Surgical stress response and central neural blockade: something to talk about!
Arleziana FlorescuEditorial, no. 2, 2008
* Anaesthesia & Intensive Care Center, Fundeni Clinical Institute, Bucharest, Romania
Despite continuous advances in surgery, perioperative care and anaesthesia, major surgical procedures are still beset with undesirable events such as pain, cardiopulmonary complications, infective and thromboembolic complications, cerebral dysfunction, nausea and ileus, fatigue and prolonged convalescence. Such postoperative morbidity or even mortality may occur regardless of skill, often as "unexpected" complications.
It is well known that during and after surgery the body responds with profound changes in neural, endocrine and metabolic systems, so called surgical stress response (1). Surgical incision is considered to be the trigger for these changes and they are related to the magnitude of surgical trauma, namely tissue destruction. The magnitude and duration of the surgical stress is variable, depending on the site and magnitude of the surgery. Less invasive, more peripheral procedures are associated with a mild or moderate intensity and length of the stress response as compared to the more invasive upper abdominal and thoracic surgery. The stress response to surgery lasts for 3 - 4 days after major surgery, but some changes may last up to one to three weeks. Although these responses represent a defence mechanism, they may, if amplified and prolonged, also be implicated in the development of changes in organ function, surgical stress syndrome (2). The result will be a poor surgical outcome, longer hospital stay and higher costs of medical care, prolonged convalescence and a worth quality of patients' life.
A wide range of neuroendocrinologic, haematologic and immunologic changes characterizes surgical stress response. Surgical trauma elicits a neuroendocrine and metabolic response by activation of the sympathetic and somatic nervous system. Pain, somatic and visceral, is the major afferent pathway of the surgical stress response. The efferent pathways of this response include sympathetic nervous system activation and release of neuroendocrine hormones. Sympathetic nervous system activity is augmented and circulating concentrations of norepinephrine and epinephrine are increased. Changes in endocrine functions include increased secretion of catabolic hormones with suppression of anabolic hormones. There is increased secretion of adrenocorticotrop hormone, rennin-angiotensin-aldosterone, and vasopressin. Pancreatic secretion of glucagons is also increased, and the response to insulin is impaired during surgery. The effect of increased levels of the catabolic hormones is the development of a hypremetabolic status with muscular tissue loss, lipolysis and hyperglycemia. Other changes during the surgical stress syndrome include modifications in the coagulatory-fibrinolytic systems favouring coagulation and thrombosis, immuno-suppression with the risk of infective complications as well as the development of cancer metastases or recurrences (3, 4). Several biological cascade systems are activated, such as cytokines, complement, nitric oxide, arachidonic acid metabolites and free oxygen radicals. All surgical procedures are followed by pain, which unrelieved may amplify surgical stress response. Started initially to promote the provision of substrates from the catabolism of stored fuels for a maximum chance of survival, the prolonged and overreacted neuro-endocrine stress response is more harmful than beneficial.
A variety of different techniques are available to reduce the magnitude of the surgical stress response, and this is the main goal of the surgeons as well as of the anaesthetists. Development of the minimally invasive techniques such as laparoscopic, thoracoscopic and robotic-assisted surgery have significantly reduced the magnitude of the surgical trauma, therefore the magnitude of the surgical stress response.
Central neural blockade, spinal or epidural, is another important technique to reduce stress response to surgery, and the anaesthetists extensively use it during the peri-operative period.
In this issue of the Journal, Malenkoviº et al. report their clinical investigation to evaluate the effect of combined spinal/lumbar epidural and general anaesthesia (CSEGA) versus combined spinal general anaesthesia (CSGA) on some aspects of hormonal and metabolic responses to surgical stress in patients undergoing oncologic colorectal surgery. Serum concentrations of cortisol and glucose were determined at four perioperative intervals and urinary catecholamine at two intervals in both groups. The authors concluded that CSEGA is more suitable as compared to CSGA in order to reduce neuroendocrine stress response in patients undergoing colorectal surgery. This finding is in contradiction with older investigations, which have identified no additional benefit on neuroendocrine response of intraoperative combined spinal/ thoracic epidural analgesia as compared to continuous thoracic epidural analgesia during colonic resection (5). Large amounts of data have demonstrated that the modifying effects of central neural blockade, spinal or epidural, with local anaesthetics on surgical stress response are most pronounced in lower body surgery as compared to upper abdominal and thoracic procedures. Spinal or epidural anaesthesia may provide a near total afferent neural blockade in the somatic and visceral nervous system when utilized with procedures performed on the lower body (6, 7).
