Anaesth. Intens. Care (1979), 7, 267
CASE REPORT: ALTHESIN IN STATUS EPILEPTICUS D. WONGt AND R. G. HICKS:j: The Prince Henry Hospital, Sydney
ALBERT SAADY*,
SUMMARY
A case of status epilepticus, resistant to conventional anti-epileptic treatment is described. Althesin rapidly abolished the epileptic activity, and control was achieved by a continuous infusion of Althesin. A 68 year old male, weight approximately 70 kg, was referred from a peripheral hospital with status epilepticus which had not responded to chlormethiazole (Hemineurin) infusion, together with intravenous sodium phenytoin and dexamethasone. He had a past history of considerable alcohol intake. On arrival at The Prince Henry Hospital he was having frequent left sided twitching movements involving the face and upper arm predominantly, but also the left lower limb. These episodes were occurring every five minutes and lasting ten to twenty seconds. MANAGAMENT
An intravenous infusion of diazepam 20 mg in 100 ml Hartmann's solution per hour was commenced and supplemented with intravenous diazepam 10-20 mg and dexamethasone 4 mg intravenously every six hours. Two hours later, after 110 mg of diazepam, he was still having left sided fits every five to ten minutes. Bilateral carotid angiograms were performed without any abnormality being detected, after which he was transferred to the Intensive Care Unit (I.C.U.) where diazepam and dexamethasone was continued and after two separate intravenous injections of thiopentone 100 mg failed to stop the fits, it was decided to paralyse the patient with pancuronium and institute intermittent positive pressure ventilation. • M.B., B.Sc., F.F.A.R.A.C.S., Honorary Anaesthetist.
t M.B., B.Sc., F.F.A.R.A.C.S .. Anaesthetics Registrar.
t Senior EEG Recordist, Clinical Neurophysiology Unit,
Division of Neurology. Address for reprints: Dr. A. Saady, Department of Anaesthesia, Prince Henry Hospital, Anzac Parade, Little Bay, N.S.W. 2036, Australia.
Anaesthesia and Intensive Care, Vol. Vll, No. 3, August, 1979
Despite increasing the concentration of the diazepam infusion to 30 mg per hour and 2 mg increments of pancuronium intravenously every 30 minutes, he continued to have frequent twitching movements of the mouth on the left side and left leg and arm. Approximately twelve hours after admission to the I.CU. clonazepam 1.0 mg was given intravenously without effect while the electroencephalogram (EEG) was monitored. Thiopentone 100 mg intravenously completely abolished all EEG activity. An infusion of thiopentone 100 mg/hour was then commenced and the diazepam suspended. Even after increasing the concentration of the thiopentone to 150 mg/hour and with additional boluses of 50-100 mg, the fits continued and thiopentone was ceased after 22 hours. Under EEG control, Althesin (Alphaxolone-alphadolone acetate) 2 ml was then given intravenously, and this abolished all epileptic activity completely for six minutes, after which three increments of Althesin 1.0 ml over the next 15 minutes had an equally satisfactory effect. An infusion of Althesin 7 ml in 100 ml Hartmann's solution was then administered over one hour. Good control continued for the first thirty minutes, when a minor episode of facial twitching lasting 5 secs occurred, and this recurred four hours later. At this time, intravenous sodium phenytoin 250 mg was added every six hours for 24 hours followed by 100 mg into the intragastric tube. Intravenous phenobarbitone 200 mg three times a day had been started earlier. During the next 24 hours, four fits involving the left facial muscles occurred when the Althesin infusion had' stopped inadvertently.
