National ICU Registries as Enablers of Clinical Research and Quality Improvement.

OBJECTIVES: Clinical quality registries (CQRs) have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. This narrative review describes the challenges, proposed solutions, and evidence generated by National ICU registries as facilitators for research and quality improvement. DATA SOURCES: English language articles were identified in PubMed using phrases related to ICU registries, CQRs, outcomes, and case-mix. STUDY SELECTION: Original research, review articles, letters, and commentaries, were considered. DATA EXTRACTION: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review. DATA SYNTHESIS: CQRs have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. The initial experience in European countries and in Oceania ensured that through locally generated data, ICUs could assess their performances by using risk-adjusted measures and compare their results through fair and validated benchmarking metrics with other ICUs contributing to the CQR. The accomplishment of these initiatives, coupled with the increasing adoption of information technology, resulted in a broad geographic expansion of CQRs as well as their use in quality improvement studies, clinical trials as well as international comparisons, and benchmarking for ICUs. CONCLUSIONS: ICU registries have provided increased knowledge of case-mix and outcomes of ICU patients based on real-world data and contributed to improve care delivery through quality improvement initiatives and trials. Recent increases in adoption of new technologies (i.e., cloud-based structures, artificial intelligence, machine learning) will ensure a broader and better use of data for epidemiology, healthcare policies, quality improvement, and clinical trials.

Epidemiology of Renal Replacement Therapy for Critically Ill Patients across Seven Health Jurisdictions.

INTRODUCTION: Acute kidney injury (AKI) requiring treatment with renal replacement therapy (RRT) is a common complication after admission to an intensive care unit (ICU) and is associated with significant morbidity and mortality. However, the prevalence of RRT use and the associated outcomes in critically patients across the globe are not well described. Therefore, we describe the epidemiology and outcomes of patients receiving RRT for AKI in ICUs across several large health system jurisdictions. METHODS: Retrospective cohort analysis using nationally representative and comparable databases from seven health jurisdictions in Australia, Brazil, Canada, Denmark, New Zealand, Scotland, and the USA between 2006 and 2023, depending on data availability of each dataset. Patients with a history of end-stage kidney disease receiving chronic RRT and patients with a history of renal transplant were excluded. RESULTS: A total of 4,104,480 patients in the ICU cohort and 3,520,516 patients in the mechanical ventilation cohort were included. Overall, 156,403 (3.8%) patients in the ICU cohort and 240,824 (6.8%) patients in the mechanical ventilation cohort were treated with RRT for AKI. In the ICU cohort, the proportion of patients treated with RRT was lowest in Australia and Brazil (3.3%) and highest in Scotland (9.2%). The in-hospital mortality for critically ill patients treated with RRT was almost fourfold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37 to 65%. CONCLUSION: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests that differences in access to and provision of this therapy are contributing factors.

Biomarkers: Are They Useful in Severe Community-Acquired Pneumonia?

Community acquired pneumonia (CAP) is a prevalent infectious disease often requiring hospitalization, although its diagnosis remains challenging as there is no gold standard test. In severe CAP, clinical and radiologic criteria have poor sensitivity and specificity, and microbiologic documentation is usually delayed and obtained in less than half of sCAP patients. Biomarkers could be an alternative for diagnosis, treatment monitoring and establish resolution. Beyond the existing evidence about biomarkers as an adjunct diagnostic tool, most evidence comes from studies including CAP patients in primary care or emergency departments, and not only sCAP patients. Ideally, biomarkers used in combination with signs, symptoms, and radiological findings can improve clinical judgment to confirm or rule out CAP diagnosis, and may be valuable adjunctive tools for risk stratification, differentiate viral pneumonia and monitoring the course of CAP. While no single biomarker has emerged as an ideal one, CRP and PCT have gathered the most evidence. Overall, biomarkers offer valuable information and can enhance clinical decision-making in the management of CAP, but further research and validation are needed to establish their optimal use and clinical utility.

Effect of Tele-ICU on Clinical Outcomes of Critically Ill Patients: The TELESCOPE Randomized Clinical Trial.

