بسم الله الرحمن الرحيم

Stress Response And Severely Obese For OP _ CAB Amr Abdelmonem, M.D. By Amr Abdelmonem,MD. Assistant professor of anesthesia,surgical intensive care and clinical nutrition in faculty of medicine, Cairo university Member of North American Association For The Study Of Obesity Member of the American society of regional anesthesia and pain medicine

Obesity is a well-recognized risk factor for mortality from cardiovascular diseases McGee DL.body mass index and mortality.Ann Epidemiol 2005;15:87-97

Obesity is associated with a 3-or- more-fold increase in the risk of fatal and nonfatal myocardial infarction Dagenais GR, Yi Q, Mann JF et al. Prognostic impact of body weight and abdominal obesity in women and men with cardiovascular disease. Am Heart J 2005; 149:54–60. The American Heart Association has reclassified obesity as a major, modifiable risk factor for coronary heart disease Poirier P, Giles TD, Bray GA et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2006; 113:898–918

Waist circumference maintains the strongest association with cardiovascular disease risk factors than other measures of obesity(BMI,TBF,%BF, skin fold thickness) Andy M,et al.Measures of adiposity and cardiovascular disease risk factors.Obes Res.2007;15:785

Definition Neurohormonal changes that are reproducible from patient to patient With a host of biologic alterations following tissue injury NCHS.Advance report of final mortality statistics,1992.Hyattsville,Maryland: US Department of Health and Human services, Public Health Service,CDC,1994

Biologic Adaptation

Cardiovascular alterations

Neurohormonal changes Desborough JP, Hall GM. Endocrine response to surgery. In: Kaufman L. Anaesthesia Review, Vol. 10. Edinburgh: Churchill Livingstone,1993; 131–48 Autonomic nervous system Autonomic nervous system Sympathetic nervous system activation Sympathetic nervous system activation Excess release of catecholamines (from nerves, ganglia and the heart) Adrenal medulla Adrenal medulla Excess release of catecholamines Excess release of catecholamines (epinephrine and nor-epinephrine) Adrenal cortex Adrenal cortex Excess release of aldosterone (mineralocoticoid) Posterior pituitary gland Posterior pituitary gland Excess release of vasopressin (ADH)

Patients with American Society of Anesthesiology physical status 1 SA node stimulation ➞ tachycardia ➞ ↑ myocardial oxygen demand SA node stimulation ➞ tachycardia ➞ ↑ myocardial oxygen demand Re –entry excitation ➞ tachyarrhythmia's ➞ ↑ myocardial oxygen demand Re –entry excitation ➞ tachyarrhythmia's ➞ ↑ myocardial oxygen demand Stimulation of beta-adrenergic receptors on the cardiac cell membrane ➞ ↑ intracellular cAMP ➞ activating Ca 2+ channels ➞ ↑ contractility ➞ ↑ myocardial oxygen demand Stimulation of beta-adrenergic receptors on the cardiac cell membrane ➞ ↑ intracellular cAMP ➞ activating Ca 2+ channels ➞ ↑ contractility ➞ ↑ myocardial oxygen demand Salt and water retention ➞ ↑ preload ➞ ↑ myocardial oxygen demand Salt and water retention ➞ ↑ preload ➞ ↑ myocardial oxygen demand Hypokalemia ➞ tachycardia ➞ ↑ myocardial oxygen demand Hypokalemia ➞ tachycardia ➞ ↑ myocardial oxygen demand

The Myocardial Oxygen Supply Alexander RW,Schlant RC,Fuster V,et al:Hurst's The Heart,9th ed.New York,McGraw- Hill,1998 Normally CBF is coupled to O demand Normally CBF is coupled to O 2 demand CBF = 80 ml/min/100g CBF = 80 ml/min/100g Normal O 2 delivery= 16 ml/min/100g Normal O 2 delivery= 16 ml/min/100g Normal O 2 consumption= 8-12 ml/min/100g Normal O 2 consumption= 8-12 ml/min/100g O 2 extraction ratio is 60-75% O 2 extraction ratio is 60-75% Therefore the myocardium Therefore the myocardium is supply dependent is supply dependent

SNS Stimulation α adrenoceptors stimulation ➞ VC ➞ followed by VD (sympatholysis) α adrenoceptors stimulation ➞ VC ➞ followed by VD (sympatholysis) The mechanism ↑ myocardial O 2 demand ➞ accumulation of VD metabolites Active hyperemia ➞ prolonged coronary VD (increased supply) ➞ balancing the demand ➞ no ischemia Active hyperemia ➞ prolonged coronary VD (increased supply) ➞ balancing the demand ➞ no ischemia

