Perioperative Management of Chronic Medications in Noncardiac Surgery

Full update September 2019

The following chart provides information to help with decisions regarding stopping and restarting medications before and after noncardiac surgery. Use clinical judgment and individualize decisions. Consider consulting prescriber to clarify individual’s risk of stopping. Keep in mind there is a lack of high-quality evidence for most recommendations. Also see our chart, Managing Chronic Meds in Patients Undergoing Colonoscopy.

Abbreviations: ACEI = angiotensin-converting-enzyme inhibitor; ARB = angiotensin receptor blocker; DOAC = direct oral anticoagulant; IBD = inflammatory bowel disease; LMWH = low-molecular-weight heparin; TNF = tumor necrosis factor; VTE = venous thromboembolism

Drug Class

Pertinent Information or Resource

ACEI and ARBs

Consider holding these meds up to 24 hours pre-op to limit the risk of hypotension [Evidence level B-1 and B-3].3,4 But keep in mind that the safety of holding these meds in specific groups such as patients with heart failure or uncontrolled hypertension has not been examined.

Restart with oral intake.1 Monitor for postoperative hypertension.3 If the patient cannot take oral meds, consider an appropriate parenteral agent for treatment of hypertension or heart failure.1

Anticoagulants, oral

The decision to hold an anticoagulant before surgery or a procedure has several considerations: bleeding risk of the surgery/procedure thrombosis; risk of holding the anticoagulant; whether the surgery/procedure could be postponed until thrombotic risk is lower; how long before the surgery/procedure the anticoagulant should be stopped (if indicated); whether the anticoagulant needs to be bridged; and when it is likely safe to restart the anticoagulant.

For general guidance on duration of preprocedure washout, if indicated, see our chart, Comparison of Oral Anticoagulants.

  • For specifics on duration of preprocedure DOAC (e.g., apixaban) washout based on procedural bleeding risk, see our chart, Managing Bleeding with Direct Oral Anticoagulants. This chart also contains information to help in situations where a washout isn’t feasible (e.g., emergency surgery), including labs to assess bleeding risk and reversal agents, such as clotting factors.
  • Consider restarting DOACs the day after a minor procedure or two to three days after other procedures.29 If the DOAC isn’t held, consider delaying the dose until four to six hours post-procedure.32 After surgery, consider need for VTE prophylaxis starting six to eight hours post-op, until the DOAC is restarted.30 Before restarting rivaroxaban 15 or 20 mg tablets, ensure patients have good oral intake; these doses must be taken with food for full therapeutic effect.30,31
  • For help classifying surgical bleeding risk and patient thrombotic risk, see our chart, Bridging Warfarin,
  • Thrombosis Canada’s guidance on perioperative management of DOACs also includes examples of high bleeding-risk procedures (https://thrombosiscanada.ca/wp-content/uploads/2019/05/NOACs-DOACs-Perioperative-Management.pdf.)

If regional anesthesia is planned, see our chart, Antithrombotic Management in Regional Anesthesia, for guidance on stopping and restarting anticoagulants around epidurals or spinals.

Bridging may need to be considered for patients in whom warfarin therapy is interrupted. See our chart, Bridging Warfarin, for guidance in specific scenarios, including atrial fibrillation. DOACs generally do not need to be bridged. However, if surgery is postponed, or if there is a delay in restarting the DOAC post-op, bridging may be needed.30 For patients whose DOAC indication is VTE prevention, VTE prophylaxis may be all that is needed.30

Pre-op evaluation can be an opportunity to de-escalate or discontinue unneeded antithrombotic regimens. Our charts, Combination Antithrombotic Therapy: FAQs and Venous Thromboembolism Prophylaxis, might help you identify such patients.

Antidepressants

Generally, continue antidepressants; abruptly stopping them can lead to withdrawal symptoms.1

Consider bleeding risk with SSRI and SNRI antidepressants.

  • If depression is stable and the patient is at high bleeding risk (e.g., elderly, clinically significant liver disease, antiplatelet or anticoagulant use, surgery with high bleeding risk), consider tapering and discontinuing before surgery.1,7 For help, see our chart, Common Oral Medications that May Need Tapering.
  • If depression is unstable, consider switching to an antidepressant with lower bleeding risk (e.g., bupropion, mirtazapine).7 For help, see our chart, Choosing and Switching Antidepressants.

