Acta Anaesthesiol Scand 1992: 36: 119-124
Serum steroids and prolactin during and after . major surgical trauma A. LINDH,K. CARLSTROM, J. EKLUND and N. WILKING Department of Anesthesiology, Danderyds Hospital, Danderyd, Departments of Obstetrics and Gynecology and Anesthesiology, Karolinska Institute, Huddinge University Hospital, Huddinge and Department of Oncology, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden
Serum levels of cortisol, dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3, I 7-dione (A-4), 17-alfa-hydroxy-progesterone(17 OHP), testosterone (T, only in males), unconjugated ( E l ) and total estrone (tEl >85% estrone sulfate) were studied in six male and two female patients before, during and up to 30 days after aortic graft surgery. All steroids except 17 OHP decreased following induction of anesthesia but, except for testosterone, rose again during surgery to preoperative levels or slightly above. Extremely high peak values for El and tEl and a less pronounced peak for cortisol were noted on postoperative day 2; after that, the levels of these steroids returned to normal. The levels of 17-OHP, DHA and DHAS decreased after surgery and were below preoperative values from postoperative day 4 to day 16 or (DHAS) day 30. In males, 17 OHP showed a pronounced peak 30 min after initiation of surgery, but decreased after that to below preoperative values. Testosterone levels decreased further during surgery and remained very low until postoperative day 16. Major surgical trauma has a rapid, profound and long-lasting effect on gonadal activity, as judged from decreased testosterone levels, while the effect on adrenal steroids is less pronounced. Adrenal A4 and A5-steroids showed different patterns in the postoperative period, indicating differences in their regulation. The highly elevated estrogen levels on postoperative day 2 probably reflect either transiently elevated peripheral aromatization or decreased estrogen metabolism rather than increased levels of substrate steroids (A-4). The biological significance of this remains to be elucidated.
Rcceiued 22 Februay, accepted f o r publication I 1 3ub 1991
Key words: Aortic graft surgery; prolactin; serum steroids.
Surgical trauma induces changes in the hormonal environment. The changes are usually related to the severity of trauma; however, this response may be influenced by the mode of anesthesia used (1-3). The increase in “stress-related” hormone levels such as ACTH, cortisol and prolactin during surgery is well known. However, except for the well-known decrease in testosterone levels in men, the effects of surgery upon androgens and estrogens and related steroids have been little studied. In a study on postmenopausal women, Adami and co-workers (4)observed decreased levels of the adrenal androgen dehydroepiandrosterone and increased levels of estrone during the first postoperative days. The aim of the present investigation was to study the effect of surgical trauma on adrenal and gonadal androgens and related steroids. Many previous reports have dealt with relatively minor or moderate surgery and have included short observation times (1-3). We have therefore chosen to study a standardized, major surgical trauma, i.e. elective operations
for aortic aneurysm, for a period of more than 30 days after surgery.
PATIENTS AND METHODS Patients Six men and two women, aged 62-75 years, undergoing elective abdominal aortic surgery were studied. Individual patient data are given in Table 1. None of the patients had any preoperative symptoms from their abdominal aortic aneurysms, which were either palpated at physical examination or discovered by accident radiographically. All patients were previously in good health, without history of major heart, lung or renal disease and had normal values for ASAT, ALAT and creatinine on admission to hospital. The patients were premedicated with morphine 0.1 mg. kg-’ and scopolamine 0.004 mg. kg-’ i.m. 45 min before anesthesia. Epidural anesthesia was initiated before induction of general anesthesia. The epidural catheter was inserted between L, and L, and bupivacaine 0.5% 12-16 ml was injected. The aim was to obtain a sensory level of epidural anesthesia at thoracic level dermatome 4-5. Every second hour, a bolus of half of the initial bolus dose of bupivacaine was injected. General anesthesia was induced with thiopenthone, pancuronium and fentanyl and maintained with nitrous oxide-oxygen, fentanyl
120
A. LINDH
Er AL.
Table 1 Clinical data for individual patients operated upon for aortic aneurysm. Patient no. 1.
2. 3. 4. 5. 6. 7.
a.
