- Email: [email protected]
CIMETIDINE AND OBSTETRIC ANAESTHESIA
252 ineffective. He also pointed out that early steroid made it impossible to ascertain the number of spontaneous remissions. In such circumstances the use of steroids may be considered as less-than-best therapeutic treatment. If it can be shown by measurement of blood viscosity at low shear rates that minimal change disease is associated with increased blood viscosity then it can be expected that alternative methods of treatment will be devised. cases
they
were
treatment
Pathology Department, University of Otago Medical School,
L. O. SIMPSON
Dunedin, New Zealand
CHEMOTHERAPY FOR ADVANCED RESISTANT HODGKIN’S DISEASE
SIR,-In 1975 we reported preliminary results of treating 39 patients with advanced Hodgkin’s disease resistant to standard chemotherapy with CVB (lomustine 6 vinblastine, and bleomycin). We have recently updated these results (table). Nine of FOLLOW-UP DATA
ON
39 PATIENTS TREATED
WITH CVB FOR
ADVANCED RESISTANT HODGKIN’S DISEASE: STATUS ON DEC.
,
31,
1980
CR complete remission; PR partial response; NR no response.
the original patients were alive at the end of 1980. Eight had achieved complete remission after treatment with CVB but had subsequently relapsed and been treated again with further chemotherapy, radiotherapy, or both; at the end of 1980, 6 of these 8 patients were free of disease. 1 patient who had responded only partly to CVB subsequently achieved complete remission when CVB was continued; he has been free of active disease since 1975 and could be cured. Patients with advanced Hodgkin’s disease who relapse after initial treatment with MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) may be treated again with the same combination:2the likelihood of a second response may be predicted by the duration of the first remission and second remissions may be long. However, for those who do not respond to initial treatment with MOPP or who relapse during or soon after completion of the first series, combinations of other non-cross-resistant drugs are usually selected. Our results and those of others3suggest that a proportion of the patients with resistant disease who respond to apparently "second-line" combinations may survive for some years, and the occasional oatient mav indeed bv cured. M.R.C. Leukaemia Unit, Hammersmith Hospital, London W12 0HS
University Department of Medicine, Foresterhill, Aberdeen
JOHN M. GOLDMAN AUDREY A. DAWSON
CIMETIDINE AND OBSTETRIC ANAESTHESIA
potential
1. Goldman 2.
JM, Dawson AA. Combination chemotherapy for advanced resistant Hodgkin’s disease. Lancet 1975; ii: 1224-27. Fisher RI, DeVita VT, Hubbard SP, Simon R, Young RC. Prolonged disease-free survival in Hodgkin’s disease with MOPP reinduction after first relapse. Ann Intern
Med 1979; 90: 761-63. 3. Santoro A, Bonadonna G. Prolonged disease-free survival in MOPP-resistant Hodgkin’s disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Cancer Chemother Pharmacol 1979; 2: 101-05.
in
reducing
the
gastric acidity of women just before
Aspiration of gastric contents, although less common than it used be, remains a preventable cause of death in patients having general anaesthesia for operative delivery. Improved anaesthetic technique and regular oral alkali treatment during labour have had a major effect on the incidence of gastric aspiration. However, doubts have been cast on the safety of antacids,and we have been studying cimetidine as an alternative. Our published and unpublished experience now totals administration to about 5000 patients. Preliminary trials of intravenous2,3 and oral4 cimetidine led to a large field trials in which a 400 mg oral loading dose was given at establishment of labour followed by 200 mg by mouth every 2 hours for a total of seven doses, continuing with alkalis if labour lasted longer than 14 hours. We now give cimetidine throughout labour. Failures (i.e., intragastric pH less than 2 - 5) have been due to the drug not being given at the prescribed times or because anaesthesia was given less than 90 min after the loading dose, as might happen in an emergency. After exclusion of these cases only 4% of patients have had gastric pH values not above 2-5. We cannot be certain of the safety of this technique but every known precaution has been taken, maternal and fetal levels of the drug have been estimated, and a close follow-up of the neonate has
to
shown no abnormalities which could be attributed to cimetidine. The major problem with cimetidine in this type of patient is its brevity of action, and we would welcome a longer acting drug where slight variations from the expected time of administration would not decrease efficacy. Until such a preparation becomes available mothers are given a single 30 ml dose of 0 - 3 mol/1 sodium citrate before being taken to theatre. Cimetidine is more acceptable to many mothers than the repeated use of the magnesium trisilicate or other conventional alkalis, and we hope that, if an alternative to cimetidine emerges, the need for regular administration of such unpalatable preparations to mothers in labour can be avoided. J. W. DUNDEE Department of Anaesthetics, Queen’s University of Belfast, Whitla Medical Building, Belfast BT9 7BL
J. MOORE J. R. JOHNSTON W. MCCAUGHEY
SODIUM VALPROATE AND NELSON’S SYNDROME
SIR,-Dr Jones and colleagues (May 30, p. 1179) describe the effect of sodium valproate on corticotrophin secretion in patients with Nelson’s syndrome. We too have found that sodium valproate, when administered in a dose as low as 300 mg orally, can significantly lower the plasma concentration of ACTH in patients with Nelson’s syndrome. Further data (unpublished) on normal volunteers have shown that the short term administration of valproic acid (250 mgx4for 1 day) lowered the early morning ACTH surge, indicating an effect on the normal secretion of ACTH.7 Though valproic acid produces a rise in brain y-aminobutyric acid (GABA) levels, it also lowers brain aspartate leve1s.7,8 Since aspartate is an excitatory neurotransmitter, the effect of valproic acid on ACTH secretion may be due to changes in the brain concentration of this compound rather than an increase in brain GABA. The effect of GABA analogues such as baclofen and 1. Gibbs CP, Schwartz DJ, Wynne JW, Hood CI, Kuck EJ. Antacid pulmonary aspiration in the dog. Anesthesiology 1979; 51: 380-85. 2. McGowan WAW. Safety of cimetidine in obstetric patients. J Roy Soc Med 1979, 72:
902-07.
