ANESTHESIA AND THE DRUG-ABUSING PARTURIENT

THE HIGH-RISK OBSTETRIC PATIENT

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ANESTHESIA AND THE DRUGABUSING PARTURIENT David J. Birnbach, MD

DRUGABUSEANDTHEPARTURIENT

The drug-abusing parturient presents many challenges to the anesthesiologist. The unusual and clinically challenging situations that may arise in this patient population may be due to many factors including failure on the part of many of these patients to receive medical treatment during pregnancy, the effects of illicit drug use, unstable home environment, poor diet, and the presence of untreated co-existing disease. The absence of prenatal care has been shown to be a major factor in the outcome of these patients.I5 Substance abuse in pregnancy has emerged as a major public health problem of the 1 9 9 0 Because ~~ of this, obstetricians, pediatricians, and anesthesiologists are now encountering an increasing number of pregnant patients who use illicit substances. In particular, cocaine use during pregnancy in the United States has increased dramatically during the past decade.76 Although it has been suggested that substance abuse may be on the decline in the United States, illicit substance abuse among women of childbearing age continues to be a major problem. Reports on the growing numbers of pregnant patients who are using illicit drugs has increased throughout the world. Chasnoff et a1 reported that almost 15%of pregnant women in one patient population in the United States had a positive urine toxicology screen for cocaine, marijuana, alcohol, or heroin.I4Multiple drug use is not un~ommon.~ A recent study which examined the drug use patterns of pregnant women in two inner city sites found that women who used cocaine were much more likely to have used a combination of drugs? Recent data suggest that consumption of illicit drug use is also a problem in Europe, with reports from Italy’6,%; Spain56;Amsterdam-; and Eastem Europe.” The use of illicit drugs in pregnant patients can present very difficult challenges to the anesthesiologist. For example, the management of a

From the College of Physicians and Surgeons of Columbia University; and the Department of Anesthesiology, St. Luke’s-Roosevelt Hospital Center, New York, New York ANESTHESIOLOGY CLINICS OF NORTH AMERICA VOLUME 16 * NUMBER 2

JUNE 1998

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drug-abusing patient admitted in preterm labor with massive hemorrhage (due to abruptio placentae), fetal distress, and maternal cardiac arrhythmias who is to undergo an emergency cesarean section would present a challenge to even the most seasoned practitioner. The substance-abusing pregnant patient may also require surgery due to an acute injury. Reports indicate that recent substance abuse was documented in 48% of all injury deaths to pregnant patients in New York.Is Although all high-risk patients should be questioned regarding the use of illicit drugs, self reporting of drug abuse by pregnant patients underestimates actual use as determined by laboratory t e ~ t i n g ? Among ~,~ patients who do abuse illicit substances, polydrug use is the rule rather than the exception6with narcotics, amphetamines, marijuana, alcohol, and cigarettes all being COCAINE

Cocaine has been described as a major public health threat in the United States. The use of cocaine has increased dramatically, to the point where more than five million Americans abuse this drug regularly.ffiThe prevalence of cocaine in the obstetric population has dramatically increased during the past decade and has resulted in a variety of maternal and perinatal complication^.^^ Positive cocaine toxicology results have been reported in pregnant patients from all geographic, socioeconomic, and cultural groups. Because many cocaineabusing patients deny drug abuse7 the exact extent of perinatal cocaine use is unknown. It has been estimated, however, that a large number of high-risk women cared for at many urban hospitals in the United States may be using cocaine.@Although patients who do not receive prenatal care tend to have the highest rates of cocaine use, registered private patients in suburban settings have also been found to be cocaine positive.81Although comprehensive care of the cocaine-abusing parturient appears to be associated with improved outcomes, prenatal care appears to be the primary factor and is associated with improved outcomes, even if not specialized or linked to drug treatment.15 The Effects of Cocaine Use

