis should encourage randomized trials evaluating the impact of vasodilators on mortality in sepsis.

Surviving Sepsis Campaign.

Surviving Sepsis Campaign.

Persistently Elevated Soluble Triggering Receptor Expressed on Myeloid Cells 1 and Decreased Monocyte Human Leucocyte Antigen DR Expression Are Associated With Nosocomial Infections in Septic Shock Patients.

Observational study. University Hospital in France. One hundred sixteen adult septic shock patients as a post hoc study from the IMMUNOSEPSIS cohort (NCT04067674). None. Plasma sTREM-1 and monocyte HLA-DR were measured at day 1 or 2 (D1/D2), D3/D4, and D6/D8 after admission. Associations with nosocomial infection were evaluated through multivariable analyses. At D6/D8, both markers were combined, and association with increased risk of nosocomial infection was evaluated in the subgroup of patients with most deregulated markers in a multivariable analysis with death as a competing risk. Significantly decreased mHLA-DR at D6/D8 and increased sTREM-1 concentrations were measured at all time points in nonsurvivors compared with survivors. Decreased mHLA-DR at D6/D8 was significantly associated with increased risk of secondary infections after adjustment for clinical parameters with a subdistribution hazard ratio of 3.61 (95% CI, 1.39-9.34; p = 0.008). At D6/D8, patients with persistently high sTREM-1 and decreased mHLA-DR presented with a significantly increased risk of infection (60%) compared with other patients (15.7%). This association remained significant in the multivariable model (subdistribution hazard ratio [95% CI], 4.65 [1.98-10.9]; p < 0.001). In addition to its prognostic interest on mortality, sTREM-1, when combined with mHLA-DR, may help to better identify immunosuppressed patients at risk of nosocomial infections.

Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock

BackgroundPharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient.MethodsSecondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters.Results8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes.ConclusionsIdentifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result.Trial registrationNCT02750163.

Benchmarking of two bioinformatic workflows for the analysis of whole-genome sequenced Staphylococcus aureus collected from patients with suspected sepsis

BackgroundThe rapidly growing area of sequencing technologies, and more specifically bacterial whole-genome sequencing, could offer applications in clinical microbiology, including species identification of bacteria, prediction of genetic antibiotic susceptibility and virulence genes simultaneously. To accomplish the aforementioned points, the commercial cloud-based platform, 1928 platform (1928 Diagnostics, Gothenburg, Sweden) was benchmarked against an in-house developed bioinformatic pipeline as well as to reference methods in the clinical laboratory.MethodsWhole-genome sequencing data retrieved from 264 Staphylococcus aureus isolates using the Illumina HiSeq X next-generation sequencing technology was used. The S. aureus isolates were collected during a prospective observational study of community-onset severe sepsis and septic shock in adults at Skaraborg Hospital, in the western region of Sweden. The collected isolates were characterized according to accredited laboratory methods i.e., species identification by MALDI-TOF MS analysis and phenotypic antibiotic susceptibility testing (AST) by following the EUCAST guidelines. Concordance between laboratory methods and bioinformatic tools, as well as concordance between the bioinformatic tools was assessed by calculating the percent of agreement.ResultsThere was an overall high agreement between predicted genotypic AST and phenotypic AST results, 98.0% (989/1006, 95% CI 97.3–99.0). Nevertheless, the 1928 platform delivered predicted genotypic AST results with lower very major error rates but somewhat higher major error rates compared to the in-house pipeline. There were differences in processing times i.e., minutes versus hours, where the 1928 platform delivered the results faster. Furthermore, the bioinformatic workflows showed overall 99.4% (1267/1275, 95% CI 98.7–99.7) agreement in genetic prediction of the virulence gene characteristics and overall 97.9% (231/236, 95% CI 95.0–99.2%) agreement in predicting the sequence types (ST) of the S. aureus isolates.ConclusionsAltogether, the benchmarking disclosed that both bioinformatic workflows are able to deliver results with high accuracy aiding diagnostics of severe infections caused by S. aureus. It also illustrates the need of international agreement on quality control and metrics to facilitate standardization of analytical approaches for whole-genome sequencing based predictions.

Prognostic Value of PCO2 Gap in Adult Septic Shock Patients: A Systematic Review and Meta-Analysis.

