Convulsions After Enflurane in a Schizophrenic Patient Receiving

420 Convulsions after enflurane in a schizophrenic patient

receiving neuroleptics S.B. Vohra MBBS MD FFARCSI

A schizophrenic patient suffered from an episode of unexpected Enflurane is one of the many anaesthetic agents known grand mal seizure following an enflurance anaesthetic for bi- to produce convulsive effects. These effects are precip- opsy of an orbital lesion. The seizure was brief and subsided itated at high concentrations especially in the presence spontaneously. An assessment of the anaesthetic technique and of hypocarbia as the seizure threshold is lowered, i Ad- a thorough neurological examination which included a CTscan ditive and synergistic roles of various drugs or their me- and an EEG, failed to demonstrate any obvious cause for the tabolites, in potentiating seizure activity produced by en- convulsion. The patient was not an epileptic and was receiving flurane have been suggested. 1-5 A case of possible neuroleptic drugs preoperatively for the treatment of schizo- synergism between enflurane and phenothiazines and thi- phrenia. A synergistic role of enflurane and neuroleptic drugs oxanthines in producing convulsions is reported. in producing seizure activity in this patient is a distinct possibility. Caution is therefore recommended when administering Case report enflurane to patients on neuroleptic drugs. A 39-yr-old 50-kg man was admitted for investigation of a left orbital lesion associated with pain, photophobia Un patient schizophr~ne est saisi d'un accbs de grand real d and redness of the eye of one week duration. There were la suite d'une anesthdsie ~ l'enflurane pour la chirurgie d'une no symptoms or signs of intracranial extension. He was Idsion orbitaire. La crise a dtd brbve et s'est rdsolue sponta- a known schizophrenic who had been treated with electro- ndment. La rdvision de la technique anesthdsique et I'examen convulsive therapy and chlopromazine 100 mg four times neurologique complet avec tomodensitomdtrie et EEG n'ont a day for five years. Flupenthixol 40 mg On every two pas rdvdl~2 la cause de la convulsion. Le patient n~tait pas ~pi- weeks had then been added to his regimen and chlor- leptique et recevait auparavant un neuroleptique pour le trai- promazine reduced to 50 mg three times a day. This ther- tement de sa schizoph~nie. I1 est possible que l'association de apy continued for ten years. At the time of admission, l'enflurane et du neuroleptique ait jou~ un r6le dans le d~clen- the patient had been taking chlopromazine irregularly, chement de la crise convulsive. La prudence est recommandde parenteral flupenthixol being continued as before. There quand on administre de I'enflurane dun patient sous neu- was no history of epilepsy in the family. He had had roleptique. two other uneventful general anaesthetics in the past for minor procedures. Preoperative systemic examination, biochemical studies including thyroid function tests and haematology were all normal. A provisional diagnosis of orbital lymphoma or a pseudotumour was made. An ultrasound examination of the eye and CT scan of the brain were carried out to exclude an intracranial extension. A biopsy of the Key words mass was scheduled for the following week. The day be- ANAESTHETICS,VOLATILE: enflurane; fore surgery he took 100 mg of chlopromazine at 15.00 ATARACTICS: phenothiazines, thioxanthines; hr and again at 22.00 hr. COMPLICATIONS: convulsions. The patient was premedicated with lorazepam 2 mg From the Department of Anaesthesia, Manchester Royal two hours before the operation. Intravenous access was Infirmary, Manchester, U.K. established with an indwelling cannula. Anaesthesia was Address correspondence to: Dr. S.B. Vohra, Department of induced with thiopentone 300 mg and fentanyl 100 ~g, Anaesthesia, Manchester Royal Infirmary, Oxford Road, and muscle relaxation was achieved with atracurium 25 Manchester MI3 9WL, U.K. mg. The trachea was intubated with a 9 mm cuffed tube. Acceptedfor publication 26th January, 1994. Anaesthesia was maintained with nitrous oxide 4

