Transcript Management of Medications in the Perioperative Period: An

Management of Medications in
the Perioperative Period:
An Evidence Based Approach
Eric J Milie, D.O.
Medical Consultant
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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
Medical Consultant continued
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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
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.
When to Discontinue Aspirin
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Irreversible inhibitor of of platelet cyclooxygenase
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
Case 1 continued
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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.
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).
Case 2 continued
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Acetaminophen
relatively safe
Little bleeding risk
Can be continued safely in patients
undergoing surgery
Case 2 continued
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NSAID usage
Reversible inhibitors of platelet cyclooxygenase
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.
Case 2 continued
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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 postop
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.
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
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.
Case 3: Med List
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Digoxin 0.125 mg
Atenolol 50 mg
Atorvastatin 40 mg
Amiodarone 100 mg
Furosemide 40 mg
Clopidogrel 75 mg
Lisinopril 10 mg
“Inhalers”
Case 3 continued
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Clopidogrel
Irreversible platelet inhibitor
Discontinue 7-10 days prior to major surgery
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Nitrates, Digoxin, Clonidine, Beta
Blockers, Calcium Channel Blockers,
and Antiarrhythmic drugs
Essentially safe to continue perioperatively
For patients who cannot take PO and therapy cannot be
interrupted, consider transdermal or intravenous routes of
administration
Case 3 continued
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Diuretics, ACE Inhibitors, ARBS
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
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Non-statin cholesterol medications
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.
Case 3 continued
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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 antiinflammatory 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.
Perioperative recommendations for
common cardiovascular drugs
Drug/ Drug Category
Recommendations
Clopidogrel
Discontinue 7-10 days before major
surgery (irreversible antiplatelet
effect)
Nitrates, Digoxin, Clonidine, βblocker, 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, ARB
Hold on morning of surgery,
especially if indication is heart
failure
Niacin, Fibric acid derivatives,
Cholestyramine, Colestipol
Hold at least 1 day prior to surgery
Statins
Continue in perioperative period
Case 3 continued
Pulmonary Medications
 Theophylline
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
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Other Pulmonary Medications
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.
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.
Case 4 continued
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Medication List
Aspirin 81mg
Plavix 75mg
Atenolol 50mg
Atorvastatin 40mg
Recommendations???
Case 4 continued
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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.
Case 4 continued
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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.
Case 4 continued
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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
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.
Case 5 continued
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Medication List
NPH Insulin 20U in AM, 10U in PM
Lispro 8U with meals
Metformin 1000mg BID
Actos 30mg daily
Case 5 continued
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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.
Case 5 continued
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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
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
Jacober, SJ, Sowers, JR. An update on perioperative management of diabetes. Arch Intern Med 1999;
159:2405.
Case 6
A 36 year old woman with severe
depression is scheduled for a
mastectomy for breast cancer.
Case 6 continued
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Medications
Fluoxetine
Olanzapine
lorazepam
Case 6 continued
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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
Case 6 continued
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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. 166166.
2. Kroenke, K, Gooby-Toedt, D, Jackson, JL. Chronic medications in the perioperative
period. South Med J 1998; 91:358.
Case 6 continued
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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
Case 6 continued
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Benzodiazepines
Very safe in perioperative period, and abrupt withdrawal may
lead to agitation, mood exacerbation, so continued throughout
perioperative course
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Antipsychotics
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
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.
Case 7 continued
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Medications
Metoprolol
HCTZ
Alendronate
Ginko Baloba
Echinacea
How do we manage the herbal products?
Case 7 continued
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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.
Case 7 continued
THE THREE ‘G’s
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Ginko
Can cause bleeding through inhibition of platelet-activating
factor. D/C at least 36 hours prior to surgery
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Ginseng
Inhibits platelet aggregation (potentially irreversible), increases
risk of hypoglycemia, and inhibits warfarin’s anticoagulation
activity. D/C 7 days prior to surgery
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Garlic
Inhibits platelet aggregation (potentially irreversible), may
promote fibrinolysis, and has antihypertensive activity. Should
be discontinued at least 7 days prior to surgery
Case 7 continued
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Ephedra (ma huang)
Increased risk of heart attack, stroke, and hemodynamic
instability
D/C 24 hours prior to surgery
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Echinacea
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
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Kava
Increases sedative effect of anesthetic; D/C 24 hours pre-op
FDA warning about fatal hepatotoxicity
Case 7 continued
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St. John’s Wort
Many potential drug-drug interactions through induction of
cytochrome P-450 enzymes
D/C 5 days prior to surgery
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Valerian
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
Case 7 continued
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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.
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??
Case 8 continued
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Hydroxychloroquine
Few potential side effects
Can be safely continued in perioperative period if patient taking oral
meds
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Methotrexate
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.
Case 8 continued
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Sulfasalazine/ Azothiaprine
Hold one week prior to surgery, resume after surgery
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Leflunamide
Hold two weeks prior to surgery, resume after surgery
Case 8 continued
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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.
Case 8 continued
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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