بسم الله الرحمن بسم الله الرحمن الرحيمالرحيم

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 diseasesMcGee 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 injuryNCHS.Advance report of final mortality statistics ,1992.Hyattsville,Maryland: US Department

of Health and Human services, Public Health Service ,CDC,1994

Biologic Adaptation

Cardiovascular alterationsCardiovascular alterations

Neurohormonal changesDesborough JP, Hall GM. Endocrine response to surgery. In: Kaufman L. Anaesthesia Review, Vol. 10. Edinburgh:

Churchill Livingstone,1993; 131–48 Autonomic nervous systemAutonomic nervous system Sympathetic nervous system activationSympathetic nervous system activationExcess release of Excess release of catecholamines (from nerves , ganglia catecholamines (from nerves , ganglia

and and the heartthe heart) )

Adrenal medullaAdrenal medulla Excess release of Excess release of catecholamines catecholamines (epinephrine and nor-epinephrine)(epinephrine and nor-epinephrine)

Adrenal cortex Adrenal cortex Excess release of Excess release of aldosteronealdosterone (mineralocoticoid) (mineralocoticoid)

Posterior pituitary glandPosterior pituitary glandExcess release of Excess release of vasopressinvasopressin (ADH) (ADH)

Patients with American Society of Anesthesiology physical status 1

SA node stimulationSA node stimulation ➞ ➞ tachycardiatachycardia ➞ ➞ ↑myocardial ↑myocardial oxygen demandoxygen demand

Re –entry excitationRe –entry excitation ➞ ➞ tachyarrhythmia'stachyarrhythmia's➞ ➞ ↑myocardial ↑myocardial oxygen demandoxygen demand

Stimulation of beta-adrenergic receptors on the cardiac Stimulation of beta-adrenergic receptors on the cardiac cell membranecell membrane ➞ ➞ ↑intracellular cAMP↑intracellular cAMP ➞ ➞ activating Caactivating Ca2+ 2+

channelschannels ➞ ➞ ↑contractility↑contractility ➞ ➞ ↑myocardial oxygen ↑myocardial oxygen demanddemand

Salt and water retentionSalt and water retention ➞ ➞ ↑preload↑preload➞ ➞ ↑myocardial ↑myocardial oxygen demandoxygen demand

Hypokalemia Hypokalemia ➞➞ tachycardiatachycardia ➞ ➞ ↑myocardial oxygen ↑myocardial oxygen demanddemand

The Myocardial Oxygen SupplyThe Myocardial Oxygen SupplyAlexander RW,Schlant RC,Fuster V,et al:Hurst's The Heart ,9th ed.New York,McGraw-Alexander RW,Schlant RC,Fuster V,et al:Hurst's The Heart ,9th ed.New York,McGraw-

Hill,1998Hill,1998

Normally CBF is coupled to ONormally CBF is coupled to O2 demand demand

CBF = 80 ml/min/100gCBF = 80 ml/min/100g

Normal ONormal O22 delivery= 16 ml/min/100g delivery= 16 ml/min/100g

Normal ONormal O22 consumption= 8-12 ml/min/100g consumption= 8-12 ml/min/100g

OO22 extraction ratio is 60-75% extraction ratio is 60-75%

Therefore the myocardium Therefore the myocardium

is supply dependentis supply dependent

SNS StimulationSNS Stimulation

αα adrenoceptors stimulation adrenoceptors stimulation ➞➞VCVC ➞ ➞ followed by VDfollowed by VD (sympatholysis)(sympatholysis)

The mechanismThe mechanism

↑↑myocardial Omyocardial O22 demand demand ➞ ➞ accumulation of VD metabolitesaccumulation of VD metabolites

Active hyperemiaActive hyperemia ➞ ➞ prolonged coronary VD (increased supply)prolonged coronary VD (increased supply) ➞ ➞ balancing the demandbalancing the demand ➞ ➞ no ischemiano ischemia

For OP-CAB patientsFor OP-CAB patients

InsulinReaven 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

LeptinIoanna S,et al. Baroreflex sensitivity in obesity.Obes Res 2007;15:1685

Reduction of baroreflex sensitivity

Ventricular dilatation and eccentric hypertrophyPiercarlo B,et al . Impact of obesity on left ventricular mass . Obes Res 2007;15:2019

