Professor George M Hall Anaesthesia and Intensive Care Medicine St Georges, University of London, London SW17 0RE Anaesthetic

modulation of the stress response to surgery The stress response to surgery consists of a variety of physiological, psychological and behavioural changes. The physiological aspects of the response have been studied in most detail and include hormonal, metabolic, immunological and haematological disturbances. Psychological changes include the feeling of malaise, usually referred to as fatigue, and behavioural changes, such as a reluctance to move, are also common. These changes probably evolved to aid survival in an injured animal living in a primitive environment. The overall effect is retention of water and sodium, mobilisation of substrates, limitation of tissue damage, destruction of micro-organisms and activation of repair processes. The benefits of the stress response are not obvious in modern anaesthetic/surgical practice when physiological disturbances are easily corrected. Instead, it has been argued that some of the changes may be detrimental, so that methods to modify the response have been investigated in an effort to improve patient outcome. The stress response is initiated by two main mechanisms. Firstly, afferent neuronal input from the injured site to the central nervous system and, secondly, by the synthesis of cytokines by macrophage/monocyte cells at the site of tissue damage. It is well recognised that not only somatic, but also autonomic, fibre activity is important in initiating the response. A simple distinction can be drawn between the effects of neuronal stimulation and cytokine production. The former triggers the release of the classical neuroendocrine response with consequent substrate mobilisation, while the latter evokes the acute phase response. There are aspects of the stress response for which this division is over-simplistic. For example, it is clear that the immune and neuroendocrine systems are inter-related. Some cytokines are capable of stimulating ACTH secretion and cytokine production is limited by cortisol secretion. Attempts to modify the stress response have been constrained by the inability to alter pharmacologically the inflammatory response to trauma and hence cytokine production. Large doses of glucocorticoids suppress cytokine synthesis but are associated with deleterious side-effects. Non steroidal anti-inflammatory drugs are ineffective unless given preoperatively for 24 h. The most effective means of decreasing the cytokine-actue phase response is for the surgeon to alter their technique. The adoption of laparascopic techniques markedly reduces the inflammatory changes and is associated with enhanced recovery and discharge. It is notable that the neuroendocrine response is similar in both laparascopic surgery and also open laparatomy. The most practical method of decreasing the neuroendocrine changes is by the use of regional anaesthesia. This has been extensively investigated over the past 25 years. Neuraxial blockade provides excellent analgesia after major abdominal surgery and may result in a substantial decline in catabolic hormone secretion and substrate mobilisation. However, these changes are dependent on achieving autonomic as well as somatic afferent blockade. Other operative sites at which neuroendocrine effects are found include limb and eye surgery.

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Professor George M Hall (continued) There is a continuing debate, often heated, about the potential benefits of regional anaesthesia on mortality and major morbidity after major surgery. Several systematic reviews have indicated improvements in morbidity and even mortality, but these have not been confirmed by large, randomised controlled trials and large retrospective surveys. The reasons for this discrepancy are not obvious. On the one hand, the critics of systematic reviews point out the heterogeneity of patients and treatments, the inclusion of out-dated studies and the initial failure to publish negative data. On the other hand, the regional anaesthesia protagonists criticise the controlled trials for protocol design, evolution and timeliness and statistical evaluation. It is conceivable that the argument will never be adequately resolved. Many intergrated packages of perioperative care include laparascopic or laparascopically-assisted surgery, regional anaesthesia, early mobilisation, feeding and psychological support and the individual contributions cannot be determined. At present, a tentative conclusion would be that changes in surgical technique, with a decreased acute phase response, have had more impact on recovery and possibly major outcomes than the use of regional anaesthesia to blunt the neuroendocrine changes. Perhaps, choosing your surgeon is more important than choosing your anaesthetist.

References (1) Baumann H, Gauldie J. The acute phase response. Immunology Today 1994; 15: 74-9 (2) Desborough JP. The stress response to surgery. Br J Anaesth 2000; 85: 109-17 (3) Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997; 78: 201-19 (4) Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth 1997; 78: 606-17 (5) Burton D, Nicholson G, Hall GM. Endocrine and metabolic response to surgery. CEACCP 2004; 4: 144-7

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