بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Stress Response And Severely Obese For OP_CAB 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 Amr Abdelmonem , M.D.

3. 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

4. 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

5. 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

8. 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

9. Biologic Adaptation

10. Cardiovascular alterations

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

12. Patients with American Society of Anesthesiology physical status 1 • SA node stimulation➞ tachycardia ➞ ↑myocardial oxygen demand • Re –entry excitation ➞ tachyarrhythmia's➞ ↑myocardial oxygen demand • Stimulation of beta-adrenergic receptors on the cardiac cell membrane ➞ ↑intracellular cAMP ➞ activating Ca2+ channels ➞ ↑contractility➞ ↑myocardial oxygen demand • Salt and water retention➞ ↑preload➞ ↑myocardial oxygen demand • Hypokalemia ➞tachycardia ➞ ↑myocardial oxygen demand

13. The Myocardial Oxygen SupplyAlexander RW,Schlant RC,Fuster V,et al:Hurst's The Heart ,9th ed.New York,McGraw-Hill,1998 • Normally CBF is coupled to O2 demand • CBF = 80 ml/min/100g • Normal O2 delivery= 16 ml/min/100g • Normal O2 consumption= 8-12 ml/min/100g • O2 extraction ratio is 60-75% Therefore the myocardium is supply dependent

14. SNS Stimulation • α adrenoceptors stimulation➞VC ➞ followed by VD(sympatholysis) The mechanism ↑myocardial O2 demand➞ accumulation of VD metabolites Active hyperemia ➞ prolonged coronary VD (increased supply) ➞ balancing the demand ➞ no ischemia

15. For OP-CAB patients

17. 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

18. 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 O2 demand Galinier M,et al. obesity and cardiac failure .Arch Mal Coeur Vaiss.2005;98:39

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

20. Patients with American Society of Anesthesiology physical status 1 ADH Catecholamines Aldosterone SIADH Hypokalemia and hypomagnesemia Hyponatremia + Hypokalemia + Hypomagnesemia

21. Severe obese for OP-CAP Hypokalemia+ ↓BRS Ioanna S,et al. Baroreflex sensitivity in obesity.Obes Res 2007;15:1685 Hypomagnesemia Fluid overload 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

22. 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

23. Neurohormonal changes • Autonomic nervous system Sympathetic nervous system activation Excess release of catecholamines • Adrenal medulla Excess release of catecholamines (epinephrine and nor-epinephrine) • Adrenal cortex Excess release of cortisol (glucocoticoid) • Anterior pituitary gland Increased secretion of ACTH and Growth hormone. • Pancreas Increased glucagon secretion and decreased insulin secretion • Thyroid gland Decreased free T4 and free T3 Increased conversion of Free T4 to inactive T3(rT3) • White adipose tissue Decreased leptin hormone secretion Zeev N,etal.Endocrinology.1999;84:2438

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

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

26. Hematologic Alterations

27. Neurohormonal changes • 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 Excess release of catecholamines (epinephrine and nor-epinephrine) Desborough J,et al . The stressresponseto trauma and surgery . Br J Anaesth 2000; 85: 109–17 • Increased release of cytokines Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997; 78: 201–19

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

29. Severely obese for OP-CAB • Tendency toward hypercoagulability Rimm EB,et al. Body size and fat istribution as predictors of coronary heart disease ,Am J Epidemiol.1995;141:1117 • Acute phase proteins (increased) • Plasminogen activator inhibitor (increased) Consequences Clotting of grafts, acute coronary thrombosis and MI • White blood cell and cell mediated immunity Low grade inflammation Allison D, et al . Obesity as a disease .Obes Res 2008;16:1161

30. Mechanisms responsible for surgical trauma-induced hormonal and autonomic changes

31. Neural stimuli arising at the site of injured tissues 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 ↑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 ↑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 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 HypomagnesemiaAnastasios K.Endocrinology.2003

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

33. 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). 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_CABDesborough 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 Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth 1997; 78: 606–17

34. Perioperative thoracic epidural anaesthesia has been used successfully in the management of patients undergoing coronary artery bypass surgeryLiem 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 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

35. 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

36. Anesthetic Management of the Patient Receiving Unfractionated Heparin during cardiac surgeryRegional 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. 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.

37. ● 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.

38. Recommendations: Limiting, Diagnosing, and Treating Neuraxial InjuryASRA practice Advisory on neurologic complications in regional anesthesia and pain medicine,Regional Anesthesia and pain medicine,Vol 33,No 5(september-october)2008:pp4040-415 •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)

39. 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)

40. Home message

41. 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.

42. Thank You