In 22 patients undergoing elective surgery, adrenal function was assessed before and on the day of surgery. Patients receiving corticosteroid therapy but with a ...
Br. J. Anaesth. (1981), 53, 949
PHYSIOLOGICAL CORTISOL SUBSTITUTION OF LONG-TERM STEROID-TREATED PATIENTS UNDERGOING MAJOR SURGERY T. SYMRENG, B. E. KARLBERG, B. KAGEDAL AND B. SCHILDT SUMMARY
In 22 patients undergoing elective surgery, adrenal function was assessed before and on the day of surgery. Patients receiving corticosteroid therapy but with a normal cortisol response to a corticotropin stimulation tcit (group II, n = 8) were not given hydroconisone on the day of operation. Their cortisol concentration increased in a manner similar to patients (group I, n = 8) who had never had corticosteroid treatment. The plasma cortisol concentrations in these two groups were less than in subjects (group III, n = 6) with an impaired cortisol response to corticotropin stimulation, who were given hydrocortisone 25 mg at the induction of anaesthesia followed by a continuous infusion of hydrocortisone 100 mg during the next 24 h. There were no clinical signs of circulatory insufficiency in any group. The low-dose hydroconisone therapy regimen is sufficient for substitution of adrenal function during surgery and in the early postoperative phase. It could lead to mild oversubstitution in patients with impaired adrenal insufficiency undergoing major surgery.
Patients receiving long-term corticosteroid 2-3 days the cortisol production declined and therapy may have suppression of adrenal function returned to control in uneventful cases. Kehlet (Sampson, Winstone and Brooke, 1962) and be proposed a bolus of hydrocortisone 25 mg at the unable to respond physiologically to surgery or induction of anaesthesia followed by lOOmg as a other forms of stress. As a result, supplementation continuous infusion for the following 24 h; this he with corticosteroids was suggested and various considered sufficient to avoid adrenal insufficiency regimens proposed (Plumpton, Besser and Cole, (Kehlet, 1975). 1969). The suggested dosages were large (varying When patients receiving long-term treatment between 300 and 600 mg of hydrocortisone per with corticosteroids undergo surgery the question 24 h). Although effective in avoiding adrenal of supplementation arises. However, the majority insufficiency such regimens were advocated of these patients receive corticosteroid treatment empirically. not because of proven adrenocortical insufficiency, However, little thought has been given to the but for other reasons and their adrenocortical adverse effects of corticosteroids, such as an function may or may not be impaired as a result of increased susceptibility to infection, impaired that therapy. wound healing and a decrease in glucose tolerance No attempts have been made to distinguish (Dujovne and Azarnoff, 1973) during and after patients with an inadequate adrenal response from operation in patients undergoing major surgery. those responding normally to stress and conIn contrast to this empirical high-dose substitu- sequently requiring either low-dose substitution tion regimen, a rational low-dose substitution was or no substitution at all. proposed by Kehlet and Binder (1973). From The purpose of the present investigation was: studies of the normal adrenocortical response the (a) to differentiate patients with a normal adrenal total increment of cortisol was found to be stress response from those with an inadequate 75-150 mg per 24 h in association with major response, using a preoperative corticotropin test: surgery (Kehlet, 1976). During the subsequent (b) to measure plasma cortisol concentrations during and following major surgery in patients with a normal adrenal response without TOMMY SYMRENG, M.D., BO SCHILDT, M JJ., PH.D. (Department administering cortisol substitution; (c) to evaluate of Anaesthcsiology); BENGT E. KARLBERG, MJ>., PH.D. the low-dose substitution regimen in patients with (Department of Internal Medicine, Section of Endocrinology); proven adrenal insufficiency by measuring plasma BERTIL KAGEDAL, M.D., PH.D. (Department of Clinical Chemistry); University Hospital, S-58185 Linkoping, cortisol concentrations during and following major surgery. Sweden. 0007-0912/81/090949-06 $01.00
©Macmillan Publishers Ltd 1981
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BRITISH JOURNAL OF ANAESTHESIA PATIENTS AND METHODS