A. SAADY ET AL.
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There was one fit, lasting 10 seconds, which also involved the left leg and arm, and this responded immediately to Althesin 1.0 ml. During the next day, no fits occurred, and the Althesin was gradually withdrawn, and finally ceased approximately 70 hours after commencement. Later that day he was extubated. The patient had a residual left hemiparesis, and was also found to have gross bilateral cerebellar signs and peripheral neuropathy. He showed a moderate impairment of intellectual faculties and his rehabilitation was prolonged and difficult. DISCUSSION
Thiopentone is in general use for the treatment of convulsions such as might occur in local anaesthetic toxicity, tetanus and status epilepticus. Structure-activity relations of the barbiturates are such that certain structural changes can result in selective anticonvulsant activity independent of hypnotic effects. In some circumstances, the same drug may possess both stimulant and depressant properties (Sharpless 1965). Excitatory phenomena such as abnormal muscular movements and tremor may occur with thiobarbiturates, and these are more marked with methylated barbiturates, e.g. methohexitone (Barron and Dundee 1967)
appearing with increasing frequency with larger doses (Barron and Dundee 1961). Convulsions have been associated with methohexitone (Thornton 1970). As with thiobarbiturates, but less frequently, minor excitatory effects may occur during induction with Althesin, and their incidence is increased with higher doses (Clarke et al. 1971, Savege et al. 1971). Convulsions have also been reported with AIthesin (Uppington 1973, Rees 1975, McGown 1976). This present report describes the use of Althesin in the management of status epilepticus which had not responded to conventional anticonvulsant therapy. The EEG in this patient prior to the administration of Althesin showed continuous epileptic activity in the right hemisphere, with fast rhythms on the left (Fig. 1). The initial bolus of Althesin given under EEG control rapidly suppressed the epileptic activity so that the EEG record 50 seconds afterwards showed only low voltage intermittent activity (Fig. 2). This rapid suppression of epileptic activity also occurred with the subsequent injections. Good control of the fitting was achieved by a continuous infusion of Althesin at the rate of 0.1 ml/kg/hour (7 ml/ hour). The EEG at one hour (Fig. 3) and five hours (Fig. 4) after the infusion illustrates this degree of control, although the EEG remained abnormal.
1 .
~. -'~'.
.'
/: /.'.: '
'- ' :
,00.. 1 '---:,-".--
FIGURE I.-Before the Althesin is given. The EEG is asymmetrical with epileptic features over the right hemisphere - a progressive seizure pattern after 20 seconds.
Allanchesia alld IlItell.,;,·e Care, Vol. VIl. No. 3, August, 1979
ALTHESIN IN STATUS EPILEPTICUS
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2
~----~~--~--------~----------~~--------~~----------~~------~ 2.-EEG 50 secs after Althesin 2 rol injection. Low voltage 6-10 HZ activity with intermittent slow waves is seen. The epileptiforro features no longer appear. FIGURE
3.-After 1 hour on 0.1 mllkg/hr Althesin infusion. Periodic sharp waves are most prominent on the right with a background of low amplitude fast rhythms. No more paroxysmal activity occurs.
FIGURE
Anaesthesia and Intensive Care, Vol. Vll, No. 3, August, 1979
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~~~J./-f'-"V
FIGURE 4.-After 5 hours on O. I mllkg/hr Althesin infusion. Occasional sharpish waves are noted over the right anterior quadrant; the background activity is at 3-10 HZ with intermixed low voltage fast rhythms.
