Shaffner DH, Eleff SM, Brambrink AM, Sugimoto H, Izuta M, Koehler RC, Traystman RJEffect of arrest time and cerebral perfusion pressure during cardiopulmonary resuscitation on cerebral blood flow, metabolism, adenosine triphosphate recovery, and pH in dogs. Crit Care Med 27:1335-1342

Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Critical Care Medicine (Impact Factor: 6.31). 08/1999; 27(7):1335-42. DOI: 10.1097/00003246-199907000-00026
Source: PubMed


To test the hypothesis that greater cerebral perfusion pressure (CPP) is required to restore cerebral blood flow (CBF), oxygen metabolism, adenosine triphosphate (ATP), and intracellular pH (pHi) levels after variable periods of no-flow than to maintain them when cardiopulmonary resuscitation (CPR) is started immediately.
Prospective, randomized, comparison of three arrest times and two perfusion pressures during CPR in 24 anesthetized dogs.
University cerebral resuscitation laboratory.
We used radiolabeled microspheres to determine CBF and magnetic resonance spectroscopy to derive ATP and pHi levels before and during CPR. Ventricular fibrillation was induced, epinephrine administered, and thoracic vest CPR adjusted to provide a CPP of 25 or 35 mm Hg after arrest times of O, 6, or 12 mins.
When CPR was started immediately after arrest with a CPP of 25 mm Hg, CBF and ATP were 57 +/- 10% and 64 +/- 14% of prearrest (at 10 mins of CPR). In contrast, CBF and ATP were minimally restored with a CPP at 25 mm Hg after a 6-min arrest time (23 +/- 5%, 16 +/- 5%, respectively). With a CPP of 35 mm Hg, extending the no-flow arrest time from 6 to 12 mins reduced reflow from 71 +/- 11% to 37 +/- 7% of pre-arrest and reduced ATP recovery from 60 +/- 11% to 2 +/- 1% of pre-arrest. After 6- or 12-min arrest times, brainstem blood flow was restored more than supratentorial blood flow, but cerebral pHi was never restored.
A CPP of 25 mm Hg maintains supratentorial blood flow and ATP at 60% to 70% when CPR starts immediately on arrest, but not after a 6-min delay. A higher CPP of 35 mm Hg is required to restore CBF and ATP when CPR is delayed for 6 mins. After a 12-min delay, even the CPP of 35 mm Hg is unable to restore CBF and ATP. Therefore, increasing the arrest time at these perfusion pressures increases the resistance to reflow sufficient to impair restoration of cerebral ATP.

