130
Amphetamine ingestion presenting as eclampsia A case of amphetamine abuse in latepregnancy is reported. The presenting features of convulsions, confusion, agitation with hypertension and proteinuria led to a diagnosis of eclampsia for which a caesarean section was performed. Investigations and differential diagnosis of convulsions in late pregnancy are reviewed. A general urinary drug screen gives results after 24 hr whereas, if amphetamine abuse is suspected, this can be confirmed within three hr if a specific test for urinary amphetamines is performed. The sympathomimetic effects of a single dose of amphetamine are contrasted with the depression of the sympathetic nervous system which occurs after long-term use. Implications for anaesthesia are discussed. Nous prdsentons un cas d' intoxication aux amphetamines en fin de grossesse. L'agitation, la confusion, les convulsions assocites gz de l'hypertension et ~une proMinurie conduirent ~ un diagnostic d' ~clampsie et on fit une cdsarienne. Nous revoyons le diagnostic diff~rentiel et l'investigation gl faire, face d, des convulsions en fin de grossesse. La mesure sp~cifique des amphetamines urinaires donne des rdsultats en trois heures alors qu ' avec un test de ddpistage g~ndral, il faut attendre plus d'une journ~e. Avec les amphetamines, l'activation du systdme nerveux sympathique observde en phase aigu# se transforme en d~pression gt l' usage chronique. Nous en revoyons les implications anesthdsiques.
Key words ANAESTHESIA:obstetrical; ANALEPTICS: amphetamines; cOMPLICATIONS:eclampsia; PHARMACOLOGY:overdose, amphetamine. From the Department of Anaesthesia* and Obstetrics and Gynaecologyl", University Hospital, Nottingham, NG7 2UH United Kingdom. Address correspondence to: Dr. R.H. Elliott.
CAN J ANAESTH 1990 / 37:1 /pp130-3
Richard H. Elliott MBBc, FFARCS,* Gareth B. Rees MAMBBChir,MRCOGt
Illicit drug ingestion is common, but it may be overlooked by the physician during differential diagnosis and thus cause problems in clinical management. We describe a case in which acute amphetamine abuse in late pregnancy presented with features similar to those of eclampsia and was not diagnosed until after an emergency caesarean section was performed.
Case history A 19-year-old gravida 3, para 2 patient was admitted to the labour suite at 36 wk gestation. The friends who accompanied the patient gave a history consistent with convulsions, which they had witnessed, soon after they returned with her from a nightclub. The pregnancy had been otherwise uneventful. There was no other significant medical history and she was not taking any prescribed medication. Her clinical records indicated that she had had a pregnancy terminated when aged 14 and a full term normal delivery following an uneventful pregnancy at age 17. In this pregnancy, she was first seen at 32 weeks' gestation, when no abnormalities were detected. Her blood pressure then was 130/70 mmHg and her weight was 80 kg. On examination she was confused and agitated. Her heart rate was 90 bpm and her blood pressure 95/60 mmHg, when measured in the left lateral position. Her pupils were dilated but reacted to light and fundoscopy was normal. She had "heavy" proteinuria, as assessed by Dipstix urinalysis, but no red or white blood cells were found at urine microscopy. Subsequent 24 hr urine collection showed only 0.1 g protein per 24 h. Prothrombin time, partial thromboplastin time, thrombin time, fibrin degradation products and platelet count were normal, as were plasma creatinine, urea and electrolytes and serum glucose, uric acid concentrations and liver function tests. Her blood pressure became labile, with one isolated value of 160/100 mmHg. More typical values were 140/80 mmHg. Six hours after admission, a grand mal convulsion, witnessed by medical staff, was controlled by diazepam 10 mg IV. A diagnosis of eclampsia was made and caesarean section was arranged. Because of her agitation and confusion with labile blood pressure a general anaesthesic was given.
