THE STRESS RESPONSE OF CRITICAL ILLNESS
1999; Elsevier BV; Volume: 15; Issue: 1 Linguagem: Inglês
10.1016/s0749-0704(05)70037-3
ISSN1557-8232
AutoresJ.I. Epstein, Michael J. Breslow,
Tópico(s)Anesthesia and Neurotoxicity Research
ResumoMaintenance of homeostasis in the setting of acute and significant injury is crucial to survival. In the perioperative period, threats to homeostasis occur as a result of either elective surgery (deliberate tissue injury) or unplanned trauma (inadvertent tissue injury). Resuscitation of patients during these periods of tissue injury and resulting organ dysfunction is a core activity of anesthesiologists and intensivists. In addition to resuscitation, however, these practitioners must understand how host responses to injury can affect homeostasis and represent a threat to survival. This article describes changes in autonomic and endocrine function caused by surgery; examines how host, anesthetic, and surgical factors influence this physiologic response; delineates relationships between organ-specific alterations in function and elements of the stress response; examines data indicating a relationship between stress-induced alterations in organ function and the development of clinically important complications; and evaluates how changes in practice patterns might alter outcome.Tissue injury elicits a large number of neural and hormonal responses that result in predictable physiologic alterations. Many of these neuroendocrine changes have been recognized for some time and are generally regarded as appropriate responses.7Cannon W.B. Bodily changes in pain, hunger, fear, rage. ed 2. Appleton & Co., New York1934Google Scholar, 11Chernow B. Alexander H.R. Smallridge R.C. et al.Hormonal responses to graded surgical stress.Arch Intern Med. 1987; 147: 1273Crossref PubMed Scopus (415) Google Scholar Circulating concentrations of norepinephrine and epinephrine are increased by augmented sympathetic nervous system activity.3Breslow M.J. Jordan D.A. Christopherson R. et al.Epidural morphine decreases postoperative hypertension by attenuating sympathetic nervous system hyperactivity.JAMA. 1989; 261: 3577Crossref PubMed Scopus (125) Google Scholar, 27Halter J.B. Pflug A.E. Porte Jr, D. Mechanism of plasma catecholamine increases during surgical stress in man.J Clin Endocrinol Metab. 1977; 45: 936Crossref PubMed Scopus (229) Google Scholar Although rigorous documentation is lacking, it is likely that there is a parallel decrease in parasympathetic nervous system activity. Alterations in autonomic nervous system activity are accompanied by diffuse changes in endocrine function. The more important of these responses are summarized in Table 1. There is increased secretion of adrenocorticotropin hormone (ACTH), growth hormone, prolactin, vasopressin, and endorphin from the pituitary, while secretion of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are either unchanged or decreased.1Arnetz B.B. Lahnborg G. Eneroth P. et al.Age-related differences in the serum prolactin response during standardized surgery.Life Science. 1984; 35: 2675Crossref PubMed Scopus (14) Google Scholar, 10Chan V. Wang C. Yeung R.T. Pituitary-thyroid responses to surgical stress.Acta Endocrinol. 1978; 88: 490PubMed Google Scholar, 16Dubois M. Pickar D. Cohen M.R. et al.Surgical stress in humans is accompanied by an increase in plasma betaendorphin immunoreactivity.Life Science. 1981; 29: 1249Crossref PubMed Scopus (123) Google Scholar, 37Newsome H.H. Rose J.C. The response of human adrenocorticotrophic hormone and growth hormone to surgical stress.J Clin Endocrinol Metab. 1971; 33: 481Crossref PubMed Scopus (78) Google Scholar Peripheral endocrine function largely parallels changes in the regulatory pituitary hormones; adrenal secretion of cortisol and ACTH is augmented,8Casey J.H. Bickel E.Y. Zimmerman B. The pattern and significance of aldosterone secretion in the postoperative patient.Surg Gynecol Obstet. 1957; 105: 179PubMed Google Scholar, 44Sandberg A.A. EikNes K. Samuels L.T. et al.The effects of surgery on the blood levels and metabolism of 17-hydroxycorticosteroids in men.J Clin Invest. 1954; 33: 1509Crossref PubMed Scopus (30) Google Scholar while thyroid function tends to be depressed.10Chan V. Wang C. Yeung R.T. Pituitary-thyroid responses to surgical stress.Acta Endocrinol. 1978; 88: 490PubMed Google Scholar Pancreatic secretion of glucagon is increased.In contrast, insulin secretion, when corrected for changes in glucose concentration, is attenuated.26Halter J.B. Pflug A.E. Relationship of impaired insulin secretion during surgical stress to anesthesia and catecholamine release.J Clin Endocrinol Metab. 1980; 51: 1093Crossref PubMed Scopus (75) Google Scholar In addition to changes in autonomic nervous system and endocrine function, traumatic injury also alters the pattern of protein synthesis in the liver. There is increased synthesis and release of the so-called "acute phase reactants," while synthesis of albumin and other hepatic products is decreased. More recently, it has been recognized that traumatic injury is associated with increased plasma concentrations of select cytokines, particularly interleukin-6.36Naito Y. Tamai S. Shingu K. et al.Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery.Anesthesiology. 1992; 77: 426Crossref PubMed Scopus (222) Google Scholar, 39Pullicino E.A. Carli F. Poole S. et al.The relationship between circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor (TNF) and the acute phase response of elective surgery and accidental injury.Lymphokine Res. 1990; 9: 231PubMed Google Scholar In contrast, tumor necrosis factor increases only slightly following major injury and interleukin-1 concentrations do not appear to change with isolated trauma.36Naito Y. Tamai S. Shingu K. et al.Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery.Anesthesiology. 1992; 77: 426Crossref PubMed Scopus (222) Google Scholar, 39Pullicino E.A. Carli F. Poole S. et al.The relationship between circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor (TNF) and the acute phase response of elective surgery and accidental injury.Lymphokine Res. 1990; 9: 231PubMed Google Scholar Maintenance of homeostasis in the setting of acute and significant injury is crucial to survival. In the perioperative period, threats to homeostasis occur as a result of either elective surgery (deliberate tissue injury) or unplanned trauma (inadvertent tissue injury). Resuscitation of patients during these periods of tissue injury and resulting organ dysfunction is a core activity of anesthesiologists and intensivists. In addition to resuscitation, however, these practitioners must understand how host responses to injury can affect homeostasis and represent a threat to survival. This article describes changes in autonomic and endocrine function caused by surgery; examines how host, anesthetic, and surgical factors influence this physiologic response; delineates relationships between organ-specific alterations in function and elements of the stress response; examines data indicating a relationship between stress-induced alterations in organ function and the development of clinically important complications; and evaluates how changes in practice patterns might alter outcome. Tissue injury elicits a large number of neural and hormonal responses that result in predictable physiologic alterations. Many of these neuroendocrine changes have been recognized for some time and are generally regarded as appropriate responses.7Cannon W.B. Bodily changes in pain, hunger, fear, rage. ed 2. Appleton & Co., New York1934Google Scholar, 11Chernow B. Alexander H.R. Smallridge R.C. et al.Hormonal responses to graded surgical stress.Arch Intern Med. 1987; 147: 1273Crossref PubMed Scopus (415) Google Scholar Circulating concentrations of norepinephrine and epinephrine are increased by augmented sympathetic nervous system activity.3Breslow M.J. Jordan D.A. Christopherson R. et al.Epidural morphine decreases postoperative hypertension by attenuating sympathetic nervous system hyperactivity.JAMA. 1989; 261: 3577Crossref PubMed Scopus (125) Google Scholar, 27Halter J.B. Pflug A.E. Porte Jr, D. Mechanism of plasma catecholamine increases during surgical stress in man.J Clin Endocrinol Metab. 1977; 45: 936Crossref PubMed Scopus (229) Google Scholar Although rigorous documentation is lacking, it is likely that there is a parallel decrease in parasympathetic nervous system activity. Alterations in autonomic nervous system activity are accompanied by diffuse changes in endocrine function. The more important of these responses are summarized in Table 1. There is increased secretion of adrenocorticotropin hormone (ACTH), growth hormone, prolactin, vasopressin, and endorphin from the pituitary, while secretion of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are either unchanged or decreased.1Arnetz B.B. Lahnborg G. Eneroth P. et al.Age-related differences in the serum prolactin response during standardized surgery.Life Science. 1984; 35: 2675Crossref PubMed Scopus (14) Google Scholar, 10Chan V. Wang C. Yeung R.T. Pituitary-thyroid responses to surgical stress.Acta Endocrinol. 1978; 88: 490PubMed Google Scholar, 16Dubois M. Pickar D. Cohen M.R. et al.Surgical stress in humans is accompanied by an increase in plasma betaendorphin immunoreactivity.Life Science. 1981; 29: 1249Crossref PubMed Scopus (123) Google Scholar, 37Newsome H.H. Rose J.C. The response of human adrenocorticotrophic hormone and growth hormone to surgical stress.J Clin Endocrinol Metab. 1971; 33: 481Crossref PubMed Scopus (78) Google Scholar Peripheral endocrine function largely parallels changes in the regulatory pituitary hormones; adrenal secretion of cortisol and ACTH is augmented,8Casey J.H. Bickel E.Y. Zimmerman B. The pattern and significance of aldosterone secretion in the postoperative patient.Surg Gynecol Obstet. 