Temazepam Overdose Associated with Bullous Eruptions
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ACADEMIC EMERGENCY MEDICINE • October 1999, Volume 6, Number 10 1071 BRIEF REPORTS Temazepam Overdose Associated with Bullous Eruptions Toxic doses of several agents have been associated with bullous erup- tions (BE). BE have been described with barbiturates, methadone, imip- ramine, and glutethimide over- doses. 1 Among the benzodiazepines, nitrazepam, 2 diazepam, 3 and oxaze- pam 4 have been associated with BE. We describe an 83-year-old woman presenting with coma and BE after an overdose with temazepam. Al- though extensive, fixed-drug erup- tions have been described with tem- azepam, 5 to our knowledge, the association with BE has not been previously reported. CASE REPORT An 83-year-old woman was brought to the ED after her niece found her unconscious one morning. The pa- tient had been in her usual state of good health until the night prior to admission when she complained of feeling unusually tired. She had no significant past medical history but had been prescribed temazepam, 7.5 milligrams, at night for insomnia. On arrival to the ED she was co- matose and afebrile. Blood pressure was 110/70 mm Hg, heart rate 66 beats/min. Respiration was shallow with a rate of 8 breaths/min. Gaze was midline, pupils were 3 millime- ters and reactive, and oculovestibu- lar reflexes were present. The pa- tient withdrew all four extremities to painful stimulation. She did not have abnormal posturing but was hypotonic with generalized hypore- flexia and bilateral extensor plantar responses. Cardiac, chest, and ab- dominal examinations were normal. She was noted to have bilateral thin- walled BE over the medial aspect of the knees measuring 5 centimeters and containing a serous fluid. No other skin lesions were seen. The white blood cell count was 32,000 cells/cm 3 with 99% lympho- cytosis (subsequent workup, includ- ing bone marrow examination, re- vealed the cause of the leukocytosis to be chronic lymphocytic leukemia). Other hematologic and chemical val- ues were normal. Urine toxicology was positive for benzodiazepines. Lumbar puncture had normal open- ing pressure and normal cerebrospi- nal fluid (CSF) examination. Urine, blood and CSF cultures and viral studies were negative. Electrocar- diography, chest x-ray, and head CT were normal. The patient showed a dramatic response to the intravenous admin- istration of flumazenil, 1 mg, ti- trated over 5 minutes, with improve- ment of the level of consciousness. She did not develop any further skin lesions during her hospital stay. She later admitted to unintentionally taking about seven temazepam tab- lets. When contacted three months later, she was doing well. She had taken regular doses of temazepam without untoward effects, but had discontinued it on her doctor’s ad- vice. DISCUSSION Temazepam, an intermediate-acting benzodiazepine that acts on the gamma-aminobutyric acid A (GABA A ) receptor, is a commonly prescribed hypnotic. Overdose can result in coma with respiratory depression, which can be safely and rapidly re- versed with the benzodiazepine re- ceptor antagonist flumazenil. It is hence essential to identify and treat these patients early. A variety of skin lesions may be seen with drug overdoses. 1 BE are commonly seen over pressure points. Central hyperthermia, sweat-gland necrosis, and direct drug toxicity have been suggested as possible causes for BE. 3 In our patient the BE did not recur when the drug was taken again at the regular nontoxic dose. The investigations in our pa- tient did not suggest other causes such as infection. Although leuke- mia may be associated with BE, we are satisfied that there was a clear causal relationship between the overdose and the development of the lesions. Flumazenil can be safely used in overdoses with benzodiazepines. There should be a slow dose titration under close observation. It allows an improvement in level of conscious- ness, permits the return of protec- tive airway reflexes, and lessens the potential for aspiration. However, it may potentiate seizures in patients who have been given benzodiaze- pines for life-threatening conditions (e.g., status epilepticus) or when there is evidence of overdose with tricyclic agents. It is hence contra- indicated in these situations. 6 CONCLUSIONS Intentional or unintentional drug overdoses are common in elder pa- tients. It may be difficult to obtain a history of drug overdose in drowsy or comatose elder patients. While in- fective causes need to be ruled out with appropriate tests, the possibil- ity of drug overdose needs to be kept in mind while evaluating comatose elder patients with skin lesions.— JOE VERGHESE, MRCPI, and JOSE ´ MERINO, MD, MPhil, Department of Neurology, Albert Einstein College of Medicine, Bronx, NY Key words. temazepam; bullous eruptions; elders. References 1. Breathnach SM. Drug reactions. In: Champion RH, Burton JL, Ebling FJG (eds). Textbook of Dermatology (5th Ed). Oxford: Blackwell Scientific Publica- tions, 1992, pp 2961–3035. 2. Ridley CM. Bullous lesions in nitra- zepam overdose. Br Med J. 1971; iii:28. 3. Verma AJ, Fisher BK, Sarin MK. Di- azepam-induced coma with bullae and eccrine sweat gland necrosis. Arch Intern Med. 1977; 137:1207–10. 4. Moshkowitz M, Pines A, Finkelstein A, Hershkowitz R, Levo Y. Skin blisters as a manifestation of oxazepam toxicity. J Toxicol Clin Toxicol. 1990; 28:383–6. 5. Archer CB, English JSC. Extensive fixed drug eruptions induced by temaze- pam. Clin Exp Dermatol. 1988; 13:336– 8. 6. Ellenhorn MJ, Schonwald S, Ordog G, Wassenberg J. Ellenhorn’s Medical Tox- icology. Diagnosis and Treatment of Hu- man Poisoning. Baltimore: Williams & Wilkins, 1997, pp 698–702.
