Correspondence
Vasopressors in Cardiopulmonary Resuscitation
N Engl J Med 2008; 359:1624-1625October 9, 2008
- Article
To the Editor:
Gueugniaud et al. (July 3 issue)1 report that administering the combination of vasopressin and epinephrine, as compared with epinephrine alone, during advanced cardiac life support for out-of-hospital cardiac arrest does not improve outcome. The results of this study, however, are not surprising, considering that the average time from collapse to the arrival of advanced cardiac life support (downtime) was 16.3 minutes in each group and that only 9% of the patients in each group had ventricular fibrillation and thus a greater chance of survival than the patients with pulseless electrical activity or asystole. Studies have shown that downtimes longer than 10 minutes result in poor return of spontaneous circulation.2 In addition, coronary perfusion pressure was not measured and is an important determinant of the return of spontaneous circulation. Coronary perfusion pressure above 15 mm Hg is required for a return of spontaneous circulation, and vascular tone deteriorates over time after the cessation of circulation.3 A small number of patients in the study by Gueugniaud et al. did receive advanced cardiac life support after less than 12 minutes of downtime, and for these patients combination treatment was more effective. One could speculate that in this subgroup, the additional epinephrine increased the coronary perfusion pressure. Finally, this study did not standardize the critical care patients received after resuscitation,4 a factor that could have improved the outcome with respect to secondary end points.
4 ReferencesDaniel C. Morris, M.D.
Henry Ford Health Systems, Detroit, MI 48202
dmorris4@hfhs.org 1
Gueugniaud P-Y ,David J-S ,Chanzy E , et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med 2008;359:21-30
Full Text | Web of Science | Medline2
Stiell IG ,Hebert PC ,Weitzman BN , et al. High-dose epinephrine in adult cardiac arrest. N Engl J Med 1992;327:1045-1050
Full Text | Web of Science | Medline3
Paradis NA ,Martin GB ,Rivers EP , et al. Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA 1990;263:1106-1113
CrossRef | Web of Science | Medline4
Rivers EP ,Rady M ,Martin GB , et al. Venous hyperoxia after cardiac arrest: characterization of a defect in systemic oxygen utilization. Chest 1992;102:1787-1793
CrossRef | Web of Science | Medline
To the Editor:
In the study by Gueugniaud et al., more than 90% of the patients presented with asystole or pulseless electrical activity at the rescue scene. Current1 and past2 international guidelines recommend administering atropine after the first vasopressor drug in such patients. Therefore, it is surprising that the authors provide no explanation for omitting atropine in their study. More important, less than 1% of all the patients had good neurologic performance at the time of hospital discharge. Although the focus of the study was on patients presenting with asystole, the percentage of patients with a favorable neurologic outcome after asystole is not reported. If patients presenting with asystole were underrepresented among those with a good neurologic outcome, this would suggest that even larger studies will probably fail to show a relevant benefit of any therapeutic option in patients with asystole. Finally, there was a strong trend toward improved survival after 1 year in the epinephrine group. Why then do the authors not report the neurologic outcome after 1 year?
2 ReferencesFabian A. Spöhr, M.D.
Peter Teschendorf, M.D., D.E.A.A.
Bernd W. Böttiger, M.D., D.E.A.A.
University of Cologne, 50937 Cologne, Germany
fabian.spoehr@uk-koeln. de 1
Nolan JP ,Deakin CD ,Soar J ,Bottiger BW ,Smith G . European Resuscitation Council guidelines for resuscitation 2005. 4. Adult advanced life support. Resuscitation 2005;67:Suppl 1:S39-S86
CrossRef | Web of Science | Medline2
International Guidelines 2000 for CPR and ECC -- a consensus on science. Resuscitation 2000;46:1-448
CrossRef | Medline
Author/Editor Response
Since no randomized clinical trial has ever shown a survival benefit with the use of atropine in patients with asystole or pulseless electrical activity, and in accordance with the most recent French recommendations,1 we chose not to include atropine in our study protocol. As stated in our article, the outcome was partly related to the long duration of ischemia (about 45 minutes between the onset of cardiac arrest and the return of spontaneous circulation in both groups), and not only to the quality of and specific therapy used in cardiac resuscitation. Nevertheless, because Wenzel et al.2 reported that vasopressin alone was superior to epinephrine alone in patients with asystole, whereas the time from collapse to the first injection of study drugs was 3 minutes shorter than in our study (18 vs. 21 minutes), we evaluated the subgroup of patients who had received the drugs less than 18 minutes after collapse. In this subgroup, 158 of 606 patients (26.1%) in the epinephrine-only group versus 147 of 587 (25.0%) in the combined-therapy group were admitted (P=0.68).
Whatever the time from collapse to treatment, we can state that adding vasopressin to epinephrine did not improve the outcome. We agree, however, that any study of cardiopulmonary resuscitation suffers from a lack of statistical power,3 since long-term survival rates are at best 10%.2 Accordingly, with the hospital-discharge rate being only about 2%, it was decided that any stratification of the neurologic outcome according to the initial electrocardiographic rhythm would have been susceptible to random effects. But to address the question posed by Spöhr et al., the number of patients with good neurologic performance at discharge among patients with asystole was 5 of 1194 (0.4%) in the epinephrine-only group versus 3 of 1197 (0.3%) in the combination-therapy group (relative risk, 1.00; 95% confidence interval [CI], 1.00 to 1.01) and for all patients after 1 year, 16 of 1447 (1.1%) versus 12 of 1437 (0.8%) (relative risk, 1.00; 95% CI, 1.00 to 1.01). We agree that there may be only a small window of time in which to achieve both successful restoration of spontaneous circulation and full neurologic recovery.
Although it would be very elegant to measure the quality of ongoing cardiac-resuscitation efforts invasively, we did not want to burden investigators in this academic multicenter trial, involving about 3000 patients, with the task of performing an invasive blood-pressure measurement.
In our opinion, future trials may have to focus more on patients with a greater chance of long-term survival and less on patients with an extremely low chance of survival.
3 ReferencesPierre-Yves Gueugniaud, M.D., Ph.D.
University of Lyon 1, 69373 Lyon CEDEX 08, France
pierre-yves.gueugniaud@chu-lyon. fr Volker Wenzel, M.D.
Innsbruck Medical University, 6020 Innsbruck, AustriaHervé Hubert, Ph.D.
University of Lille 2, 59120 Lille, France1
Recommandations formalisées d'experts: prise en charge de l'arrêt cardiaque. Paris: Société Française d'Anesthésie et de Réanimation, 2006. (Accessed September 19, 2008, at http://www.sfar.org/t/IMG/pdf/ac_rfe07.pdf.)
2
Wenzel V ,Krismer AC ,Arntz HR ,Sitter H ,Stadlbauer KH ,Lindner KH . A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004;350:105-113
Full Text | Web of Science | Medline3
Riou B ,Landais P ,Vivien B ,Stell P ,Labbene I ,Carli P . Distribution of the probability of survival is a strategic issue for randomized trials in critically ill patients. Anesthesiology 2001;95:56-63
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Theresa M. Olasveengen, Lars Wik, Kjetil Sunde, Petter A. Steen. (2011) Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial. Resuscitation
CrossRef
