PREOPERATIVE EVALUATION

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• Patients are often sent to primary care providers to be "cleared" for surgery. The provider is then tasked with determining what testing is necessary to declare a patient fit for their procedure. This can be a daunting task given that patients often have undiagnosed conditions (e.g. CAD, CHF) that increase their risk of perioperative mortality. Professional guidance does exist, but much of it is fragmented, inconsistent, nonspecific, and based on expert opinion and observational data. The information presented here is derived from sources that provided the most specific recommendations.

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• Overview
• Surgery can place significant stress on the heart, and patients with heart disease are particularly vulnerable. A study that looked at over 10 million hospitalizations for noncardiac surgery (mean age 66 years) in the U.S. found that major cardiovascular and cerebrovascular events occurred in 3% of patients, with vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%) having the greatest risk. Furthermore, elevated troponin levels are seen in up to 20% of patients after noncardiac surgery. The recommendations below can help to identify which patients may be at increased risk. [1,2]

• Reference [2,3,20]

AHA algorithm for preoperative cardiac testing in nonemergent, noncardiac surgery
Patient population This algorithm is for patients undergoing nonemergent, noncardiac surgery who have established CVD, symptoms of CVD, or CVD risk factors, including any of the following: hypertension, smoking, high cholesterol, diabetes, women age ≥ 65 years old; men ≥ 55 years old; obesity; or family history of premature CAD (CAD in a first-degree male relative < 55 years old or female < 65 years old)
Step 1 - If the patient has any of the following, consult cardiology: Symptoms of acute coronary syndrome Symptomatic heart failure New dyspnea, physical examination findings of heart failure, or suspected new/worsening ventricular dysfunction Unstable cardiac arrhythmia Moderate or greater stenosis or regurgitation of any heart valve (order an echocardiogram if the patient has not had one within the past year or if there has been a significant change in clinical status or physical examination since the last evaluation) Severe pulmonary hypertension Elevated-risk congenital heart disease (CHD) defined as single-ventricle patients (palliated or status post Fontan procedure), unrepaired or palliated cyanotic CHD, double outlet right ventricle, pulmonary atresia, truncus arteriosus, transposition of the great arteries (TGA) (classic or d-TGA; CCTGA or l-TGA), or interrupted aortic arch Prior coronary stents or CABG Recent stroke Cardiovascular implantable electronic device (e.g., pacemaker or ICD) Fraility (assessed using validated tools such as the Fried Frailty Phenotype or the Clinical Frailty Scale. See fraility assessment instruments.) If none of the above are present, proceed to Step 2
Step 2 - Estimate the patient's perioperative MACE risk with the ACS NSQIP surgical risk calculator ACS NSQIP surgical risk calculator Test results If the risk of cardiac complications is < 1%, no further testing is required, and the patient can proceed to surgery If the risk of cardiac complications is ≥ 1%, proceed to Step 3
Step 3 - Assess patient's functional status See functional status assessment ECG Consider 12-lead ECG in asymptomatic patients without established CVD. See ECG recommendations. Test results If the patient's functional status is ≥ 4 metabolic equivalents (METs) or their Duke Activity Status Index (DASI) score is > 34, they can proceed to surgery If the patient's functional status is < 4 METs, their DASI score is ≤ 34, or their functional status is unknown, proceed to Step 4
Step 4 - Order biomarkers Order BNP or NT-proBNP Consider ordering troponin Test results If the patient has normal biomarkers, they can proceed to surgery If the patient has abnormal biomarkers, refer them to cardiology

• Procedure risk
• The risk of perioperative cardiovascular events for different types of surgery is provided in the table below

• MACCE defined as in-hospital all-cause death, acute myocardial infarction, or acute ischemic stroke
• Reference [1]

Risk of MACCE with noncardiac surgery
Surgery type	Perioperative MACCE
Vascular	7.7%
Thoracic	6.5%
Transplant	6.3%
Neurosurgery	4.6%
General	3.9%
Skin/burn	3.8%
Otolaryngology	1.8%
Genitourinary	1.6%
Orthopedic	1.6%
Cataract	< 1%
Plastic	< 1%
Endocrine	0.95%
Breast	0.35%
Gynecologic	0.31%
Obstetric	0.12%

• Surgery risk calculators
• Risk calculators have been developed that use patient data and procedure type to estimate the risk of surgery-related MACCE. Algorithms from professional organizations incorporate these estimates into preprocedural decision-making. Two widely used systems are presented below. The Revised Cardiac Risk Index for Pre-Operative Risk is a simple tool that uses 6 variables to estimate the 30-day risk of death, MI, or cardiac arrest. The ACS NSQIP is a more complex tool that uses 21 variables to estimate the risk of 13 surgery-related complications, including cardiac events. When using the AHA decision algorithm, the ACS NSQIP tool is preferred.


• ACS NSQIP surgical risk calculator (online calculator) - uses 21 variables to estimate the risk of a number of surgery-related complications, including cardiac events. One variable used in the tool is the ASA physical status class which is defined here - ASA Physical Status Classification System.


• Revised Cardiac Risk Index for Pre-Operative Risk (online calculator) - uses 6 variables to estimate the 30-day risk of death, MI, or cardiac arrest

• History / Physical exam
• The preoperative medical history and physical exam should focus on detecting signs and symptoms of cardiopulmonary disease
• History
• Exertional chest pain
• Dyspnea
• Orthopnea
• Palpitations
• Recent syncope
• Physical
• HEENT - jugular venous distension in heart failure
• Heart - third heart sound in heart failure, murmurs,
• Lungs - rales in heart failure
• Lower extremities - peripheral edema may be present in heart failure [3]

• Functional status (METs)
• Functional status has been shown to be a reliable predictor of perioperative cardiac events, and it serves as a major decision point in the AHA perioperative algorithm (see algorithm). Functional status is described in terms of metabolic equivalents (METs), a measure of energy expenditure during different activities. One MET is defined as 1 kcal/kg/hour and is roughly equivalent to the energy expended while sitting quietly. Researchers have established MET values for a broad range of activities, and functional status is determined by the MET level of activities a patient can perform. Patients with MET values of less than 4 have a two-fold increased risk of perioperative complications. [2,3]


