Cocaine-Related Sudden Death Not So Rare

January 13, 2010

January 13, 2010 (Seville, Spain) — A prospective investigation into the causes of sudden death in southwest Spain has revealed that 3% of such deaths are cocaine-related and that the majority of these are due to cardiac causes [1].

"The most important finding is that cocaine is a very dangerous substance, with effects on many different parts of the body, with one of the main targets being the heart," lead author Dr Joaquin Lucena (Institute of Legal Medicine, Seville, Spain) told heartwire . The paper, published online January 12, 2010 in the European Heart Journal, illustrates that cocaine-associated deaths are not as rare as was thought and that there is no such thing as "safe" recreational use of small amounts of the drug, he notes.

I still suspect they're just barely scratching the surface with this report.

In an accompanying editorial [2], Drs Richard A Lange and L David Hillis (University of Texas Health Science Center, San Antonio) agree. "The notion that recreational cocaine use is 'safe' should be dispelled, since even small amounts may have catastrophic consequences. Physicians should consider the possibility of cocaine abuse in a young individual with cardiovascular disease or sudden death, especially in those without traditional risk factors for atherosclerosis," they observe. Lange told heartwire this new European study is "terrific" because it employed a standard, systematic toxicological investigation on autopsy, "but I still suspect they're just barely scratching the surface with this report."

Cardiac Disease, MI, the Most Frequent Cause of Cocaine-Related Death

Lucena et al say their study is one of the first to investigate the prevalence of cocaine-related sudden deaths in such a detailed and methodical way. In their prospective case-control study, they autopsied a consecutive series of more than 600 sudden-death victims in the Seville region of Spain from November 2003 to June 2006, with the postmortems performed according to the European standardized protocol, with toxicology including blood alcohol analysis and blood and urine investigation for drugs of abuse and medications.

Of the 660 sudden deaths, 21 (3.1%) turned out to be cocaine-related, and all were in males. These were compared with 10 age- and sex-matched controls who died of violent causes with no prior history of cocaine consumption and negative toxicology. Lucena said he was not surprised that all cocaine-associated sudden deaths were in males, because sudden deaths affect many more males than females, in a ratio of seven to one, and also men are more likely to abuse cocaine. But "this does not mean that women are less affected by cocaine," he cautioned.

The cause of sudden death in the cocaine-related cases was cardiovascular in 62%, cerebrovascular in 14%, excited delirium in 14%, and respiratory and metabolic in 5% each, respectively.

MI was the most common cardiac condition responsible for sudden death following cocaine use. Cardiac hypertrophy, obstructive small vessel disease, and premature coronary artery atherosclerosis, with or without lumen thrombosis, were the main structural abnormalities that likely led to myocardial ischemia and arrhythmic cardiac arrest, the researchers say. Lucena told heartwire that a very distinctive observation on autopsy in cocaine-associated deaths is hypertrophy of the walls of the small intermyocardial vessels and that if pathologists see this it should alert them to the possibility of cocaine involvement.

They also found a wide range of serum cocaine concentrations (from 0.1 to 24 mg/L) among those who died following its use. "Any amount of the drug can be considered to have the potential for toxicity. . . . Some patients have poor outcomes with relatively low blood concentrations, whereas others tolerate large quantities without consequences," they observe. The editorialists agree, saying that this--as well as other prior studies--suggests "that no blood concentration is always safe."

High Concomitant Use of Tobacco, Alcohol, May Exacerbate Events

The Spanish doctors also found that 81% of the victims of cocaine-associated sudden death smoked cigarettes. "This combination is not innocuous," comment Lange and Hillis "as human studies conducted during cardiac catheterization showed that concomitant cigarette smoking substantially exacerbates the deleterious effects of cocaine on myocardial oxygen supply and demand."

And 76% of the victims had also consumed alcohol. This combination is popular, the editorialists continue, "because ethanol enhances the euphoria of cocaine and minimizes the dysphoria that often occurs during its withdrawal." But ethanol and cocaine together are associated with enhanced myocardial depression, decreased coronary arterial blood flow, dysrhythmias, and sudden death, "all of which may be due, in part, to cocaethylene, a pharmacologically active metabolite of cocaine that is synthesized by the liver if ethanol is present," they note. Animal studies indicate that this metabolite could be more toxic and arrhythmogenic than either cocaine or alcohol alone, they add.

Doctors also need to be aware that some medications--for example, beta blockers--can worsen the adverse effects of cocaine, Lange told heartwire .

Cocaine Use a Growing Problem: Education Needed About Adverse Effects

Lucena and colleagues say their data show that cocaine users in their region of Spain are generally employed, with deaths often occurring at home and mostly on weekends, indicating mainly recreational use rather than chronic, daily use, a different demographic from heroin use.

And statistics from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) indicate that cocaine is a growing public-health issue and the most commonly used illicit substance in the general population of Europe after cannabis, they note. Almost 8% of the UK population, 7% of Spaniards, and almost 7% of Italians are thought to use cocaine, with use highest among young adults aged 15 to 34. 

Doctors, the scientific community, and lay people consider cocaine a safe substance, but pharmacologically it's more dangerous than heroin.

"In Spain, and I imagine elsewhere, doctors, the scientific community, and lay people consider cocaine a safe substance, consumed on weekends recreationally," Lucena commented. "But pharmacologically it's more dangerous than heroin and other opiates."

Lange agrees wholeheartedly. A cardiologist who has been studying the cardiovascular effects of cocaine since 1989, he told heartwire : "People need to be educated about the effects of cocaine. They think because they are not chronic, heavy users they are okay, but we need to make them aware that this is not benign. Many of the recreational abusers are not addicted and if they become aware this is a potentially life-threatening thing, you can potentially get them to stop using it."

In the US, Lange says the best estimates suggest a lifetime prevalence of recreational cocaine use of around 15% of the population, with two million people currently using it. "This has been an identified problem in the US for a while. We see a lot of MIs and not uncommonly sudden death." For any doctor seeing a young patient presenting with chest pain, myocardial injury, shortness of breath, or an aborted episode of sudden death, "suspicion should be high" regarding cocaine abuse, he says.

"We've got good data in the US on how many emergency-room visits there are," with around half a million due to cocaine-related events, Lange continues, "but the precise figures in terms of sudden death and incidence are very hard to come by. We don't have any standard ways of reporting how many deaths are due to cocaine."

Lucena says for the correct diagnosis of sudden death, especially in young adults, "it is important to use a uniform autopsy protocol, including a toxicology investigation of the blood and urine for illicit drugs. We can only monitor the prevalence [of cocaine-associated deaths] by performing these detailed autopsies whenever someone dies suddenly.”

Lange says the same standard is required in the US: "We don't have routine postmortem analyses; it's left to the discretion of the pathologist.

"It is important to implement procedures with which drug use can be monitored and reported systematically and consistently. Until these are accomplished, the prevalence of cocaine and other illicit drug use will be underestimated, and cocaine-related complications will not be recognized," he and Hillis conclude.


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