Single-dose etomidate is not associated with increased mortality in ICU patients with sepsis: analysis of a large electronic ICU database.

OBJECTIVE: Retrospective analyses of several trials suggest etomidate may be unsafe for intubation in patients with sepsis. We evaluated the association of etomidate and mortality in a large cohort of septic patients to determine if single-dose etomidate was associated with increased in-hospital mortality. DESIGN AND SETTING: Retrospective cohort study at the Philips eICU Research Institute ICU clinical database. INTERVENTIONS: None. PATIENTS: Among 741,036 patients monitored from 2008 through 2010, we identified 2,014 adults intubated in the ICU 4-96 hrs after admission, having clinical criteria consistent with sepsis, severe sepsis, or septic shock. In all, 1,102 patients received etomidate and 912 received other induction agents for intubation. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was in-hospital mortality, but we also evaluated demographic and clinical factors, severity of illness, ICU mortality, ICU length of stay, hospital length of stay, ventilator days, and vasopressor days. Competing risk Cox proportional hazard regression models were used for primary outcomes. Demographics and illness severity were similar between the groups. Hospital mortality was similar between the groups (37.2% vs. 37.8%, p = 0.77), as were ICU mortality (30.1% vs. 30.2%, p = 0.99), ICU length of stay (8.7 days vs. 8.9 days, p = 0.66), and hospital length of stay (15.2 vs. 14.6 days, p = 0.31). More patients in the etomidate group received steroids before and after intubation (52.9% vs. 44.5%, p \u3c 0.001), but vasopressor use and duration of mechanical ventilation were similar. No regression model showed an independent association of etomidate with mortality, shock, duration of mechanical ventilation, ICU or hospital length of stay, or vasopressor use. A hospital mortality model limited to only patients with septic shock (n = 650) also showed no association of etomidate and hospital mortality. CONCLUSION: In a mixed-diagnosis group of critically ill patients with sepsis, severe sepsis, and septic shock, single-dose etomidate administration for intubation in the ICU was not associated with higher mortality or other adverse clinical outcomes

Valproate for agitation in critically ill patients: a retrospective study.

PURPOSE: The purpose was to describe the use of valproate therapy for agitation in critically ill patients, examine its safety, and describe its relationship with agitation and delirium. MATERIALS AND METHODS: This retrospective cohort study evaluated critically ill adults treated with valproate for agitation from December 2012 through February 2015. Information on valproate prescribing practices and safety was collected. Incidence of agitation, delirium, and concomitant psychoactive medication use was compared between valproate day 1 and valproate day 3. Concomitant psychoactive medication use was analyzed using mixed models. RESULTS: Fifty-three patients were evaluated. The median day of valproate therapy initiation was ICU day 7, and it was continued for a median of 7 days. The median maintenance dose was 1500 mg/d (23 mg/kg/d). The incidence of agitation (96% vs 61%, P \u3c .0001) and delirium (68% vs 49%, P = .012) significantly decreased by valproate day 3. Treatment with opioids (77% vs 65%, P = .02) and dexmedetomidine (47% vs 24%, P = .004) also decreased. In mixed models analyses, valproate therapy was associated with reduced fentanyl equivalents (-185 μg/d, P = .0003) and lorazepam equivalents (-2.1 mg/d, P = .0004). Hyperammonemia (19%) and thrombocytopenia (13%) were the most commonly observed adverse effects. CONCLUSIONS: Valproate therapy was associated with a reduction in agitation, delirium, and concomitant psychoactive medication use within 48 hours of initiation

Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial

BACKGROUND: Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality. METHODS: The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring \u3c 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years. DISCUSSION: The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021