For OP-CAB patients

Insulin Reaven GM. Role of insulin resistance in human disease.Diabetes.1988;37:1595 Increased sodium retention Increased sympathetic nervous system activity Alteration in the mechanics of blood vessels Leptin Ioanna S,et al. Baroreflex sensitivity in obesity.Obes Res 2007;15:1685 Reduction of baroreflex sensitivity

Ventricular dilatation and eccentric hypertrophy Piercarlo B,et al. Impact of obesity on left ventricular mass. Obes Res 2007;15:2019 Diastolic dysfunction+ systolic dysfunction Kenchaiah S,et al.obesity and the risk of heart failure.N Engl J Med.2002;347:305 Obesity cardiomyopathy ↑ myocardial O 2 demand Galinier M,et al. obesity and cardiac failure.Arch Mal Coeur Vaiss.2005;98:39 ↓ ↓ ↓

Kidney functions and electrolyte Kidney functions and electrolyte imbalance Desborough JP. Physiological responses to surgery and trauma. In: Hemmings HC Jr, Hopkins PM, eds. Foundations of Anaesthesia. London: Mosby, 1999: 713–20

ADH CatecholaminesAldosterone SIADH Hypokalemia and hypomagnesemia Hyponatremia + Hypokalemia + Hypomagnesemia Patients with American Society of Anesthesiology physical status 1 Patients with American Society of Anesthesiology physical status 1

Severe obese for OP-CAP Fluid overload Hypokalemia+ ↓BRS Ioanna S,et al. Baroreflex sensitivity in obesity.Obes Res 2007;15:1685 Hypomagnesemia CHF Galinier M,et al. obesity and cardiac failure.Arch Mal Coeur Vaiss.2005;98:39 Tachyarrhythmia Ioanna S,et al. Baroreflex sensitivity in obesity.Obes Res 2007;15:1685 Cellular edema Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997; 78: 201–19 Intensify the stress response Tepaske R. Immunonutrition. Curr Opin Anaesthesiol 1997; 10: 86–91

Diffuse metabolic alterations 1.Aantaa R, Scheinin M. Alpha2-adrenergic agents in anaesthesia. Acta Anaesthesiol Scand 1993; 37: 1–16 2. Cuthbertson DP. Observations on the disturbance of metabolism produced by injury to the limbs. Q J Med 1932; 1: 233–46 3. UKPDS group. Effect of intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risks of complications in patients with type 2 diabetes. Lancet 1998; 352: 837–53

Neurohormonal changes Autonomic nervous system Autonomic nervous system Sympathetic nervous system activation Sympathetic nervous system activation Excess release of catecholamines Adrenal medulla Adrenal medulla Excess release of catecholamines Excess release of catecholamines (epinephrine and nor-epinephrine) Adrenal cortex Adrenal cortex Excess release of cortisol (glucocoticoid) Anterior pituitary gland Anterior pituitary gland Increased secretion of ACTH and Growth hormone. Increased secretion of ACTH and Growth hormone. Pancreas Pancreas Increased glucagon secretion and decreased insulin secretion Thyroid gland Thyroid gland Decreased free T 4 and free T 3 Increased conversion of Free T 4 to inactive T 3 (rT 3 ) White adipose tissue White adipose tissue Decreased leptin hormone secretion Zeev N,etal.Endocrinology.1999;84:2438

Glycogen Glucose -6-phosphate Liver Glucagon + epinephrine+ GH Blood Cells Insulin Hypoinsulinemia + Insulin resistance Cortisol +catecho +GH +FFA Hyperglycemia Adipocytes catecholamines FFA 25%oxidised 75% Re-esterified hydrolysis glycerol Skeletal Muscle Visceral ptns Cortisol +catecho aa Diabetes of stress

Severely obese for OP-CAB Insulin resistance Cortisol FFA Cytokines Type –II diabetes + Diabetes of stress Diabetic ketoacidosis Resistin

Hematologic Alterations

Neurohormonal changes Autonomic nervous system Autonomic nervous system Sympathetic nervous system activation Excess release of catecholamines Aantaa R, Scheinin M. Alpha2-adrenergic agents in anaesthesia. Acta Anaesthesiol Scand 1993; 37: 1–16 Adrenal medulla Adrenal medulla Excess release of catecholamines Excess release of catecholamines (epinephrine and nor-epinephrine) Desborough J,et al. The stress response to trauma and surgery. Br J Anaesth 2000; 85: 109–17 Increased release of cytokines Increased release of cytokines Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997; 78: 201–19

