551
instances in which the auditors would recommend
surgical delivery. The total effect of audit on the overall caesarean section rate is therefore likely to be small. 65 % of the caesarean sections surveyed were done as emergency operations. Of these, 64% were indicated for intrapartum fetal distress; this proportion represented approximately 5% of all deliveries in 1985 at St James’s, where the caesarean section rate that year was
13-6% (unpublished). A third of the operations for
(15%
of the
total)
were
intrapartum fetal distress judged by 4 or 5 auditors to have
been unnecessary. If in a third of these another indication for section or unequivocal evidence of fetal distress subsequently developed, then the total expected reduction in our caesarean section rate would be 1 %. A 1 % reduction in caesarean section rate of 13-6% is a worthwhile objective if the drop could be achieved without increasing fetal risk. Furthermore, audit may point out aspects of labour management that may be amenable to alteration-eg, limited use of fetal scalp pH sampling. For audit to be widely accepted and practised it should have the confidence and support of those whose work is being audited. The wide inter-assessor variation, along with inconsistency of the assessors on review of the cases, must diminish confidence in this form of peer review.
Besides highlighting the inadequacies of our present methods of intrapartum fetal assessment and stressing the need for more objective data, our findings are relevant in the sphere of medical jurisprudence. The data presented to medical assessors in malpractice cases is very similar to that which were given to the assessors in this study. In conclusion, this study suggests that attempts to reduce an increasing caesarean section rate by audit must begin with a self audit on the part of the assessors; that there should be further research into methods of intrapartum monitoring that would discriminate well between sick and healthy babies; and that the limitations of present methods of audit be realised by all called upon to bear "expert witness". REFERENCES 1. Patel YA. 2.
Changing trends in the incidence of caesarean section. J Obstet Gynaecol 1983; 3: 253-57. Lomas J. Holding back the tide of caesarean sections. Br Med J 1988; 297: 569-71.
Haverkamp AD, Orleans M, Langendoerfer S, et al. A controlled trial of the different effects of intrapartum fetal monitoring. Am J Obstet Gynaecol 1983; 134: 399. 4. Hughey MJ, LaPata RE, McElin TW, et al. The effect of fetal monitoring on the incidence of cesarean section. Obstet Gynecol 1977;
3.
49: 513. 5. Lee WK,
Baggish MS. The effect of unselected intrapartum fetal monitoring. Obstet Gynecol 1976; 47: 516-20.
EPILEPSY OCTET Status
epilepticus in adults MARTIN J. BRODIE
A working definition of status epilepticus is a seizure lasting more than 30 minutes or several distinct episodes without restoration of consciousness. Generalised tonic-clonic status is a life-threatening disorder that requires prompt treatment. The longer the fits continue the more difficult it is to control the seizures, and morbidity and mortality increased Convulsive status can also be partial (epilepsia partialis continuans); this condition may be refractory to standard pharmacological measures and responds best to high doses of corticosteroids. Pseudostatus should be suspected if there is aberrant motor activity, poor response to treatment, an on/off pattern of seizure activity, and lack of metabolic consequences despite some hours of apparent fitting.2 Correct diagnosis is essential since the hazards of the condition arise from treatment undertaken in the mistaken belief that the patient is in true status epilepticus.3 Non-convulsive status, which usually presents with longterm clouding of consciousness and orofacial dyskinetic movements,4can also be partial or generalised (absence). Most cases of status epilepticus are symptomatic (table I), so when fitting is controlled, an underlying cause should be sought if not previously diagnosed (eg, a tumour) or not immediately apparent (eg, poor anticonvulsant compliance).5 If status is due to drug withdrawal (eg, phenobarbitone) reinstitution of the original treatment can be very effective.
Management Treatment
plans for convulsive status differ slightly depending on the centre and the country. Most schedules recommend
initial
with an intravenous benzodiazepine, usually diazepam, to abort the status, with immediate infusion of phenytoin to prevent recurrence.1M Lorazepam has its advocates because of its longer duration of action.8 Some neurologists prefer to use intravenous phenytoin alone.9 My own approachlO is outlined in table II. Both diazepaml and phenytoin" will abolish about 80% of episodes of convulsive status epilepticus. A similar pharmacological approach can be used in patients with other forms of status, but it may be possible to avoid intravenous treatment
therapy. All benzodiazepines have the potential to depress respiration although apnoea is an uncommon complication. Hypotension and cardiac arrhythmias have been reported with intravenous phenytoin12 and cardiac rhythm should be monitored as a precaution. A history of current oral phenytoin use should not temper the treatment of status because the blood levels will usually be low as a result of erratic compliance.5 Even if the phenytoin concentration is ADDRESS: Epilepsy Research Unit, Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK (Dr M. J. Brodie, FRCP).
