Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 49, Num. 3, 2003, pp. 285

Journal of Postgraduate Medicine, Vol. 49, No. 3, July-Sept, 2003, pp. 285

Letter to Editor

Gabapentin and Propofol for Treatment of Status Epilepticus in Acute Intermittent Porphyria

Pandey CK, Singh N, Bose N, Sahay S

Department of Anaesthesiology and Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226014
Correspondence Address: Department of Anaesthesiology and Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226014

Code Number: jb03078

Sir,

Seizures may be one of the manifestations of acute intermittent porphyria (AIP) in about 20% of patients.[1],[2] Since patients in porphyric crisis may develop generalised convulsions, safe anticonvulsant therapy is necessary. We report a case of the successful management of status epilepticus in acute intermittent porphyria with gabapentin and propofol.

A 26-year-old female with family history of AIP presented with history of single dose alprazolam intake. On examination she was disoriented, unresponsive to verbal command and quadriparetic with shallow and laboured respiration. Urine porphobilinogen was positive. She was shifted to the intensive care unit (ICU) and intubated with fentanyl and pancuronium and was put on ventilator for respiratory support.

In the ICU, she received 20% dextrose infusion (100 ml/hr) and propranolol 100 mg twice a day. Haematin therapy could be started (4mg/kg/day) on the fifth day of admission. On the twelfth day, the patient developed right facial and upper limb twitching. She was given gabapentin 300 mg thrice a day but the twitching increased in frequency. Gabapentin was increased to 600 mg thrice a day. On the fourteenth day, the patient developed convulsive status epilepticus. Propofol 100 mg was given over five minutes followed by a continuous infusion (2mg/kg/hr). Convulsions stopped within 10 minutes, but propofol infusion was gradually tapered over three hours. Gabapentin was increased to 900 mg thrice a day. From the sixteenth day onwards she became arousable and responsive to verbal command. She was transferred to the neurology ward. At the time of transfer she was able to walk with support and was receiving gabapentin 900 mg thrice a day along with a diet rich in carbohydrates.

Acute intermittent porphyria results from decreased activity of porphobilinogen-deaminase, leading to an increased concentration of haeme precursors.[2] The rate-limiting step in haeme biosynthesis is delta-amino-levulinic-acid which is catalysed by the enzyme amino-levulinic-acid-synthetase.[2] Haeme exerts negative feedback on amino-levulinic-acid-synthetase activity. Decreased negative feedback from haeme increases amino-levulinic-acid-synthetase activity, resulting in increased levels of haeme precursors proximal to the site of the deficient enzymes.[2]

Porphyric crisis can be precipitated by fasting, dehydration, hypothermia, surgical stress and many anaesthetics and nonanaesthetic drugs.[2] The precipitation of porphyric crisis with alprazolam is not known but coincidence of its intake and porphyric crisis in this case raises doubts of its safety in patients with porphyria.

Seizures affect 15-20% of patients with AIP and they tend to occur during an acute attack.[2],[3] In our case, it started with right upper limb and facial twitching, which progressed into convulsing status epilepticus. Phenytoin, barbiturates, carbamazepine, sodium valproate and clonazepam are not safe in AIP with seizures[1],[4] Because gabapentin is not metabolised in humans and does not have effects on hepatic microsomal enzymes, it can be used safely to control seizures in AIP but this drug could not control twitching in our patient.[1],[3] Propofol was selected to control convulsions in this case because it has been found to be effective in human as well as animal studies. Propofol has barbiturate- and benzodiazipine- like effects on the delta-aminobutyric acid and can suppress central nervous system metabolic activity.[5] The safe use of propofol in a susceptible patient for sedation in the ICU has been reported.[6]

Based on our experience of this case we suggest that propofol is an effective anticonvulsant and it should be considered with gabapentin in crisis of AIP with status epilepticus for long-term management where the use of conventional antiepileptic therapy is unsafe.

 REFERENCES

1.	Arora A, Mahajan V. Gabapentin in seizures due to Acute Intermittent Porphyria. Neurol India 2000;48:194-5.  Back to cited text no. 1">  [PUBMED]  [FULLTEXT]
2.	Bloomer JR, Bonkovsky HL. The porphyrias. Dis Mon 1989;35:1-54.  Back to cited text no. 2">  [PUBMED]
3.	Tantum WO 4th, Zachariah SB. Gabapentin treatment of seizures in acute intermittent porphyria. Neurology 1995;45:1216-7.  Back to cited text no. 3">
4.	Reynolds NC Jr, Miska RM. Safety of anticonvulsants in hepatic porphyrias. Neurology 1981;31:480-4.  Back to cited text no. 4">  [PUBMED]
5.	Stecker MM, Kramer TH, Raps EC, O'Meeghan R, Dulaney E, Skaar DJ. Treatment of refractory status epilepticus with propofol: Clinical and pharmacokinetic findings. Epilepsia 1998;39:18-26.  Back to cited text no. 5">  [PUBMED]
6.	Shaw IH, McKeith IG. Propofol and electroconvulsive therapy in a patient at risk from acute intermittent porphyria. Br J Anaesth 1998;80:260-2.  Back to cited text no. 6">  [PUBMED]

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