Cocaine (benzoylmethylecgonine,C17H21N04) is an alkaloid derived from the plant Eythroxylon coca which is indigenous to Peru, Bolivia, and Ecuador?6 The alkalinized form of cocaine, which can be smoked, is known as "crack and is presently widely used in the United States.33The pharmacologic effects of cocaine are mediated through the norepinephrine, dopamine, and serotonin neurotransmitter systems.30By blocking the presynaptic reuptake of norepinephrine, cocaine produces an accumulation of this neurotransmitter and the side effects including hypertension, tachycardia, and vasoconstriction. This effect has been seen in the human uterus.% One of the most difficult aspects of medical care for the cocaine-abusing parturient is recognition of their cocaine use. A majority of cocaine abusers deny drug use when interviewed by physicians, and physical examination may be misleading due to difficulty in differentiatingbetween preeclampsia and cocaine use.1z*89 Lack of prenatal care and cigarette smoking have been shown to be of predictive value in the recognition of a cocaine abuser and some authors have suggested that some of the fetal effects of cocaine may actually be due, at least in part, to other factors including lack of prenatal care, cigarette smoking, and

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poor nutrition.59It has also been suggested that the abuse of cocaine to the exclusion of other drugs is probably so rare that most cocaine users are polydrug abusers who also use cocaine.39 Perinatal cocaine abuse has been linked to many maternal complications such as placental abruptionZ1,3; pneum~thorax~; uterine ruptureN,60; preterm laborlo;renal failure50;hepatic rupture61; and cardiac dy~rhythmias.'~ It has been suggested that pregnancy causes an increased sensitivity to the cardiovascular effects of c0caine.9~Studies in pregnant and non-pregnant animals treated with progesterone to produce pregnancy levels have suggested that the metabolism of cocaine could be altered by the pregnant state.n Fetal complications of maternal cocaine abuse include intrauterine fetal demises5;congenital abnormalities"; and fetal myocardial ischemia.58 There is now adequate data to demonstrate that cocaine use in pregnancy is dangerous to both mother and Even after confounding variables such as age, race, alcohol abuse, and smoking are taken into account, these complications are still seen and are due to the vasoconstriction of uterine and umbilical vessels. There is evidence that cocaine may have a direct effect on several biochemical processes in the placenta.28The interaction of cocaine with the human placental serotonin transporter has been investigated and it appears that the function of the placental serotonin transporter may be severely impaired by maternal use of cocaine during pregnancy.74Cocaine is rapidly transferred across the placenta by simple diffusion without metabolic c o n ~ e r s i o n The .~~ effects of maternal cocaine use are thought to be incremental and cumulative, although it has been reported that the erratic use of cocaine in pregnancy results in perinatal complications that are as severe as those occurring with daily binging." The American College of Obstetrics and Gynecology has recognized that cocaine use has become a major public health concern and has published a committee opinion which reviews the complications of cocaine abuse in pregnancy.' They report that the medical complications which are found in association with cocaine use include the following: acute myocardial infarction; cardiac arrhythmias, including life-threatening ventricular arrhythmias; rupture of the ascending aorta; stroke; seizures; bowel ischemia; hyperthermia; malnutrition; sexually transmitted diseases; and hepatitis. s

Laboratory Testing for Cocaine

Current laboratory screening methods for cocaine metabolites include gas chromatography, mass spectrometry, and radioimmunoassay. The difficulty with some of these laboratory tests is the lag time between sending the sample and the reporting of results. In some hospitals, it may take several days to receive mass spectrometry toxicology results and, therefore, these results may be of little benefit to the anesthesiologist. Although the reliability of urine testing depends on the time since the last exposure to the cocaine and the pharmacokinetics, alternative testing methods are available. An instant latex agglutination test for cocaine metabolites (OnTrak Assay@,Roche Diagnostic Systems, Branchburg, NJ) can provide an accurate result within 4 minutes and has been shown to be highly sensitive and specific when used by anesthesiologist^.^ Recent studies have evaluated the use of newborn meconium and maternal hair and have found that they can greatly improve detection of cocaine use in pregnancy?z,48.69