• Functional status categories:
• Excellent: MET > 10
• Good: MET 7 - 10
• Moderate: MET 4 - 6
• Poor: MET < 4


• Assessing functional status (simple method)
• There are several ways to establish a patient's MET value. The simplest method is to ask the patient several questions about their activity level. Patients who report they can perform the following activities regularly and without significant symptoms have a MET value of at least 4.
• Walking on a flat surface at a 4-mph pace
• Walking up a hill or flight of stairs without stopping
• Mowing the lawn with a hand mower
• Heavy housework such as vacuuming


• Assessing functional status (detailed method)
• The Duke Activity Status Index tool is more detailed and calculates a MET value of 2 to 10 based on the patient's ability to perform 12 activities. A link to an online version of the tool is available below.
• Duke Activity Status Index (online calculator)

• Electrocardiogram (ECG)
• Findings on ECGs may offer clues to underlying heart disease that can affect patient management. Preoperative ECGs are also useful for comparison to postoperative ECGs when operative cardiac injury is suspected. However, the prognostic significance of ECG abnormalities has been inconsistent in observational studies, and there are no evidence-based recommendations on how to deal with many common findings. Recommendations from the AHA on perioperative ECGs are detailed below.


• ECG findings that may indicate underlying heart diease
• ST-segment elevation
• ST depression
• T-wave inversions
• Left ventricular (LV) hypertrophy
• Significant pathologic Q-waves
• Mobitz type II or higher atrioventricular block
• Bundle branch block
• QT prolongation
• Atrial fibrillation


• AHA preoperative ECG recommendations
• Preoperative ECGs should be obtained 1 - 3 months before the procedure
• Preoperative resting 12-lead ECG is reasonable for patients with known coronary heart disease, significant arrhythmia, peripheral arterial disease, cerebrovascular disease, other significant structural heart disease, or symptoms of CVD undergoing elevated-risk surgery
• If ECG exhibits new abnormalities (as outlined above), further evaluation is reasonable to refine assessment of cardiovascular risk
• For asymptomatic patients undergoing elevated-risk surgeries without known CVD, a preoperative resting 12-lead ECG may be considered to establish a baseline and guide perioperative management
• For asymptomatic patients undergoing low-risk surgical procedures, a routine preoperative resting 12-lead ECG is not recommended to improve outcomes [20]

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• Overview
• Postoperative pulmonary complications are significant, accounting for 25% of deaths within 6 days of surgery. Identifying patients at greater risk is important, but there is a lack of good clinical data and little definitive guidance from professional associations on how to achieve this.
• Recommendations on chest x-rays and some common conditions are reviewed below. Patients undergoing lung resection surgery should be evaluated by a pulmonologist and/or thoracic surgeon. [4]

• Chest X-rays
• Chest X-ray is the most common perioperative imaging study performed. In years past, routine preoperative chest x-rays were the norm, but studies have found they have little prognostic value or management implications, so they have largely been abandoned. The ACRAD performed an extensive literature review and published the recommendations outlined below.
• ACRAD recommendations for preoperative chest X-ray
• Do not obtain a chest X-ray in asymptomatic patients with no concerning history or physical exam findings
• Preoperative chest X-ray may be of value in patients with any of the following:
• Age > 70 years
• History of cardiopulmonary disease or symptoms/exam findings suspicious for cardiopulmonary disease
• Unreliable history or physical exam
• High-risk surgery [5]

• Asthma / COPD
• Patients with asthma or COPD are at increased risk of perioperative pulmonary complications, and every patient should have their therapy optimized before surgery. Disease-specific diagnostic testing, including pulmonary function tests and arterial blood gasses, is not routinely recommended because studies have found that results are not predictive of postoperative complications.
• No guidelines have been published that specifically address the preoperative care of these patients. A handful of interventions have been studied in small trials and are discussed below.


• Preoperative interventions for patients with asthma or COPD
• Smoking cessation - smoking cessation of any duration can be beneficial. Studies have shown that cessation for ≥ 8 weeks prior to surgery offers the most benefit.
• Perioperative steroids - small studies have found that perioperative systemic corticosteroids can benefit patients with suboptimal control of their asthma or COPD. Patients who receive steroids for more than 3 weeks could have hypothalamic-pituitary-adrenal axis suppression, and stress-dose corticosteroids may be considered (see corticosteroids for more).
• Inspiratory muscle training (IMT) - during IMT, the patient forces air through a device that provides variable degrees of airflow resistance. This is supposed to strengthen the diaphragm over time. Small studies have found that 2 - 4 weeks of IMT before surgery improves surgical outcomes in high-risk patients. [PMID 17047215] [4]

• Obstructive sleep apnea (OSA)
• Observational studies have found that patients with OSA have higher rates of perioperative complications, including atrial fibrillation, severe hypoxemia, cardiac ischemia, pulmonary embolism, and pneumonia. The role of OSA in these events is difficult to know since affected patients often have other comorbidities associated with poor outcomes (e.g. obesity, diabetes). In 2016, the Society of Anesthesia and Sleep Medicine (SASM) published guidelines on the perioperative management of patients with OSA or suspected OSA. Recommendations relevant to the preoperative evaluation are presented below. [4,6]


• SASM 2016 recommendations on perioperative management of OSA
• Patients without a diagnosis of OSA
• Adult patients at risk for OSA should be identified before surgery. Screening tools such as STOP-Bang, P-SAP, Berlin, and ASA Check List can be used.
• There is insufficient evidence to support canceling or delaying surgery to perform more advanced screening techniques or sleep testing to diagnose OSA in those patients identified as being at high risk of OSA preoperatively, unless there is evidence of an associated significant or uncontrolled systemic disease or additional problems with ventilation or gas exchange
• Patients who have a high probability of having OSA may proceed to surgery in the same manner as those with a confirmed diagnosis, provided strategies for mitigation of postoperative complications are implemented. Alternatively, they may be referred for further evaluation and treatment. The risks and benefits of the decision should include consultation and discussion with the surgeon and the patient.
• Additional evaluation for preoperative cardiopulmonary optimization should be considered in patients who have a high probability of having OSA and where there is indication of uncontrolled systemic conditions or additional problems with ventilation or gas exchange. These conditions include, but may not be limited to (1) hypoventilation syndromes, (2) severe pulmonary hypertension, and (3) resting hypoxemia not attributable to other cardiopulmonary disease.