Patients with American Society of Anesthesiology physical status 1 Increased tendency toward hypercoagulability Increased tendency toward hypercoagulability 1. Increased conc. of plasma fibrinogen 2. Increased platelets aggregation(PAF) 3. Increased conc. of plasminogen activator inhibitor (impaired fibrinolysis) White blood cell and immune function White blood cell and immune function Abnormalities in cell mediated immunity

Severely obese for OP-CAB Tendency toward hypercoagulability Tendency toward hypercoagulability Rimm EB,et al. Body size and fat istribution as predictors of coronary heart disease,Am J Epidemiol.1995;141: Acute phase proteins (increased) 2. Plasminogen activator inhibitor (increased) Consequences Clotting of grafts, acute coronary thrombosis and MI White blood cell and cell mediated immunity White blood cell and cell mediated immunity Low grade inflammation Allison D, et al. Obesity as a disease.Obes Res 2008;16:1161

Mechanisms responsible for surgical trauma-induced hormonal and autonomic changes

Neural stimuli arising at the site of injured tissues ↑ Catecholamines Egdahl RH. Pituitary–adrenal response following trauma to the isolated leg. Surgery 1959; 6: 9–21 ↑ cortisol Enquist A, Brandt MR, Fernandes A, Kehlet H. The blocking effect of epidural analgesia on the adrenocortcial and hyperglycaemic response s to surgery. Acta Anaesthesiol Scand 1977; 21: 330–35 Release of cytokines Helmy SAK, Wahby MAM, El-Nawaway M. The effect of anaesthesia and surgery on plasma cytokine production. Anaesthesia 1999; 54: 733–8 Hypothermia Frank SM,etal.Anesthesiology.1995;82:83 Transient hypotension,hypoxemia and hypercarbia Michael J.Critical Care.1997 Hypoleptinemia ( ↓TSH) Zeev N.Clinical Endocrinology,1999 Hypomagnesemia Anastasios K.Endocrinology.2003 ↑ Acute phase proteins ↓albumin &transferrin ↓zinc&iron Kehlet H. Multimodal approach to control postoperative pathophysiolog y and rehabilitation. Br J Anaesth 1997; 78 Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997

Anne-Sopie M,et al.Circulating IL-6 concentrations and abdominal adiposity.Obey Res2008;16:1487

The effect of anaesthesia on the stress response to cardiac surgery Large doses of morphine (4 mg kg–1) block the secretion of growth hormone and inhibit cortisol release until the onset of cardiopulmonary bypass (CPB). Large doses of morphine (4 mg kg–1) block the secretion of growth hormone and inhibit cortisol release until the onset of cardiopulmonary bypass (CPB). Desborough JP. Physiological responses to surgery and trauma. In: Hemmings HC Jr, Hopkins PM, eds. Foundations of Anaesthesia. London: Mosby, 1999: 713–20 Desborough JP. Physiological responses to surgery and trauma. In: Hemmings HC Jr, Hopkins PM, eds. Foundations of Anaesthesia. London: Mosby, 1999: 713–20 Fentanyl (50–100 µg kg–1), sufentanil (20 µg kg–1) and alfentanil (1.4 mg kg–1) suppress pituitary hormone secretion for OP_CAB Desborough JP, Hall GM. Modification of the hormonal and metabolic response to surgery by narcotics and general anaesthesia. Clin Anaesthesiol 1989; 3: 317–34. Fentanyl (50–100 µg kg–1), sufentanil (20 µg kg–1) and alfentanil (1.4 mg kg–1) suppress pituitary hormone secretion for OP_CAB Desborough JP, Hall GM. Modification of the hormonal and metabolic response to surgery by narcotics and general anaesthesia. Clin Anaesthesiol 1989; 3: 317–34. A high-dose opioid technique leads inevitably to prolonged ventilatory support A high-dose opioid technique leads inevitably to prolonged ventilatory support Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth 1997; 78: 606–17

