perioperative medication management - cecity · perioperative medication management pier is...

Quality Ratings: The preponderance of data supporting guidance statements are derived from:

level 1 studies, which meet all of the evidence criteria for that study type;

level 2 studies, which meet at least one of the evidence criteria for that study type; or

level 3 studies, which meet none of the evidence criteria for that study type or are derived from expert opinion, commentary, or consensus.

Study types and criteria are defined at http://smartmedicine.acponline.org/criteria.html

Disclaimer: The information included herein should never be used as a substitute for clinical judgement and does not represent an official position of the American College of Physicians. Because all PIER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete.

Therefore, PIER users should compare the module updated date on the offical web site with any printout to ensure that the information is the most

current available.

CME Statement: The American College of Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide

continuing education for physicians. The American College of Physicians designates this enduring material for a maximum of 1 AMA PRA Category 1

CreditTM. Physicians should claim only credit commensurate with the extent of their participation in the activity. Purpose: This activity has been

developed for internists to facilitate the highest quality professional work in clinical applications, teaching, consultation, or research. Upon completion

of the CME activity, participants should be able to demonstrate an increase in the skills and knowledge required to maintain competence, strengthen

their habits of critical inquiry and balanced judgement, and to contribute to better patient care. Disclosures: Steven L. Cohn, MD, FACP, SFHM,

current author of this module, serves on advisory boards for Janssen, Bristol-Myers Squibb/Pfizer; owns stock in Bristol-Myers Squibb, GlaxoSmithKline, AstraZeneca, Pfizer, Merck. Deborah Korenstein, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical

companies, biomedical device manufacturers, or health-care related organizations. Richard B. Lynn, MD, FACP, Co-Editor, PIER, has no financial

relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations.

PIER is copyrighted ©2014 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.

Perioperative Medication Management View online at http://pier.acponline.org/physicians/diseases/d835/d835.html

Module Updated: 2014-05-02

CME Expiration: 2017-05-02

Author

Steven L. Cohn, MD, FACP, SFHM

Table of Contents

1. Screening ..........................................................................................................................2

2. Diagnosis ..........................................................................................................................5

3. Consultation ......................................................................................................................9

4. Hospitalization ...................................................................................................................11

5. Therapy ............................................................................................................................12

6. Patient Counseling ..............................................................................................................17

7. Follow-up ..........................................................................................................................19

References ............................................................................................................................22

Glossary................................................................................................................................39

Tables ...................................................................................................................................41

http://pier.acponline.org/physicians/diseases/d835/d835.html

Perioperative Medication Management


of 74

1. Screening Top

Ask all preoperative patients about medication intake.

1.1 Ask preoperative patients about all prescription medications.

Recommendations

• Ask the patient to bring in the actual medications or a list with the names, doses, and frequencies.

• Review medications used with all patients to determine the indication for the drug, the possible

effects (both risks and benefits) of each medication perioperatively, and whether or not the patient

has adhered to the medication and dosage.

Evidence

• In a study of 304 patients admitted to a general internal medicine inpatient unit, 25% of drugs in

use were not recorded, and 61% of patients had at least one drug unrecorded. These drugs

included medications that require management in the perioperative period, including cardiovascular

agents and NSAIDs (1).

• A cross-sectional study compared patient-reported medication use with medications documented in

the medical records of 312 outpatients. Discrepancies were found in 76% of patients; 51% were

taking unrecorded medications, 29% were not taking a recorded medication, and 20% were taking

a different dosage from what was recorded (2).

• A cross-sectional study compared medication lists generated in the clinic (using pill bottles and

patient reports) with medications found in the home in 50 patients who were newly referred to a

geriatrics clinic. Overall, 48% of patients were taking at least one medication that they did not

report and 19% were taking at least one prescription medication that they did not report (3).

Rationale

• Patients are often on numerous medications, some of which they may not take and others that

they may not need.

• Patients may forget to inform the physician of a medication they are taking.

• Patients taking multiple medications may be at increased risk for potential adverse drug

interactions.

1.2 Ask all preoperative patients about OTC and herbal medication use.

Recommendations

• Review OTC and herbal medication use with the patient to prevent any potential adverse effects,

and highlight the paucity of human data on many herbal medications.

• Stop herbal medications before surgery.

Evidence

• A 2014 systematic review of the effect of preoperative aspirin on outcomes of coronary artery

bypass surgery included 8 randomized trials and 19 observational trials. Aspirin increased

postoperative bleeding in randomized trials (difference of means, 132 mL; P=0.002) and

observational studies (difference in means, 133 mL; P=0.003), transfusion requirements in

randomized trials (difference in means, 0.67; P=0.02) and observational studies (difference in

means, 0.19; P=0.02), and the need for reoperation for bleeding in randomized trials (OR, 1.76

[CI, 1.05 to 2.93]) but not in observational studies (OR, 1.13 [CI, 0.91 to 1.42]) (4).

• A 2001 systematic review of the use of herbal medications in the perioperative period found no

randomized trials but summarized the findings of case series and observational studies of the most

commonly used products, including echinacea, ephedra, garlic, ginkgo, ginseng, kava, St. John's

http://jama.jamanetwork.com/article.aspx?articleid=194003



of 74

wort, and valerian. The review noted that complications during the perioperative period can arise

from direct and pharmacodynamic or pharmacokinetic effects of medications. Effects described

included immunostimulatory effects from echinacea; tachycardia, hypertension, and

vasoconstriction from ephedra; platelet dysfunction from garlic; platelet inhibition and bleeding

from ginkgo and ginseng; CNS effects from kava; drug metabolism changes from St. John's wort;

and sedation from valerian (5).

• A 2001 systematic review of drug interactions between the seven top-selling herbal medicines and

prescribed drugs included 17 clinical trials and 41 case reports or case series. Garlic, ginkgo, and

ginseng had interactions with warfarin and appeared to cause bleeding. St. John's wort decreased

levels of many drugs (e.g., digoxin, warfarin, oral contraceptive, and cyclosporine) and precipitated

serotonin syndrome, and kava had dopaminergic antagonistic properties (6).

• A prospective cohort study evaluated the relationship between traditional and herbal medication

use and perioperative events in 601 patients undergoing elective surgery. In the multivariate

analysis, patients who were prescribed Chinese herbal medications were more likely to have

preoperative events (adjusted RR, 2.21 [CI, 1.14 to 4.29]) but not intraoperative or postoperative

events compared with patients who did not take herbal medications. Use of traditional Chinese

herbal medicines appeared to cause hypokalemia; patients taking ginseng did not have prolonged

PTTs, and those taking ginger did not have elevated INRs or prolonged PTTs (7).

• A cross-sectional study evaluated the use of alternative medication in 2560 patients awaiting

elective surgery. Overall, 39.2% admitted to using some form of alternative medicine supplements;

44.4% did not consult with their primary physicians, and 56.4% did not inform the

anesthesiologists (8).

• A cross-sectional study evaluated the use of alternative medicines among 3106 patients seen in a

preoperative clinic. Herbal medications were used by 22%, and 51% used vitamins (9).

• A cross-sectional study evaluated herbal medication use among 2723 patients in the UK before

anesthesia. Overall, 131 patients (4.8%) were taking herbal medications, but it was recorded on

the patient's chart in only two cases (10).

• A cross-sectional study evaluated self-reported use of herbal medications in 2186 patients

undergoing elective surgery. Overall, 57% had ever taken herbal medications, 38% had taken

herbal medications in the last 2 years, and 16% used herbal medicines during the month of

surgery. Use was higher among those undergoing gynecologic procedures (OR, 1.68 [CI, 1.29 to

2.18]) and those with a self-perception of good health (OR, 1.32 [CI, 1.04 to 1.69]) and was lower

in black patients (OR, 0.69 [CI, 0.51 to 0.95]), patients with pulmonary symptoms (OR, 0.77 [CI,

0.62 to 0.94) or diabetes (OR, 0.46 [CI, 0.32 to 0.68]), and patients undergoing vascular surgery

(OR, 0.19 [CI, 0.07 to 0.48]) (11).

Rationale

• Many patients are using OTC and herbal meditations that can have potential drug interactions, and

many are used for symptomatic relief only.

Comments

• Vitamin E and alternative therapies may potentially interact with warfarin (12).

1.3 Screen for conditions that may affect drug metabolism.

Recommendations

• Ask about any history of liver, kidney, or thyroid disease.

• Obtain lab tests as indicated to evaluate renal (BUN/creatinine), hepatic (transaminases, bilirubin),

and thyroid (TSH, T4) function in appropriate patients.

Evidence



of 74

• Consensus.

Rationale

• Hepatic and renal insufficiency may lead to increased levels of drugs metabolized by those

systems.

• Hyperthyroidism may accelerate metabolism in general.



of 74

2. Diagnosis Top

Confirm the diagnostic indication for therapy, and perform a risk-benefit analysis of continuing, stopping, or starting a drug preoperatively.

2.1 Determine the nature and extent of comorbid conditions to assess the

need for and timing of drug therapy.

Recommendations

• Assess patients for:

Left ventricular dysfunction by history (known heart failure, dyspnea, paroxysmal nocturnal dyspnea,

orthopnea), physical exam (tachypnea, jugular venous distension, S3, rales, edema), and diagnostic tests (echocardiography, when indicated). Optimize medications (diuretics, ACE inhibitors, β-blockers, digoxin) for heart failure to prevent perioperative decompensation

CAD (clinical risk factors, history of MI, angina, chest pain, dyspnea, ischemic changes on ECG), and continue or start antianginal medications to minimize perioperative ischemia

Stage II-III hypertension (systolic BP ≥160 mm Hg, diastolic BP ≥100 mm Hg), and start, continue, or add medications and adjust doses to obtain better control to minimize perioperative BP lability

Valvular heart disease based on history (rheumatic fever, murmurs), physical exam (murmur), and diagnostic tests (echocardiography) when indicated, and initiate appropriate endocarditis prophylaxis based on the cardiac condition and type of surgical procedure

Bronchospasm (COPD or asthma), and optimize pulmonary status with bronchodilators and steroids as indicated

Any change in sputum quantity or quality that may suggest an infection requiring antibiotic treatment in patients with COPD

Symptoms (hot or cold intolerance or weight loss or gain) and signs (goiter, tremor) of thyroid disease, particularly hyperthyroidism; start or continue appropriate treatment such as propylthiouracil, β-blockers,

or thyroxine as needed

Renal insufficiency (risk factors, BUN/creatinine) and liver disease (history of hepatitis, alcohol and drug use, abdominal exam, liver function tests) because these conditions may alter drug metabolism

Risk profile for DVT, including age, history, comorbid conditions, immobility, and surgical procedure, and prescribe an appropriate regimen for prophylaxis

• Optimize glycemic control in patients with diabetes before surgery, using oral medication or insulin

as needed, and consider perioperative insulin in patients undergoing major surgery.

• Be willing to use medications with known potential for adverse effects during surgery if these drugs

are essential to the patient's health.

• See module Preoperative Evaluation.

• See module Perioperative Management of Diabetes Mellitus.

• See module Perioperative Management of Heart Failure.

• See module Perioperative Management of Hypertension.

• See module Perioperative Management of Hyperthyroid Patients.

• See module Perioperative Management of Hypothyroid Patients.

• See module Preoperative Cardiac Risk Assessment and Management.

• See module Venous Thromboembolism Prophylaxis in the Surgical Patient.

Evidence

http://pier.acponline.org/physicians/diseases/preopr833/preopr833.html

http://pier.acponline.org/physicians/diseases/periopr879/periopr879.html





http://pier.acponline.org/physicians/diseases/preopr157/preopr157.html




of 74

• The 2007 ACC/AHA guidelines for perioperative evaluation recommended assessing for the

presence of active cardiac conditions. The guideline recommended continuing β-blockers in patients

who are already receiving them and considering β-blockers in patients at high risk for cardiac

complications or those undergoing high-risk surgery (13).

• A 2008 systematic review of the effect of perioperative β-blockers on mortality included 33 trials

with 12,306 patients and found that treatment with β-blockers did not lead to improved all-cause

or cardiovascular mortality. Treatment was associated with a decrease in nonfatal MI (NNT, 63)

and an increase in nonfatal stroke (NNH, 293) (14; 15).

• A retrospective cohort study evaluated the impact of β-blocker discontinuation after vascular

surgery among 140 patients who were treated with β-blockers perioperatively, among whom 8

were taken off the medication postoperatively. Withdrawal was associated with increased

cardiovascular mortality (0% vs. 25%, P=0.005) and postoperative MI (16).

• In a case-controlled study of patients with deep sternal site infections after CABG, those patients

with diabetes with a preoperative glucose level >110 mg/dL had a higher risk for deep sternal

wound infections (OR, 1.4 [CI, 0.4 to 4.8]; P=0.6) (17).

• A 2012 noninferiority randomized, controlled trial compared liberal (120 mg/dL to 180 mg/dL) with

tight (90 mg/dL to 120 mg/dL) glucose goals in 189 patients with diabetes undergoing CABG.

There were no differences in rates of infection between the groups, but the liberal group had fewer

episodes of hypoglycemia (18).

• A 2011 randomized, controlled trial compared liberal (120 mg/dL to 180 mg/dL) with tight (90

mg/dL to 120 mg/dL) glucose goals (achieved with insulin infusion) in 82 patients undergoing

CABG. There were no differences in the rates of major adverse events between the groups, but

there were more episodes of hypoglycemia in the tight-control group (NNH, 1.6) (19).

• A prospective cohort study evaluated the relationship between hypokalemia and perioperative

complications in 2402 patients who underwent elective CABG. Perioperative arrhythmias were seen

in 53.7% of patients. Patients with preoperative hypokalemia were more likely to have serious

perioperative arrhythmia (OR, 2.2 [CI, 1.2 to 4.0]) (20).

Rationale

• Untreated or uncontrolled medical illness may have a more deleterious impact on outcome than the

medications used to treat it.

Comments

• Preoperative treatment can prevent thyroid storm in hyperthyroid patients.

• Consider the consequences of discontinuing a drug (e.g., for uncontrolled hypertension,

uncontrolled diabetes, exacerbation of asthma).

2.2 Consider the risk associated with the particular surgical procedure when planning medication use.

Recommendations

• Consider using intravenous (as opposed to subcutaneous) insulin for better glucose control in

diabetics undergoing complex, high-risk surgical procedures (e.g., CABG).

• Avoid the use of sliding-scale insulin in preference for long-acting and prandial regimens.

• Consider supplemental steroid coverage when indicated, based on the type of surgery and the

likelihood of adrenal suppression.

• Consider perioperative β-blockers in patients with multiple cardiac risk factors (RCRI >2)

undergoing intermediate- to high-risk noncardiac surgery or vascular surgery.

http://circ.ahajournals.org/content/116/17/1971.full.pdf

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2808%2961560-3/fulltext



of 74

• Use appropriate DVT prophylaxis based on the risk of the surgical procedure along with the

patient's age and underlying risk factors.

• Use appropriate endocarditis prophylaxis based on the risk associated with the specific type of

surgery and the patient's underlying cardiac disease.

• Consider the risk for bleeding based on the procedure in determining the use of perioperative

anticoagulation.

• Consider the risk for postoperative wound infection based on the type of surgery, and use

appropriate antibiotic prophylaxis.

• See table Surgical Risk Stratification and Associated VTE Incidence.

Evidence

• A 2012 guideline from the American College of Chest Physicians provided evidence-based

guidelines for the assessment of risk and the use of VTE prophylaxis, and recommended different

DVT prophylaxis based on the risk associated with the procedure (21).

• The 2007 ACC/AHA guidelines for perioperative evaluation recommended assessing for the

presence of active cardiac conditions. The guideline recommended continuing β-blockers in patients

who are already receiving them and considering β-blockers in patients at high risk for cardiac

complications or those undergoing high-risk surgery (13).




and an increase in nonfatal stroke (NNH, 293) (14; 15).

• A study used a prospective database with over 200,000 surgical patients to identify factors

predicting cardiac events. In the logistic regression analysis, the type of surgery was predictive of

cardiac events; particularly high risk was seen with aortic (OR, 4.96 [CI, 3.55 to 6.93]), upper

abdominal (OR, 4.02 [CI, 2.89 to 5.60]), and brain (OR, 4.04 [CI, 1.79 to 9.13]) procedures, and

low risk was seen with breast procedures (OR, 0.20 [CI, 0.08 to 0.50]) (22).

• A 2012 noninferiority randomized, controlled trial compared liberal (120 mg/dL to 180 mg/dL) with

tight (90 mg/dL to 120 mg/dL) glucose goals in 189 patients with diabetes undergoing CABG.

There were no differences in rates of infection between the groups, but the liberal group had fewer

episodes of hypoglycemia (18).

• A 2011 randomized, controlled trial compared liberal (120 mg/dL to 180 mg/dL) with tight (90

mg/dL to 120 mg/dL) glucose goals (achieved with insulin infusion) in 82 patients undergoing

CABG. There were no differences in the rates of major adverse events between the groups, but

there were more episodes of hypoglycemia in the tight-control group (NNH, 1.6) (19).

• A 2002 narrative review of corticosteroid supplementation for adrenal insufficiency noted that

major surgery is associated with increased levels of stress and requires more intensive steroid

supplementation than less stressful procedures (23).

Rationale

• Different surgical procedures have varying levels of risk with respect to stress, DVT, endocarditis,

bleeding, and wound infection.

Comments

• A patient on chronic anticoagulation with warfarin may require “bridging therapy” before a

procedure associated with a high risk for thromboembolism, as opposed to just discontinuing it

several days before a low-risk procedure (24).

http://journal.publications.chestnet.org/article.aspx?articleid=1159399

http://circ.ahajournals.org/content/116/17/1971.full.pdf




of 74

2.3 Use lab testing preoperatively to measure drug levels, assess potential

drug toxicity, and assess control of a disease.

Recommendations

• Measure drug levels to assess adherence and efficacy when indicated for seizures, arrhythmias, or

other chronic illness.

• Obtain drug levels when toxicity is suspected.

• Obtain liver or kidney function tests for potentially hepatotoxic or nephrotoxic drugs.

• Obtain glucose levels perioperatively to assess control of diabetes and adjust therapy.

• Obtain thyroid function tests (TSH, T4) preoperatively to assess thyroid status if significant

hyperthyroidism or hypothyroidism is suspected.

• See table Laboratory and Other Studies for Drug Prescribing in the Surgical Patient.

Evidence

• Consensus.

Rationale

• Knowledge of drug levels may be useful, especially when adherence needs to be confirmed or

toxicity is suspected.

• Drug absorption, distribution, metabolism, and elimination may be altered by anesthesia or

analgesic drugs; therefore, dose, frequency, and mode of administration may need to be adjusted

to achieve therapeutic and avoid toxic levels.

• Uncontrolled diabetes is associated with poor wound healing, and more intensive therapy may

decrease morbidity.

• Untreated hyperthyroidism may be related to the development of thyroid storm perioperatively.

Comments

• Some of the lab tests may need to be monitored both intraoperatively (glucose) and

postoperatively (glucose, BUN/creatinine, potassium, certain drug levels), as well as

preoperatively.



of 74

3. Consultation Top

Consider consultation with all physicians involved in patients' care to define their medical condition and prescription medication needs. Consult appropriate medical subspecialists for help in managing perioperative medication use.

3.1 Discuss underlying medical conditions, the need for current medication or

alternatives, and an anesthetic plan with the anesthesiologist and the patient's primary and specialist physicians.

Recommendations

• Consult the patient's physician to obtain detailed information about medical problems and

medications and to ascertain whether a particular drug may be indicated or contraindicated.

• Consider a medical subspecialty and/or anesthesiology consultation if there are questions about a

patient's fitness for surgery, need for further diagnostic tests before surgery, or need to modify

medications.

Evidence

• Mainly consensus.

• A 2003 narrative review discussed interactions between anesthetic agents and other drugs (25).

Rationale

• More information regarding the stability and severity of the patient's disease may be needed to

decide on the use or modification of specific drugs.

• The anesthesiologist should be aware of the patient's medications and the potentially important

drug interactions with anesthetics.

3.2 Consult medical subspecialists to help determine the benefits and risks of stopping a medication before surgery, identify possible safer alternatives, or

start medications in the perioperative period.

Recommendations

• Consult specialists as needed and ensure communication among all consultants.

• Consider consultation with a cardiologist:

To manage chronic anticoagulation in patients with heart disease

To determine the need for specific therapy in patients with risk factors for CAD

To treat perioperative arrhythmias

To manage antiplatelet agents in patients with recent stents

• Consider consultation with a nephrologist to adjust medications in patients with chronic or acute

kidney disease.

• Consider consultation with a neurologist:

To manage antiepileptic medications

To optimize the timing of antiplatelet therapy in patients with cerebrovascular disease

• Consider consultation with an endocrinologist:

For help with the perioperative management of insulin or oral hypoglycemic agents in patients with diabetes



of 74

To advise regarding stress-dose steroids

Evidence

• Consensus.

Rationale

• Medical specialists may be helpful in making a decision about withholding a medication in the

perioperative period.

• Treatment of a condition after surgery may be different from that in the nonsurgical setting.

Comments

• It is important to consult with the anesthesiologist about agents used in the operating room and

the surgeon about the extent and complications of a given procedure to determine implications for

medication management.

• A 2013 Cochrane review of computerized drug-dosage advice found some benefits in

anticoagulation dosing and the correct administration of some antibiotics (26).



of 74

4. Hospitalization Top

Consider hospitalization for serious comorbid illness or preoperative adjustment of specific medical regimens that would be difficult to perform on an outpatient basis.

4.1 Consider hospitalization to adjust perioperative medication in patients

with severe comorbid illness or drug toxicity.

Recommendations

• Consider hospitalization preoperatively for:

Anticoagulant “bridge therapy” with warfarin to heparin or LMWH

Toxicity with warfarin, digoxin, or other drugs requiring monitoring

Uncontrolled diabetes (diabetic ketoacidosis/hyperosmolar state) for intravenous insulin

Bowel prep in an elderly, debilitated patient to minimize risk for dehydration

Detoxification of an alcoholic or drug abuser

Instituting certain antiarrhythmic therapy

Abrupt discontinuation of a drug that may trigger an exacerbation of a chronic illness, such as asthma, arrhythmia, or seizure

New illness or exacerbation of a chronic illness (pneumonia, COPD, angina) requiring inpatient observation, monitoring, or treatment not available in the outpatient setting

Evidence

• Consensus.

Rationale

• Certain regimens are difficult or impossible to follow at home due to the nature of the regimen

itself, potential side effects, or the lack of finances or drug coverage to obtain the medication as an

outpatient.



of 74

5. Therapy Top

Continue or institute drug therapy when there is clear diagnostic indication after thorough risk-benefit assessment and discussion with the patient, and discontinue or adjust medications that may have potentially adverse effects. Consider the use of non-drug therapy whenever possible to minimize the potential for drug interactions or adverse effects.

5.1 Continue necessary therapies for chronic medical problems.

Recommendations

• Continue current medications perioperatively unless they are likely to have an adverse effect or

significant drug interactions.

• Consider necessary dose adjustments mandated by anesthesia or surgery.

• In patients with diabetes:

Hold metformin for 1 or more days before surgery

Advise patients on other oral medications to continue them up until the morning of surgery

Plan to use dextrose-containing intravenous solutions in patients who have been on sulfonylureas

Never withhold basal insulin

In patients receiving insulin, adjust insulin dosage before the surgical procedure to avoid hypoglycemia

• In patients with hypertension:

Continue β-blockers, clonidine, and calcium-channel blockers in the preoperative period, including on the day of surgery

Discontinue ACE inhibitors, ARBs, and diuretics on the morning of surgery if possible

• Consult established guidelines and carefully consider need for bridging anticoagulant therapy

depending on risk for thromboembolic events.

• Provide appropriate prophylaxis as indicated to prevent DVT, endocarditis, ischemia, and wound

infection.

• Discuss the need for a given drug with the patient.

• See table Perioperative Cardiovascular Medication Management.

• See table Perioperative Rheumatologic Medication Management.

• See table Perioperative Pulmonary Medication Management.

• See table Perioperative Endocrine Medication Management.

• See table Perioperative Neurologic Medication Management.

• See table Perioperative Psychiatric Medication Management.

• See table Perioperative Gastrointestinal Medication Management.

• See table Perioperative HIV Medication Management.

• See table Perioperative Herbal Medication Management.


• See module Perioperative Management of Hypertension.





of 74

Evidence

• A 2012 guideline from the American College of Chest Physicians recommended the use of VTE

prophylaxis for all patients undergoing surgery, with specific interventions dependent upon the

surgical risk (21).

• Withdrawal syndromes after cessation of antihypertensive agents have occurred with β-blockers,

methyldopa, clonidine hydrochloride, guanabenz, and bethanidine sulfate, with signs and

symptoms ranging from nervousness, tachycardia, headache, and nausea to exacerbation of

myocardial ischemia (β-blockers) or hypertension (clonidine, methyldopa) in the post-treatment

period (27).

Rationale

• Specific medications are necessary to control various medical conditions.

• Prophylactic medications can reduce perioperative morbidity and mortality.

• Adherence will be improved if the patient understands how the medications are to be taken

perioperatively, especially if it differs from the usual regimen, and the importance of the drug

therapy and the risk of withholding treatment.

Comments

• Abrupt discontinuation of clonidine resulted in 14 of 14 patients developing excessive increases in

heart rate and BP and 7 of 14 having subjective symptoms (28).

• After clonidine withdrawal, both systolic and diastolic blood pressures increased to values

significantly greater than during clonidine administration (29).

• β-blocker discontinuation after vascular surgery was associated with increased cardiovascular

mortality (0% vs. 25%, P=0.005) and postoperative MI in 8 patients who discontinued β-blockers

postoperatively compared with 132 patients who continued β-blockers (16).

5.2 Adjust drug doses or substitute drugs as needed in the perioperative setting.

Recommendations

• Adjust doses as necessary to maintain therapeutic levels of crucial drugs (e.g., phenytoin and

theophylline) and avoid toxicity.

• Withhold or discontinue medications (e.g., anticoagulants or oral hypoglycemic agents) with

significant potential for adverse events.

• Consider alternative drugs (longer acting or of a related class) or routes of administration

(intravenous or transdermal for nitrates or clonidine if NPO) when necessary.

• Be aware of potential drug interactions when prescribing additional medications, especially with

drugs that have a low therapeutic index (e.g., warfarin, digoxin, or hypoglycemic agents).












of 74


Evidence

• A 2005 systematic review of warfarin interactions with drugs and foods included 181 studies, of

which 84% were of poor quality, mostly case reports. Most interactions (72%) potentiated the

effects of warfarin. The review presented a long list of culprit medications (30).

• A randomized trial compared insulin plus metformin to insulin alone in 200 postoperative patients

with diabetes who had undergone CABG. The primary outcome was levels of lactate. After 2.5

days, lactate levels did not differ between the groups and no patient in either group developed

lactic acidosis (31).

• A 2003 narrative review discussed interactions between anesthetic agents and other drugs (25).

Rationale

• Anesthetic agents may alter hepatic metabolism and renal excretion.

• Surgical patients may be NPO for several days and, therefore, unable to take their usual

medications orally.

• Medications may potentiate the effects of anesthetic or analgesic drugs.

• Continuation of these medications may have a more deleterious effect on surgical outcome than

their withdrawal would on the underlying disease.

• Patients on multiple medications are at risk for multiple-drug interactions that may be additive,

antagonistic, or difficult to predict.

5.3 Start new medications prophylactically when appropriate to minimize risk for DVT, endocarditis, wound infection, myocardial ischemia, or gastric

aspiration.

Recommendations

• Provide DVT prophylaxis to all patients undergoing surgery, and choose a specific strategy based

on risk stratification:

Consider both drug and mechanical measures in prescribing prophylactic regimens for all patients undergoing surgery

Base the choice of VTE prophylaxis on risk factors associated with the procedure, patient comorbidities,

and bleeding risk

Closely monitor perioperative patients for complications of VTE prophylaxis

Determine the appropriate duration of VTE prophylaxis

• Provide endocarditis prophylaxis to patients with:

Prosthetic valves

Complex congenital heart disease (not repaired or repaired within the past 6 months)

Previous endocarditis

Heart transplant with valvular heart disease

Patients undergoing specific dental and upper respiratory tract procedures

• Consider perioperative β-blockade titrated to heart rate and BP:

For patients undergoing vascular surgery who are known to have CAD or ischemia on preoperative testing

or who are at high risk for cardiac complications

For some patients undergoing intermediate-risk surgery who are known to have CAD or who are at high risk for cardiac complications

In patients already receiving β-blockers for the treatment of other conditions

http://archinte.jamanetwork.com/article.aspx?articleid=486574



of 74

• Provide prophylaxis for surgical wound infection for most procedures, including major intra-

abdominal, intrathoracic, intracranial, and vascular surgery.

• Provide gastric aspiration prophylaxis for morbidly obese or pregnant patients.

• See table VTE Prophylaxis Regimens by Surgical Procedure.










Evidence

• A 2012 guideline from the American College of Chest Physicians recommended the use of VTE

prophylaxis for all patients undergoing surgery, with specific interventions dependent upon the

surgical risk (21).

• A 2011 guideline from the American Society of Anesthesiologists on preoperative fasting and the

use of drug agents to reduce the risk for pulmonary aspiration recommended against the routine

use of gastric acid blockers in surgical patients. The guideline did not address the use of

medications in patients at increased risk for aspiration (32).

