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Preoperative and Postoperative Steroid Therapy
Preoperative and Postoperative Steroid Therapy w. s. REVENO, M.D. * PAUL G. FIRNSCHILD, M.D.**
WITH increasing use of the steroids for a wide variety of disturbances it is imperative, when contemplating surgical intervention, to know whether the patient has had or is being given steroids. This knowledge can prevent disaster and with properly planned therapy make the postoperative course smoother and safer. That some degree of adrenal cortical atrophy may accompany corticosteroid therapy is now well documented. This may remain dormant for many months after cessation of therapy, its frequency and extent not being easily recognized. The added stress of surgery may precipitate shock and even death. Furthermore, in patients subjected to prolonged steroid therapy there exist potentialities for lowered immunity and infection as well as the development of osteoporosis, steroid diabetes and acute psychosis. It is therefore necessary to provide protective cover for those previously treated with the corticosteroids or corticotropin and to this end acquaintance with the more frequently used agents becomes important. AGENTS IN COMMON USE
Corticotropin (ACTH) stimulates functioning adrenal cortical tissue to liberate steroids of the adrenal cortex. It is available as an aqueous solution to be used intravenously or intramuscularly or comes combined with gelatin or zinc to be given intramuscularly for prolonged action. While not representing the entire secretion of the adrenal cortex, cortisone and particularly hydrocortisone predominate among the secretory products of the human adrenal cortex1 and exert most of the major action of the corticosteroids with the exception of aldosterone. 2 Prednisone and prednisolone, analogues of cortisone and hydrocorti-
*Associate Professor of Clinical M edicine, Wayne State University, College of M edicine; Attending Physician, Harper and Receiving Hospitals, Detroit, Michigan.
** Voluntary Assistant, Department of Surgery, 1691
Harper Hospital, Detroit, Michigan.
1692
W. S. Reveno, Paul G. Firnschild
sone, have been widely accepted because they are three to four times more potent than their parent steroids and in therapeutic doses3 do not produce comparable sodium retention. They do, however, have similar ulcerogenic effects on the gastrointestinal tract. Newer derivatives such as triamcinolone and decadron, while of greater potency and lesser sodium-retaining effect, still have generally similar actions and reactions. The dosage levels of the steroids necessary to produce clinical improvement in any situation far exceed the normal daily output or physiological requirements of the individual. Thus there is produced a diminution in the functional capacity of the adrenal cortex primarily by the inhibition of corticotropin production. Similarly, the administration of corticotropin also depresses the pituitary and reduces endogenous corticotropin production. These consequences of therapy usually reflect daily dosage schedules of more than 30 units of ACTH, 75 mg. of cortisone or 20 mg. of prednisone for longer than seven days. The adrenal deficient patient is therefore potentially in danger of collapse during stressful situations such as surgery or illness. While it is possible to measure adrenocortical deficiency by the eight-hour intravenous or intramuscular corticotropin test, 4 the routine use of this test on surgical patients is impractical. PROCEDURE FOR PATIENTS UNDER PROLONGED CONTINUOUS TREATMENT
