Anaesthesia, 1975, Volume 30, pages 56-58 CASE REPORTS
Post-operative convulsions due to penicillin applied to the spinal theca A. B O R D B A R
AND
M. BEHESHTI
Penicillin has been recognised as a convulsant agent since Walker & Johnson' discovered that it produces epileptiform convulsions when applied to the cerebral cortex of animals and man.' Convulsions due to penicillin have also been seen clinically after injections into the cerebo-spinal fluid during the treatment of pneumococcal meningitis ; intrathecal doses greater than 100,000 units in the adult or greater than 10,000 units in children has induced seizures in such case^.^,^ The mechanism of penicillin convulsions is not This communication reports two cases of convulsions after anaesthesia, due to the direct use of penicillin powder on the external aspect of the theca at the end of surgery to relieve compression of the lumbar spinal cord. Case histories Case 1 A man aged 40 years was admitted for surgery to relieve compression of the lumbar cord due to a prolapsed intervertebral disc. He was a healthy man with no significant past history. He was anaesthetised with thiopentone, pethidine 50 mg and tubocurarine and ventilated with nitrous oxide and oxygen. Five hundred thousand units of crystalline penicillin powder were placed in the wound superficial to the theca a t the conclusion of the laminectomy. Anaesthesia was uneventful. The patient was awake within half-an-hour of completing surgery and his condition was satisfactory apart from some pain for which he was given 50 mg pethidine. He had a convulsion approximately 4 hours following surgery. This was initially controlled by oxygen and 100 mg of thiopentone given intravenously but, 15 minutes later, he developed status epilepticus which failed to respond to repeated doses of thiopentone 100 mg and oxygen therapy. The patient remained cyanosed and died before further measures to control the convulsions could be implemented. A. Bordbar, MD, DA (England), Associate Professor and Head of the Department of Anaesthesia and M. Beheshti, MD, FRCS (Ed), Assistant Professor, General Surgery, Faculty of Medicine, University of Esfahan, Iran.
56
Convulsions caused by penicillin
57
Case 2 A woman aged 46 years was admitted for surgical excision of a dural tumour. She was otherwise healthy with no history of serious illness. She was induced with thiopentone, gallamine and halothane 0.5% and then ventilated with nitrous oxide and oxygen. A large dose of penicillin powder (10,000,000 units) was placed in the wound on the theca following excision of the tumour. Anaesthesia was uneventful. The patient regained consciousness in the recovery room and was given 10 mg morphine sulphate intramuscularly for analgesia. A convulsion occurred about 4 hours after surgery. This was controlled by 100 mg of thiopentone given intravenously and the administration of oxygen. Two further convulsions occurred 10 minutes and 30 minutes after the initial seizure. These were controlled by intravenous diazepam 10 mg and 50 mg respectively. Further less severe convulsions occurred over the following 3 hours. Five more doses of 10 mg of intravenous diazepam were given, but these failed to prevent recurrent episodes of fitting. It was therefore decided to paralyse the patient with tubocurarine 20 mg and control ventilation. Intermittent positive pressure ventilation (IPPV) was continued for 24 hours, during which time convulsions were completely controlled by a total of 45 mg of tubocurarine and a further 80 mg of diazepam; mechanical ventilation was then discontinued and the patient was extubated. She was conscious but remained confused and restless for some time. The restlessness was controlled by repeated doses of diazepam (15 mg in 10 hours), and within 3 days she was symptom free and thereafter made an uneventful recovery. Discussion
The first patient died of hypoxia before adequate oxygenation and control of the convulsions could be achieved, but the second patient survived after a period of curarisation and IPPV. The application of penicillin solutions to the human cerebral cortex or injection into the ventricles can precipitate c o n v ~ l s i o n s ~ but * ~penicillin does not readily penetrate the meninges unless they are inflamed.' Penetration may have been facilitated by surgical trauma to the theca and by the use of large doses in the cases reported above. The delay between the administration of the dose and the onset of convulsions presumably reflects the time taken for the powder to dissolve and penetrate the theca and to achieve sufficiently high levels of penicillin in the cerebro-spinal fluid to cause convulsions. Summary
Two cases are described and discussed in which penicillin powder applied to the theca at the end of laminectomy caused delayed convulsions. References 1. WALKER,A.E. &JOHNSON,H.C. (1945) Convulsive factor in commercial penicillin. Archiues of Surgery (Chicago), 50, 69.