Thc efficacy of Althesin as described in this case confirms the report of Chin, Havill and Rothwcll (1979), and disputes the consideration that Althesin is contraindicated in epilepsy. It is also significant that one of the authors in a recently completed clinical trial using Althesin infusion as an anaesthetic agent for intracranial operations found no increase in the incidence of EEG abnormalities or convulsions in the perioperative or postoperative periods (Saady 1979). Thus, unlike methohexitone, Althesin does not appear to facilitate an epileptic focus. It is suggested that Althesin should be considered early in the treatment of status epilepticus when traditional antiepileptic agents fail. ACKNOWLEDGEMENTS
The co-operation of Glaxo Laboratories is gratefully acknowledged. We wish to thank Mrs. Elizabeth Benson for her typing assistance, Miss V. Foster and the Dept. of Medical Illustration, University of New South Wales. REFERENCES
Barron, D. W. and Dundee, J. W. (1961): "Further
experience with methylated thiobarbiturates", Brit. J. Allaesth., 33, 130. Harron, D. W., and Dundee, J. W. (1967): "Clinical Studies of Induction agents XVII. Relationship between dosage and side effects of intravenous barbiturates", Brit. J. Allaesth., 39, 24. Chin, L. S., Havill, J. H., and Rothwell, R. P. G. (1979): "Status epilepticus controlled by althesin infusion", Allaesth. [lIfells. Care, 7, 50. Clarke, R. S. J., Montgomery, S. T., Dundee, J. W., and Bovill, J. G. (1971): "Clinical studies of Induction agents XXXIX. CT1341 - a new steroid anaesthetic", Brit. J. Allaesth., 43, 947. McGown, R. G. (1976): "Convulsion and Althesin", A lIaesthesia. 31, 112. Rees, L. T. (1975): "Convulsions immediately following Althcsin", Anaesthesia, 30, 54. Saady, A. (1979): "Althesin for Neuroanaesthesia", Allaesth. [litem. Care. 7, 158. Savege, T. M., Foley. E. I., Coultas, R. J., Walton, B., Strunin, L., Simpson, B. R., and Scott, D. F. (1971): "CT1341: some effects in man", Anaesthesia, 26, 402. Sharpless, S. K. (1965): "Hypnotics and Sedatives J. The Barbiturates; in The Pharmacological Basis of Therapeutics (ed. L. S. Goodman and A. Gilman), 3rd edn. PI06, New York. Macmillan Company. Thornton. 1. A. (1970): "Methohexitone and its application in dental anaesthesia", Brit. I. Anaesth., 42, 255. Uppington. 1. (1973): "Epileptiform convulsion with Althesin", Anaesthesia, 28, 546. Allile>thesia alld IlItellsi,"
Care, Vol. VII, No. 3, August, 1979
CASE REPORT: ALTHESIN IN STATUS EPILEPTICUS D. WONGt AND R. G. HICKS:j: The Prince Henry Hospital, Sydney
ALBERT SAADY*,
SUMMARY
A case of status epilepticus, resistant to conventional anti-epileptic treatment is described. Althesin rapidly abolished the epileptic activity, and control was achieved by a continuous infusion of Althesin. A 68 year old male, weight approximately 70 kg, was referred from a peripheral hospital with status epilepticus which had not responded to chlormethiazole (Hemineurin) infusion, together with intravenous sodium phenytoin and dexamethasone. He had a past history of considerable alcohol intake. On arrival at The Prince Henry Hospital he was having frequent left sided twitching movements involving the face and upper arm predominantly, but also the left lower limb. These episodes were occurring every five minutes and lasting ten to twenty seconds. MANAGAMENT
An intravenous infusion of diazepam 20 mg in 100 ml Hartmann's solution per hour was commenced and supplemented with intravenous diazepam 10-20 mg and dexamethasone 4 mg intravenously every six hours. Two hours later, after 110 mg of diazepam, he was still having left sided fits every five to ten minutes. Bilateral carotid angiograms were performed without any abnormality being detected, after which he was transferred to the Intensive Care Unit (I.C.U.) where diazepam and dexamethasone was continued and after two separate intravenous injections of thiopentone 100 mg failed to stop the fits, it was decided to paralyse the patient with pancuronium and institute intermittent positive pressure ventilation. • M.B., B.Sc., F.F.A.R.A.C.S., Honorary Anaesthetist.
t M.B., B.Sc., F.F.A.R.A.C.S .. Anaesthetics Registrar.
t Senior EEG Recordist, Clinical Neurophysiology Unit,
Division of Neurology. Address for reprints: Dr. A. Saady, Department of Anaesthesia, Prince Henry Hospital, Anzac Parade, Little Bay, N.S.W. 2036, Australia.