It must be assumed that those under extended treatment for conditions such as rheumatoid arthritis, bronchial asthma, the various dermatoses and blood dyscrasias have varying degrees of adrenal insufficiency and their established maintenance dose of steroids must therefore be continued up to the day of operation. Then just before operation 200 to 300 mg. of cortisone or hydrocortisone intramuscularly, or 100 units of aqueous corticotropin intravenously, should be given and repeated on the following day. On the second day the steroids may be reduced to 100 mg. intramuscularly and on the third day may be further reduced to 50 or 75 mg. Cortisone in three divided doses is given orally if tolerated. If not, 10 to 15 units of corticotropin may be given intravenously. From then on gradual reduction to the previous maintenance dose is instituted and reached by the end of the first week or sooner. Protective antibiotics must of course accompany this treatment. To illustrate, a 57 year old white woman, n.R., with rheumatoid arthritis treated with corticosteroids for 6 years, was admitted for patellectomy in 1956. She had been maintained on 5 mg. of prednisone twice daily. Just before operation she was given 200 mg. of cortisone intramuscularly. Following operation she was able to resume oral prednisone, 5 mg. every 4 hours. The next day this was reduced to 5 mg. every 6 hours; then 5 mg. 3 times daily for 3 days and by the end of the week she was back on the former maintenance dose of 5 mg. of prednisone twice daily. The same patient was admitted in 1958 for cholecystectomy, the prednisone having been replaced by triamcinolone, 10 mg. daily in 3 divided doses. Because
Preoperative and Postoperative Steroid Therapy
1693
she was just recovering from an acute attack of biliary colic the corticosteroid was increased to 4 mg. 4 times daily 2 days before operation. For the same reason, on the day before operation she was given 100 mg. of cortisone intramuscularly in addition, and on the morning of operation a similar dose was given. Following operation 50 mg. was given intramuscularly every 4 hours for 6 doses. This was then reduced to 25 mg. intramuscularly every 4 hours for 6 doses; then 25 mg. orally for 6 more doses; and 25 mg. orally for 4 doses. The maintenance dose of 10 mg. triamcinolone daily in 3 divided doses was then resumed.
Recovery was uneventful following each operation. More steroids were used during the second operation because of the added stress during the recent acute biliary colic and because the procedure was more involved and prolonged. Where there is insufficient time for preparation, intravenous hydrocortisone, followed by oral hydrocortisone or cortisone when they can be tolerated, is definitely in order, as illustrated in the following case. L.E.D., a white man, aged 63, had been taking 5 mg. of prednisone daily for three years to control a longstanding bronchial asthma when he suffered a fracture of the femur. On the morning after the accident, just before the femur was to be nailed, he was given 100 mg. of hydrocortisone in an intravenous drip of 1000 cc. of 5 per cent glucose. This was continued during the operation and followed postoperatively by 100 gm. of cortisone intramuscularly for 4 doses in 24 hours. Then he was given 50 mg. of cortisone orally three times a day; then 25 mg. twice a day and finally his original maintenace dose of 5 mg. of prednisone daily. Recovery was uneventful.
When there is sufficient time for cortical reactivation, intravenous corticotropin is ideal for carrying the patient through a critical period. An exception is when allergic sensitivity exists as in the following patient who had bronchial asthma and atopic dermatitis. Here the possibility of added sensitization by proteins in the corticotropin made the use of the corticosteroids preferable. Mrs. E.K., aged 58, had been taking 2.5 mg. of prednisone 4 times daily for 5 years to control a severe, extensive atopic dermatitis and recurrent bronchial asthma. She was hospitalized to have a troublesome procidentia corrected and was given 200 mg. of cortisone intramuscularly on the morning of the operation. Later that day, when she had reacted and was taking nourishment she was started on 5 mg. of prednisone every 8 hours orally. This was continued for 3 days, then the former maintenance dose of 2.5 mg. of prednisone 4 times daily was resumed. Recovery was uneventful.