Perioperative thoracic epidural anaesthesia has been used successfully in the management of patients undergoing coronary artery bypass surgery Liem TH, Hasenbos MAWM, Booij LHDJ, Gielen MJM. Coronary artery bypass grafting using two different anaesthetic effects: Part 2: Postoperative outcome. J Cardithorac Vasc Anesth 1992; 6: 156–61 Perioperative thoracic epidural anaesthesia has been used successfully in the management of patients undergoing coronary artery bypass surgery Liem TH, Hasenbos MAWM, Booij LHDJ, Gielen MJM. Coronary artery bypass grafting using two different anaesthetic effects: Part 2: Postoperative outcome. J Cardithorac Vasc Anesth 1992; 6: 156–61 A study showed that thoracic epidural anaesthesia and general anaesthesia in cardiac surgery attenuated the myocardial sympathetic response and was associated with decreased myocardial damage as determined by less release of troponin T A study showed that thoracic epidural anaesthesia and general anaesthesia in cardiac surgery attenuated the myocardial sympathetic response and was associated with decreased myocardial damage as determined by less release of troponin T Loick HM, Schmidt C, van Aken H et al. High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting. Anesth Analg 1999; 88: 701–9 Loick HM, Schmidt C, van Aken H et al. High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting. Anesth Analg 1999; 88: 701–9

In medical patients, The sympatholytic effects of the blockade of cardiac sympathetic efferents and afferents may improve the balance of oxygen delivery and consumption Meissner A, Rolf N, Van Aken H. Thoracic epidural anesthesia and the patient with heart disease: benefits, risks and controversies. Anesth Analg 1997; 85: 598 – 612

Anesthetic Management of the Patient Receiving Unfractionated Heparin during cardiac surgery Regional Anesthesia and pain medicine,Vol 29,No 2 Suppl1 (March-April),2004:pp1-11 Currently, insufficient data and experience are available to determine if the risk of neuraxial hematoma is increased when combining neuraxial techniques with the full anticoagulation of cardiac surgery. Currently, insufficient data and experience are available to determine if the risk of neuraxial hematoma is increased when combining neuraxial techniques with the full anticoagulation of cardiac surgery. Combining neuraxial techniques with intraoperative anticoagulation with heparin during cardiac surgeries seems acceptable with the following cautions: ● Avoid the technique in patients with other coagulopathies. ● Heparin administration should be delayed for 1 hour after needle placement. ● Indwelling neuraxial catheters should be removed 2 to 4 hours after the last heparin dose and the patient’s coagulation status is evaluated; ●Reheparinization should occur 1 hour after catheter removal.

● ● Monitor the patient postoperatively to provide early detection of motor blockade and consider use of minimal concentration of local anesthetics to enhance the early detection of a spinal hematoma. ● Although the occurrence of a bloody or difficult neuraxial needle placement may increase risk, there are no data to support mandatory cancellation of a case. ● Direct communication with the surgeon and a specific risk- benefit decision about proceeding in each case is warranted. ● Antiplatelet medications, low molecular weight heparin (LMWH) and oral anticoagulants may increase the risk of bleeding complications for patients receiving standard heparin.

Recommendations: Limiting, Diagnosing, and Treating Neuraxial Injury ASRA practice Advisory on neurologic complications in regional anesthesia and pain medicine,Regional Anesthesia and pain medicine,Vol 33,No 5(september- october)2008:pp Epidural anesthetic procedures using the thoracic approach are neither safer nor riskier than using the lumbar approach. (Class I) Surgical positioning and specific space-occupying extradural lesions (e.g., severe spinal stenosis, epidural lipomatosis, ligamentum flavum hypertrophy, or ependymoma) have been associated with temporary or permanent spinal cord injury in conjunction with neuraxial regional anesthetic techniques. Awareness of these conditions should prompt consideration of risk vs. benefit when contemplating neuraxial regional anesthetic techniques. (Class II)

Diagnosis and treatment Magnetic resonance imaging (MRI) is the diagnostic modality of choice for suspected neuraxial lesions. Computed tomography (CT) should be used for rapid diagnosis if MRI is not immediately unavailable, especially when neuraxial compression injury is suspected. (Class I) Diagnosis of a compressive lesion within or near the neuraxis demands immediate neurosurgical consultation for consideration of decompression. (Class I)

Home message

The stress response to surgery comprises a number of hormonal changes initiated by neuronal activation of the hypothalamic–pituitary–adrenal axis The overall metabolic effect is one of catabolism of stored body fuels In general, the magnitude and duration of the response are proportional to the surgical injury therefore exaggerated in cardiac surgeries Understanding the neurobiological and pathophysiological natures of the of the severely obese patients will enable physicians and scientists to approach the proper management of their stress response especially for CAB surgeries Regional anesthesia with low concentrations local anesthetic agents inhibits the stress response to surgery and can also influence postoperative outcome by beneficial effects on organ function.