Never underestimate the ingenuity of illegal drug makers nor the lack of basic common sense of those who consume their products. It seems like homemade mind-altering drugs spring up frequently, making it difficult to keep abreast of new arrivals.
Like the common street drugs Idiscussed previously, synthetic cannabinoids (spice and K2) and MDMA, bath salts are readily available and highly abusable. Most aficionados of bath salts never make it to the emergency department, but those who do can have serious medical problems, and fatalities have occurred. As with synthetic cannabinoids and a variety of other street drugs, there is no easy way for clinicians or the hospital's toxicology laboratory to identify bath salts. Fortunately, treatment is symptomatic, and the clinician only needs to know what to do and not the culprit behind the symptoms.
Psychoactive “Bath Salts:” Not So Soothing
Baumann MH, Partilla JS, Lehner KR
Eur J Pharmacol
This article is a good review of psychoactive bath salts, products recently introduced to serve as alternatives to cocaine and amphetamines. Bath salts contain one or more synthetic derivatives of the naturally occurring stimulant, cathinone. Cathinone derivatives in low doses produce euphoria and increased alertness. High doses or chronic use can cause serious effects such as tachycardia, hallucinations, agitation, delirium, psychosis, hyperthermia, and multisystem failure. Many countries have made cathinone derivatives illegal, specifically mephedrone, methylone, and MDPV. All of these drugs target the membrane transporters for dopamine, norepinephrine, and serotonin. Some popular synthetic cathinones are illegal, but some are still available and new replacements are always appearing on the market.
Bath salts can usually be found on the Internet and in retail shops. These products had no legitimate use as bath additives, but are purchased as legal highs that mimic the effects of drugs such as cocaine, methamphetamine, and MDMA. The packages often stated that they were not for human consumption, but the user knew full well their potential. Bath salts are available as tablets, capsules, granules, and powder. They are often administered by nasal insufflation but also by the oral and intravenous routes.
Bath salts are manmade derivatives of cathinone, a structural analog of amphetamines found in the khat plant that has been chewed as a stimulant daily for centuries by the general population in many African countries without serious adverse effects. The exact mechanism of action is unknown, but these drugs all interfere with the normal handling of serotonin, dopamine, and norepinephrine, probably by decreasing reuptake. MDPV's ability to block dopamine and norepinephrine reuptake is 10 times that of cocaine. Given this mechanism of action, it is obvious that these drugs can cause the individual to display agitation, combative behavior, psychosis, tachycardia, and hyperthermia. The clinical scenario is very similar to cocaine, methamphetamines, MDMA, PCP, and a variety of synthetic cannabinoids. They essentially produce an excited delirium syndrome.
Synthetic Cathinones (Bath Salts): Legal Status and Patterns of Abuse
Fass JA, Fass AD, Garcia AS
This article details some of the legal parameters and patterns of bath salts use, particularly the substances MDPV and mephedrone. Manufactured in China and Eastern Europe, these have been available in Japan and Europe for years. In the mid-2000s, they surfaced in U.S. head shops, convenience stores, and even gas stations. They have become popular drugs of abuse for teens and young adults. Apparently many abusers already have an excessive history of drug abuse.
These drugs are described as designer drugs of the phenethylamine class. The Drug Enforcement Administration (DEA) placed mephedrone, MDPV, and methylone under Schedule I of the Controlled Substances Act in October 2011, identifying them as substances that had no accepted medical use and a high potential for abuse. Starting in 2010, poison centers started receiving calls, and case reports have surfaced revealing the many adverse effects. These authors also provide a summary of various selected studies reporting the effects of bath salts. High levels of MDPV were detected in most cases. Many also had marijuana and prescription drugs on board, commonly marijuana, opiates, benzodiazepines, cocaine, and amphetamines.
The most common methods of use were injection (60%), snorting (25%), and oral ingestion (11%), but snorting is currently the most popular route. The major adverse effects are neurologic, cardiovascular, and psychological. The overall experience is enjoyable and rated as positive by many users. Some users rated mephedrone as a better high and longer lasting than cocaine. The withdrawal state is characterized by tiredness, insomnia, nasal congestion, and impaired concentration.
Comment: Most clinicians have heard the term bath salts and are generally familiar with them. Many of the effects are enjoyable, but those who come for medical attention most often report symptoms similar to cocaine and amphetamines. Most clinicians, however, have seen agitated, confused, combative, tachycardic, hypertensive, and febrile patients that defervesce after treatment, but otherwise have negative drug screens, leaving the clinician no wiser about which drug is responsible.