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Transcript of Temazepam Overdose Associated with Bullous Eruptions
ACADEMIC EMERGENCY MEDICINE • October 1999, Volume 6, Number 10 1071
BRIEF REPORTS
Temazepam Overdose Associated withBullous Eruptions
Toxic doses of several agents havebeen associated with bullous erup-tions (BE). BE have been describedwith barbiturates, methadone, imip-ramine, and glutethimide over-doses.1 Among the benzodiazepines,nitrazepam,2 diazepam,3 and oxaze-pam4 have been associated with BE.We describe an 83-year-old womanpresenting with coma and BE afteran overdose with temazepam. Al-though extensive, fixed-drug erup-tions have been described with tem-azepam,5 to our knowledge, theassociation with BE has not beenpreviously reported.
CASE REPORT
An 83-year-old woman was broughtto the ED after her niece found herunconscious one morning. The pa-tient had been in her usual state ofgood health until the night prior toadmission when she complained offeeling unusually tired. She had nosignificant past medical history buthad been prescribed temazepam, 7.5milligrams, at night for insomnia.
On arrival to the ED she was co-matose and afebrile. Blood pressurewas 110/70 mm Hg, heart rate 66beats/min. Respiration was shallowwith a rate of 8 breaths/min. Gazewas midline, pupils were 3 millime-ters and reactive, and oculovestibu-lar reflexes were present. The pa-tient withdrew all four extremitiesto painful stimulation. She did nothave abnormal posturing but washypotonic with generalized hypore-flexia and bilateral extensor plantarresponses. Cardiac, chest, and ab-dominal examinations were normal.She was noted to have bilateral thin-walled BE over the medial aspect ofthe knees measuring 5 centimetersand containing a serous fluid. Noother skin lesions were seen.
The white blood cell count was32,000 cells/cm3 with 99% lympho-cytosis (subsequent workup, includ-ing bone marrow examination, re-vealed the cause of the leukocytosisto be chronic lymphocytic leukemia).Other hematologic and chemical val-ues were normal. Urine toxicology
was positive for benzodiazepines.Lumbar puncture had normal open-ing pressure and normal cerebrospi-nal fluid (CSF) examination. Urine,blood and CSF cultures and viralstudies were negative. Electrocar-diography, chest x-ray, and head CTwere normal.
The patient showed a dramaticresponse to the intravenous admin-istration of flumazenil, 1 mg, ti-trated over 5 minutes, with improve-ment of the level of consciousness.She did not develop any further skinlesions during her hospital stay. Shelater admitted to unintentionallytaking about seven temazepam tab-lets. When contacted three monthslater, she was doing well. She hadtaken regular doses of temazepamwithout untoward effects, but haddiscontinued it on her doctor’s ad-vice.
DISCUSSION
Temazepam, an intermediate-actingbenzodiazepine that acts on thegamma-aminobutyric acidA (GABAA)receptor, is a commonly prescribedhypnotic. Overdose can result incoma with respiratory depression,which can be safely and rapidly re-versed with the benzodiazepine re-ceptor antagonist flumazenil. It ishence essential to identify and treatthese patients early.
A variety of skin lesions may beseen with drug overdoses.1 BE arecommonly seen over pressure points.Central hyperthermia, sweat-glandnecrosis, and direct drug toxicityhave been suggested as possiblecauses for BE.3 In our patient theBE did not recur when the drug wastaken again at the regular nontoxicdose. The investigations in our pa-tient did not suggest other causessuch as infection. Although leuke-mia may be associated with BE, weare satisfied that there was a clearcausal relationship between theoverdose and the development of thelesions.
Flumazenil can be safely usedin overdoses with benzodiazepines.There should be a slow dose titrationunder close observation. It allows animprovement in level of conscious-ness, permits the return of protec-tive airway reflexes, and lessens thepotential for aspiration. However, itmay potentiate seizures in patientswho have been given benzodiaze-pines for life-threatening conditions(e.g., status epilepticus) or whenthere is evidence of overdose withtricyclic agents. It is hence contra-indicated in these situations.6
CONCLUSIONS
Intentional or unintentional drugoverdoses are common in elder pa-tients. It may be difficult to obtain ahistory of drug overdose in drowsyor comatose elder patients. While in-fective causes need to be ruled outwith appropriate tests, the possibil-ity of drug overdose needs to be keptin mind while evaluating comatoseelder patients with skin lesions.—JOE VERGHESE, MRCPI, and JOSEMERINO, MD, MPhil, Department ofNeurology, Albert Einstein College ofMedicine, Bronx, NY
Key words. temazepam; bullouseruptions; elders.
References
1. Breathnach SM. Drug reactions. In:Champion RH, Burton JL, Ebling FJG(eds). Textbook of Dermatology (5th Ed).Oxford: Blackwell Scientific Publica-tions, 1992, pp 2961–3035.2. Ridley CM. Bullous lesions in nitra-zepam overdose. Br Med J. 1971; iii:28.3. Verma AJ, Fisher BK, Sarin MK. Di-azepam-induced coma with bullae andeccrine sweat gland necrosis. Arch InternMed. 1977; 137:1207–10.4. Moshkowitz M, Pines A, FinkelsteinA, Hershkowitz R, Levo Y. Skin blistersas a manifestation of oxazepam toxicity.J Toxicol Clin Toxicol. 1990; 28:383–6.5. Archer CB, English JSC. Extensivefixed drug eruptions induced by temaze-pam. Clin Exp Dermatol. 1988; 13:336–8.6. Ellenhorn MJ, Schonwald S, Ordog G,Wassenberg J. Ellenhorn’s Medical Tox-icology. Diagnosis and Treatment of Hu-man Poisoning. Baltimore: Williams &Wilkins, 1997, pp 698–702.