Sepsis cases caused substantial mortality and a significant burden on healthcare costs and resources. To tackle this problem, there has been discussion surrounding O2 parameters as it has a distinct outcome in septic patients. This review aimed to evaluate the prognostic value of the central venous-arterial carbon dioxide difference (PCO2) gap in patients with septic shock. A comprehensive systematic search was performed through electronic databases including Pubmed, Scopus, and Embase for studies focusing on the use of PCO2 gap as a mortality predictor in septic shock patients. Other secondary outcomes such as mean arterial pressure, lactate clearance, the acute physiology and chronic health evaluation II score, and intensive care unit length of stay were also measured. The Newcastle-Ottawa Scale tool was used to assess the risk of bias. A total of 8 studies were analysed. The mortality rate (odds ratio=0.50, 95% CI=0.28-0.87, P < .01) and lactate levels (mean difference [MD] = -0.98; 95% CI=-1.62 to -0.35; P=.001) of the low PCO2 gap group were significantly lower than the high gap group. The low gap group had a significantly higher mean arterial pressure compared to the high gap group (MD=4.54; 95% CI=2.14 to 6.95; P=.001). There were no pronounced outcomes in acute physiology and chronic health evaluation score and intensive care unit length of stay. PCO2 gap can potentially be used as a marker for mortality rate in septic shock patients. It is also significantly associated with other predictors, such as mean arterial pressure and lactate clearance.

P(v-a)CO2/C(a-v)O2 as a red blood cell transfusion trigger and prognostic indicator for sepsis-related anaemia: protocol for a prospective cohort study

IntroductionRed blood cell (RBC) transfusion primarily aims to improve oxygen transport and tissue oxygenation. The transfusion strategy based on haemoglobin concentration could not accurately reflect cellular metabolism. The ratio of...

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial

BackgroundHemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis.MethodsA multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80–85 mmHg (high-target) and 65–70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients’ condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization.DiscussionThe result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients.Trial registrationUMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

Evaluation of the role of hydrocortisone either alone or combined with fludrocortisone in the outcome of septic shock in adults

BackgroundManagement of sepsis is a time critical procedure; the consequences of improperly managed sepsis and septic shock can cause multiple organ dysfunction and death. The aim of this study was to evaluate of the role of hydrocortisone either alone or with fludrocortisone on the outcome septic shock in adults. This study was conducted on 66 patients who were assigned randomly to 3 groups each containing 22 patients. Control group had received standard therapy for sepsis, and H group had received standard therapy for sepsis plus hydrocortisone. HF group had received standard therapy for sepsis plus hydrocortisone and fludrocortisone.ResultsIt showed that the use of corticosteroids (the hydrocortisone or the hydrocortisone plus fludrocortisone) in septic patients was associated with significant reduction in the time to wean from vasopressors and length of intensive care unit stay. Meanwhile, there were no significant effect of the mortality rate, Sepsis-Related Organ Failure Assessment (SOFA) score reduction, gastrointestinal bleeding, and superinfection as corticosteroids adverse effects between the three groups.ConclusionsThe corticosteroids in septic shock have significant positive impacts on some aspects in treatment of septic shock but it does not affect the mortality rate of the patients.

No benefit of hydrocortisone, ascorbic acid, and thiamine in reducing mortality in adult sepsis patients: a systematic review and meta-analysis

Abstract Background Supplementation of corticosteroid, ascorbic acid and thiamine in adult septic patients remains controversial. We aimed to evaluate the efficacy and safety of hydrocortisone, ascorbic acid and thiamine (HAT) in adult septic patients. Methods Data search included Pumbed, EMBASE, and the Cochrane Library from inception to Sep, 2021. Only studies with classifications of sepsis and intravenous HAT treatment were included. Adult patients with sepsis (aged ≥18 years) were divided into 2 groups. The treatment group received HAT therapy, whereas the control group received standard care and/or intravenous hydrocortisone. The primary outcome was hospital mortality. Results Eleven studies including 4579 patients who fulfilled the predefined criteria were analyzed (6 randomized controlled trials [RCTs] and 5 clinical cohort studies). No hospital mortality reduction was demonstrated in patients treated with HAT when compared to the reference (OR: 0.99; 95% CI: 0.77 to 1.27; I 2 = 39%) group. Sequential organ failure assessment (SOFA) score decrement at 72hours was more significant in HAT-treated patients (mean difference [MD]: –1.23; 95% CI: –1.94 to –0.53; I 2 = 81%). There was no difference in the duration of vasopressor use between HAT-treated patients and controls (MD: –4.92; 95% CI: –24.38 to 14.53; I 2 = 97%). Statistical heterogeneity was noted with no sign of significant publication bias. Conclusion In adult sepsis and septic shock patients, HAT treatment failed to reduce mortality or shorten vasopressor duration, but reduced SOFA scores.