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Anesthetic Management

Because cocaine-abusingpatients have a higher incidence of cesarean section due to fetal distress,” 45 anesthesiologists often meet these patients in an emergency setting. The choice of anesthetic may be dictated by the hemodynamic consequences of cocaine use. Severe hypertension often occurs as a result of the vasoconstriction. Severe hypotension, however, may occur as a result of hemorrhage or myocardial dysfunction. General endotracheal anesthesia is usually selected for the profoundly hypotensive parturient. In more controlled situations, however, the anesthesiologist should choose the anesthetic technique based on the risks and benefits of regional and general anesthesia in each individual patient. Epidural or spinal anesthesia may be successfully used to 45 Recently reported anesthetize the cocaine-abusingpatient for cesarean ~ection.~, data on life-threatening events that occurred under anesthesia in the cocaineabusing parturient showed that severe hypertension and arrhythmias were more common during general anesthesia than during regional ane~thesia.~ Since severe hypertension occurred most often after laryngoscopy, blood pressure should be controlled prior to intubation. Beta blockade using propranolol to control blood pressure in the cocaineabusing patient is relatively contraindicated, since beta blockade may cause unopposed alpha adrenergic stimulation and, therefore, worsen the hypertension.” In addition, beta blockade has been reported to enhance cocaine-induced coronary vasoconstriction.51An evaluation of hydralazine for the treatment of hypertension in cocaine-positive patients has concluded that hydralazine resulted in profound maternal tachycardia and did not restore uterine blood fl0w.9~ Hughes et a137compared hydralazine to labetalol and concluded that ”labetalol may be preferable to hydralazine for treatment of the acutely cocaine-intoxicated parturient.” Hollander, however, suggested that labetalol should not be used in cocaine-abusing patients, since the beta antagonistic effects are more potent than the alpha effects and in animal studies labetalol increased seizure activity and mortality.36Calcium channel blockers have been found to be ineffective in treating or preventing cocaine toxicity in animals, but human research is 0ngoing.9~ Sodium bicarbonate appears to have an important role in the acute setting of cocaine abuse.93This may be due to the metabolic and respiratory acid-base abnormalities which are often associated with cocaine Nitroglycerin has been found to be safe and possibly effective in the treatment of cocaine associated chest pain.35Despite theoretical concerns that lidocaine may enhance cocaine toxicity, lidocaine has been used to treat arrhythmias in cocaine-abusing patients and has not been associated with significant cardiovascular or central nervous system toxicity!2 Signs of CNS hyperexcitability can be treated with a benzodia~epine.9~ Cocaine is an arrhythmogenic agent. Arrhythmias which have been reported after cocaine use include sinus tachycardia, ventricular premature contractions, ventricular tachycardia, ventricular fibrillation, and asystole.63Because of the high risk for development of arrhythmias, in the event that a general anesthetic becomes necessary, any agent such as halothane, which sensitizes the myocardium to the effects of catecholamines, should be avoided.8 Although isoflurane has been administered to cocaine-abusing patients without problem, it has been reported that cocaine toxicity during isoflurane anesthesia is associated with a marked increase in systemic vascular resistance and a tendency to produce cardiac arrhythmia^.^ Ketamine should be used with extreme caution in the cocaine-abusing patient since it may potentiate the cardiac effects of cocaine by further increasing catecholamine levels.62 There has also been a report of a

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prolonged block from succinylcholine in a cocaine-abusing patient, so caution should be taken if using this muscle relaxant.42Patients with a history of chronic cocaine use need to be monitored preoperatively, intraoperatively, and postoperatively for signs of myocardial ischemia. Cocaine toxicity is often seen many hours after its administration, pointing to a potential role of cocaine metabolites in toxicity.80 The use of regional anesthesia in the cocaine-abusing parturient may also be associated with life-threatening risks7 Thrombocytopenia has been reported as being associated with cocaine abuse@and, therefore, there may be a risk of epidural hematoma. Profound hypotension may occur after achievement of a sympathetic block and the cocaine-abusing patient may not respond appropriately to ephedrine: Should these patients develop ephedrine-resistant hypotension, they do respond to small doses of phenylephrine. AMPHETAMINE ABUSE

