ANESTH ANALG 58528-530, 1979
Cardiac Arrest during Cesarean Section in a Chronic Amphetamine Abuser Stanley I. Samuels, MB, BCh,* Aubrey Maze,MB, ChB,t and George Albright, MD* There has been general concern but little documentation among anesthesiologists that interactions between general anesthetic agents and drugs of abuse such as amphetamines may lead to sudden cardiovascular collapse.’.’ In fact a recent textbook commented on the fact that there were no case reports in the literature concerning abnormal reactions in amphet. ~ presamine users during anesthesia a n d s ~ r g e r yWe ent the case of a patient who sustained a cardiac arrest during cesarean section in which the primary cause of the arrest may have been due to chronic drug abuse.
Case Report A 27-year-old black gravida 5 para 3 was admitted to Stanford University Hospital at term and in active labor. Past medical history was significant in that she had been a drug abuser of many years standing. As far as could be ascertained the main drugs of abuse had been heroin and amphetamines. She denied any recent drug usage. She had had three low transverse cesarean sections in 1964, 1967, and 1973 under regional anesthesia without complication. Clinical examination was negative except for the presence of sclerosed veins in both arms, and a history of vomiting for 12 hours prior to admission to hospital. There were no clinical signs of dehydration. Continous epidural anesthesia was planned for the cesarean section. An epidural catheter was easily inserted at the W-L4 interspace. Following a test dose, 10 ml of lidocaine 2% with epinephrine 1/200,OOO was injected through the catheter and a T12 level of analgesia was obtained.
* Assistant Professor of Anesthesia.
t Assistant Professor of Anesthesia and Pediatrics. Received from the Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305. Accepted for publication August 14, 1979. Reprint requests to Dr. Samuels.
528
ANESTHESIA AND ANALGESIA Vol58. No 6. Nov-Dec 1979
About 45 minutes later the patient was transferred to the delivery room. Chloroprocaine 3%, 12 ml, without epinephrine was injected through the catheter in preparation for operation. Ten minutes later because of an inadequate level of analgesic block (T12) a second injection of chloroprocaine (6 ml of 3% solution) was given. No analgesic effect was noted. It was then decided to induce general anesthesia. Twenty minutes after the second injection of chloroprocaine general anesthesia was induced. At time of induction of anesthesia the systolic blood pressure was 100 torr, the pulse rate was 80 beats/min and the ECG showed sinus rhythm. Following left uterine displacement, preoxygenation, atropine (0.5 mg) and precurarization (curare 3 mg), thiopental, 200 mg, and succinylcholine, 100 mg, were injected intravenously, cricoid pressure was applied and endotracheal intubation performed. Following an easy intubation both lung apices moved well, equal breath sounds were heard bilaterally. The pulse rate was 110 beats/min and the systolic blood pressure was 120 torr. ECG showed sinus rhythm. Oxygen 2 L/min and nitrous oxide 4 L/min were begun together with positive pressure ventilation. The operation commenced immediately following intubation at which time it was noted that the patient’s tongue was dark in color and examination of the operating field disclosed the presence of very dark blood. Nitrous oxide was discontinued and the heart sounds which previously had been well heard via a precordial stethoscope disappeared. No pulse was felt in either the radial or carotid arteries and no blood pressure could be obtained. At this time both pupils were dilated and the ECG was a flat line. Cardiopulmonary resuscitation (CPR) was begun immediately using external cardiac massage. This produced a palpable carotid pulse. Drugs used for treatment of the cardiac arrest included sodium bicarbonate, 100 meq, epinephrine 1/1O,c00, 5 ml, isoproterenol hydrochloride infusion, 2 pg/min, and decadron, 8 mg. Sinus tachycardia occurred about 8 minutes after resuscitation and brachial blood pressure was palpable at 60 torr. Coincidental with the resuscitation, a healthy 3 kg male infant was delivered. The Apgar score at 1minute was 7. Fifteen minutes after CPR had commenced the pupils started to respond to light pulse and blood pressure returned to pre-induction values. Five minutes later the patient began to breathe spontaneously. An arterial blood sample obtained during the arrest showed pH 7.41, PCO, 27 torr, pHco, 17.0 meq/L, andPo, 77 torr. About 90 minutes after the onset of the cardiac arrest she was returned to the intensive care unit awake but disoriented. She was later extubated and vital signs remained stable. Two days later she elaborated on her drug history. She had been taking amphetamines since age 13 and had continued to take them both intravenously and orally up to time of her admission to the hospital. Her use of heroin was intermittent; she last took heroin about 7 days before hospital admission. Toxicologic analysis of her urine obtained the
CLINICAL REPORTS
day after her arrest showed levels of amphetamine and methamphetamine of 0.4 and 0.2 pg/ml, respectively. These figures indicated only that amphetamines had been taken; they do not indicate either when the last amphetamine was taken or the amount taken. The patient was discharged on the sixth postoperative day with no apparent sequelae from her cardiac arrest.
