Stress Response to Surgery and Possible Ways of Its Correction

Open access

The stress response to surgery has two main systemic effects in an organism: neuroendocrine and haemato-immunological. Neuroendocrine effects are induced by changes in the hypothalamic- pituitary-adrenal axis and the sympathetic-adrenal-medullary axis. Haematoimmunological effects are characterised by cytokine production, acute phase reaction and lymphocyte and neutrophil proliferation. All of these responses interact closely. Prolongation of the stress response can increase morbidity and worsen postoperative outcome. Surgical stress can be affected by preoperative, perioperative and postoperative factors. In this paper, we review the main neuroendocrine and haemato-immunological changes related to stress and discuss different possible approaches to minimise the stress response to surgery

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Ahonen J. Jokela R. Uutela K. Huiku M. (2007). Surgical stress index reflects surgical stress in gynaecological laparoscopic day-case surgery. Brit. J. Anaesth.98 (4) 456-461.

  • Alvarez-Olmos M. Oberhelman R. (2001). Probiotic agents and infectious diseases: A modern perspective on a traditional therapy. Clin. Infect. Dis.32 1567-1576.

  • Anonymous (1998). Effect of intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risks of complications in patients with type 2 diabetes. UKPDS group. Lancet352 837-853.

  • Bagry H. de la Cuadra Fontaine J. C. Asenjo J. F. Bracco D. Carli F. (2008). Effect of a continuous peripheral nerve block on the inflammatory response in knee arthroplasty. Reg. Anest. Pain Med.33 (1) 17-23.

  • Barczynski M. Konturek A. Herman R. M. (2006). Superiority of preemptive analgesia with intraperitoneal instillation of bupivacaine before rather than after the creation of pneumoperitoneum for laparoscopic cholecystectomy: A randomized double-blind placebo-controlled study. Surg. Endoscopy 20 (7) 1088-1093.

  • Bengmark S. (2006). Bioecological control of inflammation and infection in critical illness. Anest. Clin. North Amer. 24 325-337.

  • Benschop R. J. Rodriguez-Feuerhahn M. (1996). Catecholamine induced leukocytosis: Early observations current research and future directions. Brain Behav. Immun.10 77-91.

  • Borgdorff P. J. Ionescu T. I. Houweling P. L. Knape J. T. A. (2004). Large-dose intrathecal sufentanil prevents the hormonal stress response during major abdominal surgery: A comparison with intravenous sufentanil in a prospective randomized trial. Anesth. Analg99 (4) 1114-1120.

  • Bowdle A. Hines R. (2002). Guest editor introduction: Pharmacology up-date 2002 seminars in anaesthesia. Perioper. Med. Pain11 247-257.

  • Brand J.-M. Frohn C. Luhm J. Kirhner H. Schmucker P. (2003). Early alterations in the number of circulating lymphocyte subpopulation and enchanced proinflammatory immune responce during opioid-based general anaesthesia. Shock 20 (3) 213-217.

  • Brunicardi F. C. (2010). Schwartz’s Principles of Surgery. 9thed. The McGraw-Hill Companies Inc. USA. 1866 pp.

  • Buunen M. Gholghesaei M. Veldkamp R. Maijer D. W. Bonjer H. J. Bouvy N. D. (2004). Stress response to laparoscopic surgery: A review. Surg. Endosc. 18 (7) 1022-1028.

  • Chaudhary S. Sethi A. K. Motiani P. Adatia C. (2008). Pre-operative intravenous fluid therapy with crystalloids or colloids on post-operative nausea & vomiting. Indian J. Med. Res. 127 (6) 577-581.

  • Chumbley G. M. Hall G. M. (1997). Recovery after major surgery: Does the anaesthetic make any difference? Brit. J. Anaesth.78 347-348.

  • Coderre T. J. Katz J. Vaccarino A. L. Melzack R. (1993). Contribution of central neuroplasticity to pathological pain: Review of clinical and experimental evidence. Pain53 259-285.

  • Deborah B. Grainne N. George H. (2004). Endocrine and metabolic response to surgery. Contin. Educ. Anaesth. Crit. Care Pain4 (5) 144-147.

  • Desborough J. P. (2000). The stress response to trauma and surgery. Brit. J. Anaesth.85 (1) 109-117.

