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ObjectiveTo identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.DesignA consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.MethodsEach committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science.ResultsThe Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?ConclusionsWhile the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Clinical decision-making often simplifies continuous risk data into discrete levels using round-number thresholds. These simplifications can distort risk assessments. To systematically uncover these distortions, we develop an interpretable machine learning model that identifies anomalies caused by threshold-based practices. Through simulations, real-world data, and longitudinal studies, we demonstrate how round-number thresholds can lead to discontinuities and counter-causal paradoxes in mortality risk. Despite advances in medicine, these anomalies persist, underscoring the need for dynamic and nuanced risk assessment methods in healthcare. Our findings suggest continuous reassessment of clinical protocols, especially in critical settings like intensive care, to improve patient outcomes by aligning thresholds with the continuous nature of risk.

Background We proposed that the behaviors that demonstrate compassionate care in the intensive care unit (ICU) can be self-assessed and improved among ICU clinicians. Literature showing views of intensivists about their own compassionate care attitudes is missing. Methods This was an observational, prospective, cross-sectional study. We surveyed clinicians who are members of professional societies of intensive care using the modified Schwartz Center Compassionate Care Scale® (SCCCS) about their self-reported compassionate care. A modified SCCCS instrument was disseminated via an email sent to the members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine between March and June 2021. Results Three hundred twenty-three clinicians completed the survey from a cohort of 1000 members who responded (32.3% response rate). The majority (54%) of respondents were male physicians of 49 (+ − 10 SD) years of age and 19 (12 + − SD) years in practice. The mean SCCCS was 88.5 (out of 100) with an average score of 8 for each question (out of 10), showing a high self-assessed physician rating of their compassionate care in the ICU. There was a positive association with age and years in practice with a higher score, especially for women ages 30–50 years ( P  = 0.03). Years in practice was also independently associated with greater compassion scores ( p  < 0.001). Lower scores were given to behaviors that reflect understanding perspectives of families and patients and showing caring and sensitivity. In contrast, the top scores were given to behaviors that included conducting family discussions and showing respect. Conclusion Physicians in the ICU self-score high in compassionate care, especially if they are more experienced, female, and older. Self-identified areas that need improvement are the humanistic qualities requiring sensitivity, such as cognitive empathy, which involves perspective-taking, reflective listening, asking open-ended questions, and understanding the patient’s context and worldview. These can be addressed in further clinical and ICU quality improvement initiatives.

Objective To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. Design A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Results Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pa o 2 /Fi o 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pa o 2 /F i o 2 <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Conclusions Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol use disorder. Although benzodiazepines are the mainstay of treatment, some patients may be resistant to them, requiring rapidly escalating doses. Phenobarbital has emerged as an effective adjunct therapy in severe alcohol withdrawal, but studies have yielded inconsistent results and carry safety risks. The purpose of our study was to examine the effectiveness and the potential harm of phenobarbital in AWS. In this multi-center, retrospective cohort study, patients who were admitted for AWS and received phenobarbital with benzodiazepine were compared to patients who received benzodiazepine monotherapy. The primary outcome was time to AWS resolution. Other secondary and safety outcomes included length of stay (LOS), rate of mechanical ventilation, and incidence of aspiration pneumonia. The phenobarbital group received significantly higher doses of benzodiazepines compared to the benzodiazepine monotherapy group (660 mg vs 340 mg, p < 0.0001). After adjustment, the use of phenobarbital was associated with significantly reduced time to AWS resolution (141.65 h vs 165.72 h, p < 0.0001). However, the use of phenobarbital was associated with the likelihood of mechanical ventilation (19.42 %vs. 0.96 %, p < 0.0001), aspiration pneumonia (22.33 % vs 5.77 %, p = 0.0006), and increased hospital LOS (8 days vs. 6 days, p = 0.0197). In the combination group, earlier phenobarbital initiation (within 24 h) was associated with significantly lower cumulative benzodiazepine dose (530 mg vs 887.50 mg, p = 0.002) and hospital LOS (6 days vs 10 days, p = 0.0017). In our study, patients who received phenobarbital in combination with benzodiazepines had a quicker resolution of AWS but also had a higher incidence of mechanical ventilation, prolonged hospital LOS, and an increased risk of aspiration pneumonia. For patients at high risk of severe alcohol withdrawal, earlier initiation of phenobarbital appeared to yield the most optimal benefit.