The authors also concluded despite the efficacy of CSEAG on neuroendocrine stress response reduction that the full suppression of this response was not achieved in their study. The human body like a danger recognizes surgery as well as trauma and the surgical stress response is the defence mechanism (8). Reducing the magnitude of surgical trauma and prevented an overreacted, prolonged response seems to be the most important goal during the perioperative period. Perhaps none of the techniques available at this moment can completely suppress the surgical stress response.
There may be some reasons why the suppression of neuro-endocrine response was in a lesser extent as the authors have expected, not only because the neural blockade was at the lumbar level and not at as high as at the fourth thoracic level. The central neural blockade techniques, spinal and spinal/ epidural, were used as an analgesic component of general anaesthesia, not as an anaesthetic on their own combined with light general anaesthesia. Local anaesthetic was administered in analgesic concentrations in spinal as well as in epidural technique. However, "complete anaesthetic" concentrations of local anaesthetic are more efficient than lower concentrations in blocking neuroendocrine surgical stress response (9). Local anaesthetic was administered intermittent via epidural catheter during surgery, and epidural analgesia was disconnected at the end of surgery. There is extensive literature to support the role of continuous epidural anaesthesia and continuous epidural postoperative analgesia, up to the day 4 in major surgery, in suppressing the neuro-endocrine surgical stress response (10). There are no data regarding the monitoring of core temperature during surgery but the authors have mentioned it at the monitoring of the deep of anaesthesia. The deep of the anaesthesia is best moni-tored by bispectral index. Core temperature monitoring is important because intraoperative hypothermia is frequently observed, particularly with moderate to prolonged procedures, longer than 2 hours. The cold stress may amplify the surgical stress (11). Blood loss during procedures was not mentioned, and this is another risk factor for surgical stress. There is no information on the intensity of pain during the first 24 postoperative hours when the neuroendocrine response to surgery was evaluated. Pain during postoperative period is known as a major risk factor, which may amplify neuroendocrine and metabolic responses.
There is little data to assess whether there are differences between spinal and epidural perioperative analgesia in suppressing surgical neuroendocrine stress responses. Two older studies that compared spinal with epidural anaesthesia for hysterectomy showed no difference (12, 13). In contrast, studies in colon surgery showed continuous spinal anaesthesia (14) or combined spinal-epidural anaesthesia (15) more effectively reduce the cortisol and glucose response as compared with epidural anaesthesia alone. However, this study (16) is in accordance with some data rising from the older studies.
References
1. KEHLET, H. - The stress response to anesthesia and surgery. Release mechanism and modifying factors. Clin. Anesthesiol., 1984, 2:315.
2. KEHLET, H. - Multimodal approach to control postoperative pathophysiology and rehabilitation. Br. J. Anaesth., 1997, 78: 606.
3. SALO, M. - Effects of anaesthesia and surgery on the immune response. Acta Anaesthesiol. Scand., 1992, 36:201.
4. WADA, H., SEKI, S., TAKAHASHI, T., KAWAR ABAYASHI, N., HIGUCHI, H., HABU, Y., SUGAHARA, S., KAZAMA, T. - Combined Spinal and General Anesthesia Attenuates Liver Metastasis by Preserving Th1/Th2 Cytokine Balance. Anesthesiology, 2007, 106:499.
5. SCOTT, N.B., JAMES, K., MURPHY, M., KEHLET, H. - Continuous thoracic epidural analgesia versus combined spinal/epidural analgesia on pain, pulmonary function and the metabolic response following colonic resection. Acta Anaesthesiol. Scand., 1996, 40:691.
6. KEHLET, H. - Acute pain control and accelerated postoperative surgical recovery. Surg. Clin. North America, 1999, 79:431.
