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Print version ISSN 0034-7094On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.56 no.2 Campinas Mar/Apr. 2006
Anesthesia and the Ecstasy user*
Anestesia y el usuario de Ecstasy
Eduardo Toshiyuki Moro, TSA, M.D.I; Alexandre A. Fontana Ferraz, TSA, M.D.II; Norma Sueli Pinheiro Módolo, TSA, M.D.III
do CET/SBA do Conjunto Hospitalar de Sorocaba, PUC/SP. Pós-Graduando em
Anestesiologia da FMB - UNESP, Nível de Mestrado
IIInstrutor do CET/SBA do Conjunto Hospitalar de Sorocaba, PUC/SP
IIIProfessora Adjunta Livre-Docente do Departamento de Anestesiologia da FMB - UNESP
AND OBJECTIVES: The number of new users of illicit substances has been growing
steadily all over the world over the last few years. Marijuana and cocaine have
been mentioned most often, but the last few years saw a marked increase in the
number of users of other psychostimulants or hallucinogens, taken with the aim
of intensifying social experiences. The aim of this article is to discuss the
clinical presentation, the damaging effects and the potential interactions with
anesthesia of the surgical patient who is a user of these illicit substances.
CONTENTS: The article discusses the action mechanisms, the clinical presentation, the damaging effects and the potential repercussions observed during anesthesia in users of MDMA (3,4-methylenedioxymethamphetamine), also known as Ecstasy.
CONCLUSIONS: Anesthesiologists should be made aware of the clinical presentation and the damaging effects brought about by 3,4 - methylenedioxymethamphetamine (Ecstasy), as well as the potential interactions with anesthesia, since people who use these substances may find themselves in surgery many times, either due to an emergency situation or by choice.
Key words: COMPLICATIONS: illicit drugs; PHARMACOLOGY: methylenedioxymethamphetamine
Y OBJETIVOS: En los últimos años el número de nuevos
usuarios de drogas ilícitas ha aumentado de forma significativa en todo
el mundo. La marihuana y la cocaína, además del alcohol y del tabaco,
han sido las drogas citadas frecuentemente, sin embargo, hubo un aumento significativo
de usuarios de otros agentes psicoestimulantes o alucinógenos, como el
Ecstasy, el GHB, el LSD y la metanfetamina, empleados con el objetivo de intensificar
las experiencias sociales. El objetivo del presente artículo fue el de
traer a colación la presentación clínica, los efectos destructivos
y las potenciales interacciones con el acto anestésico en el paciente quirúrgico
usuario de esas drogas ilícitas.
CONTENIDO: El artículo discute los mecanismos de acción, la presentación clínica, los efectos destructivos y las posibles repercusiones observadas durante la anestesia en el usuario de MDMA (3,4-metilenodioximetamfetamina), conocido también como Ecstasy .
CONCLUSIONES: La presentación clínica y los efectos destructivos provocados por el 3,4-metilenodioximetamfetamina (Ecstasy), como también potenciales interacciones con el acto anestésico, deben ser del conocimiento del anestesiólogo, pues en muchas situaciones esos usuarios serán sometidos a cirugías de emergencia, o incluso electivas.
The number of new users of illicit substances has been growing steadily all over the world over the last few years. In the United States, there were approximately 19 million people over the age of 12 using illicit drugs in 2003, that is, 8.2% of the country's population. Marijuana and cocaine has been mentioned most often, but the last few years a new market has increased in the number of users of other psychostimulants or hallucinogens, taken with the aim of intensifying social experiences. As these are often found in night clubs, raves or parties playing electronic music, these drugs are generically referred to as Club Drugs. Substances such as 3,4-methylenedioxymethamphetamine (MDMA), commonly called Ecstasy, gamma-hydroxybutyrate (GHB), flunitrazepam (Rohypnol®), ketamine (Ketalar®), methamphetamine e lysergic acid (LSD) are the main substances that make up this group 2 (Chart I). According to Demetriades et al. 3 in a study conducted at the University of Southern California, 53% of patients with fire gun wounds, 33% of victims of car accidents and 29% of people hit by cars tested positive for alcohol and/or illicit drugs. Hence, anesthesiologists should be made aware of the clinical conditions and the damaging effects that these psychostimulant and hallucinogenic substances have on the body, since there may be many situations in which users of such substances need to be given an anesthetic.