Discussion Unexpected cardiac arrest is one of the most dramatic and frightening events that can occur in the operating room. When it occurs in the delivery room during a cesarean section it becomes doubly threatening, for not one but two lives are threatened. Previous studies indicate that the incidence of cardiac arrest in the operating room vanes from 1/800 to 1/3,400 operation^.^ The paucity of articles in the literature on cardiac arrest in previously healthy obstetrical patients undergoing cesarean section indicates it is a rare occurrence. Possible causes for the cardiac arrest in this patient include high epidural block, aortocaval compression, light anesthesia, anesthetic overdose, and drug interaction. A less common cause of cardiac arrest would include a pulmonary embolus from either air or amniotic fluid. Aortocaval compression by the gravid uterus is a well documented cause of maternal hypotension especially when combined with profound sympathetic blockade from a high epidural block. However, it was believed that neither of these two factors played any part in the cardiac arrest as the epidural anesthesia was ineffective and the blood pressure was stable, both of which makes it unlikely that the two factors were related to the cardiac arrest. Furthermore, precautions had been taken to prevent aortocaval compression. It was felt that the catheter probably become dislodged from epidural space during transportation of the patient to the operating room. Light anesthesia can lead to an outpouring of catecholamines with consequent ventricular premature contractions, ventricular tachycardia, and finally ventricular fibrillation. However, the stability of the vital signs following induction and intubation made this sequence an unlikely cause of cardiac arrest. A drug reaction from inadvertent intravenous injection of the chloroprocaine solution was considered. This was considered an unlikely cause of the cardiac arrest as a drug reaction would be expected to occur within seconds of injection. Pulmonary embolus from either air or amniotic
fluid is rare and did not fit the clinical picture. Consequently it was suspected that the drug abuse contributed to the arrest. There is evidence from histochemical, biochemical, and pharmacologic studies that acute amphetamine administration leads to release of catecholamine from adrenergic nerve terminals both in the central nervous sytem and peripherally.w Experiments in dogs have shown that acute amphetamine intoxication significantly increases mean alveolar concentration (MAC) for h a l ~ t h a n eOn . ~ the otherhand, chronic administration of dextroamphetamine, 5 mg/kg/day for 7 days, decreases MAC for halothane by 21 f 5%' The latter was believed to be due to depletion of central nervous system catecholamines. The clinical implications are 2-fold in the chronic drug abuser. First, the patient's anesthetic drug requirements may be less than in a nonaddicted patient, should halothane be used; and, second, patients taking amphetamines may respond poorly to the usual doses of indirectly acting sympathomimetic agents. Our patient also had a history of heroin abuse, though the drug was used less frequently than the amphetamines. Hypotension in narcotic users is not unusual, with blood pressure levels as low as 50/20 torr even before induction of anesthesia. lo However, narcotic users seem to tolerate anesthesia well, and, in fact, may need higher doses of anesthetic agents than nonusers. During maintenance of anesthesia, hypotension may develop because of inadequate blood levels of narcotic or because of adrenal insufficiency." Preoperative or intraoperative administration of a narcotic will eliminate hypotension associated with narcotic withdrawal. Morphine has a depressive action on adrenocortical function and 17hydroxycorticosteroid blood values are decreased in opium addiction. It is likely that long-term narcotic useage may lead to adrenocortical suppression and impaired adrenal response to surgical stress.I2Should volume replacement, narcotics, and direct acting vasopressors fail to increase the blood pressure then hydrocortisone, 100 mg IV, may help to restore the blood pressure to normal levels. It was felt, but difficult to prove, that chronic catecholamine depletion played an important role in this patient's cardiac arrest. It is postulated that the sequence of events could have been as follows. The chronic use of amphetamine led to an inability to respond to the stress of induction of anesthesia. Thiopental induction of anesthesia led to an increase in venous capacitance, a decrease in pre-load, a decrease ANESTHESIA AND ANALGESIA VOI 58. NO 6, NOV-DW 1979
