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Management of Medications in the Perioperative Period: An Evidence Based Approach Eric J Milie, D.O.

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Presentation on theme: "Management of Medications in the Perioperative Period: An Evidence Based Approach Eric J Milie, D.O."— Presentation transcript:

1 Management of Medications in the Perioperative Period: An Evidence Based Approach Eric J Milie, D.O.

2 Medical Consultant Primary role: understand the patient and his/ her diseases Medications: to continue or not? Need to understand risk/ benefit of continuing or holding a medication

3 Medical Consultant continued Medications thought to increase the risk of surgical complications that are not essential for short term improvement in quality of life should be held in the perioperative period Muluk V, Macpherson DS. Perioperative medication management. UpToDate Online

4 Case 1 A 28 year old female patient scheduled for a wisdom tooth extraction has a history of migraines, for which she takes Fiorinol (aspirin, caffeine, and butalbitol) almost daily.


6 When to Discontinue Aspirin Irreversible inhibitor of of platelet cyclo- oxygenase Leads to increased intraoperative blood loss and transfusion requirements¹ CABG, Peripheral vascular surgeries: increased in hospital mortality with aspirin withdrawal²’³ 1. Taggart DP, Siddiqui A, Wheatley DJ. Low dose preoperative aspirin therapy, postoperative blood loss, and transfusion requirements. Snn Thorac Surg 1990; 50:424-428. 2. Mangano DT. Aspirin and mortality from cornoary bypass surgery. NEJM 2002; 347:1309-1317. Dacey LJ, et al. Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients. Ann Thorac Surg 2000; 70:1986-1990. 3. Nelipovitz DT, et al. The effect of perioperative aspirin therapy in peripheral vascular surgery: a decision analysis. Anesth Annalg 2001;93:573-580

7 Case 1 continued Aspirin should be withheld before surgery in which perioperative hemorrhage could be catastrophic (CNS surgery) Circulating platelet pool replaced every 7-10 days Cheng A, Zaas A. The Osler Medical Handbook. St Louis, MO:C.V.Mosby; 2003:518-519.

8 Case 2 A 68 year old woman with severe osteoarthritis is scheduled for a total hip replacement. She takes acetaminophen and ibuprofen for her arthritis, and she is also receiving postmenopausal hormone replacement therapy (HRT).

9 Case 2 continued Acetaminophen relatively safe Little bleeding risk Can be continued safely in patients undergoing surgery

10 Case 2 continued NSAID usage  Reversible inhibitors of platelet cyclo-oxygenase  Can induce renal failure, especially in the face of ACE inhibitors, particularly in the setting of hypotension and dehydration (common in perioperative period)  Generally accepted to hold 3 days before surgery (no evidence to support this)¹ Goldenberg NA, Jacobson L, Manco-Johnson MJ. Brief communication: duration of platelet dysfunction after a 7-day course of ibuprofen. Ann Int Med 2005; 142:506-509.

11 Case 2 continued HRT  Heart and Estrogen/progestin Replacement Study (HERS) 2000  Postmenopausal HRT increases risk for DVT and PE in women with CAD¹  Risk increased after lower extremity fracture  Risk magnified after surgery, and remained elevated for 3 months post- op  General consensus is to hold for 4 weeks preop  HERS study evaluated only women with known CAD; routine discontinuation of HRT for noncardiac surgery controversial  Recent case-control study with 108 cases and 210 controls found no association between HRT and venous thromboembolism² 1.Grady D, Wenger NK, Herrington D et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Ann Int Med 2000; 132:689-696. 2.Hurdanek JG, Jaffer AK, Morra N, Brotman DJ. Postmenopausal hormone replacement and venous thromboembolism following hip and knee arthroplasty. Thromb Haemost 2004; 92:337-343.

12 Key findings of HERS trial of hormone replacement therapy and venous thromboembolic risk ♦HRT increased risk of VTE 2.7-fold overall ♦HRT increased risk of VTE 18-fold in patients with lower extremity fracture ♦HRT increased risk of VTE approximately 5-fold in the 90 days following inpatient surgery ♦HRT increased risk of VTE 5.7-fold in the 90 days following hospitalization

13 Case 3 A 64 year old man with a history of stable angina, congestive heart failure, ventricular tachycardia, and COPD is scheduled for inguinal hernia repair.

