The stress response to surgery: release mechanisms and the modifying effect of pain relief

This short review updates information on the release mechanisms of the systemic response to surgical injury and the modifying effect of pain relief. Initiation of the response is primarily due to afferent nerve impulses combined with release of humoral substances (such as prostaglandins, kinins, leukotrienes, interleukin-1, and tumor necrosis factor), while amplification factors include semi-starvation, infection, and hemorrhage. The relative role of the various signals in producing the complex injury response has not been finally determined, but the neural pathway is probably most important in releasing the classical endocrine catabolic response, while humoral factors are important for the hyperthermic response, changes in coagulation and fibrinolysis immunofunction, and capillary permeability. The modifying effect of pain relief on the surgical stress response is dependent upon the technique of analgesia. However, the effect on humoral-mediated responses is small, regardless of the technique used. Afferent neural blockade with local anesthetics is the most effective technique for reducing the endocrine-metabolic response, but only in operations in the lower part of the abdomen, probably because of insufficient afferent blockade during thoracic epidural analgesia. Systemic opiate administration, as well as non-steroidal antiinflammatory drugs, exert only a small modifying effect on the response. Low-dose combined analgesic regimens may provide total pain relief, but exert no important effect on the stress response. In summary, pain alleviation itself may not necessarily lead to an important modification of the stress response, and a combined approach with inhibition of the neural and humoral release mechanisms is necessary for a pronounced inhibition or prevention of the response to surgical injury.