PROPOFOL INFUSION FOR THE TREATMENT OF STATUS EPILEPTICUS

480

IgG class ARA titres (Rl type) were measured in the serum by indirect immunofluorescence.8 Children with positive ARA titres were asked to join the study, which included small-bowel biopsy. Those with flat intestinal mucosa were considered to have CD and were prescribed a gluten-free diet. ARA titres were followed sequentially after introduction of the diet and follow-up biopsy was done to confirm mucosal healing. Over 7 years 12 children (mean age 10-8 years, range 4-16) with arthritis or arthralgia were found to have positive serum ARA titres (table). All 9 children with positive IgA-ARA were found to have small, flat intestinal mucosa. The 3 children positive for IgG-ARA only had normal mucosa. No case had IgA deficiency. All the children with flat intestinal mucosa were treated with a gluten-free diet. Serum ARA titres rapidly decreased in all and became negative within a year (table). The first biopsy was done recently in cases 8 and 9. Further biopsies after treatment were done in 5 children after 6 months to 5 years on a gluten-free diet. The disappearance of ARA correlted with mucosal recovery. Case 9 had been treated for JRA and recurrent fluid on the joint from the age of 2. Her serum as well as synovial fluid contained ARA before introduction of the gluten-free diet.

SERUM ARA AND Sl’vlALL-BOB1VEL BIOPSY FINDINGS IN CHILDREN WITH

JOINT MANIFESTATIONS BEFORE AND AFTER TREATMENT WITH GLUTEN-FREE DIET

M, Kallonen K, Lahdeaho M-L, Visakorpi JK Changing pattern of childhood coeliac disease in Finland. Acta Paediatr Scand (in press). 2. Cooke WT, Holmes GKT Coeliac disease. Edinburgh. Churchill Livingstone, 1984 3 Adelizzi RA, Pecora AA, Chiesa JC. Celiac disease: Case report with an associated arthropathy. Am J Gastroenterol 1982; 77: 481-85. 4 Parke AL, Fagan EA, Chadwick VS, Hughes GR Coeliac disease and rheumatoid arthritis. Ann Rheum Dis 1984; 43: 378-80 5 Bourne JT, Kumar P, Huskisson EC, Mageed R, Unsworth DJ, Wojtulewski JA. Arthritis and coeliac disease Ann Rheum Dis 1985; 44: 592-98. 6 Pinals RS Arthritis associated with gluten-sensitive enteropathy. J Rheumatol 1986; 13: 201-04. 7. Pelkonen P, Savilahti E, Makela AL. Persistent and transient IgA deficiency in juvenile rheumatoid arthritis. ScandJ Rheumatol 1983, 12: 273-79. 8. Maki M, Hallstrom O, Huupponen T, Vesikari T, Visakorpi JK Increased prevalence of coeliac disease in diabetes. Arch Dis Child 1984, 59: 739-42. 9. Teppo A-M, Maki M, Hallstrom O, Maury CPJ Antibodies to 90 kilodalton glycoprotein in childhood and adolescent celiac disease Relationship to reticulin antibodies. J Pediatr Gastroenterol Nutr 1987, 6: 908-14. 10. Maki M, Hallstrom O, Viaskorpi JK. Gluten challenge m postpubertal children with coeliac disease: Detection of mucosal relapse with IgA-class reticulin antibody Pediatr Res 1987; 22: 103. 11 Savilahti E, Pelkonen P, Visakorpi JK IgA deficiency in children. Arch Dis Child 1971; 46: 665-70. 1. Maki

PROPOFOL INFUSION FOR THE TREATMENT OF STATUS EPILEPTICUS SiR,—Propofol, a new intravenous anaesthetic agent, has been used via continuous infusion for short-term sedation in intensive care. We report its use over 18 days to treat status epilepticus caused by Coxsackie B encephalitis. A 21-year-old woman was being mechanically ventilated in the intensive care unit for uncontrolled seizures and hypoxia due to Coxsackie B encephalitis. Phenytoin, phenobarbitone, and intravenous diazepam had not controlled the seizures. After endotracheal intubation and mechanical ventilation, a continuous intravenous infusion of midazolam controlled the seizures for 48 h -

only. Combined

diazepam,

phenytoin,

phenobarbitone, and of propofol (100

chlormethiazole also failed. Because a single bolus

mg) completely suppressed the seizures, a continuous infusion was started at a rate of 5-7 mg/kg/h. The lungs were hyperventilated and dexamethasone was given to reduce cerebral oedema. Arterial blood pressure and heart rate were normal throughout the infusion. Arterial blood gases, full blood count, blood glucose, urea, electrolytes, and liver function tests were estimated daily. Blood was twice transfused when the haemoglobin concentration fell to 8-9 g/dl (packed cell volume 0-270). This was predictable from a previous study. Rapid and easy neurological assessment was effected by temporary interruption of the propofol infusion. When this was done on the eighteenth day, no improvement in the seizures was *"-Iegdtive = less T