Elliott and Rees: AMPHETAMINES AND PREGNANCY A rapid sequence induction of anaesthesia was performed using pre-oxygenation, thiopentone 250 mg and succinylcholine 100 mg for tracheal intubation with cricoid pressure. Anaesthesia was maintained by nitrous oxide 50 per cent and halothane 0.4 per cent in oxygen until delivery. A female infant weighing 1.92 kg was delivered with an Apgar score of nine at one minute. Fentanyl 50 ~g and vecuronium 2 mg were given after delivery, when nitrous oxide weas increased to 65 per cent. The anaesthetic was uneventful and the patient's trachea was extubated after the neuromuscular blockade was reversed with neostigmine 2.5 mg and glycopyrrolate 0.5 mg. Postoperatively, the maximum recorded blood pressure was 140/80 mmHg and there was no further proteinuria. Her temperature reached 39.2 ~ C, but blood and urine cultures were negative. A C T brain scan and lumbar puncture were normal. The day after her anaesthetic the patient was completely lucid. Although she denied drug ingestion, a urine drug screen (taken 8 hr after admission) revealed amphetamine by gas chromatography. Her friends confirmed that she used to take amphetamine before she became pregnant. Discussion
Two aspects of this case are of interest. The first is the differential diagnosis of convulsions in late pregnancy if the presenting features are not typical of eclampsia. The second is the manner in which amphetamines may affect the conduct of anaesthesia. If a patient has a first convulsion during pregnancy eclampsia is the most likely diagnosis, but intracerebral conditions (haemorrhage, thrombosis, tumour and infection), hypertensive encephalopathy, metabolic abnormalities and drug ingestion should be considered, l Eclampsia is usually characterised by convulsions supervening upon a pre-eclamptic syndrome, which comprises hypertension with proteinuria and frequently oedema. 2 Despite much research, pre-eclampsia remains a clinical diagnosis with supportive laboratory evidence. 3 Prostaglandins may be involved, 4 but the most commonly agreed theory of pathophysiology is of diffuse vasospasm with increased vascular reactivity, as shown by increased sensitivity to Angiotensin I1. 5 This leads to reduced plasma volume 6 and renal abnormalities, which include reduced renal blood flow and glomerular filtration rate and increased glomerular permeability to protein. 7 Serum uric acid concentration increases which although not diagnostic, 3 may reflect the severity of the condition and poor fetal prognosis. 8 Evidence of abnormal coagulation and low platelet counts are also f o u n d . 3"9'1~ The aim of therapy is control of maternal blood pressure and convulsions. Early delivery of the fetus is
131 indicated because eclampsia usually resolves after delivery ~l and also because the fetus, frequently premature, has a high mortality due to hypoxia from placental vasospasm, abruption and maternal convulsions. 10,t2 In this case antenatal care was almost absent and no history could be obtained from the patient. Convulsions, hypertension and proteinuria had been observed, metabolic abnormalities were absent and there was no clinical evidence of intracerebral pathology, as later confirmed by normal CT scan and lumbar puncture. As eclampsia was considered the most likely diagnosis, at 36-wk gestation, an urgent operative delivery was most appropriate. ~l Certain features were, however, atypical. It is unusual for eclampsia to present for the first time during a third pregnancy, unless a different father is involved, 13 and the concentration of serum uric acid and coagulation factors were both normal. This patient's clinical features, particularly convulsions, confusion, agitation, dilated pupils and labile blood pressure, were compatible with amphetamine ingestion, 14 although the lack of clinical features specific to amphetamine has also been documented. 15 A full urine drug screen takes at least 24 hr, although a specific urine test for amphetamines can be performed within 3 hr at some laboratories. 16 Metabolites persist for 5-7 days after a single dose,17 and 20 per cent of orally ingested amphetamine is excreted unchanged in the urine. Amphetamine is excreted faster in acid urine in which it is completely ionised. 18 In retrospect, all the investigations could have been undertaken before delivery, providing that maternal blood pressure and convulsions were satisfactorily controlled without important side effects, so the caeserean section might have been avoided. However, convulsions of eclamptic origin carry a high fetal and maternal mortality and the risks from delay in surgical intervention need to be carefully assessed. Amphetamines were introduced in 1932 and, because of their mood enhancing and fatigue resisting properties, were initially widely and legally used. Many armies in World War II disributed them to combat troops. 19 As the harmful and addictive effects of amphetamine became known, the drug has become more controlled and is now overshadowed by cocaine, with which it shares many actions. 2~ However, amphetamine abuse is still widespread - of 2,900 toxicology profiles performed in San Diego in the year 1986-87, ten per cent were positive for amphetamine. 2i The effects of amphetamine ingestion may simulate other pathological conditions and interact with anaesthetic drugs. Acute and chronic amphetamine abuse present in different ways:
Acute ingestion of amphetamine releases catecholamines from adrenergic nerve terminals. The drug is an alpha and
132
beta adrenergic agonist and also inhibits catecholamine uptake. These actions cause agitation, confusion, dilated pupils and hyperreflexia. 14 Fever with hyperpyrexia can occur, together with tachycardia and vasoconstriction leading to hypertension, arrhythmias, pulmonary oedema and circulatory collapse. Moderate hypertension may occur after quite small doses 22'23 and can be severe enough to cause cerebral haemorrhage, so that care should be taken in areas of potential anaesthetic risk, for example tracheal intubation. Raised intracranial pressure in an amphetamine abuser has been recorded during neurosurgery, 24 and in animals amphetamine increases cerebral oxygen uptake and blood flow. 25 Arrhythmias may be controlled by propranolol and hypertension by diazoxide or alpha adrenergic antagonists. 22 If fever occurs, chlorpromazine reduces temperature and blood pressure and provides sedation. 26 Barbiturates have been similarly employed although anaesthetic doses are required. 22 The MAC for halothane is increased but this increase can be prevented by hyperventilation. 27 Because halothane sensitises the myocardium to catecholamines, isoflurane might be a more suitable volatile agent.
CANADIAN JOURNAL OF ANAESTHESIA
varies and drug ingestion, if not suspected, may cause life-threatening complications.
Acknowledgements The authors would like to thank Prof. E.M. Symonds for permission to report a patient under his care and Dr. J.R. Maltby for help with the manuscript.
References I Taber B-Z. Convulsive seizures in pregnancy. In:
Manual of Gynecologic and Obstetric Emergencies, 2nd ed. Philadelphia: W.B. Saunders Co. 1984: 154-5. 2 Davey DA, MacGillivray 1. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988; 158: 892-8. 3 Sibai BM, Anderson GD, McCubbin JH. Eclampsia II. Clinical significance of laboratory findings. Obstet Gynecol 1982; 59: 153-7. 4 Friedman SA. Preclampsia: a review of the role of prostaglandins. Obstet Gynecol 1988; 71: 122-37. 5 Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC. A study of angiotensin II pressor response through-
out primigravid pregnancy. J Ciin Invest 1973; 52: 2682-9. Chronic ingestion of amphetamine depletes the neurones
6 PrichardJA. In: Williams Obstetrics, 17th ed. Prichard
of catecholamines, impairs the response to sympathomimetics and obtunds the stress response.. Cardiovascular collapse during anaesthesia for caesarean section has been reported. 2s'29 Epidural and particularly spinal techniques may precipitate severe and resistant hypotension. In contrast to acute ingestion, the MAC of volatile agents is reduced in chronic abusers. 27 In chronic abusers the euphoric effect is less marked and most amphetamine users take it as a "weekend drug" - for recreational purposes when they are not at work. Patients may present with severe mental disturbances such as psychoses with paranoid delusions, hallucinations and aggressive behaviour. 3~ Because the precise condition of the patient with regard to acute or chronic ingestion may be very difficult to establish, invasive cardiovascular monitoring may be indicated for a patient with a known history of amphetamine ingestion. There are few reports of the effects of amphetamine in pregnancy. One small series showed few maternal complications, but a high incidence of prematurity and low birth weight. 3~ Amphetamines have been shown to have teratogenic properties, particularly in the cardiac conduction system. 32 Cocaine may also cause hypertension, convulsions and hyperreflexia 33 and could also mimic eclampsia, although its clinical effects are of shorter duration than those of amphetamine. 2~ Amphetamine, cocaine and other sympathomimetic drugs of abuse need to be considered in a differential diagnosis of eclampsia and specific urinalysis is available. The presentation
JA, MacDonald PC, Gant NF (Eds.). Norwalk: Appleton-Century-Crofts, 1985: 534. 7 Chesley LC. The Kidney. In: Hypertensive Disorder~fin Pregnancy, 2nd ed. New York: Appleton-Cefft~r~- ~ Crofts, 1978: 154-97. 8 Redman CWG, Beilin L J, Bonnar J, Wilkinson RH.
