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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.57 no.3 Campinas May/June 2007
Anesthesia in cocaine users*
Anestesia en el paciente usuario de cocaína
Ana LuftI; Florentino Fernandes Mendes, TSAII
Pós-Graduanda em Ciências Médicas da Fundação
Faculdade Federal de Ciências Médicas de Porto Alegre (FFFCMPA),
nível de Mestrado
IIDoutor em Medicina Faculdade de Ciências Médicas da Santa Casa de São Paulo; Professor de Anestesiologia da FFFCMPA
AND OBJECTIVES: Cocaine is the illicit drug most frequently associated with
death, and the anesthesiologist should be aware of the perioperative complications
of this drug in patients with acute intoxication or with a history of chronic
use. The knowledge of the neurophysiology, pharmacology, and physiopathological
consequences of cocaine abuse may facilitate the care of these patients. The
objective of this work was to review the information on cocaine and its interactions
CONTENTS: This paper discusses the pharmacology, physiopathological consequences of cocaine use, and its interactions with anesthesia.
CONCLUSIONS: The knowledge and early recognition of the complications associated with the use of cocaine are essential for the adequate management of cocaine users. The anesthesiologist should be prepared because both regional and general anesthesia carry significant risks in those patients.
Key Words: COMPLICATIONS: illicit drugs; DRUGS: cocaine.
Y OBJETIVOS: La cocaína es la droga ilícita más frecuentemente
asociada a decesos, y sus implicaciones perioperatorias en los pacientes agudamente
intoxicados o con historial de uso crónico necesitan ser muy bien conocidas
por los anestesiólogos. El conocimiento de la neurofisiología,
de la farmacología y de las consecuencias fisiopatológicas provenientes
del uso de la cocaína podrá facilitar el cuidado de esos pacientes.
El objetivo de este trabajo fue revisar las informaciones sobre la cocaína
y sus interacciones con la anestesia.
CONTENIDO: El artículo discute la farmacología de la cocaína, las consecuencias fisiopatológicas provenientes de su uso y las interacciones con la anestesia.
CONCLUSIONES: La comprensión y el reconocimiento precoz de las complicaciones asociadas al uso de la cocaína son esenciales para el manejo adecuado de pacientes usuarios de esa droga. El anestesiólogo debe estar preparado, pues tanto las anestesias regionales como la general presentan riesgos significativos en esos pacientes.
Several factors are responsible for the increase in cocaine use, including the ease of administration, availability, purity of the drug, reduction in costs, and the false perception that its use is safe. Cocaine is the illicit drug most frequently associated with death 1. Perioperative implications in patients with acute intoxication or chronic users are well known to the anesthesiologist. During the perioperative evaluation, a detailed history on drug abuse should be obtained. This evaluation will help planning the perioperative management and is an opportunity to reduce the anxiety about the surgery. The knowledge of the neurophysiological, pharmacological, and physiopathological consequences of cocaine use may facilitate the control of these patients during procedures requiring anesthesia.
The objective of this paper was to review the information on cocaine and its interactions with anesthesia.
The word crack has been used for a little over 15 years, but the use of cocaine products is very old. There are reports on the use of the leaves of the bush Erythoxylon coca (native to South America, in the Amazon region) on Peruvian tribes 2,000 years before the discovery of this continent. When chewed, the leaf releases low doses of cocaine, the active substance of the plant. In 1862, Schroff and Demarle observed that cocaine produced analgesia in the tongue and began to use it for the relief of laryngeal pain, contributing to popularize its use in England and the United States 2. During the 1880's, Freud undertook experiments with cocaine, using it in the treatment of opioid addiction. At the same time, Carls Koller, a Viennese ophthalmologist, introduced cocaine as a local anesthetic for ophthalmologic procedures. In 1898, several physicians used cocaine as a local anesthetic in spinal anesthesia 2.
In Europe, at the end of the 19th Century, since the aspiration of the white powder produced a greater effect, its consumption reached the proportion of an epidemic. In 1914, cocaine was prohibited in the Americas and Europe as a consequence of the complications associated with its use. The prohibition had important consequences, and its use only reappeared in the beginning of the 1970s, reaching a peak in 1985 in the United States, and five years later in Brazil 3. Studies to evaluate the abuse of drugs in Brazil showed that, since 1987, hospital admissions related to cocaine have been increasing. In the last five years it represents the second cause of hospital admission among the illicit drugs, supplanted only by alcohol 4-7.