529
CLINICAL REPORTS
in cardiac output and thus to cardiac arrest. It may be that in the chronic drug abuser clinical assessment of function of the sympathetic system may be of value in detecting patients at risk from autonomic insufficiency. Symptoms and signs that point to abnormalities of the sympathetic system include orthostatic hypotension and failure of the pulse rate to increase when the patient assumes an erect position. Valsalva's maneuver or exhalation against a closed glottis in a patient with an abnormal sympathetic pathway will not show the usual increase in heart rate during the period of increased intrathoracic pressure; also the phenomenon of systolic and diastolic overshoot are absent.13
Pathouhvsiolwical and Clinical Considerations. Philadelphia, WB !5au~ders,-1973 4. Taylor G, Larson P Jr, Prestwich R: Unexpected cardiac arrest during anesthesia and surgery: an environmental study. JAMA
REFERENCES
10.Eiseman B, Lam RC, Rush B: Surgery of the narcotic addict. Ann Surg 159:748, 1964 11, Mark LC: Hypotension during anesthesia in narcotic addicts.
236:2758-2760,1976
5.
Carr LA, Moore KE: Norepinephrine release from brain by d-
.
amphetamine in vivo Science 164322-323, 1969 6. Hanson LCF: Evidence that the central action of (+)-amphetamine is mediated via catecholamines. Psychopharmacologia 10289-297, 1967 7. Sulser F, Owens ML, Howich
MR, et al: The relative role of storage and synthesis of brain norepinephrine in the psychomotor stimulation evoked by amphetamine or by desipramine and tetrabenazine. Psychopharmacologia 12:322-332,1968 8. Carlson A, Fuxe K, Hamberger B, et al: Biochemical and histochemical studies on the effects of imipramine-like drugs and (+)-amphetamine on central and peripheral catechoiamine neurons. Acta Physiol Scand 67481-497,1966 9 . Johnston RR, Way WL, Miller RD: Alteration in anesthetic requirement with amphetamines. Anesthesiology 34357-363, 1972
1. Albright G Anesthesia in Obstetrics: Maternal, Fetal and Neo-
natal Aspects. Menlo Park, CA, Addison Wesley Publishing co, 1978 2. Joyce TH: Anesthetic considerations in the high risk pregnancy. American Society of Anesthesiologists Refresher Courses, No 127,1978
3. Katz J, Kavin LB (eds) Anesthesia and Uncommon Diseases:
NY State J Med 662685, 1966 12. Tinckber-LF, Baratham: Opium addiction and surgery. Br Surg 53576, 1966
13. Melmon KL, Marelli HF: Clinical Pharmacology Basic Principles in Therapeutics. Second edition. New York, MacMillian Publishing Co, Inc, 1978, pp 163-166
Drug-Induced Disorders of Neuromuscular Transmission More than 30 drugs in current clinical use, other than those used in anesthesia, may interfere with neuromuscular transmission. The most common clinical presentation reported has been postoperative respiratory depression. Antibiotics, particularly those of the aminoglycoside group have been the drugs most frequently implicated, but many other drugs may interfere with neuromuscular transmission in the penanesthetic period. Unmasking or aggravation of myasthenia gravis is a second possible clinical presentation. In addition, several drugs may cause a reversible myasthenic disorder in patients with no evidence of a preexisting defect of neuromuscular transmission. Mechanisms of interference with neuromuscular transmission include either a direct effect on the various components of the neuromuscular junction or an immunologically mediated reaction directed against the motor end plate. Supportive therapy as appropriate, plus correction of associated abnormalitites (e.g., acid base, electrolyte) is advocated as the primary approach to treatment. In some circumstances, specific therapy may be indicated. (Argov Z, Mastaglia FL: Disorders of neuromuscular transmission caused by drugs. N Engl J Med 301:409-413,1979)
530
ANESTHESIA AND ANALGESIA Vol58, No 6 , Nov-Dec 1979
J
Cardiac Arrest during Cesarean Section in a Chronic Amphetamine Abuser Stanley I. Samuels, MB, BCh,* Aubrey Maze,MB, ChB,t and George Albright, MD* There has been general concern but little documentation among anesthesiologists that interactions between general anesthetic agents and drugs of abuse such as amphetamines may lead to sudden cardiovascular collapse.’.’ In fact a recent textbook commented on the fact that there were no case reports in the literature concerning abnormal reactions in amphet. ~ presamine users during anesthesia a n d s ~ r g e r yWe ent the case of a patient who sustained a cardiac arrest during cesarean section in which the primary cause of the arrest may have been due to chronic drug abuse.