Plasma urate measurements in predicting fetal death in hypertensive pregnancy. Lancet 1976; i: 1370-3. 9 Pritchard JA, Cunningham FG, Mason RA. Coagulation changes in eclampsia. Their frequency and pathogenesis. Am J Obstet Gynecol !976; 124: 855-64. 10 Sibai BM, Spinnato JA, Watson DL, Hill GA, Anderson GD. Pregnancy outcome in 303 cases with severe preeclampsia. Obstet Gynecol 1984; 64: 319-25. l I Dennis E J, Hester L L Jnr. The preeclampsia-eclarnp.sia
syndrome. In: Obstetrics and Gynecology, 3rd ed. Danforth DN (Ed.). Hagerstown: Harper and Row, 1977: 391-409. 12 Knutsen VK, Davey DA. Hypertension in pregnancy and perinatal mortality. S Aft Med J 1977; 51: 675-9. 13 Feeney.JG. Pre-eclampsia and changed paternity. In: Pregnancy Hypertension. Bonnar J, MacGillivray I, Symonds EM (Eds.). Proceedings of the First Congress of the International Society for Study of Hypertension in Pregnancy at Univ. Coll. Dublin (Sept 1978). Baltimore: University Park Press. 1980: 41-4. 14 Ong BH. Dextro-amphetamine poisoning. Hazards to Health. N Engl J Med 1962; 266: 1321-2.
Elliott and Rees: AMPHETAMINES AND PREGNANCY 15 Neuberg R. Drug dependence and pregnancy: a review of the problems and their management. JObs Gynae Brit Comm 1970; 77:1 ! 17-22. 16 Bost RO, Sutheimer CA, Sunshine 1. Relative merits of some methods for amphetamine assay in biology fluids. Clin Chem 1976; 22: 789-801. 17 CaldweU J, Dring LG, Williams RT. Metabolism of 14C metamphetamine in man, guinea pig and rat. Biochem J 1972; 129: 11-22. 18 Angaard E, Gunne LM, Johnson LE, Nicklasson F. Pharmacokinetic and clinical studies on amphetamine dependant subjects. Eur J Clin Pharmacol 1970; 3: 3-11. 19 Brecher EM. Licit and Illicit Drugs. Boston: Little, Brown & Co. 1972: 278-9. 20 Ashley R. Cocaine - Its History, Uses and Effects. New York: Warner 1975: 125. 21 Bailey DN. Amphetamine detection during toxicology screening of a university medical centre population. J Toxicol Clin Toxicol 1987; 25: 399-409. 22 Caldwell TB. In: Katz J, Benumof J, Kadis LB. (Eds.). Anesthesia and Uncommon Diseases. 2nd ed. Philadelphia: Saunders, 1981. 724-9. 23 Caldwell J, Sever PS. The biochemical pharmacology of abused drugs, l-Amphetamine, cocaine and LSD. Clin Pharmacol Ther 1974; 16: 625-38. 24 Michael RI Adams AP. Acute amphetamine abuse problems during general anaesthesia for neurosurgery. Ahaesthe'sia 1979; 34: 1016-9. 25 Berntman L, Carlsson C, Hagerdal M, Siesjo BK. Excessive increase in oxygen uptake and blood flow in the brain during amphetamine intoxication. Acta Physiol Scand 1976; 97: 264-6. 26 Espelin DE, Dove AK. Amphetamine poisoning effectiveness of chlorpromazine. N Engl J Med 1968; 278: 1361-5.
