Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

Abstract

Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in failing human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors during the hypothermia period. The initial LVEF was 32.6 ± 1.2% indicating a significantly impaired LV function. During hypothermia induction, the infusion rate of epinephrine could be significantly reduced from 9.1 ± 1.3 μg/min [arrival intensive care unit (ICU) 35.4°C] to 4.6 ± 1.0 μg/min (34°C) and 2.8 ± 0.5 μg/min (33°C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure remained stable. The mean heart rate significantly decreased from 91.8 ± 1.7 bpm (arrival ICU) to 77.3 ± 1.5 bpm (34°C) and 70.3 ± 1.4 bpm (33°C). In vitro we investigated the effect of hypothermia on isolated ventricular muscle strips from explanted failing human hearts. With decreasing temperature, the contractility increased to a maximum of 168 ± 23% at 27°C (n = 16, P < 0.05). Positive inotropic response to hypothermia was accompanied by moderately increased rapid cooling contractures as a measure of sarcoplasmic reticulum (SR) Ca2+ content, but can be elicited even when the SR Ca2+ release is blocked in the presence of ryanodine. Contraction and relaxation kinetics are prolonged with hypothermia, indicating increased Ca2+ sensitivity as the main mechanism responsible for inotropy. In conclusion, mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might contribute to improved survival rates in these patients. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium most likely by increasing Ca2+-sensitivity.Electronic supplementary materialThe online version of this article (doi:10.1007/s00392-010-0113-2) contains supplementary material, which is available to authorized users.

Cardiac Index During Therapeutic Hypothermia: Which Target Value Is Optimal?

“…Although systolic performance is clearly improved at all temperature steps investigated, pronounced hypothermia may impair diastolic function [10]. However, in the temperature range recommended for mild therapeutic hypothermia in cardiac arrest patients (32-34°C) [11,12] , dias tolic function seems to be preserved [6]. Al though mild therapeutic hypothermia may have direct repercussions on the myocardium, a study by Bernard et al showed no clinically signifi cant eff ect on cardiac arrhythmias in the hypothermia group [13].…”

“…Th e phenomenon of increased inotropism during mild therapeutic hypothermia is not associated with increased sarcoplasmic reticulum Ca 2+ -content or increased Ca 2+ -transients [5] . Moreover, recent studies using animal species and in humans have provided accumulating evidence suggesting that mild therapeutic hypothermia may also improve cardiac performance [5,6]. Th erefore, the higher survival rates may also be related to positive hemodynamic eff ects of cooling in patients already suff ering from cardiac disease.…”

Mild Induced Therapeutic Hypothermia for Survivors of Cardiac Arrest

“…In 2006, the National Registry of Cardiopulmonary Resuscitation (CPR) published statistics on 19,819 adults and 524 children with return of spontaneous circulation after cardiac arrest. The mortality rates were 67% among adults and 55% among children (Jacobshagen et al, 2010). Currently, less than half of cardiac arrest patients survive to discharge and less than a third of those discharged have a good neurologic outcome as defined by the Cerebral Performance Category (CPS) Scale (Adler et al, 2011).…”

“…The coiling provides a mechanism to increase surface area, thereby increasing the heat exchange between blood passing over the catheter. Internal cooling and rewarming is much faster and superior to other techniques in tightly regulating target temperature; it is possible to cool patients by 1.46°C -1.59°C per hour (Jacobshagen et al, 2010). A potential advantage of using catheter-based cooling combined with anxiolytics is that it may avoid the need to use paralytics to decrease the shiver seen in surface cooling techniques.…”

“…Potassium administraction should be stopped to avoid hyperkalemia during the re-warming phase. After re-warming to 36°C, sedation and paralytic agents should be discontinued and the patient should be weened off ventilator support (Jacobshagen et al, 2010). Neurologic recovery can take several hours after discontinuation of hypothermia.…”