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The influence of surgical stress on the psychoneuro-endocrine-immune axis. SA Dahanukar, UM Thatte, UD Deshmukh, MK Kulkarni, RD BapatDepartment of Pharmacology, GS Medical College & KEM Hospital, Parel, Mumbai.
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 0009715290
Stress is known to depress the immune system severely. This study was done to evaluate whether surgical stress influenced polymorphonuclear (PMN) and monocyte functions in association with serum cortisol and the anxiety score as measured on the HARS Rating Scale. We found that surgery (irrespective of whether it was major or minor) significantly depressed PMN and monocyte functions and increased serum cortisol levels. PMN phagocytosis correlated significantly (p < 0.05) with the rise in serum cortisol. In spite of these changes, postoperative clinical recovery was uneventful. No major alterations in the HARS scores were noted pre and post operatively. This study demonstrates that surgical stress depresses the immune system with a concomitant rise in cortisol. Keywords: Convalescence, psychology,Human, Hydrocortisone, blood,Immune Tolerance, immunology,Monocytes, immunology,Neutrophils, immunology,Psychoneuroimmunology, Stress, blood,immunology,psychology,Stress, Psychological, blood,immunology,psychology,Surgical Procedures, Operative, adverse effects,psychology,
The harmful influence of psychological or physical stress on post-operative recovery has been previously explored[1]. There is also sufficient laboratory evidence to show that general anaesthesia exerts an unfavourable effect on host defences, thus negatively influencing postoperative recovery[2],[3],[4]. However, no study has attempted to examine the link between the psychology, endocrine and immune effects occurring after surgical stress. The present study is an attempt to investigate the influence of major and minor surgical procedures on the postoperative recovery, immune status, serum cortisol and the level of anxiety before and after surgery.
Patients undergoing routine surgical intervention in a major surgical unit of our hospital were screened and divided into two groups. Patients in Gr A underwent major surgery which included cases when the surgical procedure involved opening the peritoneum e.g. appendicectomy, prostatectomy, cholecystectomy etc. Patients in Gr B, which included minor surgery like hydrocoele drainage, herniorrhaphy and ligation or excision of piles. History, complete physical examination and organ function tests were performed prior to inclusion into the study. Those patients who showed evidence of gross organ dysfunction, which was likely to influence post-operative recovery per se were excluded. On the day prior to surgery 15 ml blood was collected into heparin and utilised for investigating immune function. The functions studied included phagocytosis and bactericidal capacities of polymorphs as well as phagocytosis of S aureus and Candida albicans by monocytes and fungicidal capacity of monocytes. On the test day, 10 ml heparinized blood was collected and layered on Ficoll-hypaque (Sigma). Monocytes and polymorphs were isolated by the method of Botum[5]. Polymorphonuclear phagocytosis and bactericidal capacity of S.aureus  was determined using the method described by Wilkinson[6]. Monocyte phagocytosis and fungicidal capacity was assessed by the method of Lehrer and Cline[7],[8].The rest (5 ml) was collected in a plain test tube, centrifuged and serum separated. This was stored at - 20 deg. C the assay for serum cortisol was performed. Serum cortisol was estimated by radio immunoassay using the methodology specified in the vitro diagnostic radio immunoassay (RIA) kit supplied by Leeco Diagnostic Systems Laboratories Inc. The anxiety level was determined pre and post operatively by applying Hamilton's Anxiety Rating Scale (HARS). The clinical parameters that were used to judge post-operative recovery included general clinical condition and wound status (specifically infection, gaping and scar formation). All these parameters were evaluated 72 hrs after surgery. If during surgery, any major untoward surgical complication such as excessive bleeding or any anaesthetic complication occurred, the patient was excluded from the study, as these complications would themselves alter the course of surgery. Analysis was done from the following angles. 1. Influence of surgery on the 4 different parameters individually (i.e. clinical recovery, immune functions, serum steroid levels and anxiety scores). Statistical significance was tested by applying the paired t-test in the case of immune functions and steroid levels while the Mann-Whitney test was used to analyse the data on anxiety scores. 2. The data was also analysed to find out whether the type of surgery (i.e. major or minor) influenced the effect of surgery on the different parameters. 3. An attempt was made to find out whether any correlation existed between the depression in any immune function and rise in serum cortisol level.
A total of 23 patients were studied. Of these, 7 had undergone major surgeries (Prostatectomy 2, Vagotomy and Pyloroplasty 1, Appendicectomy 2, Cholecystectomy 1, repair of paraumbilical hernia 1). The rest were cases of minor surgery: hydrocoeles 7, hernia repairs 6, ligation and excision of piles 1, fistulectomy 1 and mastectomy 1. When the PMN and monocyte function of all 23 patients were collectively compared to their basal there was a significant depression [Table - 1]. This was associated with a rise in serum cortisol. The data was then separately analysed to find out whether the type of surgery influenced the degree of depression. No such effect was found. Anxiety scores of the patients before and after surgery are shown in [Table - 2]. The type of surgery the patient was to undergo did not seem to influence the anxiety score as measured on the HARS before surgery. There was also no consistent effect of the surgery on the score post-operatively. The serum cortisol level increased significantly (p<0.001) following surgery [Table - 1]. However, the type of surgery did not influence the rise in serum cortisol. As there was an immunodepression associated with an increase in serum cortisol, we tried to find out whether there was any correlation between the two effects. The depression in PMN phagocytosis post operatively correlated significantly with the rise in serum cortisol (p < 0.05). The depression in the other three parameters did not correlate significantly with the rise in serum cortisol. Clinical recovery of all patients was uneventful.
The results of the present study showed that there was a significant post-operative depression in PMN and monocyte functions associated with a rise in serum cortisol level. Both phagocytic and bactericidal functions of these cell types were depressed. The type of surgery (major or minor) did not influence any of the parameters. Serum cortisol is known to rise following any stressful situation and is often used as a marker to evaluate the effects of stress[8],[9]. Our results confirmed that surgical stress does elevate serum cortisol. This endogenous hormone is known to adversely affect different aspects of immunity, as well as have powerful anti-inflammatory activity. In our study, we found that only the depression of PMN function correlated with serum cortisol. This suggests that other factors may be operational in causing the depression of monocyte functions. Further, the immunodepression or rise in serum cortisol did not alter clinical recovery. An important point to note was that, though the depression in PMN and monocyte functions and rise in serum cortisol was significant statistically, it did not have much clinical significance as all patients had an uneventful recovery. A similar observation had been made by Chestnut and Noe (1986) when they noted that the risk of infection was not more following general anaesthesia[10]. Thus it appears that in other wise normal individuals, the depression in immune cellular function or rise in cortisol does not lead to any significant deleterious effect on post-operative recovery. It may be more relevant in patients who are basically immunodepressed like patients with impaired liver functions or diabetes mellitus. One of the aims of this study had been to find out whether the psychological status of the patient influenced immune functions, serum cortisol or clinical recovery. However, as the anxiety scores obtained showed no consistent pattern no such correlation could be found. This study shows the effect that surgery (irrespective of whether major or minor) depresses immune functions and causes rise in serum cortisol, although this does not influence clinical recovery.
[Table - 1], [Table - 2]
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