Does anesthetic provide similar neuroprotection to therapeutic hypothermia after cardiac arrest?

In the previous issue of Critical Care, Meybohm and colleagues provide evidence to support hypothermia as a kind of therapeutic option for patients suffering cardiac arrest. Although anesthetics had been used to induce hypothermia, sevoflurane post-conditioning fails to confer additional anti-inflammatory effects after cardiac arrest. Further research in this area is warranted.

Th erapeutic hypothermia has been shown to provide neuro protection against ischemic injury after cardiac arrest in in vitro and in vivo models. In the previous issue of Critical Care, Meybohm and colleagues [1] demonstrate that cardiac arrest triggers the release of cerebral infl ammatory cytokines in pigs' cerebral cortex. Th erapeutic hypothermia alters infl ammatory response in cardiac arrest and subsequent cardiopulmonary resuscitation. Th e combination of hypothermia with sevofl urane post-conditioning does not confer additional antiinfl ammatory eff ects compared with hypothermia alone.
Cardiac arrest remains the leading cause of death in the US and Europe, with an out-of-hospital cardiac arrest survival-to-discharge rate of less than 10%. In-hospital cardiac arrest presents a dismal prognosis. According to a large in-hospital registry, the survival-to-discharge rate is 18%, whereas that of a developing country is 6.9% [2,3]. Without prompt care, the chance for meaningful survival falls dramatically within minutes of arrest onset. When immediate care is available and victims are successfully resuscitated, the majority of these initial survivors subsequently suff er crippling neurologic injury or die in the few days following the cardiac arrest event. Th us, improving survival and brain function after initial resuscitation from cardiac arrest remains a critical challenge. Th erapeutic hypothermia, introduced more than six decades ago, remains an impor tant neuroprotective factor in cardiac arrest. Laboratory studies have demonstrated that cooling after resuscitation from cardiac arrest improves both survival as well as subsequent neurologic and cardiac function and has few side eff ects. Th ese fi ndings have been reproduced using a variety of cooling techniques in diff erent species, including rats, dogs, and pigs.
However, physician use of hypothermia induction in patients resuscitated from cardiac arrest is low. In 2003, Abella and colleagues [4] reported that 87% of US physicians did not use therapeutic hypothermia following cardiac arrest. Various reasons for non-use were cited: 49% felt that there were not enough data, 32% mentioned lack of incorporation of hypothermia into advanced cardiovascular life support protocols, and 28% felt that cooling methods were technically too diffi cult or too slow. In 2002, a European group demonstrated an improve ment in survival-to-discharge rate with favorable neurologic status in cooled patients, compared with normo thermic patients surviving after cardiac arrest (53% versus 35%, respectively), and with no signifi cant adverse events from cooling; thereafter, induced hypothermia was considered the best practice for patients following cardiac arrest [5]. In 2005, the American Heart Asso ciation recommended the consideration of therapeutic hypothermia for unconscious adult patients with return of spontaneous circulation following out-ofhospital cardiac arrest due to ventricular fi brillation. In 2008, Binks and colleagues [6] reported that 85.6% of intensive care units in the UK were using hypothermia as part of post-cardiac arrest management.

Abstract
In the previous issue of Critical Care, Meybohm and colleagues provide evidence to support hypothermia as a kind of therapeutic option for patients suff ering cardiac arrest. Although anesthetics had been used to induce hypothermia, sevofl urane post-conditioning fails to confer additional anti-infl ammatory eff ects after cardiac arrest. Further research in this area is warranted. of therapeutic hypothermia via the reduction of the upregulation expression of IL-1β, IL-6, IL-10, TNFα and intercellular adhesion molecule-1, Bcl-2, and Bax mRNA and IL-1β protein in cerebral cortex after cardiac arrest in a pig model.
Small reductions in core temperature lead to vasoconstriction and shivering, eff ectively hindering hypothermia. Th us, prevention of vasoconstriction and shivering has become a major goal during induction of therapeutic hypothermia. Anesthetics and sedatives can lower the vasoconstriction and shivering threshold, thus allowing hypothermia. Sevofl urane pre-conditioning and early post-conditioning reduced both cerebral infarct size and neurological defect score, reduced impairment of hippocampus long-term potentiation resulting from myocardial ischemia, and increased nuclear factor inhibitory kappaBalpha content in THP-1 cells [11][12][13]. Sevofl urane pre-conditioning preserves myocardial function in patients undergoing coronary artery bypass graft surgery under cardiologic arrest [14]. An in vivo study showed that combination hypothermia with sevofl urane attenuates the infl am matory response during endotoxemia [15]. However, Meybohm and colleagues [1] could not provide evidence to support the view that sevofl urane post-conditioning confers additional antiinfl ammatory eff ects in pigs' cerebral cortex after cardiopulmonary resuscitation.
In summary, Meybohm and colleagues [1] provide useful evidence to support the clinical use of therapeutic hypothermia for cardiac arrest, but they did not study the anti-infl ammatory eff ects of sevofl urane in this model. It is even possible that in the setting of clinical practice, anesthetics may not provide signifi cant neuroprotection beyond that which is already being produced by therapeutic hypothermia. Th us, at this time, it is diffi cult to recommend anesthetics for the purpose of neuroprotection in cardiac arrest.