Endocrine Management/Perioperative Heart Failure

From Anesthesia Update 2009, sponsored by the University of California, San Diego, School of Medicine

Educational Objectives

The purpose of this program is to improve the management of stress-induced adrenal insufficiency and hyperglyce­mia, and perioperative heart failure. After hearing and assimilating this program, the clinician will be better able to:

1.   Diagnose stress-induced adrenal insufficiency and hyperglycemia.

2.   Describe the management of each condition, including recommendations from the 2008 Surviving Sepsis guidelines and research on the use of intensive insulin therapy for treating stress-induced hyperglycemia.

3.   Discuss the pharmacologic and nonpharmacologic management of heart failure.

4.   Identify the etiology of most perioperative congestive heart failure.

5.   Explain the importance of the preoperative examination for patients with heart failure.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of in­terest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.

Acknowledgements

Drs. Minokadeh and Dueck were recorded at Anesthesia Update 2009, held January 14-17, 2009, in San Diego, CA, and spon­sored by the University of California, San Diego, School of Medicine. The Audio-Digest Foundation thanks the speakers and the University of California, San Diego, School of Medicine for their cooperation in the production of this program.

Endocrine Management in the Operating Room

Anushirvan Minokadeh, MD, Assistant Clinical Professor of Anesthesiology, University of California, San Di­ego, School of Medicine

Adrenal insufficiency

Pathophysiology: primary —  autoimmune processes (eg, Addison’s disease); idiopathic; congenital adrenal hyper­plasia; adrenal tumors; trauma; secondary —  drugs (eg, steroids); stress (eg, surgery, infections); hypothalamic or pituitary insult (eg, traumatic brain injury)

Epidemiology: noted in 10% to 20% of critically ill patients; prevalence in septic shock £60%; secondary insuffi­ciency usually associated with long-term glucocorticoid use

Synthesis: cholesterol converted to cortisol through series of enzymatic reactions (etomidate blocks 17-a-hydroxy­lase and 11-b-hydroxylase)

Signs and symptoms: weakness, fatigue, muscle aches, nausea, vomiting, diarrhea, and mood and personality changes; hypovolemia (as in orthostatic hypotension); electrolyte abnormalities (low sodium; high potassium; low glucose); hypotension despite fluid resuscitation (shock)

Diagnosis: baseline cortisol <10 µg/dL, or adrenocorticotropic hormone (ACTH) stimulation test with rise of <9 µg/dL; if total cortisol <10 µg/dL, adrenal insufficiency diagnosed and steroids prescribed; if total cortisol >40 µg/dL, patient not adrenally insufficient; stimulation test typically performed when total cortisol >10 g/dL but <40 µg/dL; test involves administering ACTH in dose 200 times endogenous level; normal response is rise in cor­tisol of 9 µg/dL within next hour

Treatment: 300 mg intravenous (IV) hydrocortisone daily

Stress-dose steroids: 25 to 150 mg hydrocortisone, depending on degree of adrenal insufficiency; doses >300 mg not recommended

Therapeutic action of steroids: improve vascular tone and raise blood pressure; enhance action of nitric oxide syn­thetase; decrease aggregation of immune cells at site of inflammation; raise glucose level; promote breakdown of lipids and proteins; increase activity of mineralocorticoids, inhibit antidiuretic hormone, and increase calcium re­sorption

Harmful effects: osteoporosis, depression, poor wound healing, immunosuppression, stomach ulcers, and hypergly­cemia