JP, Moore J, Dundee JW. Cimetidine in elective Caesarean acidity. Anaesthesia 1981; 36: 167-72. 4. Johnston JR, McCaughey W, Moore J, Dundee JW. Cimetidine as an oral antacid before elective caesarean section. Anaesthesia (in press). 5. Johnston JR, McCaughey W, Moore J, Dundee JW. A field trial of cimetidine as the sole oral antacid in obstetric anaesthesia. Anaesthesia (in press). 6. Elias AN, Gwinup G, Valenta LJ. Effects of hydrocortisone, naloxone and valproic acid in patients with Nelson’s syndrome and Cushing’s disease Clin Endocrinol (in press). 7. Schechter PJ, Trainer Y, Grove J. Effect of n-dipropylacetate on ammo acid concentrations in mouse brain: Correlation with anti-convulsant activity. J Neurochem 1978; 31: 1325-27. 8. Kukino K, Deguchi T. Effects of sodium dipropylacetate on gamma-aminobutyric acid and biogenic amines in rat brain. Chem Pharm Bull (Tokyo) 1977; 25: 2257-62 3.
SIR,-Your April 18 editorial (p. 875) does not deal with all the uses of cimetidine. While a clear picture is emerging of this drug’s value in gastrointestinal disease there has been little mention of its
use
childbirth.
McCaughey W,
section: effect
Howe on
gastric
they
were
treatment
Pathology Department, University of Otago Medical School,
L. O. SIMPSON
Dunedin, New Zealand
CHEMOTHERAPY FOR ADVANCED RESISTANT HODGKIN’S DISEASE
SIR,-In 1975 we reported preliminary results of treating 39 patients with advanced Hodgkin’s disease resistant to standard chemotherapy with CVB (lomustine 6 vinblastine, and bleomycin). We have recently updated these results (table). Nine of FOLLOW-UP DATA
ON
39 PATIENTS TREATED
WITH CVB FOR
ADVANCED RESISTANT HODGKIN’S DISEASE: STATUS ON DEC.
,
31,
1980
CR complete remission; PR partial response; NR no response.
the original patients were alive at the end of 1980. Eight had achieved complete remission after treatment with CVB but had subsequently relapsed and been treated again with further chemotherapy, radiotherapy, or both; at the end of 1980, 6 of these 8 patients were free of disease. 1 patient who had responded only partly to CVB subsequently achieved complete remission when CVB was continued; he has been free of active disease since 1975 and could be cured. Patients with advanced Hodgkin’s disease who relapse after initial treatment with MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) may be treated again with the same combination:2the likelihood of a second response may be predicted by the duration of the first remission and second remissions may be long. However, for those who do not respond to initial treatment with MOPP or who relapse during or soon after completion of the first series, combinations of other non-cross-resistant drugs are usually selected. Our results and those of others3suggest that a proportion of the patients with resistant disease who respond to apparently "second-line" combinations may survive for some years, and the occasional oatient mav indeed bv cured. M.R.C. Leukaemia Unit, Hammersmith Hospital, London W12 0HS
University Department of Medicine, Foresterhill, Aberdeen
JOHN M. GOLDMAN AUDREY A. DAWSON
CIMETIDINE AND OBSTETRIC ANAESTHESIA
potential
1. Goldman 2.
JM, Dawson AA. Combination chemotherapy for advanced resistant Hodgkin’s disease. Lancet 1975; ii: 1224-27. Fisher RI, DeVita VT, Hubbard SP, Simon R, Young RC. Prolonged disease-free survival in Hodgkin’s disease with MOPP reinduction after first relapse. Ann Intern
Med 1979; 90: 761-63. 3. Santoro A, Bonadonna G. Prolonged disease-free survival in MOPP-resistant Hodgkin’s disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Cancer Chemother Pharmacol 1979; 2: 101-05.