The synthetically produced amphetamine MDMA, also known as Ecstasy, is a compound with hallucinogenic and stimulant properties on the central nervous system 4. There are two other substances with similar pharmacological properties that can be found in the black market: N-ethyl-3,4 methylenedioxyamphetamine, popularly referred to as Eve, and MDMA's active metabolite 3,4-methylenedioxyamphetamine or MDA. In 2003, it was estimated that 2.1 million Americans over the age of 12 (0.9%) had taken Ecstasy at least once during the year course prior to when the research was conducted 5. In Brazil, according to a national survey on the use of psychoactive substances, approximately 0.6% of the people interviewed over the age of 12 reported that they had taken Ecstasy 6 or another hallucinogen at least once in their lives and there are evidences that the number of users grows with each passing year 7,8.
MDMA was manufactured and patented by the pharmaceutical company Merck in 1912 as an appetite suppresant, but it was found to not be commercially feasible. In the 1950's, it was once again released as a way of decreasing the inhibition of patients undergoing psychoanalysis 9. In 1985 it was officially declared illegal for any use in the United States, as its employ as a recreational drug was already rampant. This was also the case in Europe, where Ecstasy had never been considered legal. Although there are indications that the chronic use of MDMA causes lesions in the serotoninergic neurons, limitations involving the methodology of studies conducted so far do not allow for a definite conclusion regarding the toxicity of this substance to human beings 10 .
MDMA is taken orally and is found in pill form or in capsules in a variety of colors and sizes. As it is a drug produced illegally, there is no control over the composition of the pills, which may contain a large variety of substances such as methylenedioxyamphetamine (a toxic metabolite of MDMA), caffeine, atropine, ketamina, ephedrine, diphenhydramine, amphetamine and methamphetamine11. Ecstasy begins to take effect approximately 20 minutes after the user ingests the pill and its duration varies from 4 to 8 hours. Despite uncertainty regarding the pills' composition, studies involving the effect caused by different makes of Ecstasy appear to have the same effects 12-14.
A single mechanism is probably not enough to explain the effects induced by MDMA. The complex spectrum of its activity on the human behavior suggests that the effects produced by the consumption of this substance are a result of multiple neurochemical processes involving serotonin, dopamine and noradrenaline, which makes it similar to the other amphetamines 13.
According to de Almeida et al. 14, in a research project conducted in São Paulo, users of MDMA described the sensation as happiness, energy, peace, euphoria, "having an open mind," "lacking in worries" and "having a sense of calmness." An important piece of information obtained in this study was that many users reported that they also consumed other illicit substances in addition to Ecstasy, such as marijuana, lysergic acid (LSD) and cocaine, as well as tobacco and alcohol. Chart II summarizes the possible adverse reactions, as well as the neurological mechanisms that are probably involved.
Hyperthermia induced by MDMA has been reported in humans 15,16 and observed in studies conducted on animals of different species.
According to Fiege et al. 17, malignant hyperthermia was induced in pigs that were genetically susceptible to this syndrome after having been exposed to high doses of MDMA. However, the use of dantrolene, which is employed in the treatment of malignant hyperthermia, has not proved effective in controlling the thermogenic effects induced by MDMA, suggesting there is another mechanism involved in this complicated picture 18. Some authors are suggesting that the drug induces a large amount of serotonine to be released from the serotoninergic nerve terminals, which in turn is responsible for the group of symptoms that include hyperthermia (body temperature of up to 42 ºC), altered mental states, hemodynamic instability, muscular hypertonia, rhabdomyolysis, and kidney and cardiac failure19.
