Optimal dosing of dobutamine for treating post-resuscitation left ventricular dysfunction
Introduction
Treatment of cardiac arrest with standard cardiopulmonary resuscitation (CPR) results in successful resuscitation in only 30–40% of such cases [1], [2]. Unfortunately, of those initially resuscitated, less than 50% survive to leave the hospital [3], [4], [5]. Such high post-resuscitation mortality rates can be attributed to both central nervous system and myocardial injury [2].
A significant amount of research has focused on investigating the prevention and treatment of cerebral damage associated with cardiac arrest and CPR. More recently, attention has been increasingly directed towards improving post-resuscitation myocardial dysfunction. The initial detailed descriptions of post-resuscitation myocardial dysfunction came from animal experiments utilizing rodent and swine models of ventricular fibrillation arrest, and showed not only profound systolic and diastolic myocardial dysfunction, but also that the majority of such animals succumb before recovery of ventricular function can be achieved [6], [7], [8]. Clinical reports have corroborated this phenomenon and its devastating effect on long-term survival after resuscitation from prolonged cardiac arrest [9]. This premature death is potentially avoidable, in that post-resuscitation myocardial failure is reversible and merely a manifestation of profound global ventricular stunning [8]. Such myocardial stunning can and will improve if supported during the critical early period [10]. Dobutamine can effectively overcome such dysfunction, but previously studied doses were associated with significant increases in heart rate [10]. Such therapy-derived tachycardia is worrisome, due to the potential for increasing myocardial oxygen consumption and for worsening the ischemic burden of an already stressed myocardium. The aim of this study was to investigate the optimal dose of dobutamine in a well-described porcine model of post-resuscitation myocardial dysfunction, where adequate myocardial support could be provided without excessively raising the heart rate and myocardial oxygen consumption.
Section snippets
Methods
All trials were conducted in accordance with the position of the American Heart Association on Research Animal Use (1984) and with the approval of The University of Arizona Institutional Animal Care and Use Committee.
Twenty-two domestic swine, weighing 24±0.4 kg, were anesthetized with isoflurane in oxygen, delivered by facemask. They were endotracheally intubated and maintained at a surgical plane of anesthesia using 1–2% isoflurane and oxygen, until they were euthanized 6 h post-resuscitation.
Hemodynamic data
The major hemodynamic changes from baseline through 6 h after resuscitation are presented in Table 1. Right atrial pressure, mean pulmonary artery pressure and mean pulmonary artery occlusion pressures were initially increased, though not significantly. Those values returned to baseline in the treatment groups by the end of the study period.
Systolic function and dobutamine
Table 2 summarizes the parameters of myocardial function, blood flow and oxygen consumption.
An expected decline in ejection fraction was noted in all groups
Discussion
Previous work by our group demonstrated that dobutamine at a dose of 10 mcg/kg min results in successful treatment of post-resuscitation left ventricular systolic and diastolic dysfunction, at the expense of significant tachycardia [10]. Limited pilot data at that time revealed less tachycardia at doses of 5 mcg/kg min, but the improvement in left ventricular dysfunction appeared to be less pronounced [10]. In the present study, dobutamine dose response curves for a variety of left ventricular
Conclusions
Intravenous dobutamine can ameliorate, in a dose-dependent fashion, the severe systolic and diastolic dysfunction that ensues after successful resuscitation following prolonged cardiac arrest. A 2 mcg/kg min dose appears ineffective, while a dose of either 5 or 7.5 mcg/kg min can correct left ventricular systolic and diastolic dysfunction to baseline and even supernormal levels, with an expected rise in baseline heart rate. While an increase in myocardial blood flow was seen with the 7.5 mcg/kg min
Acknowledgements
This work was funded through grants from the American Heart Association Desert/Mountain Affiliate, and the Max and Victoria Dreyfus Foundation Inc., White Plains, NY.
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