Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy.

OBJECTIVES: To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock. DESIGN: Multicenter, double-blinded, randomized controlled trial. SETTING: One academic medical ICU and four community ICUs. PATIENTS: Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis. INTERVENTIONS: IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline. MEASUREMENTS AND MAIN RESULTS: Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569. CONCLUSIONS: Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.

A qualitative study to understand barriers to implementation of national guidelines for prehospital termination of unsuccessful resuscitation efforts.

BACKGROUND: The American Heart Association's (AHA's) Advanced Cardiac Life Support guidelines act as the national standards for termination of resuscitation (TOR) in cases of refractory out-of-hospital cardiac arrest. However, local emergency medical services (EMS) implementation of these guidelines has been nonuniform. OBJECTIVE: To identify the operational issues within local EMS systems that may serve as barriers or facilitators to full acceptance of national guidelines for prehospital TOR in appropriate circumstances. Methods. We conducted three focus groups at the January 2008 National Association of EMS Physicians (NAEMSP) annual meeting. Snowball sampling was used to recruit 19 physicians, two EMS providers, one research director, one nurse, and one medical student attending the conference. Two reviewers analyzed the data in an iterative process to identify recurrent and unifying themes. RESULTS: We identified three distinct stakeholder groups whose current beliefs and practices may influence local implementation of TOR: EMS providers with variations in education and work culture; EMS medical directors with responsibility but little authority; and online medical control physicians who do not communicate effectively with the other groups. Our focus group participants suggested that national organizations, such as the AHA and the American College of Emergency Physicians, may serve a role in overcoming the overarching barriers of communication, standardized educational requirements, and coordination of local services. CONCLUSION: We have identified operational barriers that may impede implementation of TOR guidelines. Three influential stakeholder groups will need to work with national organizations to overcome these local barriers.

Prehospital termination of resuscitation in cases of refractory out-of-hospital cardiac arrest.

CONTEXT: Identifying patients in the out-of-hospital setting who have no realistic hope of surviving an out-of-hospital cardiac arrest could enhance utilization of scarce health care resources. OBJECTIVE: To validate 2 out-of-hospital termination-of-resuscitation rules developed by the Ontario Prehospital Life Support (OPALS) study group, one for use by responders providing basic life support (BLS) and the other for those providing advanced life support (ALS). DESIGN, SETTING, AND PATIENTS: Retrospective cohort study using surveillance data prospectively submitted by emergency medical systems and hospitals in 8 US cities to the Cardiac Arrest Registry to Enhance Survival (CARES) between October 1, 2005, and April 30, 2008. Case patients were 7235 adults with out-of-hospital cardiac arrest; of these, 5505 met inclusion criteria. MAIN OUTCOME MEASURES: Specificity and positive predictive value of each termination-of-resuscitation rule for identifying patients who likely will not survive to hospital discharge. RESULTS: The overall rate of survival to hospital discharge was 7.1% (n = 392). Of 2592 patients (47.1%) who met BLS criteria for termination of resuscitation efforts, only 5 (0.2%) patients survived to hospital discharge. Of 1192 patients (21.7%) who met ALS criteria, none survived to hospital discharge. The BLS rule had a specificity of 0.987 (95% confidence interval [CI], 0.970-0.996) and a positive predictive value of 0.998 (95% CI, 0.996-0.999) for predicting lack of survival. The ALS rule had a specificity of 1.000 (95% CI, 0.991-1.000) and positive predictive value of 1.000 (95% CI, 0.997-1.000) for predicting lack of survival. CONCLUSION: In this validation study, the BLS and ALS termination-of-resuscitation rules performed well in identifying patients with out-of-hospital cardiac arrest who have little or no chance of survival.