Screen for patients who may get methylene blue, a monoamine oxidase inhibitor, during procedures (e.g., for parathyroid imaging, colon staining) and discontinue SSRIs or SNRIs one to two weeks before surgery (five weeks for fluoxetine).8

Restart with oral intake.1 If patient received methylene blue, antidepressant may be restarted 24 hours after the last dose.15,26 When restarting, if the previous dose was high and the washout was prolonged, it may be prudent to start with a low dose and retitrate.16

Antiplatelets

The decision to hold an antiplatelet before surgery or a procedure has several considerations: bleeding risk of the surgery/procedure; thrombosis risk of holding the antiplatelet; whether the surgery/procedure could be postponed until thrombosis risk is lower; how long before the surgery/procedure the antiplatelet should be stopped (if indicated); whether the antiplatelet needs to be bridged; and when it is likely safe to restart the antiplatelet.

For general guidance on duration of preprocedure washout, if indicated, see our chart, Comparison of Oral Antiplatelets.

If regional anesthesia is planned, see our chart, Antithrombotic Management in Regional Anesthesia, for guidance on stopping and restarting antiplatelets.

Bridging may need to be considered for patients in whom antiplatelet therapy is interrupted. See our chart, Bridging Antiplatelets in Stent Patients.

For help with perioperative decisions in patients with coronary artery disease, see our chart, Dual Antiplatelet Therapy for Coronary Artery Disease.

Our chart, Combination Antithrombotic Therapy: FAQs, might also help inform decisions regarding your patient.

Blood Pressure Meds

Continue beta-blockers, calcium channel blockers, and clonidine.1,2,6

See ACEI and ARBs, above, and Diuretics, below.

Corticosteroids

Try to taper to <10 to 15 mg/day prior to surgery to reduce infection risk [Evidence Level B-3].9,10

Patients taking more than prednisone 5 mg or its equivalent for more than three weeks may need stress doses of hydrocortisone, especially those on doses >20 mg/day.1,5,18,19,28

Diabetes Meds

See our chart, Perioperative Management of Diabetes, for information regarding management of home antidiabetic regimens in preparation for and after surgery or procedures, including oral agents, injectables, subcutaneous insulin, and insulin pumps. Treatment of glucose excursions is also reviewed.

Disease-Modifying Anti-rheumatics (DMARDS), Biologic

Evidence regarding holding these immunocompromising agents (infliximab, adalimumab [Humira], etanercept [Enbrel]) to reduce complications comes from observational studies in joint replacement and IBD.12 There is less evidence for newer biologics.12

In rheumatic disease, hold before hip or knee arthroplasty.14 For other surgeries, individualize decisions.12 For surgeries with low-risk of complications (i.e., endoscopic procedure, dermatologic surgery, breast biopsy, or eye surgery), consider continuing.12,20

Most studies did not find increased infection risk in patients being treated with anti-TNF agents for IBD.12 Individualize decisions.21 Consider patient’s response to treatment and urgency of surgery.28

If the decision is made to hold an injectable biologic, consider scheduling surgery around the time the held dose would have been due, and restarting two to four weeks later, assuming no infection or healing problems.11,28 For tofacitinib (Xeljanz), stop seven days prior to surgery, and consider restarting two weeks post-op, assuming no infection or healing problems.11

Disease-Modifying Anti-rheumatics (DMARDS), Non-Biologic

Experts recommend continuation of hydroxychloroquine and sulfasalazine.11,22

Leflunomide is associated with impaired wound healing, but a washout requires advanced planning.22 See product labeling for instructions on using cholestyramine to hasten elimination.