In ulcerative colitis, surgical intervention may be lifesaving in some cases; in others, it may restore a chronically ill patient to a normal existence. However, inadequate intake of food and excessive losses of nitrogen, fluids and electrolytes in the feces produce severe nutritional deficiencies. Prolonged corticoid therapy often contributes to fluid and electrolyte disturbance, nitrogen loss and depression of adrenocortical
1694
w. s. Reveno, Paul G. Firnschild
function. Intensive short-term preoperative preparation is necessary. Careful use of steroids in the preoperative period allows many patients to undergo a surgical procedure without serious difficulty. The anabolic, antipyretic and euphoric effect of ACTH and corticosteroids prepare the seriously ill patient for operation. Preoperatively, 200 mg. of hydrocortisone may be given intramuscularly. Hydrocortisone, 100 mg., is then given intravenously over each six-hour period for 24 hours, after which the dosage is gradually diminished over the first two weeks of convalescence. A similar dosage schedule may be used to prepare the ser ously ill patient with regional enteritis for operation. In idiopathic thrombocytopenic purpura corticosteroids may be used not only to reduce bleeding through a nonspecific effect on blood vessels, but also to raise the platelet count. In acute fulminating idiopathic thrombocytopenic purpura the use of prednisone and fresh whole blood may permit splenectomy to be done safely" It is worth noting that tissue healing is not interrupted when a steroid or corticotropin is used in reasonable amounts. SUBSTITUTION THERAPY
In contrast to the situation in which steroid therapy must be temporarily augmented to help meet the stress of surgery, is that in which sufficient corticosteroids must be permanently administered following adrenalectomy. Here the situation is comparable to induced primary Addison's disease with loss of both mineralo- and gluco-corticosteroids. In these patients on the day of operation and the first postoperative day, 200 to 300 mg. of either cortisone or hydrocortisone should be given intramuscularly, followed by gradually reduced doses until a daily maintenance level of 25 to 50 mg. of oral cortisone or hydrocortisone has been reached. Loss of salt may be controlled either by added salt intake or the use of desoxycorticosterone acetate daily, or one of the long-acting derivatives given intramuscularly at two- to four-week intervals. Preferred is fiudrocortisone, 0.1 to 0.2 mg. daily orally, which appears to meet this need adequately. In general, this is the plan to be followed, with modifications introduced to meet the needs of the individual case. This is demonstrated in the following patients with metastasized breast carcinoma who were subjected to adrenalectomy. L.G., aged 57, who was markedly debilitated, was given 100 mg. of cortisone intramuscularly the day before and again on the morning of operation. Following bilateral adrenalectomy and oophorectomy 100 mg. of cortisone was given intramuscularly and repeated every 4 hours for 6 doses. Then the dose was reduced to 50 mg. every 6 hours but on the second day, because of a shocklike state, 100 mg. of hydrocortisone was added intravenously and this same amount was given three times daily in a drip of 5 per cent glucose and isotonic saline in place of the cortisone. This was continued for 3 days when sufficient improvement occurred to permit return to 50 mg. of cortisone intramuscularly every 8 hours plus 2 mg. of buccal desoxycorticosterone acetate twice daily. After 2 days 50 mg. of cortisone was given orally 3 times daily, then reduced to 25 mg.
Preoperative and Postoperative Steroid Therapy
1695
3 times daily with buccal desoxycorticosterone 4 mg. daily, which constituted the final maintenance therapy. The second patient, A.G., aged 53, in fairly good general condition, was started on oral cortisone 50 mg. every 6 hours the day before operation. On the morning of the operation she was given 100 mg. of cortisone intramuscularly and this was repeated in the evening. For the next three days 100 mg. of cortisone was given daily orally then reduced to 25 mg. 3 times daily and finally to 12.5 mg. 4 times daily which was established as the maintenance dose. Apparently there was no need here for added salt since the cortisone seemed to prevent any undue salt loss. The third patient, D.R., aged 68, was given no preoperative medication but was started on 50 mg. of cortisone intramuscularly every 6 hours at the time of operation. On the day after operation the same dosage was given orally, supplemented by 1 gram of sodium chloride 3 times daily. On successive days the cortisone was reduced to 25 mg. 4 times then 3 times daily, and at the end of 1 week a maintenance dose of 25 mg. twice daily (cortisone) was reached. The salt that had been added was replaced by 0.1 mg. of fludrocortisone.