  • Desborough J. P. (1999). Physiological responses to surgery and trauma. In: Foundations of Anaesthesia (pp. 713-720). Hemmings H. C. Jr Hopkins P. M. (eds.). London: Mosby.

  • Desborough J. P. Hall G. M. (1993). Endocrine response to surgery. In: AnaesthesiaReview. Vol. 10 (pp. 131-148). Kaufman L. (Ed.). Edinburgh: Churchill Livingstone.

  • Dimitrov S. Lange T. Born J. (2010). Selective mobilization of cytotoxic leukocytes by epinephrine. J. Immunol.184 503-511. Edwards R. (1997). Thyroid and parathyroid disease. Int. Anesthesiol Clin35 63-83.

  • Elenkov I. J. Chrousos G. P. (2002). Stress hormones proinflammatory and antiinflammatory cytokines and autoimmunity. Ann. NY Acad. Sci.966 290-303.

  • Elenkov I. J. Wilder R. L. Chrousos G. P. Vizi E. S. (2000). The sympathetic nerve-an integrative interface between two supersystems: The brain and the immune system. Pharmacol. Rev.52 (4) 595-638.

  • Franke A. Lante W. Kurig E. Zöller L.G. Weinhold C. Markewitz A. (2006). Hyporesponsiveness of T cell subsets after cardiac surgery: A product of altered cell function or merely a result of absolute cell count changes in peripheral blood? Eur. J. Cardiothorac. Surg.30 (1) 64-71.

  • Freitas M. Tavan E. Cayuela C. Diop L. Sapin C. Trugnan G. (2003). Host-pathogens cross-talk. Indigenous bacteria and probiotics also play the game. Biol. Cell95 503-506.

  • Golubovska I. Vanags I. (2008). Anaesthesia and stress response to surgery. Proc. Latv. Acad. Sci. Section B 62 (5) 141-147.

  • Gorbach S. L. (2000). Probiotics and gastrointestinal health. Amer. J. Gastroenterol. 95 (suppl) S2- S4.

  • Grainne N. (2005). Hormonal and metabolic responses to trauma. Anaest. Int. Care Med. 6 (9) 313-314.

  • Grocott M. P. Mythen M. G. Gan T. J. (2005). Perioperative fluid management and clinical outcomes in adults. Anesth. Analg. 100 (4) 1093-1106.

  • Hall G. M. Salmon P. (2002). Physiological and psychological influences on postoperative fatigue. Anesth. Analg.95 1446-1450.

  • Hart A. L. Lammers K. Brigidi P. Vitali B. Rizzello F. Gionchetti P. Campieri M. Kamm. M. A. Knight S. C. Stagg A. J. (2004). Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut53 1602-1609.

  • Hollmann M. W. Durieux M. E.(2000). Local anaesthetics and the inflammatory response: A new therapeutic indication? Anasthesiology 93 858-875.

  • Insler S. R. Sessler D. I. (2006). Perioperative thermoregulation and temperature monitoring. Anesthesiol. Clin. 24 (4) 823-837.

  • Ichikawa H. Kuroiwa T. Inagaki A. Shineha R Nishihira T Satomi S Sakata T. (1999). Probiotics bacteria stimulate gut epithelial cell proliferation in rat. Dig. Dis. Sci. 44 (10) 2119-2123.

  • Ivanovs I. Pavars A. Vetra J. Saba M. (2006). Probiotics use in early postoperative period after large bowel resection. Colorect. Dis. 8 (4) (suppl.) 29.

  • Jokela R. Ahonen J. Valijus M. Seppälä T. Korttila K. (2007). Premedication with controlled-release oxycodone does not improve management of postoperative pain after day-case gynaecological laparoscopic surgery. Brit. J. Anaesth.98 (2) 255-260.

  • Karabiyik L. Sardas S. (2001). Comparison of genotoxicity of sevoflurane and isoflurane in human lymphocytes studied in vivo using comet assay. Mutat. Res.492 99-107.

  • Kawasaki T. Ogata M. Kawasaki C. Okamoto K. T. Sata. (2007). Effects of epidural anaesthesia on surgical stress-induced immunosuppression during upper abdominal surgery. Brit. J. Anaesth.98 (2) 196-203.

  • Kehlet H. (1997). Multimodal approach to control postoperative pathophysiology and rehabilitation. Brit. J. Anaesth.78 606-617.

