Prevalence of Rhabdomyolysis in Sympathomimetic Toxicity: a Comparison of Stimulants

Abstract

Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK>1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25-42)years with a range of 14-65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n=55), synthetic cathinone (n=19), cocaine (n=9), and other sympathomimetic (n=6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK>10,000 IU/L) for each of the four groups was synthetic cathinone with 5/19 (26 %), methamphetamine with 2/55 (3.6 %), cocaine with 1/9 (11 %), and other with 0/6 (0 %). Median maximal CK (range) by groups was as follows: synthetic cathinone, 2638 (62-350,000+)IU/L; methamphetamine, 665 (61-50,233)IU/L; cocaine, 276 (87-25,614)IU/L; and other, 142 (51-816)IU/ L. A statistically significant difference (p=0.004) was found when comparing maximal CK among the four groups. Exposure to a synthetic cathinone compared with other sympathomimetics was associated with increased risk of developing rhabdomyolysis and severe rhabdomyolysis with odds ratios of 3.09 and 7.98, respectively. In this cohort of patients with sympathomimetic toxicity, 42 % developed rhabdomyolysis. Synthetic cathinones were associated with an increased risk of rhabdomyolysis and severe rhabdomyolysis compared with other stimulants.

Emerging and Underrecognized Complications of Illicit Drug Use

“…One clue that a person with hyperthermia and tachycardia might be using these drugs is acute kidney injury secondary to rhabdomyolysis. In a similar manner to cocaine, MDMA, cathinone derivatives, synthetic cannabinoids, and piperazine derivatives may cause rhabdomyolysis and acute kidney injury by increasing skeletal muscle use and metabolic demand while also causing vasoconstriction, resulting in hypoperfusion and poor heat dissipation [12,34]. Tachycardia, agitation and chest pain can also be seen in persons exposed to clenbuterol (β 2 -agonist similar in chemical structure ephedrine), which is used illicitly by bodybuilders to increase muscle mass and lose weight and also used as a bulking agent for heroin [23,24].…”

Analytical quantification, intoxication case series, and pharmacological mechanism of action for N‐ethylnorpentylone (N‐ethylpentylone or ephylone)

“…All of the cases with accompanying laboratory results exhibited high creatine kinase levels, a symptom which is often associated with rhabdomyolysis after synthetic cathinone intoxication. O'Conner et al40 showed that the risk for rhabdomyolysis is greater after synthetic cathinone administration when compared to other stimulant drugs of abuse. It is noteworthy that the fatal case of N-ethylnorpentylone overdose described here had diffuse alveolar hemorrhage which likely contributed to death.…”

The hot patient: acute drug-induced hyperthermia

“…Rhabdomyolysis is thought to be multifactorial and related to possible overuse of skeletal muscles as a result of excited delirium or repetitive behaviours as well as extreme vasoconstriction. 14…”