These patients were stabilized promptly after operation and presented no difficulty in continued maintenance on substitution therapy. In patients undergoing operation for Cushing's syndrome due to adrenal tumor, atrophy of the contralateral adrenal gland is a characteristic feature. This has been shown to be the result of pituitary suppression by the excessive corticoids secreted by the tumor. With the removal of the hyperfunctioning tumor, the patient is immediately rendered adrenal deficient. Replacement therapy is needed, often for prolonged periods. Although corticogenic adrenal atrophy can be effectively reversed by the administration of ACTH, it has been shown that this reversal is not maintained, apparently because of a severe prolonged inhibition of endogenous ACTH production. SHORT-TERM ADJUNCTIVE THERAPY
In recent years corticotropin and cortisone have been used for shortterm adjunctive therapy to rehabilitate patients steadily losing ground in spite of all eff orts to aid them. However their action is explained, these agents have achieved significant results and are worth a trial as illustrated in the following two cases. 5 A man, aged 63, with a ruptured gangrenous appendix failed to rally postoperatively and by the fourth day was losing ground rapidly as a result of peritonitis in spite of seemingly adequate drainage and heroic treatment with antibiotics. He was started on corticotropin 10 units every 4 hours for a total of 12 doses and within 3 days was well on the way to recovery. Another patient, a white man, aged 61, with an abscess surrounding a ruptured diverticulum of the colon was losing ground steadily in spite of drainage and antibiotics. After twelve 10 mg. doses of corticotropin at 4-hour intervals he too began to improve and recovered completely after 4 days.
Corticotropin here served to relieve highly critical situations.
w.
1696
s. Reveno, Paul G. Firnschild
SUMMARY
In summary, the increasing use of steroid therapy makes it mandatory for the surgeon to inquire carefully of each patient whether he has had or is having steroids before undertaking surgical intervention of any kind. If steroids are being used, the kind and amount should be determined and their administration continued up to the time of operation. On the day of operation and the day following, 200 to 300 mg. of cortisone or hydrocortisone intramuscularly or 100 units of aqueous corticotropin intravenously should be given daily. By the third day the steroids may be reduced to 50 to 75 mg. daily orally and if not tolerated given either intramuscularly or replaced by 10 to 15 units of corticotropin intravenously. The dosage of the steroids may then be gradually reduced to the former maintenance level. When steroids have not been taken for some time and it is suspected that there may be depression or atrophy of the adrenal cortex, intravenous corticotropin is ideal for reactivation; but intravenous hydrocortisone may serve as well and is especially useful when there is little time for preoperative preparation. Steroid substitution therapy, essential following adrenalectomy, is readily instituted with combinations of cortisone and either desoxycorticosterone or fludrocortisone to meet the needs for both gluco- and mineralo-corticosteroids. Adjunctive therapy for short periods with either 'corticotropin or the corticosteroids is useful for aiding patients through critical periods when other therapy has failed. In using either corticotropin or the corticosteroids it is important to remember their interference with immunologic processes and the risk of subtle infection. Also their salt-retaining qualities may play havoc with the cardiac patient unless due precautions are taken. Tissue healing is neither delayed nor prevented when either the corticosteroids or corticotropin are used in reasonable amounts. REFERENCES 1. Hector, O. and Pincus, G.: Genesis of Adrenocortical Secretion. Physiol. Rev. 34: 459-493, 1954. 2. Hills, A. G., Zintel, H. A. and Parsons, D. W.: Observations of Human Adrenccortical Deficiency. Am. J. Med. 21: 358-377, 1956. 3. Caplan, P. S.: Use of Methylprednisolone in Rheumatoid Arthritis. Metabolism 7: 505-509, 1958. 4. Thorn, G. W., Forsham, P. H., Frawley, J. F., Renold, A. E., Fredrickson, D. S. and Jenkins, D.: Advances in Diagnosis and Treatment of Adrenal Insufficiency. Am. J. Med. 10: 595-611, 1951. 5. Reveno, W. S., Rosenbaum, H. and Buell, J. H.: Short Term Use of Corticotropin as Adjunctive Therapy. J.A.M.A. 149: 1308-09 (August 2) 1952. 968 Fisher Building Detroit 2, Michigan (Dr. Reveno)