  • Kehlet H. (1999). Acute pain control and accelerated postoperative surgical recovery. Surg. Clin. N. Amer.79 431-443.

  • Kitching A. J. O’Neill S. S. (2009). Fast-track surgery and anaesthesia. Contin. Educ. Anaesth. Crit. Care Pain 9 (2) 39-43.

  • Kraehenbuhl J. P. Corbett M. (2004). Immunology. Keeping the gut microflora at bay. Science303 1624-1625.

  • Krüger K. Mooren F. C. (2007). T cell homing and exercise. Exerc. Imm. Rev 13 37-54.

  • Latterman R. Carli F. Wykes L. Schricker T. (2003) Perioperative glucose infusion and catabolic response to surgery: The effect of epidural block. Anesth. Analg.96 555-562.

  • Ledowski T. Bein B. Hanss R. Paris A. Fudickar W. Scholz J. Tonner P. H. (2005). Neuroendocrine stress response and heart rate variability: A comparison of total intravenous versus balanced anesthesia. Anesth. Analg.101 1700-1705.

  • Lin E. Lowry F. S. Calvano E. S. (1999). The systemic response to injury. In: Principles of Surgery. 7th edn. (pp. 3-53). New York: McGraw Hill.

  • Lyons F. M. Meeran K. (1997). The physiology of the endocrine system. Int. Anesthesiol. Clin.35 1-21.

  • Macpherson A. J. Uhr T. (2004). Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science303 1662-1665.

  • Maharaj C. H. Kallam S. R. Malik A. Hassett P. Grady D. Laffey J. G. (2005). Preoperative intravenous fluid therapy decreases postoperative nausea and pain in high risk patients. Anesth. Analg. 100 (3) 675-682.

  • Manorama S. (2003). Stress response and anaesthesia altering the peri and post-operative management. Inidan J. Anaesth. 47 (6) 427-434.

  • Marc G. H. Timmerman H. M. et al. (2005). Prevention of infectious complications in surgical patients: Potential role of probiotics. Digest. Surg.22 234-244.

  • Matsuoka H. Kurosawa S. Horinouchi T. (2001). Inhalation anaesthetics induce apoptosis in normal peripheral lymphocytes in vitro. Anaesthesiology95 1467-1472.

  • Menigaux C. Fletcher D. Dupont X. Guingard B. Guirimand F. Chauvin M. (2000). The benefits of intraoperative small-dose ketmine on postoperative pain after anterior cruciate ligamentrepair. Anaesth. Analg.90 129-135.

  • Miller G. E. Chen E. Zhou E. S. (2007). If it goes up must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychol. Bull. 133 25-45.

  • Nathan C. (2006). Neutrophils and immunity: Challenges and opportunities. Nat. Rev. Immunol. 6 173-182.

  • Niers L. E. M. Rijkers G. T. Timmerman H. M. Van Bleek G. M. Van Uden N. O. P. Kimpen J. L. L.(2004). A central immunoregulatory role for IL-10 in the suppression of type 2 T-helper cell cytokines by probiotic bacteria. In: Proceedings of the XXIII European Academy of Allergologyand Clinical Immunology Congress Amsterdam. Amsteram.

  • Ogawa K. Hirai M. Katsube T. Murayama M. Hamaguchi K. ShimakawaT. Nritake Y. Hosokawa T. Kajiwara T. (2000). Suppression of cellular immunity by surgical stress. Surgery 127(3) 329-336.

  • Pepys M. B. Hirschfield G. M. (2003). C-reactive protein: A critical update. J. Clin. Invest. 111 (12)1805-1812.

  • Pöpping D. Elia N. Marret E. Remy C. Tramèr M. (2008). Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: A meta-analysis. Arch. Surg.143 (10) 990-999.

  • Puura A. Puolakka P. Rorarius M. Salmelin R. Lindgren L. (2006). Etoricoxib pre-medication for post-operative pain after laparoscopic cholecystectomy. Acta Anaesthesiol Scand50 (6) 688-693.

  • Rigg J. R. Jamrozik K. Myles P. S. Silbert B. S. Peyton P. J. Parsons R. W. Collins K. S. (2002). Epidural anaesthesia and analgesia and outcome of major surgery: A randomised trial. MASTER Anaesthesia Trial Study Group. Lancet359 1276-1282.