7. CARLI, F., KEHLET, H. - Continuous epidural analgesia for colonic surgery - but what about the future? Reg. Anesth. and Pain Medicine, 2005, 30:140.
8. VELICOVIC, I., YAN, J., GRASS, J.A. - Modifying the Neuroendocrine Stress Response. Semin Anesth., 2002, 21: 16.
9. KEHLET, H. - Modification of response to surgery by neural blockade: Clinical implications. In “Neural Blockade“ sub redactia Cusin M.J., Bridenbaugh P.O., Ed. Lippincot-raven (Philadelphia) 1998, pag. 129-179.
10. GRASS, J.A. - The role of epidural anesthesia and analgesia in postoperative outcome. Anestheisol. Clin. North America, 2000, 18:407.
11. ARKILIC, C.F., AKCA, O, TAGUCHI, A., SESSLER, D.I.,KURZ, A. - Temperature monitoring and management during neuraxial anesthesia: an observational study. Anesth. Analg., 2000, 91:662.
12. ENGQUIST, A., BRANDT, M.R., FERNANDES, A., KEHLET, H. - The blocking effect of epidural analgesia on the adrenocortical and hyperglycemic response to surgery. Acta Anaesthesiol. Scand., 1977, 21:330.
13. MOLLER, I.W., HJORTSO, E., KRANTZ, T., WAMDALL, E., KEHLET, H. - The modifying effects of spinal anaesthesia on intra and postoperative adrenocortical and hyperglycemic response to surgery. Acta Anaesthesiol. Scand., 1984, 28:266.
14. DAHL, J.B., ROSENBERG, J., DIRKES, W.E., MOGENSEN, T., KEHLET, H. - Prevention of postoperative pain by balanced analgesia. Br. J. Anaesthesia, 1990, 64:518.
15. WEBSTER, J., BARNARD, M., CARLI, F. - Metabolic response to colonic surgery: Extradural vs. continuous spinal. Br. J. Anaesthesia, 1991, 67:467.
16. MALENCOVIC, V., BARICEVIC, IVONA, JONES, D.R., NEDIC, OLGICA, BILANOVIC, D. - Enhanced suppression of hormonal and metabolic responses to stress by application of combined spinal-epidural and general anaesthesia compared with combined spinal general anaesthesia during colorectal surgery. Chirurgia (Bucur.), 2008, 103:211.
It is well known that during and after surgery the body responds with profound changes in neural, endocrine and metabolic systems, so called surgical stress response (1). Surgical incision is considered to be the trigger for these changes and they are related to the magnitude of surgical trauma, namely tissue destruction. The magnitude and duration of the surgical stress is variable, depending on the site and magnitude of the surgery. Less invasive, more peripheral procedures are associated with a mild or moderate intensity and length of the stress response as compared to the more invasive upper abdominal and thoracic surgery. The stress response to surgery lasts for 3 - 4 days after major surgery, but some changes may last up to one to three weeks. Although these responses represent a defence mechanism, they may, if amplified and prolonged, also be implicated in the development of changes in organ function, surgical stress syndrome (2). The result will be a poor surgical outcome, longer hospital stay and higher costs of medical care, prolonged convalescence and a worth quality of patients' life.
A wide range of neuroendocrinologic, haematologic and immunologic changes characterizes surgical stress response. Surgical trauma elicits a neuroendocrine and metabolic response by activation of the sympathetic and somatic nervous system. Pain, somatic and visceral, is the major afferent pathway of the surgical stress response. The efferent pathways of this response include sympathetic nervous system activation and release of neuroendocrine hormones. Sympathetic nervous system activity is augmented and circulating concentrations of norepinephrine and epinephrine are increased. Changes in endocrine functions include increased secretion of catabolic hormones with suppression of anabolic hormones. There is increased secretion of adrenocorticotrop hormone, rennin-angiotensin-aldosterone, and vasopressin. Pancreatic secretion of glucagons is also increased, and the response to insulin is impaired during surgery. The effect of increased levels of the catabolic hormones is the development of a hypremetabolic status with muscular tissue loss, lipolysis and hyperglycemia. Other changes during the surgical stress syndrome include modifications in the coagulatory-fibrinolytic systems favouring coagulation and thrombosis, immuno-suppression with the risk of infective complications as well as the development of cancer metastases or recurrences (3, 4). Several biological cascade systems are activated, such as cytokines, complement, nitric oxide, arachidonic acid metabolites and free oxygen radicals. All surgical procedures are followed by pain, which unrelieved may amplify surgical stress response. Started initially to promote the provision of substrates from the catabolism of stored fuels for a maximum chance of survival, the prolonged and overreacted neuro-endocrine stress response is more harmful than beneficial.