not

so

intrathecal interferon

was

following day the woman’s temperature gram-negative septicaemia, hypotension,

In recent years wehave seen 3 children with CD among 150 children with JRA. The association of CD and JRA would seem to be more frequent than that expected by chance. However, it should be remembered that the index case with CD and JRA had IgA deficiency, which has a high prevalence of CD." Furthermore case 1 also had diabetes mellitus. Gastrointestinal diseases such as ulcerative colitis, Crohn’s disease, and diseases caused by invasive enteropathogens can cause joint manifestations. Therefore it is not surprising to find arthritis and arthralgia in children with active CD and heavily inflamed small-bowel mucosa. Our study shows that arthritis and arthralgia should be included in the list of monosymptomatic forms of CD. The results also emphasise the importance of measuring serum IgA-ARA in detecting flat intestinal mucosa. The role of IgG-ARA in children with joint complaints and normal intestinal mucosa is unknown.

Departments of Paediatrics and Microbiology, University Central Hospital of Tampere SF-33520 Tampere, Finland

administered. On the 40°C and she had and metabolic acidosis. She was resuscitated from a cardiac arrest but disseminated intravascular coagulation and acute renal failure supervened. she died on the twenty-third day. Minor biochemical and haemotological changes are noted when propofol is used as an anaesthetic agent. Anaemia and a small rise in blood-glucose have been reported,2 and we noted this too (blood glucose 65-7-2 mmol/1). This raised blood glucose preceded the propofol infusion. Insulin was not given. Liver-function tests were normal throughout, as with single-dose propofol.3 Possible adrenal gland dysfunction is a major worry when intravenous anaesthetic drugs are used for long-term sedation."" In this patient, daily serum cortisol levels were not measured. Exogenous steroid was administered and then tapered off after 14 days. A single serum cortisol measurement on the day before death was very high (1075 nmol/1; normal 140-170). The ability of the adrenal cortex to respond to stress was then unimpaired. A continuous propofol infusion was an effective anticonvulsant in this case. This is interesting since the effects of propofol on the electroencephalogram (EEG) and seizure activity have been the subject of conflicting reports. The suggestion of Hodkinson et al6 that a proconvulsant tendency of propofol can be demonstrated by electrocorticography, thus making it a suitable agent for electroconvulsive therapy, has been refuted by Rampton et all and is certainly not in keeping with our experience. Our patient had four observed

than 1’50.

tested

MARKKU MAKI OLAVI HALLSTROM PAULA VERRONEN TIMO REUNALA MARJA-LEENA LAHDEAHO KATI HOLM JARMO K. VISAKORPI

was

481 EEGs done during her illness. All

were abnormal varying in with her clinical state, but the characteristic pattern of methohexitone anaesthesia was never present. So far, propofol infusions have only been used for short periods.1 Wider and long-term use must await further metabolic and

severity

physiological studies. Departments of Anaesthesia, St Stephen’s Hospital, London SW10 9TH; and Charing Cross and Westiminster Hospitals, London

P. R. WOOD G. P. R. BROWNE S. PUGH

RM, Lalor JT, Lumley J, Royston D, Morgan M. Propofol infusion for sedation in the intensive care unit: Preliminary report. Br Med J 1987; 294: 397-450 2 Sear JW, Uppmgton K, Kay NG. Haematology and biochemical changes dunng anaesthesia with propofol (Diprivan). Postgrad Med J 1985; 61 (suppl 3): 165-68. 3 Robinson FP, Patterson CC. Changes in liver function tests after propofol (Diprivan). Postgrad Med 1985, J 61 (suppl 3): 160-61. 4. Ledingham IA, Watt I Influence of sedation on mortality m critically ill multiple trauma patients. Lancet 1983; i 1270. 5 Prizios P Etomidate, sedative and neuroendocrine changes Lancet 1983, ii. 276 6. Hodkmson BP, Frith RW, Mee EW. Propofol and the electroencephalogram. Lancet 1987, ii 1518. 7 Rampton AJ, Griffin RM, Durcan JJ, Stuart CS. Propofol and electroconvulsive therapy Lancet 1988, i: 296

transmission of infection with HIV in the workplace remains the mainstay of prevention. However, establishing the efficacy of a post-exposure chemoprophylactic measure is a desirable goal: besides preventing a few HIV infections in health-care workers it might make them less apprehensive about working with HIVinfected patients. Prophylactic regimens cannot be evaluated by studying health-care workers after parenteral exposure: the rate of seroconversion is so low that huge numbers of exposed workers would be needed to demonstrate a protective effect. However, prophylactic zidovudine or similar drugs could be tested in non-human primates experimentally infected with HIV.

