Elsevier

Resuscitation

Volume 61, Issue 2, May 2004, Pages 199-207
Resuscitation

Optimal dosing of dobutamine for treating post-resuscitation left ventricular dysfunction

https://doi.org/10.1016/j.resuscitation.2004.01.002Get rights and content

Abstract

Objectives: This study was designed to determine the optimal dose of dobutamine in the treatment of post-resuscitation left ventricular dysfunction. Background: Global left ventricular dysfunction following successful resuscitation from prolonged, ventricular fibrillation cardiac arrest, negatively impacts long-term survival. Dobutamine can overcome this global myocardial stunning. Previous data indicate a dose of 10 mcg/kg min improves systolic and diastolic function, but markedly increases the heart rate. Methods: Twenty swine (24±0.4 kg) were randomized to one of four doses (0, 2, 5, and 7.5 mcg/kg min) of dobutamine for the treatment of post-resuscitation myocardial dysfunction following 12.5 min of untreated ventricular fibrillation cardiac arrest. Cardiac function was measured at pre-arrest baseline and serially for 6 h post-resuscitation. Left ventricular function was evaluated by contrast ventriculograms, left ventricular pressures, +dP/dt, Tau, −dP/dt, and cardiac output. Myocardial oxygen consumption and myocardial blood flow were measured to assess the functional significance of any dobutamine-mediated heart rate responses. Results: Left ventricular dysfunction was evident at 25 min and peaked 4 h post-resuscitation. Significant (P<0.05) improvements in ventricular systolic (EF, CO) and diastolic (LVEDP, Tau) function were evident within minutes of dobutamine initiation and persisted at 6 h for the 5 and 7.5 mcg/kg min groups. Tachycardia manifested with all dobutamine doses, but only affected myocardial oxygen consumption significantly (P<0.05) at the highest dose (7.5 mcg/kg min). Conclusions: Dobutamine at 5 mcg/kg min appears optimal for restoring systolic and diastolic function post-resuscitation without adversely affecting myocardial oxygen consumption.

Sumàrio

Objectivos: Este estudo tem como objectivo determinar a dose óptima de dobutamina para o tratamento da disfunção ventricular pós paragem cardiorespiratória. Antecedentes: A disfunção ventricular esquerda global depois da reanimação de paragem cardio-respiratória prolongada em fibrilhação ventricular, tem impacto negativo na sobrevida a longo prazo. A Dobutamina pode tratar este “stunning” miocárdico. Estudos anteriores mostraram que uma dose de 10 mcg/Kg/min melhora a função ventricular sistólica e diastólica com aumento marcado da frequência cardı́aca. Métodos: Foram aleatorizados 20 porcos (24±0,4 Kg) para uma de quatro doses de Dobutamina (0, 2, 5 e 7,5 mcg/Kg/min) para o tratamento da disfunção ventricular após PCR não tratada durante 12,5 minutos. A função cardı́aca foi medida antes e cada 6 horas após PCR por ventriculografia, medição da pressão ventricular e débito cardı́aco. O consumo de oxigénio e o fluxo sanguı́neo miocárdico foram também medidos. Resultados: A disfunção do ventrı́culo esquerdo era evidente aos 25 minutos e o seu pico máximo foi às 4 horas. Foram, evidentes melhorias na função sistólica e diastólica minutos depois do inı́cio da Dobutamina, que persistiam ás 6 horas para os subgrupos dos 5 e 7,5 mcg/Kg/min. Verificou-se taquicardia com todas as doses de Dobutamina mas que só afectaram significativamente o consumo de oxigénio (P<0.05) pelo miocárdio nas doses de 7,5 mcg/Kg/min. Conclusões: A Dobutamina na dose de 5 mcg/Kg/min parece óptima para o restabelecimento da função miocárdica diastólica e sistólica pós PCR sem efeitos adversos sobre a oxigenação do miocárdio.

Resumen

Objetivos: Este estudio fue diseñado para determinar la dosis óptima de dobutamina en el tratamiento de la disfunción de ventrı́culo izquierdo post resucitación. Antecedentes: La disfunción global del ventrı́culo izquierdo, que se presenta después de una resucitación exitosa de un paro cardı́aco prolongado por fibrilación ventricular, impacta negativamente la sobreviva a largo plazo. La dobutamina puede atenuar el efecto de este estupor miocárdico. Datos previos indican una dosis de 10 mcg/kg mejora la función sistólica y diastólica, pero aumenta marcadamente la frecuencia cardiaca. Métodos: Veinte cerdos (24±0,4 kg) fueron randomizados a una de cuatro dosis (0, 2, 5 y 7,5 mcg/kg min) de dobutamina para el tratamiento de la disfunción miocárdica post resucitación después de 12,5 min. de paro cardı́aco en fibrilación ventricular no tratada. La función cardiaca fue medida en la lı́nea basal antes del paro y en forma seriada por 6 hrs post resucitación. La función de ventrı́culo izquierdo fue evaluada por ventriculogramas de contraste, presiones de ventrı́culo izquierdo, +dP/dt, Tau, −dP/dt, y gasto cardı́aco. El consuno de oxı́geno miocárdico y el flujo sanguı́neo miocárdico fueron medidos para calcular la significancia funcional de cualquier respuesta de frecuencia cardiaca mediada por dobutamina. Resultados: La disfunción de ventrı́culo izquierdo fue evidente a los 25 minutos y aumentó bruscamente 4 h post resucitación. Mejorı́as significativas (P<0,05) de la función sistólica (EF, CO) y función diastólica (LVEDP, Tau) fueron evidentes dentro de minutos desde el inicio de la dobutamina y persistieron a las 6 hrs en los grupos de 5 y 7,5 mcg/kg min. La taquicardia se manifestó en todas las dosis de dobutamina, pero solo afectó significativamente (P<0,05) el consumo de oxı́geno a la dosis mas alta (7,5 mcg/kg min). Conclusiones: La dobutamina a una dosis de 5 mcg/kg min parece óptima para restaurar las funciones sistólica y diastólica después de la resucitación sin afectar adversamente el consumo de oxı́geno miocárdico.

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.

References (17)

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