552
TABLE I-CAUSES OF TONIC-CLONIC STATUS
Background of epilepsy Poor anticonvulsant compliance Recent dose reduction or discontinuation Alcohol withdrawal Pseudostatus
preferred. Mortality figures vary depending on the underlying cause of the status and on the duration of seizures before therapeutic intervention. These factors also influence the neurological outcome. Maintenance treatment
Presenting de novo Cerebrovascular disease
Meningoencephalitis Acute head injury Cerebral tumour Brain abscess Metabolic disorder--eg, renal failure, hypoglycaemia, post cardiac arrest, hepatic encephalopathy
hyponatraemia,
Drug overdose-eg, tricyclic antidepressant, phenothiazine, theophylline, isoniazid, cocaine Inflammatory arteritis--eg, systemic lupus erythematosus
within the target range, patients do not appear to come to any harm.13 Correction of metabolic abnormalities such as hypoxia and hypoglycaemia is also important. In general, bicarbonate should not be given to correct acidosis since it is usually unnecessary and may be harmful. The course of action in the few patients whose seizure activity does not respond to intravenous diazepam and phenytoin infusion varies in different countries. In the UK, chlormethiazole is often the next choice and if seizures are not abolished the patient is usually transferred to an intensive care facility before further action is taken. Elsewhere, phenobarbitone9 or lignocaine14 may be
When seizures have been abolished, an appropriate oral regimen should be instituted immediately. If poor compliance is likely to have been the precipitating factor, a loading dose of the patient’s previous anticonvulsant should be provided. Carbamazepine liquid can be given via a nasogastric tube. The intravenous preparation of sodium valproate can be used if the patient is unconscious. In a previously untreated patient, oral phenytoin would be an appropriate choice. The previously administered intravenous dose of 15-18 mg/kg will produce concentrations at the lower end of the target range for 24 hours after administration.12 A further oral loading dose should be given 6-12 hours after the infusion; the amount can be derived from the following formula:15 Loading dose (mg) 0-65 weight (kg) x (C desired - C current), where C is the phenytoin concentration in mg/1 (divide by 4 if in Eunol/1) A reasonable target for C desired would be 15 mg/1 (60 umol/1). The next day a maintenance dose can be introduced =
according to body weight: Oral maintenance dose = 300 mg
x
weight(kg) 70
population value would be about 5 mg/kg day. Thereafter, the dose should be tailored according to further concentration measurements. The regimen should be reassessed after 24 hours if there are any clinical difficulties—eg, poor control or toxicity-otherwise, the drug can be measured every 2-3 days until steady-state levels are attained. An average
TABLE II-MANAGEMENT OF STATUS EPILEPTlCUSIN ADULTS Immediate Remove false teeth Turn to lateral semiprone position Intravenous diazepam (or rectal if no venous access) Inject first 10 mg diazepam quickly If fits continue, give further 10 mg over 30 s Transfer to hospital Accident and emergency department Initial management 10 litres 02/min via high-flow mask If diazepam not given, administer as above If fits continue, try another 20 mg Take blood for urea and electrolytes, glucose, Ca + +, Mg + +, full blood count, arterial gases, and anticonvulsant concentrations Subsequent management Infuse phenytoin 15-18 mg/kg in 0-9% saline at 50 mg/min Monitor cardiac rhythm If known to have tumour, arteritis, or parasitic central nervous system infection, give high-dose dexamethasone intravenously If alcoholic, administer 100 mg thiamine intravenously Resistant status
Regimen Infuse 40-100 ml chlormethiazole 0-8% solution over 10 min If fits stop, reduce to 0’S-1 ml/min Monitor respiration frequently Alternative regimen Dilute 10 ml paraldehyde in 100 ml 09% saline and infuse over 10-15 min or until fits stop
Refractory status Transfer
to
intensive
care
unit
Regimen one Inject phenobarbitone 15 mg/kg no faster than 100 mg/min or until seizures stop only if patient has not recently received oral phenobarbitone or primidone Careful observation of respiratory state is mandatory Regimen two Lignocaine 100 mg by slow intravenous injection If effective, infuse 50-100 mg lignocaine in 250 ml of 5% dextrose at a rate of 1-2 mg/min Monitor electrocardiogram to detect widening of QRS complexes Regimen three Anaesthetise with thiopentone, paralyse, and ventilate Monitor electroencephalogram to detect abnormal electrical activity
