Although epidural analgesia alone has been used in most of the aforementioned studies, addition of general anesthesia, which usually is endocrine and metabolically inert, does not change the modifying effect of regional anesthesia on the stress response.13
Although systematic comparative studies have not been performed, the available data suggest that the modulatory effects of intrathecal and epidural anesthesia on the stress response are similars However, future studies should consider the modulatory effect of intrathecal anesthesia on the stress of upper abdominal procedures and the effect of continuous intrathecal anesthesia.
Epidural Intrathecal Opioids and a2 -Adrenergic Agonists
Knowledge of the modulatory mechanisms of nociceptive transmission in the spinal cord has increased tremendously, but it is still far from complete. Of the many transmitters known to be involved in nociceptive modulation, only various opioids and ok agonists have been used in surgical patients.
Several studies have been published on the effects of epidural and intrathecal opioid administration on the surgical stress response. The main conclusion has been that, despite acceptable postoperative pain relief, these techniques have no major effect on the overall postoperative stress response.13 13 Thus, the modifying effect is not comparable with that observed during epidural local anesthesia. However, long-term intrathecal opioids may lead to hypogonadism, hypocorticism, and growth hormone deficiency.113
Systematic studies comparing the differential effects of different opioids on the injury response have not been performed, but no important differences are anticipated. Comparative studies of the effect of intrathecal versus epidural opioid administration on the stress response are not available either.
Although clinical studies have shown that intrathecal and epidural ok -adrenergic agonists have antinociceptive effects, the effects on the stress response are relatively small and transient.13
Effect of Pain Relief Per Se on the Surgical Stress Response
The clinician using regional anesthetic techniques often considers postoperative pain relief as an indication of afferent neural blockade. However, it must be emphasized that pain-conducting stimuli represent only a part of the total afferent barrage after a surgical stimulus. Although most of the studies investigating the effect of regional anesthesia on the surgical stress response have not at the same time looked at the degree of pain relief, there are studies that have simultaneously assessed pain and measured stress responses, which have demonstrated that relief of postoperative pain may not necessarily be followed by a reduction in metabolic demands.12 Thus, even combined analgesic techniques using epidural bupivacaine and morphine to achieve total pain relief after upper abdominal surgery did not significantly reduce the stress response to any important degree; neither did total pain relief with combined analgesia using epidural local anesthetics and morphine reduce metabolic responses to upper abdominal surgery.12
These findings emphasize that although pain may release a stress response, pain relief per se may not necessarily lead to a blockade of the stress response to surgery. Therefore, although a combination of analgesic regimens (balanced analgesia) undoubtedly will have a major place in the future treatment of postoperative pain, measures to provide more efficient neural blockade should be explored to evaluate the role of the nervous system in mediating the injury response as well as to improve measures to suppress these responses.
Regional Anesthesia and Modification of the Surgical Stress Response: Clinical Implications
Neural stimuli have a major role in releasing the endocrine metabolic response to surgical injury; therefore, the important question is whether inhibition of the stress response is beneficial to postoperative outcome.12 12 Although this question is still debatable, modern treatment of the surgical patient aims at reducing the catabolic drive by better anesthetic and surgical techniques, by more efficient control of infection and fluid balance, and by removal of other stimuli to thermogenesis, such as a cool environment.12 This approach aims to minimize the potential detrimental effects of the injury-induced demands of the organs. However, the implications of removing homeostatic controls by regional anesthesia are complicated and should be further explored with regard to safety. Nevertheless, a summary of data from controlled studies comparing postoperative morbidity in patients receiving different techniques of regional anesthesia versus general anesthesia suggests that reduction of surgically induced neural activity may be beneficial112 (see Chapter 9 ). The most beneficial effects on morbidity were seen in the same procedures for which regional anesthesia with local anesthetics was found to be most effective in reducing the stress response12 112 suggesting that reduction in at least some parameters of the stress response may be beneficial. However, it remains to be determined whether a causal relationship exists between reduction in morbidity and stress after regional anesthesia or whether this is just a coincidental event. Nevertheless, use of regional anesthesia with local anesthetics provides a rational basis for modern patient care, and this approach should be integrated into fast-track programs to shorten hospital stay and improve outcome.12 112 112 112
In conclusion, evidence from clinical research during the last decades demonstrates that regional anesthesia may inhibit various reflex responses as well as endocrine metabolic changes, thereby reducing demands on the body and probably improving postoperative outcome. These data support the original hypothesis of anociassociation developed by George Crile at the beginning of this century, and there is growing evidence that these physiologic effects of neural blockade also translate to an improved postoperative outcome.
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