Importance: Despite its implementation in several countries, there has not been a randomized clinical trial to assess whether telemedicine in intensive care units (ICUs) could improve clinical outcomes of critically ill patients. Objective: To determine whether an intervention comprising daily multidisciplinary rounds and monthly audit and feedback meetings performed by a remote board-certified intensivist reduces ICU length of stay (LOS) compared with usual care. Design, Setting, and Participants: A parallel cluster randomized clinical trial with a baseline period in 30 general ICUs in Brazil in which daily multidisciplinary rounds performed by board-certified intensivists were not routinely available. All consecutive adult patients (aged ≥18 years) admitted to the participating ICUs, excluding those admitted due to justice-related issues, were enrolled between June 1, 2019, and April 7, 2021, with last follow-up on July 6, 2021. Intervention: Remote daily multidisciplinary rounds led by a board-certified intensivist through telemedicine, monthly audit and feedback meetings for discussion of ICU performance indicators, and provision of evidence-based clinical protocols. Main Outcomes and Measures: The primary outcome was ICU LOS at the patient level. Secondary outcomes included ICU efficiency, in-hospital mortality, incidence of central line-associated bloodstream infections, ventilator-associated events, catheter-associated urinary tract infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation, and rate of patients with oxygen saturation values under that of normoxemia, assessed using generalized linear mixed models. Results: Among 17 024 patients (1794 in the baseline period and 15 230 in the intervention period), the mean (SD) age was 61 (18) years, 44.7% were female, the median (IQR) Sequential Organ Failure Assessment score was 6 (2-9), and 45.5% were invasively mechanically ventilated at admission. The median (IQR) time under intervention was 20 (16-21) months. Mean (SD) ICU LOS, adjusted for baseline assessment, did not differ significantly between the tele-critical care and usual care groups (8.1 [10.0] and 7.1 [9.0] days; percentage change, 8.2% [95% CI, -5.4% to 23.8%]; P = .24). Results were similar in sensitivity analyses and prespecified subgroups. There were no statistically significant differences in any other secondary or exploratory outcomes. Conclusions and Relevance: Daily multidisciplinary rounds conducted by a board-certified intensivist through telemedicine did not reduce ICU LOS in critically ill adult patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03920501.

Hospital Length of Stay and 30-Day Mortality Prediction in Stroke: A Machine Learning Analysis of 17,000 ICU Admissions in Brazil.

BACKGROUND: Hospital length of stay and mortality are associated with resource use and clinical severity, respectively, in patients admitted to the intensive care unit (ICU) with acute stroke. We proposed a structured data-driven methodology to develop length of stay and 30-day mortality prediction models in a large multicenter Brazilian ICU cohort. METHODS: We analyzed data from 130 ICUs from 43 Brazilian hospitals. All consecutive adult patients admitted with stroke (ischemic or nontraumatic hemorrhagic) to the ICU from January 2011 to December 2020 were included. Demographic data, comorbidities, acute disease characteristics, organ support, and laboratory data were retrospectively analyzed by a data-driven methodology, which included seven different types of machine learning models applied to training and test sets of data. The best performing models, based on discrimination and calibration measures, are reported as the main results. Outcomes were hospital length of stay and 30-day in-hospital mortality. RESULTS: Of 17,115 ICU admissions for stroke, 16,592 adult patients (13,258 ischemic and 3334 hemorrhagic) were analyzed; 4298 (26%) patients had a prolonged hospital length of stay (> 14 days), and 30-day mortality was 8% (n = 1392). Prolonged hospital length of stay was best predicted by the random forests model (Brier score = 0.17, area under the curve = 0.73, positive predictive value = 0.61, negative predictive value = 0.78). Mortality prediction also yielded the best discrimination and calibration through random forests (Brier score = 0.05, area under the curve = 0.90, positive predictive value = 0.66, negative predictive value = 0.94). Among the 20 strongest contributor variables in both models were (1) premorbid conditions (e.g., functional impairment), (2) multiple organ dysfunction parameters (e.g., hypotension, mechanical ventilation), and (3) acute neurological aspects of stroke (e.g., Glasgow coma scale score on admission, stroke type). CONCLUSIONS: Hospital length of stay and 30-day mortality of patients admitted to the ICU with stroke were accurately predicted through machine learning methods, even in the absence of stroke-specific data, such as the National Institutes of Health Stroke Scale score or neuroimaging findings. The proposed methods using general intensive care databases may be used for resource use allocation planning and performance assessment of ICUs treating stroke. More detailed acute neurological and management data, as well as long-term functional outcomes, may improve the accuracy and applicability of future machine-learning-based prediction algorithms.

What intensive care registries can teach us about outcomes.

