Preoperative medication management

Preoperative medication managment

1. Pre-operative medication management

2. At least 50 percent of patients undergoing surgery take medications on a regular basis . Clinicians often must decide if chronic medications should be continued in the peri -operative period.

3. Outline Principles of medication management. Cardiovascular medications, GI agents, pulmonary agents, Endocrine agents. Preo-perative managements of patients receiving anticoagulants.

4. PRINCIPLES OF MEDICATION MANAGEMENT A complete medication history should be obtained, and all clinicians involved in patient management ( eg , surgeon, anesthesiologist, medical consultants ) . Medications associated with known medical morbidity if withdrawn abruptly should be continued in the peri -operative period or tapered if feasible. Medications thought to increase the risk of anesthetic or surgical complications and not essential for the short-term should be held through the perioperative period.

5. Preoperative medication Benefit/Risk Continue/discontinue. Formulations/alternatives

6. CARDIOVASCULAR MEDICATIONS

7. Beta blockers Benefit/risk  – Beta blockers have a number of potential beneficial effects when taken perioperatively . Beta blockers reduce : ischemia by decreasing myocardial oxygen demand due to increased catecholamine release. They may also help prevent or control arrhythmias. Patients who take beta blockers chronically for management of angina are at risk of ischemia with withdrawal of beta blockade. Acute withdrawal of a beta blocker pre- or postoperatively can lead to substantial morbidity and even mortality . Withdrawal issues are of less concern when beta blockers are used for hypertension or migraine prophylaxis . Potential adverse effects of perioperative beta blockade include bradycardia and hypotension. Nonselective beta blockers can interact with epinephrine, used for infiltration anesthesia or management of intraoperative anaphylaxis

8. Beta blockers Continue/discontinue   -we recommend that BBx to be continued in the perioperative period and continued throughout the hospital stay. The dose of the beta blocker should be closely regulated throughout the perioperative period to maintain the blood pressure and heart rate (rate-pressure product) below the patient's ischemic threshold. Formulations/alternatives  – Intravenous forms of beta blockade, such as  metoprolol ,   propranolol , and  labetalol , should be given if the patient cannot take oral medications .  Esmolol  is also available to be used intraoperatively or in an intensive care unit (ICU) but cannot be administered on a regular hospital floor. We have a slight preference for beta 1 cardioselective beta blockers , since they are less likely to cause adverse pulmonary and peripheral vascular effects and may be associated with a lower risk of postoperative stroke.

9. Calcium channel blockers Benefit/risk  – A meta-analysis found that use of calcium channel blockers was associated with reduced ischemia and atrial arrhythmia in patients undergoing non-cardiac surgery . There are no serious interactions between calcium channel blockers and anesthetic agents . A withdrawal syndrome is not typical, although abrupt discontinuation of these drugs has been reported to cause severe vasospasm in patients undergoing coronary revascularization.

10. Continue/discontinue  – we recommend that calcium channel blockers be continued in patients who are already taking them preoperatively . Formulations/alternatives  – Intravenous  diltiazem  is available for patients who are unable to tolerate oral agents. Short-acting calcium channel blockers are available ( diltiazem ,  verapamil ) and can be substituted with appropriate dosing interval adjustments. Short-acting  nifedipine  should be avoided, because it can cause rapid decreases in blood pressure.  Amlodipine  has a long washout period, and short-acting substitutes may not be necessary.

11. ACE inhibitors and angiotensin II receptor blockers Benefit/risk  – The management of patients taking (ACE) /(ARBs) preoperatively is controversial . ACE inhibitors and ARBs can theoretically blunt the compensatory activation of the renin-angiotensin system during surgery and result in prolonged hypotension. most studies indicating some increased risk for peri - and postoperative hypotensive episodes but variable adverse effect on cardiovascular outcomes or respiratory outcomes when the medications are continued.

