New Application of a Traditional Vasoactive Agent, Sodium Nitroprusside, in Targeted Temperature Management During Cardiac Arrest and Resuscitation* Zhengfei Yang, MD Wanchun Tang, MD, MCCM Weil Institute of Critical Care Medicine Rancho Mirage, CA; Keck School of Medicine of the University of Southern California Los Angeles, CA; UC San Diego School of Medicine San Diego, CA; and Sun Yat-sen Memorial Hospital Sun Yat-sen University Guangzhou, China


ild therapeutic hypothermia has been proven to be effective on myocardial and neurological protection after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in both animal and human studies (1–4). It is well recognized that, to achieve the greatest benefit from hypothermia, rapid cooling to the targeted temperature should be initiated as early as possible after CA (5–7). However, current methods for inducing hypothermia have limitations and difficulties when applied in out-of-hospital cardiac arrest (OHCA) patients. Endovascular cooling is invasive and technically inadequate for field use (8). Despite the effectiveness of cold saline infusion during CPR or postresuscitation demonstrated by animal studies, the efficacy and the safety of large volume cold fluid for the patients are still questionable (9, 10). Although recent promising methods of inducing hypothermia, such as nasopharyngeal cooling or pharmacologically induced hypothermia with WIN55, 212-2, have been proven to be effective, the cost-effective and clinical safety have limited their widespread use in a short term (7, 11). Surface cooling with ice packs or cooling blankets is now widely used in the OHCA setting because of its convenience, low cost, and safety. However, it is slow and difficult to reach the target temperature due to peripheral vasoconstriction and shivering. Therefore, the feasible and low-cost auxiliary mean to enhance inducing hypothermia has been a promising endeavor. Sodium nitroprusside (SNP), a traditional vasodilator agent, has been approved by the U.S. Food and Drug

*See also p. 849. Key Words: cardiac arrest; cardiopulmonary resuscitation; hypothermia; sodium nitroprusside; ventricular fibrillation The authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000000844


Administration for the treatment of severe hypertension since 1974. Recently, the combination of SNP with mechanical CPR (SNPeCPR) has been proven to optimize hemodynamics during CPR and improve myocardial and neurologic function and therefore the survival outcome in animal studies (12, 13). Based on the publication, in this issue of Critical Care Medicine, Debaty et al (14) investigated the effect of SNPeCPR on heat exchange during surface cooling in a prolonged ventricular fibrillation (VF) porcine model. In this prospective randomized controlled animal study, 28 pigs with induced VF were randomized into three groups: SNPeCPR group, SNPeCPR plus epinephrine group, and control group. Surface cooling was initiated at the onset of CPR. The animals in the SNPeCPR group were treated with active compressiondecompression CPR combined with an inspiratory impedance threshold device (ACD-ITD) plus abdominal binding and 2 mg of SNP at 1, 4, and 8 minutes of CPR, whereas an additional 0.5 mg of epinephrine was administrated at 4.5 and 9 minutes of CPR in the SNPeCPR plus epinephrine group. For the control group, the animals were treated with ACDITD with epinephrine. Hemodynamics and the temperature in the brain, inferior vena cava, and skin were continuously monitored during CPR and 2 hours postresuscitation. The time required to reach a brain temperature of 35°C was significantly shorter in the SNPeCPR group when compared with the other two groups. Carotid blood flow was greater during CPR in the SNPeCPR group. They therefore concluded that SNPeCPR significantly accelerates intra-CPR heat exchange with surface cooling, whereas an additional dose of epinephrine to SNPeCPR attenuates its effect on heat exchange. Since vasoconstriction is induced by hypothermia, diversion of the blood from the cold skin to the internal organs might block the core blood flow from the surface cooling agent. Although vasoconstriction is stopped in the animals treated with SNP, the body should follow Newton’s law of cooling, which might be one of the rational explanations for effectively induced hypothermia during CPR (15). Optimal blood flow generated by CPR that exchanges heat more efficiently might be an alternative rational explanation in this study. A traditional and low-cost agent—SNP—is introduced to enhance intra-CPR hypothermia. It is promising during CPR in the OHCA setting because SNP is already in the first aid equipment. However, several issues should be noted: first, the adverse effect on hemodynamics of SNP is hypotension. Although no negative hemodynamic effects were observed in this pig study, convincing data for human CPR are still lacking. Second, it is unknown whether SNP improves the heat exchange and outcomes of manual CPR only during intra-CPR hypothermia when SNPeCPR is unavailable. Third, the optimal dose and April 2015 • Volume 43 • Number 4