PURPOSE OF REVIEW: Critical care registries are synonymous with measurement of outcomes following critical illness. Their ability to provide longitudinal data to enable benchmarking of outcomes for comparison within units over time, and between units, both regionally and nationally is a key part of the evaluation of quality of care and ICU performance as well as a better understanding of case-mix. This review aims to summarize literature on outcome measures currently being reported in registries internationally, describe the current strengths and challenges with interpreting existing outcomes and highlight areas where registries may help improve implementation and interpretation of both existing and new outcome measures. RECENT FINDINGS: Outcomes being widely reported through ICU registries include measures of survival, events of interest, patient-reported outcomes and measures of resource utilization (including cost). Despite its increasing adoption, challenges with quality of reporting of outcomes measures remain. Measures of short-term survival are feasible but those requiring longer follow-ups are increasingly difficult to interpret given the evolving nature of critical care in the context of acute and chronic disease management. Furthermore, heterogeneity in patient populations and in healthcare organisations in different settings makes use of outcome measures for international benchmarking at best complex, requiring substantial advances in their definitions and implementation to support those seeking to improve patient care. SUMMARY: Digital registries could help overcome some of the current challenges with implementing and interpreting ICU outcome data through standardization of reporting and harmonization of data. In addition, ICU registries could be instrumental in enabling data for feedback as part of improvement in both patient-centred outcomes and in service outcomes; notably resource utilization and efficiency.

What Is the Role of Steroids for Septic Shock in 2021?

Corticosteroids have been used for decades in the adjunctive treatment of severe infections in intensive care. The most frequent scenario in intensive care is in septic shock, where low doses of glucocorticoids appear to restore vascular responsiveness to norepinephrine. There is a strong body of evidence suggesting that hydrocortisone reduces time on vasopressor, and may modulate the immune response. In this review, we explore the current evidence supporting the use of corticosteroids in septic shock, its benefits, and potential harms. In addition to landmark clinical trials, we will also describe new frontiers for the use of corticosteroids in septic shock which should be explored in future studies.

Systemic Severity and Organ Dysfunction in Subarachnoid Hemorrhage: A Large Retrospective Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Acute physiologic derangements and multiple organ dysfunction are common after subarachnoid hemorrhage. We aimed to evaluate the simplified acute physiology score 3 (SAPS-3) and the sequential organ failure assessment (SOFA) scores for the prediction of in-hospital mortality in a large multicenter cohort of SAH patients. METHODS: This was a retrospective analysis of prospectively collected data from 45 ICUs in Brazil, during 2014 and 2015. Patients admitted with non-traumatic subarachnoid hemorrhage (SAH) were included. Clinical and outcome data were retrieved from an electronic ICU quality registry. SAPS-3 and SOFA scores, without the neurological components (i.e., nSAPS-3 and nSOFA, respectively) were recorded, as well as the World Federation of Neurological Surgeons (WFNS) scale. We used multilevel logistic regression analysis to identify factors associated with in-hospital mortality. We evaluated performance using the area under the receiver operating characteristic curve (AUROC), as well as calibration belts and precision-recall plots. RESULTS: The study included 997 patients, from which 426 (43%) had poor clinical grade (WFNS 4 or 5) and in-hospital mortality was 34%. Median nSAPS-3 and nSOFA score at admission were 46 (IQR: 38-55) and 2 (0-5), respectively. Non-survivors were older, had higher nSAPS-3 and nSOFA, and more often poor grade. After adjustment for age, poor grade and withdrawal of life sustaining therapies, multivariable analysis identified nSAPS-3 and nSOFA score as independent clinical predictors of in-hospital mortality. The AUROC curve that included nSAPS-3 and nSOFA scores significantly improved the already good discrimination and calibration of age and WFNS to predict in-hospital mortality (AUROC: 0.89 for the full final model vs. 0.85 for age and WFNS; P < 0.0001). CONCLUSIONS: nSAPS-3 and nSOFA scores were independently associated with in-hospital mortality after SAH. The addition of these scores improved early prediction of hospital mortality in our cohort and should be integrated to other specific prognostic indices in the early assessment of SAH.

A Comparison of Mortality From Sepsis in Brazil and England: The Impact of Heterogeneity in General and Sepsis-Specific Patient Characteristics.