12. Representative studies of outcomes involving noncardiac surgery include the following : patients on ACE inhibitors undergoing noncardiac (mainly orthopedic and spine) surgery, those who omitted their last preoperative ACE inhibitor dose were compared with those who continued the medication uninterrupted . Intraoperative and postoperative hypotension occurred less frequently in the group who omitted the last dose, but postoperative hypertensive events were more frequent. withholding the ACE inhibitor/ARB 24 hours before noncardiac surgery was associated with a reduction in composite 30-day all-cause death, stroke, or myocardial injury and intraoperative hypotension. Withholding perioperative ACE inhibitor/ARB was not associated with risk of myocardial infarction or postoperative hypotension. In an observational study of over 12,000 patients on chronic diuretic therapy undergoing noncardiac surgery, ACE inhibitor/ARB treatment was associated with more frequent episodes of hypotension . However, there were no differences in the rates of postoperative myocardial infarction or renal failure between the two groups. In a propensity match study of 18,000 patients undergoing noncardiac surgery, no association was found between continued use of ACE inhibitors and intraoperative or postoperative upper-airway complications . Furthermore, uninterrupted perioperative ACE inhibitor use was not associated with in-hospital complications or increased 30-day mortality.

13. Additional studies have evaluated the effect of ACE inhibitor therapy in patients undergoing coronary artery bypass graft (CABG) surgery: •A trial randomly assigned 40 patients with good left ventricular function who were undergoing CABG surgery to continue or omit ACE inhibitors before surgery . Patients who omitted their ACE inhibitors required less vasopressors during surgery but required more vasodilators to control hypertension in the early postoperative period. •A randomized trial of 47 patients on  ramipril  undergoing CABG on cardiopulmonary bypass (CPB) found that ACE inhibitor therapy predisposed to hypotension upon induction and in the post-CPB period, but prophylactic low-dose  vasopressin  infusion prevented post-CPB hypotension . •Nonrandomized studies suggest a possible myocardial protective effect of ACE inhibitors in patients undergoing CABG surgery . •Reports conflict on the effect of ACE inhibitors on the risk of acute kidney injury (AKI) .

14. Continue/discontinue: patients, we usually withhold them on the morning of surgery. However, when the indication is for heart failure or poorly controlled hypertension, we continue them to avoid further exacerbation of these conditions. Many anesthesiologists may prefer to withhold these medications on the morning of surgery based on concerns about possible hypotension, and in such cases when we favor continuation, we inform the anesthesiologist of our justification. We recommend resuming these agents as soon as possible postoperatively, as failure to restart ARBs within 48 hours after surgery has been associated with increased 30-day mortality Formulations/alternatives  –  Enalapril  is available for short-term intermittent intravenous administration, although it is used infrequently.

15. Diuretics ● Benefit/risk  – The two major physiologic effects of concern of loop and thiazide -type diuretics: Hypokalemia can theoretically increase the risk of perioperative arrhythmia, although observational studies of patients with structural heart disease have failed to find such a relationship . Additionally, hypokalemia might potentiate the effects of muscle relaxants used during anesthesia, as well as provoke paralytic ileus. Systemic vasodilatation induced by anesthetic agents may cause hypotension in patients who are intravascularly depleted from diuretics. However, in a study of elective, noncardiac surgeries in patients chronically treated with  furosemide , the administration of furosemide on the day of surgery did not significantly increase the risk for intraoperative hypotension

16. Continue/discontinue   We advise patients who are taking diuretics for hypertension to hold the medication on the morning of surgery. For patients receiving diuretic therapy to treat heart failure, diuretic continuation is based upon assessment of volume status If diuretics are held the morning of surgery and volume overload develops, a quick diuresis can be initiated by intravenous administration perioperatively . For patients who require perioperative diuretics, clinicians should pay close attention to potassium replacement. ● Formulations/alternatives  – Intravenous preparations of loop diuretics are available.

17. Digoxin ● Benefit/risk  – Studies on  digoxin  in the perioperative period are limited. A subgroup analysis of patients undergoing intrathoracic surgery found that digoxin decreased the incidence of postoperative supraventricular arrhythmias . ● Continue/discontinue  – We recommend continuing  digoxin   perioperatively . Obtaining a drug level preoperatively is not usually required. ● Formulations/alternatives  – Intravenous  digoxin  is available if needed. Statins  — Evidence has become convincing that HMG CoA reductase inhibitors (statins) may prevent vascular events in the perioperative period. We recommend continuing statins throughout the perioperative period.