1957; 105: 179PubMed Google Scholar, 44Sandberg A.A. EikNes K. Samuels L.T. et al.The effects of surgery on the blood levels and metabolism of 17-hydroxycorticosteroids in men.J Clin Invest. 1954; 33: 1509Crossref PubMed Scopus (30) Google Scholar while thyroid function tends to be depressed.10Chan V. Wang C. Yeung R.T. Pituitary-thyroid responses to surgical stress.Acta Endocrinol. 1978; 88: 490PubMed Google Scholar Pancreatic secretion of glucagon is increased. In contrast, insulin secretion, when corrected for changes in glucose concentration, is attenuated.26Halter J.B. Pflug A.E. Relationship of impaired insulin secretion during surgical stress to anesthesia and catecholamine release.J Clin Endocrinol Metab. 1980; 51: 1093Crossref PubMed Scopus (75) Google Scholar In addition to changes in autonomic nervous system and endocrine function, traumatic injury also alters the pattern of protein synthesis in the liver. There is increased synthesis and release of the so-called "acute phase reactants," while synthesis of albumin and other hepatic products is decreased. More recently, it has been recognized that traumatic injury is associated with increased plasma concentrations of select cytokines, particularly interleukin-6.36Naito Y. Tamai S. Shingu K. et al.Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery.Anesthesiology. 1992; 77: 426Crossref PubMed Scopus (222) Google Scholar, 39Pullicino E.A. Carli F. Poole S. et al.The relationship between circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor (TNF) and the acute phase response of elective surgery and accidental injury.Lymphokine Res. 1990; 9: 231PubMed Google Scholar In contrast, tumor necrosis factor increases only slightly following major injury and interleukin-1 concentrations do not appear to change with isolated trauma.36Naito Y. Tamai S. Shingu K. et al.Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery.Anesthesiology. 1992; 77: 426Crossref PubMed Scopus (222) Google Scholar, 39Pullicino E.A. Carli F. Poole S. et al.The relationship between circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor (TNF) and the acute phase response of elective surgery and accidental injury.Lymphokine Res. 1990; 9: 231PubMed Google Scholar Classic thinking is that the stress response serves an important compensatory role in the response to injury. Sympathetic nervous system activation protects central blood pressure and augments cardiac output, and thus maintains vital organ perfusion. Increases in aldosterone and vasopressin act to conserve intravascular volume. Endorphins provide analgesia. Increased concentrations of cortisol, glucagon, and epinephrine serve to increase blood glucose levels and to redirect metabolism so as to increase concentrations of fuel substrates. Finally, there appears to be a tendency towards hypercoagulability, which would likely improve hemostasis. More recently, however, the overall utility of this integrated set of responses in the modern medical setting has been called into question. With surgical repair of injuries, skilled replacement of intravascular volume, and administration of alternate fuel substrates, the need for the stress response is less clear. Furthermore, the diverse physiologic sequelae of the stress response have the potential to precipitate clinically important complications, particularly in patients with major underlying medical problems. The past decade has seen intense scrutiny of adverse outcomes in surgical patients. Underlying this effort is the belief, that by elucidating mechanisms, physicians will be able to alter practice patterns and reduce morbidity and mortality. Thus far, results demonstrate a low incidence of deaths directly related to anesthesia or surgery, with the preponderance of adverse outcomes attributable to the presenting surgical problem and preexisting medical conditions.6Buck N. The report of a confidential enquiry into perioperative death.Nuffield Provincial Hospitals Trust Lond Tab. 1982; 3.22: 76Google Scholar These findings clearly indicate the need to define how anesthesia and surgery interact with preexisting problems to produce clinically important complications. An emerging body of evidence suggests that stress-related changes in autonomic nervous system activity and endocrine function play important roles in the genesis of perioperative adverse events. Patients may be subject to both psychologic and physiologic stresses in the perioperative period. There is evidence that the emotional anticipation of a surgical procedure can have far reaching cellular implications. For example, immunocyte desensitization is seen in patients awaiting elective cardiac surgery.19Fricchione G. Bilfinger T.V. Jandorf L. et al.Surgical anticipatory stress manifests itself in immunocyte desensitizations: Evidence for autoimmunoregulatory involvement.Int J Cardiol. 