Local Cerebral Blood Flow with Fentanyl-Induced Seizures

Abstract

Summary: Local cerebral blood flow (LCBF) was eval uated with the [14C]iodoantipyrine quantitative autoradio graphic technique in 29 brain structures in conscious con trol rats and during fentanyl-induced electroencephalo graphic (EEG) spike and/or seizure activity and in the postseizure EEG suppression phase. During spike ac tivity, LCBF increased in all structures; the increase reached statistical significance (p < 0.05) in the superior colliculus, sensorimotor cortex, and pineal body (+ 130%, + 187%, and + 185% from control, respec tively). With progressive development of seizure activity, LCBF significantly increased in 24 brain structures (range, +58% to +231% from control). During the post seizure EEG suppression phase, LCBF remained ele vated in all structures (+ 80% to + 390% from control).High-dose narcotic anesthesia can elicit seizure activity in laboratory animals as well as under clin ical conditions (De Castro et aI., 1979; Sebel et aI., 1981; Bovill et aI., 1982; Rao et aI., 1982). In a re cent report, the increase in brain oxygen uptake due to fentanyl-elicited convulsive activity was not matched by an equivalent compensatory elevation in overall CBF (Carlsson et aI., 1982). This finding suggests that cerebral ischemia could result due to This paper was presented in part at the Annual Meeting of the American Society of Anesthesiologists, Las Vegas, Nevada, Oc tober 1982.Dr. Maekawa is a Research Fellow in Neuroanesthesia Re search at the University of California at San Diego; he is also affiliated with the Department of Anesthesiology, Yamaguchi University, Yamaguchi, Japan.Dr. Tommasino is a Research Fellow in Neuroanesthesia Re search at the University of California at San Diego; she is also affiliated with the Department of Anesthesia, University of Na ples, First Medical School, Italy.Address correspondence and reprint requests to Dr. Shapiro at Neuroanesthesia Research, M-004, University of California at San Diego, La Jolla, California 92093, U.S.A.Abbreviations used: CMR, Cerebral metabolic rate; LCBF, local cerebral blood flow; LCMR g 1u, local cerebral metabolic rate for glucose; LCVR, local cerebrovascular resistance. 88The local cerebrovascular resistance (LCYR) signifi cantly decreased in 10 of 29 structures with the onset of spike activity (range, -24% to -64%), and remained decreased in all brain structures during seizure activity (range, -34% to -67%) and during the EEG suppression phase (range, -24% to -74%). This reduction of LCVR METHODS Local cerebral blood flow (LCBF) was measured in 23Sprague-Dawley rats with the [14C]iodoantipyrine quan titative autoradiographic technique (Reivich et aI., 1969; Sakurada et a1., 1978). The rats weighed 289 ± 20 g (mean ± SD) and were studied while conscious and during fen tanyl administration, resulting in electroencephalographic (EEG) patterns consisting of spike, seizure, and postsei zure suppression activity. Fentanyl-treated animalsThe rats were briefly anesthetized with 1.5% halothane and 70% nitrous oxide in oxygen to permit tracheost...

Effects of Fentanyl on Local Cerebral Blood Flow in the Rat

“…The data on 1-CBF presented here and by Maekawa et al (13), and the data on 1-CMRgl presented by Tommasino et al (14) and Young et al (15), are consistent with the electrophysiologic work of Henriksen et al (16) and Nicoll et al (17), which showed that local deposition of P-endorphin or leucine-or methionine-enkephalin produced excitatory activity in the hippocampus or limbic system seizures. These findings for narcotics are similar to those for lidocaine, a compound that produces limbic system epileptogenic activity at fairly low doses compared to those required for cortical propagation (18,19).…”

“…They found marked increases in 1-CBF compared to controls in animals with seizures, but the basic pattern, including the predilection for limbic system structures, is similar to our findings. The increases in 1 -CBF noted by Maekawa et al (13) were considerably greater than the changes noted by us. However, the measurements we made were after 20 min of fentanyl infusion, and some of our animals were not actively seizing at the moment the CBF was measured.…”

Pharmacokinetic‐pharmacodynamic modelling of the EEG effect of alfentanil in rats: assessment of rapid functional adaptation

“…An important question is to what extent opioid induced CNS over‐excitation may explain this apparent discrepancy. It is well established that administration of (synthetic) opioids may result in epileptiform activity (Urca et al , 1977; Carlsson et al , 1982; Maekawa et al , 1984; Tommasino et al , 1984; Young et al , 1984; Keykhah et al , 1985; Kofke et al , 1993; Cox et al , 1997). Seizure activity may be a confounding factor in the assessment of spectral EEG parameters of opioids.…”

Effect of fentanyl on the electrophysiological recovery following incomplete global cerebral ischemia

“…Studies on fentanyl-induced convulsive activity in rats by Carlsson et al [ 19821 indicated that there was a mismatch between cerebral blood flow and cerebral oxygen utilization [Carlsson et al, 19821, in that there was no increase in the blood flow to match the increased oxygen de:mand of the brain during seizure activity. However, Maekawa et al [1984] demonstrated that there was an increase in the blood flow and a decrease in the cerebrovascular resistance in all the structures during high-dose fentanyl-induced seizure activity time and that the flows remained elevated even during postseizure EEG suppression phase. Although there is increased EEG spike activity in the high-dose fentanyl group in the preischemic period, it appears that this effect of high dose fentanyl does not reflect changes in the latency of the SSER before inducing ischemia.…”

“…In addition to their use in the clinical setting, opioids have become useful anesthetic agents in a variety of experimental studies [Carlsson et al, 1982;Maekawa et al, 1984;and Tommasino et al, 19841. Although opioids have been implicated in the pathophysiology of cerebral ischemic damage [Furui et al, 19841, the role of fentanyl in potentiating an ischemic/ reperfusion injury remains unclear.…”