Search

Importance: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock., Objective: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock., Design, Setting, and Participants: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019., Interventions: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102)., Main Outcomes and Measures: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses., Results: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively)., Conclusions and Relevance: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock., Trial Registration: ClinicalTrials.gov Identifier: NCT03389555.

Importance: Tracheal intubation is common during pediatric in-hospital cardiac arrest, although the relationship between intubation during cardiac arrest and outcomes is unknown., Objective: To determine if intubation during pediatric in-hospital cardiac arrest is associated with improved outcomes., Design, Setting, and Participants: Observational study of data from United States hospitals in the Get With The Guidelines-Resuscitation registry. Pediatric patients (<18 years) with index in-hospital cardiac arrest between January 2000 and December 2014 were included. Patients who were receiving assisted ventilation, had an invasive airway in place, or both at the time chest compressions were initiated were excluded., Exposures: Tracheal intubation during cardiac arrest ., Main Outcomes and Measures: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation and neurologic outcome. A favorable neurologic outcome was defined as a score of 1 to 2 on the pediatric cerebral performance category score. Patients being intubated at any given minute were matched with patients at risk of being intubated within the same minute (ie, still receiving resuscitation) based on a time-dependent propensity score calculated from multiple patient, event, and hospital characteristics., Results: The study included 2294 patients; 1308 (57%) were male, and all age groups were represented (median age, 7 months [25th-75th percentiles, 21 days, 4 years]). Of the 2294 included patients, 1555 (68%) were intubated during the cardiac arrest. In the propensity score-matched cohort (n = 2270), survival was lower in those intubated compared with those not intubated (411/1135 [36%] vs 460/1135 [41%]; risk ratio [RR], 0.89 [95% CI, 0.81-0.99]; P = .03). There was no significant difference in return of spontaneous circulation (770/1135 [68%] vs 771/1135 [68%]; RR, 1.00 [95% CI, 0.95-1.06]; P = .96) or favorable neurologic outcome (185/987 [19%] vs 211/983 [21%]; RR, 0.87 [95% CI, 0.75-1.02]; P = .08) between those intubated and not intubated. The association between intubation and decreased survival was observed in the majority of the sensitivity and subgroup analyses, including when accounting for missing data and in a subgroup of patients with a pulse at the beginning of the event., Conclusions and Relevance: Among pediatric patients with in-hospital cardiac arrest, tracheal intubation during cardiac arrest compared with no intubation was associated with decreased survival to hospital discharge. Although the study design does not eliminate the potential for confounding, these findings do not support the current emphasis on early tracheal intubation for pediatric in-hospital cardiac arrest.