'Superpill': The Anesthesia and Surgery Survival Pill

Educational Objectives

The goal of this program is to improve strategies for perioperative premedication. After hearing and assimilating this program, the clinician will be better able to:

1. Cite current literature that compares the benefits and disadvantages of premedication agents.

2. Select optimal agents for surgical premedication.

Summary

Introduction to β-blockers: in 1970s, routinely held preoperatively; labetalol has α and β effects; in animal studies, pretreatment with β-blocker shown to decrease mortality and size of infarcts after clipping of coronary artery; administration of propranolol (Inderal) to animals 3 hr after infarct decreased size of infarct; survival doubled if animals pretreated with propranolol before infarct

In humans: decrease coronary blood flow, myocardial oxygen (O2) consumption, workload, and ischemic burden; decrease nitric oxide, cause dilation, and improve modeling; impair adhesion of leukocytes and rupture of plaque; limit thromboxane and minimize events of thrombosis; effects beneficial for patients with history of hypertension (HTN), myocardial infarction (MI), and stroke

Stone et al (1988): patients with history of HTN randomized to receive preoperative β-blocker or placebo; in placebo group, evidence of perioperative ischemia seen on 12-lead electrocardiography (ECG) in 28%, compared with 2% of β-blocker group

Reduction of ischemia: β-blockers reduce heart rate, effects of catecholamines, and metabolism, and cause systolic shortening and diastolic relaxation; impaired diastolic relaxation increases consumption of O2; β-blockers improve balance of endocardial vs epicardial distribution of blood, thereby increasing rates of survival in patients with history of MI

Data showing no benefit: Brady et al (2005) found no difference in mortality between patients receiving perioperative metoprolol and those on placebo; Yang et al (2006) randomized patients to receive perioperative metoprolol or placebo and found no difference in rates of mortality or cardiovascular events; Juul et al (2006) found no difference in mortality between patients receiving metoprolol vs placebo; POISE Study Group et al (2008) — randomized patients to perioperative metoprolol or placebo; metoprolol group received up to 200 mg metoprolol for 30 days postoperatively, and experienced fewer MIs but higher rates of death (3.1% vs 2.3%) and stroke

Current recommendation for MI: patients experiencing acute MI should receive intravenous β-blocker early regardless of reperfusion therapy; β-blockers in this setting reduce morbidity and mortality

Advantages and disadvantages of β-blockers: do not necessarily reduce hospitalization, mortality, or rates of MI; reduce dysrhythmias; likely to increase hypotension and bradycardia; may increase death and stroke in large doses

Current recommendations for β-blockers: maintain current β-blockade; limit initiation of β-blockade to high-risk patients undergoing high-risk surgery; avoid high-dose β-blockade

Speaker’s recommendations: use low doses of β-blockers; avoid hypotension; use β-blockers only on day of surgery; single doses may modify outcomes; use β-blockers for patients with documented risk (eg, coronary artery disease, HTN); ensure patients taking β-blockers receive dose within 24 hr before surgery

Statins: 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors; affect pathway leading to formation of cholesterol and block CoQ10, among other actions; used to treat states of elevated cholesterol that lead to atherosclerosis, coronary disease, and death; additional benefits of statins include vasodilation, inhibition of platelets, fibrinolysis, antiproliferative effects on plaques, antioxidant effects, anti-inflammatory effects, and stabilization of existing plaques

Acute coronary syndromes: review article found shift in presentation of acute coronary syndromes in United States, from primarily sudden death, tachyarrhythmias, ventricular fibrillation, and cardiac arrest to crushing chest pain and abnormal ECG; fewer patients died suddenly and more received treatment

Kertai et al (2004): investigated patients receiving statins and β-blockers who underwent high-risk surgery; patients stratified according to presence of risk factors; found no effect for statins or β-blockers in low-dose, low-risk group; incidence of morbidity or mortality >50% for patients in high-risk group taking neither medication, vs <10% for patients taking both

Infection-related mortality: Almog et al (2007) investigated ≈11,000 patients with coronary disease and found higher probability of survival in patients taking statins; Nielsen et al (2012) found use of statins associated with lower pneumonia-related mortality

Overall mortality: Mehta et al (2006) investigated population of veterans and found mean age of death 2 yr older among veterans taking statins compared with veterans who did not; Collard et al (2006) found preoperative statin use associated with reduced mortality after coronary artery bypass grafting

