Abstract
Gabapentin toxicity should be considered one of the differential diagnoses of altered consciousness in patients with compromised renal function, even after a single dose. We report a 57-year-old woman with diabetes mellitus and uraemia on regular haemodialysis who developed severe dizziness and lethargy after a single recommended dose of gabapentin for bilateral leg dysthesia. Because of progressive drowsiness and decreasing level of consciousness, one session of haemodialysis was performed and clinical recovery was dramatic. The adverse effects of gabapentin seem to vary from person to person and should be viewed with a high degree of suspicion, especially in patients taking this drug at the beginning.
BACKGROUND
Second generation antiepileptic drugs have created a new therapeutic option for chronic neuropathic pain. Gabapentin is one of the agents that is used very commonly, and has been shown to be safe and non-toxic. We report the case history of a 57-year-old woman with diabetes mellitus and uraemia on regular haemodialysis who developed severe dizziness and predominant lethargy after a single recommended dose of gabapentin for bilateral leg dysthesia.
CASE PRESENTATION
A 57-year-old woman with diabetes mellitus and uraemia who was receiving regular haemodialysis three times a week presented to the emergency department (ED) with severe dizziness and vomiting for 2 h. She did not have a headache, unsteady gait, focal limb weakness, blurred vision or sensory deficiency. Her temperature was 36.9°C (98.4°F), pulse rate 81 beats/min, respiratory rate 16 breaths/min, and blood pressure 175/78 mm Hg. Physical examination and neurological signs were unremarkable. Laboratory tests showed haematocrit 33.4%, serum creatinine 5.1 mg/dl, sodium 134 mEq/l, potassium 3.7 mEq/l and glucose 154 mg/dl. The clinical impression was dizziness and she was observed in the ED. Four hours later, altered consciousness with lethargy was noted. The Glasgow Coma Scale was E2V3M5. There was no focal neurological deficiency. Her family denied that she had taken any hypnotic agents recently. A non-contrast computed tomography (CT) scan of the head was performed and excluded obvious abnormalities. The arterial blood gas profile was also checked and was within normal limits.
We reviewed her history of medication. She had been taking acarbose, glimepiride and rosiglitazone to control her blood sugar for a long time. Her clinician had prescribed one half tablet of gabapentin (600 mg/tablet) as-needed for bilateral leg dysthesia because of recent painful diabetic neuropathy. She had taken the first half tablet of gabapentin for her leg discomfort 2 h before arrival at the ED, and acute onset of dizziness was experienced. Because gabapentin induced altered consciousness was suspected, a single session of haemodialysis was performed and the symptoms resolved dramatically. She was then discharged after 24 h observation without any further sequelae.
DISCUSSION
Since diabetic nephropathy is the main reason for haemodialysis in patients with end stage renal disease, concomitant neuropathy with numbness and pain in the limbs is a very common complaint. Gabapentin has a role in painful diabetic neuropathy and is expected to be used more and more frequently. The mechanism by which gabapentin helps neuropathic pain is unclear. However, a selective inhibitory effect on the sodium channel and calcium channel alpha2-delta1 and a reduction of several monoamine neurotransmitters have been found in previous studies. It structurally resembles the neurotransmitter gamma-aminobutyric acid (GABA) but does not convert into GABA or a GABA agonist. The pharmacological action is due to the activity of gabapentin itself as it is not metabolised to any extent.2
Gabapentin is generally safe and non-toxic, although there have been several published case reports of adverse effects with gabapentin including severe myopathy, severe myoclonus, neutropenia, hypoglycaemia episodes and altered consciousness.3 The recommended dose of gabapentin in patients with creatinine clearance >60 ml/min is 1200 mg/day, but it is suggested that patients on haemodialysis start with a loading dose of 300–400 mg and then take 200–300 mg following each session of haemodialysis.4 In our case, however, acute central nervous system adverse effects still occurred at the recommended dosage.
The clearance of gabapentin is dependent on renal function. A study of gabapentin in anuric uraemic patients4 has shown that the mean (SD) maximum concentration of 6.0 (2.4) μg/ml is achieved at 4.7 (2.1) h after a single oral dose of 400 mg. The average elimination half-life of gabapentin in uraemic patients without haemodialysis is 132 h, which shortens to 4 h during haemodialysis. This might explain the rapid improvement after a single session of haemodialysis in patients with adverse effects to gabapentin.
Compared with the adverse effects of star fruit (Averrhoa carambola) in patients with impaired renal function, gabapentin and carambola both cause acute alteration of consciousness and other central nervous system disorientation such as dizziness, nausea and vomiting within hours to days. Haemodialysis is effective in both conditions. However, carambola, with its unspecified toxin, is nephrotoxic while gabapentin does not seem to affect renal function and its duration of effect depends solely on creatinine clearance. In addition, the adverse effects of gabapentin on the central nervous system vary from person to person.
In conclusion, emergency physicians should be aware that gabapentin toxicity should be considered as one of the differential diagnoses of altered consciousness in patients with compromised renal function, even after taking a single recommended dose. A single session of haemodialysis is sufficient for treatment; compromised renal function or serious sequelae are not observed.
LEARNING POINTS
Gabapentin is used as an anti-epileptic and for neuropathic pain.
Adverse effects with gabapentin include severe myopathy, severe myoclonus, neutropenia, hypoglycaemia episodes and altered consciousness.
Gabapentin is renally excreted; dose adjustments are required to prevent accumulation and toxicity.
Acknowledgments
This article has been adapted with permission from Hung TY, Seow VK, Chong CF, Wang TL, Chen CC. Gabapentin toxicity: an important cause of altered consciousness in patients with uraemia. Emerg Med J 2008;25:178–9.
Footnotes
Competing interests: none.
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