133 27 Johnson RR, Way WL, Miller RD. Alteration in anesthetic requirement with amphetamines. Anesthesiology 1972; 34: 357-63. 28 Samuels IS, Maze A, Albright G. Cardiac arrest during Cesarean section in a chronic amphetamine abuser. Anesth Analg 1979; 58: 528-30. 29 Smith DS, Gutsche BB. Amphetamine abuse and obstetrical anesthesia. Anesth Analg 1980; 59:710-I 1. 30 Geerlings PJ. Social and psychiatric factors in amphetamine users. Psychiatr Neurol Neurochir 1972; 75: 219-24. 31 Eriksson M, Larsson G, Windbladh B, Zetterstrom R. The influence of amphetamine addiction on pregnancy and the newborn infant. Acta Paediatr Scand 1978; 67: 95-9. 32 Fein A, Shviro Y, Manoach M, Nebel L. Teratogenic effect of D-amphetamine sulphate: histodifferentiation and electrocardiogram pattern of mouse embryonic heart. Teratology 1987; 35: 27-34. 33 Gay GR, lnaba DS, Rappolt RT, Gushue GF, Perkner JJ. Cocaine in current perspective. Anesth Analg 1976; 55: 582-7.
Amphetamine ingestion presenting as eclampsia A case of amphetamine abuse in latepregnancy is reported. The presenting features of convulsions, confusion, agitation with hypertension and proteinuria led to a diagnosis of eclampsia for which a caesarean section was performed. Investigations and differential diagnosis of convulsions in late pregnancy are reviewed. A general urinary drug screen gives results after 24 hr whereas, if amphetamine abuse is suspected, this can be confirmed within three hr if a specific test for urinary amphetamines is performed. The sympathomimetic effects of a single dose of amphetamine are contrasted with the depression of the sympathetic nervous system which occurs after long-term use. Implications for anaesthesia are discussed. Nous prdsentons un cas d' intoxication aux amphetamines en fin de grossesse. L'agitation, la confusion, les convulsions assocites gz de l'hypertension et ~une proMinurie conduirent ~ un diagnostic d' ~clampsie et on fit une cdsarienne. Nous revoyons le diagnostic diff~rentiel et l'investigation gl faire, face d, des convulsions en fin de grossesse. La mesure sp~cifique des amphetamines urinaires donne des rdsultats en trois heures alors qu ' avec un test de ddpistage g~ndral, il faut attendre plus d'une journ~e. Avec les amphetamines, l'activation du systdme nerveux sympathique observde en phase aigu# se transforme en d~pression gt l' usage chronique. Nous en revoyons les implications anesthdsiques.
Key words ANAESTHESIA:obstetrical; ANALEPTICS: amphetamines; cOMPLICATIONS:eclampsia; PHARMACOLOGY:overdose, amphetamine. From the Department of Anaesthesia* and Obstetrics and Gynaecologyl", University Hospital, Nottingham, NG7 2UH United Kingdom. Address correspondence to: Dr. R.H. Elliott.
CAN J ANAESTH 1990 / 37:1 /pp130-3
Richard H. Elliott MBBc, FFARCS,* Gareth B. Rees MAMBBChir,MRCOGt
Illicit drug ingestion is common, but it may be overlooked by the physician during differential diagnosis and thus cause problems in clinical management. We describe a case in which acute amphetamine abuse in late pregnancy presented with features similar to those of eclampsia and was not diagnosed until after an emergency caesarean section was performed.
Case history A 19-year-old gravida 3, para 2 patient was admitted to the labour suite at 36 wk gestation. The friends who accompanied the patient gave a history consistent with convulsions, which they had witnessed, soon after they returned with her from a nightclub. The pregnancy had been otherwise uneventful. There was no other significant medical history and she was not taking any prescribed medication. Her clinical records indicated that she had had a pregnancy terminated when aged 14 and a full term normal delivery following an uneventful pregnancy at age 17. In this pregnancy, she was first seen at 32 weeks' gestation, when no abnormalities were detected. Her blood pressure then was 130/70 mmHg and her weight was 80 kg. On examination she was confused and agitated. Her heart rate was 90 bpm and her blood pressure 95/60 mmHg, when measured in the left lateral position. Her pupils were dilated but reacted to light and fundoscopy was normal. She had "heavy" proteinuria, as assessed by Dipstix urinalysis, but no red or white blood cells were found at urine microscopy. Subsequent 24 hr urine collection showed only 0.1 g protein per 24 h. Prothrombin time, partial thromboplastin time, thrombin time, fibrin degradation products and platelet count were normal, as were plasma creatinine, urea and electrolytes and serum glucose, uric acid concentrations and liver function tests. Her blood pressure became labile, with one isolated value of 160/100 mmHg. More typical values were 140/80 mmHg. Six hours after admission, a grand mal convulsion, witnessed by medical staff, was controlled by diazepam 10 mg IV. A diagnosis of eclampsia was made and caesarean section was arranged. Because of her agitation and confusion with labile blood pressure a general anaesthesic was given.