• Patients with a diagnosis of OSA
• Consideration should be given to obtaining results of the sleep study and the recommended PAP setting before surgery
• Patients should continue to wear their PAP device at appropriate times during their stay in the hospital, both preoperatively and postoperatively
• Untreated OSA patients with optimized comorbid conditions may proceed to surgery provided strategies for mitigation of postoperative complications are implemented. The risks and benefits of the decision should include consultation and discussion with the surgeon and the patient.
• Additional evaluation for preoperative cardiopulmonary optimization should be considered in patients who have a known diagnosis of OSA and are nonadherent or poorly adherent to PAP therapy and where there is indication of uncontrolled systemic conditions or additional problems with ventilation or gas exchange. These conditions include, but may not be limited to (1) hypoventilation syndromes, (2) severe pulmonary hypertension, and (3) resting hypoxemia not attributable to other cardiopulmonary disease [6]

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• Overview
• The NICE guidelines on preoperative laboratory testing are presented below. Other professional guidance exists but is mostly nonspecific and offers little advice beyond discouraging routine labs. The NICE recommendations are divided into categories based on the type of surgery and the patient's ASA physical status class.

• Timing
• The NICE guidelines do not give recommendations on timing, but the ASA states that testing performed within 6 months of surgery is generally acceptable if the patient’s medical history has not changed substantially

• See ASA classification system
• See risk factors for acute kidney injury
• Reference [7]

NICE recommendations on routine preoperative laboratory testing
To use the NICE recommendations, first determine the following: Patient's ASA physical status class If the patient has any risk factors for acute kidney injury
Minor surgery
Examples: skin lesion excision, breast abscess drainage ASA class I or II No routine labs recommended ASA class III or IV Consider serum creatinine in patients at risk for acute kidney injury
Intermediate surgery
Examples: inguinal hernia repair, varicose vein excision, tonsillectomy or adenotonsillectomy, knee arthroscopy ASA class I No routine labs recommended ASA class II Consider serum creatinine in patients at risk for acute kidney injury ASA class III or IV CBC - consider for people with cardiovascular or renal disease if any symptoms not recently investigated PT/INR, PTT Consider in people with chronic liver disease Consider in people receiving anticoagulants. PT/INR is appropriate in patients receiving vitamin K antagonists. DOACs (e.g. dabigatran, factor Xa inhibitors) have inconsistent and variable effects on clotting parameters. See periprocedural antithrombotic recommendations. Serum creatinine - consider in patients at risk for acute kidney injury
Major or complex surgery
Examples: total abdominal hysterectomy, endoscopic resection of prostate, lumbar discectomy, thyroidectomy, total joint replacement, lung operations ASA class I CBC - everyone Serum creatinine - consider in patients at risk for acute kidney injury ASA class II CBC - everyone Serum creatinine - everyone ASA class III or IV CBC - everyone Serum creatinine - everyone PT/INR, PTT Consider in people with chronic liver disease Consider in people receiving anticoagulants. PT/INR is appropriate in patients receiving vitamin K antagonists. DOACs (e.g. dabigatran, factor Xa inhibitors) have inconsistent and variable effects on clotting parameters. See periprocedural antithrombotic recommendations.

• Risk factors for acute kidney injury
• Chronic kidney disease (especially if GFR < 60 ml/min)
• Heart failure
• Liver disease
• Diabetes
• Use of drugs within the last week that can cause or exacerbate kidney injury (e.g. NSAIDs, ACE inhibitors, ARBs, diuretics, aminoglycosides), especially if hypovolemic
• History of acute kidney injury
• Oliguria (urine output less than 0.5 ml/kg/hour)
• Neurological or cognitive impairment or disability, which may mean limited access to fluids because of reliance on a carer
• Hypovolemia
• Sepsis
• Age ≥ 65 years [7]

• Other testing
• Urine testing - routine urine testing is not recommended except for urologic procedures and surgery that involves implantation of foreign material (e.g. prosthetic joints, heart valves)

• Pregnancy testing - on the day of surgery, pregnancy testing may be offered to female patients of childbearing age and for whom the result would alter the patient’s management

• Hemoglobin A1C - offer A1C testing to diabetics who have not had one in the last 3 months.

• Cardiac biomarkers - in observational studies, preoperative cardiac biomarkers, including BNP and NT-ProBNP, have been shown to be predictive of perioperative cardiovascular events. The AHA 2024 testing algorithm recommends cardiac biomarkers for certain patients. [3,7,8]

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• Antithrombotics
• Recommendations for the perioperative management of anticoagulants and antiplatelet therapies are covered here - perioperative antithrombotic recommendations

• Reference [9]

