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 < 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.

Accuracy of Point-of-Care Blood Glucose Level Measurements in Critically Ill Patients with Sepsis Receiving High-Dose Intravenous Vitamin C.

STUDY OBJECTIVE: High-dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point-of-care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results. DESIGN: Prospective observational pilot study. SETTING: Intensive care unit in a large academic tertiary care medical center. PATIENTS: Five consecutive critically ill adults hospitalized between April 1 and June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for the treatment of sepsis and had at least two paired POC BG levels and laboratory venous BG levels measured within 1 hour of each other during vitamin C therapy. MEASUREMENTS AND MAIN RESULTS: The performance of POC BG level measurement was compared with the reference method of laboratory BG level measurement. The concordance to minimum accuracy criteria for BG meters set forth by the International Organization for Standardization (ISO) 15197:2013, the measurement of agreement between POC BG level and laboratory BG level using the Bland-Altman method, and the clinical accuracy through Parkes error grid analysis were assessed. A total of 16 paired POC and laboratory BG level measurements from the five patients were included. The accuracy of POC BG with laboratory BG level measurements during vitamin C administration according to ISO 15197:2013 criteria was 81.3%, which did not meet the minimum accuracy criteria of 95%. The Bland-Altman analysis showed a mean difference between POC and laboratory BG levels of 8.9 mg/dl, and the Parkes error grid analysis showed that the differences between POC and laboratory BG level measurements would not have resulted in a change in clinical action. CONCLUSION: The accuracy and agreement of POC and laboratory BG level measurements in critically ill patients receiving vitamin C were consistent with previously published reports in critically ill patients not receiving vitamin C and did not demonstrate clinically significant interference due to vitamin C dosing for sepsis.

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 < .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.

Inadequacy of Headache Management After Subarachnoid Hemorrhage.

BACKGROUND: Headache profoundly affects management of spontaneous subarachnoid hemorrhage but is poorly characterized. OBJECTIVE: To characterize headache after spontaneous subarachnoid hemorrhage. METHODS: Medical records of patients with Hunt and Hess grades I-III subarachnoid hemorrhage admitted from 2011 to 2013 were reviewed. Demographics, clinical and radiographic features, medications, and pain scores were recorded through day 14 after hemorrhage. Headache pain was characterized on the basis of a numeric rating scale and analgesic use. Severe headache was defined as 2 or more days with maximum pain scores of 8 or greater or need for 3 or more different analgesics for 2 or more days. Univariate and multivariable models were used to analyze factors associated with severe headache. RESULTS: Of the 77 patients in the sample, 57% were women; median age was 57 years. Severe headache (73% overall) was associated nonlinearly with Hunt and Hess grade: grade I, 58%; grade II, 88%; and grade III, 56% (P = .01), and with Hijdra score: score 0-10, 56%; score 11-20, 86%; score 21-30, 76% (P = .03). By univariate analysis, patients with low Hijdra scores were less likely to have severe headache (27% vs 57%; P = .02). In a multivariable model, younger age and higher Hijdra score tended to be associated with severe headache. CONCLUSIONS: Headache after spontaneous subarachnoid hemorrhage was often severe, necessitating multiple opioid and nonopioid analgesics. Many patients reported persistent headache and inadequate pain control.

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 < 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.