Elliott and Rees: AMPHETAMINES AND PREGNANCY A rapid sequence induction of anaesthesia was performed using pre-oxygenation, thiopentone 250 mg and succinylcholine 100 mg for tracheal intubation with cricoid pressure. Anaesthesia was maintained by nitrous oxide 50 per cent and halothane 0.4 per cent in oxygen until delivery. A female infant weighing 1.92 kg was delivered with an Apgar score of nine at one minute. Fentanyl 50 ~g and vecuronium 2 mg were given after delivery, when nitrous oxide weas increased to 65 per cent. The anaesthetic was uneventful and the patient's trachea was extubated after the neuromuscular blockade was reversed with neostigmine 2.5 mg and glycopyrrolate 0.5 mg. Postoperatively, the maximum recorded blood pressure was 140/80 mmHg and there was no further proteinuria. Her temperature reached 39.2 ~ C, but blood and urine cultures were negative. A C T brain scan and lumbar puncture were normal. The day after her anaesthetic the patient was completely lucid. Although she denied drug ingestion, a urine drug screen (taken 8 hr after admission) revealed amphetamine by gas chromatography. Her friends confirmed that she used to take amphetamine before she became pregnant. Discussion
Two aspects of this case are of interest. The first is the differential diagnosis of convulsions in late pregnancy if the presenting features are not typical of eclampsia. The second is the manner in which amphetamines may affect the conduct of anaesthesia. If a patient has a first convulsion during pregnancy eclampsia is the most likely diagnosis, but intracerebral conditions (haemorrhage, thrombosis, tumour and infection), hypertensive encephalopathy, metabolic abnormalities and drug ingestion should be considered, l Eclampsia is usually characterised by convulsions supervening upon a pre-eclamptic syndrome, which comprises hypertension with proteinuria and frequently oedema. 2 Despite much research, pre-eclampsia remains a clinical diagnosis with supportive laboratory evidence. 3 Prostaglandins may be involved, 4 but the most commonly agreed theory of pathophysiology is of diffuse vasospasm with increased vascular reactivity, as shown by increased sensitivity to Angiotensin I1. 5 This leads to reduced plasma volume 6 and renal abnormalities, which include reduced renal blood flow and glomerular filtration rate and increased glomerular permeability to protein. 7 Serum uric acid concentration increases which although not diagnostic, 3 may reflect the severity of the condition and poor fetal prognosis. 8 Evidence of abnormal coagulation and low platelet counts are also f o u n d . 3"9'1~ The aim of therapy is control of maternal blood pressure and convulsions. Early delivery of the fetus is
131 indicated because eclampsia usually resolves after delivery ~l and also because the fetus, frequently premature, has a high mortality due to hypoxia from placental vasospasm, abruption and maternal convulsions. 10,t2 In this case antenatal care was almost absent and no history could be obtained from the patient. Convulsions, hypertension and proteinuria had been observed, metabolic abnormalities were absent and there was no clinical evidence of intracerebral pathology, as later confirmed by normal CT scan and lumbar puncture. As eclampsia was considered the most likely diagnosis, at 36-wk gestation, an urgent operative delivery was most appropriate. ~l Certain features were, however, atypical. It is unusual for eclampsia to present for the first time during a third pregnancy, unless a different father is involved, 13 and the concentration of serum uric acid and coagulation factors were both normal. This patient's clinical features, particularly convulsions, confusion, agitation, dilated pupils and labile blood pressure, were compatible with amphetamine ingestion, 14 although the lack of clinical features specific to amphetamine has also been documented. 15 A full urine drug screen takes at least 24 hr, although a specific urine test for amphetamines can be performed within 3 hr at some laboratories. 16 Metabolites persist for 5-7 days after a single dose,17 and 20 per cent of orally ingested amphetamine is excreted unchanged in the urine. Amphetamine is excreted faster in acid urine in which it is completely ionised. 18 In retrospect, all the investigations could have been undertaken before delivery, providing that maternal blood pressure and convulsions were satisfactorily controlled without important side effects, so the caeserean section might have been avoided. However, convulsions of eclamptic origin carry a high fetal and maternal mortality and the risks from delay in surgical intervention need to be carefully assessed. Amphetamines were introduced in 1932 and, because of their mood enhancing and fatigue resisting properties, were initially widely and legally used. Many armies in World War II disributed them to combat troops. 19 As the harmful and addictive effects of amphetamine became known, the drug has become more controlled and is now overshadowed by cocaine, with which it shares many actions. 2~ However, amphetamine abuse is still widespread - of 2,900 toxicology profiles performed in San Diego in the year 1986-87, ten per cent were positive for amphetamine. 2i The effects of amphetamine ingestion may simulate other pathological conditions and interact with anaesthetic drugs. Acute and chronic amphetamine abuse present in different ways:
Acute ingestion of amphetamine releases catecholamines from adrenergic nerve terminals. The drug is an alpha and
132
beta adrenergic agonist and also inhibits catecholamine uptake. These actions cause agitation, confusion, dilated pupils and hyperreflexia. 14 Fever with hyperpyrexia can occur, together with tachycardia and vasoconstriction leading to hypertension, arrhythmias, pulmonary oedema and circulatory collapse. Moderate hypertension may occur after quite small doses 22'23 and can be severe enough to cause cerebral haemorrhage, so that care should be taken in areas of potential anaesthetic risk, for example tracheal intubation. Raised intracranial pressure in an amphetamine abuser has been recorded during neurosurgery, 24 and in animals amphetamine increases cerebral oxygen uptake and blood flow. 25 Arrhythmias may be controlled by propranolol and hypertension by diazoxide or alpha adrenergic antagonists. 22 If fever occurs, chlorpromazine reduces temperature and blood pressure and provides sedation. 26 Barbiturates have been similarly employed although anaesthetic doses are required. 22 The MAC for halothane is increased but this increase can be prevented by hyperventilation. 27 Because halothane sensitises the myocardium to catecholamines, isoflurane might be a more suitable volatile agent.
CANADIAN JOURNAL OF ANAESTHESIA
varies and drug ingestion, if not suspected, may cause life-threatening complications.
Acknowledgements The authors would like to thank Prof. E.M. Symonds for permission to report a patient under his care and Dr. J.R. Maltby for help with the manuscript.
References I Taber B-Z. Convulsive seizures in pregnancy. In:
Manual of Gynecologic and Obstetric Emergencies, 2nd ed. Philadelphia: W.B. Saunders Co. 1984: 154-5. 2 Davey DA, MacGillivray 1. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988; 158: 892-8. 3 Sibai BM, Anderson GD, McCubbin JH. Eclampsia II. Clinical significance of laboratory findings. Obstet Gynecol 1982; 59: 153-7. 4 Friedman SA. Preclampsia: a review of the role of prostaglandins. Obstet Gynecol 1988; 71: 122-37. 5 Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC. A study of angiotensin II pressor response through-
out primigravid pregnancy. J Ciin Invest 1973; 52: 2682-9. Chronic ingestion of amphetamine depletes the neurones
6 PrichardJA. In: Williams Obstetrics, 17th ed. Prichard
of catecholamines, impairs the response to sympathomimetics and obtunds the stress response.. Cardiovascular collapse during anaesthesia for caesarean section has been reported. 2s'29 Epidural and particularly spinal techniques may precipitate severe and resistant hypotension. In contrast to acute ingestion, the MAC of volatile agents is reduced in chronic abusers. 27 In chronic abusers the euphoric effect is less marked and most amphetamine users take it as a "weekend drug" - for recreational purposes when they are not at work. Patients may present with severe mental disturbances such as psychoses with paranoid delusions, hallucinations and aggressive behaviour. 3~ Because the precise condition of the patient with regard to acute or chronic ingestion may be very difficult to establish, invasive cardiovascular monitoring may be indicated for a patient with a known history of amphetamine ingestion. There are few reports of the effects of amphetamine in pregnancy. One small series showed few maternal complications, but a high incidence of prematurity and low birth weight. 3~ Amphetamines have been shown to have teratogenic properties, particularly in the cardiac conduction system. 32 Cocaine may also cause hypertension, convulsions and hyperreflexia 33 and could also mimic eclampsia, although its clinical effects are of shorter duration than those of amphetamine. 2~ Amphetamine, cocaine and other sympathomimetic drugs of abuse need to be considered in a differential diagnosis of eclampsia and specific urinalysis is available. The presentation
JA, MacDonald PC, Gant NF (Eds.). Norwalk: Appleton-Century-Crofts, 1985: 534. 7 Chesley LC. The Kidney. In: Hypertensive Disorder~fin Pregnancy, 2nd ed. New York: Appleton-Cefft~r~- ~ Crofts, 1978: 154-97. 8 Redman CWG, Beilin L J, Bonnar J, Wilkinson RH.