Diastolic dysfunction+ systolic dysfunctionKenchaiah S,et al .obesity and the risk of heart failure.N Engl J Med.2002;347:305

Obesity cardiomyopathy

↑myocardial O2 demandGalinier M,et al. obesity and cardiac failure .Arch Mal Coeur Vaiss.2005;98:39

↓

↓

↓

Kidney functions and electrolyte 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

ADH Catecholamines Aldosterone

SIADH Hypokalemia and hypomagnesemia

Hyponatremia + Hypokalemia + Hypomagnesemia

Patients with American Society of Anesthesiology physical status 1Patients 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

CHFGalinier 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 edemaSheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997; 78: 201–19

Intensify the stress responseTepaske R. Immunonutrition. Curr Opin Anaesthesiol 1997; 10: 86–91

Diffuse metabolic alterationsDiffuse metabolic alterations

1.Aantaa R, Scheinin M. Alpha2-adrenergic agents in anaesthesia. Acta Anaesthesiol Scand 1993; 37: 1–162. 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 changesNeurohormonal changes

Autonomic nervous systemAutonomic nervous system Sympathetic nervous system activationSympathetic nervous system activationExcess release of catecholaminesExcess release of catecholamines Adrenal medullaAdrenal medulla Excess release of catecholamines Excess release of catecholamines (epinephrine and nor-epinephrine)(epinephrine and nor-epinephrine) Adrenal cortex Adrenal cortex Excess release of cortisol (glucocoticoid)Excess release of cortisol (glucocoticoid) Anterior pituitary glandAnterior pituitary gland Increased secretion of ACTH and Growth hormone.Increased secretion of ACTH and Growth hormone. Pancreas Pancreas

Increased glucagon secretion and Increased glucagon secretion and decreased insulin secretiondecreased insulin secretion Thyroid glandThyroid glandDecreased free TDecreased free T44 and free T and free T33 Increased conversion of Free TIncreased conversion of Free T44 to inactive T to inactive T33(rT(rT33)) White adipose tissueWhite adipose tissueDecreased leptin hormone secretionDecreased leptin hormone secretionZeev N,etal.Zeev N,etal.EndocrinologyEndocrinology.1999;84:2438.1999;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 MuscleVisceral 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 systemAutonomic nervous systemSympathetic nervous system activationSympathetic nervous system activationExcess release of catecholaminesExcess release of catecholaminesAantaa R, Scheinin MAantaa R, Scheinin M. . Alpha2-adrenergic agents in anaesthesia. Alpha2-adrenergic agents in anaesthesia. Acta Anaesthesiol Acta Anaesthesiol

ScandScand 1993; 37: 1–16 1993; 37: 1–16

Adrenal medulla Adrenal medulla Excess release of catecholamines Excess release of catecholamines (epinephrine and nor-epinephrine)(epinephrine and nor-epinephrine)DesboroughDesborough J,et al . The J,et al . The stressstress responseresponse toto trauma and trauma and surgersurgery . y . Br J AnaesthBr J Anaesth 2000; 2000; 8585: :

109–17 109–17

Increased release of cytokinesIncreased release of cytokinesSheeran P, Hall GM. Cytokines in anaesthesia. Sheeran P, Hall GM. Cytokines in anaesthesia. Br J AnaesthBr J Anaesth 1997; 78: 201–19 1997; 78: 201–19

Patients with American Society of AnesthesiologyPatients with American Society of Anesthesiology physical status 1 physical status 1

Increased tendency toward hypercoagulabilityIncreased tendency toward hypercoagulability1.1. Increased conc. of plasma fibrinogenIncreased conc. of plasma fibrinogen

2.2. Increased platelets aggregation(PAF)Increased platelets aggregation(PAF)

3.3. Increased conc. of plasminogen activator inhibitor Increased conc. of plasminogen activator inhibitor (impaired fibrinolysis)(impaired fibrinolysis)

White blood cell and immune functionWhite blood cell and immune functionAbnormalities in cell mediated immunity Abnormalities in cell mediated immunity

Severely obese for OP-CAB

Tendency toward hypercoagulabilityTendency toward hypercoagulabilityRimm EB,et al. Body size and fat istribution as predictors of coronary heart disease ,Am J Rimm EB,et al. Body size and fat istribution as predictors of coronary heart disease ,Am J