Anaesthesia and Intensive Care, Vol. Vll, No. 3, August, 1979
Despite increasing the concentration of the diazepam infusion to 30 mg per hour and 2 mg increments of pancuronium intravenously every 30 minutes, he continued to have frequent twitching movements of the mouth on the left side and left leg and arm. Approximately twelve hours after admission to the I.CU. clonazepam 1.0 mg was given intravenously without effect while the electroencephalogram (EEG) was monitored. Thiopentone 100 mg intravenously completely abolished all EEG activity. An infusion of thiopentone 100 mg/hour was then commenced and the diazepam suspended. Even after increasing the concentration of the thiopentone to 150 mg/hour and with additional boluses of 50-100 mg, the fits continued and thiopentone was ceased after 22 hours. Under EEG control, Althesin (Alphaxolone-alphadolone acetate) 2 ml was then given intravenously, and this abolished all epileptic activity completely for six minutes, after which three increments of Althesin 1.0 ml over the next 15 minutes had an equally satisfactory effect. An infusion of Althesin 7 ml in 100 ml Hartmann's solution was then administered over one hour. Good control continued for the first thirty minutes, when a minor episode of facial twitching lasting 5 secs occurred, and this recurred four hours later. At this time, intravenous sodium phenytoin 250 mg was added every six hours for 24 hours followed by 100 mg into the intragastric tube. Intravenous phenobarbitone 200 mg three times a day had been started earlier. During the next 24 hours, four fits involving the left facial muscles occurred when the Althesin infusion had' stopped inadvertently.
A. SAADY ET AL.
268
There was one fit, lasting 10 seconds, which also involved the left leg and arm, and this responded immediately to Althesin 1.0 ml. During the next day, no fits occurred, and the Althesin was gradually withdrawn, and finally ceased approximately 70 hours after commencement. Later that day he was extubated. The patient had a residual left hemiparesis, and was also found to have gross bilateral cerebellar signs and peripheral neuropathy. He showed a moderate impairment of intellectual faculties and his rehabilitation was prolonged and difficult. DISCUSSION
Thiopentone is in general use for the treatment of convulsions such as might occur in local anaesthetic toxicity, tetanus and status epilepticus. Structure-activity relations of the barbiturates are such that certain structural changes can result in selective anticonvulsant activity independent of hypnotic effects. In some circumstances, the same drug may possess both stimulant and depressant properties (Sharpless 1965). Excitatory phenomena such as abnormal muscular movements and tremor may occur with thiobarbiturates, and these are more marked with methylated barbiturates, e.g. methohexitone (Barron and Dundee 1967)
appearing with increasing frequency with larger doses (Barron and Dundee 1961). Convulsions have been associated with methohexitone (Thornton 1970). As with thiobarbiturates, but less frequently, minor excitatory effects may occur during induction with Althesin, and their incidence is increased with higher doses (Clarke et al. 1971, Savege et al. 1971). Convulsions have also been reported with AIthesin (Uppington 1973, Rees 1975, McGown 1976). This present report describes the use of Althesin in the management of status epilepticus which had not responded to conventional anticonvulsant therapy. The EEG in this patient prior to the administration of Althesin showed continuous epileptic activity in the right hemisphere, with fast rhythms on the left (Fig. 1). The initial bolus of Althesin given under EEG control rapidly suppressed the epileptic activity so that the EEG record 50 seconds afterwards showed only low voltage intermittent activity (Fig. 2). This rapid suppression of epileptic activity also occurred with the subsequent injections. Good control of the fitting was achieved by a continuous infusion of Althesin at the rate of 0.1 ml/kg/hour (7 ml/ hour). The EEG at one hour (Fig. 3) and five hours (Fig. 4) after the infusion illustrates this degree of control, although the EEG remained abnormal.
1 .
~. -'~'.
.'
