The use of esmolol in whole-body hyperthermia: Cardiovascular effects

Abstract

Whole-body hyperthermia (WBH) is a well-described investigational adjunct to systemic chemotherapy for the treatment of advanced malignancies. The hemodynamic consequences of this physiologic state may include tachycardia, which can produce acute myocardial ischemia in patients with coronary artery disease. Ischemic heart disease is currently considered a contraindication to WBH. We chose to investigate the consequences of using a new beta 1-adrenergic antagonist, esmolol, to attempt to control the tachycardia associated with WBH. After institutional approval and patient consent, nine consecutive patients with normal cardiac function presenting for WBH with carboplatin infusion were studied. Along with standard monitors, radial arterial and oximetric thermodilution pulmonary artery catheters were placed. Patients were sedated and heated in a radiant warmer (Enthermics). Spontaneous ventilation was maintained and hemodynamic data were gathered at 37 degrees C, and at 41.8 degrees C (before, during and after esmolol infusion). Heart rate and cardiac output increased (by 46% (p = 0.001) and 35% (p = 0.04) respectively) while mean arterial pressure and systemic vascular resistance fell (by 18% (p = 0.02) and 44% (p = 0.006) respectively) during hyperthermia. Heart rate was significantly reduced during esmolol administration (mean dose 180 micrograms/kg/min) in the absence of changes in cardiac index and calculated oxygen delivery. Ventricular filling pressures and stroke work were unchanged. No heart failure, pulmonary edema, or other adverse event was observed. Hemodynamic changes seen during esmolol administration were completely reversed 15 min after the infusion was stopped. We conclude that the administration of moderate doses of esmolol is safe for this population of patients undergoing WBH, and that this technique raises the question of whether patients with ischemic heart disease could safely undergo WBH.

Monitoring arterial blood pressure during whole body hyperthermia

“…Previously, treatment with WBH has been repeatedly associated with severe toxicities, such as heart failure, pulmonary aspiration, hepato‐ and nephro‐toxicity (1, 2, 7). Furthermore, the application of WBH results in extensive changes in hemodynamics, as described in previous studies (6, 8–10). Therefore the control of arterial blood pressure (ABP) under these hypercirculatory conditions is difficult and often requires the application of large amounts of fluid replacement and of catecholamines.…”

Whole body hyperthermia: a secure procedure for patients with various malignancies?

“…To make WBH more tolerable, hyperglycemia and hyperoxemia were induced [5]. There are differing findings concerning the use of beta-receptor antagonists (propranolol, esmolol) under WBH to reduce the cardiovascular reactions, in animal experiments and in humans [18,19]. Furthermore, the increased efficacy achieved by integrating immunotherapeutic approaches and the influence on apoptosis processes by hyperthermia have been described [12].…”

Stress induced changes in lymphocyte subpopulations and associated cytokines during whole body hyperthermia of 41.8–42.2°C

“…Application of therapeutic WBH is associated with extreme acute stress reactions, indicated by significant increase of heart rate, cardiac output and oxygen consumption (Berry et al 1997;Faithfull et al 1984;Kerner et al 1999). In addition, elevated plasma levels of stress hormones have been observed under hyperthermic conditions (Kappel et al 1991;Kearns et al 1999;Robins et al 1987) and suppressive effects of these stress hormones on lymphocyte subpopulations as well as associated cytokines are well known (Elenkov and Chrousos 2002;Iwakabe et al 1998;Kohm and Sanders 2001;Madden et al 1995).…”