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NEGATIVE SYNACTHEN TEST DURING ETOMIDATE INFUSION
848 TABLE III-SPERM COUNTS
(MILLIONS/ML),
% LIVE
SPERM, AND
MOTILITY SCORES IN SEMEN OF VASOVASOSTOMISED MEN WHOSE WIVES BECAME PREGNANT OR DID NOT BECOME PREGNANT
.
I
I
I
I
Results as mean±SEM (number of men). Patients showmg only counts ofO or less than a million not included. Patients showing one or two counts of less than a million as well as more concentrated samples averaged by arbitrarily assigning the low count a value of0’5. *Determined as previously described ’ Normal 150 or more. t Dates unknown for 2 pregnancies and more than 96 weeks elapsed for 3 pregnancies.
viability in vasovasostomised men. We were, however, struck by the poor sperm motility post-vasovasostomy in both men whose wives became pregnant and men whose wives did not (table ill). Elton and Hargreave have reported8 that sperm motility is a much less significant guide to the fertility of the couple than sperm concentration is.
R. J. T. Departments of Urology and Surgery, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA
HANCOCK*
D. DUNCAN S. CAREY A. T. K. COCKETT A. MAY
*Present address: National Institute for Medical Research, London NW7 IAA.
NEGATIVE SYNACTHEN TEST DURING ETOMIDATE INFUSION
SIR,-Dr Fellows and colleagues (July 2, p 54) described two patients in intensive care who did not respond to a short ’Synacthen’ test during prolonged etomidate sedation. They also found a consistently depressed level of plasma cortisol. The possible connection with etomidate infusion has been suggested by Professor Ledingham and Mr Watt (June 4, p 1270) and in the experimental studies of Professor Preziosi (July 30, p 276). It was suggested that this effect of etomidate was due to direct inhibition of cortisol release from the adrenals. We are at present investigating etomidate in comparison with thiopentone for total intravenous anaesthesia for craniotomy. In four consecutive patients we have made to a short preliminary observations on adrenal responsiveness I anaesthesia. test during synacthen The patients (three men and one woman) were to undergo elective surgery for intracranial tumours but were otherwise healthy. All were premedicated with pentobarbitone 1 mg/kg. Surgery was in all cases uncomplicated and was carried out with the patients in the supine position. Blood loss was in all patients below 300 ml, and cardiovascular stability during induction and surgery was excellent. Anaesthesia with etomidate was given to the first three patients according to a schedule given by Wiberg-Joergensen and colleagues.1 Induction was with fentanyl 10 0 J.lg/kg and an infusion of etomidate 50 pg/kg/min and fentanyl 0 -55 pg/kg/min. The infusion was reduced after 10 min to etomidate 10 ug/kg/min and fentanyl 0-01 tg/kg/min supplemented with small bolus injections of fentanyl 0 . O1 mg as required. Infusion was stopped 5-10 min before the end of surgery. Patient 4 received thiopentone 450 g/kg/min and 25-50 g/kg/min for induction and maintenance of anaesthesia. All patients quickly awoke after the operation. Patients 1 and 3 did not receive corticosteroid treatment, and patient 2 received 4 mg dexamethasone four times a day before and after operation. Patient 4 received 4 mg dexamethasone just before 8. Elton RA, Hargreave TB. A statistical model to evaluate the prognosis for fertility and the results of fertility treatments. Paper presented to British Andrology Society (Edinburgh, March, 1983): abstr. 1. Wiberg-Joergensen F, Engquist A, Klausen NO, Janstrup F, Andersen HB, Petersen T. Total intravenous anaesthesia with etomidate-fentanyl. 16th Congress of the Scandinavian Society of Anaesthesiologists. Oslo, June, 1981.