Analytical procedures The corticotropin stimulation test was performed in all patients at 8 a.m. after an overnight fast. After a baseline (zero time) blood sample had been taken, tetracosactid 0.25 mg (Synacthen, Ciba) was given as a bolus injection i.v. and blood samples withdrawn at 30, 60, 90 andl20min after the injection. The samples were centrifuged within 1 h and plasma stored at — 20 °C until assayed. Plasma cortisol concentration was measured by TABLE I. Details of surgery undergone by patients in each group fluorimetry (de Moor et al., 1962) and plasma aldosterone concentration by the specific radioNumber of patients immunoassay of McKenzie and Clements (1974) as validated in our laboratory (Tolagen and Group Group Group I III Type of surgery II Karlberg, 1978). Preoperative evaluation of adrenal function. The Procto-colcctomy 3 3 3 results of the corticotropin stimulation test are 2 1 — Gastric resection 3 1 1 Small bowel or limited summarized in table III. The subjects who had large bowel resection never received corticosteroid treatment (group I) — 2 — Hemi-colectomy had, as expected, a normal cortisol response. Of — 1 1 Splenectomy the subjects who had received corticosteroid treat— — 1 Bilateral subtotal ment previously, eight had a peak plasma cortisol thyroid resection concentration greater than 500nmol litre"'. They constituted group II and were not given corticooperation with corticosteroids for varying lengths steroid treatment during surgery. The remaining of time (2months-12yr; mean 34 months). The six subjects (including one with Addison's disease) indications for this medication varied (table II) had low basal cortisol concentrations and suband the daily dose range (prednisolone 5-80 mg) normal peak values. They constituted group III and were given low-dose cortisol on the day of was considerable. operation. The aldosterone response to corticotropin TABLE II. Indications for long-term corticosteroid medication stimulation was also studied in a limited number of Number of subjects in order to evaluate its sensitivity as an patients indicator of adrenal insufficiency (table III). All three groups had normal basal aldosterone concenCrohn's disease 4 trations. In groups II and III the plasma Ulcerative colitis 3 aldosterone concentration increased significantly Thrombocytopaenia 2 Bronchial asthma 2 (Pie Cortisolkonzentrationen in diescn bciden Gruppen waren geringer als bei den Patienten (Gruppe III, n = 6), dcren Cortisol-Reaktion auf Kortikotropin beeintrachtigt war und die Hydrocortison 25 mg bei Narkosebeginn crhielten, gefolgt von einer kontinuierlichen Infusion von Hydrocortison lOOmg uber die nachsten 24 Stunden. In kciner der drei Gruppen gab es klinische Anzeichen einer Kreislaufinsuffizienz. Die niedrig dosierte Hydrocortison-Behandlung ist ausreichend fur den Ersatz der Nebennierenfunktion wahrend des Eingriffs, sowie in der ersten postoperativen Phase. Sie konntc bei Patienten mit beeintrachtigter Nebennierenfunktion bei grossen Operationen zu einer milden Ubersubstitution fuhren.
SUSTITUCION FISIOLOGICA DE CORTISOL EN PACIENTES QUE HAN RECIBIDO UN PROLONGADO TRATAMIENTO DE ESTEROIDES Y QUE ESTAN SOMETIDOS A OPERACION QUIRURJICA MAYOR Se evaluo la funcion adrenal en el dia de la operacion de 22 pacientes sometidos a operacion quirurjica facultative y des-
BRITISH JOURNAL OF ANAESTHESIA pues de dicha operacion. A los pacientes bajo terapia de corticosteroidcs pero con una respucsta de cortisol normal ante una prueba de corticotropin de estimulacion (grupo II, n = 8), no se les administro hidrocortisona el dia de la operacion. Su concentration de cortisol incremento de modo similar a la de los pacientes (grupo I, n = 8) que no habian rccibido nunca tratamiento de corticosteroides. Las concentraciones de cortisol en cstos grupos fueron inferiores a las de los sujetos (grupo III, n = 6) quc presentaban una respuesta de cortisol anormal ante la esnmulacion de corticotropin y a los que se les administraron 25 mg de hidrocortisona durante la induction de la anestesia, seguidos de una infusion continua de lOOmg de hidrocortisona durante las 24 horas siguientes. No se presentaron signos de insuficiencia circulatoria en ninguno de los grupos. El regimen terapeutico de baja dosis de hidrocortisona es suficiente para sustituir la funcion adrenal durante la operacion quirurjica y en la fase posoperariva inicial. Podria llevar a una sobresustitucion moderada en aquellos pacientes que presenten una insuficiencia adrenal anormal y que esten sometidos a una operacion quirurjica de importancia.