1. Grounds

POST-EXPOSURE PROPHYLAXIS AGAINST HIV INFECTION IN HEALTH CARE WORKERS

S!R,—A 24-year-old laboratory technician pricked

a

finger

with a broken haematocrit tube filled with blood from a patient with seropositive AID S and a history of Pneumocystis carinii pneumonia and Kaposi sarcoma. The wound bled. The AIDS patient’s blood, drawn 4 days later, grew HIV. The risk of transmission of HIV associated with a single parenteral occupational exposure is estimated at 0-13% (95% confidence interval O’01-O 74%), but the risk may depend on how much blood is injected and on whether the blood is viraemic.2 These two factors would have put our technician at increased risk. It has been reported that substances acting as reverse transcriptase (RT) inhibitors protect susceptible T cells in vitro from viral replication and from the cytopathic effects of HIV, provided the inhibitor is added before inoculation. This protection occurred despite a high multiplicity of infection (1000 virus particles per target cell). After 30 days of incubation, the cells were thoroughly washed to remove any RT inhibitor and extracellular remaining virion. During the ensuing 80 days neither virus replication nor viral protein expression was observed, suggesting that the inhibitors had conferred definite protection against the infectivity and replication of HIV / Other experiments, on Kirsten murine sarcoma virus, have demonstrated that even a single cycle of retroviral infection can be prevented.’ Mitsuya and Broder5 have suggested that after phosphorylation, nucleoside analogues such as zidovudine bring about a selective chain termination as a RNA form of the virus attempts to make DNA copies of itself. The inherent RNAse H activity of the RT or cellular nucleases would then be expected to degrade the viral RNA, giving the virus no second chance. We wondered if early administration of zidovudine might prevent HIV infection in our technician. With the approval of the chairman of the hospital’s ethics committee and after pregnancy had been ruled out, the facts were explained to her and she was offered a 4-day course of zidovudine 500 mg four times daily. Treatment began 2 h after the exposure. 3 months after exposure she remains free of any serological marker of HIV infection (anti-HIV ELISA, confirmatory anti-env and anti-core ELISAs, HIV antigen p24, and western blot). We accept that our offer of prophylactic zidovudine is debatable. We had to weigh the very small risk that the exposed women would contract a potentially lethal disease against prophylaxis of unknown efficacy. Furthermore, though acute side-effects of the drug would probably be mild with such a short course of treatment, the long term side-effects are unknown. We do not think that zidovudine prophylaxis can yet be offered to health-care workers with parenteral HIV exposure. Compliance with Centers for Disease Control recommendations for preventing

deeply

P. R. MEYLAN P. FRANCIOLI H. DECREY J. PH. CHAVE M. P. GLAUSER

Division of Infectious Diseases, Department of Internal Medicine, CHU Vaudois, 1011 Lausanne, Switzerland

DK, Saah AJ, Fahey BJ, et al. Prospective assessment of the nsk for occupational/nosocomial infection with human immunodeficiency virus in a large

1. Henderson

care workers. Presented at the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy (New York, 1987): abstr 76. 2 Friedland GH, Klem RS Transmission of the human immunodeficiency virus. N Engl J Med 1987; 317: 1125-35 3 Mitsuya H, Jarret RF, Matsukura M, et al. Long-term inhibition of human T-lymphotropic virus type III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T-cells protected by 2’,3’-dideoxynucleosides in vitro. Proc Natl Acad Sci USA 1987; 84: 2033-37. 4 Dahlberg JE, Mitsuya H, Blam SB, et al Broad spectrum antiretroviral activity of 2’,3,-dideoxynucleosides Proc Natl Acad Sci USA 1987; 84: 2469-73. 5. Mitsuya H, Broder S. Strategies for antiviral therapy in AIDS. Nature 1987, 325:

cohort of health

773-78.

EYE

PROTECTION, HIV, AND ORTHOPAEDIC SURGERY

SIR,-Operating theatres expose health workers to close contact with body fluids and so to the risk of contracting blood-borne infections. In the UK eye protection is advised when there is a risk of contamination. We have been trying to find out, in a trauma centre, those procedures most likely to lead to contamination. All surgeons nurses, nurses, anaesthetists, and technicians in the orthopaedic and general surgery theatres were provided with a 10 cm2 target to detect the risk of skin contamination by tissue and fluids. The targets (graph paper on a headband immediately above eyes) were changed after every operation. The eye is the least protected part of a theatre worker’s anatomy. Under x 10 magnification targets were inspected for contamination with fluids, and contaminating particles were counted. 54 consecutive orthopaedic operations (24 soft tissue, 30 bone) and 40 general surgical operations involving all but vascular cases were studied. TARGET STRIKES RECORDED DURING

30 INVASIVE BONE

PROCEDURES

Only staff who were scrubbed were contaminated. General surgery and soft tissue orthopaedic surgery carried little risk, but operations such as those involving bone cutting and intramedullary reaming exposed all scrubbed personnel to considerable contamination (table). The conjunctiva of the eye offers a portal of entry for infection and an abrasive mixture of bone, marrow, and blood propelled at speed by power tools and reamers could damage any epithelial surface. By its nature emergency orthopaedic surgery cannot be delayed until the patient has been screened for antibody to human immunodeficiency virus (HIV) or other blood borne infectious agents. The probability of an injured patient being HIV positive is low, but it may well rise.2 HIV infection acquired occupationally by