The amphetamine drugs are sympathomimetics that have the potential to cause profound central nervous system stimulation. These drugs may be abused by themselves or in conjunction with other drugs. Acute administration of amphetamines produces signs and symptoms similar to and as with As cocaine these symptoms may be mistaken for preeclampsia or e~lampsia.2~ with cocaine, amphetamines may precipitate fetal distress and necessitate emergency cesarean section. The acute ingestion of amphetamines increases the dose requirements for general anesthetic agents, whereas the chronic ingestion of these drugs causes a decrease in minimal alveolar concentration (MAC) of volatile agents.“ Since it is often difficult to differentiate between chronic and acute use, it is prudent to titrate doses of anesthetic to effect. As with cocaine, agents such as halothane which have been found to sensitize the myocardium to catecholamines, should be avoided in the patient who has taken amphetamines. Although regional anesthesia has been safely used in these patients, severe hypotension may occur and the response to pressor agents is unpredictable. Reports of cardiac arrest in amphetamine-abusingpatients undergoing cesarean section under general79and regionals6anesthesia have appeared in literature. NARCOTIC ABUSE

The abuse of heroin, morphine, meperidine, and methadone have all been reported in pregnant patients and it has been estimated that 250,000 women in the United States are intravenous drug abusers, with 90% of them being of childbearing Perinatal abuse of narcotics may be associated with numerous medical problems including AIDS; hepatitis; endocarditis; and pulmonary, renal, and cardiac disease?” Acute withdrawal syndrome may be recognized by tremors, anxiety, muscle pains, nausea, vomiting, anorexia, gastrointestinal pain, tachycardia, hypertension, and mydriasis. These signs peak at 48 to 72 hours after the last narcotic intake. The use of narcotic antagonists or agonistantagonist drugs may precipitate acute withdrawal and, therefore, should not be used in these patients?’ Recognition of maternal withdrawal is essential when treating an opioid-abusing patient. Withdrawal symptoms include yawning, lacrimation, rhinorrhea, diarrhea, dehydration, fever, and sweating. These sympt o m usually begin approximately 12 hours following the last opioid dose and have been treated with clonidine or narcotics.” To prevent withdrawal in a

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known opioid-abusing patient, the patient's daily narcotic dose should be calculated and administered as a minimum daily requirement, irrespective of additional considerations such as labor pain Narcotic overdose can be identified by coma, miosis, or respiratory depression. When treating the parturient with a narcotic overdose with a diminished mental status, the airway should be secured immediately to decrease the risk of aspiration. Anesthetic Management

Regional anesthetic techniques can provide a comfortable patient without the need for narcotic administration. The narcotic-abusing patient may have a pain intolerance due to decreased level of endogenous opioid peptides and, therefore, may be intolerant of the pain of labor. In the rehabilitated narcotic abuser, the use of a regional anesthetic allows for a comfortable patient without the administration of opioids. Local anesthetics can also be used for postoperative pain management in these patients. ALCOHOL ABUSE

It has been estimated that there are over 15 million alcoholics in the United States and that approximately one fourth of them are women.92Alcohol abuse has been associated with cardiomyopathy, decreased albumin concentration, coagulopathy, liver disease, ascites, and electrolyte abnormalities. Alcohol is a known teratogen and alcohol use in pregnancy is associated with fetal alcohol ~ y n d r o r n eSigns . ~ ~ and symptoms of this syndrome include craniofacial, cardiac, renal, and musculocutaneous abnormalities. Children with complete fetal alcohol syndrome are usually born to mothers who consume large amounts of alcohol throughout pregnancy. However, because a safe level of alcohol intake in pregnancy has not been established, abstinence is considered the safest course during ~regnancy.'~ Anesthetic Management