Sex
F M M M M
F M M
Age (years) Major complications 68 76
68 75 73 67 70 62
1OOO-
20-
15
P
&;I 200
10
-
8-
r
64-
2'
O'
2750 8000
None Intermittent renal failure Wound rupture day 1 Ischemic colitis Postop. bleeding, Reop. day 2 None None None
and isoflurane (0.5-1 %) or efrane (0.5-1.5% (Abbott Laboratories, Chicago, USA)). Warmed (37 "C) colloid or crystalloid solutions were administered throughout surgery and recovery to maintain positive CVP (central venous pressure). CVP was obtained through a central venous catheter inserted via the right internal jugular vein. The epidural catheter was used for pain relief postoperatively (bupivacaine 0.25%, 6-8) ml until the first postoperative day. The epidural catheter was then removed and the analgesic drug used for pain relief was morphine or ketobemidone. All patients were brought to the intensive care unit (ICU) postoperatively and stayed on the ventilator until circulation was stable and the body temperature was normal. Blood samples were obtained perioperatively from a routinely inserted catheter in the radial artery. Venous blood was collected before surgery and after the patient had left the ICU. The blood samples were taken between 07.30-08.00 a.m. on the day prior to surgery and on the operative day after premedication with morphine-
400
Peroperative blood loss (ml)
P
Hospital stay (days)
2100 2400 5000
22 30 21 > 30 > 30
2500 2300 2000
15 16 12
scopolamine, but prior to induction of anesthesia. O n the operative day further blood samples were taken 0.5, I , 2, 4 and 8 h after the start ofsurgery. The surgical procedure lasted between 2.5-5 h. Blood samples were then obtained on days 1, 2, 4, 8, 16 and 30 between 7.3Cb8.00 a.m. Serum was separated by centrifugation, frozen and stored at - 70 "C until analyzed. The study was approved by the Ethics Committee, Karolinska Institute, and full and informed consent was obtained from each subject participating in the study. Assay methods Serum concentrations of cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), 4-androstene-3,17-dione (A-4), 1 7 alfa-hydroxyprogesterone (17 OHP), testosterone (T),unconjugated ( E l ) and total estrone (t-El; sum of unronjugated and conjugated estrone, > 85% estrone sulfate) and prolactin were determined by radioimmunological methods described previously (5-8). For the determination of DHA, DHAS and A-4, the antibodies speci-
.
-
'0-
5-
drostcrone, 4-androstene-3, I 7-dione (A-4), dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS) in patients operated upon for aortic aneurysm. Mean? s.e.mean. For symbols and indications, see Methods section. Significant changes from preoperative levels: Cortisol: Op, 2 days ( P
Serum steroids and prolactin during and after . major surgical trauma A. LINDH,K. CARLSTROM, J. EKLUND and N. WILKING Department of Anesthesiology, Danderyds Hospital, Danderyd, Departments of Obstetrics and Gynecology and Anesthesiology, Karolinska Institute, Huddinge University Hospital, Huddinge and Department of Oncology, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden
Serum levels of cortisol, dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3, I 7-dione (A-4), 17-alfa-hydroxy-progesterone(17 OHP), testosterone (T, only in males), unconjugated ( E l ) and total estrone (tEl >85% estrone sulfate) were studied in six male and two female patients before, during and up to 30 days after aortic graft surgery. All steroids except 17 OHP decreased following induction of anesthesia but, except for testosterone, rose again during surgery to preoperative levels or slightly above. Extremely high peak values for El and tEl and a less pronounced peak for cortisol were noted on postoperative day 2; after that, the levels of these steroids returned to normal. The levels of 17-OHP, DHA and DHAS decreased after surgery and were below preoperative values from postoperative day 4 to day 16 or (DHAS) day 30. In males, 17 OHP showed a pronounced peak 30 min after initiation of surgery, but decreased after that to below preoperative values. Testosterone levels decreased further during surgery and remained very low until postoperative day 16. Major surgical trauma has a rapid, profound and long-lasting effect on gonadal activity, as judged from decreased testosterone levels, while the effect on adrenal steroids is less pronounced. Adrenal A4 and A5-steroids showed different patterns in the postoperative period, indicating differences in their regulation. The highly elevated estrogen levels on postoperative day 2 probably reflect either transiently elevated peripheral aromatization or decreased estrogen metabolism rather than increased levels of substrate steroids (A-4). The biological significance of this remains to be elucidated.
Rcceiued 22 Februay, accepted f o r publication I 1 3ub 1991
Key words: Aortic graft surgery; prolactin; serum steroids.