Serum/urine drug testing is not available in most hospitals for identifying synthetic cathinones, so it's almost always a clinical diagnosis. This is based on a history of abuse and clinical features consistent with a sympathomimetic syndrome. Unlike amphetamines or cocaine, synthetic cathinone toxicity can last for several days. Of course, one also has to consider thyrotoxicosis, pheochromocytoma, heat stroke, and paranoid schizophrenia in addition to drug effect. After attempts at diagnosis, treatment will be empiric.
As with most forms of psychomotor agitation, probably the best and safest intervention is a benzodiazepine. They should be given very early in the course in adequate amounts because struggling against restraints is counterproductive. Generally higher-than-normal doses are required, and it is reasonable to initially administer either 2 mg lorazepam or 10 mg diazepam as a starting dose. It is prudent to repeat these doses every five to seven minutes until agitation is controlled. If benzodiazepines are not effective, one can try haloperidol (Haldol), ziprasidone (Geodon), or olanzapine (Zyprexa), although these drugs can lower the seizure threshold and interfere with heat dissipation. Ketamine is likely not a drug of choice here because of the drug's sympathomimetic effects.
Generous IV fluids will be appropriate for hypovolemia. Hyperthermia should be evaluated and treated aggressively. Hypertension and hyperthermia are generally treated with appropriate sedation paralysis and assisted ventilations. Seizures can be treated with benzodiazepines, but one should also consider intracranial hemorrhage, hyponatremia, or hypoglycemia in patients with seizures. Of course, rhabdomyolysis is not uncommon, and most patients have some elevation of the CPK. There is much crossover in signs, symptoms, and treatment of bath salts and amphetamines.
Death Following Recreational Use of Designer Drug Bath Salts Containing 3,4-Methylenedioxypyrovalerone (MDPV)
Murray BL, Murphy CM, Beuhler MC
J Med Toxicol
The authors believe that this 2012 report is the first to describe a death secondary to MDPV, the designer stimulant drug that has gained popularity in the United States. They report on a 40-year-old man with a history of bipolar disorder who snorted and injected an unknown amount of bath salts. He had previously used cocaine heavily but switched to bath salts. Shortly after consumption, he became aggressive, uncontrollable, and delusional, took off all of his clothes, and ran outside.
Police were called and took him into custody. He displayed aggression, considerable strength, and violent behavior. He was TASERed three times, but continued to yell incomprehensively, and was noted to have dilated pupils. Vital signs demonstrated a heart rate of 164 bpm, blood pressure of 131/72 mm Hg, respiration rate of 24 bpm, and oxygen saturation of 100% on a rebreathing mask. A small dose of lorazepam was unsuccessful in gaining any sedation.
His aggressive behavior continued in the ED, and within five minutes of arrival, he developed bradycardia and essentially cardiac arrest with pulseless electrical activity. Resuscitation included epinephrine, atropine, lidocaine, naloxone, and flumazenil. He subsequently regained spontaneous circulation, and was placed on vasopressors. His rectal temperature following resuscitation was 105.4°F. Despite aggressive treatment, his hypotension, coma, hyperkalemia, and liver failure progressed. He developed worsening metabolic acidosis, renal failure, and coagulopathy, and a CT showed anoxic brain injury. He died 42 hours after admission.
All drug screening tests were negative. Serum and urine were sent to a tertiary laboratory for further evaluation where MDPV was identified and considered a lethal drug. The authors deemed this case as consistent with MDPV toxicity causing excited delirium syndrome followed by multisystem failure.
Comment: This is a classic case of excited delirium ending in death. It has been well described after amphetamines, cocaine, and other stimulants, and once developed, likely has no beneficial treatment. Patients start out agitated, confused, and delirious, become violent and hyperactive, often find themselves being TASERed by police, and then end up in the emergency department. Their downhill course is rather similar to rhabdomyolysis, renal failure, ARDS, cerebral edema, hypotension, and coagulopathy. A number of years ago, patients with cocaine poisoning exhibited this scenario, but it appears to be relevant to many stimulants. Bath salts are now included in that class. (Myriad articles on excited delirium by Dr. Roberts and other authors are available on the EMN website at http://bit.ly/EMNExD.)
As with most cases, the identification of the synthetic cathinones required a sophisticated tertiary laboratory, with results returning a number of days later. Regardless of the insulting agents, however, the clinical syndrome is often the same, as is the fatal outcome. I don't know whether patients who have advanced excited delirium can be saved by any method, but one should certainly aggressively sedate, cool, and otherwise support these patients. My guess is that most will die regardless of any intervention once multisystem failure surfaces.
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