REFERENCES 1. Simon PR. Management of status epilepticus. In: Pedley TA, Meldrum BS, eds. Recent advances in epilepsy 2. Edinburgh: Churchill Livingstone, 1985: 137-63. 2. Howell SJL, Owen L, Chadwick DW. Pseudostatus epilepticus. QJ Med
1989; 7: 509-19. 3. Editorial. Pseudostatus epilepticus. Lancet 1989; ii: 485. 4. Dunne JW, Summers QA, Stewart-Wynne EG. Non-convulsive status epilepticus: a prospective study in an adult general hospital. QJ Med 1987; 62: 117-26. 5. Aminoff MJ, Simon RP. Status epilepticus: causes, clinical features and consequences in 98 patients. Am J Med 1980; 69: 657-66. 6. Bruni J. Treatment of status epilepticus in adults. Can Med Assoc J 1983; 128: 531-33. 7. Swartz BE, Delgado-Escuedo AV. The management of status epilepticus. In: Hopkins A, ed. Epilepsy. London: Chapman and Hall, 1987: 417-22. 8. Treiman DM. Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus. Epilepsia 1989; 30 (suppl 2):
S4-10. 9. Uthman BM, Wilder BJ. Emergency management of seizures: an overview. Epilepsia 1989; 30 (suppl 2): S33-37. 10. Brodie MJ. Management of status epilepticus in adults. Prescribers J 1989; 29: 48-56. 11. Wilder BJ. Efficacy of phenytoin in treatment of status epilepticus. Adv Neurol 1983; 34: 441-46. 12. Earnest MP, Mark JA, Drury LR. Complications of intravenous phenytoin for acute treatment of seizures. JAMA 1983; 249: 762-65. 13. Cranford RE, Patrick B, Anderson CB, Kostick B. Intravenous phenytoin: clinical and pharmacokinetic aspects. Neurology 1978; 28: 874-80. 14. Pascual J, Sedano NJ, Polo JM, Berciano J. Intravenous lidocaine for status epilepticus. Epilepsia 1988; 29: 584-89. 15. Winter ME, Tozer TN. Phenytoin. In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied pharmacokinetics. Spokane: Applied Therapeutics, 1986: 493-539.
instances in which the auditors would recommend
surgical delivery. The total effect of audit on the overall caesarean section rate is therefore likely to be small. 65 % of the caesarean sections surveyed were done as emergency operations. Of these, 64% were indicated for intrapartum fetal distress; this proportion represented approximately 5% of all deliveries in 1985 at St James’s, where the caesarean section rate that year was
13-6% (unpublished). A third of the operations for
(15%
of the
total)
were
intrapartum fetal distress judged by 4 or 5 auditors to have
been unnecessary. If in a third of these another indication for section or unequivocal evidence of fetal distress subsequently developed, then the total expected reduction in our caesarean section rate would be 1 %. A 1 % reduction in caesarean section rate of 13-6% is a worthwhile objective if the drop could be achieved without increasing fetal risk. Furthermore, audit may point out aspects of labour management that may be amenable to alteration-eg, limited use of fetal scalp pH sampling. For audit to be widely accepted and practised it should have the confidence and support of those whose work is being audited. The wide inter-assessor variation, along with inconsistency of the assessors on review of the cases, must diminish confidence in this form of peer review.
Besides highlighting the inadequacies of our present methods of intrapartum fetal assessment and stressing the need for more objective data, our findings are relevant in the sphere of medical jurisprudence. The data presented to medical assessors in malpractice cases is very similar to that which were given to the assessors in this study. In conclusion, this study suggests that attempts to reduce an increasing caesarean section rate by audit must begin with a self audit on the part of the assessors; that there should be further research into methods of intrapartum monitoring that would discriminate well between sick and healthy babies; and that the limitations of present methods of audit be realised by all called upon to bear "expert witness". REFERENCES 1. Patel YA. 2.
Changing trends in the incidence of caesarean section. J Obstet Gynaecol 1983; 3: 253-57. Lomas J. Holding back the tide of caesarean sections. Br Med J 1988; 297: 569-71.
Haverkamp AD, Orleans M, Langendoerfer S, et al. A controlled trial of the different effects of intrapartum fetal monitoring. Am J Obstet Gynaecol 1983; 134: 399. 4. Hughey MJ, LaPata RE, McElin TW, et al. The effect of fetal monitoring on the incidence of cesarean section. Obstet Gynecol 1977;
3.