1996; 53: 65Abstract Full Text PDF Scopus (15) Google Scholar Other potential stressors include hypovolemia, anemia, hypothermia, hypotension, hypoxia and hypercarbia. Pain and fasting also initiate elements of the stress response. The diverse stimuli that incite the physiologic responses to surgery can be modulated by anesthetic agents and techniques. An extensive body of literature exists defining the diverse hormonal and autonomic nervous system changes that occur following elective surgery. Elective surgery serves as a useful paradigm for examining the stress response to trauma in that the nature of the injury is reproducible from patient to patient. Furthermore, the absence of compounding stressors, such as tissue hypoperfusion and sepsis, provides insight into the isolated effects of tissue injury. In addition, the ability to pretreat patients prior to surgical trauma has allowed investigators to evaluate mechanisms responsible for the stress response, and allow correlations between specific hormonal/autonomic nervous system alterations and discrete physiologic effects. Finally, by modifying the stress response to surgery, it has been possible to evaluate how it contributes to clinically important outcomes. There are a host of physiologic alterations that occur following surgical trauma. In general, the magnitude of the stress response is proportional to the magnitude of the tissue trauma11Chernow B. Alexander H.R. Smallridge R.C. et al.Hormonal responses to graded surgical stress.Arch Intern Med. 1987; 147: 1273Crossref PubMed Scopus (415) Google Scholar; accordingly, the extent to which these physiologic alterations manifest themselves vary depending upon the extent of tissue injury associated with particular operations. Cardiovascular alterations include increases in heart rate, arterial blood pressure, and cardiac output. As these physiologic changes all act to increase myocardial oxygen consumption, it is almost certain that this latter variable is also markedly increased. Several investigators have demonstrated a correlation between increases in arterial blood pressure following surgery and changes in plasma concentrations of epinephrine and norepinephrine,27Halter J.B. Pflug A.E. Porte Jr, D. Mechanism of plasma catecholamine increases during surgical stress in man.J Clin Endocrinol Metab. 1977; 45: 936Crossref PubMed Scopus (229) Google Scholar suggesting that high levels of sympathetic activity are responsible for most perioperative cardiovascular changes. Diffuse metabolic alterations also occur following surgery. Blood sugar concentrations increase as a result of increased gluconeogenesis and reduced glucose uptake by peripheral tissues. These effects are mediated by the synergistic actions of glucagon, cortisol, and epinephrine.46Shamoon H. Hendler R. Sherwin R.S. Synergistic interactions among antiinsulin hormones in the pathogenesis of stress hyperglycemia in humans.J Clin Endo Meta. 1981; 52: 1235Crossref PubMed Scopus (203) Google Scholar Another important metabolic consequence of the stress response is an increase in protein catabolism. This has been quantified by measuring urinary protein excretion, which can rise by more than 100%.50Tsuji H. Shirasaka C. Asoh T. et al.Effects of epidural administration of local anaesthetics or morphine on postoperative nitrogen loss and catabolic hormones.Br J Surg. 1987; 74: 421Crossref PubMed Scopus (35) Google Scholar Human volunteer studies have demonstrated augmented alanine release into the systemic circulation with infusion of glucagon, cortisol, and epinephrine.25Gore D.C. O'Brien R. Reines H.D. Derangements in peripheral glucose and oxygen utilization induced by catabolic hormones.Crit Care Med. 1993; 21: 1712Crossref PubMed Scopus (12) Google Scholar Finally, an increase in lipolysis has also been noted. The third major category of physiologic alterations following surgery involves kidney function and maintenance of fixed concentrations of select electrolytes. There is a marked rise in plasma vasopressin (ADH) concentrations following elective surgery.2Bormann B.V. Weidler B. Dennhardt R. et al.Influence of epidural fentanyl on stress-induced elevation of plasma vasopressin (ADH) after surgery.Anesth Analg. 1983; 62: 727Crossref PubMed Scopus (28) Google Scholar Plasma ADH concentrations required for the control of plasma osmolality range from undetectable to 8 pM. Surgical trauma results in concentrations of plasma vasopressin that are often many times higher than those encountered in the normal control of plasma osmolality; concentrations in excess of 50 pM have been described following major surgery. Furthermore, plasma vasopressin concentrations remain elevated for 7 days postoperatively. The consequence of this elevation in plasma vasopressin concentrations is an impaired ability to excrete free water. Essentially, all surgical patients have the syndrome of inappropriate ADH, in that postoperative ADH concentrations are not related to the control of plasma osmolality. Other renal and electrolyte