Review Of: Yannopoulous D, Matsuura T, Shultz J, et al. Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest. Crit Care Med. 2011;39(6):1269–1274.
The Science: This is a randomized blinded animal study used to assess the impact of sodium nitroprusside (SNP) on neurological outcomes of pigs after prolonged cardiac arrest. A total of 24 pigs were randomized into three groups:
• 8 received standard CPR—compressions only with epinephrine administered every 5 minutes;
• 8 received enhanced CPR active compression decompression (ACD) CPR, an impedance threshold device (ITD), and abdominal binding;
• 8 received SNP with enhanced CPR—same protocol as enhanced CPR but with the addition of SNP.
Each pig had induced ventricular fibrillation (v fib) and remained in cardiac arrest for 8 minutes before any interventions were attempted. CPR was performed for 25 minutes before defibrillation was attempted. Once the pigs were resuscitated, their neurological function was assessed at 1 hour and 24 hours after the arrest. Results of the study were astonishing: no pigs survived in the standard CPR group; two pigs survived in the enhanced CPR group, and seven pigs survived in the SNP with enhanced CPR group. The authors conclude that enhanced CPR with SNP greatly improves neurological outcomes and hemodynamics during cardiac arrest.
Dr. Wesley: We’ve come a long way in our understanding of the pathophysiology of cardiac arrest. First, we learned that chest compressions are more important than ventilations. Then, we learned that quality CPR included pushing hard and pushing fast, with minimal interruptions. Next, we learned that creating a negative intrathoracic pressure with the ResQPod (ITD) increased blood return to the heart and improved both survival and neurological outcome. And most recently, we’ve learned that high concentration oxygen is toxic to the ischemic brain during and following cardiac arrest.
Throughout this exodus of discovery, no evidence has proved that epinephrine or any other cardiac arrest medication improved survival. As the authors suggest, I believe that our use of epinephrine was an attempt to improve blood return to the heart through vasoconstriction. However, if we can accomplish this in a more physiological manner through quality CPR using an ACD device and an ITD, then, clearly, there is no benefit to epinephrine. In fact, epinephrine may significantly worsen neurological outcomes by causing deleterious cerebral vasoconstriction and ischemia.
The authors not only showed that quality CPR with an ACD mechanical CPR device and ITD makes a difference, but they also demonstrated that the addition of nitroprusside to counteract physiologic cerebral vasoconstriction further improves neurological outcomes.
I foresee a day when we place cardiac arrest patients in a machine that performs CPR, induces hypothermia and administers medications based on lab analysis and transcranial perfusion monitoring. Defibrillation occurs only when the amplitude of v fib is optimal and levels of oxygen and acidosis are normalized.
Medic Marshall: I agree with the Doc on the evolution of cardiac arrest research, insomuch as how far we’ve come to understand what really matters. I’ve been around long enough to see a few changes in how cardiac arrests have been managed, and now it’s come back to good ol’ chest compressions along with a few other additions like the ITD and the advancement of ACD CPR.
I believe this study is laying the foundation for some major changes in the way cardiac arrests are managed pharmacologically. Like the Doc pointed out, we’ve been using epinephrine as means to improve circulation to the heart via vasoconstriction. But based on previous research pioneered by Dr. Keith Lurie, we know we can accomplish that through the use of ITDs and ACD CPR.
Like I said, this only lays the foundation. All pigs had v fib induced cardiac arrest, so all we can really take away is this: The protocol works with v fib, but what about the pulseless electrical activity/asystole cardiac arrests? Secondly, a new component exists that, at least to my knowledge, isn’t readily practiced by EMS: abdominal binding. The authors state that this is to help reduce blood flow through the descending aorta and improve circulation to the heart and brain. I’m not sure if and/or when this will become practice in EMS. I guess we’ll just have to wait in see.
In the end, I think this is truly novel research, and I look forward to seeing more studies similar to this in the future.
Objective: To assess the effectiveness of sodium nitroprusside (SNP)-“enhanced” cardiopulmonary resuscitation (SNPeCPR) on 24-hr survival rates compared to standard CPR in animals after cardiac arrest. SNPeCPR consists of large intravenous SNP bolus doses during CPR enhanced by active compression-decompression CPR, an inspiratory impedance threshold device (ITD), and abdominal binding (AB). The combination of active compression-decompression CPR+ITD+AB without SNP will be called “enhanced” or eCPR.
Design: Randomized, blinded, animal study.
Setting: Preclinical animal laboratory.
Subjects: Twenty-four female farm pigs (30 =1 kg).
Interventions: Isoflurane anesthetized and intubated pigs were randomized after 8 mins of untreated ventricular fibrillation to receive either standard CPR (n =8), SNPeCPR (n = 8), or eCPR (n = 8) for 25 minutes followed by defibrillation.
Measurements and Main Results: The primary end point was carotid blood flow during CPR and 24-hr survival with good neurologic function defined as an overall performance category score of <2 (1 being normal, 5 being braindead or dead). Secondary end points included hemo- dynamics and end-tidal CO2. SNPeCPR significantly improved carotid blood flow and 24-hr survival rates with good neurologic function compared to standard CPR or eCPR (six of eight vs. zero of eight vs. one of eight, p < .05). The improved survival rates were associated with higher coronary perfusion pressure and ETCO2 during CPR.
Conclusion: In pigs, SNPeCPR significantly improved hemodynamics, resuscitation rates, and 24-hr survival rates with good neurologic function after cardiac arrest when compared with standard CPR or eCPR alone. Crit Care Med. 2011;39(6):1269–1274.