EFFICACY OF FLUMAZENIL IN COPD PATIENT WITH THERAPEUTIC DIAZEPAM LEVELS

392 Mean aspartate transaminase (AST) levels were comparable among groups before treatment, but fell significantly afterwards only in group A. Follow-up liver biopsies have not yet been done. Patients from the two studies are not entirely comparable, because of the younger mean age and of the possible role of siderosis in p-thalassaemia. However, patients with massive iron overload, in whom metal toxicity is more likely, were excluded, and the younger patients in group A were all responders to IFN. Although different types of IFN have been used, other reports suggest that lymphoblastoid and recombinant IFN are equally effective. We conclude that the low response rate in p-thalassaemia is accounted for by the different type of exposure to NANB, which might cause a high NANB viral load and/or reinfection with the virus or with different types of hepatitis virus. In the absence of indicators of NANB viraemia and replication of possible responders cannot be identified pre-treatment. If our data are confirmed by the final results of these and other trials, resistance to ’:/.- IFN may have to be taken into account when treating patients such as haemophilics or drug addicts, whose medical condition or lifestyle entails a high chance of multiple exposures to viruses. A. CRAXÌ V. DI MARCO Divisions of Internal Medicine R. VOLPES and Haematology, R. BRUNO Institute of Clinical Medicine R, Ospedale V. Cervello, 90146 Palermo, Italy

U. PALAZZO A. MAGGIO

EFFICACY OF FLUMAZENIL IN COPD PATIENT WITH THERAPEUTIC DIAZEPAM LEVELS

SIR,-A 77-year-old former coalminer with pneumosilicosis and

emphysema that had been slowly progressive for 5 years was admitted to hospital with signs of bradyphrenia, anisocoria, and mild dyspnoea. 1 week earlier he had an exacerbation of his chronic obstructive pulmonary disease (COPD), successfully treated with amoxycillin, but he had subsequently deterioriated mentally with loss of verbal contact, diminished daily activities, anorexia, and urinary incontinence at night. On examination he was found to be bradyphrenic, slow in action, and unable to answer questions, but there were no clear signs of depressed consciousness. His right pupil was wider than the left. He had mild respiratory distress. His capillary blood POZ was very low (table). Neurological examination revealed no other disturbances and routine laboratory tests were normal, except for signs of a past infection. Chest X-ray revealed pneumosilicosis but no other abnormality. His medication was oral diazepam 25 mg twice daily and ipratropium bromide by aerosol four times daily. Diazepam was stopped on admission. Because the patient’s neurological condition might have been caused by a combination of central hypoxia and the use of diazepam, blood samples were drawn for measurement of diazepam and desmethyldiazepam. While the results of the diazepam assay were awaited the patient was given two 0-2 mg intravenous dosages of flumazenil, 1 min apart. This resulted in rapid improvement, with complete clearance of all symptoms. Diazepam and desmethyldiazepam levels turned out to be therapeutic. At the same time intravenous aminophylline (720 mg over 24 h) and prednisolone were started. Respiratory function steadily improved. BLOOD GASES AND DRUG LEVELS ——————————————————& mdash;———[————————[—————— —————————————

Diazepam and desmethyldiazepam levels were virtually unchanged 24 h and 48 h later, but the patient’s neurological status remained excellent. We conclude that the use of benzodiazepines, even at low dosages, should be restricted in COPD patients. When there is neurological deterioration in such patients, flumazenil may be helpful even when benzodiazepine serum levels are not raised. Department of Internal Medicine and Clinical Pharmacy, Maasland Hospital, 6130 MB Sittard, Netherlands

M. APPEL H. N. L. M. BRON P. M. HOOYMANS

R. JANKNEGT

ARTHROPOD VENOM AND BONE MARROW

APLASIA/RHABDOMYOLYSIS SIR,--On April 30,1987, a 34-year-old woman felt a painful sting on her left leg while hanging out the washing, she could not identify the creature. After a few hours she became febrile (38°C), with vomiting, diarrhoea, and dermatitis on the left leg. On May 1 she was admitted to the Galliera Hospital, where she remained for 4 days. Severe haematological changes were found, and on May 4 she was transferred to S. Martino Hospital. Diffuse muscle pains and dyspnoea added to the symptoms. Total bone marrow aplasia and rhabdomyolysis were observed: leucocytes 300/pl, platelets 5000/1, creatine phosphokinase (CPK) 97000 IU/1, lactate dehydrogenase 12 000 IU/1, SGOT 2500 IU/1, SGPT 100 IU/1, myoglobin 6300 ng/ml, creatinine 1 mg/dl. Acute renal failure developed and the patient died on May 6 of heart failure. Necropsy confirmed dermatitis, with pulmonary oedema, congestion, hepatic steatosis. A 50-year-old woman who had had pharyngitis for 3 months, with hyperpyrexia and leucopenia was stung or bitten on the back of her right hand by an arthropod, which she was unable to identify, about 3 days before hospital admission. After a few hours her fever increased and erythema and oedema appeared. On July 15 she was admitted to the S. Martino hospital with hyperpyrexia (40°C), nausea, diarrhoea, pharyngitis, syncope, and dermatitis of the right arm, with a hard oedema extending up to the armpits, axillary lymphadenopathy, and haemorrhagic blisters leading to the back of the hand. Lymphangitis and diffuse ecchymoses appeared, and the oedema became very severe. Blood culture was positive for Pseudomonas aeruginosa. Her condition steadily worsened. On July 17 sternal marrow biopsy revealed global aplasia. A blood test gave the following results: leucocytes 500/1, red blood cells 2930 000/jI, urea 78 mg/dl, glucose 36 mg/dl, CPK 2000 IU/1, SGOT 380 IU/1, SGPT 430 IU/1. Plasmapheresis was not tolerated and she was transferred to intensive care because of dyspnoea, peripheral circulatory failure, and severe acidosis. Respiratory and cardiac arrest were promptly treated, but she remained in a coma, with mydriasis and areflexia, and died half an hour later. Necropsy revealed necrotising fasciitis of her upper arm, pulmonary oedema and congestion, and hepatic steatosis. Some of the doctors who treated these patients wrongly blamed the two deaths on bites from the black widow spider (Latrodectits tredecimguttatus). We do not understand this: the symptoms were in no way typical of latrodectism, which is essentially a clinical diagnosis.! The reaction of the national press instilled groundless fears about this spider in Italy. The possibility that the sting of an arthropod might lead to bone-marrow aplasia and/or rhabdomyolysis has not been reported before in Italy. Neither patient could identify what had bitten them. In the second case the sting of an arthropod is not a likely cause of the bone marrow aplasia. The patient was leucopenic (1500/fil) before admission, and for months she had been intensively using anti-inflammatory drugs to cure pharyngitis. The sting may, at most, have caused necrostising fasciitis and contributed to the rapid development and fatal outcome in a woman who was already immunodeficient, as indicated by the Pseudomonas sepsis. The first case is different; there was no relevant history, except for the sting. The fact that the patient was stung on the calf, while standing, favours an arthropod of the order Hymenoptera (genus Vespa or Vespula, for example). As far as we know, bone marrow