Surgical trauma induces changes in the hormonal environment. The changes are usually related to the severity of trauma; however, this response may be influenced by the mode of anesthesia used (1-3). The increase in “stress-related” hormone levels such as ACTH, cortisol and prolactin during surgery is well known. However, except for the well-known decrease in testosterone levels in men, the effects of surgery upon androgens and estrogens and related steroids have been little studied. In a study on postmenopausal women, Adami and co-workers (4)observed decreased levels of the adrenal androgen dehydroepiandrosterone and increased levels of estrone during the first postoperative days. The aim of the present investigation was to study the effect of surgical trauma on adrenal and gonadal androgens and related steroids. Many previous reports have dealt with relatively minor or moderate surgery and have included short observation times (1-3). We have therefore chosen to study a standardized, major surgical trauma, i.e. elective operations
for aortic aneurysm, for a period of more than 30 days after surgery.
PATIENTS AND METHODS Patients Six men and two women, aged 62-75 years, undergoing elective abdominal aortic surgery were studied. Individual patient data are given in Table 1. None of the patients had any preoperative symptoms from their abdominal aortic aneurysms, which were either palpated at physical examination or discovered by accident radiographically. All patients were previously in good health, without history of major heart, lung or renal disease and had normal values for ASAT, ALAT and creatinine on admission to hospital. The patients were premedicated with morphine 0.1 mg. kg-’ and scopolamine 0.004 mg. kg-’ i.m. 45 min before anesthesia. Epidural anesthesia was initiated before induction of general anesthesia. The epidural catheter was inserted between L, and L, and bupivacaine 0.5% 12-16 ml was injected. The aim was to obtain a sensory level of epidural anesthesia at thoracic level dermatome 4-5. Every second hour, a bolus of half of the initial bolus dose of bupivacaine was injected. General anesthesia was induced with thiopenthone, pancuronium and fentanyl and maintained with nitrous oxide-oxygen, fentanyl
120
A. LINDH
Er AL.
Table 1 Clinical data for individual patients operated upon for aortic aneurysm. Patient no. 1.
2. 3. 4. 5. 6. 7.
a.
Sex
F M M M M
F M M
Age (years) Major complications 68 76
68 75 73 67 70 62
1OOO-
20-
15
P
&;I 200
10
-
8-
r
64-
2'
O'
2750 8000
None Intermittent renal failure Wound rupture day 1 Ischemic colitis Postop. bleeding, Reop. day 2 None None None
and isoflurane (0.5-1 %) or efrane (0.5-1.5% (Abbott Laboratories, Chicago, USA)). Warmed (37 "C) colloid or crystalloid solutions were administered throughout surgery and recovery to maintain positive CVP (central venous pressure). CVP was obtained through a central venous catheter inserted via the right internal jugular vein. The epidural catheter was used for pain relief postoperatively (bupivacaine 0.25%, 6-8) ml until the first postoperative day. The epidural catheter was then removed and the analgesic drug used for pain relief was morphine or ketobemidone. All patients were brought to the intensive care unit (ICU) postoperatively and stayed on the ventilator until circulation was stable and the body temperature was normal. Blood samples were obtained perioperatively from a routinely inserted catheter in the radial artery. Venous blood was collected before surgery and after the patient had left the ICU. The blood samples were taken between 07.30-08.00 a.m. on the day prior to surgery and on the operative day after premedication with morphine-
400
Peroperative blood loss (ml)
P
Hospital stay (days)
2100 2400 5000
22 30 21 > 30 > 30
2500 2300 2000
15 16 12
scopolamine, but prior to induction of anesthesia. O n the operative day further blood samples were taken 0.5, I , 2, 4 and 8 h after the start ofsurgery. The surgical procedure lasted between 2.5-5 h. Blood samples were then obtained on days 1, 2, 4, 8, 16 and 30 between 7.3Cb8.00 a.m. Serum was separated by centrifugation, frozen and stored at - 70 "C until analyzed. The study was approved by the Ethics Committee, Karolinska Institute, and full and informed consent was obtained from each subject participating in the study. Assay methods Serum concentrations of cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), 4-androstene-3,17-dione (A-4), 1 7 alfa-hydroxyprogesterone (17 OHP), testosterone (T),unconjugated ( E l ) and total estrone (t-El; sum of unronjugated and conjugated estrone, > 85% estrone sulfate) and prolactin were determined by radioimmunological methods described previously (5-8). For the determination of DHA, DHAS and A-4, the antibodies speci-
.
-
'0-
5-
drostcrone, 4-androstene-3, I 7-dione (A-4), dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS) in patients operated upon for aortic aneurysm. Mean? s.e.mean. For symbols and indications, see Methods section. Significant changes from preoperative levels: Cortisol: Op, 2 days ( P
