Suspended animation for delayed resuscitation from prolonged cardiac arrest that is unresuscitable by standard cardiopulmonary-cerebral resuscitation

Abstract

Standard cardiopulmonary-cerebral resuscitation fails to achieve restoration of spontaneous circulation in approximately 50% of normovolemic sudden cardiac arrests outside hospitals and in essentially all victims of penetrating truncal trauma who exsanguinate rapidly to cardiac arrest. Among cardiopulmonary-cerebral resuscitation innovations since the 1960s, automatic external defibrillation, mild hypothermia, emergency (portable) cardiopulmonary bypass, and suspended animation have potentials for clinical breakthrough effects. Suspended animation has been suggested for presently unresuscitable conditions and consists of the rapid induction of preservation (using hypothermia with or without drugs) of viability of the brain, heart, and organism (within 5 mins of normothermic cardiac arrest no-flow), which increases the time available for transport and resuscitative surgery, followed by delayed resuscitation. Since 1988, we have developed and used novel dog models of exsanguination cardiac arrest to explore suspended animation potentials with hypothermic and pharmacologic strategies using aortic cold flush and emergency portable cardiopulmonary bypass. Outcome evaluation was at 72 or 96 hrs after cardiac arrest. Cardiopulmonary bypass cannot be initiated rapidly. A single aortic flush of cold saline (4 degrees C) at the start of cardiac arrest rapidly induced (depending on flush volume) mild-to-deep cerebral hypothermia (35 degrees to 10 degrees C), without cardiopulmonary bypass, and preserved viability during a cardiac arrest no-flow period of up to 120 mins. In contrast, except for one antioxidant (Tempol), explorations of 14 different drugs added to the aortic flush at room temperature (24 degrees C) have thus far had disappointing outcome results. Profound hypothermia (10 degrees C) during 60-min cardiac arrest induced and reversed with cardiopulmonary bypass achieved survival without functional or histologic brain damage. Further plans for the systematic development of suspended animation include the following: a) aortic flush, combining hypothermia with mechanism-specific drugs and novel fluids; b) extension of suspended animation by ultraprofound hypothermic preservation (0 degrees to 5 degrees C) with cardiopulmonary bypass; c) development of the most effective suspended animation protocol for clinical trials in trauma patients with cardiac arrest; and d) modification of suspended animation protocols for possible use in normovolemic ventricular fibrillation cardiac arrest, in which attempts to achieve restoration of spontaneous circulation by standard external cardiopulmonary resuscitation-advanced life support have failed.

Rapid Induction of Therapeutic Hypothermia Using Transnasal High Flow Dry Air

“…Several studies have shown that moderate systemic hypothermia (30°C) or mild hypothermia (*34°C) markedly mitigates brain damage after CA in dogs (Safar et al, 2000;Behringer et al, 2003;Kuboyama et al, 2003). The mechanism is thought to be a reduction in cerebral oxygen consumption among other multifactorial chemical and physical mechanisms during and after ischemia (Lyon et al, 2010).…”

Anoxia-Induced Suspended Animation in Budding Yeast as an Experimental Paradigm for Studying Oxygen-Regulated Gene Expression

“…These include many popular model organisms, such as nematodes (53), fruit flies (20), zebrafish (26), and mice (51). In addition, much work has been done on less well-studied systems, including brine shrimp (21), turtles (55), carp (15), sharks (37), and dogs (47). These organisms all appear to manifest physiological and behavioral changes that are consistent with a decrease in metabolism when exposed to lower-than-normal oxygen concentrations.…”

Is Hypothermia Useful in Managing Critically Ill Patients? Which Ones? Under What Conditions?

“…44 Safar's group followed that work, showing benefit in experimental CA. 45 These studies provided evidence that even mild hypothermia could significantly improve outcome in CA.…”