Cases have also been registered of seizures supposedly caused by hyponatremia and by brain edema, that in turn were probably brought about by water intoxication as a result of the excessive water intake in people with heavy sweating provoked by the increase in body temperature induced by MDMA and aggravated by the intense physical activity expended during parties with electronic music 20. Hepatic lesion was determined among the first registered cases of death due to MDMA abuse in the United Kingdom and it appeared to have been a result of hyperthermia or disseminated intravascular coagulation 21. Reneman et al. 22 found that users of MDMA had a predisposition towards cerebral vascular accidents. The chronic use of the substance may trigger memory dysfunction, changes in cognitive abilities and in behavior as a consequence of the lesions caused by the serotoninergic neurons on the central nervous system 23.
The treatment for MDMA intoxication should be fast and efficient, since complications tend to increase in number and degree of gravity if this is not the case. Certain support measures should also be included, such as: maintaining the permeability of the respiratory tract, ventilatory support, supplying the patient with 100% oxygen, maintaining urinary output and supplying cold fluids (via the stomach, gall bladder and veins) in cases of hyperthermia. The increase in temperature should be treated with urgency, since untreated cases may result in rhabdomyolysis and disseminated intravascular coagulation 24-26. Although dantrolene is recommended as a treatment option, in cases of hyperthermia induced by MDMA, there is little evidence in the literature supporting its effectiveness 11. Hydration and electrolyte reposition should be undertaken with caution in patients with suspected hyponatremia and water intoxication 1.
A neuromuscular blocker should be employed in cases where there is muscular rigidity induced by the excessive release of serotonin on the central nervous system. High blood pressure should be treated with sodium nitroprussiate, phentolamine or with labetalol. You should avoid using b-blockers employed with previously administering a1 blocking agents in patients with symptoms suggesting MDMA intoxication 27. Vasoconstrictors should be applied with caution in patients who are Ecstasy users, even when the spinal block leads to low blood pressure, because this association commonly results in sympathetic hyperactivity 28.
Illicit substance abuse is one of the largest public health concerns the world is facing. Marijuana and cocaine are the most commonly used substances, but the last few years has seen a steady increase in the number of users of other psychostimulants and/or hallucinogens, such as MDMA (also known as Ecstasy), which is associated to countless adverse reactions. Anesthesiologists should be made aware of the clinical presentation and the damaging effects brought about by this drug, as well as the potential interactions with the anesthesia, since people who use these substances will often find themselves in surgery, either due to an emergency situation or elective.
01. Hernandez M, Birnbach DJ, van Zundert AJC Anesthetic management of the illicit-substance-using patient. Curr Opin Anaesthesiol, 2005;18:315-324. [ Links ]
02. Parks KA, Kennedy CL - Club drugs: reasons for and consequences of use. J Psychoactive Drugs, 2004;36: 295-302. [ Links ]
03. Demetriades D, Gkiokas G, Velmahos GC et al Alcohol and illicit drugs in traumatic deaths: prevalence and association with type and severity of injuries. J Am Coll Surg, 2004;199:687-692. [ Links ]