Epidemiol.1995;141:1117 Epidemiol.1995;141:1117

1.1. Acute phase proteins (increased)Acute phase proteins (increased)2.2. Plasminogen activator inhibitor (increased)Plasminogen activator inhibitor (increased)

ConsequencesConsequencesClotting of grafts, acute coronary thrombosis and MIClotting of grafts, acute coronary thrombosis and MI

White blood cell and cell mediated immunityWhite blood cell and cell mediated immunityLow grade inflammationLow grade inflammationAllison D, et al . Obesity as a disease .Obes Res 2008;16:1161Allison 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

↑CatecholaminesEgdahl RH. Pituitary–adrenal response following

trauma to the isolated leg. Surgery 1959; 6: 9–21

↑cortisolEnquist 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 cytokinesHelmy 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 Large doses of morphine ((4 mg kg–1) block the 4 mg kg–1) block the secretion of growth hormone and inhibit cortisol release secretion of growth hormone and inhibit cortisol release until the onset of cardiopulmonary bypass (CPB). until the onset of cardiopulmonary bypass (CPB).

Desborough JPDesborough JP. . Physiological responses to surgery and trauma. In: Hemmings HC Jr, Hopkins PM, eds. Physiological responses to surgery and trauma. In: Hemmings HC Jr, Hopkins PM, eds. Foundations of Foundations of

AnaesthesiaAnaesthesia. London: Mosby, 1999: 713–20. London: Mosby, 1999: 713–20

Fentanyl Fentanyl ((50–100 µg kg–1), sufentanil (20 µg kg–1) and 50–100 µg kg–1), sufentanil (20 µg kg–1) and alfentanil (1.4 mg kg–1) suppress pituitary hormone alfentanil (1.4 mg kg–1) suppress pituitary hormone secretion for OP_CABsecretion for OP_CAB Desborough JP, Hall GM. Modification of the hormonal and metabolic Desborough JP, Hall GM. Modification of the hormonal and metabolic

response to surgery by narcotics and general anaesthesia. response to surgery by narcotics and general anaesthesia. Clin AnaesthesiolClin Anaesthesiol 1989; 3: 317–34 1989; 3: 317–34 . .

A A highhigh--dose opioid technique leads inevitably to dose opioid technique leads inevitably to prolonged ventilatory support 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 Perioperative thoracic epidural anaesthesia has been used successfully in the management of patients used successfully in the management of patients undergoing coronary artery bypass undergoing coronary artery bypass surgerysurgeryLiem TH, Hasenbos MAWM, Booij Liem TH, Hasenbos MAWM, Booij

LHDJ, Gielen MJM. Coronary artery bypass grafting using two different anaesthetic effects: Part 2: Postoperative outcome. LHDJ, Gielen MJM. Coronary artery bypass grafting using two different anaesthetic effects: Part 2: Postoperative outcome.

J Cardithorac Vasc AnesthJ Cardithorac Vasc Anesth 1992; 6: 156–61 1992; 6: 156–61

A study showed that thoracic epidural A study showed that thoracic epidural anaesthesia and general anaesthesia in anaesthesia and general anaesthesia in cardiac surgery attenuated the myocardial cardiac surgery attenuated the myocardial sympathetic response and was associated with sympathetic response and was associated with decreased myocardial damage as determined decreased myocardial damage as determined by less release of troponin Tby less release of troponin T

Loick HM, Schmidt C, van Aken H Loick HM, Schmidt C, van Aken H et al. et al. High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative 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 stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass

grafting. grafting. Anesth AnalgAnesth Analg 1999; 88: 701–9 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: Meissner A, Rolf N, Van Aken H. Thoracic epidural anesthesia and the patient with heart disease:

benefits, risks and controversies. benefits, risks and controversies. Anesth AnalgAnesth Analg 1997; 1997; 8585: 598–612 : 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 Currently, insufficient data and experience are available to determine if the risk of neuraxial hematoma is increased determine if the risk of neuraxial hematoma is increased when combining neuraxial techniques with the full when combining neuraxial techniques with the full anticoagulation of cardiac surgery. 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: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)

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 messageHome 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.