Cocaine comes in two forms, hydrochloride (white power) and freebase (crack), made by the combination of the hydrochloride and alkali (sodium bicarbonate or ammonium). The hydrochloride can be dissolved in water and injected intravenously or, more commonly, used by inhalation.
Cocaine is a benzoylmethylecgonine; ecgonine is a tropine derivative, a component similar to atropine and scopolamine. It is the only naturally occurring local anesthetic 8. After intravenous administration, its plasma half-life varies from 60 to 90 minutes, but it can be longer after nasal or oral administration 9. When inhaled, it reaches the brain circulation in 6 to 8 seconds, and intravenously in 12 to 16 seconds. Its nasal use causes severe vasoconstriction, what limits absorption. The peak plasma concentration is achieved in 60 minutes and persists for up to 6 hours.
Approximately 80 to 90% of cocaine is metabolized. Metabolisms start in the plasma by hydrolysis of the ester radical; ecgonine methyl ester is the first metabolite, being degraded to bezoylecgonine, the main urine metabolite. Norcaide, another metabolite, is produced by demethylation in the liver through the cytochrome P450 system. From 1 to 5% of the active substance remain unchanged, and the metabolites are eliminated in the urine 6 to 14 hours after administration 2. Tests to detect the use of cocaine can be performed in the blood, urine, and hair. The urine toxicological test is the test of reference. It identifies the metabolite bezoylecgonine, which can be detected 4 to 48 hours after exposure to the drug 10.
The effects of cocaine can be explained by its action on several receptors. Cocaine blocks the reuptake of catecholamines in the sympathetic pre-synaptic receptors, resulting in accumulation of catecholamines in the synaptic cleft, and increased stimulation of receptor cells. The psychostimulating effect can be explained by its capacity to increase the levels of dopamine, norepinephrine, and serotonin in the brain 11. Cocaine exerts a local anesthetic effect by blocking the sodium channels in neurons, which blocks the transmission of nervous impulses. The systemic effects result from its ability to simultaneously increase the levels of catecholamines and to block its reuptake, leading to a continual antagonism of both alpha and beta receptors 12. The exposure to cocaine produces a myriad of signs and symptoms. Acute exposure can be associated with hyperthermia, hypertension, tachycardia, mydriasis, stupor, and respiratory and cardiac depression, and it can also inhibit the classical response to trauma and hemorrhagic shock. In the myocardial cell, it decreases the speed of depolarization, the amplitude and speed of conduction of the action potential, causing cardiac arrhythmias and sudden death 2-13. The use of cocaine brings a feeling of power and infatigability; in high doses, it causes agitation, insomnia, hallucination, and seizures 14. The chronic use is associated with the development of psychosis and paranoia 15. Both presentations of cocaine, the hydrochloride and free-base (crack), have a highly addictive potential.
The knowledge and early recognition of the cardiovascular complications related to cocaine are essential for their proper management. Studies in anesthetized animals suggest that the parenteral administration of cocaine induces the peripheral accumulation of norepinephrine and hypertension 16. However, recent studies in non-anesthetized humans showed that the hypertensive effect of inhaled cocaine is caused by a large increase in cardiac output coinciding with the peripheral constriction and direct sympathetic cardiac stimulation 16. Thus, the reason why beta-adrenergic antagonists may precipitate hypertensive crisis, which may lead to death, when used to treat cocaine toxicity is now known 12. The isolated use of beta-adrenergic antagonists may increase alpha agonist action, worsening the hypertension.
After acute administration, the rapid increase in blood pressure is associated with sudden death caused by subarachnoid hemorrhage and rupture of aortic aneurism 12. Ventricular tachycardia and sudden death with ventricular fibrillation have also been documented. The most common etiology is ischemia secondary to cardiac overload. In general anesthesia, the most frequent problem is severe hypertension, which occurs during induction, laryngoscopy, and tracheal intubation. Drugs, such as ketamine, that increase the levels of circulating catecholamines, and those that sensitize the myocardium to the actions of epinephrine, such as halothane, should be avoided or used with extreme caution.
