The Effects of High-Dose Fentanyl on Cerebral Circulation and Metabolism in Rats

Carlsson, Christer; Smith, David S.; Keykhah, M. Mehdi; Englebach, Isabella; Harp, James R.

doi:10.1097/00000542-198211000-00005

Cited by 94 publications

(40 citation statements)

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“…In Carlsson's study, seizures occurred as an incidental finding after a period of fentanyl loading followed by a maintenance infusion (Carlsson et al, 1982). While Carlsson's total fentanyl dose was two to three times greater than that employed in our experiments, we postulate that the seizures oc curred as blood levels of fentanyl were declining in his rats.…”

Section: Resultsmentioning

confidence: 52%

Local Cerebral Blood Flow with Fentanyl-Induced Seizures

Maekawa¹,

Tommasino²,

Shapiro³

1984

J Cereb Blood Flow Metab

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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...

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Section: Resultsmentioning

confidence: 52%

Local Cerebral Blood Flow with Fentanyl-Induced Seizures

Maekawa¹,

Tommasino²,

Shapiro³

1984

J Cereb Blood Flow Metab

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“…We are unable to find any specific data to support this hypothesis. However, the central time constant is known to be inversely proportional to cerebral blood flow and, despite some controversy, there is considerable evidence that narcotics reduce cerebral blood flow (Takeshita, Michenfelder & Theye, 1972;Vernhiet, Renou, Orgogozo, Constant & Caille, 1978;Carlsson, Smith, Keykhah, Englebach & Harp, 1982). It should be noted that most of the research relating narcotics to reductions in cerebral blood flow has been done with much higher, that is, anaesthetic, doses (1-3 mg kg-') of morphine than the analgesic doses (0 07 and 0-21 mg kg-1) used in our study.…”

Section: Discussionmentioning

confidence: 99%

The steady‐state and rebreathing methods compared during morphine administration in humans.

Bourke

Warley

1989

The Journal of Physiology

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SUMMARY1. We examined the quantitative and qualitative differences between the steadystate and rebreathing methods of determining C02-response curves before and after each of two doses of intravenous morphine (0 07 and 0-14 mg kg-') in four healthy male humans.2. During each study session steady-state and rebreathing C02-response curves were determined as an ordered pair (separated by 15 min). Carbon dioxide-response curves were determined for control, after 0 07 mg kg-' morphine, and after a total of 0-21 mg kg-1 morphine. Each subject was studied on a second occasion when the order of the C02-response pairing was reversed.3. The results are discussed and related to a model that may account for the differences based on the step increase in CO2 at the onset of rebreathing, the rate of rise of CO2 during rebreathing and the time constant for the central chemoreflex.4. Our empirical conclusion is that morphine causes a parallel right shift of the steady-state CO2-response curve and causes a non-specific decrease in the slope of the rebreathing C02-response curve. We suggest that the parallel shift of the steadystate C02-response curve is specific to drugs acting on opioid receptors.

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“…6 Electrical seizure activity induced by opiates has been well documented with electroencephalogram (EEG) recording in animals. 2 The correlation between abnormal movements and electrical seizures is less consistent in adult humans receiving opiates 5,[7][8][9] and is lacking in the neonatal patient. The objective of our study is to report on two infants with abnormal electroencephalographic findings while receiving opioids.…”

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confidence: 99%

Seizure and Electroencephalographic Changes in the Newborn Period Induced By Opiates and Corrected By Naloxone Infusion

Alexandrou

Knoppert

et al. 1999

J Perinatol

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OBJECTIVE:To describe the association between opioid administration in the newborn period and neurologic abnormalities STUDY DESIGN:Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxone RESULTS:The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration. CONCLUSION:Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.Opiates are widely used in neonatal intensive care units for routine sedation/analgesia of critically ill neonates receiving mechanical ventilation, as well as for postoperative pain control. 1 Seizure activity as a complication of opioid administration has been reported in the literature in laboratory animals, 2 adult humans 3-5 and neonates. 6 Electrical seizure activity induced by opiates has been well documented with electroencephalogram (EEG) recording in animals. 2 The correlation between abnormal movements and electrical seizures is less consistent in adult humans receiving opiates 5,7-9 and is lacking in the neonatal patient. The objective of our study is to report on two infants with abnormal electroencephalographic findings while receiving opioids. One infant presented with clinical and electroencephalographic seizure activity. The second infant had a grossly abnormal EEG pattern. CASE 1Baby girl M was born at 39 weeks' gestation by elective cesarean section to a 34-year-old mother. The birth weight was 3975 gm, the cord arterial pH was 7.34, and the Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. The baby was admitted to the normal newborn nursery for routine care. She was transferred to the neonatal intensive care unit (NICU) at 24 hours of age due to abdominal distention and bilious vomiting. Radiologic studies revealed a small bowel obstruction and she was operated at 35 hours of age for congenital ileal atresia. She received a cumulative dose of 20 g (5 g/kg) of fentanyl for anesthesia and 1 mg (0.25 mg/kg) of morphine in the operating suite for pain control (increased heart rate and increased blood pressure during operation). There were no complications during the surgery. Fifteen minutes postoperatively she was noted to have abnormal movements (fasciculation of the tongue and lips). A continuous infusion of fentanyl was started at a rate of 5 g/kg per hour beginning 30 minutes postsur...

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The Effects of High-Dose Fentanyl on Cerebral Circulation and Metabolism in Rats

Cited by 94 publications

References 0 publications

Local Cerebral Blood Flow with Fentanyl-Induced Seizures

Local Cerebral Blood Flow with Fentanyl-Induced Seizures

The steady‐state and rebreathing methods compared during morphine administration in humans.

Seizure and Electroencephalographic Changes in the Newborn Period Induced By Opiates and Corrected By Naloxone Infusion

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