Thiamine for the Treatment of Cardiac Arrest–Induced Neurological Injury: A Randomized, Blinded, Placebo‐Controlled Experimental Study

Abstract

Background Thiamine supplementation has demonstrated protective effects in a mouse model of cardiac arrest. The aim of this study was to investigate the neuroprotective effects of thiamine in a clinically relevant large animal cardiac arrest model. The hypothesis was that thiamine reduces neurological injury evaluated by neuron‐specific enolase levels. Methods and Results Pigs underwent myocardial infarction and subsequently 9 minutes of untreated cardiac arrest. Twenty minutes after successful resuscitation, the pigs were randomized to treatment with either thiamine or placebo. All pigs underwent 40 hours of intensive care and were awakened for assessment of functional neurological outcome up until 9 days after cardiac arrest. Nine pigs were included in both groups, with 8 in each group surviving the entire intensive care phase. Mean area under the curve for neuron‐specific enolase was similar between groups, with 81.5 μg/L per hour (SD, 20.4) in the thiamine group and 80.5 μg/L per hour (SD, 18.3) in the placebo group, with an absolute difference of 1.0 (95% CI, −57.8 to 59.8; P =0.97). Likewise, there were no absolute difference in neurological deficit score at the end of the protocol (2 [95% CI, −38 to 42]; P =0.93). There was no absolute mean group difference in lactate during the intensive care period (1.1 mmol/L [95% CI, −0.5 to 2.7]; P =0.16). Conclusions In this randomized, blinded, placebo‐controlled trial using a pig cardiac arrest model with myocardial infarction and long intensive care and observation for 9 days, thiamine showed no effect in changes to functional neurological outcome or serum levels of neuron‐specific enolase. Thiamine treatment had no effect on lactate levels after successful resuscitation.

Animal research in cardiac arrest

“…An additional tool to be utilized to strengthen the methodology of preclinical studies is publication of protocols prior to completing the study (e.g., preclinicaltrials.eu ). 33 This can help to increase transparency and reduce reporting bias including bias induced by selective outcome reporting.…”

Neuroprotective Approaches for Brain Injury After Cardiac Arrest: Current Trends and Prospective Avenues

“…Although several pharmacological agents targeting the oxidative stress, brain edema, inflammation, and cell death in the context of CA have been extensively studied and resulted in promising results across various preclinical studies, very few have been translated into the clinical setting and majority have failed to exert significant beneficial effects in CA patients. Unlike its benefits in rodent CA model, thiamine treatment at a dose of 10 mg/kg starting at 20 minutes after ROSC and every 12 hours over 48 hours had no effect in improvement of functional neurological outcome or serum levels of NSE in a 9-minute ventricular fibrillation pig CA model [ 102 ]. Thiamine showed no difference in survival and neurological functions in an RCT including 37 adult OHCA patients when given IV at a dose of 100 mg every 8 hours (starting at 3.5 h from hospital admission) for 7 days [ 103 ].…”