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Epinephrine Vs. Vasopressin


Review of:Mally S, Jelatancev A, Grmec S: "Effects of epinephrine and vasopressin on end-tidal carbon dioxide tension and mean arterial blood pressure in out-of-hospital cardiopulmonary resuscitation: an observational study." Critical Care. 11(2):R39, 2007.

The Science

This study comes to us from Maribor, Slovenia. In this city of 200,000, ALS is provided by a physician and two nurses. The authors prospectively studied the results of cardiac arrest patients from 2000 to 2005 following the Utstein data set. In the beginning, they used only epinephrine for V Fib/V Tach and asystole/PEA. Sometime during 2003, they instituted vasopressin and used that as first-line pressor instead of epinephrine. They were allowed to follow vasopressin with epinephrine every five minutes at their discretion. They collected data on 598 cardiac arrests and specifically measured end-tidal CO2 (EtCO2) and mean arterial pressure (MAP). They also measured the usual rates of return of spontaneous circulation (ROSC), survival to admission, survival to discharge and neurological outcome.

The authors found that EtCO2 and MAP were significantly higher with the vasopressin group, which they defined as those who received either vasopressin alone and those who received vasopressin and epinephrine. This group also had a significantly greater rate of survival to admission and 24-hour survival. However, there was no difference between vasopressin and epinephrine on survival to discharge. A subset analysis showed that vasopressin improved survival to discharge for asystole patients. Finally, neurological outcome was better for patients resuscitated with vasopressin.

The Street

Many were surprised to see vasopressin in the 2005 AHA guidelines. There was very little evidence to support it. Since then, several studies have attempted to validate its use. This research is one of the few to have undertaken the extremely difficult task of examining its effect on human patients. More importantly, by also measuring EtCO2 and MAP, these researchers have provided us an additional data point to determine the impact of any cardiac-arrest intervention. EtCO2 clearly correlates with perfusion and consequently with ROSC.

With that said, did the study prove vasopressin is superior to epinephrine? I'm not sure. The study has some problems. First of all, it's prospective. CPR techniques and other resuscitation modalities may have changed over the study period to account for the outcomes. The ALS teams weren't blinded to the drugs they were administering, but this is impossible in current cardiac-arrest research on humans and probably had little to no impact. On the other hand, I'm concerned the authors combined the results of the vasopressin-only group with the vasopressin/epinephrine combination group. What were the results of the vasopressin-only group? Why did combination group receive both drugs? Were their resuscitations longer or more complex? This lack of study control raises some questions on data validity.

Additionally, further reading of the study reveals the epinephrine-only group received significantly greater amounts of epinephrine as well as more doses of atropine, bicarb and other vasopressors. Was this due to the inability of epinephrine to sufficiently resuscitate the patient or was this part of old protocols in the early years of the study? If it was the latter, then this may have contributed to the lower rates of ROSC. I suspect this is the case since the combination of vasopressin and epinephrine "appears" to be beneficial. Therefore, epinephrine is not harmful but may need to be combined or given at a different point in the resuscitation.

Are you more confused now than you were before? I am too. What is clear is that sufficient science shows vasopressin preserves cerebral perfusion and epinephrine negatively impacts pulmonary perfusion. This study clearly indicated that EtCO2 and MAP are linked to ROSC and survival to admission. However, the question of each drug's role still remains, as do the questions of under what circumstances and in what dosages they should be administered.


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