/: /.'.: '
'- ' :
,00.. 1 '---:,-".--
FIGURE I.-Before the Althesin is given. The EEG is asymmetrical with epileptic features over the right hemisphere - a progressive seizure pattern after 20 seconds.
Allanchesia alld IlItell.,;,·e Care, Vol. VIl. No. 3, August, 1979
ALTHESIN IN STATUS EPILEPTICUS
269
2
~----~~--~--------~----------~~--------~~----------~~------~ 2.-EEG 50 secs after Althesin 2 rol injection. Low voltage 6-10 HZ activity with intermittent slow waves is seen. The epileptiforro features no longer appear. FIGURE
3.-After 1 hour on 0.1 mllkg/hr Althesin infusion. Periodic sharp waves are most prominent on the right with a background of low amplitude fast rhythms. No more paroxysmal activity occurs.
FIGURE
Anaesthesia and Intensive Care, Vol. Vll, No. 3, August, 1979
A. SAADY ET AL.
270
~~~J./-f'-"V
FIGURE 4.-After 5 hours on O. I mllkg/hr Althesin infusion. Occasional sharpish waves are noted over the right anterior quadrant; the background activity is at 3-10 HZ with intermixed low voltage fast rhythms.
Thc efficacy of Althesin as described in this case confirms the report of Chin, Havill and Rothwcll (1979), and disputes the consideration that Althesin is contraindicated in epilepsy. It is also significant that one of the authors in a recently completed clinical trial using Althesin infusion as an anaesthetic agent for intracranial operations found no increase in the incidence of EEG abnormalities or convulsions in the perioperative or postoperative periods (Saady 1979). Thus, unlike methohexitone, Althesin does not appear to facilitate an epileptic focus. It is suggested that Althesin should be considered early in the treatment of status epilepticus when traditional antiepileptic agents fail. ACKNOWLEDGEMENTS
The co-operation of Glaxo Laboratories is gratefully acknowledged. We wish to thank Mrs. Elizabeth Benson for her typing assistance, Miss V. Foster and the Dept. of Medical Illustration, University of New South Wales. REFERENCES
Barron, D. W. and Dundee, J. W. (1961): "Further
experience with methylated thiobarbiturates", Brit. J. Allaesth., 33, 130. Harron, D. W., and Dundee, J. W. (1967): "Clinical Studies of Induction agents XVII. Relationship between dosage and side effects of intravenous barbiturates", Brit. J. Allaesth., 39, 24. Chin, L. S., Havill, J. H., and Rothwell, R. P. G. (1979): "Status epilepticus controlled by althesin infusion", Allaesth. [lIfells. Care, 7, 50. Clarke, R. S. J., Montgomery, S. T., Dundee, J. W., and Bovill, J. G. (1971): "Clinical studies of Induction agents XXXIX. CT1341 - a new steroid anaesthetic", Brit. J. Allaesth., 43, 947. McGown, R. G. (1976): "Convulsion and Althesin", A lIaesthesia. 31, 112. Rees, L. T. (1975): "Convulsions immediately following Althcsin", Anaesthesia, 30, 54. Saady, A. (1979): "Althesin for Neuroanaesthesia", Allaesth. [litem. Care. 7, 158. Savege, T. M., Foley. E. I., Coultas, R. J., Walton, B., Strunin, L., Simpson, B. R., and Scott, D. F. (1971): "CT1341: some effects in man", Anaesthesia, 26, 402. Sharpless, S. K. (1965): "Hypnotics and Sedatives J. The Barbiturates; in The Pharmacological Basis of Therapeutics (ed. L. S. Goodman and A. Gilman), 3rd edn. PI06, New York. Macmillan Company. Thornton. 1. A. (1970): "Methohexitone and its application in dental anaesthesia", Brit. I. Anaesth., 42, 255. Uppington. 1. (1973): "Epileptiform convulsion with Althesin", Anaesthesia, 28, 546. Allile>thesia alld IlItellsi,"
Care, Vol. VII, No. 3, August, 1979