Diabetes Medications
Insulins
Long-acting insulins (e.g. Lantus, Levemir, Basaglar, Tresiba) Continue basal insulin before and on the day of surgery In type 2 diabetics and those prone to hypoglycemia, consider administering 60% - 80% of the usual dose the evening before surgery (or the morning of surgery, if normally taken in the morning) Short- and rapid-acting insulins (e.g. Humalog, Novolog, Regular) Continue on the day before surgery and hold on the morning of surgery May use on the morning of surgery if treatment of hyperglycemia is needed Intermediate-acting insulins (e.g. NPH) Continue before surgery and reduce the dose by 50% on the morning of surgery Consider 25% dose reduction the evening before surgery, especially in patients with type 2 diabetes and those at increased risk for hypoglycemia Insulin pump Continue before surgery, and on the day of surgery, reduce basal infusion to 60% - 80% of the usual rate and do not provide boluses Premixed insulin (e.g. Humulin 70/30, Humalog 75/25) Continue before surgery. On the morning of surgery, do the following: Fasting glucose ≤ 200 mg/dl: hold the premixed insulin, and give half the dose of the intermediate- or long-acting component Fasting glucose > 200 mg/dl: give half the usual dose of the premixed insulin
Non-insulin Diabetes Medications
Metformin Continue before surgery and hold the morning of surgery In patients without contraindications and with GFR > 50 ml/min undergoing ambulatory surgeries for which no more than one meal is expected to be omitted, non-interruption may be acceptable Sulfonylureas and Meglitinides (e.g. glyburide, glipizide, glimepiride repaglinide, nateglinide) Continue before surgery and hold the morning of surgery GLP-1 agonists (e.g. liraglutide, lixisenatide, semaglutide, dulaglutide) Prior to the procedure For patients on daily dosing consider holding GLP-1 agonists on the day of the procedure/surgery. For patients on weekly dosing consider holding GLP-1 agonists a week prior to the procedure/surgery. Recommendation is irrespective of indication (e.g., weight loss, DM2). If GLP-1 agonists prescribed for diabetes management are held for longer than the dosing schedule, consider consulting an endocrinologist for bridging the antidiabetic therapy to avoid hyperglycemia Day of procedure If gastrointestinal (GI) symptoms such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain are present, consider delaying elective procedure, and discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient If the patient has no GI symptoms, and the GLP-1 agonists have been held as advised, proceed as usual If the patient has no GI symptoms, but the GLP-1 agonists were not held as advised, proceed with ‘full stomach’ precautions or consider evaluating gastric volume by ultrasound, if possible and if proficient with the technique. If the stomach is empty, proceed as usual. If the stomach is full or if gastric ultrasound inconclusive or not possible, consider delaying the procedure or treat the patient as ‘full stomach’ and manage accordingly. Discuss the concerns of potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient. There is no evidence to suggest the optimal duration of fasting for patients on GLP-1 agonists. Therefore, until we have adequate evidence, we suggest following the current ASA fasting guidelines. [19] SGLT-2 inhibitors (e.g. dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) SGLT2 inhibitors can increase the risk of DKA in type 2 diabetics who are fasting for surgery; therefore, they should be stopped prior to surgery Canagliflozin, dapagliflozin, and empagliflozin: discontinue at least 3 days prior to scheduled surgery Ertugliflozin: discontinue at least 4 days prior to scheduled surgery DPP-4 inhibitors (e.g. sitagliptin, saxagliptin, linagliptin, alogliptin) Continue before surgery and hold the morning of surgery For patients undergoing ambulatory surgery in which no more than one meal is expected to be omitted, noninterruption may be acceptable Glitazones (e.g. pioglitazone, rosiglitazone) Continue before surgery and hold the morning of surgery Alpha-glucosidase inhibitors (e.g. acarbose, miglitol) Continue before surgery and hold the morning of surgery

• Reference [3,10,11]

Cardiovascular Medications

ACE inhibitors and ARBs In observational studies and small randomized trials, ACE inhibitors and ARBs have been associated with an increased risk of intraoperative hypotension. However, an increase in serious events has not been observed. Professional organizations give differing guidance on managing preoperative ACE inhibitors and ARBs. Recommendations from the AHA, CCS, and ESC are provided below. STUDIES A randomized trial (N=7490) published in 2023 found no difference in cardiovascular outcomes between patients who held ACE inhibitors or ARBs before noncardiac surgery and those who continued them. [PMID 37094336] A second study (N=2222) published in 2024 also found no difference. [PMID 39212270] AHA 2024 recommendations In patients with controlled BP undergoing elevated-risk surgical procedures on chronic RAAS inhibitors for hypertension, omission 24 hours before surgery may be beneficial to limit intraoperative hypotension In patients on chronic RAAS inhibitors for HFrEF, perioperative continuation is reasonable [20] CCS 2016 recommendations We recommend withholding ACE inhibitors and ARBs starting 24 hours before noncardiac surgery in patients treated chronically with these medications Because the risk of hypotension is greatest within 24 hours of surgery, physicians should consider restarting ACE inhibitors and ARBs on day 2 after surgery, if the patient is hemodynamically stable ESC 2014 recommendations Continuation of ACE inhibitors or ARBs, under close monitoring, should be considered during noncardiac surgery in stable patients with heart failure and LV systolic dysfunction Initiation of ACE inhibitors or ARBs should be considered at least 1 week before surgery in cardiac-stable patients with heart failure and LV systolic dysfunction Transient discontinuation of ACE inhibitors or ARBs before noncardiac surgery in hypertensive patients should be considered Alpha blockers (e.g. doxazosin, prazosin, terazosin) Continue before surgery and take the day of surgery For patients undergoing cataract surgery, make sure the ophthalmologist is aware of alpha-blocker therapy due to the risk of floppy iris syndrome Alpha-2 agonists (e.g. clonidine) Continue before surgery and take the day of surgery Do not initiate alpha-2 agonists prior to surgery for the purpose of reducing surgical cardiovascular events Beta blockers Patients taking beta blockers chronically: continue before surgery and take the day of surgery Patients not taking beta blockers: Beta blockers have cardioprotective effects, and studies have looked at initiating them just before surgery to improve outcomes. Results from these studies have been mixed. AHA recommendations for preoperative initiation of beta blockers are available here - AHA preoperative beta blocker recommendations Calcium channel blockers Continue before surgery and take the day of surgery Diuretics In general, diuretics should be continued before surgery and taken the morning of surgery in patients with hypertension and/or heart failure. If hypokalemia or hypovolemia is present, holding diuretics the day before and the day of surgery may be indicated. Dose adjustments may also be considered. Statins For patients already on statin therapy, continue before surgery and take the day of surgery Pre-operative initiation of statin therapy should be considered in patients undergoing vascular surgery, ideally at least 2 weeks before surgery

