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Cortisol and Antidiuretic Hormone Responses to Stress in Cardiac Surgical Patients

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Cortisol and Antidiuretic Hormone Responses to Stress in Cardiac Surgical Patients CORTISOL AND ANTIDIURETIC HORMONE RESPONSES TO STRESS IN CARDIAC SURGICAL PATIENTS YASU OKA, SHIGEHARU WAKAYAMA, TSUTOMU OYAMA, Lou[s R. ORKIN, RONALD M. BECKER, M. DONALD BLAUFOX AND ROBERT W.M. FRATER ABSTRACT The hormonal responses to anaesthesia and cardiac surgery were studied in patients undergoing valve or coronary bypass surgery. Marked increases in antidiuretic hormone levels as a result of surgical stress were seen, and were of approximately equal magnitude in both groups. Although both groups also showed marked increases in plasma cortisol levels in response to operations, this response appeared to be relatively bhmted in valve surgery patients, especially at the end of operation and in the intensive care unit. This blunted cortisol response may be a manifestation of exhaustion of adrenocortical reserves in valvular surgical patients whose sympathoadrenal system has already been chronically stimulatcd by a low output state. The important role of the neuroendocrine system in maintaining homeostasis postopera- tively has long been recognized; this relative cortisol deficiency may be aetiologically related to poor postoperative recovery in critically ill valvular surgery patients. KEY WORDS: CARDIAC SURGERY, stress response. A NUMBER OF INVESTIGATORSI-6 have indicated The present study was undertaken to evaluate that the function of the cardiovascular autonomic whether cortisol and antidiuretic hormone re- nervous system is altered in patients with val- sponses to stress are different in patients with vular heart disease. The loss of sympathetic coronary artery disease and valvular disease, as nervous system control associated with depletion we have previously found in regard to sympathe- of cardiac norepinephrine, when coupled with tic response. the impairment in parasympathetic cardiovas- cular regulation, limits the ability to augment MATERIALS AND METHODS cardiac output by increasing either stroke volume Twenty-two patients undergoing open heart or heart rate. These derangements of the auto- surgery were studied; 12 patients had coronary nomic nervous system may well play critical artery surgery (CAS) and ten had valvular sttr- roles in the limited cardiac response to stress in gery (VS). The patients were otherwise compa- these patients. rable except for a significantly lower ejection We have also reported studies 7-~~ of neuro- fraction in the VS group. (Table I). humoral and circulatory responses to stress in Premedication consisted of scopolamine cardiac surgical patients. Our studies generally (0.015 rag- kg -I) and morphine sulphate indicated that patients with coronary artery dis- (0.15 rag. kg-I for coronary patients or ease showed an excitatory sympathetic response 0.10 rag. kg -~ for valvular patients) intramuscu- to stress, while patients with valvular disease had larly, one hour before anaesthesia. Anaesthesia marginal or limited sympathetic response to was begun at 8-8:30 a.m. Induction was accom- stress. plished 3 mg d-tubocurarine and thiopentone so- Yasu Oka, M.D., Shigeharu Wakayama, M.D., dium 4-5 mg-kg -~ , followed by enflurane 0.5 to 2 Tsutomu Oyama, M.D., Louis R. Orkin, M.D., Ronald per cent and oxygen. The trachea was intubated M. Becker, M.D., M. Donald Blaufox, M.D., and Robert W.M. Frater, M.B., Ch.B. Department of with the aid of succinylcholine 1.5 mg. kg -L in- Anesthesiology, Cardiothoracic Surgery and Nuclear travenously and following topical application of Medicine. Albert Einstein College of Medicine, Bronx, lidocaine (4%-4ml). Anaesthesia was main- New York and Department of Anesthesiology, Uni- tained with enflurane 0.5 to 2 per cent with versity of Hirosaki, Hirosaki, Japan. oxygen, supplemented with either pancuronium Reprint requests to Dr. Oka at Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, or d-tubocurarine. Five per cent dextrose in New York, 10461. water was ad ministered at a rate of 10 ml. kg- n/hr 334 Canad. Anaesth. Soc. J., vol. 28, no. 4, July 1981 OKA, el al.: CORTISOL & ANTIDIURETIC RESPONSES TO STRESS 335 TABLE I osmolalities were measured by the freezing point PREOPERATIVE PATIENTCHARACTERISTICS depression method using an Osmette precision osmometer. Coronary Artery Valvular Surgery Surgery Arterial pressure (AP), right and left atrial pressures (RAP, LAP), heart rate (HR) and Patients No. 12 10 cardiac output (CO) were recorded. Pressures NYHA Class (11) 7 6 were measured and recorded continuously (Ill) 5 4 Age (Year) 59 + 10 59 4- 9 through a Statham transducer on a Hewlett- Ejection Fraction (%) 71 "r 18 58 + 11' Packard multichannel recorder (Model 775A). LVEDP (Torr) 16 q- 9 17 4- 7 Cardiac output was determined by dye dilution CPB lime (rain.) 154 + 85 144 _+ 63 technique using an Electronics for Medicine Mean + SD *P < 0.05. output computer (Model DTCCO). Systemic