WITH increasing use of the steroids for a wide variety of disturbances it is imperative, when contemplating surgical intervention, to know whether the patient has had or is being given steroids. This knowledge can prevent disaster and with properly planned therapy make the postoperative course smoother and safer. That some degree of adrenal cortical atrophy may accompany corticosteroid therapy is now well documented. This may remain dormant for many months after cessation of therapy, its frequency and extent not being easily recognized. The added stress of surgery may precipitate shock and even death. Furthermore, in patients subjected to prolonged steroid therapy there exist potentialities for lowered immunity and infection as well as the development of osteoporosis, steroid diabetes and acute psychosis. It is therefore necessary to provide protective cover for those previously treated with the corticosteroids or corticotropin and to this end acquaintance with the more frequently used agents becomes important. AGENTS IN COMMON USE
Corticotropin (ACTH) stimulates functioning adrenal cortical tissue to liberate steroids of the adrenal cortex. It is available as an aqueous solution to be used intravenously or intramuscularly or comes combined with gelatin or zinc to be given intramuscularly for prolonged action. While not representing the entire secretion of the adrenal cortex, cortisone and particularly hydrocortisone predominate among the secretory products of the human adrenal cortex1 and exert most of the major action of the corticosteroids with the exception of aldosterone. 2 Prednisone and prednisolone, analogues of cortisone and hydrocorti-
*Associate Professor of Clinical M edicine, Wayne State University, College of M edicine; Attending Physician, Harper and Receiving Hospitals, Detroit, Michigan.
** Voluntary Assistant, Department of Surgery, 1691
Harper Hospital, Detroit, Michigan.
1692
W. S. Reveno, Paul G. Firnschild
sone, have been widely accepted because they are three to four times more potent than their parent steroids and in therapeutic doses3 do not produce comparable sodium retention. They do, however, have similar ulcerogenic effects on the gastrointestinal tract. Newer derivatives such as triamcinolone and decadron, while of greater potency and lesser sodium-retaining effect, still have generally similar actions and reactions. The dosage levels of the steroids necessary to produce clinical improvement in any situation far exceed the normal daily output or physiological requirements of the individual. Thus there is produced a diminution in the functional capacity of the adrenal cortex primarily by the inhibition of corticotropin production. Similarly, the administration of corticotropin also depresses the pituitary and reduces endogenous corticotropin production. These consequences of therapy usually reflect daily dosage schedules of more than 30 units of ACTH, 75 mg. of cortisone or 20 mg. of prednisone for longer than seven days. The adrenal deficient patient is therefore potentially in danger of collapse during stressful situations such as surgery or illness. While it is possible to measure adrenocortical deficiency by the eight-hour intravenous or intramuscular corticotropin test, 4 the routine use of this test on surgical patients is impractical. PROCEDURE FOR PATIENTS UNDER PROLONGED CONTINUOUS TREATMENT