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    • "Different from DHCA, clinical application of EPR in management of ExCA would only be feasible after a normothermic ExCA has occurred. Brain energy reserve is depleted B5 mins after normothermic CA (Shaffner et al, 1999; Eleff et al, 1991). Thus, to postpone energy failure, it may be important for preservation strategies to prevent energy depletion in brain and restore energy levels during induction of hypothermia. "
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    ABSTRACT: We have used a rapid induction of profound hypothermia (<10 degrees C) with delayed resuscitation using cardiopulmonary bypass (CPB) as a novel approach for resuscitation from exsanguination cardiac arrest (ExCA). We have defined this approach as emergency preservation and resuscitation (EPR). We observed that 2 h but not 3 h of preservation could be achieved with favorable outcome using ice-cold normal saline flush to induce profound hypothermia. We tested the hypothesis that adding energy substrates to saline during induction of EPR would allow intact recovery after 3 h CA. Dogs underwent rapid ExCA. Two minutes after CA, EPR was induced with arterial ice-cold flush. Four treatments (n=6/group) were defined by a flush solution with or without 2.5% glucose (G+ or G-) and with either oxygen or nitrogen (O+ or O-) rapidly targeting tympanic temperature of 8 degrees C. At 3 h after CA onset, delayed resuscitation was initiated with CPB, followed by intensive care to 72 h. At 72 h, all dogs in the O+G+ group regained consciousness, and the group had better neurological deficit scores and overall performance categories than the O-groups (both P<0.05). In the O+G- group, four of the six dogs regained consciousness. All but one dog in the O-groups remained comatose. Brain histopathology in the O-G+ was worse than the other three groups (P<0.05). We conclude that EPR induced with a flush solution containing oxygen and glucose allowed satisfactory recovery of neurological function after a 3 h of CA, suggesting benefit from substrate delivery during induction or maintenance of a profound hypothermic CA.
    Full-text · Article · Mar 2008 · Journal of Cerebral Blood Flow & Metabolism
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    • "Shaffner et al. demonstrated the importance of early institution of cardiopulmonary resuscitation because a delay beyond 6 min markedly impairs the ability to generate viable levels of cerebral blood flow in dogs (23). Furthermore, even at cerebral perfusion pressure of 35 mmHg after 6 mins of CVC, cerebral metabolic recovery is incomplete and inadequate to restore full reperfusion. "
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    ABSTRACT: Although levobupivacaine (LBUP) is less cardiotoxic than racemic bupivacaine (RBUP), the resuscitation from the LBUP-induced cardiovascular collapse (CVC) has not been easy as expected. Following the recent reports that proposed the resuscitative action of insulin for the RBUP-induced CVC, a controlled trial was performed to assess the feasibility of insulin for the LBUP-induced CVC. Fourteen dogs were randomly allocated into two groups: the RBUP and LBUP groups. Each group received continuous intravenous infusions of RBUP or LBUP until the mean arterial pressure (MAP) reached 40 mmHg. Then, an intravenous bolus of insulin (2 U/kg) was administered. Both groups were successfully resuscitated. At CVC, a decrease of cardiac output and an increase of systemic vascular resistance were observed but to a lesser degree in the LBUP group (p<0.05). After insulin injection, the MAP further declined to under 40 mmHg for several minutes, which was more protracted in the LBUP group (p<0.05). The CVCs induced by LBUP or RBUP in anesthetized dogs could be successfully resuscitated by insulin. Compared with RBUP, however, the less degree of vasoconstriction by LBUP and the innate vasodilatory property of insulin yielded a delayed increment of MAP during the immediate resuscitation period in the LBUP-induced CVC.
    Full-text · Article · Apr 2007 · Journal of Korean Medical Science
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    • "In an animal experiment of CPR Shaffner and colleagues assessed cerebral energy metabolism using a non invasive magnet resonance spectroscopy (MRS) [24]. They described fundamental changes of adenosine triphosphate levels during the experiment comparing dogs resuscitated with a cerebral perfusion pressure (CPP) of 25, respectively 35 mmHg after different arrest times. "
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    ABSTRACT: Microdialysis is an established tool to analyse tissue biochemistry, but the value of this technique to monitor cardiopulmonary resuscitation (CPR) effects on cerebral metabolism is unknown. The purpose of this study was to assess the effects of active-compression-decompression (ACD) CPR in combination with an inspiratory threshold valve (ITV) (=experimental CPR) vs. standard CPR on cerebral metabolism measured with microdialysis. Fourteen domestic pigs were surfaced-cooled to a body core temperature of 26 degrees C and ventricular fibrillation was induced, followed by 10 min of untreated cardiac arrest; and subsequently, standard (n=7) CPR vs. experimental (n=7) CPR. After 8 min of CPR, all animals received 0.4 U/kg vasopressin IV, and CPR was maintained for an additional 10 min in each group; defibrillation was attempted after a total of 28 min of cardiac arrest, including 18 min of CPR. In the standard CPR group, microdialysis measurements showed a 13-fold increase of the lactate-pyruvate ratio from 7.2+/-1.3 to 95.5+/-15.4 until the end of CPR (P<0.01), followed by a further increase up to 138+/-32 during the postresuscitation period. The experimental group developed a sixfold increase of the lactate-pyruvate ratio from 7.1+/-2.0 to 51.1+/-8.7 (P<0.05), and a continuous decrease after vasopressin. In the standard resuscitated group, but not during experimental CPR, a significant increase of cerebral glucose levels from 0.6+/-0.1 to 2.6+/-0.5 mM was measured (P<0.01). Using the technique of microdialysis we were able to measure changes of brain biochemistry during and after the very special situation of hypothermic cardiopulmonary arrest. Experimental CPR improved the lactate-pyruvate ratio, and glucose metabolism.
    Full-text · Article · Dec 2003 · Resuscitation
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