Increased hypothalamic-pituitary-adrenal (HPA) activation, culminating in elevated circulating cortisol levels is a fundamental response to stressors. In animals, this neuroendocrine change is highly reliable and marked (approximately 5-10-fold elevations), whereas in humans, the increase of cortisol release is less pronounced, and even some potent life-threatening events (anticipation of surgery) only elicit modest cortisol increases. Meta-analysis of factors that influenced the increase of cortisol release in a laboratory context pointed to the importance of social evaluative threats and stressor controllability in accounting for the cortisol rise. The present meta-analysis, covering the period from 1978 through March 2007, was undertaken to identify the factors most closely aligned with cortisol increases in natural settings. It appeared that stressor chronicity was fundamental in predicting cortisol changes; however, this variable is often confounded by the stressor type, the stressor's controllability, as well as contextual factors, making it difficult to disentangle their relative contributions to the cortisol response. Moreover, several experiential factors (e.g. previous stressor experiences) may influence the cortisol response to ongoing stressors, but these are not readily deduced through a meta-analysis. Nevertheless, there are ample data suggesting that stressful events, through their actions on cortisol levels and reactivity, may influence psychological and physical pathology.

Impact of stressors in a natural context on release of cortisol in healthy adult humans: a meta-analysis.

Background Previously, we have demonstrated that surgical stress rapidly induced transient hyporesponsiveness of blood cells to endotoxin and that monocyte mCD14 and HLA-DR expression decreased soon after the start of surgery under general anaesthesia. This study was designed to investigate the effects of epidural anaesthesia on surgical stress-induced immunosuppression in patients undergoing upper abdominal surgery. Methods After having obtained informed consent, patients were randomly allocated to receive general anaesthesia (Group G) or general anaesthesia with epidural anaesthesia (Group E). Perioperative changes in neutrophil phagocytic activity, neutrophil respiratory burst activity, monocyte mCD14 and HLA-DR expression, plasma IL-10 concentration, and the LPS-induced TNF-α production in whole blood were measured. Results Surgical stress rapidly depressed neutrophil phagocytic activity, monocyte mCD14 and HLA-DR expression, and LPS-induced TNF-α production ex vivo ( P vs preoperation) in both Group G and Group E. In contrast, the plasma IL-10 concentration increased significantly 2 h after the start of surgery ( P Conclusion This study showed that the innate immune system is suppressed from the early period of upper abdominal surgery. Subgroup analysis suggested that epidural anaesthesia to T4 dermatome as well as general anaesthesia may not protect patients from this immunosuppression. These results in part explain the impairment of host-defense mechanisms seen in the perioperative period.

Effects of epidural anaesthesia on surgical stress-induced immunosuppression during upper abdominal surgery

Background The first goal was to test the hypothesis that 100% inspired oxygen maintained for approximately 8 h intraoperatively is not associated with impaired pulmonary oxygenation. The authors also tested the hypothesis that intraoperative inhalation of 100% oxygen augments proinflammatory and antimicrobial responses of alveolar macrophages during anesthesia and surgery. Methods The authors studied patients administered 100% oxygen (n = 30) and 30% oxygen (n = 30) during propofol-fentanyl general anesthesia. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, 2, 4, and 6 h after induction of anesthesia, and at the end of surgery. The authors measured "opsonized" and "unopsonized" phagocytosis and microbicidal activity. RNA was extracted from harvested cells and cDNA was synthesized. The expression of interleukin(IL)-1beta, IL-6, IL-8, interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) was measured by semiquantitative polymerase chain reaction. Results Gene expression of all proinflammatory cytokines except IL-6 increased fourfold to 20-fold over time in both groups. However, expression of TNF-alpha and IL-8, IFN-gamma, and IL-6 and IL-1beta was 2-20 times greater in patients administered 100% than in those administered 30% oxygen. Unopsonized and opsonized phagocytosis and microbicidal activity decreased progressively, with the decreases being nearly twice as great during inhalation of 30% oxygen versus 100% oxygen. Conclusion Inhalation of 100% oxygen improved intraoperative decreases in phagocytic and microbicidal activity possibly because expression of proinflammatory cytokines was augmented. These data therefore suggest that intraoperative inhalation of 100% oxygen augments antimicrobial and proinflammatory responses in alveolar macrophages during anesthesia and surgery.

Supplemental intraoperative oxygen augments antimicrobial and proinflammatory responses of alveolar macrophages

It is well known that altered host defenses in general can play a significant role in the development of infection in any patient but their role becomes even more important in surgical patients where infections are the result of individual risk factors associated with the patient and other specific factors associated with the surgery itself. Thus all possible factors that can help modify the immune response should be taken into account in order to intervene, whenever possible, with therapies based on defined abnormalities to reduce the rate of post-surgical infections. Many factors associated with the patient have been clearly identified as responsible for a decreased immune response: old age, concomitant diseases (diabetes, renal and liver failure, solid and hematologic neoplasias, malnutrition, autoimmune diseases, AIDS) and concomitant therapies (corticosteroid, cytotoxic agents). Old age can affect both humoral and cell-mediated immune responses. Chronic diseases can be responsible for a reduced primary response or depression of delayed hypersensitivity reactions (renal failure, neoplasias) or changes in leukocyte function (diabetes, leukemia, lymphomas). Malnutrition frequently accompanies diseases such as cancer, chronic and acute pancreatitis, inflammatory bowel diseases. Deficiencies in important vitamins and minerals (B6, A, folate, biotin, riboflavin...) can alter significantly the leukocyte function and immune response. Finally, there appears to be innate immune-suppression following any form of injury which is correlated with its magnitude and can affect any aspect of immunity. This has been well studied both in burn and surgical trauma. Alteration of phagocytosis, opsonization and chemotaxis are typically affected in burns, whereas surgical stress can include some reduction of cell mediated immunity. The best approach today to minimizing post-surgical infections is probably, besides use of antibiotic prophylaxis, to reduce the surgical trauma which consequently reduces the stress response and immune-suppression and to optimize the immune response by maintaining homeostasis through nutritional support.

Immune system and surgical site infection.

BackgroundTobacco smoking inhibits alveolar macrophage function, but cessation of smoking markedly reduces the risk of postoperative pulmonary complications. The authors therefore evaluated the effect of nonsmoking duration on both antimicrobial and inflammatory functions of alveolar macrophages dur

Recovery of intraoperative microbicidal and inflammatory functions of alveolar immune cells after a tobacco smoke-free period

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.

MK Kulkarni

Papers

The influence of surgical stress on the psychoneuro-endocrine-immune axis.