It must be assumed that those under extended treatment for conditions such as rheumatoid arthritis, bronchial asthma, the various dermatoses and blood dyscrasias have varying degrees of adrenal insufficiency and their established maintenance dose of steroids must therefore be continued up to the day of operation. Then just before operation 200 to 300 mg. of cortisone or hydrocortisone intramuscularly, or 100 units of aqueous corticotropin intravenously, should be given and repeated on the following day. On the second day the steroids may be reduced to 100 mg. intramuscularly and on the third day may be further reduced to 50 or 75 mg. Cortisone in three divided doses is given orally if tolerated. If not, 10 to 15 units of corticotropin may be given intravenously. From then on gradual reduction to the previous maintenance dose is instituted and reached by the end of the first week or sooner. Protective antibiotics must of course accompany this treatment. To illustrate, a 57 year old white woman, n.R., with rheumatoid arthritis treated with corticosteroids for 6 years, was admitted for patellectomy in 1956. She had been maintained on 5 mg. of prednisone twice daily. Just before operation she was given 200 mg. of cortisone intramuscularly. Following operation she was able to resume oral prednisone, 5 mg. every 4 hours. The next day this was reduced to 5 mg. every 6 hours; then 5 mg. 3 times daily for 3 days and by the end of the week she was back on the former maintenance dose of 5 mg. of prednisone twice daily. The same patient was admitted in 1958 for cholecystectomy, the prednisone having been replaced by triamcinolone, 10 mg. daily in 3 divided doses. Because
Preoperative and Postoperative Steroid Therapy
1693
she was just recovering from an acute attack of biliary colic the corticosteroid was increased to 4 mg. 4 times daily 2 days before operation. For the same reason, on the day before operation she was given 100 mg. of cortisone intramuscularly in addition, and on the morning of operation a similar dose was given. Following operation 50 mg. was given intramuscularly every 4 hours for 6 doses. This was then reduced to 25 mg. intramuscularly every 4 hours for 6 doses; then 25 mg. orally for 6 more doses; and 25 mg. orally for 4 doses. The maintenance dose of 10 mg. triamcinolone daily in 3 divided doses was then resumed.
Recovery was uneventful following each operation. More steroids were used during the second operation because of the added stress during the recent acute biliary colic and because the procedure was more involved and prolonged. Where there is insufficient time for preparation, intravenous hydrocortisone, followed by oral hydrocortisone or cortisone when they can be tolerated, is definitely in order, as illustrated in the following case. L.E.D., a white man, aged 63, had been taking 5 mg. of prednisone daily for three years to control a longstanding bronchial asthma when he suffered a fracture of the femur. On the morning after the accident, just before the femur was to be nailed, he was given 100 mg. of hydrocortisone in an intravenous drip of 1000 cc. of 5 per cent glucose. This was continued during the operation and followed postoperatively by 100 gm. of cortisone intramuscularly for 4 doses in 24 hours. Then he was given 50 mg. of cortisone orally three times a day; then 25 mg. twice a day and finally his original maintenace dose of 5 mg. of prednisone daily. Recovery was uneventful.
When there is sufficient time for cortical reactivation, intravenous corticotropin is ideal for carrying the patient through a critical period. An exception is when allergic sensitivity exists as in the following patient who had bronchial asthma and atopic dermatitis. Here the possibility of added sensitization by proteins in the corticotropin made the use of the corticosteroids preferable. Mrs. E.K., aged 58, had been taking 2.5 mg. of prednisone 4 times daily for 5 years to control a severe, extensive atopic dermatitis and recurrent bronchial asthma. She was hospitalized to have a troublesome procidentia corrected and was given 200 mg. of cortisone intramuscularly on the morning of the operation. Later that day, when she had reacted and was taking nourishment she was started on 5 mg. of prednisone every 8 hours orally. This was continued for 3 days, then the former maintenance dose of 2.5 mg. of prednisone 4 times daily was resumed. Recovery was uneventful.