Speaker’s comments: speaker suggests statins reduce mortality after any type of surgery; outcomes further improved with addition of aspirin; use of statins currently requires current diagnosis; statins decrease colorectal, lung, and all-cause cancers; 4 studies document lower incidence of delirium in patients admitted to intensive care unit (ICU) who use statins; speaker advocates serious consideration of incorporation of statins into standard preoperative medical therapy, and suggests patients should undergo genetic testing in preparation for preoperative use of statins

Fish oils: have little effect on death from cardiac causes; no data indicate any vitamin or combination of vitamins confers significant benefit

Heydari et al (2016): patients experiencing acute MI randomized to high-dose Ω-3 fatty acids or placebo; Ω-3 fatty acids associated with decreased left ventricular end-stroke volume, decreased size of infarct, decreased fibrosis, increased left ventricular ejection fraction, and better remodeling

Vitamins: studies indicate no benefit; large doses of vitamin E increase likelihood of hemorrhagic stroke

Coenzyme Q10: naturally produced antioxidant; coadministration with statins advised

Dietary supplements: no evidence or slight evidence to indicate benefit from goji, chondroitin, copper, acacia, vitamin A, ginkgo, or β-carotene; evidence indicates benefit for folic acid, green tea, fish oil, vitamin D, cranberry, and ginger root; studies indicate better survival after MI in patients with low levels of folic acid who received supplemental vitamins B12 and B6; supplements provided no benefit for patients without deficiency

Melatonin: endogenous melatonin synthesized from tryptophan; effects include regulation of circadian rhythm, adaptation to environmental changes, antioxidant activity, regulation of immune system, neuroprotection, and regulation of sleep; speaker prescribes for preoperative anxiety; Samarkandi et al (2005) — compared premedication with melatonin, midazolam, or placebo in children; found trend for prolonged recovery in midazolam group; found no emergence excitement at 20, 30, or 45 min in melatonin group; additional studies — melatonin found to reduce required dose of propofol, and to provide perioperative anxiolysis, reduce pain scores, and reduce consumption of opioids; speaker’s recommendation — melatonin 5 mg on evening before surgery and 5 mg on morning of surgery

Additional effects of melatonin: longer time to postoperative analgesia, lower consumption of nonsteroidal anti-inflammatory drugs, lower intraocular pressure, and less need for analgesia during cataract surgery; studies demonstrate patients who develop delirium in ICU have low levels of melatonin; melatonin reduces incidence of perioperative migraine

Gabapentin: effects include increased postoperative analgesia, perioperative anxiolysis, attenuation of response to laryngoscopy and intubation, decreased postoperative nausea and vomiting, decreased pruritis, and increased sedation; ideal dose 600 to 1200 mg

Dexamethasone: effects include decreased pain and inflammation; low-dose (<0.1 mg/kg) has no statistical impact on 24-hr consumption of opioids but reduces pain scores; moderate doses of 8 to 10 mg demonstrate opiate-sparing effects; optimal dose ≈5 mg; speaker avoids use in patients at risk for infection; 8-mg dose elevates glucose and causes difficulties with dosing of insulin for 24 hr

Ketamine: literature indicates small dose of ketamine provides dramatic analgesia for 24 hr; recommended dose 0.5 mg/kg; at speaker’s institution, most patients receive 20 to 30 mg for any major procedure or 10 to 20 mg for minor procedure; speaker’s institution offers acute postoperative ketamine infusion 1 to 10 mg/hr; ketamine used to treat depression

Green tea: studies indicate association with decreases in mortality, strokes, and major cardiovascular events

Readings

Almog Y et al: The effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases. Crit Care Med 2007 Feb;35(2):372-8; Amsterdam EA et al: 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014 Dec 23;130(25):e344-426; Brady AR et al: Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery: results of a randomized double-blind controlled trial. J Vasc Surg 2005 Apr;41(4):602-9; Group PS et al: Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet 2008 May 31;371(9627):1839-47; Heydari B et al: Effect of omega-3 acid ethyl esters on left ventricular remodeling after acute myocardial infarction: the OMEGA-REMODEL randomized clinical trial. Circulation 2016 Aug 02;134(5):378-91; Juul AB et al: Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial. BMJ 2006 Jun 24;332(7556):1482; Nielsen AG et al: The impact of statin use on pneumonia risk and outcome: a combined population-based case-control and cohort study. Crit Care 2012 Jul 12;16(4):R122; Schnyder G et al: Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA 2002 Aug 28;288(8):973-9.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Leslie was recorded at Scottsdale Anesthesia, held October 8-14, 2016, in Scottsdale, AZ, and presented by Holiday Seminars. For information about upcoming CME opportunities from Holiday Seminars, please visit holidayseminars.com.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

AN591901

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.