u
L,mg
Response to synacthen test in patients anaesthetised with etomidate (patients 1, 2, 3) or thiopentone (patient 4). induction and 4 mg four times a day postoperatively. Cortisol measurements were taken in relation to events during anaesthesia, and a short-time synacthen test was performed during steady-state anaesthesia. A rise in plasma cortisol in above 200 nmol/1 was
regarded as a positive test. The results are presented in the figure. In patients 1 and 4 a linear decline in plasma cortisol was seen, whereas in patients 2 and 3 plasma cortisol was suppressed before the start of anaesthesia and remained low during anaesthesia. The synacthen test during anaesthesia was negative in all 3 patients who received etomidate but positive in patient 4, who received thiopentone. A short synacthen test (in patient 2 only) 1 h after anaesthesia was also negative. On the second postoperative day a positive short synacthen test was found in the three patients who had had negative tests the day before. This points to a peripheral, but reversible, adrenocortical inhibition of cortisol release effected by etomidate, as suggested by Dr Allolio and colleagues (Sept 10, p 626). Fentanyl in doses similar to the doses used in this study does not
surgery.2
The concomitant suppress the stress response to administration of etomidate and fentanyl has previously been shown to suppress the plasma cortisol increase during surgical stress, but adrenocortical responsiveness to synacthen was not investigated in that study. The figures from patient 4 suggests that the combination of thiopentone and fentanyl also suppresses the stress-induced rise in plasma cortisol level, but with maintained responsiveness of the adrenal glands. The pathophysiological significance of adrenocortical inhibition during short-term surgical stress may be questioned. However, in view of these preliminary results we have stopped using etomidate. We are now awaiting the results of a controlled study comparing the adrenal effects of etomidate and thiooentone. N. O. KLAUSEN J. MOELGAARD A. H. FERGUSON Departments of Anaesthesia and J. KAALUND JENSEN Clinical Biochemistry, C. LARSEN Aalborg Hospital, Denmark P. PAABY
ASTHMA, MAST CELLS, AND SODIUM CROMOGLYCATE
SIR,-In reply Dr Howarth and Dr Holgate (April 9, p 822), Dr Lee and colleagues (July 16, p 164) discuss the role of mast cells in exercise- induced asthma (EIA) and other forms of asthma and assert "that there is no firm evidence that in EIA, SCG [sodium cromoglycate] inhibits by any other mechanism than mast cell stabilisation" and they assume that, by default, mast cell stabilisation must underly the capacity of SCG to prevent bronchospasm and inhibit release of mediators (histamine and neutrophil chemotactic factor) during EIA. By attributing the antiasthma activity of SCG exclusively to mast cell stabilisation, they ignore the evidence that contests this viewpoint. to
2. Haxholdt OS, Kehlet H,
Dysberg V. Effect of fentanyl on the cortisol and hyperglycaemic response to abdominal surgery. Acta Anaesthesiol Scand 1981, 25:
434.
(MILLIONS/ML),
% LIVE
SPERM, AND
MOTILITY SCORES IN SEMEN OF VASOVASOSTOMISED MEN WHOSE WIVES BECAME PREGNANT OR DID NOT BECOME PREGNANT
.
I
I
I
I
Results as mean±SEM (number of men). Patients showmg only counts ofO or less than a million not included. Patients showing one or two counts of less than a million as well as more concentrated samples averaged by arbitrarily assigning the low count a value of0’5. *Determined as previously described ’ Normal 150 or more. t Dates unknown for 2 pregnancies and more than 96 weeks elapsed for 3 pregnancies.
viability in vasovasostomised men. We were, however, struck by the poor sperm motility post-vasovasostomy in both men whose wives became pregnant and men whose wives did not (table ill). Elton and Hargreave have reported8 that sperm motility is a much less significant guide to the fertility of the couple than sperm concentration is.
R. J. T. Departments of Urology and Surgery, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA
HANCOCK*
D. DUNCAN S. CAREY A. T. K. COCKETT A. MAY
*Present address: National Institute for Medical Research, London NW7 IAA.
