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cyclosporin 7’ 5 mg/kg daily. At this point, the patient had a severeCushing syndrome, and the serum levels of muscle enzymes hadincreased further, suggestive of severe myolysis. After 5 days onCyA, the patient improved his muscle strength considerably, andthe pain and sensation of illness vanished. The serum creatinekinase became normal and the aldolase concentration fell to threetimes the upper normal limit.We feel that cautious optimism is justified concerning

cyclosporin treatment of severe myositis. The beneficial effect maybe seen within a week, and irreversible muscle damage may beprevented by prompt administration of cyclosporin if conventionaltherapy fails.

Department of Medicine TA,Rigshospitalet University Hospital,DK-2200 Copenhagen N, Denmark

K. BENDTZENN. TVEDEV. ANDERSENG. BENDIXEN

ACYCLOVIR IN CREUTZFELDT-JAKOB DISEASE

SIR,-In the unsuccessful treatment ofCreutzfeldt-Jakob diseasewith acyclovir reported by Dr David and colleagues (March 3,p 512), the drug was given late in the course of the disease. I report asimilar failure of response in a female patient treated at a muchearlier stage, when symptoms had been present for barely 3 months.Acyclovir was given intravenously at a dose of 500 mg thrice dailyfor 10 days but relentless clinical and EEG progression continued.Subsequent histological analysis of the brain confirmed the clinicaldiagnosis. Given the putative viral aetiology of Creutzfeldt-Jakobdisease, it is reasonable to explore the use of new antiviral drugs inthis condition, but acyclovir must join the list of agents which fail toinfluence the course of the disease.

Department of Neurology,Middlesbrough General Hospital,Middlesbrough, Cleveland TS5 5AZ P. K. NEWMAN

LOW-DOSE INFUSION OF MORPHINE PREVENTSRESPIRATORY DEPRESSION

SiR,-After our Jan 14 Lancet report we received several lettersasking about respiratory depression with low-dose epiduralinfusion, in contrast to 10 ml bolus injections. No patient hasexperienced respiratory depression while on continuous morphineinfusion, even when increasing morphine rates have been needed interminal cancer. 1-3 However, we also have some experimentalsupport for the safety of the method. Cisternal cerebellomedullaryCSF morphine concentrations were measured after epidural bolusinjections of 2 mg morphine in 10 ml saline and during morphineinfusion of 0 16 mg/h over 48 h (after an initial bolus of2 mg in 1 mlsaline) in dogs. Morphine concentrations were measured byradioimmunoassay (Diagnostic Products Corporation, Los

Angeles). Peak CSF concentrations were 3594±910 ng/ml(mean±SEM, n=7 and 139±51 ng/ml, n=7), respectively, within20 min of the 10 ml morphine bolus injection and within 2 h of the1 ml bolus injection and during morphine infusion (see figure). CSFmorphine concentrations did not vary significantly over the

remaining 2-48 h of the infusion.We conclude that the high peak CSF morphine levels seen after

the 10 ml bolus injection of 2 mg morphine are due in part to thecephalad ’mental spread of the high volume injected into theepidural spare. High peak CSF-morphine levels can be avoided bylow-volume injection, where morphine concentrations near therespiratory centre are the result of the rostral movement of

morphine in the CSF fluid alone. 5

1. Coombs DW, Saunders RL, Gaylor M, Pageau MG. Epidural narcotic infusionreservoir: Implantation technique and efficacy. Anesthesiology 1982; 56: 469-73.

2. Müller H, Vogelsberger W, Aigner K, Herget HF, Hemplemann G. Kontinuierlicheperidurale Opiatapplikation mit einer implantierten Pumpe. Regional-Anaesthesie1983; 6: 47-51

3. Harbough RE, Coombs DW, Saunders RL, Gaylor M, Pageau M. Implantedcontinuous epidural morphine infusion system. Preliminary report. J Neurosurg1982; 56: 803-06.

4. Erdemir H, Soper LE, Sweet RB. Studies of factors affecting peridural anesthesia.Anesth Analg 1965; 44: 400-404.

5. Bromage PR, Camporesi EM, Durant PA, Nielson CH. Rostral spread of epiduralmorphine. Anesthesiology 1982; 56: 431-36.

Cisternal cerebellomedullary CSF concentrations.

CSF morphine concentrations do increase dose-dependently afterepidural bolus injection6,7 and there is no doubt that a connectionbetween lumbar CSF-morphine concentrations and late respiratorydepression does exist.6-8 Moreover, additional systemic opioidsincrease the risk of respiratory depression, as do repeated epiduralbolus injections of morphine.9 Provided opioids are not given forpremedication or during the operation low-volume bolus injectionsof morphine will decrease the risk of respiratory depression, andcontinuous low-dose infusion of morphine will prevent it. Paintreatment by high-volume bolus epidural injections of morphineshould be abandoned.

Department of Anaesthesiology,University of Freiburg,78 Freiburg, West Germany

J. CHRUBASIKK. L. SCHOLLERK. WIEMERS

Department of Neurosurgery,University of Freiburg K. WEIGEL

Department of Forensic Medicine,University of Freiburg G. FRIEDRICH

IDENTIFYING TRUE PREMATURE LABOUR

SIR,-We have attempted to follow Castle and Turnbull’s

techniquel° for predicting which women are in true prematurelabour by looking for in utero breathing. The technique has notworked for us; we noted fetal breathing in four cases who weredelivered within 12 h, despite all our efforts to prevent them fromdoing so. In retrospect, in three of the four cases, there was

suggestion, from very high maternal white cell counts, positiveC-reactive proteins, or positive bacterial cultures, ofchorioamnionitis. The Oxford technique may work well in areaswhere silent chorioamnionitis is not a factor in the onset of

premature labour; however, amongst our patients, the in uteroassessment of fetal breathing does not seem to be much help.Department of Obstetrics and Gynecology,University of Nebraska Medical Center,Omaha, Nebraska 68105, USA ROBERT C. GOODLIN

6. Jörgensen BC, Andersen HB, Engquist A. CSF and plasma morphine after epiduraland intrathecal application. Anesthesiology 1982; 55: 714-15.

7. Nordberg G, Hedner T, Mellstrand T, Dahlström B. Pharmacokinetic aspects of

epidural morphine analgesia. Anesthesiology 1983; 58: 545-51.8 Glynn CJ, Mather LE, Cousins MJ, Wilson PR, Graham JR. Spinal narcotics and

respiratory depression. Lancet 1980; ii: 356-57.9. Gustafson LL, Schildt B, Jacobson K. Adverse effects of extradural and intrathecal

opiates: Report of a nationwide survey in Sweden. Br J Anaesth 1982; 54: 479.10. Castle BM, Turnbull AC. The presence or absence of fetal breathing movements

predicts the outcome of preterm labour. Lancet 1983; ii: 471-72.