duration of SNP have not been clarified. The metabolism of the SNP might change during CA and hypothermia. It is therefore unknown how much is an overdose for humans under the above conditions. In addition, as shown in the present study, it is noted that high-quality CPR was performed prior to drugs for optimal blood flow even during intra-arrest hypothermia. Several limitations in the present study should be stated. First, the healthy porcine model does not always indicate the real condition of patients in a clinical setting. Successful resuscitation from CPR and counter shock would not be anticipated unless the underlying precipitating cause is corrected, such as revascularization of coronary occlusions. Negative effects of SNP on coronary perfusion are unknown in CA patients who have suffered from coronary artery disease. Second, abdominal binding during CPR only in SNPeCPR and SNPeCPR combined with epinephrine may reduce the circulation in the lower body. However, it might be possible to improve the cerebral perfusion and therefore facilitate the heat exchange during surface cooling. It is difficult to clarify the beneficial effects on the heat exchange and carotid blood flow from SNP-enhanced CPR or abdominal binding. Third, neurologically intact survival outcomes were not observed. Further experimental research should be developed to clarify the optimal dose and usage of SNP and assess the clinically relevant outcomes for SNPeCPR during intra-arrest hypothermia. Finally, human trials are needed to prove the clinical effects of SNP on the intra-CPR hypothermia.


1. Ye S, Weng Y, Sun S, et al: Comparison of the durations of mild therapeutic hypothermia on outcome after cardiopulmonary resuscitation in the rat. Circulation 2012; 125:123–129 2. Tsai MS, Barbut D, Wang H, et al: Intra-arrest rapid head cooling improves postresuscitation myocardial function in comparison with delayed postresuscitation surface cooling. Crit Care Med 2008; 36:S434–S439

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3. Bernard SA, Gray TW, Buist MD, et al: Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346:557–563 4. Hypothermia after Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346:549–556 5. Abella BS, Zhao D, Alvarado J, et al: Intra-arrest cooling improves outcomes in a murine cardiac arrest model. Circulation 2004; 109:2786–2791 6. Guan J, Barbut D, Wang H, et al: A comparison between head cooling begun during cardiopulmonary resuscitation and surface cooling after resuscitation in a pig model of cardiac arrest. Crit Care Med 2008; 36(11 Suppl):S428–S433 7. Yu T, Barbut D, Ristagno G, et al: Survival and neurological outcomes after nasopharyngeal cooling or peripheral vein cold saline infusion initiated during cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest. Crit Care Med 2010; 38:916–921 8. Safar P, Klain M, Tisherman S: Selective brain cooling after cardiac arrest. Crit Care Med 1996; 24:911–914 9. Nordmark J, Rubertsson S: Induction of mild hypothermia with infusion of cold (4 degrees C) fluid during ongoing experimental CPR. Resuscitation 2005; 66:357–365 10. Kim F, Nichol G, Maynard C, et al: Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: A randomized clinical trial. JAMA 2014; 311:45–52 11. Sun S, Tang W, Song F, et al: Pharmacologically induced hypothermia with cannabinoid receptor agonist WIN55, 212-2 after cardiopulmonary resuscitation. Crit Care Med 2010; 38:2282–2286 12. Schultz JC, Segal N, Caldwell E, et al: Sodium nitroprussideenhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models. Crit Care Med 2011; 39:2705–2710 13. Schultz J, Segal N, Kolbeck J, et al: Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest. Resuscitation 2012; 83:374–377 14. Debaty G, Matsuura TR, Bartos JA, et al: Sodium Nitroprusside– Enhanced Cardiopulmonary Resuscitation Facilitates Intra-Arrest Therapeutic Hypothermia in a Porcine Model of Prolonged Ventricular Fibrillation. Crit Care Med 2015; 43:849–855 15. Dhruva AJ, Javeri PM, Parulkar GB, et al: Mechanism of temperature fall during hypothermia by surface cooling. An experimental and clinical study. Anesth Analg 1963; 42:306–315


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New application of a traditional vasoactive agent, sodium nitroprusside, in targeted temperature management during cardiac arrest and resuscitation.

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