Plasma Diltiazem Levels, Cardiovascular Function, and Coronary Hemodynamics during Enflurane Anesthesia in the Dog

Abstract

KAPUR PA, CAMPOS JH, BUCHEA OC. Plasma diltjazem levels, cardiovascular function, and coronary hemodynamics during enflurane anesthesia in the dog. Anesth Analg 1986;65:918-24.Diltiazein 7ons ndininistered to dogs by a n intraueiious illfiisiori protocol, which resulted in plasma levels of 71 ? 6 ( I i = 7 ) , 139 ? 9 ( n = 7), 353 i 33 ( n = l o ) , and 1064 ? 143 (11 = 6) ng/ml, to ezialunte the effects of diltiazetn on i-nrrfiouasculur functioii mid coronar>y heinodynainics in the prescnce of mesthetic concentratioiis of enfluranc. An additional xroup of six dogs receizied enf7iirane only. The only c h a n p olwrued zilith eiiflurnne alone were 17 decrease in Icft z~entricular (LV) dPldt, cardinc index (Cl), nnd coronariy blood f7ozi1 60 inin after the haselirie m m i i r m e n t s were rnadr. I n all of fhe diltiazem groups, p l a s m leuel-related donga at ion of tkc PR interval of the elecfrocnrdiogrnrn iias observed, iiiith developinent of second degree henrt block and jrriictionnl rhythms in animals at the tziio hiRher plasma Jc~w/s. Mean nrterial pressure and LV dPidt decreased nt the two higher diltiazein plusinn leuels after 30 inin (if itrfusion, nnd three of six dogs in the highest group had to be dropped froin the study because of severe hypotension. The cardiac index ZORS no different from enflurane alone with the three lower plasma diltiazem levels. No changes were obserued in coronary sinus blood flow, coronary vascular resistnnce, inyocardinl oxygen uptake, or myocardial lactate extraction. Circulating norepinephrine levels were elevated in the tzoo higher diltiazein groups. In the presence of anesthetic coticentrations of enflurane, over the range of plasma diltiazein leziels investigated in this study, conduction effects w r e proriiinent and decreases in left ventricular performance and hlood pressure occurred as plasma diltiazem levels iiicreased. No untoward effects on global myocardial metnholisin zuere detected at plasma levels less than 500 ngi nil. However, the occurrence of circulatory collapse in half of the nninials at the highest plasma levels prevented evaluation of nietabolic effects of high levels of diltiazem during enflurane anesthesia.Diltiazem has a spectrum of clinical usefulness similar to that of verapamil (1-6). Because combined cardiovascular depressant effects may limit the use of verapamil in the presence of inhalation anesthestics (7), diltiazem may be a potential alternative if therapeutically indicated during inhalation anesthesia. Previous work in our laboratory has demonstrated that clinically relevant plasma levels of diltiazem are generally well-tolerated during 1.5% end-tidal isoflurane anesthesia in a canine model (8). Plasma level-related prolongation of the PR interval of the electrocardiogram and mild depression of left ventricular dPidt were the major findings. No alterations in global left ventricular oxygen consumption or coronary hemodynamics were noted. However, the previous study was limited to isoflurane and to plasma levels of diltiazem less than 60...

Cardiovascular Effects of Diltiazem in the Dog

“…The effects of diltiazem on the coronary circulation appear to vary with the baseline anaesthetic. In contrast to the results of this study, CVR did not change in dogs anaesthetized by isoflurane or enflurane [17,18].…”

“…In contrast to the preservation of global RV and LV function during fentanyl anaesthesia noted in this study, in the presence of volatile anaesthetics, diltiazem has been shown to be a potent myocardial depressant [10,17,18]. This might have been the result of absence of afterload reduction, underlying myocardial depression caused by inhalation anaesthetics or impaired baroreceptor reactivity.…”

“…before induction of anaesthesia, and on fentanyl given as a continuous infusion and supplemented with additional bolus doses when required. While adverse interactions have been described between diltiazem and inhalation anaesthetic agents [10,17,18], the effects of diltiazem during i.v. anaesthesia have not been studied as yet.…”

Haemodynamic Effects of Diltiazem During Fentanyl-Nitrous Oxide Anaesthesia †

“…The potential use of diltiazem in clinical anaesthesia may be limited by adverse electrophysiological effects, which occur at plasma concentrations necessary to achieve haemodynamic changes. Second degree AV block and junctional escape rhythm at plasma concentrations of less than 300 ng ml" 1 have been reported during enflurane [8] and isoflurane [5] anaesthesia in dogs. In the present study, during fentanyl-nitrous oxide anaesthesia, second degree AV block was not observed consistently until relatively high plasma diltiazem concentrations were achieved (greater than 400 ng ml" 1 ).…”

Acute Closed-Chest Canine Model for Anaesthesia Research

“…Studies undertaken at the cardiopulmonary research laboratory of the Department of Anesthesiology at the UCLA School of Medicine, have been related to various aspects of the cardiovascular interactions of newer cardioactive drugs with anaesthetics. These have included: arrhythmia studies with verapamil [6,7], comparison of the influence of the different inhalation anaesthetics upon verapamil pharmacodynamics [3], pharmacodynamic studies of diltiazem with varying anaesthetics [4,5], interactions of betaadrenergic blockers with verapamil comparing barbiturate with halothane anaesthesia [8,18], a series of studies related to the properties of the newer cardiotonic drug amrinone [11][12][13], and continuing studies of the cardiovascular relationships between local anaesthetic compounds and calcium channel blocking drugs.…”