The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.

Cerebral Performance Category (CPC) scores are often an outcome measure for post-arrest neurologic function, collected worldwide to compare performance, evaluate therapies, and formulate recommendations. At most institutions, no formal training is offered in their determination, potentially leading to misclassification. We identified 171 patients at 2 hospitals between 5/10/2005 and 8/31/2012 with two CPC scores at hospital discharge recorded independently - in an in-house quality improvement database and as part of a national registry. Scores were abstracted retrospectively from the same electronic medical record by two separate non-clinical researchers. These scores were compared to assess inter-rater reliability and stratified based on whether the score was concordant or discordant among reviewers to determine factors related to discordance. Thirty-nine CPC scores (22.8%) were discordant (kappa: 0.66), indicating substantial agreement. When dichotomized into "favorable" neurologic outcome (CPC 1-2)/"unfavorable" neurologic outcome (CPC 3-5), 20 (11.7%) scores were discordant (kappa: 0.70), also indicating substantial agreement. Patients discharged home (as opposed to nursing/other care facility) and patients with suspected cardiac etiology of arrest were statistically more likely to have concordant scores. For the quality improvement database, patients with discordant scores had a statistically higher median CPC score than those with concordant scores. The registry had statistically lower median CPC score (CPC 1) than the quality improvement database (CPC 2); p<0.01 for statistical significance. CPC scores have substantial inter-rater reliability, which is reduced in patients who have worse outcomes, have a non-cardiac etiology of arrest, and are discharged to a location other than home.

Most successfully resuscitated cardiac arrest patients do not survive to hospital discharge. Many have withdrawal of life sustaining therapy (WLST) as a result of the perception of poor neurologic prognosis. The characteristics of these patients and differences in their post-arrest care are largely unknown. Utilizing the Penn Alliance for Therapeutic Hypothermia Registry, we identified a cohort of 1311 post-arrest patients from 26 hospitals from 2010 to 2014 who remained comatose after return of spontaneous circulation. We stratified patients by whether they had WLST post-arrest and analyzed demographic, arrest, and post-arrest variables. In our cohort, 565 (43%) patients had WLST. In multivariate regression, patients who had WLST were less likely to go to the cardiac catheterization lab (OR 0.40; 95% CI: 0.26-0.62) and had shorter hospital stays (OR 0.93; 95% CI: 0.91-0.95). When multivariate regression was limited to patient demographics and arrest characteristics, patients with WLST were older (OR 1.18; 95% CI: 1.07-1.31 by decade), had a longer arrest duration (OR 1.14; 95% CI: 1.05-1.25 per 10min), more likely to be female (OR: 1.41; 95% CI: 1.01-1.96), and less likely to have a witnessed arrest (OR 0.65; 95% CI: 0.42-0.98). Patients with WLST differ in terms of demographic, arrest, and post-arrest characteristics and treatments from those who did not have WLST. Failure to account for this variability could affect both clinical practice and the interpretation of research.