in
reducing
the
gastric acidity of women just before
Aspiration of gastric contents, although less common than it used be, remains a preventable cause of death in patients having general anaesthesia for operative delivery. Improved anaesthetic technique and regular oral alkali treatment during labour have had a major effect on the incidence of gastric aspiration. However, doubts have been cast on the safety of antacids,and we have been studying cimetidine as an alternative. Our published and unpublished experience now totals administration to about 5000 patients. Preliminary trials of intravenous2,3 and oral4 cimetidine led to a large field trials in which a 400 mg oral loading dose was given at establishment of labour followed by 200 mg by mouth every 2 hours for a total of seven doses, continuing with alkalis if labour lasted longer than 14 hours. We now give cimetidine throughout labour. Failures (i.e., intragastric pH less than 2 - 5) have been due to the drug not being given at the prescribed times or because anaesthesia was given less than 90 min after the loading dose, as might happen in an emergency. After exclusion of these cases only 4% of patients have had gastric pH values not above 2-5. We cannot be certain of the safety of this technique but every known precaution has been taken, maternal and fetal levels of the drug have been estimated, and a close follow-up of the neonate has
to
shown no abnormalities which could be attributed to cimetidine. The major problem with cimetidine in this type of patient is its brevity of action, and we would welcome a longer acting drug where slight variations from the expected time of administration would not decrease efficacy. Until such a preparation becomes available mothers are given a single 30 ml dose of 0 - 3 mol/1 sodium citrate before being taken to theatre. Cimetidine is more acceptable to many mothers than the repeated use of the magnesium trisilicate or other conventional alkalis, and we hope that, if an alternative to cimetidine emerges, the need for regular administration of such unpalatable preparations to mothers in labour can be avoided. J. W. DUNDEE Department of Anaesthetics, Queen’s University of Belfast, Whitla Medical Building, Belfast BT9 7BL
J. MOORE J. R. JOHNSTON W. MCCAUGHEY
SODIUM VALPROATE AND NELSON’S SYNDROME
SIR,-Dr Jones and colleagues (May 30, p. 1179) describe the effect of sodium valproate on corticotrophin secretion in patients with Nelson’s syndrome. We too have found that sodium valproate, when administered in a dose as low as 300 mg orally, can significantly lower the plasma concentration of ACTH in patients with Nelson’s syndrome. Further data (unpublished) on normal volunteers have shown that the short term administration of valproic acid (250 mgx4for 1 day) lowered the early morning ACTH surge, indicating an effect on the normal secretion of ACTH.7 Though valproic acid produces a rise in brain y-aminobutyric acid (GABA) levels, it also lowers brain aspartate leve1s.7,8 Since aspartate is an excitatory neurotransmitter, the effect of valproic acid on ACTH secretion may be due to changes in the brain concentration of this compound rather than an increase in brain GABA. The effect of GABA analogues such as baclofen and 1. Gibbs CP, Schwartz DJ, Wynne JW, Hood CI, Kuck EJ. Antacid pulmonary aspiration in the dog. Anesthesiology 1979; 51: 380-85. 2. McGowan WAW. Safety of cimetidine in obstetric patients. J Roy Soc Med 1979, 72:
902-07.
JP, Moore J, Dundee JW. Cimetidine in elective Caesarean acidity. Anaesthesia 1981; 36: 167-72. 4. Johnston JR, McCaughey W, Moore J, Dundee JW. Cimetidine as an oral antacid before elective caesarean section. Anaesthesia (in press). 5. Johnston JR, McCaughey W, Moore J, Dundee JW. A field trial of cimetidine as the sole oral antacid in obstetric anaesthesia. Anaesthesia (in press). 6. Elias AN, Gwinup G, Valenta LJ. Effects of hydrocortisone, naloxone and valproic acid in patients with Nelson’s syndrome and Cushing’s disease Clin Endocrinol (in press). 7. Schechter PJ, Trainer Y, Grove J. Effect of n-dipropylacetate on ammo acid concentrations in mouse brain: Correlation with anti-convulsant activity. J Neurochem 1978; 31: 1325-27. 8. Kukino K, Deguchi T. Effects of sodium dipropylacetate on gamma-aminobutyric acid and biogenic amines in rat brain. Chem Pharm Bull (Tokyo) 1977; 25: 2257-62 3.
SIR,-Your April 18 editorial (p. 875) does not deal with all the uses of cimetidine. While a clear picture is emerging of this drug’s value in gastrointestinal disease there has been little mention of its
use
childbirth.
McCaughey W,
section: effect
Howe on
gastric