• Reference [15]

Over-the-counter Medications
Acetaminophen (e.g. Tylenol) Continue before surgery and take the day of surgery Antihistamines (e.g. diphenhydramine, cetirizine, loratadine, fexofenadine) Continue before surgery and hold the day of surgery Decongestants (e.g. pseudoephedrine, phenylephrine) Continue before surgery and hold the day of surgery NSAIDs (e.g. ibuprofen, naproxen) See periprocedural NSAID recommendations

• ¹SPAQI recommendation
• ²ACR recommendation for patients with rheumatic diseases undergoing total hip or knee arthroplasty
• Reference [12,13,15,16,17]

Immunosuppressants

NOTE: The recommendations for immunosuppressants come from SPAQI and the ACR guidelines for patients with rheumatic diseases undergoing elective total hip or knee arthroplasty. The ACR states that "while the principles surrounding these recommendations may be extrapolated and applied to other surgical procedures, it should be noted that the evidence and consensus used to inform this guideline were drawn primarily from orthopedic literature." The following medications should be continued before surgery and taken the day of surgery 5-Aminosalicylic acid (mesalamine, balsalazide, olsalazine, sulfasalazine)1 6-Mercaptopurine (6MP)1 Apremilast (Otezla)1,2 Hydroxychloroquine1,2 Leflunomide (Arava)1,2 Methotrexate1,2 Sulfasalazine1,2 Azathioprine (Imuran) GI indication: continue before surgery and take the day of surgery1 Severe SLE: continue before surgery and take the day of surgery1,2 Nonsevere SLE: withhold for 7 days before surgery.1,2 Restart 3 - 5 days postoperatively as long as there are no issues with wound healing or infection at the surgical site or elsewhere.1 Baricitinib (Olumiant) Withhold for 3 days before surgery. Schedule surgery 4 days after the last dose.1,2 May be resumed postoperatively after 3 days if there are no issues with wound healing or infection1 Corticosteroids Continue before surgery and take the day of surgery1,2 For patients taking ≥ 5 mg/day of prednisone or equivalent for ≥ 4 weeks, consider stress dosing Perioperative stress-dose corticosteroids used to be a standard recommendation for all patients on chronic steroid therapy, but recent studies have found that they do not necessarily improve outcomes and may be harmful. Current ACR guidelines for patients undergoing hip/knee replacement do not recommend stress dosing during chronic steroid therapy. An exception is patients receiving steroids for adrenal insufficiency, where stress dosing is always indicated. The Society for Endocrinology UK gives the following guidance for adrenal patients: Hydrocortisone 100 mg IV should be given at induction of anesthesia in adult patients with adrenal insufficiency from any cause, followed by a continuous infusion of hydrocortisone at 200 mg/24 hours, until the patient can take double their usual oral glucocorticoid dose by mouth. This should then be tapered back to the appropriate maintenance dose, in most cases within 48 hours, although for up to a week if surgery is more major/complicated - clinical judgment should be used to guide this. Cyclosporine (Sandimmune, Neoral, Gengraf) Severe SLE: continue before surgery and take the day of surgery1,2 Nonsevere SLE: withhold for 7 days before surgery.1,2 Restart 3 - 5 days postoperatively as long as there are no issues with wound healing or infection at the surgical site or elsewhere.1 Mycophenolate (Cellcept) Severe SLE: continue before surgery and take the day of surgery1,2 Nonsevere SLE: withhold for 7 days before surgery1,2 May be resumed 14 days postoperatively if there are no issues with wound healing or infection.2 Ozanimod (Zeposia) Ulcerative colitis: withhold for at least 60 days before surgery1 Multiple sclerosis: continue before surgery and take the day of surgery1 Tacrolimus (Prograf) Severe SLE: continue before surgery and take the day of surgery1,2 Nonsevere SLE: withhold for 7 days before surgery.1,2 Restart 3 - 5 days postoperatively as long as there are no issues with wound healing or infection at the surgical site or elsewhere.1 Tofacitinib (Xeljanz) GI indication: withhold for 7 days before surgery1 Rheumatologic indication: withhold for 3 days before surgery. Schedule surgery 4 days after the last dose.1,2 May be resumed postoperatively after 3 days if there are no issues with wound healing or infection.1 Upadacitinib (Rinvoq) Withhold for 3 days before surgery. Schedule surgery 4 days after the last dose.1,2 May be resumed postoperatively after 3 days if there are no issues with wound healing or infection1 Voclosporin (Lupkynis) Severe SLE: continue before surgery and give the day of surgery2

• ¹SPAQI recommendation
• ²ACR recommendation for patients with rheumatic diseases undergoing total hip or knee arthroplasty
• Reference [12,13,16,17]

