Seizure Induced by a Small Dose of Fentanyl

Takahiro Fujimoto, M.D.* *Correspondence Author　

Department of Anesthesiology, The University of Tokyo, Faculty of Medicine, Tokyo, Japan.

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Key word: Fentanyl, Seizure, Electroencephalogram
Clinically, fentanyl-induced seizures are rarely seen, while in animal experiments, high doses of fentanyl induced seizures. [1] The reported clinical cases of seizures were usually associated with a high dose of fentanyl. [2.5] However, two patients have been reported to have seizure after 100_g [3] or 200_g [4] fentanyl. The following case might be the third report of a patient who had a seizure after the administration of 100_g fentanyl.

Case Report

A 79-year-old woman (54 kg in body weight) was scheduled for an elective laminoplasty for C3-C7 cervical spondylosis. She has had benign tremors of her upper extremities for 16 years with unknown origin for which she has taken propranolol 30 mg/day. She had a cholecystectomy under general anesthesia 6 years ago without any complications. Laboratory data, physical examination, and echocardiography showed no abnormalities. One year ago, a computed tomography (CT) of the brain, and an electroencephalogram (EEG) illustrated normal results. (Fig.1A) She came to the operating room without premedication. Blood pressure was 180/100mmHg and heart rate was 64 beats・min-1. Arterial blood gas analysis was; PH 7.475, Paco2 37.2 mmHg, PaO2 77.9 mmHg, HCO3- 27.5 mmol・l-1, Base Excess 4.0 mmol・l-1, and AaDO2 22.1 mmHg (FiO2=0.21).
After a venous catheter and a gastric tube were inserted under inhalation of 100% oxygen by a mask, fentanyl 50_g was administrated twice at 5 min interval, with vecuronium 1mg. Approximately 5 min after the second dose of fentanyl, she began to show repeated jerking movements of her left hand and arm. Within seconds, similar movements were observed on the right side. She lost her consciousness and did not respond to verbal commands. Ventilation by a mask was easy with no evidence of laryngospasm or muscle rigidity. But systolic blood pressure increased to over 250 mmHg, and diastolic blood pressure to 150 mmHg, with heart rate to 95 beats・min-1. Only nicardipine 0.5 mg was administered and systolic blood pressure went down to under 180 mmHg. After 5 minutes, she came to herself spontaneously but the surgery was postponed.
Brain CT taken 30 minutes later showed normal findings. However, brain MRI indicated multiple small infarctions in both basal ganglia. The single photon emission computed tomography (SPECT) detected an old defect in the border region between the cerebrum and the cerebellum. A standard 16-lead EEG showed occasional epileptic sharp waves focused on the right central. (Fig.1B)
Phenytoin sodium 200 mg・day-1 was administered for 7days, and the surgery was performed 7days later. Anesthesia was induced with thiamylal 100mg and tracheal intubation was facilitated with vecuronium 7mg. Anesthesia was maintained with isoflurane 0.8%-1.0% in oxygen 3l・mim-1 and air 2l・min-1. The duration of surgery was 3 hours and 30 mins and no particular problems occurred during or after surgery.

Discussion

Most of the patients with seizures have some structural brain lesions or metabolic abnormalities. [6] Idiopathic seizures occur in children but may persist in adulthood. [6] Cerebrovascular disease is the most common cause of focal or generalized seizures in the age over 50 years. [7] Our patient did not have any prior cerebrovascular diseases, while she had been suffered from tremor with unknown origin. Furthermore, the CT and EEG taken a year ago (Fig.1A) showed no abnormalities. A seizure-like movement developed on the patientﾕs left side during the induction of anesthesia. This was inconsistent with a seizure focus on the left cerebral hemisphere detected by the MRI and the SPECT after the event. The primary lesion to induce seizure can not always be a focus of continuing epilepsy. [7]
Carlson et.al. [1] reported seizures with over 20_g・kg-1 in cats and higher doses in rats (400_g・kg-1 )and dogs(1250_g・kg-1). In human, two cases with generalized seizures were reported during rapid intravenous administration of fentanyl 44-78.1_g・kg-1. However, grand mal seizures were reported in two patients with only 200_g [3] or 100_g [4] fentanyl. The present case also had a seizure with 100 _g fentanyl.
Partial curarization by vecuronium 1mg might threaten her, but she did not complain any abnormal sensation during induction. Scott and Sarnquist [5] suggested two possible mechanisms of seizure induced by fentanyl. One is that these movements are only exaggerations of fentanyl-induced muscle rigidity that can occur even after a very low dose. The present case might not be with this mechanism because ventilation was easy with a mask. The other mechanism is that these abnormal movements are myoclonus secondary to fentanyl-induced depression of inhibitory neurons. [5] Although the seizure in the present case can not be attributed to fentanyl definitely, only fentanyl was administerd before the seizure. Therefore, fentanyl might induce seizure.
Even 100_g fentanyl might induce seizure in patients with some neurological deficits.

Acknowledgement

We would like to give our special thanks to Prof. Chingmuh Lee, M.D., Department of Anesthesiology, University of California Los Angeles School of Medicine for pre-editing our manuscript.

Reference

1. Carlsson C, Smith D.S, M. Mehdi Keykhah,　Englebach I, Harp J.R (1982) The effects of high dose fentanyl on cerebral circulation and metabolism in rats. Anesthesiology 57: 375-80
2. Tadikonda L.K.Rao, Nagaprasadarao Mummaneni, Adel A. El-Etr (1982) Convulsions: An unusual response to intravenous fentanyl administration. Anesth Analg 61: 1020-1
3. Safwat A.M, Daniel D. (1983) Grand mal seizure after fentanyl administration (letter). Anesthesiology 59: 78
4. Hoien A.O. (1984) Another case of grand mal seizure after fentanyl administration (letter). Anesthesiology 60:387
5. James C. Scott, Frank H. Sarnquist (1985) Seizure-like Movements after a Fentanyl Infusion with absence of seizure activity in a simultaneous EEG recording. Anesthesiology 62: 812-4
6. G.Edward Morgan Jr. , Maged S. Mikhail (1996) Clinical
Anesthesiology 2ndEdition. Appleton&Lange, Stamford, pp506-8
7. Kurt J. Isselbacher et.al. (1994) Harrisonﾕs Principles of Internal Medicine 13th Edition. McGraw-Hill, New York, pp2226-7
Figure legend
Figure 1A
EEG one year before surgery
Basically normal beta-waves are seen.
Figure 1B
EEG immediately after anesthesia
Basically alpha-waves with few sharp waves focused on right central were observed.