- Email: [email protected]
IDENTIFYING TRUE PREMATURE LABOUR
793
cyclosporin 7’ 5 mg/kg daily. At this point, the patient had a severe Cushing syndrome, and the serum levels of muscle enzymes had increased further, suggestive of severe myolysis. After 5 days on CyA, the patient improved his muscle strength considerably, and the pain and sensation of illness vanished. The serum creatine kinase became normal and the aldolase concentration fell to three times the upper normal limit. We feel that cautious optimism is justified concerning cyclosporin treatment of severe myositis. The beneficial effect may be seen within a week, and irreversible muscle damage may be prevented by prompt administration of cyclosporin if conventional
therapy fails. Department of Medicine TA, Rigshospitalet University Hospital, DK-2200 Copenhagen N, Denmark ACYCLOVIR IN
K. BENDTZEN N. TVEDE V. ANDERSEN G. BENDIXEN
CREUTZFELDT-JAKOB DISEASE
SIR,-In the unsuccessful treatment ofCreutzfeldt-Jakob disease acyclovir reported by Dr David and colleagues (March 3, p 512), the drug was given late in the course of the disease. I report a with
similar failure of response in a female patient treated at a much earlier stage, when symptoms had been present for barely 3 months. Acyclovir was given intravenously at a dose of 500 mg thrice daily for 10 days but relentless clinical and EEG progression continued. Subsequent histological analysis of the brain confirmed the clinical diagnosis. Given the putative viral aetiology of Creutzfeldt-Jakob disease, it is reasonable to explore the use of new antiviral drugs in this condition, but acyclovir must join the list of agents which fail to influence the course of the disease. Department of Neurology, Middlesbrough General Hospital,
Middlesbrough, Cleveland
TS5 5AZ
P. K. NEWMAN
LOW-DOSE INFUSION OF MORPHINE PREVENTS RESPIRATORY DEPRESSION
SiR,-After our Jan 14 Lancet report we received several letters asking about respiratory depression with low-dose epidural infusion, in contrast to 10 ml bolus injections. No patient has experienced respiratory depression while on continuous morphine infusion, even when increasing morphine rates have been needed in terminal cancer. 1-3 However, we also have some experimental Cisternal cerebellomedullary CSF morphine concentrations were measured after epidural bolus injections of 2 mg morphine in 10 ml saline and during morphine infusion of 016 mg/h over 48 h (after an initial bolus of2mg in 1 ml saline) in dogs. Morphine concentrations were measured by radioimmunoassay (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, within 20 min of the 10 ml morphine bolus injection and within 2 h of the 1 ml bolus injection and during morphine infusion (see figure). CSF morphine 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 the cephalad ’mental spread of the high volume injected into the epidural spare.High peak CSF-morphine levels can be avoided by low-volume injection, where morphine concentrations near the of the rostral movement of respiratory centre are the result morphine in the CSF fluid alone.5
support for the
safety of the method.
DW, Saunders RL, Gaylor M, Pageau MG. Epidural narcotic infusion Implantation technique and efficacy. Anesthesiology 1982; 56: 469-73. 2. Müller H, Vogelsberger W, Aigner K, Herget HF, Hemplemann G. Kontinuierliche peridurale Opiatapplikation mit einer implantierten Pumpe. Regional-Anaesthesie 1983; 6: 47-51 3. Harbough RE, Coombs DW, Saunders RL, Gaylor M, Pageau M. Implanted continuous epidural morphine infusion system. Preliminary report. J Neurosurg 1982; 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 epidural morphine. Anesthesiology 1982; 56: 431-36. 1. Coombs
Cisternal
cerebellomedullary
CSF concentrations.
CSF morphine concentrations do increase dose-dependently after epidural bolus injection6,7 and there is no doubt that a connection between lumbar CSF-morphine concentrations and late respiratory depression does exist.6-8 Moreover, additional systemic opioids increase the risk of respiratory depression, as do repeated epidural bolus injections of morphine.9 Provided opioids are not given for premedication or during the operation low-volume bolus injections of morphine will decrease the risk of respiratory depression, and continuous low-dose infusion of morphine will prevent it. Pain treatment by high-volume bolus epidural injections of morphine should be abandoned. Department of Anaesthesiology, University of Freiburg, 78 Freiburg, West Germany Department of Neurosurgery, University of Freiburg Department of Forensic Medicine, University of Freiburg
J. CHRUBASIK K. L. SCHOLLER K. WIEMERS
K. WEIGEL G. FRIEDRICH
IDENTIFYING TRUE PREMATURE LABOUR
SIR,-We have attempted to follow Castle and Turnbull’s for predicting which women are in true premature labour by looking for in utero breathing. The technique has not worked for us; we noted fetal breathing in four cases who were delivered within 12 h, despite all our efforts to prevent them from doing so. In retrospect, in three of the four cases, there was suggestion, from very high maternal white cell counts, positive C-reactive proteins, or positive bacterial cultures, of chorioamnionitis. The Oxford technique may work well in areas
techniquel°
where silent chorioamnionitis is not a factor in the onset of premature labour; however, amongst our patients, the in utero assessment 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
reservoir:
Jörgensen BC, Andersen HB, Engquist A. CSF and plasma morphine after epidural and 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 ofa 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. 6.