A . Bordbar and M . Beheshti
58
2. BOEKOWSKI, W.J. & FORSTER, F.M. (1947) Convulsant effects of penicillin in the cerebral cortex. Journal of Neuropathology and Experimental Neurology, 6, 201. 3. VALLERY-RADOT, P., MILLIEZ, P., LAROCHE, C. & HAZARD,J. (1951) Etat de ma1 Bpileptique fatal apr& une injection interarachidienne de pknicilline concentrke au dkcours d'une mkningite ckrkbrospinale A meningococcus. Bulletins et Mkmoires de la Sociktk Mtfdicale des H6pitaux de Paris, 67, 769.
4. PHILIPE, L. & GOUTORBE, F. (1948) Convulsions mortelles au cours d'un traitement par la pknicilline intra-rachidienne chez un nourisson. Archives FranGaises de Pkdiatrie, 5, 639. 5 . SUTTON,G.G. & OLDSTONE, M.B.A. (1969) Evidence against pyridoxine deficiency as the mechanism of penicillin seizures. Neurology, 19, 859. 6. LAW, S. & STEIN,H. (1969) Penicillin convulsions. Electroencephalography and Clinical Neurophysiology, 27,217. I . HEWITT,W.L. (1963) The Penicillins. Journal of the American Medical Association, 185, 264. 8 . GOODMAN, L.S. & GILMAN, A. (1970) The Pharmacological Bases of Therapeutics, 4th edn, p. 1215. The Macmillan Company, London.
Post-operative convulsions due to penicillin applied to the spinal theca A. B O R D B A R
AND
M. BEHESHTI
Penicillin has been recognised as a convulsant agent since Walker & Johnson' discovered that it produces epileptiform convulsions when applied to the cerebral cortex of animals and man.' Convulsions due to penicillin have also been seen clinically after injections into the cerebo-spinal fluid during the treatment of pneumococcal meningitis ; intrathecal doses greater than 100,000 units in the adult or greater than 10,000 units in children has induced seizures in such case^.^,^ The mechanism of penicillin convulsions is not This communication reports two cases of convulsions after anaesthesia, due to the direct use of penicillin powder on the external aspect of the theca at the end of surgery to relieve compression of the lumbar spinal cord. Case histories Case 1 A man aged 40 years was admitted for surgery to relieve compression of the lumbar cord due to a prolapsed intervertebral disc. He was a healthy man with no significant past history. He was anaesthetised with thiopentone, pethidine 50 mg and tubocurarine and ventilated with nitrous oxide and oxygen. Five hundred thousand units of crystalline penicillin powder were placed in the wound superficial to the theca a t the conclusion of the laminectomy. Anaesthesia was uneventful. The patient was awake within half-an-hour of completing surgery and his condition was satisfactory apart from some pain for which he was given 50 mg pethidine. He had a convulsion approximately 4 hours following surgery. This was initially controlled by oxygen and 100 mg of thiopentone given intravenously but, 15 minutes later, he developed status epilepticus which failed to respond to repeated doses of thiopentone 100 mg and oxygen therapy. The patient remained cyanosed and died before further measures to control the convulsions could be implemented. A. Bordbar, MD, DA (England), Associate Professor and Head of the Department of Anaesthesia and M. Beheshti, MD, FRCS (Ed), Assistant Professor, General Surgery, Faculty of Medicine, University of Esfahan, Iran.