14 Case 3: Med List Digoxin 0.125 mg Atenolol 50 mg Atorvastatin 40 mg Amiodarone 100 mg Furosemide 40 mg Clopidogrel 75 mg Lisinopril 10 mg “Inhalers”

15 Case 3 continued Clopidogrel Nitrates, Digoxin, Clonidine, Beta Blockers, Calcium Channel Blockers, and Antiarrhythmic drugs  Irreversible platelet inhibitor  Discontinue 7-10 days prior to major surgery  Essentially safe to continue perioperatively  For patients who cannot take PO and therapy cannot be interrupted, consider transdermal or intravenous routes of administration

16 Case 3 continued Diuretics, ACE Inhibitors, ARBS Non-statin cholesterol medications  consensus recommendation to hold the AM of surgery, especially if given for CHF¹  If indication is HTN and patient hypertensive, may be used at physician discretion  Risk of renal failure with ACEI/ARB usage and induction from anesthesia²  Carry theoretical risk of rhabdomyalysis and myositis  No impact of short-term cardiovascular mortality  Hold 1 day before surgery 1. Coriat P, Richer C, Douraki T, et al. Influence of chronic angiotensin converting enzyme inhibition on anesthetic induction. Anesthesiology 1994; 81:299-307. 2. Brabant SM, Bertrand M, Eyraud D, Darmon PL, Coriat P. the hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists. Anesth Analg, 1999; 89:1388-1392.

17 Case 3 continued Statins  May prevent vascular events through mechanisms other than cholesterol reduction  Benefit lost with statin discontinuation  Animal models suggest statin discontinuation may promote pro-thrombotic state  Proposed mechanisms for protection include anti-inflammatory properties and clot adherence Durazzo AE, Machado FS, Ikeoka DT et al. Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial. J Vasc Surg 2004; 39:967-975. Lindenauer PK, Pekow P, Wang K, Guiterrez B, Benjamin EM. Lipid-lowering therapy and in-hospital mortality following major noncardiac surgery. JAMA 2004; 291:2092-2099. Poldermans D, Bax JJ, Kertai MD, et al. Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery. Circulation 2003; 107:1848-1851.

18 Perioperative recommendations for common cardiovascular drugs Drug/ Drug CategoryRecommendations ClopidogrelDiscontinue 7-10 days before major surgery (irreversible antiplatelet effect) Nitrates, Digoxin, Clonidine, β- blocker, CCB, Antiarrhythmics Continue up to and including day of surgery, particularly clonidine and β-blockers. Consider IV or transdermal route if PO not option Diuretics, ACEI, ARBHold on morning of surgery, especially if indication is heart failure Niacin, Fibric acid derivatives, Cholestyramine, Colestipol Hold at least 1 day prior to surgery StatinsContinue in perioperative period

19 Case 3 continued Theophylline Other Pulmonary Medications Pulmonary Medications  No data regarding the role of theophylline in the perioperative period  Generally held, beginning the evening prior to surgery, secondary to its potential toxicities and pro-arrhythmic properties  Inhaled agents should be continued throughout the perioperative period, may reduce perioperative pulmonay complications  Leukotriene inhibitors should be given the morning of surgery and resumed when the patient tolerates oral medications Kroenke, K, Lawrence, VA, Theroux, JF, et al. Operative risk in patients with severe obstructive pulmonary disease. Arch Intern Med 1992; 152:967 Lawrence, VA, Cornell, JE, Smetana, GW. Strategies to Reduce Postoperative Pulmonary Complications after noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Intern Med 2006;144:596.

20 Case 4 A 44 year old man is referred for medical clearance for elective total R knee replacement. His medical history is significant for known CAD, with drug eluting stent placed 8 weeks ago.

21 Case 4 continued Medication List  Aspirin 81mg  Plavix 75mg  Atenolol 50mg  Atorvastatin 40mg Recommendations???

22 Case 4 continued ß-blocker and statin discussed already- continue both Question comes from antiplatelt agents Mounting evidence to suggest premature discontinuation of antiplatelet agent leads to increased mortality¹ ² 1. Ferrari, E, Benhamou, M, Cerboni, P, Marcel, B. Coronary syndromes following aspirin withdrawal. A special risk for late stent thrombosis. J Am Coll Cardiol 2005; 45:456. 2. Kaluza, GL, Joseph, J, Lee, JR, et al. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 2000; 35:1288.

23 Case 4 continued Paclitaxel-eluting stent: minimum 6 months of uninterrupted antiplatelet therapy Sirolimus-eluting stent: minimum 3 months uninterrupted antiplatelt therapy Eagle, KA, Guyton, RA, Davidoff, R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 2004; 110:e340.