Steroid replacement therapy for adrenal insufficiency: Annane et al (2002)  —  studied hydrocortisone and fludro­cortisone in patients in septic shock; of 299 patients, ACTH stimulation test showed 229 also had adrenal insuffi­ciency; when treated with steroids, 28-day mortality 53% among nonresponders to ACTH stimulation test, compared to 63% among nonresponders in control group; of patients given etomidate, 94% nonresponders; ad­ministration of etomidate recommended for hemodynamic properties; vasopressor withdrawal at 28 days higher among patients receiving steroids; Corticosteroid Therapy in Septic Shock (CORTICUS) study  —  499 patients in septic shock; 251 patients received 50 mg hydrocortisone; 248 received placebo; no difference in 28-day mortal­ity in nonresponders; mortality 40% among 80 patients given etomidate (30% in nonetomidate group); incidence of side effects higher in steroid group; time to reversal of shock 3.3 days in steroid group, 5.8 days in placebo group

Recommendations from 2008 Surviving Sepsis guidelines: strong evidence (level 1A) for hydrocortisone dose <300 mg/day only; ACTH stimulation test not recommended; consider IV hydrocortisone for treating septic shock if patient hypotensive and poorly responsive to fluids; wean steroids after patient no longer needs vaso­pressors

Conclusions: stress-dose steroids —  administer <300 mg/day hydrocortisone, depending on stress severity; con­sider for patients in septic shock who do not respond to fluids and have escalating pressor requirements; adminis­ter 50 mg every 6 hr for 5 days, then taper over 5 days; ongoing trial looking at fludrocortisone

Glucose and insulin management: endocrine, autonomic, and inflammatory mechanisms result in stress-induced hyperglycemia (glucose levels of 180-200 mg/dL; typical critical care patient has decreased muscle glucose up­take, insulin resistance, and increased insulin levels; complications of hyperglycemia  —  osmotic diuresis, in­creased risk for wound infection; exacerbation of neuronal injury associated with stroke or traumatic brain injury; increased mortality from acute myocardial infarction, trauma, and burns; altered lipid metabolism

Benefits of insulin: anti-inflammatory effect; improved lipid metabolism; decreased endothelial injury (may help prevent hypercoagulable states and thrombosis); van den Berghe et al (2001)  —  »1600 patients in surgical inten­sive care unit (ICU) randomized to insulin drip, with glucose maintained at 80 mg/dL to 110 mg/dL, or conven­tional treatment (insulin drip to keep glucose <220 mg/dL); lower glucose levels associated with survival benefit, especially among patients in ICU >5 days; also associated with less sepsis, less bacteremia, fewer catheter-re­lated bloodstream infections, less polyneuropathy, decreased incidence of renal failure requiring dialysis, fewer red blood cell transfusions, and fewer ventilator days; however, risk for hypoglycemia (<40 mg/dL) much higher, compared to control group; in later study of patients in medical ICU, intensive insulin therapy conferred mortal­ity benefit only to patients in medical ICU >3 days; associated with less morbidity, but more hypoglycemia

Conclusions: intensive insulin therapy requires significant resources and incurs risk for hypoglycemia; glucose lev­els of 80 mg/dL to 110 mg/dL “clearly better than” 220 mg/dL, but middle ground of 90 mg/dL to 150 mg/dL ac­ceptable; when administering insulin in ICU, monitor patients frequently for hypoglycemia

Perioperative Heart Failure

Ronald Dueck, MD, Clinical Professor of Anesthesiology, University of California, San Diego, School of Med­icine

Heart failure (HF): cardiac index <2.0 L/min/m²; clinical syndrome consisting of impaired left ventricular perfor­mance, poor exercise tolerance, and ventricular arrhythmias that curtail life expectancy; annual mortality rate 6% (300,000 deaths per year in United States); congestive heart failure (CHF) now most common reason for hospital admission among patients >65 yr of age; in 2004 study, 30-day mortality rate after major noncardiac surgery signif­icantly higher among people with HF, compared to people with coronary artery disease (CAD) or no cardiovascular disease