Case Report A 27-year-old black gravida 5 para 3 was admitted to Stanford University Hospital at term and in active labor. Past medical history was significant in that she had been a drug abuser of many years standing. As far as could be ascertained the main drugs of abuse had been heroin and amphetamines. She denied any recent drug usage. She had had three low transverse cesarean sections in 1964, 1967, and 1973 under regional anesthesia without complication. Clinical examination was negative except for the presence of sclerosed veins in both arms, and a history of vomiting for 12 hours prior to admission to hospital. There were no clinical signs of dehydration. Continous epidural anesthesia was planned for the cesarean section. An epidural catheter was easily inserted at the W-L4 interspace. Following a test dose, 10 ml of lidocaine 2% with epinephrine 1/200,OOO was injected through the catheter and a T12 level of analgesia was obtained.
* Assistant Professor of Anesthesia.
t Assistant Professor of Anesthesia and Pediatrics. Received from the Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305. Accepted for publication August 14, 1979. Reprint requests to Dr. Samuels.
528
ANESTHESIA AND ANALGESIA Vol58. No 6. Nov-Dec 1979
About 45 minutes later the patient was transferred to the delivery room. Chloroprocaine 3%, 12 ml, without epinephrine was injected through the catheter in preparation for operation. Ten minutes later because of an inadequate level of analgesic block (T12) a second injection of chloroprocaine (6 ml of 3% solution) was given. No analgesic effect was noted. It was then decided to induce general anesthesia. Twenty minutes after the second injection of chloroprocaine general anesthesia was induced. At time of induction of anesthesia the systolic blood pressure was 100 torr, the pulse rate was 80 beats/min and the ECG showed sinus rhythm. Following left uterine displacement, preoxygenation, atropine (0.5 mg) and precurarization (curare 3 mg), thiopental, 200 mg, and succinylcholine, 100 mg, were injected intravenously, cricoid pressure was applied and endotracheal intubation performed. Following an easy intubation both lung apices moved well, equal breath sounds were heard bilaterally. The pulse rate was 110 beats/min and the systolic blood pressure was 120 torr. ECG showed sinus rhythm. Oxygen 2 L/min and nitrous oxide 4 L/min were begun together with positive pressure ventilation. The operation commenced immediately following intubation at which time it was noted that the patient’s tongue was dark in color and examination of the operating field disclosed the presence of very dark blood. Nitrous oxide was discontinued and the heart sounds which previously had been well heard via a precordial stethoscope disappeared. No pulse was felt in either the radial or carotid arteries and no blood pressure could be obtained. At this time both pupils were dilated and the ECG was a flat line. Cardiopulmonary resuscitation (CPR) was begun immediately using external cardiac massage. This produced a palpable carotid pulse. Drugs used for treatment of the cardiac arrest included sodium bicarbonate, 100 meq, epinephrine 1/1O,c00, 5 ml, isoproterenol hydrochloride infusion, 2 pg/min, and decadron, 8 mg. Sinus tachycardia occurred about 8 minutes after resuscitation and brachial blood pressure was palpable at 60 torr. Coincidental with the resuscitation, a healthy 3 kg male infant was delivered. The Apgar score at 1minute was 7. Fifteen minutes after CPR had commenced the pupils started to respond to light pulse and blood pressure returned to pre-induction values. Five minutes later the patient began to breathe spontaneously. An arterial blood sample obtained during the arrest showed pH 7.41, PCO, 27 torr, pHco, 17.0 meq/L, andPo, 77 torr. About 90 minutes after the onset of the cardiac arrest she was returned to the intensive care unit awake but disoriented. She was later extubated and vital signs remained stable. Two days later she elaborated on her drug history. She had been taking amphetamines since age 13 and had continued to take them both intravenously and orally up to time of her admission to the hospital. Her use of heroin was intermittent; she last took heroin about 7 days before hospital admission. Toxicologic analysis of her urine obtained the
CLINICAL REPORTS
day after her arrest showed levels of amphetamine and methamphetamine of 0.4 and 0.2 pg/ml, respectively. These figures indicated only that amphetamines had been taken; they do not indicate either when the last amphetamine was taken or the amount taken. The patient was discharged on the sixth postoperative day with no apparent sequelae from her cardiac arrest.
