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Corresponding author: Geoffrey C. Wall, PHARMD, BCPS, College of Pharmacy and Health Sciences, Drake University, 2507 University Ave, Des Moines, IA 50311-4505 (e-mail: geoff.wall{at}drake.edu).
Baclofen, a derivative of 
-aminobutyric acid, is used for symptomatic relief of skeletal muscle spasm and spasticity, particularly in patients with multiple sclerosis.1 Although its exact mechanism is not fully understood, its main effects at the spinal end of upper motor neurons are thought to cause muscle relaxation. Adverse effects of baclofen at usual doses include drowsiness, headache, dizziness, and, occasionally, orthostatic hypotension.2 Intentional or accidental overdose of this drug can cause profound central nervous system depression, including coma, hypotonia, respiratory depression, seizures, and cardiovascular effects such as bradycardia. Because baclofen is a commonly used antispasticity agent and its use as a recreational drug has been reported,3 clinicians should be ever vigilant for patients who may have overdosed on this medication. We report a case of surreptitious baclofen intoxication in a patient with seizures and coma.
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hours before the seizure. When found, he was apneic and incontinent of both bladder and bowel. He reportedly had vomited. Emergency responders intubated him at his home. Initial testing upon arrival at the community hospital included a basic metabolic panel (including serum electrolytes and creatinine), complete blood cell count, and liver function tests (including transaminases, albumin, bilirubin, and serum ammonia); all results were within the reference range. Computed tomography of the head showed no evidence of hemorrhage or other abnormality. A urine toxicology screen was positive for tetrahydrocannabinol and benzodiazepines (however, emergency medical personnel had administered diazepam because of continuing seizure activity) and negative for amphetamines, cocaine, barbiturates, and opioids. Blood alcohol level was zero. Vital signs upon admission were within the reference range except for blood pressures, which ranged from 174 to 207 mm Hg systolic and 99 to 119 mm Hg diastolic. These values decreased over the next several hours to normal without treatment.
The patient’s medical history was significant for a previous back injury for which he had taken pain medications long-term, specifically morphine in the past year, but he had reportedly stopped taking this drug about 1 month before the admission. He was not taking any other known medications at the time of hospitalization. He also had a history of alcohol abuse (he reportedly had quit drinking 8 years earlier). He received no treatment for suspected drug overdose at the outlying hospital.
Upon transfer to the intensive care unit at the referral hospital, approximately 8 hours after the onset of the seizure, the patient was nonresponsive to verbal stimuli and manifested a decerebrate posture upon deep pain stimuli. Vital signs were normal, including blood pressure 130/70 mm Hg, heart rate 75/min, and temperature 37.2°C. His pupils were 3 mm in diameter and unresponsive to light. Pulses were +1/4 bilaterally with coolness in the lower extremities. The Babinski sign was negative, and the rest of a physical examination revealed no other abnormalities. The patient had no clonus. The results of repeat laboratory studies in the intensive care unit were within the reference range, including normal serum levels of sodium, creatinine, and thyroid-stimulating hormone. Results of the initial arterial blood gas analysis of samples obtained while the patient was receiving intermittent mechanical ventilation (fraction of inspired oxygen 0.60, positive end-expiratory pressure 5 cm H2O, respirations 12/min) were pH 7.40, PCO2 38 mm Hg, PO2 180 mm Hg, bicarbonate 23.3 mmol/L, and oxygen saturation 94%. All other laboratory values were within the reference range. Electroencephalography showed a burst-suppression pattern. The results of a computed tomography angiogram of the head and a lumbar puncture did not indicate any abnormalities.
At this point, detailed questioning of the patient’s family members and investigation of his medical records were undertaken to determine if he had access to or was exposed to any toxic substance. These inquiries revealed that in the past year he had been prescribed the muscle relaxant baclofen. On the basis of this new information, approximately 12 hours after admission to the intensive care unit and 16 hours after the onset of the seizure, a serum sample was sent to a reference laboratory for determination of the baclofen level. No specific treatment for baclofen overdose, including use of activated charcoal, was initiated.