cyclosporin 7’ 5 mg/kg daily. At this point, the patient had a severe Cushing syndrome, and the serum levels of muscle enzymes had increased further, suggestive of severe myolysis. After 5 days on CyA, the patient improved his muscle strength considerably, and the pain and sensation of illness vanished. The serum creatine kinase became normal and the aldolase concentration fell to three times the upper normal limit. We feel that cautious optimism is justified concerning cyclosporin treatment of severe myositis. The beneficial effect may be seen within a week, and irreversible muscle damage may be prevented by prompt administration of cyclosporin if conventional
therapy fails. Department of Medicine TA, Rigshospitalet University Hospital, DK-2200 Copenhagen N, Denmark ACYCLOVIR IN
K. BENDTZEN N. TVEDE V. ANDERSEN G. BENDIXEN
CREUTZFELDT-JAKOB DISEASE
SIR,-In the unsuccessful treatment ofCreutzfeldt-Jakob disease acyclovir reported by Dr David and colleagues (March 3, p 512), the drug was given late in the course of the disease. I report a with
similar failure of response in a female patient treated at a much earlier stage, when symptoms had been present for barely 3 months. Acyclovir was given intravenously at a dose of 500 mg thrice daily for 10 days but relentless clinical and EEG progression continued. Subsequent histological analysis of the brain confirmed the clinical diagnosis. Given the putative viral aetiology of Creutzfeldt-Jakob disease, it is reasonable to explore the use of new antiviral drugs in this condition, but acyclovir must join the list of agents which fail to influence the course of the disease. Department of Neurology, Middlesbrough General Hospital,
Middlesbrough, Cleveland
TS5 5AZ
P. K. NEWMAN
LOW-DOSE INFUSION OF MORPHINE PREVENTS RESPIRATORY DEPRESSION
SiR,-After our Jan 14 Lancet report we received several letters asking about respiratory depression with low-dose epidural infusion, in contrast to 10 ml bolus injections. No patient has experienced respiratory depression while on continuous morphine infusion, even when increasing morphine rates have been needed in terminal cancer. 1-3 However, we also have some experimental Cisternal cerebellomedullary CSF morphine concentrations were measured after epidural bolus injections of 2 mg morphine in 10 ml saline and during morphine infusion of 016 mg/h over 48 h (after an initial bolus of2mg in 1 ml saline) in dogs. Morphine concentrations were measured by radioimmunoassay (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, within 20 min of the 10 ml morphine bolus injection and within 2 h of the 1 ml bolus injection and during morphine infusion (see figure). CSF morphine 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 the cephalad ’mental spread of the high volume injected into the epidural spare.High peak CSF-morphine levels can be avoided by low-volume injection, where morphine concentrations near the of the rostral movement of respiratory centre are the result morphine in the CSF fluid alone.5
support for the
safety of the method.
DW, Saunders RL, Gaylor M, Pageau MG. Epidural narcotic infusion Implantation technique and efficacy. Anesthesiology 1982; 56: 469-73. 2. Müller H, Vogelsberger W, Aigner K, Herget HF, Hemplemann G. Kontinuierliche peridurale Opiatapplikation mit einer implantierten Pumpe. Regional-Anaesthesie 1983; 6: 47-51 3. Harbough RE, Coombs DW, Saunders RL, Gaylor M, Pageau M. Implanted continuous epidural morphine infusion system. Preliminary report. J Neurosurg 1982; 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 epidural morphine. Anesthesiology 1982; 56: 431-36. 1. Coombs
Cisternal
cerebellomedullary
CSF concentrations.
CSF morphine concentrations do increase dose-dependently after epidural bolus injection6,7 and there is no doubt that a connection between lumbar CSF-morphine concentrations and late respiratory depression does exist.6-8 Moreover, additional systemic opioids increase the risk of respiratory depression, as do repeated epidural bolus injections of morphine.9 Provided opioids are not given for premedication or during the operation low-volume bolus injections of morphine will decrease the risk of respiratory depression, and continuous low-dose infusion of morphine will prevent it. Pain treatment by high-volume bolus epidural injections of morphine should be abandoned. Department of Anaesthesiology, University of Freiburg, 78 Freiburg, West Germany Department of Neurosurgery, University of Freiburg Department of Forensic Medicine, University of Freiburg
J. CHRUBASIK K. L. SCHOLLER K. WIEMERS
K. WEIGEL G. FRIEDRICH
IDENTIFYING TRUE PREMATURE LABOUR
SIR,-We have attempted to follow Castle and Turnbull’s for predicting which women are in true premature labour by looking for in utero breathing. The technique has not worked for us; we noted fetal breathing in four cases who were delivered within 12 h, despite all our efforts to prevent them from doing so. In retrospect, in three of the four cases, there was suggestion, from very high maternal white cell counts, positive C-reactive proteins, or positive bacterial cultures, of chorioamnionitis. The Oxford technique may work well in areas
techniquel°
where silent chorioamnionitis is not a factor in the onset of premature labour; however, amongst our patients, the in utero assessment 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
reservoir:
Jörgensen BC, Andersen HB, Engquist A. CSF and plasma morphine after epidural and 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 ofa 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. 6.