18. GASTROINTESTINAL AGENTS

19. H2 blockers and proton pump inhibitors Benefit/risk  – stress-related mucosal damage, may be minimized by administration of these drugs. Both H2 blockers and proton pump inhibitors decrease gastric volume and raise gastric fluid pH, thereby reducing the risk of chemical pneumonitis from aspiration Rare central nervous system (CNS) reactions including confusion and delirium are associated with the use of intravenous H2 blockers in critically ill postoperative patients . Patient risk factors for CNS reactions include advanced age, organ dysfunction, and preexisting cognitive impairment. It is uncertain whether any H2 blocker is less likely to cause CNS effects than others. An increased risk of  Clostridioides difficile  infection has been associated with proton pump inhibitor use. Continue/discontinue  – Based upon the potential benefits and lack of contraindications, we recommend that patients who are taking either H2 blockers or proton pump inhibitors remain on these medications in the perioperative period. Formulations/alternatives  – Patients who are unable to take oral medications for a prolonged period should be switched to an intravenous form of H2 blocker or proton pump inhibitor . Intravenous H2 blockers are less costly.

20. PULMONARY AGENTS

21. Inhaled beta agonists and anticholinergics Benefit/risk  –They have been found to reduce the incidence of postoperative pulmonary complications in patients with asthma and chronic obstructive pulmonary disease and should be continued preoperatively. Continue/discontinue  – We recommend continuing beta agonists in the perioperative period, including the day of surgery. Formulations/alternatives  – Inhaled beta agonists and anticholinergics are normally administered on the morning of surgery. The drugs can be administered through a nebulizer or in the circuit of the ventilator when use of metered-dose inhalers is not possible. Theophylline ● Benefit/risk  – There are no data indicating whether continuation of theophylline in the perioperative period decreases pulmonary complications. Theophylline has the potential to cause serious arrhythmias and neurotoxicity at a level just beyond the therapeutic range, and theophylline metabolism is affected by many common perioperative medications. ● Continue/discontinue  – We recommend theophylline medications be discontinued the evening before surgery. ● Formulations/alternatives  – Other medications for treatment of obstructive lung disease can be initiated or adjusted, including inhaled beta agonists, glucocorticoids, and anticholinergic medications.

22. Glucocorticoids Benefit/risk  – Patients with pulmonary disease who are maintained on glucocorticoids (corticosteroids) are at risk of adrenal insufficiency if steroids are abruptly withdrawn, particularly in the face of increased stress related to surgery. Additionally, glucocorticoids in such patients may be necessary to maintain optimal lung functions. The risk of possible perioperative complications related to glucocorticoids, including wound infections, is low . Continue/discontinue  – Both inhaled and systemic glucocorticoids should be continued during the perioperative period.

23. Stress dose: Nonsuppressed HPA axis  —  Prednisone  doses of less than 5 mg/day given in the morning do not suppress the hypothalamic-pituitary-adrenal (HPA) axis. The equivalent morning doses of other glucocorticoids ( eg , 4 mg/day of  methylprednisolone , 0.5 mg/day of  dexamethasone , or 20 mg/day of  hydrocortisone ) will have a similar effect. We suggest that the following groups of patients do not need additional perioperative glucocorticoid coverage, because they are  not  considered to have suppression of their HPA axis: Any patient who has been taking any dose of glucocorticoid for less than three weeks . Patients who have received  morning  doses of  less  than 5 mg/day of  prednisone  or its equivalent for any length of time. Patients being treated with  less  than 10 mg of  prednisone  or its equivalent every other day.

24. Suppressed HPA axis patients: Any patient who is currently taking more than 20 mg/day of  prednisone  or its equivalent ( eg , 16 mg/day of  methylprednisolone , 2 mg/day of  dexamethasone , or 80 mg/day of  hydrocortisone ) for more than three weeks . Any patient on glucocorticoids who has clinical Cushing's syndrome

25. ENDOCRINE AGENTS

26. Diabetic medications  : The goals of perioperative diabetic management include: avoidance of hypoglycemia prevention of ketoacidosis maintenance of fluid and electrolyte balance avoidance of marked hyperglycemia. During surgical procedures and in the postoperative phase, we aim to keep the glucose readings between 110 and 180 mg/ dL . Ideally, all patients with diabetes mellitus should have their surgery prior to 9 AM to minimize the disruption of their management routine while being nil per os (NPO).

27. Sodium-glucose co-transporter 2 (SGLT2) inhibitors   Should be stopped three to four days before surgery . These agents i ncrease the risk of urinary tract infections and hypovolemia . There have also been reports of acute kidney injury and euglycemic diabetic ketoacidosis . Euglycemic diabetic ketoacidosis may be under-recognized in the postoperative period, given its atypical presentation, and closer monitoring of ketones is required.