Level B evidence suggests low-dose methotrexate is usually safe to continue.22

In non-severe lupus patients undergoing hip or knee arthroplasty, hold azathioprine, cyclosporine, tacrolimus, or mycophenolate, but continue these in severe lupus.14 For other surgeries or rheumatic diseases, individualize decisions. For surgeries with low-risk of complications (i.e., endoscopic procedure, dermatologic surgery, breast biopsy, or eye surgery), consider continuing.12,20

Individualize decisions in IBD patients.21 Consider continuing cyclosporine, azathioprine, 6-mercaptopurine, and methotrexate in IBD.12,21,28 Some IBD experts hold on the day of surgery, and resume the next day.28

If the decision is made to hold the non-biologic DMARD, stop one week prior to surgery.14 Restart three to five days post-op, assuming no infection or healing problems.14

Diuretics

Stop diuretics in most patients the day of surgery to minimize the risk of hypokalemia and hypovolemia.1

  • Hypotension is more common in patients taking diuretics with ACEIs/ARBs, even when the ACEI/ARB is held.1

Heart failure patients may need parenteral diuretics.1

Consider restarting the diuretic when oral fluid intake is established.1

Estrogen (replacement therapy or oral contraceptives)

Consider stopping four weeks before surgery, weighing surgery-related VTE risk vs risk of pregnancy or symptoms.23

If not stopped, ensure appropriate VTE prophylaxis.23

Restart when mobility is restored.1

Fibrates

Due to rhabdomyolysis risk, hold beginning the day before surgery, and restart with oral intake.1

H2-Blockers

Continue.24 Give with sip of water on morning of surgery.24

Immunosuppressives (also see DMARDs, above)

Continue immunosuppressives for transplant patients. Consult patient’s transplant center. Some might switch sirolimus or everolimus (stronger immunosuppressives) to tacrolimus or cyclosporine for two to three months before elective surgery, then switch back once the wound has healed.13

Niacin

Due to rhabdomyolysis risk, hold beginning the day before surgery, and restart with oral intake.1

NSAIDs

Stop diclofenac, ibuprofen, indomethacin, or ketoprofen the day before the procedure.17

Stop celecoxib, diflunisal, naproxen, or sulindac two to three days before the procedure.17

Stop meloxicam, nabumetone, or piroxicam ten days before the procedure.17

Osteoporosis Medications

Hold oral bisphosphonates perioperatively due to difficulty administering appropriately.23 (Some institutions hold oral bisphosphonates during all hospital admissions.)

Hold raloxifene beginning three days before surgery (due to VTE risk), and restart once patient is fully ambulatory.25,27

Proton Pump Inhibitors

Continue.24 Give with sip of water on morning of surgery.24

Statins

In patients scheduled for noncardiac surgery, continue a statin if the patient is currently receiving one.2

In patients scheduled for vascular surgery, it is reasonable to start a statin perioperatively.2

Consider starting a statin perioperatively in patients with an indication for one.2 To help identify these patients, see our charts, 2018 ACC/AHA Cholesterol Guidelines (U.S. subscribers) and Canadian Dyslipidemia Recommendations and FAQs.

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level

Definition

Study Quality

A

Good-quality patient-oriented evidence.*

  1. High-quality RCT
  2. SR/Meta-analysis of RCTs with consistent findings
  3. All-or-none study

B

Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study

C

Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

RCT = randomized controlled trial; SR = systematic review [Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. http://www.aafp.org/afp/2004/0201/p548.pdf.]

Project Leader in preparation of this clinical resource (350923): Melanie Cupp, Pharm.D., BCPS

