From the Guidelines
Methamphetamine toxicity causes rhabdomyolysis through multiple mechanisms, including direct muscle toxicity, hyperthermia, prolonged muscle hyperactivity, vasoconstriction, and dehydration, which can lead to muscle breakdown and damage. The most recent and highest quality study, 1, published in 2023, highlights the importance of managing severe agitation from sympathomimetic poisoning, such as methamphetamine, to prevent rhabdomyolysis and other life-threatening conditions.
Mechanisms of Rhabdomyolysis
- Direct muscle toxicity: Methamphetamine and its metabolites harm muscle cell membranes, leading to cell death and release of intracellular contents, including myoglobin and creatine kinase, into the bloodstream.
- Hyperthermia: Methamphetamine disrupts temperature regulation, causing extreme body temperatures that accelerate muscle breakdown.
- Prolonged muscle hyperactivity: Methamphetamine-induced agitation, seizures, and psychomotor excitation lead to ATP depletion and muscle fiber damage.
- Vasoconstriction: Methamphetamine reduces blood flow to muscles, creating ischemic conditions that further damage tissue.
- Dehydration: Methamphetamine use often accompanies dehydration, concentrating myoglobin in the kidneys and increasing the risk of acute kidney injury.
Treatment
Aggressive IV fluid administration, typically normal saline at 200-300 mL/hour initially, is recommended to maintain urine output above 200 mL/hour, along with addressing electrolyte abnormalities, particularly hyperkalemia, which can cause cardiac arrhythmias. Sedatives, such as benzodiazepines, can be used to manage agitation and prevent rhabdomyolysis, as suggested by 1.
Key Considerations
- Early recognition and management of methamphetamine toxicity are crucial to prevent rhabdomyolysis and other life-threatening conditions.
- Treatment should focus on addressing the underlying mechanisms of rhabdomyolysis, including hyperthermia, muscle hyperactivity, and dehydration.
- Aggressive IV fluid administration and sedation are essential components of treatment, as highlighted by 1.
From the FDA Drug Label
Manifestations of amphetamine overdose include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Musculoskeletal: Rhabdomyolysis.
The cause of rhabdomyolysis in the context of methamphetamine toxicity is not explicitly stated in the drug label as a specific mechanism or pathway. However, it is listed as a potential manifestation of amphetamine overdose and as a musculoskeletal adverse reaction.
- Key points:
From the Research
Causes of Rhabdomyolysis with Methamphetamine Toxicity
- Rhabdomyolysis is a serious syndrome due to direct or indirect muscle injury, resulting in the death of muscle fibers and the release of their contents into the bloodstream 3, 4, 5, 6, 7.
- Methamphetamine toxicity is associated with an increased risk of rhabdomyolysis, with studies suggesting that the incidence of rhabdomyolysis is higher in patients with methamphetamine abuse compared to those without 3, 4, 6.
- The exact mechanisms by which methamphetamine causes rhabdomyolysis are not fully understood, but it is thought to be related to the drug's sympathomimetic effects, which can lead to increased muscle activity, hyperthermia, and muscle damage 4, 7.
- Other factors that may contribute to the development of rhabdomyolysis in patients with methamphetamine toxicity include:
- Elevated creatine kinase (CK) levels are a common finding in patients with rhabdomyolysis, and CK should be measured in patients with suspected methamphetamine toxicity as a screen for potential muscle injury 3, 6.
- Immunohistochemical studies have shown that myoglobin, a protein released from damaged muscle cells, may play a role in the development of oxidative damage and acute renal failure in patients with methamphetamine abuse 7.