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

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.

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.

Adenosine, lidocaine and Mg2+ improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model.

INTRODUCTION: The combination of Adenosine (A), lidocaine (L) and Mg(2+) (M) (ALM) has demonstrated cardioprotective and resuscitative properties in models of cardiac arrest and hemorrhagic shock. This study evaluates whether ALM also demonstrates organ protective properties in an endotoxemic porcine model. METHODS: Pigs (37 to 42 kg) were randomized into: 1) Control (n = 8) or 2) ALM (n = 8) followed by lipopolysaccharide infusion (1 µg ∙ kg(-1) ∙ h(-1)) for five hours. ALM treatment consisted of 1) a high dose bolus (A (0.82 mg/kg), L (1.76 mg/kg), M (0.92 mg/kg)), 2) one hour continuous infusion (A (300 µg ∙ kg(-1) ∙ min(-1)), L (600 µg ∙ kg(-1) ∙ min(-1)), M (336 µg ∙ kg(-1) ∙ min(-1))) and three hours at a lower dose (A (240 ∙ kg(-1) ∙ min(-1)), L (480 µg ∙ kg(-1) ∙ min(-1)), M (268 µg ∙ kg(-1) ∙ min(-1))); controls received normal saline. Hemodynamic, cardiac, pulmonary, metabolic and renal functions were evaluated. RESULTS: ALM lowered mean arterial pressure (Mean value during infusion period: ALM: 47 (95% confidence interval (CI): 44 to 50) mmHg versus control: 79 (95% CI: 75 to 85) mmHg, P < 0.0001). After cessation of ALM, mean arterial pressure immediately increased (end of study: ALM: 88 (95% CI: 81 to 96) mmHg versus control: 86 (95% CI: 79 to 94) mmHg, P = 0.72). Whole body oxygen consumption was significantly reduced during ALM infusion (ALM: 205 (95% CI: 192 to 217) ml oxygen/min versus control: 231 (95% CI: 219 to 243) ml oxygen/min, P = 0.016). ALM treatment reduced pulmonary injury evaluated by PaO2/FiO2 ratio (ALM: 388 (95% CI: 349 to 427) versus control: 260 (95% CI: 221 to 299), P = 0.0005). ALM infusion led to an increase in heart rate while preserving preload recruitable stroke work. Creatinine clearance was significantly lower during ALM infusion but reversed after cessation of infusion. ALM reduced tumor necrosis factor-α peak levels (ALM 7121 (95% CI: 5069 to 10004) pg/ml versus control 11596 (95% CI: 9083 to 14805) pg/ml, P = 0.02). CONCLUSION: ALM infusion induces a reversible hypotensive and hypometabolic state, attenuates tumor necrosis factor-α levels and improves cardiac and pulmonary function, and led to a transient drop in renal function that was reversed after the treatment was stopped.