CANJ ANAESTH 1994 / 41: 5 / pp420-2 Vohra: CONVULSIONS FOLLOWING ANAESTHESIA 421

L" min -l, oxygen 2 L" min -1. Enflurane 1% from En- psychotic drugs produce an additive and possibly syn- flurotec Mark 3 vaporiser was added to the breathing ergistic effect on the spike activity. 7 Epileptics are par- mixture. Intermittent positive pressure ventilation was ticularly susceptible to the increased paroxysmal activity carried out using a Manley ventilator (tidal volume 550 produced by chlopromazine and frank seizures have been ml approximately, respiratory rate 11 min-t). Monitoring reported after chlopromazine in epileptics stabilized on consisted of NIBP, ECG and SpO2. As a capnograph anticonvulsants and free from fits. ~0 was not available, end tidal COz concentrations could Enflurane is known to cause cerebral stimulation. Deep not be monitored. The operation lasted 30 min during levels of enflurane anaesthesia produce EEG changes which the inspired concentration of enflurane was ad- characterized by low voltage, fast frequency waves pro- justed between I-1.5% as required. The haemodynamic gressing through spikes and dome complexes. These al- parameters were within normal limits as were his SpO2 ternate with electrical silence and may finally produce observations. a frank seizure activity pattern. ~ They originate in the The residual neuromuscular blockade was reversed limbic system and then spread to all other areas. 2 These with neostigmine 2.5 mg and atropine 1.2 rag. The tra- changes may persist for as long as 30 days following en- chea was extubated after a few breaths of a mixture of flurane anaesthesia, t2 The factors suspected of predis- oxygen 7 L. min -t and CO2 0.5 L-rain -I. The vital posing to seizures are pre-existing neurological disorders, signs (heart rate, blood pressure and peripheral oxygen high (>2-3%) inspired concentration of enfhirane, and saturation) were satisfactory. At this point the patient had drug interactions with diazepam, amitriptyline, tetrahy- regained his protective reflexes. His respiratory rate and drofuran, ketamine and althesin. ~-5 There may be a syn- pattern were satisfactory and he was receiving oxygen ergistic role for laudanosine, a metabolite of atracurium, (6 L. min-t) by Me mask. About five minutes after ex- as high plasma concentrations of laudanosine have been tubation he had a classical grand real seizure lasting 30 shown to produce seizure activity in animals. Hyperven- sec. The seizure subsided spontaneously but the patient tilation and a respiratory alkalosis have potentiating ef- became apnoeic and unresponsive to external stimuli al- fects on the seizure activity produced by enflurane. 2 though his pupils were normal in size. The trachea was The patient described in this case report was not an reintubated and 100% oxygen was administered for the epileptic and had no family history of epilepsy. Diazeparn next ten minutes following which he recovered sufficiently was not used as a premedicant, the dose of atracurium to allow extubation. Oxygen was continued by mask and was modest so that a laudanosine-induced interaction is the subsequent recovery was uneventful. There was no unlikely. Previous animal research suggests that nitrous- neurological deficit postoperatively. After a normal EEG oxide confers some protection against enflurane-induced and CT scan, he was discharged on the ninth postop- hyperexcitability unless the duration of anaesthesia is pro- erative day. There was no neurological deficit at six longed. During prolonged anaesthesia a state of tolerance months followup. develops and sudden cessation of nitrous-oxide induces hyperexcitability. 13 The duration of this case was half an Discussion hour so that nitrous-oxide withdrawal-induced hyperex- One of the side effects of anti-psychotic drugs such as citability is unlikely. phenothiazines and thioxanthenes is lowering of the sei- The inspired concentration of enflurane was no more zure threshold. 6 This has been shown in animal exper- than 1.5%, and there were no undue photic or auditory iments using chlorpromazine at low and intermediate dos- stimuli in the immediate postoperative period. ~4 The pa- ages. 7 The usual electroencephalographic (EEG) effect of tient was unlikely to be hypocarbic at the time of seizure these drugs is diffuse slowing of activity. Chlorpromazine as CO2 had been added to the breathing mixture before reduces the frequency of alpha waves but increases the extubation. Also an intracranial extension of the orbital frequency of theta and delta waves, s This kind of activity tumour had already been excluded by a normal CT scan is not pathological but other types of EEG patterns pro- of brain. duced during antipsychotic drug treatment may have clin- Thus, one explanation for the cause of the epileptic ical importance. These are transient, ranging from dys- seizure in this patient appears to be the synergistic activity rhythmic groups and sharp potentials to spike and dome between enflurane and the antipsychotic drugs. As noted complexes and may be associated with epileptic seizures. in the history, the dosage regimen for chlorpromazine was These EEG changes are commonly accentuated during irregular. The patient was receiving chlorpromazine and initial period of treatment, sudden dose changes or fol- flupenthixol concurrently though somewhat inconsist- lowing an abrupt withdrawal. 9 Aliphatic phenothiazines ently. He had been given an additional dose of chlor- and thioxanthenes are more epileptogenic than the pip- promazine on the evening before the surgery. Since com- erazine derivatives. Furthermore, combinations of anti- binations of antipsychotic drugs have an additive effect 422 CANADIAN JOURNAL OF ANAESTHESIA on the spike activity and, furthermore, the sudden al- 14 DeWolfe AM, Chang JL, Larson CE, Caparosa RJ. teration of doses is known to lower the seizure threshold, Enflurane induced grand mal seizure during optic micro- it is possible that the stage was already set for seizure surgery. Anesthesia Progress 1984; 31: 136-7. when another potentially epileptogenic drug (enflurane) was added. In conclusion, the possibility of an interaction between antipsychotic drugs and enflurane should be considered. This is especially relevant if the prescribed dosage regimen has not been consistent and if there is any doubt about compliance on the part of the patient. Thus, this might be considered when choosing an inhalational agent for the patients on antipsychotic therapy.

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