  • Salmon P. Hall G. M. (1997). A theory of postoperative fatigue. J. R. Soc. Med.90 661-664.

  • Sanders V. M. Kavelaars A. (2007). Adrenergic regulation of immunity. In: Psychoneuroimmunology (4th edn.) (pp. 65-66). Ader R. (Ed.). Vol. 1. Chapter 2. New York: Elsevier Academic Press.

  • Scarlett M. Crawford-Sykes A. Nelson M. (2002). Preoperative starvation and pulmonary aspiration. New perspectives and guidelines. West IndianMed. J.51 (4) 241-245.

  • Scherer R. (1997). Intraoperative Wärmekonservierung. Viel Lärm um heiße Luft? [Intraoperative heat conservation. A lot of hot air?]. Anaesthesist46 (2) 81-90 (in German).

  • Segerstrom S. C. Miller G. E. (2004). Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry. Psychol. Bull. 130 601-630.

  • Sheeran P. Hall G. M. (1997). Cytokines in anaesthesia. Brit. J. Anaesth.78 201-219.

  • Smith E. M. (2008). Neuropeptides as signal molecules in common with leukocytes and the hypothalamic-pituitary-adrenal axis. Brain Behav. Immun.22(1) 3-14.

  • Sonohata M. Tsunoda K. Kugisaki H. Someya S. Honke H.Mitsunori Kitajima M. Mawatari M. Hotokebuchi T. (2009). Surgical stress differences between total hiparthroplasty and total knee arthroplasty. Int. J. Med. Sci. 1 (11) 505-509.

  • Steinbrook R. A. (1998). Epidural anesthesia and gastrointestinal motility. Anesth. Analg. 86 837-844.

  • Stuart P. C. (2006). The evidence base behind modern fasting guidelines. Best Pract. Res. Clin. Anaesthesiol.20 (3) 457-469.

  • Tewes U. (1999) Concepts in psychology. In: Psychoneuroimmunology. AnInterdisciplinary Introduction. Chapter 4 (pp 96-98). New York NY: Kluwer Academic/Plenum Publishers.

  • Tilbrook A.J. Turner A.I. Clarke I.J. (2000). Stress and reproduction: Central mechanisms and sex differences in non-rodent species. Stress5 (2) 83-100.

  • Timmerman H. M. Koning C. J. M. Mudler L. Rombouts F.M. Beynen A.C. (2004). Monostrain multistrain and multispecies probiotics. A comparison of functionality and efficacy. Int. J. Food Microbiol.96 219-233.

  • Veenhof A. A. Vlug M. S. van der Pas M. H. Sietses C. van der Peet D. L. de Lange-de Klerk E. S. Bonjer H. J. Bemelman W. A. Cuesta M. A. (2012). Surgical stress response and postoperative immune function after laparoscopy or open surgery with fast track or standard perioperative care: A randomized trial. Ann. Surg.255 (2) 216-221.

  • Velickovic I. Yan J. Gross A. J. (2002). Modifying the neuroendocrine stress response. Semin. Anaesth. Periop. Med. Pain21 (1) 16-25.

  • Souba W. W. Fink M. P. Jurkovich G. J. Kaiser L. P. Pearce W. H. Pemberton J. H. Soper N. J. (2007). ACS Surgery: Principles and Practice.6th edn. American College of Surgeons. Philadelphia PA: BC Decker Inc. 1956 pp.

  • Witko-Sarsat V. Rieu P. Descamps-Latscha B. Lesavre P. Halbwachs- Mecarelli L. (2000). Neutrophils: Molecules functions and pathophysiological aspects. Labor. Investig.80 617-653.

  • Wu C. L. Naqibuddin M. Rowlingson A. J. Lietman S. A. Jermyn R. M. Fleisher L. A. (2003). The effect of pain on health-related quality of life in the immediate postoperative period. Anesth. Analg.97 1078 -1108.

  • Zura M. Sakic K. Malenica B. Vrbanovic V. (2009). Immune response to surgical stress in spinal anaesthesia. Periodicum Biologorum 111 (2) 193-196.

Journal information
Impact Factor

CiteScore 2018: 0.3

SCImago Journal Rank (SJR) 2018: 0.137
Source Normalized Impact per Paper (SNIP) 2018: 0.192

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 500 213 12
PDF Downloads 282 150 3