In ulcerative colitis, surgical intervention may be lifesaving in some cases; in others, it may restore a chronically ill patient to a normal existence. However, inadequate intake of food and excessive losses of nitrogen, fluids and electrolytes in the feces produce severe nutritional deficiencies. Prolonged corticoid therapy often contributes to fluid and electrolyte disturbance, nitrogen loss and depression of adrenocortical
1694
w. s. Reveno, Paul G. Firnschild
function. Intensive short-term preoperative preparation is necessary. Careful use of steroids in the preoperative period allows many patients to undergo a surgical procedure without serious difficulty. The anabolic, antipyretic and euphoric effect of ACTH and corticosteroids prepare the seriously ill patient for operation. Preoperatively, 200 mg. of hydrocortisone may be given intramuscularly. Hydrocortisone, 100 mg., is then given intravenously over each six-hour period for 24 hours, after which the dosage is gradually diminished over the first two weeks of convalescence. A similar dosage schedule may be used to prepare the ser ously ill patient with regional enteritis for operation. In idiopathic thrombocytopenic purpura corticosteroids may be used not only to reduce bleeding through a nonspecific effect on blood vessels, but also to raise the platelet count. In acute fulminating idiopathic thrombocytopenic purpura the use of prednisone and fresh whole blood may permit splenectomy to be done safely" It is worth noting that tissue healing is not interrupted when a steroid or corticotropin is used in reasonable amounts. SUBSTITUTION THERAPY
In contrast to the situation in which steroid therapy must be temporarily augmented to help meet the stress of surgery, is that in which sufficient corticosteroids must be permanently administered following adrenalectomy. Here the situation is comparable to induced primary Addison's disease with loss of both mineralo- and gluco-corticosteroids. In these patients on the day of operation and the first postoperative day, 200 to 300 mg. of either cortisone or hydrocortisone should be given intramuscularly, followed by gradually reduced doses until a daily maintenance level of 25 to 50 mg. of oral cortisone or hydrocortisone has been reached. Loss of salt may be controlled either by added salt intake or the use of desoxycorticosterone acetate daily, or one of the long-acting derivatives given intramuscularly at two- to four-week intervals. Preferred is fiudrocortisone, 0.1 to 0.2 mg. daily orally, which appears to meet this need adequately. In general, this is the plan to be followed, with modifications introduced to meet the needs of the individual case. This is demonstrated in the following patients with metastasized breast carcinoma who were subjected to adrenalectomy. L.G., aged 57, who was markedly debilitated, was given 100 mg. of cortisone intramuscularly the day before and again on the morning of operation. Following bilateral adrenalectomy and oophorectomy 100 mg. of cortisone was given intramuscularly and repeated every 4 hours for 6 doses. Then the dose was reduced to 50 mg. every 6 hours but on the second day, because of a shocklike state, 100 mg. of hydrocortisone was added intravenously and this same amount was given three times daily in a drip of 5 per cent glucose and isotonic saline in place of the cortisone. This was continued for 3 days when sufficient improvement occurred to permit return to 50 mg. of cortisone intramuscularly every 8 hours plus 2 mg. of buccal desoxycorticosterone acetate twice daily. After 2 days 50 mg. of cortisone was given orally 3 times daily, then reduced to 25 mg.
Preoperative and Postoperative Steroid Therapy
1695
3 times daily with buccal desoxycorticosterone 4 mg. daily, which constituted the final maintenance therapy. The second patient, A.G., aged 53, in fairly good general condition, was started on oral cortisone 50 mg. every 6 hours the day before operation. On the morning of the operation she was given 100 mg. of cortisone intramuscularly and this was repeated in the evening. For the next three days 100 mg. of cortisone was given daily orally then reduced to 25 mg. 3 times daily and finally to 12.5 mg. 4 times daily which was established as the maintenance dose. Apparently there was no need here for added salt since the cortisone seemed to prevent any undue salt loss. The third patient, D.R., aged 68, was given no preoperative medication but was started on 50 mg. of cortisone intramuscularly every 6 hours at the time of operation. On the day after operation the same dosage was given orally, supplemented by 1 gram of sodium chloride 3 times daily. On successive days the cortisone was reduced to 25 mg. 4 times then 3 times daily, and at the end of 1 week a maintenance dose of 25 mg. twice daily (cortisone) was reached. The salt that had been added was replaced by 0.1 mg. of fludrocortisone.