LVEDP: Left Ventricular end-diastolic pressure. vascular resistance (SVR) was calculated from CPB = Cardiopulmonary bypass. the output and pressure data. Intergroup data were analyzed using the uncorrelated t-test and until the start of cardiopulmonary bypass, and intragroup data were analyzed using the corre- thereafter reduced to 5ml-kg-t/hr. A conven- lated t-test. tional cardiopulmonary bypass (CPB) technique RESULTS using an Optiflo II (Cobe Laboratories) bubble oxygenator was employed and the patients were Coronary Artery Surgery Group cooled to 30~ C (oesophageal temperature) during Enflurane anaesthesia alone did not increase CPB. The prime solution consisted of albumin plama cortisol levels significantly. However, 500 ml and Normosol | 2000 ml. surgical stimulation provoked a significant rise of The study was divided into eight periods: l. cortisol from the control value of 11.0 4- 0.9 to Control (before induction of anaesthesia); 2. One 18.1 + 1.6p.g/100ml and this increase was sus- hour after induction of anaesthesia (before skin tained during CPB. After CPB there was a steady incision); 3. Thirty minutes after skin incision increase in plasma cortisol levels to a peak value (pre-CPB); 4. Fifteen minutes on CPB; 5. One (210 per cent of control, P < 0.01) in the ICU hour on CPB; 6. Thirty minutes offCPB; 7. End (Figure I). of operation and; 8. One hour postoperative in The control value of plasma ADH was 5.4 4- the intensive care unit. 0.7 ~tU/ml. Enflurane did not cause ADH release. The following were determined: Plasma cor- Plasma ADH rose significantly after surgical tisol and antidiuretic hormone (ADH) levels, stimulation (290 per cent of control, P< 0.01) and arterial and venous blood gases, serum osmolal- during CPB (> 300 per cent of control, P < 0.01). ity and electrolytes, urine output and osmolality. After CPB, the level declined but it stayed Plasma cortisol levels were determined by the significantly elevated compared with the control fluorimetric method of Rudd, et al.;~ the recov- value. In the ICU, it was 177 per cent of the ery rate was 102 per cent and the coefficient of control value. There were no significant changes variation (CV) was 1.5 per cent. Plasma ADH in plasma osmolality throughout the study. levels were measured by the radioimmunoassay Plasma sodium levels decreased significantly at method of Husain, et al.: ~z recovery rate was 74 the end of operation and plasma potassium de- per cent and CV was 11 per cent. Heparinized creased significantly during the first 15 minutes venous blood for ADH was immediately iced and on CPB. Urine output increased significantly centrifuged for 15 minutes at 4~ Extraction of during and after CPB in spite of high plasma A DH plasma samples was done using cold acetone and levels. Urine osmolality decreased, but not signi- petroleum ether. Dried plasma extracts were ficantly. stored at -20~ until assayed. Arginine Vaso- Haemodynamic changes are shown in Figure pressin (AVP) from Sigma Chemical Co. used as 2. There were no statistically significant changes a standard for ADH (I-125-AVP) was purchased in any variable except for a significant (P < 0.01, from New England Nuclear. The micropressor P < 0.05) decrease in MAP and SVR at pre-CPB unit (U) is the equivalent of about 2.5 pg of AVP. and during CPB. Cardiac index decreased signi- The packed cell volume (PCV) was measured by ficantly (P < 0.05) at the end of operation. the macrohaematocrit method and used to make There was no correlation between plasma cor- corrections for the haemodilution effect of tisol or ADH levels and changes in haemody- plasma cortisol and ADH levels. Serum and urine namic variables except after 15 minutes on CPB, 336 CANADIAN ANAESTHETISTS' SOCIETY JOURNAL PLASMA CORTISOL AND ADH LEVELS HEMODYNAMIC CHANGES Oc Dc " .... * ,v CO~TF~OL A~[S Pff CPB CPB P~SI [HO IrLI 3000 Ifil~ GPB 15MIH THR CPB SLIE5 IHR ~ 2000 . .. S,pn,fIconl from r ".0-~ ".Ot S;onificonl Ifom c~onorv t "05 II ,.01 COH[ROL ANES PRE ;PB (;PB POST END FIGURE I Plasma Cortisol and ADH levels. Top, I HB CP8 l~ WIN I IfR (;P8 SURG plasma Cortisol levels in coronary artery and valvular surgical patients. Enflurane anaesthesia alone did not Significant from r e ".05 el r increase plasma levels significantly. Surgical stimula- Significanl from r 1" .05 t t ".OI tion (Pre CPB) provoked a significant rise of cortisol from the control valve and this increase was sustained FJrU~tE 2 Haemodynamic Changes. Changes in during and after CPB to a peak value in the ICU in both mean artieral pressure (MAP) cardiac index (CI) and groups. However, in general, the response in valvular systemic vascular resistance (SVR) in coronary artery surgical patients was blunted compared to that of and valvular surgical patients are shown. There were coronary artery surgical patients and a significant no statistically significant changes in any of those difference in plasma levels was noted at the end of variables except for significant decrease in MAP and operation and ICU periods.
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