Biologicals

NOTE: The recommendations for biologicals come from SPAQI and the ACR guidelines for patients with rheumatic diseases undergoing elective total hip or knee arthroplasty. The ACR states that "while the principles surrounding these recommendations may be extrapolated and applied to other surgical procedures, it should be noted that the evidence and consensus used to inform this guideline were drawn primarily from orthopedic literature." See periprocedural studies for a review of observational studies that have examined surgical infection risk with biologics. For the following medications, withhold for at least 1 dosing interval before surgery. For example, if the drug is dosed every 4 weeks, schedule surgery 5 weeks from the last dose. Medications can be resumed 14 days postoperatively if there are no issues with wound healing or infection. Tumor necrosis factor inhibitors Adalimumab (Humira)1,2 Certolizumab (Cimzia)1,2 Etanercept (Enbrel)1,2 Golimumab (Simponi)1 Infliximab (Remicade)1,2 IL-1 inhibitors Anakinra (Kineret)1,2 Canakinumab (Ilaris)1 Rilonacept (Arcalyst)1 IL-6 inhibitors Tocilizumab (Actemra)1,2 Sarilumab (Kevzara)1 IL-17 inhibitors Secukinumab (Cosentyx)1,2 Brodalumab (Siliq)1 Ixekizumab (Taltz)1,2 IL-12/23 inhibitors Ustekinumab (Stelara)1,2 IL-12/23 inhibitors Guselkumab (Tremfya)1,2 Risankizumab (Skyrizi)1 T-cell agents Abatacept (Orencia)1,2 Vedolizumab (Entyvio)1 Anifrolumab (Saphnelo) Severe SLE: do not hold before surgery. Schedule surgery 4 weeks after the last dose1,2 Belimumab (Benlysta) Severe SLE: do not hold before surgery. Schedule surgery anytime for weekly dosing (SC) and 4 weeks after the last dose for monthly dosing (IV)1,2 Nonsevere SLE: withhold for a dosing cycle. Schedule surgery 2 weeks from the last dose for weekly dosing (SC) and 5 weeks from the last dose for monthly dosing (IV)1,2 May be resumed 14 days postoperatively if there are no issues with wound healing or infection. Natalizumab (Tysabri) Crohn's disease: withhold for 1 dosing interval. Schedule surgery 5 weeks after the last dose.1 Multiple sclerosis: continue before surgery and give the day of surgery (if due)1 Rituximab (Rituxan) Severe SLE: do not hold before surgery. Schedule surgery 4 - 6 months after the last dose.1,2 Nonsevere SLE and rheumatoid arthritis: withhold for 1 dosing interval. Schedule surgery 7 months after the last dose.1,2 May be resumed 14 days postoperatively if there are no issues with wound healing or infection.

• Reference [14]

Psychiatric medications

Amphetamines (e.g. amphetamine salts, methylphenidate) Continue before surgery and hold the day of surgery Antipsychotics (first and second generation) Continue before surgery and take the day of surgery, except for Lybalvi, which contains olanzapine and samidorphan, an opioid antagonist. Lybalvi should be discontinued at least 5 days before opioids are required and replaced with olanzapine only. Atomoxetine (Strattera) Continue before surgery and hold the day of surgery Benzodiazepines (e.g. alprazolam, clonazepam, diazepam) Continue before surgery and take the day of surgery Bupropion (Wellbutrin) Continue before surgery and take the day of surgery Buspirone (Buspar) Continue before surgery and take the day of surgery Guanfacine (Tenex, Intuniv) Continue before surgery and take the day of surgery Lithium Minor procedure (e.g. same-day ambulatory procedures and endoscopies): continue before surgery and take the day of surgery Major procedure where risk of acute kidney injury is elevated: hold for 72 hours before surgery. After surgery, restart when tolerating oral intake and fluid status is stable. Resume home dose and monitor levels in 5 - 7 days. Mirtazapine (Remeron) Continue before surgery and take the day of surgery SSRIs (e.g. paroxetine, sertraline, fluoxetine) Continue before surgery and take the day of surgery SNRIs (e.g. venlafaxine, duloxetine) Continue before surgery and take the day of surgery Serotonin modulators (e.g. vilazodone, vortioxetine) Continue before surgery and take the day of surgery Trazodone Continue before surgery and take the day of surgery Tricyclic antidepressants (e.g. amitriptyline, clomipramine, desipramine) Continue before surgery and take the day of surgery

• Reference [15]

Pulmonary medications

The following medications should be continued before surgery and given the day of surgery Anticholinergics, inhaled (e.g. ipratropium, tiotropium, aclidinium, umeclidinium, revefenacin, glycopyrrolate) Antifibrotics (nintedanib, pirfenidone) Beta agonists, long- and short-acting (albuterol, metaproterenol, levalbuterol, salmeterol, formoterol, arformoterol, indacaterol, olodaterol, vilanterol) Corticosteroids, inhaled (fluticasone, budesonide, mometasone, beclomethasone) Endothelin receptor antagonists (bosentan, macitentan, ambrisentan) Leukotriene inhibitors (montelukast, zafirlukast, zileuton) N-Acetylcysteine PDE-4 inhibitor (roflumilast) PDE-5 inhibitor (sildenafil, tadalafil) - continue when taken for pulmonary hypertension. If taken for urologic reasons (ED, BPH), hold starting 72 hours before surgery. Prostacyclin analogs (epoprostenol, treprostinil, iloprost) Riociguat (Adempas) Selexipag (Uptravi) Theophylline Continue before surgery and hold the day of surgery

• Reference [15]

Gastrointestinal medications

The following medications should be continued before surgery and taken the day of surgery 5-HT 3 antagonists (ondansetron, granisetron, dolasetron, palonosetron) Aprepitant Dopamine antagonist antiemetics (promethazine, prochlorperazine, droperidol, metoclopramide) Guanylate cyclase C agonists (linaclotide, Linzess, plecanatide) H2 antagonists (e.g. famotidine, ranitidine, cimetidine) Lubiprostone Proton pump inhibitors (e.g. omeprazole, pantoprazole, esomeprazole) Serotonergic neuroenteric modulators (tegaserod, alosetron, prucalopride) The following medications should be continued before surgery and held the day of surgery Antacids (sodium citrate, magnesium trisilicate, aluminum hydroxide, calcium carbonate, sucralfate) Anticholinergics (dicyclomine, hyoscyamine) Antidiarrheals (loperamide, diphenoxylate, atropine) Gallstone solubilizing agents (ursodiol, chenodeoxycholic acid) Laxatives (e.g. Miralax, bisacodyl, lactulose, docusate) Pancreatic enzymes (Pancrelipase)

• Reference [15]