49: 513. 5. Lee WK,
Baggish MS. The effect of unselected intrapartum fetal monitoring. Obstet Gynecol 1976; 47: 516-20.
EPILEPSY OCTET Status
epilepticus in adults MARTIN J. BRODIE
A working definition of status epilepticus is a seizure lasting more than 30 minutes or several distinct episodes without restoration of consciousness. Generalised tonic-clonic status is a life-threatening disorder that requires prompt treatment. The longer the fits continue the more difficult it is to control the seizures, and morbidity and mortality increased Convulsive status can also be partial (epilepsia partialis continuans); this condition may be refractory to standard pharmacological measures and responds best to high doses of corticosteroids. Pseudostatus should be suspected if there is aberrant motor activity, poor response to treatment, an on/off pattern of seizure activity, and lack of metabolic consequences despite some hours of apparent fitting.2 Correct diagnosis is essential since the hazards of the condition arise from treatment undertaken in the mistaken belief that the patient is in true status epilepticus.3 Non-convulsive status, which usually presents with longterm clouding of consciousness and orofacial dyskinetic movements,4can also be partial or generalised (absence). Most cases of status epilepticus are symptomatic (table I), so when fitting is controlled, an underlying cause should be sought if not previously diagnosed (eg, a tumour) or not immediately apparent (eg, poor anticonvulsant compliance).5 If status is due to drug withdrawal (eg, phenobarbitone) reinstitution of the original treatment can be very effective.
Management Treatment
plans for convulsive status differ slightly depending on the centre and the country. Most schedules recommend
initial
with an intravenous benzodiazepine, usually diazepam, to abort the status, with immediate infusion of phenytoin to prevent recurrence.1M Lorazepam has its advocates because of its longer duration of action.8 Some neurologists prefer to use intravenous phenytoin alone.9 My own approachlO is outlined in table II. Both diazepaml and phenytoin" will abolish about 80% of episodes of convulsive status epilepticus. A similar pharmacological approach can be used in patients with other forms of status, but it may be possible to avoid intravenous treatment
therapy. All benzodiazepines have the potential to depress respiration although apnoea is an uncommon complication. Hypotension and cardiac arrhythmias have been reported with intravenous phenytoin12 and cardiac rhythm should be monitored as a precaution. A history of current oral phenytoin use should not temper the treatment of status because the blood levels will usually be low as a result of erratic compliance.5 Even if the phenytoin concentration is ADDRESS: Epilepsy Research Unit, Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK (Dr M. J. Brodie, FRCP).
552
TABLE I-CAUSES OF TONIC-CLONIC STATUS
Background of epilepsy Poor anticonvulsant compliance Recent dose reduction or discontinuation Alcohol withdrawal Pseudostatus
preferred. Mortality figures vary depending on the underlying cause of the status and on the duration of seizures before therapeutic intervention. These factors also influence the neurological outcome. Maintenance treatment
Presenting de novo Cerebrovascular disease
Meningoencephalitis Acute head injury Cerebral tumour Brain abscess Metabolic disorder--eg, renal failure, hypoglycaemia, post cardiac arrest, hepatic encephalopathy
hyponatraemia,
Drug overdose-eg, tricyclic antidepressant, phenothiazine, theophylline, isoniazid, cocaine Inflammatory arteritis--eg, systemic lupus erythematosus
within the target range, patients do not appear to come to any harm.13 Correction of metabolic abnormalities such as hypoxia and hypoglycaemia is also important. In general, bicarbonate should not be given to correct acidosis since it is usually unnecessary and may be harmful. The course of action in the few patients whose seizure activity does not respond to intravenous diazepam and phenytoin infusion varies in different countries. In the UK, chlormethiazole is often the next choice and if seizures are not abolished the patient is usually transferred to an intensive care facility before further action is taken. Elsewhere, phenobarbitone9 or lignocaine14 may be