28. Other oral hypoglycemic and/or noninsulin injectable drugs should be withheld starting on the morning of scheduled surgery for the reasons stated below: Metformin  is contraindicated in conditions that increase the risk of renal hypoperfusion , lactate accumulation, and tissue hypoxia. Sulfonylureas and meglitinides can cause hypoglycemia. Thiazolidinediones may worsen fluid retention and peripheral edema and could precipitate congestive heart failure . Dipeptidyl peptidase 4 (DPP-4) inhibitors and GLP-1 receptor agonists could alter gastrointestinal motility . Since DPP-4 inhibitors are generally considered not to increase the risk of hypoglycemia, some experts continue DPP-4 inhibitors on the day of surgery 

29. Basal insulin only : Patients with type 2 diabetes who take only once-daily basal insulin ( eg , NPH, glargine, detemir , degludec ) may continue basal insulin without any change to their usual regimen, as long as the basal insulin dose has been adjusted appropriately as an outpatient and results in safe morning glucose levels **Patient on Twice-daily dosing basal insulin may also be able to continue their usual regimen, as long as the basal dose has been correctly calculated. Basal and prandial insulin : Omit any prandial insulin (regular, lispro , aspart , glulisine ) after fasting begins, typically on the morning of surgery. •If basal insulin ( eg , NPH, glargine, detemir , degludec ) is given once daily in the morning, advise the patient to give between one-half to two-thirds of their usual  total   morning insulin dose  (prandial plus basal insulin)  as basal insulin  to prevent ketosis during the procedure. Pre-mixed insulin  –the dose on the evening prior to surgery should be reduced by approximately 20 percent and the dose on the morning of surgery by 50 percent . However, if the morning blood glucose is <120 mg/ dL , the morning dose should be held.

30. Drugs used for thyroid disease: Continue/discontinue  : We recommend perioperative continuation of therapy for both hyperthyroidism and hypothyroidism.In the case that a patient cannot take oral medications for several days, the approach depends upon the thyroid medication: Thyroxine (T4) has a long half-life , and patients on chronic T4 therapy who are unable to take oral medication for several days do not need parenteral T4. If oral T4 cannot be resumed within five to seven days, it should then be administered parenterally (intravenously or intramuscularly). The antithyroid thionamide medications ( methimazole and  propylthiouracil ) have a very short half-life. The decision on how long to hold antithyroid medications for a patient who is unable to take oral medications must be individualized based upon several factors, including the patient's history of thyroid disease and length of previous treatment with antithyroid medications.

31. MEDICATIONS AFFECTING HEMOSTASIS

32. Name or class of drug Clinical considerations Recommended strategy for surgery with brief NPO state Recommended strategy for surgery with prolonged NPO state Aspirin Continuation may cause perioperative hemorrhage. Discontinuation may increase the risk of vascular complications. Discontinue aspirin ~  7 days prior to noncardiovascular surgery. Resume with oral intake. P2Y12 receptor blockers ( clopidogrel , prasugrel , ticlopidine , ticagrelor ) When used after cardiac stenting procedure, if discontinued can cause cardiac ischemia perioperatively. If continued can result in bleeding complications. Ideally, elective procedures should be delayed until the mandatory period of platelet inhibition with these agents is completed. When used for long-term stroke prophylaxis, should be discontinued 7 to 10 days. If discontinuing, stop clopidogrel and ticagrelor at least  5 days , prasugrel   7 days , and ticlopidine 10 days before surgery. When restarting clopidogrel , consider using a loading dose. Resume with oral intake. Pentoxifylline If being prescribed for alcoholic hepatitis, consult with prescribing hepatologist. Take last dose the morning of surgery . However, there is generally no need to cancel/postpone surgery even if medication is continued due to low bleeding risk. Resume with oral intake. Perioperative Antiplatelets

33. Perioperative management of patients receiving anticoagulants

34. Interruption of anticoagulation temporarily increases thromboembolic risk , and continuing anticoagulation increases the risk of bleeding associated with invasive procedures; both of these outcomes can increase mortality rates . Perioperative management of anticoagulation takes into account and balances these risks

35. Estimate thromboembolic risk. Estimate bleeding risk. Determine the timing of anticoagulant interruption. Determine whether to use bridging anticoagulation. Example cases.