Hepatitis medications

NOTE: Recommendations for holding certain medications in this class are based on adverse effects, potential drug interactions with common perioperative medications, and the need to be taken with food. Anti-HBV reverse transcriptase inhibitors (e.g. entecavir, tenofovir, lamivudine, adefovir) Continue before surgery and take the morning of surgery Epclusa (sofosbuvir + velpatasvir) Continue before surgery and hold the morning of surgery Harvoni (sofosbuvir + ledipasvir) Continue before surgery and take the morning of surgery Mavyret (glecaprevir + pibrentasvir) Continue before surgery and hold the morning of surgery Pegylated interferons (Pegasys, PegIntron) When used for the treatment of viral hepatitis, stop interferons 1-2 weeks before surgery because of the potential for perioperative complications Ribavirin Continue before surgery and hold the morning of surgery Sofosbuvir (Sovaldi) Continue before surgery and take the morning of surgery Viekira Pak (dasabuvir, ombitasvir, paritaprevir, ritonavir) Continue before surgery and hold the morning of surgery Vosevi (sofosbuvir + velpatasvir + voxilaprevir) Continue before surgery and hold the morning of surgery Zepatier (elbasvir + grazoprevir) Continue before surgery and hold the morning of surgery

• Reference [13]

Neurologic medications

Alzheimer's medications The following medications should be continued before surgery and taken the day of surgery Acetylcholinesterase inhibitors (rivastigmine, donepezil, galantamine) Memantine (Namenda) Anticonvulsants The following medications should be continued before surgery and taken the day of surgery Acetazolamide (Diamox) Carbamazepine (Tegretol) Eslicarbazepine (Aptiom) Ethosuximide (Zarontin) Felbamate (Felbatol) Gabapentin (Neurontin) Lacosamide (Vimpat) Lamotrigine (Lamictal) Levetiracetam (Keppra) Oxcarbazepine (Trileptal) Perampanel (Fycompa) Phenytoin (Dilantin) Pregabalin (Lyrica) Primidone (Mysoline) Rufinamide (Banzel) Stiripentol (Diacomit) Tiagabine (Gabitril) Topiramate (Topamax) Valproic acid (Depakote) Vigabatrin (Sabril) Zonisamide (Zonegran) Migraine therapies The following medications should be continued before surgery and held the day of surgery Almotriptan (Axert) Eletriptan (Relpax) Frovatriptan (Frova) Naratriptan (Amerge) Rizatriptan (Maxalt) Sumatriptan (Imitrex) Zolmitriptan (Zomig) Ergotamine - hold for at least 2 days prior to surgery The following medications should be continued before surgery and taken the day of surgery Erenumab (Aimovig) Fremanezumab (Ajovy) Galcanezumab (Emgality) Multiple sclerosis therapies The following medications should be continued before surgery and taken the day of surgery (if due) Alemtuzumab (Lemtrada) Cladribine (Mavenclad) Dalfampridine (Ampyra) Fumarates (Tecfidera, Vumerity, Bafiertam) Glatiramer acetate (Copaxone, Glatopa) Interferons (e.g. Betaseron, Plegridy, etc.) Mitoxantrone Natalizumab (Tysabri) Ocrelizumab (Ocrevus) Ofatumumab (Kesimpta) Rituximab (Rituxan) S1P receptor modulators (Fingolimod, Gilenya, Ozanimod, Zeposia, Ponesimod, Ponvory, Siponimod, Mayzent) Teriflunomide (Aubagio) Myasthenia Gravis The following medications should be continued before surgery and taken the day of surgery (if due) Eculizumab (Soliris) Acetylcholinesterase inhibitors (e.g. Neostigmine, Pyridostigmine, Mestinon) Parkinson's disease The following medications should be continued before surgery and taken the day of surgery Amantadine Anticholinergic agents (e.g. benztropine, trihexyphenidyl) Apomorphine (Apokyn) Bromocriptine (Parlodel) Carbidopa/Levodopa (Sinemet) COMT inhibitors (entacapone, tolcapone, opicapone) MAO inhibitors (e.g. Selegiline, Eldepryl) Pramipexole (Mirapex) Ropinirole (Requip) Rotigotine (Neupro)

• Reference [9]

Hormonal Medications

The following medications should be continued before surgery and taken the day of surgery Antidiuretic hormone (Desmopressin) Antithyroid medications (methimazole, propylthiouracil) Aromatase inhibitors (anastrozole, exemestane, letrozole) Calcimimetics (cinacalcet, etelcalcetide) Calcitonin Denosumab Dopamine agonists, pituitary (cabergoline, bromocriptine) Growth hormone (somatotropin) Growth hormone antagonist (pegvisomant) Growth hormone-releasing hormone analog (tesamorelin) Parathyroid analogs (teriparatide, abaloparatide) Progestins (HRT and birth control) Recombinant insulin-like growth factor-1 (mecasermin) Somatostatin analogs (octreotide, lanreotide, pasireotide) Thyroid replacement (levothyroxine) Testosterone products (Androgel, etc.) Bisphosphonates (e.g. alendronate, ibandronate, risedronate) Continue before surgery and hold the morning of surgery Estrogen products (hormone replacement therapy and contraceptives) The prescribing information for estrogen products recommends that they be held for 4 weeks before surgery with a high risk of VTE. The SPAQI guidelines state that there is no conclusive evidence that estrogens increase the risk of postoperative VTE, and it is okay to continue them before and on the morning of surgery while "considering the increased risk of VTE." SERMs (toremifene, tamoxifen, raloxifene, ospemifene) If taken for breast cancer prevention or treatment: continue before surgery and take on the day of surgery while considering the potential for increased wound complications and VTE risk All other indications: if there are additional surgery- or patient-specific risk factors for VTE, stop 7 days before surgery

• Reference [9]

Urologic Medications

5-Alpha reductase inhibitors (dutasteride, finasteride) Continue before surgery and take the day of surgery Alpha blockers (e.g. doxazosin, prazosin, terazosin) Continue before surgery and take the day of surgery For patients undergoing cataract surgery, make sure the ophthalmologist is aware of alpha-blocker therapy due to the risk of floppy iris syndrome Anticholinergic bladder medications (e.g. oxybutynin, solifenacin, tolterodine) Continue before surgery and hold the day of surgery May reduce catheter-related bladder discomfort but carry a high potential for adverse effects in older patients Antineoplastic agents (e.g. abiraterone, apalutamide, leuprolide) Continue before surgery and take the day of surgery Mirabegron (Myrbetriq) Continue before surgery and hold the day of surgery Phosphodiesterase type 5 (PDE-5) inhibitors (avanafil, sildenafil, tadalafil, vardenafil) If taking for erectile dysfunction or benign prostatic hyperplasia: hold medication starting 3 days before surgery If taking for pulmonary hypertension: continue before surgery and take the day of surgery