Individuals admitted to emergency rooms with non-traumatic chest pain should be questioned about cocaine use. Aortic dissection and rupture, arrhythmias, myocarditis, and dilated cardiomyopathy should also be considered in patients complaining of thoracic pain 17,18. The association of cocaine, myocardial infarction (MI), and myocardial ischemia was noticed initially in 1982. The ECG in those patients may be abnormal even without patent ischemia (absence of MI). Forty-three percent of cocaine users with chest pain without myocardial infarction present electrocardiographic changes as criteria to start reperfusion treatment. Creatinophosphokinase is elevated in 50% of cocaine users without ischemia. This increase is probably secondary to rhabdomyolysis, and is not a good indicator of ischemia. The concentrations of serum troponin are more sensitive and specific to detect myocardial infarction. The pathogenesis of ischemia includes fixed or decreased oxygen myocardial delivery, vasoconstriction of the coronary vessels, both in normal and atherosclerotic segments, which is more pronounced in the latter. As a result, cocaine users with coronary heart disease are more prone to myocardial infarction, platelet aggregation, and thrombi formation. However, angiography in approximately half of cocaine users with myocardial infarction does not show evidence of atherosclerotic disease. The lethality of cocaine is related to the increase the maximal uptake of oxygen associated with coronary vasoconstriction. The myocardial demand of oxygen is increased, which may lead to ischemia or infarction. The vasoconstriction of coronary vessels occurs first by stimulation of alpha-adrenergic receptors and can be reversed by adrenergic antagonists, such as phentolamine, and exacerbated by beta-adrenergic antagonists, such as propranolol. Continual vasodilation, especially in the coronary vessels, and reduction in sympathetic cardiac activity may decrease the cardiac morbidity related to cocaine 16. Coronary artery vasoconstriction can be caused both by cocaine and its metabolites, explaining why ischemia or infarction may occur several hours after cocaine use. First line agents recommended for the treatment include oxygen, aspirin, nitroglycerine, and benzodiazepines. And, as second line agents, verapamil, phentolamine, thrombolityc agents, or primary angioplasty 17. In animal models, calcium channel blockers increase cocaine toxicity and its use is questionable 19. Labetolol, which has alpha and beta-blocking properties, reverts the hypertension caused by cocaine, but has no demonstrable effect on coronary vasoconstriction. The antagonism of beta-adrenergic receptors is greater than its effects on alpha-adrenergic receptors 20. For this reason, one should avoid using propranolol. The association between cocaine and tobacco can exacerbate the effects of cocaine on myocardial oxygen supply and demand by increasing cardiac frequency and systemic blood pressure and decreasing the caliber of diseased coronary arteries 21. Alcohol and cocaine, which produce the metabolite cocaethylene that also blocks the reuptake of dopamine in the synaptic cleft, potentiating the systemic effects of cocaine, is another combination that frequently causes death.
The chronic use of cocaine can cause left ventricular hypertrophy, systolic dysfunction, dilated cardiomyopathy, and myocardial depression. Several arrhythmias and conduction defects related to cocaine use have been reported, but the arrhythmogenic potential of the drug has not been defined. Being a sympathicomimetic agent, it increases ventricular irritability and decreases the fibrillation threshold 17. Bacterial endocarditis is another risk associated with the use of this drug (venous access, contaminants, increased heart rate, and hypertension, which cause valvular and vascular dysfunction, predisposing to bacterial invasion) 22. Despite the severe hypertension that might follow anesthetic induction and tracheal intubation, several anesthesiologists prefer to use general anesthesia due to the possibility of increased toxicity of local anesthetics and relative hipovolemia related to the chronic use of cocaine, as well as thrombocytopenia 23. Due to the severe vasoconstriction associated with the use of this drug, patients with severe trauma associated with hipovolemia may have normal mean arterial pressure. Hypotension seems to be more pronounced with spinal anesthesia, and the response to ephedrine is reduced secondary to the depletion of norepinephrine stores 11. This effect is analogous to the tachyphylaxis that occurs after repeated doses of ephedrine. Low doses of phenilephrine usually restore blood pressure to normal levels 24. The reduction in platelet count with chronic cocaine use has been described; if the individual uses other drugs, such as alcohol and opioids, which are also associated with thrombocytopenia, one should request a platelet count 23,25. Several theories have tried to explain the thrombocytopenia induced by cocaine. Elevated catecholamine levels, such as norepinephrine, cause direct arterial vasoconstriction; alpha-adrenergic agonists bind to receptors on the platelets, activating them and, in theory, the combination of arterial vasospasm and platelet activation increases the risk of thrombocytopenia in cocaine users. Other possible etiologies include bone marrow depression, autoimmune response with antiplatelet antibodies, hypersplenism, chronic hepatitis, sepsis, and AIDS 26.