NEGATIVE SYNACTHEN TEST DURING ETOMIDATE INFUSION
SIR,-Dr Fellows and colleagues (July 2, p 54) described two patients in intensive care who did not respond to a short ’Synacthen’ test during prolonged etomidate sedation. They also found a consistently depressed level of plasma cortisol. The possible connection with etomidate infusion has been suggested by Professor Ledingham and Mr Watt (June 4, p 1270) and in the experimental studies of Professor Preziosi (July 30, p 276). It was suggested that this effect of etomidate was due to direct inhibition of cortisol release from the adrenals. We are at present investigating etomidate in comparison with thiopentone for total intravenous anaesthesia for craniotomy. In four consecutive patients we have made to a short preliminary observations on adrenal responsiveness I anaesthesia. test during synacthen The patients (three men and one woman) were to undergo elective surgery for intracranial tumours but were otherwise healthy. All were premedicated with pentobarbitone 1 mg/kg. Surgery was in all cases uncomplicated and was carried out with the patients in the supine position. Blood loss was in all patients below 300 ml, and cardiovascular stability during induction and surgery was excellent. Anaesthesia with etomidate was given to the first three patients according to a schedule given by Wiberg-Joergensen and colleagues.1 Induction was with fentanyl 10 0 J.lg/kg and an infusion of etomidate 50 pg/kg/min and fentanyl 0 -55 pg/kg/min. The infusion was reduced after 10 min to etomidate 10 ug/kg/min and fentanyl 0-01 tg/kg/min supplemented with small bolus injections of fentanyl 0 . O1 mg as required. Infusion was stopped 5-10 min before the end of surgery. Patient 4 received thiopentone 450 g/kg/min and 25-50 g/kg/min for induction and maintenance of anaesthesia. All patients quickly awoke after the operation. Patients 1 and 3 did not receive corticosteroid treatment, and patient 2 received 4 mg dexamethasone four times a day before and after operation. Patient 4 received 4 mg dexamethasone just before 8. Elton RA, Hargreave TB. A statistical model to evaluate the prognosis for fertility and the results of fertility treatments. Paper presented to British Andrology Society (Edinburgh, March, 1983): abstr. 1. Wiberg-Joergensen F, Engquist A, Klausen NO, Janstrup F, Andersen HB, Petersen T. Total intravenous anaesthesia with etomidate-fentanyl. 16th Congress of the Scandinavian Society of Anaesthesiologists. Oslo, June, 1981.
u
L,mg
Response to synacthen test in patients anaesthetised with etomidate (patients 1, 2, 3) or thiopentone (patient 4). induction and 4 mg four times a day postoperatively. Cortisol measurements were taken in relation to events during anaesthesia, and a short-time synacthen test was performed during steady-state anaesthesia. A rise in plasma cortisol in above 200 nmol/1 was
regarded as a positive test. The results are presented in the figure. In patients 1 and 4 a linear decline in plasma cortisol was seen, whereas in patients 2 and 3 plasma cortisol was suppressed before the start of anaesthesia and remained low during anaesthesia. The synacthen test during anaesthesia was negative in all 3 patients who received etomidate but positive in patient 4, who received thiopentone. A short synacthen test (in patient 2 only) 1 h after anaesthesia was also negative. On the second postoperative day a positive short synacthen test was found in the three patients who had had negative tests the day before. This points to a peripheral, but reversible, adrenocortical inhibition of cortisol release effected by etomidate, as suggested by Dr Allolio and colleagues (Sept 10, p 626). Fentanyl in doses similar to the doses used in this study does not
surgery.2
The concomitant suppress the stress response to administration of etomidate and fentanyl has previously been shown to suppress the plasma cortisol increase during surgical stress, but adrenocortical responsiveness to synacthen was not investigated in that study. The figures from patient 4 suggests that the combination of thiopentone and fentanyl also suppresses the stress-induced rise in plasma cortisol level, but with maintained responsiveness of the adrenal glands. The pathophysiological significance of adrenocortical inhibition during short-term surgical stress may be questioned. However, in view of these preliminary results we have stopped using etomidate. We are now awaiting the results of a controlled study comparing the adrenal effects of etomidate and thiooentone. N. O. KLAUSEN J. MOELGAARD A. H. FERGUSON Departments of Anaesthesia and J. KAALUND JENSEN Clinical Biochemistry, C. LARSEN Aalborg Hospital, Denmark P. PAABY
ASTHMA, MAST CELLS, AND SODIUM CROMOGLYCATE
SIR,-In reply Dr Howarth and Dr Holgate (April 9, p 822), Dr Lee and colleagues (July 16, p 164) discuss the role of mast cells in exercise- induced asthma (EIA) and other forms of asthma and assert "that there is no firm evidence that in EIA, SCG [sodium cromoglycate] inhibits by any other mechanism than mast cell stabilisation" and they assume that, by default, mast cell stabilisation must underly the capacity of SCG to prevent bronchospasm and inhibit release of mediators (histamine and neutrophil chemotactic factor) during EIA. By attributing the antiasthma activity of SCG exclusively to mast cell stabilisation, they ignore the evidence that contests this viewpoint. to
2. Haxholdt OS, Kehlet H,
Dysberg V. Effect of fentanyl on the cortisol and hyperglycaemic response to abdominal surgery. Acta Anaesthesiol Scand 1981, 25:
434.