Case Review

Accidental Baclofen Toxicity in a Patient with Nephrolithiasis

Yas Moayedi, BHSc, Stefanie Lam, PharmD, Daniel Kaud, Sarah Kwon, BSc, Laurence Green, MD

About the Authors

Yas Moayedi and Sarah Kwon are first-year residents at the University of Toronto, Toronto, Ontario. At the time of this writing, Stefanie Lam was a pharmacist at Montreal General Hospital, Montreal, Quebec. Daniel Kaud is a first-year resident at McGill University, Montreal. Laurence Green is the associate physician-in-chief at Montreal General Hospital. Correspondence may be directed to Laurence.Green@mcgill.ca.

Case Report

A 35-year-old paraplegic man was transferred to our hospital with a 2-day history of confusion and abdominal pain. Three days prior to admission, he had developed right-sided flank pain, and the following evening had difficulty falling asleep due to the constant movement of his arms and trunk. On the morning of his presentation, he was both confused and agitated.

He suffered from a neurogenic bladder and associated recurrent urinary tract infections. He had a previous hemipelvectomy for testicular cancer, which led to adhesions, a chronic left hydronephrosis, and an atrophic left kidney. His baseline creatinine was 94 µmol/L (glomerular filtration rate [GFR] 75cc/min).  His regular medications at presentation included baclofen for lower limb spasticity and nortriptyline for depression. He reported taking his last dose of baclofen the evening before his presentation.

Notable examination findings at presentation included somnolence, intermittent agitation, and disorientation in time. His blood pressure was 140/80 mm Hg, his heart rate 97 beats/min, and his temperature 36.6ºC. He was tender to palpation of the abdomen and right renal angle. Investigations revealed a serum creatinine level of 641 µmol/L and a white blood cell count of 24.4 × 1012 cells/L. A urine dipstick revealed the presence of leukocytes, erythrocytes, bacteria, and protein (>3 g/L). Blood and urine cultures were negative. Baclofen was held on this day and day 2.

An abdominal ultrasonography showed the presence of a stone obstructing his right  kidney. On day 2, a nephrostomy tube was successfully inserted. His serum creatinine level peaked at 788 µmol/L prior to the procedure. On day 3, his baclofen was restarted at his usual dosing schedule of 30 mg in the morning, 20 mg at noon, 20 mg at supper, and 40 mg at bedtime. Over the course of this day, his mental status returned to normal. On day 4, he was found to be confused, agitated, and more aggressive. On day 5, his serum creatinine was 435 µmol/L, but his delirium worsened. He exhibited nonpurposeful movements of the arms and trunk, decreased orientation to time and place, and paranoid ideation. His pupils were 4 mm in diameter and unresponsive to light. Sensory and motor examination showed no focal neurological abnormalities.

We made a presumptive diagnosis of baclofen toxicity. It was not possible to monitor the plasma concentration level of baclofen because of the lack of a facility at our and surrounding institutions. After his noon-hour dose on day 5, baclofen was discontinued. On day 6, the patient’s mental status had markedly improved and his akathisia had resolved. With a creatinine of 218 µmol/L, he was re-started on baclofen 10 mg t.i.d. to prevent possible withdrawal symptoms. This dose was doubled to treat leg spasms, and on day 12 he was discharged with restored cognitive function and a serum creatinine of 153 µmol/L.

Discussion

In this report, we highlight the relationship between reversible baclofen toxicity and acute-on-chronic kidney disease. Although concentrations of the drug were not measured, the clinical findings at both presentation and again the findings on rechallenging the patient support the assumption that this was likely dose-related baclofen toxicity.

Baclofen is a synthetic gamma-aminobutyric acid (GABA) centrally acting agonist commonly used for spasticity related to spinal cord trauma and neurological disease. Spasticity is the result of overactive gamma reflex arcs in the presence of spinal cord disease.1 The therapeutic serum concentration ranges between 80 and 400 ng/mL in adults with normal renal function. There have been few cases of baclofen toxicity described in the literature. The most common findings reported include altered mental status, respiratory depression, hypo- or hypertension, arrhythmias, decreased deep tendon and pupillary reflexes, and psychosis.1

Symptoms of baclofen toxicity can occur, however, at variable serum levels even within the normal range as a result of plasma accumulation. Reports of baclofen toxicity among renal failure patients describe encephalopathy, respiratory depression, muscular hypotonia, and generalized hyporeflexia as potential findings; the most common finding is altered level of consciousness.2  

Our patient’s acute obstructive uropathy and azotemia precipitated baclofen-related neurotoxicity. Akathisia, altered mental state, and mydriasis were the first manifestations of toxicity.

Baclofen withdrawal has also been associated with serious manifestations, such as seizures, psychosis, delirium, paranoid ideation, dyskinesia, hypertonia, and hyperthermia.3 Preventing or treating withdrawal symptoms complicates the management of baclofen toxicity. Our patient did not have any symptoms with the abrupt cessation of baclofen for 24 hours followed by its reintroduction at a significantly reduced dose. Because baclofen levels were not available, we had to make crude estimates of drug levels and half-lives when calculating a new dosing regimen.

Conclusion

Patients on a regular dose of baclofen may develop an accidental overdose due to acute renal failure. Although we were unable to verify toxic baclofen levels, the patient’s presentation and response to baclofen dosing adjustments are comparable to other cases described in the literature. Clinicians should be aware of the presenting signs of baclofen toxicity and should preemptively decrease baclofen dosage in patients who present with acute renal failure. Baclofen should be used cautiously in patients with impaired renal function. Note that paraplegic patients often have low muscle mass, making the serum creatinine a less reliable measure of renal function. Although no dosing guidelines are available, and in the absence of available baclofen levels, a decrease in creatinine clearance by 50% may warrant a decrease of baclofen daily dose by 50% to prevent toxicity. The clinician must also be aware of a potentially serious withdrawal syndrome and should restart the baclofen at an adjusted dose as soon as the clinical signs have abated. Because baclofen levels are not usually available, the clinician must rely on clinical judgment to recognize toxicity and guide management.

References

1.         Roy CW, Wakefield IR. Baclofen pseudopsychosis: case report. Paraplegia 1986;24:318–21.

2.         Chen KS, Bullard MJ, Chien YY, Yuan LS. Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 1997;31:1315–20.

3.         Peng T, Ger J, Yang CC, et al. Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose. J Toxicol Clin Toxicol 1998;36:359–65.