ObjectiveTo identify priorities for administrative, epidemiologic and diagnostic research in sepsis.DesignAs a follow-up to a previous consensus statement about sepsis research, members of the Surviving Sepsis Campaign Research Committee, representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine addressed six questions regarding care delivery, epidemiology, organ dysfunction, screening, identification of septic shock, and information that can predict outcomes in sepsis.MethodsSix questions from the Scoring/Identification and Administration sections of the original Research Priorities publication were explored in greater detail to better examine the knowledge gaps and rationales for questions that were previously identified through a consensus process.ResultsThe document provides a framework for priorities in research to address the following questions: (1) What is the optimal model of delivering sepsis care?; (2) What is the epidemiology of sepsis susceptibility and response to treatment?; (3) What information identifies organ dysfunction?; (4) How can we screen for sepsis in various settings?; (5) How do we identify septic shock?; and (6) What in-hospital clinical information is associated with important outcomes in patients with sepsis?ConclusionsThere is substantial knowledge of sepsis epidemiology and ways to identify and treat sepsis patients, but many gaps remain. Areas of uncertainty identified in this manuscript can help prioritize initiatives to improve an understanding of individual patient and demographic heterogeneity with sepsis and septic shock, biomarkers and accurate patient identification, organ dysfunction, and ways to improve sepsis care.

Introduction Anesthesiologists play an important role in the management of labor and delivery during acute malaria infection. The peripartum anesthesia considerations for such cases remain unclear. Findings Important peripartum considerations include the severity of thrombocytopenia and coagulopathy, hemodynamic status and cardiac disease, and the likelihood of central nervous system (CNS) involvement. Several antimalarial drugs may interact with perioperative medications, causing hypoglycemia, methemoglobinemia, or QT prolongation. Labor should usually not be induced. Patient volume status should be optimized pre-induction, but fluids should be administered with caution given the risk of cerebral edema. In case of CNS involvement intracranial pressure should be maintained. Case reports describe the successful use of neuraxial anesthesia but this approach requires further confirmation of safety. Despite the risks accompanying airway management in pregnancy, in some cases, general anesthesia was preferred due to the chance of CNS infection and disease complications. Tight postoperative assessments of neurological and bleeding status are indicated regardless of the mode of delivery. Conclusions Despite the prevalence of malaria, the perioperative risk and preferred mode of anesthesia for pregnant patients with acute malaria remain under-researched and outcome data are limited.

Importance The spring 2020 surge of COVID-19 unprecedentedly strained ventilator supply in New York City, with many hospitals nearly exhausting available ventilators and subsequently seriously considering enacting crisis standards of care and implementing New York State Ventilator Allocation Guidelines (NYVAG). However, there is little evidence as to how NYVAG would perform if implemented. Objectives To evaluate the performance and potential improvement of NYVAG during a surge of patients with respect to the length of rationing, overall mortality, and worsening health disparities. Design, Setting, and Participants This cohort study included intubated patients in a single health system in New York City from March through July 2020. A total of 20 000 simulations were conducted of ventilator triage (10 000 following NYVAG and 10 000 following a proposed improved NYVAG) during a crisis period, defined as the point at which the prepandemic ventilator supply was 95% utilized. Exposures The NYVAG protocol for triage ventilators. Main Outcomes and Measures Comparison of observed survival rates with simulations of scenarios requiring NYVAG ventilator rationing. Results The total cohort included 1671 patients; of these, 674 intubated patients (mean [SD] age, 63.7 [13.8] years; 465 male [69.9%]) were included in the crisis period, with 571 (84.7%) testing positive for COVID-19. Simulated ventilator rationing occurred for 163.9 patients over 15.0 days, 44.4% (95% CI, 38.3%-50.0%) of whom would have survived if provided a ventilator while only 34.8% (95% CI, 28.5%-40.0%) of those newly intubated patients receiving a reallocated ventilator survived. While triage categorization at the time of intubation exhibited partial prognostic differentiation, 94.8% of all ventilator rationing occurred after a time trial. Within this subset, 43.1% were intubated for 7 or more days with a favorable SOFA score that had not improved. An estimated 60.6% of these patients would have survived if sustained on a ventilator. Revising triage subcategorization, proposed improved NYVAG, would have improved this alarming ventilator allocation inefficiency (25.3% [95% CI, 22.1%-28.4%] of those selected for ventilator rationing would have survived if provided a ventilator). NYVAG ventilator rationing did not exacerbate existing health disparities. Conclusions and Relevance In this cohort study of intubated patients experiencing simulated ventilator rationing during the apex of the New York City COVID-19 2020 surge, NYVAG diverted ventilators from patients with a higher chance of survival to those with a lower chance of survival. Future efforts should be focused on triage subcategorization, which improved this triage inefficiency, and ventilator rationing after a time trial, when most ventilator rationing occurred.