Discussion Unexpected cardiac arrest is one of the most dramatic and frightening events that can occur in the operating room. When it occurs in the delivery room during a cesarean section it becomes doubly threatening, for not one but two lives are threatened. Previous studies indicate that the incidence of cardiac arrest in the operating room vanes from 1/800 to 1/3,400 operation^.^ The paucity of articles in the literature on cardiac arrest in previously healthy obstetrical patients undergoing cesarean section indicates it is a rare occurrence. Possible causes for the cardiac arrest in this patient include high epidural block, aortocaval compression, light anesthesia, anesthetic overdose, and drug interaction. A less common cause of cardiac arrest would include a pulmonary embolus from either air or amniotic fluid. Aortocaval compression by the gravid uterus is a well documented cause of maternal hypotension especially when combined with profound sympathetic blockade from a high epidural block. However, it was believed that neither of these two factors played any part in the cardiac arrest as the epidural anesthesia was ineffective and the blood pressure was stable, both of which makes it unlikely that the two factors were related to the cardiac arrest. Furthermore, precautions had been taken to prevent aortocaval compression. It was felt that the catheter probably become dislodged from epidural space during transportation of the patient to the operating room. Light anesthesia can lead to an outpouring of catecholamines with consequent ventricular premature contractions, ventricular tachycardia, and finally ventricular fibrillation. However, the stability of the vital signs following induction and intubation made this sequence an unlikely cause of cardiac arrest. A drug reaction from inadvertent intravenous injection of the chloroprocaine solution was considered. This was considered an unlikely cause of the cardiac arrest as a drug reaction would be expected to occur within seconds of injection. Pulmonary embolus from either air or amniotic
fluid is rare and did not fit the clinical picture. Consequently it was suspected that the drug abuse contributed to the arrest. There is evidence from histochemical, biochemical, and pharmacologic studies that acute amphetamine administration leads to release of catecholamine from adrenergic nerve terminals both in the central nervous sytem and peripherally.w Experiments in dogs have shown that acute amphetamine intoxication significantly increases mean alveolar concentration (MAC) for h a l ~ t h a n eOn . ~ the otherhand, chronic administration of dextroamphetamine, 5 mg/kg/day for 7 days, decreases MAC for halothane by 21 f 5%' The latter was believed to be due to depletion of central nervous system catecholamines. The clinical implications are 2-fold in the chronic drug abuser. First, the patient's anesthetic drug requirements may be less than in a nonaddicted patient, should halothane be used; and, second, patients taking amphetamines may respond poorly to the usual doses of indirectly acting sympathomimetic agents. Our patient also had a history of heroin abuse, though the drug was used less frequently than the amphetamines. Hypotension in narcotic users is not unusual, with blood pressure levels as low as 50/20 torr even before induction of anesthesia. lo However, narcotic users seem to tolerate anesthesia well, and, in fact, may need higher doses of anesthetic agents than nonusers. During maintenance of anesthesia, hypotension may develop because of inadequate blood levels of narcotic or because of adrenal insufficiency." Preoperative or intraoperative administration of a narcotic will eliminate hypotension associated with narcotic withdrawal. Morphine has a depressive action on adrenocortical function and 17hydroxycorticosteroid blood values are decreased in opium addiction. It is likely that long-term narcotic useage may lead to adrenocortical suppression and impaired adrenal response to surgical stress.I2Should volume replacement, narcotics, and direct acting vasopressors fail to increase the blood pressure then hydrocortisone, 100 mg IV, may help to restore the blood pressure to normal levels. It was felt, but difficult to prove, that chronic catecholamine depletion played an important role in this patient's cardiac arrest. It is postulated that the sequence of events could have been as follows. The chronic use of amphetamine led to an inability to respond to the stress of induction of anesthesia. Thiopental induction of anesthesia led to an increase in venous capacitance, a decrease in pre-load, a decrease ANESTHESIA AND ANALGESIA VOI 58. NO 6, NOV-DW 1979