In the absence of a coagulopathy or neuropathy, alcoholics can be safely anesthetized using a regional anesthetic. Occasionally, regional techniques in these patients may fail due to psychotic or combative behavior. Should these patients require a general anesthetic, a major consideration is prevention of aspiration since alcohol both increases gastric acid secretion and decreases protective reflexes. Because these patients may present with severe hypoalbuminemia or cardiac manifestations of alcohol abuse, they may be sensitive to the effects of myocardial depressant anesthetics.It is commonly believed that chronic alcoholic patients require more intravenous barbiturates than normal for induction of general anesthesia.= When this was investigated, however, it was found that chronic alcohol intake did not alter the requirement, pharmacokinetics, or pharmacodynamics of thiopental for induction of general anesthesia.@ CIGARElTES

Tobacco is still the most commonly abused drug during pregnancy. It has been suggested that 15%of low-birth-weight cases could be prevented if women

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did not smoke during pregnancy.83In 1990, it was estimated that 29% of American women of childbearing age smoked cigarettes." Despite the fact that there is no longer any doubt that cigarette smoking has adverse effects on mother and fetus, only 20% of women in the United States quit smoking during pregnancy." Smoking during pregnancy has been associated with intrauterine growth retardation, spontaneous abortion, premature rupture of membranes, placenta 46 The chemical previa, abruptio placentae, and sudden infant death syndrome.25, composition of cigarette smoke is more closely related to reduction in fetal growth than the number of cigarettes smoked. The effects of smoking could be due to any of the numerous chemical substances in tobacco smoke, but apart from carbon monoxide and nicotine, little is known about the effects of other toxins which number almost 1000. Nicotine can decrease placental blood flow due to vasoconstriction." Because of the fetal risks of maternal cigarette smoking, it has been suggested that nicotine replacement therapy be used on pregnant cigarette smokers? The respiratory effects of cigarette smoke include abnormalities in mucus secretion, ciliary transport, and small airway function.70Postoperative respiratory morbidity is, therefore, a risk of general anesthesia in cigarette smoking patients. Although 4 to 6 weeks of abstinence is required to allow a decrease in the risk of postoperative respiratory complications, after as little as 48 hours of abstinence carboxyhemoglobin levels fall and oxygen delivery increases. In addition, a few days of abstinence will improve mucociliary transport. The use of regional anesthesia is particularly beneficial to the cigarette smoking patient undergoing cesarean section by allowing an alternate to general anesthesia and the risk of bronchospasm that may develop during airway manipulation. CONCLUSION

Substance abuse continues to be a problem in the parturient and physicians can be expected to encounter increasing numbers of obstetric patients who are victims of substance abuse. Substance-abusing women are a diverse group and, contrary to popular stereotypes, alcohol and drug abusers are seen among poor and non-poor people and among white people and people of It is clear that illicit substances have a multitude of negative effects on the mother and fetus and that the signs and symptoms of substance abuse may be confused with other disease states. It is vital for the anesthesiologist to be able to recognize and treat these patients and to consider the possibility that any behavioral or hemodynamic abnormalities may be due to illicit drug use. References 1. ACOG Committee Opinion: Committee on Obstetrics: Maternal and Fetal Medicine Number 114. Int J Gynaecol Obstet 41:102-105, 1993 2. Bendrsky M, Alessandri S, Gilbert P, et al: Characteristics of pregnant substance abusers in two cities in the northeast. Am J Drug Alcohol Abuse 22:349-362, 1996 3. Benowitz NL: Nicotine replacement therapy during pregnancy. JAMA 266:3174-3177, 1991 4. Bemasko JW,Brown G, Mitchell JL, et al: Spontaneous pneumothorax following cocaine use in pregnancy. Am J Emerg Med 15:107, 1997 5. Birnbach DJ, Stein DJ, Grunebaum A, et a1 Detection of multiple drug use in high risk patients using a new screening assay [abstract]. Anesthesiology 87A892, 1997