Pharmacologic management: angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to reduce renin-angiotensin activation and left ventricular afterload and improve organ perfusion; reverse b-receptor downregulation with low doses of b-blockers; working together, drugs help restore cardiac output; im­proving b-receptor function also reduces tachycardia and myocardial oxygen demand associated with tachycar­dia and hypercontractility, and shortens diastole; result is improved myocardial perfusion and oxygen supply; diuretics —  reduce fluid overload and pulmonary edema; improve pulmonary compliance and volume; result is reduced work of breathing, better oxygenation, and increased exercise tolerance; aldosterone blockers —  have potassium-sparing antihypertensive effects and reduce left ventricular remodeling, with documented survival benefit; digoxin —  improves inotropy, but rarely used due to narrow therapeutic range; reduces sympathetic stim­ulation; helps control heart rate in patients with atrial fibrillation

Nonpharmacologic: synchronized pacing —  extra electrode placed in left ventricle through coronary sinus to pace left ventricular base; electrode hastens contraction, leading to reduced remodeling and improving survival; auto­matic implanted cardioverter/defibrillator (AICD) —placed for malignant ventricular arrhythmias; associated with improved survival

Perioperative HF: causes —  withdrawal of HF drugs (emphasize during preoperative examination which drugs pa­tient must continue taking, including ACE inhibitor to control blood pressure during surgery); fluid overload; surgical anemia; tachyarrhythmias

Management: preoperative diagnosis of HF best way of preventing intraoperative problems; risk factors include preexisting CHF, CAD, diabetes, poorly managed hypertension, shortness of breath on exertion, and orthopnea; physical examination by anesthesiologist essential; tachypnea during speech identifies very high-risk patients; look for jugular venous distention; listen for dry crackles and wet rales; if sounds absent, determine if patient has pleural effusion; check heart for S₃ or S₄ gallop; if absent, consider atrial fibrillation (if both absent, patient may be on b-blocker); check ankles for swelling (if absent, patient may be on diuretic); take detailed activity history; if SpO₂ <94% and patient has HF risk factors, order posteroanterior and lateral chest x-ray

Laboratory findings: serum creatinine >1.4 mg/dL and (if available) cystatin C >1.25 mg/dL (specific for impaired renal function from reduced cardiac output) significant risk factors for HF; brain natriuretic peptide (BNP) >160 pg/mL (normal <100 pg/mL) in patient with shortness of breath highly sensitive and specific for CHF; echocardiography —  look for enlarged left atrial diameter; look for left ventricular hypertrophy and dilatation (suggests seriously impaired systolic function); systolic dysfunction —  look for ejection fraction <50%, regional hypokinesis, akinesis, dyskinesis, or global hypokinesis (always associated with impaired ejection fraction); »40% of HF patients have normal ejection fraction; diastolic dysfunction  —  visible on pulse-wave Doppler; result is reduced early diastolic vs atrial filling (abnormally low E/A ratio); if left atrium can no longer overcome rising left ventricular end-diastolic pressure, E/A ratio may appear normal (pseudonormalization); if present, check tis­sue Doppler measurement, which monitors movement of mitral valve during diastole; if ventricle noncompliant, early diastolic filling may be fast (ventricle smaller than normal); will observe ventricular “kick”, but almost no atrial “kick”; result is atrial fibrillation

Signs of CHF in anesthetized patient: unexplained hypotension; falling pulse oximetry, wave amplitude, pulse pres­sure, and oxygen saturation; decreased peak airway pressure; increasing CO₂ waveform slope with elevated phase III slope; no response to bronchodilators

Anesthetic choices: regional anesthesia best; avoid general anesthetic whenever possible; nerve blocks, local anes­thetics, monitored anesthesia care, and spinal-epidural anesthesia all associated with better outcomes than gen­eral anesthetic; avoid propofol (directly depresses myocardium); consider dexmedetomidine instead (reduces anxiety, has favorable effect on blood pressure and heart rate, and not associated with airway obstruction)

General anesthetics: IV —  narcotics and benzodiazepines to compensate for lower doses of general anesthetics; etomidate helps avoid hypotension; dexmedetomidine may minimize need for volatile agents (off-label use); inhaled —  xenon best, if available; nitrous oxide next best choice, and when combined with midazolam (Versed), provides good prevention of recall during surgery; desflurane, isoflurane, and sevoflurane depress systolic and diastolic function (use minimal doses)