The Association of High Dose Vasopressor and Delayed Vasopressor Titration with 28-Day Mortality in Adult Patients with Septic Shock

Objective: This study aimed to investigate any association between vasopressor dose and mortality, and to identify factors independently associated with 28-day mortality in adult patients with septic shock. Material and Methods: Adult septic shock patients admitted to internal medicine wards; from May 2018-November 2020, were retrospectively included. Collected data included: patient demographics and clinical characteristics, baseline vital signs, source of infection, vasopressor dose, treatment modalities and patient outcomes. The primary outcome was 28-day mortality. Results: From 253 patients, 54.9% survived, and 45.1% died. Compared to survivors, non-survivors had a significantly higher median Acute Physiology and Chronic Health Evaluation II score, higher median baseline serum lactate level and required a higher median-maximum dose of vasopressor. Multivariate analysis showed the maximum dose of vasopressor &gt;0.2 mcg/kg/min (odd ratio (OR): 2.91, 95% confidence interval (CI): 1.13-7.47; p-value=0.027), time to maximum dose of vasopressor after 24 hours (OR: 4.98, 95%Cl: 2.07-11.99; p-value&lt;0.001), Sequential Organ Failure Assessment score &gt;10 (OR: 2.92, 95%CI: 1.27-6.71; p-value=0.012), pneumonia (OR: 2.16, 95%CI: 1.01-4.61; p-value=0.047) and receiving fluid resuscitation during the first 24 hours &lt;3,000 mL (OR: 2.27, 95%CI: 1.05-4.89; p-value=0.037) to be independent predictors of 28-day mortality. Conclusions: A higher intensity of vasopressor and longer time to maximum dose of vasopressor were found to be independent predictors of septic shock mortality.

Machine learning to predict vasopressin responsiveness in patients with septic shock.

The objective of this study was to develop and externally validate a model to predict adjunctive vasopressin response in patients with septic shock being treated with norepinephrine for bedside use in the intensive care unit. This was a retrospective analysis of two adult tertiary intensive care unit septic shock populations. Barnes-Jewish Hospital (BJH) from 2010 to 2017 and Beth Israel Deaconess Medical Center (BIDMC) from 2001 to 2012. Two septic shock populations (548 BJH patients and 464 BIDMC patients) that received vasopressin as second-line vasopressor. Patients who were vasopressin responsive were compared with those who were nonresponsive. Vasopressin response was defined as survival with at least a 20% decrease in maximum daily norepinephrine requirements by one calendar day after vasopressin initiation, without a third-line vasopressor. Two supervised machine learning models (gradient-boosting machine [XGBoost] and elastic net penalized logistic regression [EN]) were trained in 1000 bootstrap replications of the BJH data and externally validated in the BIDMC data to predict vasopressin responsiveness. Vasopressin responsiveness was similar among each cohort (BJH 45% and BIDMC 39%). Mortality was lower for vasopressin responders compared with nonresponders in the BJH (51% vs. 73%) and BIDMC (45% vs. 83%) cohorts, respectively. Both models demonstrated modest discrimination in the training (XGBoost area under receiver operator curve [AUROC] 0.61 [95% confidence interval (CI) 0.61-0.61], EN 0.59 [95% CI 0.58-0.59]) and external validation (XGBoost 0.68 [95% CI 0.63-0.73], EN 0.64 [95% CI 0.59-0.69]) datasets. Vasopressin nonresponsiveness is common and associated with increased mortality. The models' modest performances highlight the complexity of septic shock and indicate that more research will be required before clinical decision support tools can aid in anticipating patient-specific responsiveness to vasopressin.

Methods for Phenotyping Adult Patients in Sepsis and Septic Shock: A Scoping Review.

OBJECTIVE:Despite its heterogeneous phenotypes, sepsis or life-threatening dysfunction in response to infection is often treated empirically. Identifying patient subgroups with unique pathophysiology and treatment response is critical to the advancement of sepsis care. However, phenotyping methods and results are as heterogeneous as the disease itself. This scoping review evaluates the prognostic capabilities and treatment implications of adult sepsis and septic shock phenotyping methods.DATA SOURCES:Medline and Embase.STUDY SELECTION:We included clinical studies that described sepsis or septic shock and used any clustering method to identify sepsis phenotypes. We excluded conference abstracts, literature reviews, comments, letters to the editor, and in vitro studies. We assessed study quality using a validated risk of bias tool for observational cohort and cross-sectional studies.DATA EXTRACTION:We extracted population, methodology, validation, and phenotyping characteristics from 17 studies.DATA SYNTHESIS:Sepsis phenotyping methods most frequently grouped patients based on the degree of inflammatory response and coagulopathy using clinical, nongenomic variables. Five articles clustered patients based on genomic or transcriptomic data. Seven articles generated patient subgroups with differential response to sepsis treatments. Cluster clinical characteristics and their associations with mortality and treatment response were heterogeneous across studies, and validity was evaluated in nine of 17 articles, hindering pooled analysis of results and derivation of universal truths regarding sepsis phenotypes, their prognostic capabilities, and their associations with treatment response.CONCLUSIONS:Sepsis phenotyping methods can identify high-risk patients and those with high probability of responding well to targeted treatments. Research quality was fair, but achieving generalizability and clinical impact of sepsis phenotyping will require external validation and direct comparison with alternative approaches.

Surviving sepsis campaign: International guidelines for management of sepsis and septic shock in adults 2021 - endorsement by the Scandinavian society of anaesthesiology and intensive care medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. The guideline serves as a useful bedside decision aid for clinicians managing adults with suspected and confirmed septic shock and sepsis‐associated organ dysfunction.