Cocaine could also precipitate seizures. They might be secondary to acute hyperthermia, to an increase in muscular activity, and to the severe vasoconstriction that hinders dissipation of body heat 27. Animal studies demonstrated that cocaine a dose-dependent effect on the thermoregulator center in the hypothalamus, causing significant changes in body temperature 28,29. There might be ischemic or hemorrhagic strokes secondary to vasospasm, thrombosis of the cerebral artery, and vasculitis, or by rupture of an aneurysm or vascular malformations 30-33.
Cocaine increases the effects of local anesthetics, which might lead to intoxication. Regional anesthesia with high doses of local anesthetics should be avoided, since it is impossible to predict a safe dose 11. Seizures related to cocaine use are resistant to gabaergic and antiseizure drugs that exert their effects through sodium or calcium channels. Traditional antiseizure drugs, such as benzodiazepines, barbiturates, phenytoin, and inhalational anesthetics, have proved ineffective in the treatment of cocaine-induced seizures. The physiological changes related to cocaine can be treated with a2-adrenergic agonists, such as dexmedetomidine and clonidine, with peripheral a1-antagonists, such as phentolamine, with hydration, and with benzodiazepines 18.
Pulmonary complications secondary to cocaine use affect approximately 25% of the individuals, varying from asthma exacerbations to fatal pulmonary hemorrhage 34. Epistaxis, perforation of the nasal septum, oropharyngeal ulcers secondary to vasoconstriction and ischemic necrosis, are frequent in the respiratory tract 34.
As a direct irritant of the airways, cocaine damages bronchial epithelial cells, stimulating and exposing vagal receptors, causing severe bronchospasm, and exacerbating asthma 35-37. In the lungs, cocaine impairs the function of alveolar macrophages and the production of cytokines, which might result in immunosuppression and infectious complications 38. The activation of polymorphonuclear cells, resulting in sudden inflammation, might also occur 39. Sustained inhalation might cause pneumothorax and pneumomediastinum, and could be associated with a reduction in pulmonary diffusion, possibly due to the vasoconstriction of pulmonary capillaries 12. Non-cardiogenic pulmonary edema due to endothelial toxicity, with increased cellular permeability, might occur 34,35,39 and the increase in vascular resistance might cause acute left ventricular failure, resulting in cardiogenic pulmonary edema 2.
Among the gastrointestinal complications in cocaine users are acute ischemia secondary to severe arterial vasoconstriction and reduction in blood flow secondary to the stimulation of a-adrenergic receptors, which could lead to duodenal ulcer and perforation, usually three days after the exposure to the drug. Its anticholinergic action causes hypomotility, an increase in gastric emptying, and prolonged exposure to gastric acid, which contributes to ulcer formation 40.
Cocaine abuse is particularly problematic in obstetrics. Its use during pregnancy is associated with obstetric and anesthetic emergencies. Pregnancy increases the cardiovascular toxicity of cocaine. In pregnant women, uterine blood flow is decreased during the exposure to cocaine. Hydralazine is used for the treatment of maternal hypertension, but it has not been demonstrated that it restores uterine blood flow 41. It can be very difficult to differentiate convulsions caused by cocaine in pregnant women with eclampsia and preeclampsia. The combination of hypertension, proteinuria, and seizures secondary to the acute use of cocaine can be mistaken by eclampsia, and laboratory exams are necessary to make the differential diagnosis 42. The management of these patients includes treatment with magnesium sulfate. Parturients undergoing cesarean sections frequently complain of pain during the surgery, even under adequate regional anesthesia, and need complementary analgesia with opioids 11.
Prolonged response to succinylcholine can also be observed in chronic cocaine users, with low levels of pseudocholinesterase. In the acute intoxication, cocaine competes with succinylcholine for metabolism by pseudocholinesterase, decreasing the metabolism of both 43. The choice of anesthetic technique should be individualized, taking into consideration the several clinical manifestations of acute and chronic cocaine abuse.
Cocaine exerts its effects in several receptors and by several mechanisms, and it is difficult to predict how it will interact with drugs that act on the central nervous system and cardiovascular system. The understanding and early recognition of complications are essential for the adequate management. Both general and regional anesthesia have significant risks, and the anesthesiologist should be prepared to adequately manage these patients.
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Dra. Ana Luft
Rua Osmar Amaro de Freitas, 200 Jardim Itu Sabará
91210-130 Porto Alegre, RS
em 11 de maio de 2006
Accepted para publicação em 24 de janeiro de 2007
* Received from Serviço de Anestesia Santa Casa, CET/SBA Faculdade de Ciências Médicas de Porto Alegre