References

  1. Castanheira L, Fresco P, Macedo AF. Guidelines for the management of chronic medication in the perioperative period: systematic review and formal consensus. J Clin Pharm Ther 2011;36:446-67.
  2. Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;130:e278-e333.
  3. Shiffermiller JF, Monson BJ, Vokoun CW, et al. Prospective randomize evaluation of preoperative angiotensin-converting enzyme inhibition (PREOP-ACEI). J Hops Med 2018;13:661-7 [abstract].
  4. Roshanov PS, Rochwerg B, Patel A, et al. Withholding versus continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before noncardiac surgery: an analysis of the vascular events in noncardiac surgery patients cohort evaluation prospective cohort. Anesthesiology 2017;126:16-27.
  5. Hamrahian AH, Roman S, Milan S. The management of the surgical patient taking glucocorticoids. (Last updated March 19, 2019). In UpTo Date, Post TW (ed), UpToDate,Waltham, MA 02013.
  6. Dutta S, Cohn SL, Pfeifer KJ, et al. Updates in perioperative medicine. J Hosp Med 2016;11:231-6.
  7. Narouze S, Benzon HT, Provenzano DA, et al. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications: guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain. Reg Anesth Pain Med 2015;40:182-212.
  8. Top WM, Gillman PK, de Langen CJ, Kooy A. Fatal methylene blue associated serotonin toxicity. Neth J Med 2014;72:179-81.
  9. George MD, Baker JF, Winthrop K, et al. Risk of biologics and glucocorticoids in patients with rheumatoid arthritis undergoing arthroplasty: a cohort study. Ann Intern Med 2019 May 21. doi: 10.7326/M18-2217.
  10. Somaryaji R, Barnabe C, Martin L. Risk factors for infection following total joint arthroplasty in rheumatoid arthritis. Open Rheumatol J 2013;7:119-24.
  11. Goodman SM, Bass AR. Perioperative medical management for patients with RA, SPA, and SLE undergoing total hip and total knee replacement: a narrative review. BMC Rheumatology 2018 Jan 30;2:2. doi: 10.1186/s41927-018-0008-9.
  12. Choi YM, Debbaneh M, Weinberg JM, et al. From the Medical Board of the National Psoriasis Foundation: perioperative management of systemic immunomodulatory agents in patients with psoriasis and psoriatic arthritis. J Am Acad Dermatol 2016;75:798-805.
  13. Lien YH. Top 10 things primary care physicians should know about maintenance immunosuppression for transplant recipients. Am J Med 2016;129:568-72.
  14. Goodman SM, Springer B, Guyatt G, et al. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty. Arthritis Care & Res 2017;69:1111-24.
  15. Locke A. Methylene blue and the risk of serotonin toxicity. APSF (Anesthesia Patient Safety Foundation) newsletter. June 2015. http://apsf.org/newsletters/html/2015/June/02blue.htm. (Accessed August 7, 2019).
  16. Pass SE, Simpson RW. Discontinuation and reinstitution of medications during the perioperative period. Am J Health Syst Pharm 2004;61:899-912.
  17. Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(Suppl 6):299S-339S.
  18. Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. Arch Surg 2008;143:1222-6.
  19. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003;348:727-34.
  20. Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol 2019;80:1029-72.
  21. Nickerson TP, Merchea A. Perioperative considerations in Crohn’s disease and ulcerative colitis. Clin Colon Rectal Surg 2016;29:80-4.
  22. Krause ML, Matteson EL. Perioperative management of the patient with rheumatoid arthritis. World J Orthop 2014;5:283-91.
  23. Muluk V, Cohn SL, Whinney C. Perioperative medication management. (Last updated April 12, 2019). In UpToDate, Post TW (ed), UpToDate, Waltham, MA 02013.
  24. The Froedtert and the Medical College of Wisconsin. Department of Anesthesiology. Preoperative medication management guidelines. Updated March 2014. http://www.froedtert.com/upload/docs/professionals/physicians/preoperative/perioperative-medication-management.pdf. (Accessed August 8, 2019).
  25. Product information for Evista. Lilly USA. Indianapolis, IN 46285. June 2018.
  26. Product information for Prozac. Lilly USA. Indianapolis, IN 46285. March 2017.
  27. Product monograph for Evista. Eli Lilly Canada. Toronto, ON M1N 2E8. October 2018.
  28. Lightner AL. Perioperative management of biologic and immunosuppressive medications in patients with Crohn’s disease. Dis Colon Rectum 2018;61:428-31.
  29. Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med 2019 Aug 5. doi: 10.1001/jamainternmed.2019.2431.
  30. Doherty JU, Gluckman TJ, Hucker WJ, et al. 2017 ACC expert consensus decision pathway for periprocedural management of anticoagulation in patients with nonvalvular atrial fibrillation: a report of the American College of Cardiology Clinical Expert Consensus Document Task Force. J Am Coll Cardiol 2017;69:871-98.
  31. Clinical Resource, Comparison of oral Anticoagulants. Pharmacist’s Letter/Prescriber’s Letter. December 2018.
  32. Thrombosis Canada. NOACS/DOACS: perioperative management. April 30, 2019. https://thrombosiscanada.ca/wp-content/uploads/2019/05/NOACs-DOACs-Perioperative-Management.pdf. (Accessed September 13, 2019).

Cite this document as follows: Clinical Resource, Perioperative Management of Chronic Medications in Noncardiac Surgery. Pharmacist’s Letter/Prescriber’s Letter. September 2019.

Related Articles