Monitoring: look for arrhythmias, ischemia, and ST changes (treat early); monitor beat-to-beat blood pressure (A-line or noninvasive T-line helpful); maintaining perfusion pressure —  labile pressure indicates early use of vasopres­sors; also consider inotropic agent; monitor pulse pressure if concerned about variation; cardiac output monitoring  —allows detection of intraoperative HF; pulmonary arterial catheter with thermodilution current gold standard; measures preload (including central venous pressure and wedge pressure) and afterload (systemic vas­cular resistance), as well as cardiac output; some catheters also measure mixed venous O₂ saturation; cardiac out­put 2 L/min/m²and S_vO₂ <60 mm Hg indicates treatment for seriously reduced tissue oxygenation; noninvasive cardiac output monitor acceptable if fluid exchange and heart function stable (permits inotropic support); meta­bolic concerns —  impaired cardiac output and hypoperfusion cause metabolic acidosis; monitor blood glucose in diabetic patients; if patient hypoglycemic, heart must struggle for substrate to meet energy demands; CO₂ elimi­nation »80 mL/min suggests hypoperfusion that should be corrected; fluid therapy —  patients cannot tolerate si­multaneous hypovolemia and anesthesia; consider having patient avoid diuretic on morning of surgery if HF well-controlled; normal filling pressure or preload “is probably not enough”; administer adequate fluid to ensure adequate filling pressure; monitor central venous pressure and pulmonary wedge pressure; red blood cells —  acute surgical anemia in HF patients results in hypotension, decreased preload, and tachycardia; avoid giving ex­cessive colloid and crystalloid; use blood transfusion if concerned about tissue oxygenation or oxygen-carrying capacity; inotropic vasopressors —  permit maintenance of adequate cardiac output and filling perfusion pressure and reduce reliance on fluid administration; may prevent intraoperative alveolar filling and CHF; dopamine and dobutamine most common choices; use if patient has hypotension and low cardiac index; tachycardia limits use; may induce pulmonary hypertension as heart rate increases; adding milrinone reduces pulmonary arterial pres­sure without affecting cardiac output; use limited by hypotension (can be overcome by titrating in enough milri­none with vasopressor to maintain pulmonary artery pressure); levosimendan —  inodilator; not yet on market; improves heart contractility by enhancing sensitivity of myocardial troponin complex to calcium; avoids calcium toxicity associated with dobutamine, dopamine, and epinephrine

Postoperative management: consider epidural and/or nerve block analgesia; monitor O₂ saturation; treat anemia if present; ensure adequate blood gases, electrolytes, and glucose; monitor cardiac output; monitor renal function (resume diuretics if necessary); obtain chest x-ray; support ventilation with noninvasive bilevel positive airway pressure device; if CHF serious, keeping endotracheal tube in place for ventilation may be indicated; resume CHF medical therapy promptly

Suggested Reading

Annane D et al: Diagnosis of adrenal insufficiency in severe sepsis and septic shock. Am J Respir Crit Care Med 174:1319, 2006; Annane D et al: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862, 2002; Brunkhorst FM et al: Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125, 2008; Hernandez AF et al: Outcomes in heart failure patients after major noncardiac surgery. J Am Coll Cardiol 44:1446, 2004; Magner JJ, Royston D: Heart failure. Br J Anaesth 93:74, 2004; Salgado DR et al: Adrenal function in different subgroups of septic shock patients. Acta Anaesthesiol Scand 52:36, 2008; Sprung CL et al: Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111, 2008; Van den Berghe G et al: Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359, 2001; Van den Berghe G et al: Intensive insulin ther­apy in the medical ICU. N Engl J Med 354:449, 2006; Vincent JL, Marshall JC: Surviving sepsis: a guide to the guide­lines. Crit Care 12:162, 2008.