OBJECTIVES: To test whether differences in both general and sepsis-specific patient characteristics explain the observed differences in sepsis mortality between countries, using two national critical care (ICU) databases. DESIGN: Cohort study. SETTING: We analyzed 62 and 164 ICUs in Brazil and England, respectively. PATIENTS: Twenty-two-thousand four-hundred twenty-six adult ICU admissions from January 2013 to December 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After harmonizing relevant variables, we merged the first ICU episode of adult medical admissions from Brazil (ORganizational CHaractEeriSTics in cRitical cAre study) and England (Intensive Care National Audit & Research Centre Case Mix Programme). Sepsis-3 definition was used, and the primary outcome was hospital mortality. We used multilevel logistic regression models to evaluate the impact of country (Brazil vs England) on mortality, after adjustment for general (age, sex, comorbidities, functional status, admission source, time to admission) and sepsis-specific (site of infection, organ dysfunction type and number) patient characteristics. Of medical ICU admissions, 13.2% (4,505/34,150) in Brazil and 30.7% (17,921/58,316) in England met the sepsis definition. The Brazil cohort was older, had greater prevalence of severe comorbidities and dependency compared with England. Respiratory was the most common infection site in both countries. The most common organ dysfunction was cardiovascular in Brazil (41.2%) and respiratory in England (85.8%). Crude hospital mortality was similar (Brazil 41.4% vs England 39.3%; odds ratio, 1.12 [0.98-1.30]). After adjusting for general patient characteristics, there was an important change in the point-estimate of the odds ratio (0.88 [0.75-1.02]). However, after adjusting for sepsis-specific patient characteristics, the direction of effect reversed again with Brazil having higher risk-adjusted mortality (odds ratio, 1.22 [1.05-1.43]). CONCLUSIONS: Patients with sepsis admitted to ICUs in Brazil and England have important differences in general and sepsis-specific characteristics, from source of admission to organ dysfunctions. We show that comparing crude mortality from sepsis patients admitted to the ICU between countries, as currently performed, is not reliable and that the adjustment for both general and sepsis-specific patient characteristics is essential for valid international comparisons of mortality amongst sepsis patients admitted to critical care units.

Worldwide Survey of the "Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Drugs, Delirium Monitoring/Management, Early Exercise/Mobility, and Family Empowerment" (ABCDEF) Bundle.

OBJECTIVES: To assess the knowledge and use of the Assessment, prevention, and management of pain; spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment; Early mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle to implement the Pain, Agitation, Delirium guidelines. DESIGN: Worldwide online survey. SETTING: Intensive care. INTERVENTION: A cross-sectional online survey using the Delphi method was administered to intensivists worldwide, to assess the knowledge and use of all aspects of the ABCDEF bundle. MEASUREMENT AND MAIN RESULTS: There were 1,521 respondents from 47 countries, 57% had implemented the ABCDEF bundle, with varying degrees of compliance across continents. Most of the respondents (83%) used a scale to evaluate pain. Spontaneous awakening trials and spontaneous breathing trials are performed in 66% and 67% of the responder ICUs, respectively. Sedation scale was used in 89% of ICUs. Delirium monitoring was implemented in 70% of ICUs, but only 42% used a validated delirium tool. Likewise, early mobilization was "prescribed" by most, but 69% had no mobility team and 79% used no formal mobility scale. Only 36% of the respondents assessed ICU-acquired weakness. Family members were actively involved in 67% of ICUs; however, only 33% used dedicated staff to support families and only 35% reported that their unit was open 24 hr/d for family visits. CONCLUSIONS: The current implementation of the ABCDEF bundle varies across individual components and regions. We identified specific targets for quality improvement and adoption of the ABCDEF bundle. Our data reflect a significant but incomplete shift toward patient- and family-centered ICU care in accordance with the Pain, Agitation, Delirium guidelines.

The current status of biomarkers for the diagnosis of nosocomial pneumonias.

PURPOSE OF REVIEW: Nosocomial pneumonia is a frequent and severe nosocomial infection divided in two distinct groups: hospital-acquired pneumonia and ventilator-associated pneumonia (VAP). In this context, the VAP is notoriously difficult to diagnose clinically, resulting from the lack of a 'gold standard' method of diagnosis. RECENT FINDINGS: The use of biomarkers may potentially improve the early diagnosis of infections allowing earlier and better identification and treatment. An exhausting list of biomarkers has been studied and although far from perfect, procalcitonin (PCT) and C-reactive protein (CRP) are the most studied biomarkers used in clinical practice. Data coming from literature suggests the use of PCT for VAP prognosis and as a based algorithm tool for the reduction of duration of pneumonia therapy, as well as, the use of the CRP dynamics to the early prediction of VAP and the response to the antibiotics. SUMMARY: The evidence for the use of biomarkers to diagnose nosocomial pneumonia as a stand-alone tool is low to moderate. Improved performance for both PCT and CRP can be obtained by using them in association with clinical features or scoring systems but prospective studies are still needed to validate this hypothesis.

Outcomes of subsyndromal delirium in ICU: a systematic review and meta-analysis.

