Search

Objectives: COVID-19 treatment guidelines recommend baricitinib or tocilizumab for the management of hospitalized patients with COVID-19. We compared the effectiveness of baricitinib vs. tocilizumab on mortality and clinical outcomes among hospitalized patients with COVID-19., Design: Multicenter, retrospective, propensity-weighted cohort study using a target trial emulation approach., Setting: The National COVID Cohort Collaborative (N3C), which is the largest electronic health records data on COVID-19 in the United States. The setting included 75 hospitals., Patients: Adults who were hospitalized for COVID-19., Interventions: Newly initiated on baricitinib or tocilizumab., Measurements and Main Results: Our primary outcome was 28-day mortality. We used propensity scores with inverse probability of treatment weights (IPTWs) to control bias and confounding while comparing treatments. Among 10,661 individuals included in the study, 6,229 (58.4%) received baricitinib and 4,432 (41.6%) tocilizumab. Overall, the mean age of the cohort was 60.0 ± 15.1 years, 6429 (60.3%) were male, and 19.2% received invasive mechanical ventilation. After IPTW adjustment, baricitinib use was associated with lower 28-day mortality (odds ratio [OR], 0.91; 95% CI, 0.85-0.98) and hospital (OR, 0.88; 95% CI, 0.82-0.94) mortality compared with tocilizumab. Baricitinib was also associated with shorter hospital length of stay (incident rate ratio, 0.92; 95% CI, 0.90-0.94) and lower rates of hospital-acquired infections (OR, 0.86; 95% CI, 0.75-0.99), although no difference in ICU length of stay was noted between the two groups., Conclusions: In this large, diverse cohort of U.S. hospitalized adults with COVID-19, baricitinib was associated with significantly lower 28-day mortality, hospital mortality, shorter hospital length of stay, and less hospital-acquired infections compared with tocilizumab., Competing Interests: Dr. Higgins is supported by a National Health and Medical Research Council Investigator Grant (GNT2008447). Dr. Mehta is supported by the National Institute on Aging (1K01AG070329). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: The objective of this study was to compare pain control and opioid consumption in critically ill patients who were treated with buprenorphine sublingual or oxycodone oral/enteral during ICU admission., Design: This was a retrospective, parallel, cohort study., Setting: General medical or surgical ICUs of a quaternary, urban hospital in Sydney, NSW, Australia., Patients: Data were obtained for all patients admitted to two general medical or surgical ICU from January 2019 to January 2023. Patients were grouped as those who received buprenorphine sublingual versus oxycodone oral/enteral., Interventions: None., Measurements and Main Results: Pain control was compared between a propensity score matched cohort of patients who received buprenorphine versus oxycodone. The primary outcome was the probability of significant pain. A significant pain score was defined as greater than or equal to 4 on the 0-10 Numeric Rating Scale or greater than or equal to 6 on the Behavioral Pain Scale. The study cohort included 1,070 patients (288 buprenorphine and 782 oxycodone). After propensity score matching, there were 288 patients in each group. The mean age of the matched cohort was 64 ± 16 years, 295 (51%) were male, and 359 (62%) had a surgical admission. The median probability of significant pain was 0.16 with buprenorphine and 0.17 with oxycodone (median difference, 0.01; 95% CI, -0.02 to 0.04; p = 0.50). Median opioid consumption in oral morphine milligram equivalents (MMEs) was 65 with buprenorphine and 70 with oxycodone (median difference, -1 mg; 95% CI, -10 to 10 mg; p = 0.73). Median MME per ICU day was 22 with buprenorphine and 22 with oxycodone (median difference, 1 mg; 95% CI, -2 to 5 mg; p = 0.38)., Conclusions: Buprenorphine sublingual is as effective as oxycodone oral/enteral with regard to pain control and opioid consumption in the ICU. Buprenorphine sublingual is an appropriate option for patients in the ICU who are unable to take oral/enteral medications., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Rationale: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI)., Objectives: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI., Design: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process., Methods: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist., Results: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence., Conclusions: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research., Competing Interests: Dr. Mosier is currently the National Course Director for the Difficult Airway Course: Critical Care. Dr. Heffner received funding as an advisor/speaker. Drs. Mosier, Hirsch, Heffner, and Gunnerson have served as expert witness. The remaining authors have disclosed that they do not have any potential conflicts of interest. A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel’s inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Competing Interests: Dr. Mosier is currently the National Course Director for the Difficult Airway Course: Critical Care. Dr. Heffner received funding as an advisor/speaker. Drs. Mosier, Hirsch, Heffner, and Gunnerson have served as expert witnesses. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Objectives: It is recommended that therapeutic monitoring of vancomycin should be guided by 24-hour area under the curve concentration. This can be done via Bayesian models in dose-optimization software. However, before these models can be incorporated into clinical practice in the critically ill, their predictive performance needs to be evaluated. This study assesses the predictive performance of Bayesian models for vancomycin in the critically ill., Design: Retrospective cohort study., Setting: Single-center ICU., Patients: Data were obtained for all patients in the ICU between 1 January, and 31 May 2020, who received IV vancomycin. The predictive performance of three Bayesian models were evaluated based on their availability in commercially available software. Predictive performance was assessed via bias and precision. Bias was measured as the mean difference between observed and predicted vancomycin concentrations. Precision was measured as the sd of bias, root mean square error, and 95% limits of agreement based on Bland-Altman plots., Interventions: None., Measurements and Main Results: A total of 466 concentrations from 188 patients were used to evaluate the three models. All models showed low bias (-1.7 to 1.8 mg/L), which was lower with a posteriori estimate (-0.7 to 1.8 mg/L). However, all three models showed low precision in terms of sd (4.7-8.8 mg/L) and root mean square error (4.8-8.9 mg/L). The models underpredicted at higher observed vancomycin concentrations (bias 0.7-3.2 mg/L for < 20 mg/L; -5.1 to -2.3 for ≥ 20 mg/L) and the Bland-Altman plots showed a great deviation between observed and predicted concentrations., Conclusions: Bayesian models of vancomycin show not only low bias, but also low precision in the critically ill. Thus, Bayesian-guided dosing of vancomycin in this population should be used cautiously., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To conduct a cost analysis of adjunctive hydrocortisone therapy for severe septic shock from the perspective of a third-party payer in the United States., Design: Estimates of outcomes were aggregate data from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials. In these trials, the outcomes of interests were ICU length of stay, vasopressor-free days, ventilation-free days, and the proportion of patients receiving blood transfusion. Each outcome was monetized into a set of mutually exclusive components and was aggregated to estimate the cost-per-patient based on each trial. Cost inputs for each outcome were obtained from literature and adjusted based on the medical care consumer price index. To estimate the budget impact using adjunctive hydrocortisone therapy, per-patient avoided cost was multiplied by expected septic shock annual incidence. Deterministic one-way sensitivity analysis evaluated the robustness of the findings, and Monte Carlo simulation estimated 95% CI of the findings., Setting: A total of 103 medical-surgical ICU (69 for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and 34 for Activated Protein C and Corticosteroids for Human Septic Shock)., Patients: Adults greater than or equal to 18 years old with septic shock., Interventions: Adjunctive hydrocortisone therapy (hydrocortisone at a dose of 200 mg/d for 7 d for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and hydrocortisone at a 50 mg IV bolus every 6 hr and fludrocortisone as a 50 μg tablet once daily)., Measurements and Main Results: Per Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $8,111 (95% CI, $3,914-$12,307) per patient, driven by improvements in ICU-free days, vasopressor-free days, ventilation-free days, and blood transfusion proportion. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $750 million. Per Activated Protein C and Corticosteroids for Human Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $25,539 per patient (95% CI, $22,853-$28,224), driven by improvements in ICU free-days, vasopressor-free days, and ventilation-free days. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $2.3 billion. The deterministic one-way sensitivity analysis showed the cost of ICU stays to be the most influential factor in both analyses. The sensitivity analysis using the reported median showed a greater monetized benefit of $10,658 (Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock) and $30,911 (Activated Protein C and Corticosteroids for Human Septic Shock) per patient., Conclusions: Using adjunctive hydrocortisone therapy yields a significant monetized benefit based on inputs from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials.