Epinephrine Versus Placebo During Resuscitation After Neonatal Hypoxic Cardiac Arrest: The Effect on ROSC and Markers of CNS Outcome Investigated in a Piglet Model

Abstract Background: Epinephrine is an integral component of neonatal resuscitation guidelines, despite sparse evidence. The association between advanced cardiopulmonary resuscitation (CPR) and poor neurodevelopment is well known, and epinephrine may improve short-term survival but at the cost of poor neurologic outcome. Our objectives were to investigate the effect of epinephrine vs placebo in a piglet model of neonatal hypoxic cardiac arrest (CA) by: 1) return of spontaneous circulation (ROSC), 2) time-to-ROSC, 3) markers of CNS outcome by magnetic resonance spectroscopy and imaging (MRS/MRI), and 4) composite endpoint of death or severe CNS outcome. Methods: Twenty-five newborn piglets under 12 hours of age underwent hypoxia. Hypoxia was induced by clamping the endotracheal tube until CA (mean arterial blood pressure <20 mmHg and heart rate <60 bpm). CPR was commenced five minutes after CA. The animals were randomized to either CPR + intravenous epinephrine or CPR + placebo (saline). MRS/MRI was performed six hours after resuscitation. Results: ROSC was more frequent in animals subjected to epinephrine than placebo; RR = 2.31 (95 % CI: 1.09 to 5.77). We found no difference between groups in time-to-ROSC. Among survivors, we found no difference between groups in brain lactate/N-acetyl-aspartate ratios (Lac/NAA), N-acetyl-aspartate/creatine ratios (NAA/Cr), diffusion-weighted-signal, or oxygenation-dependent-signal. We found a tendency towards reduced risk of the composite endpoint of death or severe CNS outcome in animals resuscitated with epinephrine compared to placebo, RR = 0.7 (95 % CI: 0.37 to 1.19).Conclusions: Resuscitation with epinephrine compared to placebo improved ROSC frequency after neonatal hypoxic CA. Surviving animals after resuscitation with epinephrine compared to placebo showed no difference in MRS/MRI markers of brain damage. These results support that epinephrine improves short-term survival without increasing brain injury measured by early imaging biomarkers.

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Empiric Tenecteplase is Associated with Increased Return of Spontaneous Circulation and Short Term Survival in Cardiac Arrest Patients Unresponsive to Standard Interventions

Journal of Emergency Medicine ◽

10.1016/j.jemermed.2007.03.028 ◽

2007 ◽

Vol 33 (1) ◽

pp. 97-98

Author(s):

C. Ryan Keay

Keyword(s):

Cardiac Arrest ◽

Spontaneous Circulation ◽

Short Term ◽

Term Survival ◽

Return Of Spontaneous Circulation ◽

Short Term Survival

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Methylene blue added to a hypertonic–hyperoncotic solution increases short-term survival in experimental cardiac arrest*

Critical Care Medicine ◽

10.1097/01.ccm.0000242517.23324.27 ◽

2006 ◽

Vol 34 (11) ◽

pp. 2806-2813 ◽

Cited By ~ 44

Author(s):

Adriana Miclescu ◽

Samar Basu ◽

Lars Wiklund

Keyword(s):

Methylene Blue ◽

Cardiac Arrest ◽

Short Term ◽

Term Survival ◽

Short Term Survival

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The effect of chest compression depth on short term survival during out of hospital cardiac arrest

Resuscitation ◽

10.1016/j.resuscitation.2010.09.056 ◽

2010 ◽

Vol 81 (2) ◽

pp. S11

Author(s):

Lukas R.-P. ◽

Harding U. ◽

Weber T.P. ◽

Quan W. ◽

Van Aken H. ◽

...

Keyword(s):

Cardiac Arrest ◽

Chest Compression ◽

Short Term ◽

Term Survival ◽

Compression Depth ◽

Hospital Cardiac Arrest ◽

Short Term Survival

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Abstract WP260: Pravastatin Improves Short-term Survival Rate Following Cardiac Arrest and Cardiopulumonary Resuscitation In Mice

Stroke ◽

10.1161/str.44.suppl_1.awp260 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Shin Nakayama ◽

Noriko Taguchi ◽

Makoto Tanaka

Keyword(s):

Body Weight ◽

Cardiac Arrest ◽

Survival Rate ◽

Neuronal Damage ◽

Pleiotropic Effects ◽

Histological Evaluation ◽

Vehicle Group ◽

Short Term ◽

Term Survival ◽

Short Term Survival

Statins (HMG-CoA reductase inhibitors) exert numerous pleiotropic effects and have been shown to attenuate ischemic injury in different rodent models of cerebral focal ischemia. Few studies have examined the effect of statins on post cardiac arrest syndrome. This study conducted cardiac arrest and cardiopulmonary resuscitation (CA/CPR) in mice and tested the hypothesis that intravenous statin after CPR improves survival rate and neurological outcomes. Methods: Adult male mice (20-26 g) were subjected to CA induced by intravenous (IV) KCL. After 8 min of CA, CPR was initiated with IV epinephrine, ventilation with 100% oxygen and chest compressions (rate 300/min). At 1 hr after return of spontaneous circulation, mice were treated with either IV injection of pravastatin (3mg/kg) or vehicle. Four days after CA/CPR, neurobehavioral assessments were performed and brains were removed for histological evaluation in hippocampus and caudateputamen. Results: No difference was found between two groups in body weight, duration of CPR and dose of epinephrine. Survival rate at 4 days after CPR was significantly higher in pravastatin group compared with vehicle group (66.7%; n=24 vs 48.4%; n=33). Neurobehavioral scores in pravastatin group were better than vehicle group at 2 to 4 days after CPR. Body weight loss in vehicle group at 4 days after CPR was higher than pravastatin group (-19.4±1.8% vs -13.4±2.0%), which indicates loss of feeding activity. Histological damages in hippocampus and caudateputamen were not statistically different between two groups (pravastatin: 23.8±7.0% vs vehicle: 35.2±9.2% in hippocampus) (pravastatin: 49.4±7.2% vs vehicle: 60.5±7.8% in caudateputamen). All values are presented as mean±SEM. Conclusions: Single IV injection of pravastatin after CA improved short-term survival and neurobehavioral score in the mouse experimental CA model. Neuronal damage in the brain region was comparable to vehicle group. These data suggest that pravastatin given after CA would be beneficial in the post resuscitation phase via systemic pleiotropic effects such as anti inflammatory response and improved vascular reactivity.

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