24 Case 4 continued Additional Factors:  Surgery is prothrombotic state  True incidence of stent thrombosis and post-op MI in patients undergoing noncardiac surgery is unknown  Most surgeons will not operate on patients currently taking antiplatelet therapy  More research underway  Surgery is elective: delay until completed course of antiplatelet  If surgery urgent or nonelective, needs to be managed on case by case basis

25 Case 5 A 72 year old white male presents with a diabetic foot infection which has not healed, despite six weeks of IV antibiotics. His diabetes is managed with both oral medications and insulin. He is scheduled to undergo amputation tomorrow.

26 Case 5 continued Medication List  NPH Insulin 20U in AM, 10U in PM  Lispro 8U with meals  Metformin 1000mg BID  Actos 30mg daily


28 Case 5 continued Insulin  Current consensus supports giving long acting insulin at half normal dosing  For long, complicated procedures, insulin infusion superior to subcutaneous insulin¹  Safety of continuous infusion well established, less variability than “sliding scale” Peters, A, Kerner, W. Perioperative management of the diabetic patient. Exp Clin Endocrinol Diabetes 1995; 103:213. Pezzarossa, A, Taddei, F, Cimicchi, MC, et al. Perioperative management of diabetic subjects. Subcutaneous versus intravenous insulin administration during glucose-potassium infusion. Diabetes Care 1988; 11:52. van den Berghe, G, Wouters, P, Weekers, F, et al. Intensive insulin therapy in the surgical intensive care unit. N Engl J Med 2001; 345:1359.

29 Case 5 continued Oral Medications¹  Metformin: held two days prior to surgery secondary to increased risk of lactic acidosis  Other oral agents: held morning of surgery to prevent hypoglycemia in the post-operative period Jacober, SJ, Sowers, JR. An update on perioperative management of diabetes. Arch Intern Med 1999; 159:2405. In general, patients with type 2 diabetes who need to undergo surgery should be triaged to the first surgical cases of the day so as not to become too hypo- or hyperglycemic

30 Case 6 A 36 year old woman with severe depression is scheduled for a mastectomy for breast cancer.

31 Case 6 continued Medications  Fluoxetine  Olanzapine  lorazepam


33 Case 6 continued SSRIs  May increase need for transfusions during surgery because of effect on platelet aggregation¹  Long washout period (3 weeks) and little effect with reinitiation for weeks could lead to exacerbation in depression, mood disorder  Patients in whom bleeding could be catastrophic (CNS procedures) should have sufficient washout; all others generally recommend continuation of medication Movig, KL, Janssen, MW, de Waal, Malefijt J, et al. Relationship of serotonergic antidepressants and need for blood transfusion in orthopedic surgical patients. Arch Intern Med 2003; 163:2354

34 Case 6 continued Tricyclic Antidepressants  May potentiate proarrhythmic state in perioperative period in presence of volatile anesthetics¹  Abrupt withdrawal leads to insomnia, sweating, nausea, increased salivation, and sweating  General consensus is to continue through perioperative period² 1. Depaulo, JR, Barker, LR. Affective disorders. In: Barker, LR, Burton, JR, Zieve, PD (Eds), Principles of Ambulatory Medicine, Baltimore, Williams and Wilkins, 1995, pp. 166- 166. 2. Kroenke, K, Gooby-Toedt, D, Jackson, JL. Chronic medications in the perioperative period. South Med J 1998; 91:358.

35 Case 6 continued MAOIs  Intraoperative exposure to ephedrine can lead to hypertensive crisis  Perioperative exposure to meperidine or dextromethorphan can lead to serotonin syndrome¹  MAO-safe anesthetic techniques exist for patients requiring emergency surgery²  If psychiatrist feels medication necessary and anesthesiologist comfortable, may be continued  In general, MAOI should be discontinued 2 weeks prior to elective surgery 1. Mason, PJ, Morris, VA, Balcezak, TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore) 2000; 79:201. 2. Stack, CG, Rogers, P, Linter, SP. Monoamine oxidase inhibitors and anaesthesia. A review. Br J Anaesth 1988; 60:222

36 Case 6 continued Benzodiazepines Antipsychotics  Very safe in perioperative period, and abrupt withdrawal may lead to agitation, mood exacerbation, so continued throughout perioperative course  Remote reports of antipsychotic associated arrhythmias, but none reported in perioperative period¹  Continue throughout perioperative period Whitwam, JG, Russell, WJ. The acute cardiovascular changes and adrenergic blockade by droperidol in man. Br J Anaesth 1971; 43:581

37 Case 7 A 75 year old female presents to the office for clearance to undergo a total right hip replacement. She has a history significant for hypertension, osteoporosis, and osteoarthritis.