About 24 hours later, movement of the patient’s extremities (left greater than right) was noted; the movement was determined to be nonpurposeful. Forty-eight hours later, the patient had a dramatic improvement in consciousness. He became alert and awake with his eyes opened. He was able to follow commands and was extubated about 12 hours later. Upon questioning, he revealed that he had attempted suicide by taking an entire bottle (unknown total quantity) of baclofen. He was eventually transferred to the inpatient psychiatric ward for treatment of major depression. The results of the serum assay for baclofen, which was received about 1 week after the patient’s transfer to the psychiatric unit, was 1.2 µg/mL (reference serum level for treatment of spasticity is 0.08–0.4 µg/mL).2
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Using MEDLINE, we found only 2 reports4,5 published in the past 25 years on the pharmacokinetics in baclofen overdose. In the first report,4 baclofen pharmacokinetics were determined in a patient after an intentional overdose of 1230 mg; in this case, the elimination half-life was 4.58 hours. In the second report,5 a patient ingested more than 2 g of the drug; in this case, the elimination half-life was 8.6 hours. The authors of the second report did not find evidence of saturable kinetics in baclofen overdose.
Interestingly, with chronic oral dosing, baclofen has an elimination half-life of about 6.5 hours.6 On the basis of this information, if we assume that the patient was found after most of the drug had been absorbed and we extrapolate back to the time of ingestion (and assume that maximum plasma concentrations occur about 2 hours after ingestion),1 we can estimate that the peak serum level ranged from 5.2 to 18.2 µg/mL (a standard first-order elimination equation was used for this calculation: CO = C x e–kT). If this estimation is accurate, the patient had a significantly higher serum level than has been usually reported in cases of baclofen overdose, though the pharmacokinetics of this drug in higher doses than those described is not known.3
In a case series of adolescent boys who overdosed on baclofen, Perry et al3 noted that serum levels of the drug were linearly correlated with duration of mechanical ventilation. One patient with a serum level of baclofen of 0.85 µg/mL 14 hours after ingestion of the drug required 61 hours of mechanical ventilation. Our patient’s serum level at 16 hours after ingestion was higher at 1.2 µg/mL, and correspondingly he required about 100 hours of mechanical ventilation. Of course, serum elimination half-life may not reflect a slower elimination rate from the central nervous system, a situation that may explain a significantly longer time on mechanical ventilation than the toxicokinetic data would suggest.
Profound central nervous system depression is a recurring finding in patients who have baclofen poisoning, including a patient who had deep coma with no deep tendon, corneal, or gag reflexes.7 In one case,7 a patient ingested approximately 1800 mg of baclofen in addition to acetaminophen with codeine and oxazepam during an 18-day period. With supportive care, the patient was extubated and fully recovered within a week of the ingestion. A teenager who ingested about 500 mg of baclofen had central nervous system depression and coma, bradycardia, and hypertension.8 With supportive care, he also recovered fully about 48 hours after the ingestion. Other reports9,10 of baclofen overdose describe other cardiac conduction abnormalities such as supraventricular tachycardias, premature atrial contractions, and first-degree heart block. Encephalopathic manifestations, including seizures and respiratory depression, in cases of baclofen overdose also have been reported.11
Management of baclofen overdose is primarily supportive. Activated charcoal would be expected to bind to the drug in the gut and is a reasonable course of action. A report12 from Taiwan described the use of hemodialysis in a patient who had been taking baclofen for leg muscle soreness. In this patient, serum levels of baclofen had decreased from 3.84 µg/mL to 0.82 µg/mL after a single 4-hour session of hemodialysis. This case suggests that hemodialysis may be an option for baclofen overdose, though more data are needed to make this procedure a routine recommendation. As our case and other cases illustrate, the prognosis is excellent if adequate supportive care (including mechanical ventilation) is provided.
Our patient had many of the features of baclofen overdose described in the literature, including profound coma, seizure activity, hypotonia, and respiratory depression. Our case also highlights the need for a thorough investigation into possible ingestants in a patient with signs and symptoms similar to those of our patient. Baclofen is not routinely detected in urine toxicology screens, and clinicians should maintain a high index of suspicion for baclofen overdose in patients with a history of muscle spasms or chronic low back pain.
In conclusion, our patient had surreptitious baclofen intoxication. Despite being in a deep coma and having hyporeflexia, respiratory depression, and seizures, he made a complete recovery. Healthcare personnel should consider baclofen overdose in any patient whose history and signs and symptoms are similar to those of our patient.
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