changes include an increase in sodium retention mediated by sympathetic outflow to the kidney (which affects proximal tubular sodium reclamation) and an increase in plasma aldosterone concentration (which affects distal tubular sodium reabsorption). In addition, reduced plasma concentrations of potassium and magnesium have been described in surgical patients. The mechanism responsible for hypokalemia in this setting appears to be beta-adrenergic receptor-mediated transcellular shifts in potassium.5Brown M.J. Brown D.C. Murphy M.B. Hypokalemia from β-2 receptor stimulation by circulating epinephrine.N Engl J Med. 1983; 309: 1414Crossref PubMed Scopus (543) Google Scholar The mechanism responsible for reduced concentrations of magnesium remains to be elucidated. Finally, two potentially important hematologic alterations occur in surgical patients. The first is a tendency towards hypercoagulability. Plasma fibrinogen concentrations are increased as a result of augmented synthesis of this protein by the liver. There is increased platelet aggregation presumably in response to the release of a variety of aggregation-promoting agonists.42Rosenfeld B.A. Faraday N. Campbell D. et al.Perioperative platelet reactivity and the effects of clonidine.Anesthesiology. 1993; 79: 255Crossref PubMed Scopus (40) Google Scholar Fibrinolysis is decreased as a result of increased plasma concentrations of plasminogen activator inhibitor, the major regulator of the plasminogen fibrinolytic system.41Rosenfeld B.A. Beattie C. Christopherson R. et al.The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis.Anesthesiology. 1993; 79: 435Crossref PubMed Scopus (270) Google Scholar The second hematologic alteration involves white blood cells and immune function, although our understanding of these changes is incomplete. While there are many studies in the literature examining immune function following surgical trauma, most have focused on abnormalities of cell mediated immunity, demonstrating abnormal intradermal reactions to skin testing and impaired in vitro mitogenic responses to phytohemagglutinin. Since most postoperative infections are bacterial in nature, however, the relevance of these abnormalities is unclear. There are considerably fewer data available examining neutrophil function in the perioperative period. Since infections account for a large percentage of major postoperative complications, this area of research is potentially of significant interest. The development of therapeutic strategies to improve postoperative immune function would likely represent a major advance. The physiologic changes documented above do not result in untoward effects in the great majority of individuals undergoing elective surgery. With the aging of the population and larger numbers of patients presenting for elective surgery with severe underlying medical problems, however, it has become increasingly apparent that these same physiologic alterations have the potential to produce important complications. Cardiovascular complications include hypertension, tachyarrhythmias, myocardial ischemia, and infarction. Despite considerable research, myocardial infarction continues to be a major cause of perioperative morbidity and mortality. Available data link many episodes of postoperative ischemia to sympathetic nervous system activation, where increased myocardial oxygen consumption outpaces the ability of patients with coronary artery disease to increase coronary blood flow. This demand-dependent ischemia may be amenable to treatment strategies that decrease myocardial work (e.g., beta adrenoceptor antagonists, antihypertensive agents, nitrates). In certain patients, acute coronary thrombosis at the site of atheromatous lesions may precipitate ischemia and infarction. While strategies to prevent postoperative hemostatic changes might be beneficial in select high-risk patients, such therapies still need to be developed and tested. Hyperglycemia is the metabolic complication observed most commonly in postoperative patients. The control of glucose homeostasis in diabetic patients, in particular, consumes resources and physician and nurse time. Standard therapy, which involves administration of reduced amounts of insulin preoperatively, often does not result in acceptable control of blood sugar nor does it uniformly prevent against dangerous hypoglycemia. Given that these regimens do not take into account the nature of the surgical procedure or the anesthetic, which are the two principal determinants of the magnitude of the stress response, the limited efficacy of this therapeutic approach is not surprising. Renal and electrolyte concerns generally include (1) potential for hypervolemia and congestive heart failure caused by impaired sodium excretion; (2) hyponatremia when excess free water is given to surgical patients that have impaired ability to excrete free water; and, (3) the development of hypokalemia and