56
Convulsions caused by penicillin
57
Case 2 A woman aged 46 years was admitted for surgical excision of a dural tumour. She was otherwise healthy with no history of serious illness. She was induced with thiopentone, gallamine and halothane 0.5% and then ventilated with nitrous oxide and oxygen. A large dose of penicillin powder (10,000,000 units) was placed in the wound on the theca following excision of the tumour. Anaesthesia was uneventful. The patient regained consciousness in the recovery room and was given 10 mg morphine sulphate intramuscularly for analgesia. A convulsion occurred about 4 hours after surgery. This was controlled by 100 mg of thiopentone given intravenously and the administration of oxygen. Two further convulsions occurred 10 minutes and 30 minutes after the initial seizure. These were controlled by intravenous diazepam 10 mg and 50 mg respectively. Further less severe convulsions occurred over the following 3 hours. Five more doses of 10 mg of intravenous diazepam were given, but these failed to prevent recurrent episodes of fitting. It was therefore decided to paralyse the patient with tubocurarine 20 mg and control ventilation. Intermittent positive pressure ventilation (IPPV) was continued for 24 hours, during which time convulsions were completely controlled by a total of 45 mg of tubocurarine and a further 80 mg of diazepam; mechanical ventilation was then discontinued and the patient was extubated. She was conscious but remained confused and restless for some time. The restlessness was controlled by repeated doses of diazepam (15 mg in 10 hours), and within 3 days she was symptom free and thereafter made an uneventful recovery. Discussion
The first patient died of hypoxia before adequate oxygenation and control of the convulsions could be achieved, but the second patient survived after a period of curarisation and IPPV. The application of penicillin solutions to the human cerebral cortex or injection into the ventricles can precipitate c o n v ~ l s i o n s ~ but * ~penicillin does not readily penetrate the meninges unless they are inflamed.' Penetration may have been facilitated by surgical trauma to the theca and by the use of large doses in the cases reported above. The delay between the administration of the dose and the onset of convulsions presumably reflects the time taken for the powder to dissolve and penetrate the theca and to achieve sufficiently high levels of penicillin in the cerebro-spinal fluid to cause convulsions. Summary
Two cases are described and discussed in which penicillin powder applied to the theca at the end of laminectomy caused delayed convulsions. References 1. WALKER,A.E. &JOHNSON,H.C. (1945) Convulsive factor in commercial penicillin. Archiues of Surgery (Chicago), 50, 69.
A . Bordbar and M . Beheshti
58
2. BOEKOWSKI, W.J. & FORSTER, F.M. (1947) Convulsant effects of penicillin in the cerebral cortex. Journal of Neuropathology and Experimental Neurology, 6, 201. 3. VALLERY-RADOT, P., MILLIEZ, P., LAROCHE, C. & HAZARD,J. (1951) Etat de ma1 Bpileptique fatal apr& une injection interarachidienne de pknicilline concentrke au dkcours d'une mkningite ckrkbrospinale A meningococcus. Bulletins et Mkmoires de la Sociktk Mtfdicale des H6pitaux de Paris, 67, 769.
4. PHILIPE, L. & GOUTORBE, F. (1948) Convulsions mortelles au cours d'un traitement par la pknicilline intra-rachidienne chez un nourisson. Archives FranGaises de Pkdiatrie, 5, 639. 5 . SUTTON,G.G. & OLDSTONE, M.B.A. (1969) Evidence against pyridoxine deficiency as the mechanism of penicillin seizures. Neurology, 19, 859. 6. LAW, S. & STEIN,H. (1969) Penicillin convulsions. Electroencephalography and Clinical Neurophysiology, 27,217. I . HEWITT,W.L. (1963) The Penicillins. Journal of the American Medical Association, 185, 264. 8 . GOODMAN, L.S. & GILMAN, A. (1970) The Pharmacological Bases of Therapeutics, 4th edn, p. 1215. The Macmillan Company, London.
