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Randomized clinical trials (RCTs) are the gold standard to evaluate intervention efficacy and effectiveness. To apply current, evidence-based interventions to daily practice, it is imperative that practicing intensivists be able to interpret the results of individual RCTs in the context of their patients. In this article, we outline an approach to interpreting critical care RCTs from the perspective of the clinician that focuses on answering four questions: (1) Would my patient have been enrolled and represented in the RCT? (2) Is the intervention feasible? (3) Are there threats to the internal validity of the RCT results? (4) Are the RCT results meaningful? Answers to these four questions can be used to assist intensivists in deciding whether to apply RCT evidence to their patients at the bedside and to avoid common pitfalls of RCT interpretation.

Background Chloride-rich fluid administration is frequently employed in the management of aneurysmal subarachnoid hemorrhage (aSAH). However, the incidence and consequences of hyperchloremia in aSAH remain poorly defined. This study aimed to describe the incidence of hyperchloremia in aSAH, the contribution of fluid sources to chloride exposure, and the potential associations of hyperchloremia with patient outcomes. Methods This was a single-center retrospective cohort study of patients admitted to a neurointensive care unit with aSAH. The primary outcome was incidence of hyperchloremia (chloride >109 mEq/L). Secondary outcomes included incidence of severe hyperchloremia (chloride >115 mEq/L), incidence of acute kidney injury (AKI), need for renal replacement therapy (RRT), intensive care unit (ICU) length of stay (LOS), hospital LOS, and in-hospital mortality. Results Of the 234 patients included in the analysis, hyperchloremia occurred in 75% (n=175), and 58% (n=101) developed severe hyperchloremia. Median time to onset was 3 days (interquartile range, 1–5) after admission. Hyperchloremia was associated with prolonged ICU LOS (12 vs. 8 days, P

OBJECTIVES:. A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022. DATA SOURCES:. PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION:. Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article. DATA EXTRACTION:. Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS:. The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia. CONCLUSIONS:. This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice.

Brain injury resulting from sepsis, or sepsis-associated encephalopathy (SAE), occurs due to impaired end-organ perfusion, dysregulated inflammation affecting the central nervous system (CNS), blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, accumulation of toxic neuropeptides and impaired toxin clearance secondary to sepsis-induced hepatic and renal dysfunction. The gut microbiome becomes pathologically altered in sepsis, which likely contributes to the pathogenesis of SAE. Herein, we review the literature detailing dysregulation of microbiota-gut-brain axis (MGBA) in SAE and highlight potential therapeutic strategies to modulate the gut microbiome to mitigate sepsis-induced brain injury.

OBJECTIVES:. Since the onset of the coronavirus disease 2019 pandemic, immune modulators have been considered front-line candidates for the management of patients presenting with clinical symptoms secondary to severe acute respiratory syndrome coronavirus 2 infection. Although heavy emphasis has been placed on early clinical efficacy, we sought to evaluate the impact of pharmacologic approach to coronavirus disease 2019 within the ICU on secondary infections and clinical outcomes. DATA SOURCES:. PubMed (inception to March 2021) database search and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION:. Articles relevant to coronavirus disease 2019, management of severe acute respiratory syndrome coronavirus 2–associated respiratory failure, and prevalence of secondary infections with pharmacotherapies were selected. The MeSH terms “COVID-19,” “secondary infection,” “SARS-CoV-2,” “tocilizumab,” and “corticosteroids” were used for article identification. Articles were narratively synthesized for this review. DATA SYNTHESIS:. Current data surrounding the use of tocilizumab and/or corticosteroids for coronavirus disease 2019 management are limited given the short follow-up period and conflicting results between studies. Further complicating the understanding of immune modulator role is the lack of definitive understanding of clinical impact of the immune response in coronavirus disease 2019. CONCLUSIONS:. Based on the current available literature, we suggest prolonged trials and follow-up intervals for those patients managed with immune modulating agents for the management of coronavirus disease 2019.