36. Thromboembolic Risk Indication for anticoagulant therapy Mechanical heart valve Atrial fibrillation VTE High thrombotic risk* Any mitral valve prosthesis Any caged-ball or tilting disc aortic valve prosthesis Recent (within 6 months) stroke or transient ischemic attack CHADS 2  score 5-6 CHA 2 DS 2 -VASc score 7-9 Recent (within 3 months) stroke or transient ischemic attack Rheumatic valvular heart disease Recent (within 3 months) VTE Severe thrombophilia ( eg , deficiency of protein C, protein S, or antithrombin; antiphospholipid antibodies; multiple abnormalities) Moderate thrombotic risk Bileaflet aortic valve prosthesis and 1 or more of the of following risk factors: atrial fibrillation, prior stroke or transient ischemic attack, hypertension, diabetes, congestive heart failure, age >75 years CHADS 2  score 3-4 CHA 2 DS 2 -VASc score 4-6 VTE within the past 3 to 12 months Nonsevere thrombophilia ( eg , heterozygous factor V Leiden or prothrombin gene mutation) Recurrent VTE Active cancer (treated within 6 months or palliative) Low thrombotic risk Bileaflet aortic valve prosthesis without atrial fibrillation and no other risk factors for stroke CHADS 2  score 0-2 CHA 2 DS 2 -VASc score 0-3 (assuming no prior stroke or transient ischemic attack) VTE >12 months previous and no other risk factors * Very high-risk patients include those with a prior stroke or TIA occurring >3 months before the planned surgery and a CHADS 2  score <5 or   CHA 2 DS 2 -VASc score <6 (those with prior thromboembolism during temporary interruption of anticoagulation, or those undergoing certain types of surgery associated with an increased risk for stroke or other thromboembolism [ eg , cardiac valve replacement, carotid endarterectomy, major vascular surgery]).

37. ESTIMATING PROCEDURAL BLEEDING RISK The risk of bleeding is dominated by the type of surgery or procedure . Comorbidities ( eg , older age, reduced kidney function) and medications that affect hemostasis. Major bleeding is generally defined as bleeding that is fatal , involves a critical anatomic site ( eg , intracranial, pericardial), requires surgery to correct , lowers the hemoglobin by ≥2 g/dL , or requires transfusion of ≥2 units PRBCs

38. High bleeding risk procedure  (two-day risk of major bleed 2 to 4%) Any major operation of duration >45 minutes Abdominal aortic aneurysm repair Coronary artery bypass Endoscopically guided fine-needle aspiration Foot/hand/shoulder surgery Heart valve replacement Hip replacement Kidney biopsy Knee replacement Laminectomy Neurosurgical/urologic/head and neck/abdominal/breast cancer surgery Polypectomy, variceal treatment, biliary sphincterectomy , pneumatic dilatation Transurethral prostate resection Vascular and general surgery Low bleeding risk procedure (two-day risk of major bleed 0 to 2%) Abdominal hernia repair Abdominal hysterectomy Arthroscopic surgery lasting <45 minutes Axillary node dissection Bronchoscopy with or without biopsy Carpal tunnel repair Cataract and noncataract eye surgery Central venous catheter removal Cholecystectomy Cutaneous and bladder/prostate/thyroid/breast/lymph node biopsies Dilatation and curettage Gastrointestinal endoscopy ± biopsy, enteroscopy , biliary/pancreatic stent without sphincterotomy, endosonography without fine-needle aspiration Hemorrhoidal surgery Hydrocele repair Noncoronary angiography Pacemaker and cardiac defibrillator insertion and electrophysiologic testing Thoracentesis Tooth extractions Bleeding Risk

39. DECIDING WHETHER TO INTERRUPT ANTICOAGULATION In general, the anticoagulant must be discontinued if the surgical bleeding risk is high . Those at very high or high thromboembolic risk should limit the period without anticoagulation to the shortest possible interval; in some cases, this involves the use of a bridging agent.