A variety of different techniques are available to reduce the magnitude of the surgical stress response, and this is the main goal of the surgeons as well as of the anaesthetists. Development of the minimally invasive techniques such as laparoscopic, thoracoscopic and robotic-assisted surgery have significantly reduced the magnitude of the surgical trauma, therefore the magnitude of the surgical stress response.
Central neural blockade, spinal or epidural, is another important technique to reduce stress response to surgery, and the anaesthetists extensively use it during the peri-operative period.
In this issue of the Journal, Malenkoviº et al. report their clinical investigation to evaluate the effect of combined spinal/lumbar epidural and general anaesthesia (CSEGA) versus combined spinal general anaesthesia (CSGA) on some aspects of hormonal and metabolic responses to surgical stress in patients undergoing oncologic colorectal surgery. Serum concentrations of cortisol and glucose were determined at four perioperative intervals and urinary catecholamine at two intervals in both groups. The authors concluded that CSEGA is more suitable as compared to CSGA in order to reduce neuroendocrine stress response in patients undergoing colorectal surgery. This finding is in contradiction with older investigations, which have identified no additional benefit on neuroendocrine response of intraoperative combined spinal/ thoracic epidural analgesia as compared to continuous thoracic epidural analgesia during colonic resection (5). Large amounts of data have demonstrated that the modifying effects of central neural blockade, spinal or epidural, with local anaesthetics on surgical stress response are most pronounced in lower body surgery as compared to upper abdominal and thoracic procedures. Spinal or epidural anaesthesia may provide a near total afferent neural blockade in the somatic and visceral nervous system when utilized with procedures performed on the lower body (6, 7).
The authors also concluded despite the efficacy of CSEAG on neuroendocrine stress response reduction that the full suppression of this response was not achieved in their study. The human body like a danger recognizes surgery as well as trauma and the surgical stress response is the defence mechanism (8). Reducing the magnitude of surgical trauma and prevented an overreacted, prolonged response seems to be the most important goal during the perioperative period. Perhaps none of the techniques available at this moment can completely suppress the surgical stress response.
There may be some reasons why the suppression of neuro-endocrine response was in a lesser extent as the authors have expected, not only because the neural blockade was at the lumbar level and not at as high as at the fourth thoracic level. The central neural blockade techniques, spinal and spinal/ epidural, were used as an analgesic component of general anaesthesia, not as an anaesthetic on their own combined with light general anaesthesia. Local anaesthetic was administered in analgesic concentrations in spinal as well as in epidural technique. However, "complete anaesthetic" concentrations of local anaesthetic are more efficient than lower concentrations in blocking neuroendocrine surgical stress response (9). Local anaesthetic was administered intermittent via epidural catheter during surgery, and epidural analgesia was disconnected at the end of surgery. There is extensive literature to support the role of continuous epidural anaesthesia and continuous epidural postoperative analgesia, up to the day 4 in major surgery, in suppressing the neuro-endocrine surgical stress response (10). There are no data regarding the monitoring of core temperature during surgery but the authors have mentioned it at the monitoring of the deep of anaesthesia. The deep of the anaesthesia is best moni-tored by bispectral index. Core temperature monitoring is important because intraoperative hypothermia is frequently observed, particularly with moderate to prolonged procedures, longer than 2 hours. The cold stress may amplify the surgical stress (11). Blood loss during procedures was not mentioned, and this is another risk factor for surgical stress. There is no information on the intensity of pain during the first 24 postoperative hours when the neuroendocrine response to surgery was evaluated. Pain during postoperative period is known as a major risk factor, which may amplify neuroendocrine and metabolic responses.