38 Case 7 continued Medications  Metoprolol  HCTZ  Alendronate  Ginko Baloba  Echinacea How do we manage the herbal products?



41 Case 7 continued Ang-Lee, Moss, and Yuan looked at 8 commonly used herbals in the perioperative setting¹ General consensus is to discontinue herbals prior to surgery because of potential deleterious effects 1. Ang-Lee, MK, Moss, J, Yuan, CS. Herbal medicines and perioperative care. JAMA 2001; 286:208.

42 Case 7 continued Ginko Ginseng Garlic THE THREE ‘G’s Can cause bleeding through inhibition of platelet-activating factor. D/C at least 36 hours prior to surgery Inhibits platelet aggregation (potentially irreversible), increases risk of hypoglycemia, and inhibits warfarin’s anticoagulation activity. D/C 7 days prior to surgery Inhibits platelet aggregation (potentially irreversible), may promote fibrinolysis, and has antihypertensive activity. Should be discontinued at least 7 days prior to surgery

43 Case 7 continued Ephedra (ma huang) Echinacea Kava  Increased risk of heart attack, stroke, and hemodynamic instability  D/C 24 hours prior to surgery  Potential for immune system dysfunction and allergic reactions secondary to its effect on cell-mediated immunity  Limited perioperative data; general consensus is to discontinue 24 hours prior to surgery  Increases sedative effect of anesthetic; D/C 24 hours pre-op  FDA warning about fatal hepatotoxicity

44 Case 7 continued St. John’s Wort Valerian  Many potential drug-drug interactions through induction of cytochrome P-450 enzymes  D/C 5 days prior to surgery  Sedative pharmacologic effect; may increase effect of anesthesia  Ideally tapered weeks prior to surgery, as there is benzodiazepine-like withdrawal  Withdrawal symptoms treated with benzo’s  Perioperative data limited

45 Case 7 continued What about vitamins????  Many surgical patients are likely taking vitamins¹  Multivitamins safe perioperatively  Vitamin E: associated with increased risk of bleeding, D/C 10 days prior to surgery Kaye, AD, Clarke, RC, Sabar, R, et al. Herbal medicines: current trends in anesthesiology practice--a hospital survey. J Clin Anesth 2000; 12:468.

46 Case 8 A 58 year-old female is scheduled to undergo laproscopic cholecystectomy in 2 weeks. She has a history significant for rheumatoid arthritis. Her medications include methotrexate and hydroxychloroquine. Recommendations??

47 Case 8 continued Hydroxychloroquine Methotrexate  Few potential side effects  Can be safely continued in perioperative period if patient taking oral meds  Limited data  No increase in infection rate in patients who continue to take methotrexate¹  Continue in the face of normal renal function Rosandich, PA, Kelley JT, 3rd, Conn, DL. Perioperative management of patients with rheumatoid arthritis in the era of biologic response modifiers. Curr Opin Rheumatol 2004; 16:192.

48 Case 8 continued Sulfasalazine/ Azothiaprine Leflunamide Hold one week prior to surgery, resume after surgery Hold two weeks prior to surgery, resume after surgery

49 Case 8 continued Glucocorticoids  Patients taking 5 to 20 mg/day of prednisone or its equivalent for more than three weeks may or may not have suppression of the HPA axis  In patients whose HPA axis status is uncertain, one can give glucocorticoids perioperatively or, if time permits, test for the responsiveness of the adrenal to ACTH stimulation  HPA axis suppression should be assumed to be present in patients taking prednisone at a dose greater than 20 mg/day for three weeks or more, and in patients with a Cushingoid appearance Salem, M, Tainsh, RE, Bromberg, J, et al. Perioperative glucocorticoid coverage: a reassessment 42 years after the emergence of a problem. Ann Surg 1994; 219:416. Shaw, M, Mandell, BF. Perioperative management of selected problems in patients with rheumatic diseases. Rheum Dis Clin North Am 1999; 25:623.

50 Case 8 continued Glucocorticoids continued  For minor procedures or surgery under local anesthesia (eg, inguinal hernia repair) take usual morning steroid dose. No extra supplementation is necessary  For moderate surgical stress (eg, lower extremity revascularization, total joint replacement) take usual morning steroid dose. Give 50 mg hydrocortisone intravenously just before the procedure and 25 mg of hydrocortisone every 8 hours for 24 hours. Resume usual dose thereafter  For major surgical stress (eg, esophagogastrectomy, total proctocolectomy) take usual am steroid dose. Give 100mg of intravenous hydrocortisone before induction of anesthesia, and 50mg every 8 hours for 24 hours. Taper dose by half per day to maintenance level


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