Plasma urate measurements in predicting fetal death in hypertensive pregnancy. Lancet 1976; i: 1370-3. 9 Pritchard JA, Cunningham FG, Mason RA. Coagulation changes in eclampsia. Their frequency and pathogenesis. Am J Obstet Gynecol !976; 124: 855-64. 10 Sibai BM, Spinnato JA, Watson DL, Hill GA, Anderson GD. Pregnancy outcome in 303 cases with severe preeclampsia. Obstet Gynecol 1984; 64: 319-25. l I Dennis E J, Hester L L Jnr. The preeclampsia-eclarnp.sia
syndrome. In: Obstetrics and Gynecology, 3rd ed. Danforth DN (Ed.). Hagerstown: Harper and Row, 1977: 391-409. 12 Knutsen VK, Davey DA. Hypertension in pregnancy and perinatal mortality. S Aft Med J 1977; 51: 675-9. 13 Feeney.JG. Pre-eclampsia and changed paternity. In: Pregnancy Hypertension. Bonnar J, MacGillivray I, Symonds EM (Eds.). Proceedings of the First Congress of the International Society for Study of Hypertension in Pregnancy at Univ. Coll. Dublin (Sept 1978). Baltimore: University Park Press. 1980: 41-4. 14 Ong BH. Dextro-amphetamine poisoning. Hazards to Health. N Engl J Med 1962; 266: 1321-2.
Elliott and Rees: AMPHETAMINES AND PREGNANCY 15 Neuberg R. Drug dependence and pregnancy: a review of the problems and their management. JObs Gynae Brit Comm 1970; 77:1 ! 17-22. 16 Bost RO, Sutheimer CA, Sunshine 1. Relative merits of some methods for amphetamine assay in biology fluids. Clin Chem 1976; 22: 789-801. 17 CaldweU J, Dring LG, Williams RT. Metabolism of 14C metamphetamine in man, guinea pig and rat. Biochem J 1972; 129: 11-22. 18 Angaard E, Gunne LM, Johnson LE, Nicklasson F. Pharmacokinetic and clinical studies on amphetamine dependant subjects. Eur J Clin Pharmacol 1970; 3: 3-11. 19 Brecher EM. Licit and Illicit Drugs. Boston: Little, Brown & Co. 1972: 278-9. 20 Ashley R. Cocaine - Its History, Uses and Effects. New York: Warner 1975: 125. 21 Bailey DN. Amphetamine detection during toxicology screening of a university medical centre population. J Toxicol Clin Toxicol 1987; 25: 399-409. 22 Caldwell TB. In: Katz J, Benumof J, Kadis LB. (Eds.). Anesthesia and Uncommon Diseases. 2nd ed. Philadelphia: Saunders, 1981. 724-9. 23 Caldwell J, Sever PS. The biochemical pharmacology of abused drugs, l-Amphetamine, cocaine and LSD. Clin Pharmacol Ther 1974; 16: 625-38. 24 Michael RI Adams AP. Acute amphetamine abuse problems during general anaesthesia for neurosurgery. Ahaesthe'sia 1979; 34: 1016-9. 25 Berntman L, Carlsson C, Hagerdal M, Siesjo BK. Excessive increase in oxygen uptake and blood flow in the brain during amphetamine intoxication. Acta Physiol Scand 1976; 97: 264-6. 26 Espelin DE, Dove AK. Amphetamine poisoning effectiveness of chlorpromazine. N Engl J Med 1968; 278: 1361-5.
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