These patients were stabilized promptly after operation and presented no difficulty in continued maintenance on substitution therapy. In patients undergoing operation for Cushing's syndrome due to adrenal tumor, atrophy of the contralateral adrenal gland is a characteristic feature. This has been shown to be the result of pituitary suppression by the excessive corticoids secreted by the tumor. With the removal of the hyperfunctioning tumor, the patient is immediately rendered adrenal deficient. Replacement therapy is needed, often for prolonged periods. Although corticogenic adrenal atrophy can be effectively reversed by the administration of ACTH, it has been shown that this reversal is not maintained, apparently because of a severe prolonged inhibition of endogenous ACTH production. SHORT-TERM ADJUNCTIVE THERAPY
In recent years corticotropin and cortisone have been used for shortterm adjunctive therapy to rehabilitate patients steadily losing ground in spite of all eff orts to aid them. However their action is explained, these agents have achieved significant results and are worth a trial as illustrated in the following two cases. 5 A man, aged 63, with a ruptured gangrenous appendix failed to rally postoperatively and by the fourth day was losing ground rapidly as a result of peritonitis in spite of seemingly adequate drainage and heroic treatment with antibiotics. He was started on corticotropin 10 units every 4 hours for a total of 12 doses and within 3 days was well on the way to recovery. Another patient, a white man, aged 61, with an abscess surrounding a ruptured diverticulum of the colon was losing ground steadily in spite of drainage and antibiotics. After twelve 10 mg. doses of corticotropin at 4-hour intervals he too began to improve and recovered completely after 4 days.
Corticotropin here served to relieve highly critical situations.
w.
1696
s. Reveno, Paul G. Firnschild
SUMMARY
In summary, the increasing use of steroid therapy makes it mandatory for the surgeon to inquire carefully of each patient whether he has had or is having steroids before undertaking surgical intervention of any kind. If steroids are being used, the kind and amount should be determined and their administration continued up to the time of operation. On the day of operation and the day following, 200 to 300 mg. of cortisone or hydrocortisone intramuscularly or 100 units of aqueous corticotropin intravenously should be given daily. By the third day the steroids may be reduced to 50 to 75 mg. daily orally and if not tolerated given either intramuscularly or replaced by 10 to 15 units of corticotropin intravenously. The dosage of the steroids may then be gradually reduced to the former maintenance level. When steroids have not been taken for some time and it is suspected that there may be depression or atrophy of the adrenal cortex, intravenous corticotropin is ideal for reactivation; but intravenous hydrocortisone may serve as well and is especially useful when there is little time for preoperative preparation. Steroid substitution therapy, essential following adrenalectomy, is readily instituted with combinations of cortisone and either desoxycorticosterone or fludrocortisone to meet the needs for both gluco- and mineralo-corticosteroids. Adjunctive therapy for short periods with either 'corticotropin or the corticosteroids is useful for aiding patients through critical periods when other therapy has failed. In using either corticotropin or the corticosteroids it is important to remember their interference with immunologic processes and the risk of subtle infection. Also their salt-retaining qualities may play havoc with the cardiac patient unless due precautions are taken. Tissue healing is neither delayed nor prevented when either the corticosteroids or corticotropin are used in reasonable amounts. REFERENCES 1. Hector, O. and Pincus, G.: Genesis of Adrenocortical Secretion. Physiol. Rev. 34: 459-493, 1954. 2. Hills, A. G., Zintel, H. A. and Parsons, D. W.: Observations of Human Adrenccortical Deficiency. Am. J. Med. 21: 358-377, 1956. 3. Caplan, P. S.: Use of Methylprednisolone in Rheumatoid Arthritis. Metabolism 7: 505-509, 1958. 4. Thorn, G. W., Forsham, P. H., Frawley, J. F., Renold, A. E., Fredrickson, D. S. and Jenkins, D.: Advances in Diagnosis and Treatment of Adrenal Insufficiency. Am. J. Med. 10: 595-611, 1951. 5. Reveno, W. S., Rosenbaum, H. and Buell, J. H.: Short Term Use of Corticotropin as Adjunctive Therapy. J.A.M.A. 149: 1308-09 (August 2) 1952. 968 Fisher Building Detroit 2, Michigan (Dr. Reveno)