40. Settings requiring anticoagulant interruption   If the very high risk of thromboembolism is  transient  ( eg , ischemic stroke within the previous 3 months ), attempts should be made to delay elective surgery , if possible, until the thromboembolic risk has returned to baseline. Individuals with a temporarily very high or high thromboembolic risk in whom surgery cannot be delayed ( eg , potentially curative cancer surgery in a patient who just had an acute VTE) should limit the interval without an anticoagulant to minimize the risk of VTE recurrence.   This generally involves stopping the usual anticoagulant as close to surgery as possible, restarting it as soon as possible , and, for those on  Warfarin , using a bridging agent before and/or after surgery while the usual anticoagulant is not therapeutic. For individuals with a chronically elevated thromboembolic risk who are receiving  warfarin  Often use bridging anticoagulation to minimize the period when anticoagulation is not being used.

41. Discontinuation : Typically omit warfarin for 5 days before elective surgery ( ie , the last dose of warfarin is given on day minus 6) and, when possible, check the PT/INR on the day before surgery. If the INR is >1.5 , Administer a  low  dose of oral vitamin K ( eg , 1 to 2 mg) to hasten normalization of the PT/INR and recheck the INR the following day . Proceed with surgery when the INR is ≤1.4. An INR in the normal range is especially important in patients undergoing surgery associated with a high bleeding risk ( eg , intracranial, spinal, urologic) or if neuraxial anesthesia is to be used. Warfarin Interruption.

42. Therapeutic dosing   – Therapeutic dosing (also called "full dose") is appropriate for bridging anticoagulation for individuals with a potential arterial thromboembolic source ( eg , AF, mechanical heart valve ) or VTE within the preceding month . Typical regimens include  Enoxaparin , 1 mg/kg subcutaneously twice daily or  Dalteparin , 100 units/kg subcutaneously twice daily. Intermediate dosing  – Intermediate-dose anticoagulation may be appropriate for individuals with atrial fibrillation or VTE within the preceding month when bridging is needed but concerns about bleeding are greater. Typical regimens include  Enoxaparin , 40 mg twice daily , or  Dalteparin , 5000 units subcutaneously twice daily.

43. DOAC Interruptions Low/moderate bleed risk   – Omit the DOAC one day before and resume one day after the procedure, provided hemostasis is secure. The total duration of interruption is two days . High bleed risk   – Omit the DOAC two days before and resume two days after the procedure, provided hemostasis is secure. The total duration of interruption is four days . Waiting an additional one day before resumption may be appropriate in some cases. Impaired kidney function   – For individuals with impaired kidney function ( CrCl <30 to 50 mL/min) who are taking  dabigatran , there is an additional one day interruption before low/moderate bleeding risk procedures and an additional two days interruption before high bleeding risk procedures . Direct factor Xa inhibitors ( Apixaban ,   Edoxaban ,  Rivaroxaban ) do not require adjustments for kidney function.

44. Temporary IVC filters Indicated in patients with a very recent (within the prior three to four weeks ) acute VTE who require interruption of anticoagulation for a surgery or major procedure in which it is anticipated that therapeutic-dose anticoagulation will need to be delayed for more than 12 hours postoperatively

45. Settings in which continuing the anticoagulant may be preferable

46. Timing for interruption of a DOAC before and after elective surgery This strategy applies to all DOACs in individuals with normal kidney function ( eg , CrCl >50 mL/min ) and individuals taking Apixaban, Edoxaban , or Rivaroxaban with CrCl 30 to 50 mL/min . For individuals taking Dabigatran who have CrCl of 30 to 50 mL/min , omit an additional dose before the procedure. For any DOAC and a high bleeding risk procedure , it may be reasonable to omit the DOAC for an additional postoperative day (5 days total interruption).