• Reference [18]

Opioids / Muscle relaxers

The following drugs should be continued before surgery and taken the day of surgery Baclofen Butorphanol Codeine Fentanyl Hydrocodone Hydromorphone Nalbuphine Methadone Morphine Oxycodone Oxymorphone Pentazocine Sufentanil Tapentadol Tizanidine Tramadol The following drugs should be continued before surgery held the day of surgery Alvimopan (Entereg) Carisoprodol - if time permits, consider tapering over 4 - 9 days Cyclobenzaprine Metaxalone Methocarbamol Methylnaltrexone (Relistor) Naldemedine (Symproic) Naloxegol (Movantik) Orphenadrine Buprenorphine (e.g. Suboxone, Belbuca, Butrans, Zubsolv) Buprenorphine may be continued before surgery and taken on the day of surgery. High-potency intravenous full opioid agonists can be used perioperatively for analgesia. If buprenorphine is discontinued before planned surgery, it should be stopped the day before or the day of surgery. It may be resumed when intravenous analgesia is no longer required. If it is withheld for 2 - 3 days, it can be restarted at the prior maintenance dose. If it is withheld for more than 3 days, re-titration may be necessary. Naloxone (e.g. Suboxone, Zubsolv) Naloxone that is a part of oral products with buprenorphine (e.g. Suboxone, Zubsolv) is only minimally absorbed and has no meaningful effect If a patient has received naloxone for opioid overdose via the subcutaneous, intramuscular, intravenous, or nasal route within 4 hours of surgery, the anesthesia team should be consulted Naltrexone Oral naltrexone should be discontinued at least 72 hours before planned surgery Intramuscular naltrexone should be stopped at least 30 days before surgery. After 30 days, oral naltrexone may be used up to 72 hours before surgery. After surgery, patients should be off opiates for 3 - 7 days before restarting naltrexone

• Reference [15,18]

Weight loss medications

Bupropion/Naltrexone (Contrave) Hold 72 hours before surgery If the procedure does not require opioid use, it may be reasonable to continue uninterrupted After surgery, patients should be off opiates for 3 - 7 days before restarting naltrexone GLP-1 agonists See GLP-1 agonists above Lisdexamfetamine (Vyvanse) Hold starting 72 hours before surgery Orlistat (Xenical) Continue before surgery and hold the day of surgery Phentermine Hold for at least 4 days before surgery Phentermine/Topiramate (Qsymia) Stop at least 4 days before surgery. The Qsymia prescribing information states that the 15/92 mg dose should be taken every other day for at least a week when stopping to prevent precipitating a seizure. The patient may be tapered in this fashion, or Qsymia can be stopped, and topiramate alone can be continued.

• SLE definitions
• Severe SLE - currently treated (induction or maintenance) for severe organ manifestations: lupus nephritis, CNS lupus, severe hemolytic anemia (hemoglobin < 9.9 gm/dl), platelets < 50,000, vasculitis (other than mild cutaneous vasculitis), including pulmonary hemorrhage, myocarditis, lupus pneumonitis, severe myositis (with muscle weakness, not just high enzymes), lupus enteritis (vasculitis), lupus pancreatitis, cholecystitis, lupus hepatitis, protein-losing enteropathy, malabsorption, orbital inflammation/myositis, severe keratitis, posterior severe uveitis/retinal vasculitis, severe scleritis, optic neuritis, anterior ischemic optic neuropathy (derived from the SELENA–SLEDAI flare index and the BILAG 2004 index)
• Nonsevere SLE - none of the above features

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• OBS
  Stopping vs Continuing bDMARDS and the Risk of Postoperative Complications Following Orthopedic Surgery, J Bone Joint Surg Am (2022) [PubMed abstract]
• Design: Meta-analysis of cohort studies (N=7344 | length - variable) in patients who underwent orthopedic surgical procedures and were taking bDMARDs
• Exposure: Withholding bDMARD vs Continuing it
• Primary outcome: Surgical site infection, delayed wound healing, and disease flares
• Findings: The present systematic review highlights the limited evidence supporting the current practice of stopping bDMARDs perioperatively. These findings suggest that patients may not be at an increased risk for developing infection or wound complications if bDMARDs are continued but are at an increased risk for disease flare if bDMARDs are withheld. However, our conclusions are limited by the retrospective and heterogeneous nature of the data, and possibly by a lack of study power.

• OBS
  Risk of Infection after Knee or Hip Replacement in Patients Taking Biologics or Glucocorticoids, Ann Intern Med (2019) [PubMed abstract]
• Design: Retrospective cohort study (N=9911 | length - 12 months) in patients with RA having elective inpatient total knee or hip arthroplasty
• Exposure: Receiving abatacept, adalimumab, etanercept, infliximab, rituximab, or tocilizumab before surgery
• Primary outcome: Comparative risks for hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery
• Findings: Risks for hospitalized infection, PJI, and readmission after arthroplasty were similar across biologics. In contrast, glucocorticoid use, especially with dosages above 10 mg/d, was associated with greater risk for adverse outcomes.

• OBS
  Perioperative Timing of Infliximab and the Risk of Serious Infection After Elective Hip and Knee Arthroplasty, Arthritis Care Res (2017) [PubMed abstract]
• Design: Retrospective cohort study (N=4288 | length - 12 months) in patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty
• Exposure: Timing of infliximab dosing before elective hip or knee replacement
• Primary outcome: Association of infliximab stop timing with hospitalized infection within 30 days or prosthetic joint infection (PJI) within 1 year
• Findings: Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short- or long-term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially > 10 mg/day, was associated with an increased infection risk.

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