04. Milroy CM Ten years of "Ecstasy". J R Soc Med, 1999;92:68-71. [ Links ]
06. Ferigolo M, Machado AGS, Oliveira NB et al Ecstasy intoxication: the toxicological basis for treatment. Rev Hosp Clin Fac Med São Paulo, 2003;58:332-341. [ Links ]
07. de Almeida SP, Silva MT History, effects and mechanisms of action of ecstasy (3,4-methylenedioxyamphetamine): review of literature. Rev Panam Salud Publica, 2000;8:393-402. [ Links ]
08. Shulgin AT The background and chemistry of MDMA. J Psychoactive Drugs, 1986;18:291-304. [ Links ]
09. Kish SJ How strong is the evidence that brain serotonin neurons are damaged in humans users of ecstasy? Pharmacol Biochem Behav, 2002;71:845-855. [ Links ]
10. Steadman JL, Birnbach DJ Patients on party drugs undergoing anesthesia. Curr Opin Anaesthesiol, 2003;16:147-152. [ Links ]
11. Vollenweider FX, Gamma A, Liechti M et al Psychological and cardiovascular effects and short-term sequela of MDMA ("ecstasy") in MDMA naive health volunteers. Neuropsychopharmacoly, 1998;19:241-251. [ Links ]
12. Ferigolo M, Medeiros FB, Barros HM Ecstasy: a pharmacological review. Rev Saúde Publica, 1998;32:487-495. [ Links ]
13. Solowij N, Hall W, Lee N Recreational MDMA use in Sydney: a profile of "Ecstasy" users and the experiences with the drug. Br J Addict, 1992;87:1161-1172. [ Links ]
14. de Almeida SP, Silva MT Ecstasy (MDMA): effects and patterns of use reported by users in São Paulo. Rev Bras Psiquiatr, 2003;25:11-17. [ Links ]
15. Dar KJ, McBrien ME MDMA induced hyperthermia: report of a fatality and review of current therapy. Intensive Care Med, 1996;22:995-996. [ Links ]
16. Green AR, Cross AJ, Goodwin GM Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Psychopharmacology, 1995;119:247-260. [ Links ]
17. Fiege M, Wappler F, Weisshorn R et al Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine ("ecstasy"). Anesthesiology, 2003;99:1132-1136. [ Links ]
18 Rusyniak DE, Banks ML, Mills EM et al Dantrolene use in 3,4-methylenedioxymethamphetamine ("Ecstasy")-mediated hyperthermia. Anesthesiology, 2004;101:263-264. [ Links ]
19. Campbell S, Qureshi T Taking ecstasy... it´s child´s play! Pediatric Anesth, 2005;15:257-259. [ Links ]
20. Klein M, Kramer F Rave drugs: pharmacological considerations. AANA J, 2004;72:61-67. [ Links ]
21. Henry JA Metabolic consequences of drug misuse. Br J Anaesth, 2000; 85: 136-142. [ Links ]
22. Reneman L, Habraken JB, Majoie CB et al MDMA ("Ecstasy") and its association with cerebrovascular accidents: preliminary findings. Am J Neuroradiol, 2000;21:1001-1007. [ Links ]
23. Greydanus DE, Patel DR Substance abuse in adolescents: a complex conundrum for the clinician. Pediatr Clin North Am, 2003;50:1179-1223. [ Links ]
24. Kain ZN, Barash PG Anesthetic implications of drug abuse. ASA Refresher Courses, 2001;29:159-173. [ Links ]
25. Gill JR, Hayes JA, de Souza IS et al Ecstasy (MDMA) deaths in New York City: a case series and review of the literature. J Forensic Sci, 2002;47:121-126. [ Links ]
26. Richards JR Rhabdomyolisis and drugs abuse. J Emerg Med, 2000;19:51-56. [ Links ]
27. O'Cain PA, Hletko SB, Ogden BA et al Cardiovascular and sympathetic responses and reflex changes elicited by NMDA. Physiol Behav, 2000;70:141-148. [ Links ]
28. Kuczkowski KM Anesthetic implications of drug abuse in pregnancy. J Clin Anesth, 2003;15:382-394. [ Links ]
Dr. Eduardo Toshiyuki Moro
Av. Araçoiaba, 85 Condomínio Lago Azul
18190-000 Araçoiaba da Serra, SP
for publication 28 de julho de 2005.
Accepted for publication 07 de janeiro de 2006
* Received from CET/SBA da Faculdade de Medicina de Botucatu da Universidade Estadual de São Paulo (FMB UNESP), Botucatu, SP