When seizures have been abolished, an appropriate oral regimen should be instituted immediately. If poor compliance is likely to have been the precipitating factor, a loading dose of the patient’s previous anticonvulsant should be provided. Carbamazepine liquid can be given via a nasogastric tube. The intravenous preparation of sodium valproate can be used if the patient is unconscious. In a previously untreated patient, oral phenytoin would be an appropriate choice. The previously administered intravenous dose of 15-18 mg/kg will produce concentrations at the lower end of the target range for 24 hours after administration.12 A further oral loading dose should be given 6-12 hours after the infusion; the amount can be derived from the following formula:15 Loading dose (mg) 0-65 weight (kg) x (C desired - C current), where C is the phenytoin concentration in mg/1 (divide by 4 if in Eunol/1) A reasonable target for C desired would be 15 mg/1 (60 umol/1). The next day a maintenance dose can be introduced =
according to body weight: Oral maintenance dose = 300 mg
x
weight(kg) 70
population value would be about 5 mg/kg day. Thereafter, the dose should be tailored according to further concentration measurements. The regimen should be reassessed after 24 hours if there are any clinical difficulties—eg, poor control or toxicity-otherwise, the drug can be measured every 2-3 days until steady-state levels are attained. An average
TABLE II-MANAGEMENT OF STATUS EPILEPTlCUSIN ADULTS Immediate Remove false teeth Turn to lateral semiprone position Intravenous diazepam (or rectal if no venous access) Inject first 10 mg diazepam quickly If fits continue, give further 10 mg over 30 s Transfer to hospital Accident and emergency department Initial management 10 litres 02/min via high-flow mask If diazepam not given, administer as above If fits continue, try another 20 mg Take blood for urea and electrolytes, glucose, Ca + +, Mg + +, full blood count, arterial gases, and anticonvulsant concentrations Subsequent management Infuse phenytoin 15-18 mg/kg in 0-9% saline at 50 mg/min Monitor cardiac rhythm If known to have tumour, arteritis, or parasitic central nervous system infection, give high-dose dexamethasone intravenously If alcoholic, administer 100 mg thiamine intravenously Resistant status
Regimen Infuse 40-100 ml chlormethiazole 0-8% solution over 10 min If fits stop, reduce to 0’S-1 ml/min Monitor respiration frequently Alternative regimen Dilute 10 ml paraldehyde in 100 ml 09% saline and infuse over 10-15 min or until fits stop
Refractory status Transfer
to
intensive
care
unit
Regimen one Inject phenobarbitone 15 mg/kg no faster than 100 mg/min or until seizures stop only if patient has not recently received oral phenobarbitone or primidone Careful observation of respiratory state is mandatory Regimen two Lignocaine 100 mg by slow intravenous injection If effective, infuse 50-100 mg lignocaine in 250 ml of 5% dextrose at a rate of 1-2 mg/min Monitor electrocardiogram to detect widening of QRS complexes Regimen three Anaesthetise with thiopentone, paralyse, and ventilate Monitor electroencephalogram to detect abnormal electrical activity
REFERENCES 1. Simon PR. Management of status epilepticus. In: Pedley TA, Meldrum BS, eds. Recent advances in epilepsy 2. Edinburgh: Churchill Livingstone, 1985: 137-63. 2. Howell SJL, Owen L, Chadwick DW. Pseudostatus epilepticus. QJ Med
1989; 7: 509-19. 3. Editorial. Pseudostatus epilepticus. Lancet 1989; ii: 485. 4. Dunne JW, Summers QA, Stewart-Wynne EG. Non-convulsive status epilepticus: a prospective study in an adult general hospital. QJ Med 1987; 62: 117-26. 5. Aminoff MJ, Simon RP. Status epilepticus: causes, clinical features and consequences in 98 patients. Am J Med 1980; 69: 657-66. 6. Bruni J. Treatment of status epilepticus in adults. Can Med Assoc J 1983; 128: 531-33. 7. Swartz BE, Delgado-Escuedo AV. The management of status epilepticus. In: Hopkins A, ed. Epilepsy. London: Chapman and Hall, 1987: 417-22. 8. Treiman DM. Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus. Epilepsia 1989; 30 (suppl 2):
S4-10. 9. Uthman BM, Wilder BJ. Emergency management of seizures: an overview. Epilepsia 1989; 30 (suppl 2): S33-37. 10. Brodie MJ. Management of status epilepticus in adults. Prescribers J 1989; 29: 48-56. 11. Wilder BJ. Efficacy of phenytoin in treatment of status epilepticus. Adv Neurol 1983; 34: 441-46. 12. Earnest MP, Mark JA, Drury LR. Complications of intravenous phenytoin for acute treatment of seizures. JAMA 1983; 249: 762-65. 13. Cranford RE, Patrick B, Anderson CB, Kostick B. Intravenous phenytoin: clinical and pharmacokinetic aspects. Neurology 1978; 28: 874-80. 14. Pascual J, Sedano NJ, Polo JM, Berciano J. Intravenous lidocaine for status epilepticus. Epilepsia 1988; 29: 584-89. 15. Winter ME, Tozer TN. Phenytoin. In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied pharmacokinetics. Spokane: Applied Therapeutics, 1986: 493-539.