hypomagnesemia. Prevention of fluid overload and heart failure requires close attention to fluid balance and the recognition that intraoperative and postoperative fluids, although necessary to maintain intravascular volume in the face of interstitial edema and third space losses, must be excreted as mobilization occurs. Diuretics may be necessary to effect fluid removal, particularly in patients with underlying renal and cardiac disease. Avoidance of hypotonic fluids is almost always sufficient to prevent hyponatremia. Finally, although physicians routinely administer potassium and magnesium to maintain plasma concentrations in the normal range, the need for such routine supplementation is unclear. Considerable recent attention has focused on the possibility that hypercoagulability contributes to the development of thrombotic complications, including deep venous thrombosis (DVT) in the veins of the leg, pulmonary emboli, clotting of arterial bypass grafts following revascularization procedures, and acute coronary thrombosis. While optimal preventative strategies have not been defined, physicians routinely use subcutaneous heparin and sequential inflation stockings for DVT prophylaxis. Infectious complications account for a large number of major complications in surgical patients. Other than prophylactic antibiotic administration in select surgical procedures, effective countermeasures have yet to be developed. Emerging evidence indicates that stress response involves discrete, disparate systems that respond to different stimuli and interact in affecting physiologic functions. Recent data suggest that cytokines can be a component of the stress response, and may be responsible for the initiation of biochemical and hormonal cascades that are remote in time and location from the inciting trauma. In the setting of tissue inflammation, activated macrophages synthesize many different cytokines, including TNF, IL-1, IL-6, and IL-8. High circulating levels of IL-1 and TNF, although not seen with isolated tissue injury, can induce hemodynamic instability and stimulate release of classic stress hormones. Many cytokines directly stimulate ACTH release from the pituitary. Cytokines also have diffuse effects on protein synthesis. They contribute to synthesis of acute phase reactants and can induce synthesis of nitric-oxide synthase, leading to enhanced production of the vasodilator, nitric oxide. Cytokines also increase expression of leukocyte and endothelial-cell-adhesion molecules. These cellular proteins cause white blood cell margination, an event thought to be an important first step in mediating tissue damage in sepsis. Cytokines may contribute to adverse outcomes. In neonates, peak levels of IL-6 and IL-8 are temporally correlated with the development of postoperative complications.49Tsang T.M. Tarn P.K. Cytokine response of neonates to surgery.J Pediatr Surg. 1994; 29: 794Abstract Full Text PDF PubMed Scopus (22) Google Scholar In other studies, IL-6 has been associated with higher norepinephrine and glucagon levels, altered energy substrate utilization, and hypermetabolism.32Kotari G. Usami M. Kasaharo H. et al.The relationship of IL-6 to hormonal mediators for utilization and systemic hypermetabolism after surgical trauma.Kobe J Med Sci. 1996; 42: 187PubMed Google Scholar Postoperative concentrations of IL-6 and IL-8 have been used to quantify the magnitude of the stress response to surgical stress.51Tsukada K. Takenoshita S. Nagamachi Y. Pentothal interleukin-6, interleukin-8, and granulocyle elastase activity after elective surgery.APMIS. 1994; 102: 837Crossref PubMed Scopus (29) Google Scholar Early animal studies demonstrated a marked attenuation of the stress response when an extremity was denervated prior to injury.30Hume D.M. Egdahl R.H. The importance of the brain in the endocrine response to injury.Ann Surg. 1959; 150: 697Crossref PubMed Scopus (83) Google Scholar Studies in paraplegic humans undergoing elective surgical procedures below the level of the spinal cord injury further supported an important role for neural stimuli in initiating the stress response. The majority of recent studies examining this issue have used regional anesthetic techniques to block afferent sensory traffic. In general, these studies have shown that, with minor peripheral surgical procedures, deafferentation markedly attenuates all stress hormone responses. With more extensive surgical procedures, however, the ability of regional anesthetic techniques to prevent the stress response is less than complete. In particular, while the increase in plasma catecholamines can be almost completely blocked, increases in ACTH and cortisol levels can be attenuated but not completely prevented. Two different mechanisms have been proposed to account for failure to block this element of the stress response. One postulates the existence of alternate neural, non-sensory
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