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6. Birnbach DJ, Stein DJ, Grunebaum A, et al: Cocaine screening of parturients without prenatal care: An evaluation of a rapid screening assay. Anesth Analg 84:76-79, 1997 7. Birnbach DJ, Stein DJ, Thomas K, et a1 Cocaine abuse in the parturient: What are the anesthetic implications? Anesthesiology 79:A988, 1993 8. Birnbach DJ: Cardiovascular disease in the pregnant patient A new risk factor. Cardiovasc Risk Factors 4:28-33, 1994 9. Boylan JF, Cheng DC, Sandler AN, et a1 Cocaine toxicity and isoflurane anesthesia: Hemodynamic, myocardial metabolic, and regional blood flow effects in swine. J Cardiothorac Vasc Anesth 10:772-777, 1996 10. Buehler BA: Cocaine. How dangerous is it during pregnancy? Neb Med J 80:116-117, 1995 11. Burkett G, Yasin SY, Palow D, et a1 Patterns of cocaine binging: Effect on pregnancy. Am J Obstet Gynecol 171:372-378, 1994 12. Campbell D, Parr MJ, Shutt LE: Unrecognized "crack cocaine abuse in pregnancy. Br J Anaesth 77553-555, 1996 13. Chao CR: Cardiovascular effects of cocaine during pregnancy. Semin Perinatol20:107114, 1996 14. Chasnoff IJ, Landress HJ, Barrett ME: The prevalence of illicit drug or alcohol use during pregnancy and discrepancies in mandatory reporting in Pinellas County, Florida. N Engl J Med 322:1202-1206, 1990 15. Chazotte C, Youcah J, Freda MC: Cocaine using during pregnancy and low birth weight: The impact of prenatal care and drug treatment. Semin Perinatol 19293-300, 1995 16. Chiarotti M, Strano-Rossi S, Offidani C, et al: Evaluation of cocaine use during pregnancy through toxicological analysis of hair. J Anal Toxic01 20:555-558, 1996 17. Council on Scientific Affairs, American Medical Association: Fetal effects of maternal alcohol use. JAMA 249(18):2517-2521, 1983 18. Dannenberg AL, Carter DM, Lawson HW, et al: Homicide and other injuries as causes of maternal death in New York City, 1987-1991. Am J Obstet Gynecol 172:1557-1564, 1995 19. Davis RB: Drug and alcohol use in the former Soviet Union: Selected factors and future considerations. Int J Addict 29:303-323, 1994 20. Derlet RW, Tseng CC, Albertson TE: Cocaine toxicity and the calcium channel blockers nifedipine and nimodipine in rats. J Emerg Med 12:14, 1994 21. Dombrowski MP, Wolfe HM, Welch RA, et a1 Cocaine abuse is associated with abruptio placentae and decreased birth weight, but not shorter labor. Obstet Gynecol 77139-141, 1991 22. Economides D, Braithwaite J: Smoking pregnancy and the fetus. J R SOCHealth 114:198-201, 1994 23. Edwards R: Anaestesia and alcohol. Br Med J 291:423-424, 1985 24. Eliot RH, Rees GB: Amphetamine ingestion presenting as eclampsia. Can J Anaesth 37130-133, 1990 25. Feng T: Substance abuse in pregnancy. Curr Opin Obstet Gynecol5(1):16-23, 1993 26. Fleming JA, Byck R, Barash PG: Pharmacology and therapeutic applications of cocaine. Anesthesiology 73518-531, 1990 27. Frank DA, Zuckerman BS, Amaro H, et a1 Cocaine use during pregnancy: Prevalence and correlates. Pediatrics 82:88%895, 1988 28. Ganapathy V, Ramamoorthy S, Leibach FH: Transport and metabolism of monoamines in the human placenta. Trophoblast Res 735-51, 1993 29. Gold MS, Pottash AL, Extein I, et a1 Clonidine in acute opiate withdrawal. N Engl J Med 302:1421-1422, 1980 30. Gold MS, Washton AM, Dackis CA: Cocaine abuse: Neurochemistry, phenomenology, and treatment. Natl Inst Drug Abuse Res Monograph Ser 61:130-150,1985 31. Goldberg ME Substance-abusing women: False stereotypes and real needs. Soc Work 40789-798, 1995 32. Grant T, Brown Z , Callahan C, et al: Cocaine exposure during p ~ g n a n c y Improving : assessment with radioimmunoassay of maternal hair. Obstet Gynecol83524-531,1994

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