47. Anticoagulant Renal function and dose Interval between last dose and procedure NOTE: No anticoagulant is administered the day of the procedure Resumption after procedure High bleeding risk Low bleeding risk High bleeding risk Low bleeding risk Dabigatran CrCl >50 mL/minute Dose 150 mg twice daily Give last dose three days before procedure ( ie , skip four doses on the two days before the procedure) Give last dose two days before procedure ( ie , skip two doses on the day before the procedure) Resume 48 to 72 hours after surgery ( ie , postoperative day 2 to 3) Resume 24 hours after surgery ( ie , postoperative day 1) CrCl 30 to 50 mL/minute Dose 150 mg twice daily Give last dose five days before procedure ( ie , skip eight doses on the four days before the procedure) Give last dose three days before procedure ( ie , skip four doses on the two days before the procedure) Rivaroxaban CrCl >50 mL/minute Dose 20 mg once daily Give last dose three days before procedure ( ie , skip two doses on the two days before the procedure) Give last dose two days before procedure ( ie , skip one dose on the day before the procedure) CrCl 30 to 50 mL/minute Dose 15 mg once daily Apixaban CrCl >50 mL/minute Dose 5 mg twice daily Give last dose three days before procedure ( ie , skip four doses on the two days before the procedure) Give last dose two days before procedure ( ie , skip two doses on the day before the procedure) CrCl ≤50 mL/minute Dose 2.5 mg twice daily Edoxaban CrCl 51 to 95 mL/minute Dose 60 mg once daily Give the last dose three days before the procedure ( ie , skip two doses on the two days before the procedure) Give the last dose two days before the procedure ( ie , skip one dose on the day before the procedure) CrCl ≤50 mL/minute* Dose 30 mg once daily Perioperative management of oral direct thrombin inhibitors and factor Xa inhibitors

48. BRIDGING ANTICOAGULATION Bridging may be appropriate during  Warfarin  discontinuation in the following individuals: Mechanical mitral valve; mechanical aortic valve with additional stroke risk factors. Embolic stroke within the previous three months or very high stroke risk ( eg , CHADS 2  score of 5 or 6). VTE within the previous 3 months. Possibly in selected individuals with recent coronary stenting. Previous thromboembolism during interruption of chronic anticoagulation.

49. A 76-year-old female with nonvalvular AF , HTN, and prior stroke three months ago, receiving  warfarin , requires elective hip replacement with neuraxial anesthesia; kidney function is normal, .and weight is 75 kg  This patient has a very high thromboembolic risk , and a high bleeding risk . Omit  warfarin  for five days before the procedure (last dose on preoperative day minus 6). Preoperative bridging with therapeutic-dose low molecular weight (LMW) heparin ( eg ,  dalteparin , 100 units/kg [7500 units] subcutaneously twice daily) starting on preoperative day minus 3, with last dose on the morning of day minus 1. Resume  warfarin  within 24 hours after surgery (usual dose). Postoperative low-dose LMW heparin for venous thromboembolism (VTE) prevention ( eg ,  dalteparin , 5000 units subcutaneously once daily) within 24 hours after surgery until postoperative bridging is started. Postoperative bridging on postoperative day 2 or 3, when hemostasis is secured ( eg ,  dalteparin , 100 units/kg [7500 units] subcutaneously twice daily); continue for at least four to five days, until the international normalized ratio (INR) is therapeutic.

50. A 70-year-old male with nonvalvular atrial fibrillation, diabetes, and hypertension (CHA 2 DS 2 -VASc score = 3) receiving  dabigatran  who requires a colon resection for cancer; kidney function is normal.  This patient has a moderate thrombotic risk and a high bleeding risk . Omit  dabigatran  for two days before the procedure (last dose of dabigatran on day minus 3). No bridging. Resume  dabigatran  on postoperative day 2 or 3, when patient is able to take medication by mouth. Use prophylactic-dose LMW heparin for VTE prophylaxis for the first two to three postoperative days.

51. A 55-year-old male with an unprovoked DVT four months ago, receiving  apixaban  5 mg twice daily, who requires a colonoscopy because of a personal history of premalignant colorectal polyps; kidney function is normal.  This patient has a high thrombotic risk and a low bleeding risk . Omit  apixaban  for one day before the procedure (last dose of apixaban on day minus 2). No bridging. Resume  apixaban  the day after the procedure, after at least 24 hours have elapsed and when hemostasis is secured. If the patient requires polyp removal, delay resumption of apixaban for one to two more days.

52. A 68-year-old female with nonvalvular atrial fibrillation, hypertension, and congestive heart failure (CHA 2 DS 2 -VASc score = 4), receiving  rivaroxaban  15 mg daily in the morning, requires a dental cleaning and two dental extractions; creatinine clearance ( CrCl ) is 35 mL/min.  This patient has a high thrombotic risk and a low bleeding risk . Omit  rivaroxaban  on the day of the procedure. Use oral  tranexamic acid  mouthwash just before the procedure and two to three times that day after the procedure. Resume  rivaroxaban  the day after the procedure, after at least 24 hours have elapsed (assuming the dental extractions were uneventful).

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