There is little data to assess whether there are differences between spinal and epidural perioperative analgesia in suppressing surgical neuroendocrine stress responses. Two older studies that compared spinal with epidural anaesthesia for hysterectomy showed no difference (12, 13). In contrast, studies in colon surgery showed continuous spinal anaesthesia (14) or combined spinal-epidural anaesthesia (15) more effectively reduce the cortisol and glucose response as compared with epidural anaesthesia alone. However, this study (16) is in accordance with some data rising from the older studies.
References
1. KEHLET, H. - The stress response to anesthesia and surgery. Release mechanism and modifying factors. Clin. Anesthesiol., 1984, 2:315.
2. KEHLET, H. - Multimodal approach to control postoperative pathophysiology and rehabilitation. Br. J. Anaesth., 1997, 78: 606.
3. SALO, M. - Effects of anaesthesia and surgery on the immune response. Acta Anaesthesiol. Scand., 1992, 36:201.
4. WADA, H., SEKI, S., TAKAHASHI, T., KAWAR ABAYASHI, N., HIGUCHI, H., HABU, Y., SUGAHARA, S., KAZAMA, T. - Combined Spinal and General Anesthesia Attenuates Liver Metastasis by Preserving Th1/Th2 Cytokine Balance. Anesthesiology, 2007, 106:499.
5. SCOTT, N.B., JAMES, K., MURPHY, M., KEHLET, H. - Continuous thoracic epidural analgesia versus combined spinal/epidural analgesia on pain, pulmonary function and the metabolic response following colonic resection. Acta Anaesthesiol. Scand., 1996, 40:691.
6. KEHLET, H. - Acute pain control and accelerated postoperative surgical recovery. Surg. Clin. North America, 1999, 79:431.
7. CARLI, F., KEHLET, H. - Continuous epidural analgesia for colonic surgery - but what about the future? Reg. Anesth. and Pain Medicine, 2005, 30:140.
8. VELICOVIC, I., YAN, J., GRASS, J.A. - Modifying the Neuroendocrine Stress Response. Semin Anesth., 2002, 21: 16.
9. KEHLET, H. - Modification of response to surgery by neural blockade: Clinical implications. In “Neural Blockade“ sub redactia Cusin M.J., Bridenbaugh P.O., Ed. Lippincot-raven (Philadelphia) 1998, pag. 129-179.
10. GRASS, J.A. - The role of epidural anesthesia and analgesia in postoperative outcome. Anestheisol. Clin. North America, 2000, 18:407.
11. ARKILIC, C.F., AKCA, O, TAGUCHI, A., SESSLER, D.I.,KURZ, A. - Temperature monitoring and management during neuraxial anesthesia: an observational study. Anesth. Analg., 2000, 91:662.
12. ENGQUIST, A., BRANDT, M.R., FERNANDES, A., KEHLET, H. - The blocking effect of epidural analgesia on the adrenocortical and hyperglycemic response to surgery. Acta Anaesthesiol. Scand., 1977, 21:330.
13. MOLLER, I.W., HJORTSO, E., KRANTZ, T., WAMDALL, E., KEHLET, H. - The modifying effects of spinal anaesthesia on intra and postoperative adrenocortical and hyperglycemic response to surgery. Acta Anaesthesiol. Scand., 1984, 28:266.
14. DAHL, J.B., ROSENBERG, J., DIRKES, W.E., MOGENSEN, T., KEHLET, H. - Prevention of postoperative pain by balanced analgesia. Br. J. Anaesthesia, 1990, 64:518.
15. WEBSTER, J., BARNARD, M., CARLI, F. - Metabolic response to colonic surgery: Extradural vs. continuous spinal. Br. J. Anaesthesia, 1991, 67:467.
16. MALENCOVIC, V., BARICEVIC, IVONA, JONES, D.R., NEDIC, OLGICA, BILANOVIC, D. - Enhanced suppression of hormonal and metabolic responses to stress by application of combined spinal-epidural and general anaesthesia compared with combined spinal general anaesthesia during colorectal surgery. Chirurgia (Bucur.), 2008, 103:211.