BACKGROUND: Subsyndromal delirium (SSD) is a frequent condition and has been commonly described as an intermediate stage between delirium and normal cognition. However, the true frequency of SSD and its impact on clinically relevant outcomes in the intensive care unit (ICU) remains unclear. METHODS: We performed a systematic search in PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 October 2016 to identify publications that evaluated SSD in ICU patients. RESULTS: The six eligible studies were evaluated. SSD was present in 950 (36%) patients. Four studies evaluated only surgical patients. Four studies used the Intensive Care Delirium Screening Checklist (ICDSC) and two used the Confusion Assessment Method (CAM) score to diagnose SSD. The meta-analysis showed an increased hospital length of stay (LOS) in SSD patients (0.31, 0.12-0.51, p = 0.002; I 2 = 34%). Hospital mortality was described in two studies but it was not significant (hazard ratio 0.97, 0.61-1.55, p = 0.90 and 5% vs 9%, p = 0.05). The use of antipsychotics in SSD patients to prevent delirium was evaluated in two studies but it did not modify ICU LOS (6.5 (4-8) vs 7 (4-9) days, p = 0.66 and 2 (2-3) vs 3 (2-3) days, p = 0.517) or mortality (9 (26.5%) vs 7 (20.6%), p = 0.55). CONCLUSIONS: SSD occurs in one-third of the ICU patients and has limited impact on the outcomes. The current literature concerning SSD is composed of small-sample studies with methodological differences, impairing a clear conclusion about the association between SSD and progression to delirium or worse ICU clinical outcomes.

Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients: A Randomized Clinical Trial.

IMPORTANCE: The effectiveness of checklists, daily goal assessments, and clinician prompts as quality improvement interventions in intensive care units (ICUs) is uncertain. OBJECTIVE: To determine whether a multifaceted quality improvement intervention reduces the mortality of critically ill adults. DESIGN, SETTING, AND PARTICIPANTS: This study had 2 phases. Phase 1 was an observational study to assess baseline data on work climate, care processes, and clinical outcomes, conducted between August 2013 and March 2014 in 118 Brazilian ICUs. Phase 2 was a cluster randomized trial conducted between April and November 2014 with the same ICUs. The first 60 admissions of longer than 48 hours per ICU were enrolled in each phase. INTERVENTIONS: Intensive care units were randomized to a quality improvement intervention, including a daily checklist and goal setting during multidisciplinary rounds with follow-up clinician prompting for 11 care processes, or to routine care. MAIN OUTCOMES AND MEASURES: In-hospital mortality truncated at 60 days (primary outcome) was analyzed using a random-effects logistic regression model, adjusted for patients' severity and the ICU's baseline standardized mortality ratio. Exploratory secondary outcomes included adherence to care processes, safety climate, and clinical events. RESULTS: A total of 6877 patients (mean age, 59.7 years; 3218 [46.8%] women) were enrolled in the baseline (observational) phase and 6761 (mean age, 59.6 years; 3098 [45.8%] women) in the randomized phase, with 3327 patients enrolled in ICUs (n = 59) assigned to the intervention group and 3434 patients in ICUs (n = 59) assigned to routine care. There was no significant difference in in-hospital mortality between the intervention group and the usual care group, with 1096 deaths (32.9%) and 1196 deaths (34.8%), respectively (odds ratio, 1.02; 95% CI, 0.82-1.26; P = .88). Among 20 prespecified secondary outcomes not adjusted for multiple comparisons, 6 were significantly improved in the intervention group (use of low tidal volumes, avoidance of heavy sedation, use of central venous catheters, use of urinary catheters, perception of team work, and perception of patient safety climate), whereas there were no significant differences between the intervention group and the control group for 14 outcomes (ICU mortality, central line-associated bloodstream infection, ventilator-associated pneumonia, urinary tract infection, mean ventilator-free days, mean ICU length of stay, mean hospital length of stay, bed elevation to ≥30°, venous thromboembolism prophylaxis, diet administration, job satisfaction, stress reduction, perception of management, and perception of working conditions). CONCLUSIONS AND RELEVANCE: Among critically ill patients treated in ICUs in Brazil, implementation of a multifaceted quality improvement intervention with daily checklists, goal setting, and clinician prompting did not reduce in-hospital mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01785966.

Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial.

INTRODUCTION: The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients. METHODS: We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality. RESULTS: A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment. CONCLUSIONS: In the present study of septic shock patients, after adjustment for treatment selection bias, we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo. TRIAL REGISTRATION: Clinicaltrials.gov NCT00604214 . Registered 24 January 2008.