529
CLINICAL REPORTS
in cardiac output and thus to cardiac arrest. It may be that in the chronic drug abuser clinical assessment of function of the sympathetic system may be of value in detecting patients at risk from autonomic insufficiency. Symptoms and signs that point to abnormalities of the sympathetic system include orthostatic hypotension and failure of the pulse rate to increase when the patient assumes an erect position. Valsalva's maneuver or exhalation against a closed glottis in a patient with an abnormal sympathetic pathway will not show the usual increase in heart rate during the period of increased intrathoracic pressure; also the phenomenon of systolic and diastolic overshoot are absent.13
Pathouhvsiolwical and Clinical Considerations. Philadelphia, WB !5au~ders,-1973 4. Taylor G, Larson P Jr, Prestwich R: Unexpected cardiac arrest during anesthesia and surgery: an environmental study. JAMA
REFERENCES
10.Eiseman B, Lam RC, Rush B: Surgery of the narcotic addict. Ann Surg 159:748, 1964 11, Mark LC: Hypotension during anesthesia in narcotic addicts.
236:2758-2760,1976
5.
Carr LA, Moore KE: Norepinephrine release from brain by d-
.
amphetamine in vivo Science 164322-323, 1969 6. Hanson LCF: Evidence that the central action of (+)-amphetamine is mediated via catecholamines. Psychopharmacologia 10289-297, 1967 7. Sulser F, Owens ML, Howich
MR, et al: The relative role of storage and synthesis of brain norepinephrine in the psychomotor stimulation evoked by amphetamine or by desipramine and tetrabenazine. Psychopharmacologia 12:322-332,1968 8. Carlson A, Fuxe K, Hamberger B, et al: Biochemical and histochemical studies on the effects of imipramine-like drugs and (+)-amphetamine on central and peripheral catechoiamine neurons. Acta Physiol Scand 67481-497,1966 9 . Johnston RR, Way WL, Miller RD: Alteration in anesthetic requirement with amphetamines. Anesthesiology 34357-363, 1972
1. Albright G Anesthesia in Obstetrics: Maternal, Fetal and Neo-
natal Aspects. Menlo Park, CA, Addison Wesley Publishing co, 1978 2. Joyce TH: Anesthetic considerations in the high risk pregnancy. American Society of Anesthesiologists Refresher Courses, No 127,1978
3. Katz J, Kavin LB (eds) Anesthesia and Uncommon Diseases:
NY State J Med 662685, 1966 12. Tinckber-LF, Baratham: Opium addiction and surgery. Br Surg 53576, 1966
13. Melmon KL, Marelli HF: Clinical Pharmacology Basic Principles in Therapeutics. Second edition. New York, MacMillian Publishing Co, Inc, 1978, pp 163-166
Drug-Induced Disorders of Neuromuscular Transmission More than 30 drugs in current clinical use, other than those used in anesthesia, may interfere with neuromuscular transmission. The most common clinical presentation reported has been postoperative respiratory depression. Antibiotics, particularly those of the aminoglycoside group have been the drugs most frequently implicated, but many other drugs may interfere with neuromuscular transmission in the penanesthetic period. Unmasking or aggravation of myasthenia gravis is a second possible clinical presentation. In addition, several drugs may cause a reversible myasthenic disorder in patients with no evidence of a preexisting defect of neuromuscular transmission. Mechanisms of interference with neuromuscular transmission include either a direct effect on the various components of the neuromuscular junction or an immunologically mediated reaction directed against the motor end plate. Supportive therapy as appropriate, plus correction of associated abnormalitites (e.g., acid base, electrolyte) is advocated as the primary approach to treatment. In some circumstances, specific therapy may be indicated. (Argov Z, Mastaglia FL: Disorders of neuromuscular transmission caused by drugs. N Engl J Med 301:409-413,1979)
530
ANESTHESIA AND ANALGESIA Vol58, No 6 , Nov-Dec 1979
J