• The 2009 update of the 2007 ACC/AHA guidelines on perioperative cardiac evaluation

recommended continuing β-blockers in patients who are already receiving them and considering β-

blockers in patients at high risk for cardiac complications or those undergoing high-risk surgery

(33).

• A 2008 guideline from the ACC/AHA recommended prophylaxis only for patients at increased risk

for bacteremia and with increased risk for infective endocarditis, with amoxicillin as the first-line

agent for most patients requiring dental prophylaxis (34).




and an increase in nonfatal stroke (NNH, 293) (14).

• A 2012 review of antimicrobial prophylaxis in surgery was published in The Medical Letter (35).

Rationale

• Surgical patients are potentially at risk for complications that can be minimized by appropriate

prophylaxis.

5.4 Substitute non-drug alternatives if appropriate.

Recommendations

• Discontinue medications used to treat benign or self-limited symptoms.

• Avoid medications in the perioperative setting if there are non-drug alternatives.

Consider using hot or cold packs instead of analgesics or anti-inflammatory drugs for pain or arthralgias


http://journals.lww.com/anesthesiology/Fulltext/2011/03000/Practice_Guidelines_for_Preoperative_Fasting_and.13.aspx

http://content.onlinejacc.org/article.aspx?articleid=1140211

http://circ.ahajournals.org/content/118/15/e523.long




of 74

Consider intermittent pneumatic compression instead of heparin for DVT prophylaxis to avoid potential

bleeding problems or if anticoagulants are contraindicated

• If time permits, initiate diet and lifestyle changes before surgery to minimize the use of

antihypertensive, hypoglycemic, or lipid-lowering medications.

• Provide patient education and reassurance to decrease anxiety and sedative requirements.

Evidence

• Consensus.

Rationale

• Alternative modalities may be less likely to cause adverse effects.



of 74

6. Patient Counseling Top

Involve patients in decision making with respect to medication use in surgery, especially when controversy exists or there are several alternatives.

6.1 Explain to the patient the potential harms vs. benefits of any medication

prescribed perioperatively.

Recommendations

• Discuss the harms and benefits of any medication proposed, prescribed, or withheld in the

perioperative period.

• Discuss the plan for continuing or restarting medications postoperatively or after discharge.

Evidence

• Consensus.

Rationale

• Patients should understand the reasons for taking or stopping their medications or for substituting

other non-drug therapies when available.

6.2 Review with the patient any medications that should be discontinued or have dose adjustments before surgery.

Recommendations

• Inform patients of medications that should be discontinued more than 24 hours before surgery:

MAO inhibitors

Chlorpropamide

Warfarin

Newer oral anticoagulants (dabigatran, rivaroxaban, apixaban)

Antiplatelet agents (depending on indication and surgical procedure)

NSAIDs (depending on half-life)

Metformin (for radiocontrast procedures only)

Herbal medications

• Review the list of medications that should be discontinued within 24 hours of surgery:

Oral hypoglycemics (including metformin)

Some NSAIDs

Heparin

Diuretics (optional)

ACE inhibitors and ARBs (optional, depending on indication and blood pressure)

• Review the list of medications that may need modification of dosage perioperatively:

Insulin

Corticosteroids

• Discuss the importance of adherence to a preoperative medication regimen.

• Discuss the rationale behind the use of prophylactic medications, including harms, benefits, and

options.

Evidence



of 74

• Consensus.

Rationale

• Patient participation in perioperative medication management is crucial to successful outcome and

minimization of adverse events.



of 74

7. Follow-up Top

Recognize that medication use in the perioperative period requires ongoing assessment, patient education, and dosage adjustments.

7.1 Adjust medication doses as dictated by perioperative circumstances.

Recommendations

• Review the intraoperative anesthetic record for agents used and evidence of hypotension.

• Monitor medication levels and adjust doses during the perioperative period.

Adjust medication dosing based on perioperative renal insufficiency

Adjust medication dosing based on perioperative hepatic dysfunction

Monitor blood glucose and oral intake in patients with diabetes


• See module Perioperative Management of Patients with Liver Disease.

Evidence

• A 1994 narrative review discussed the effect of anesthetic agents on renal function, noting that

inhalational anesthetics, opioids, barbiturates, and benzodiazepines may reduce glomerular

filtration rate and urine output (36).

• A cross-sectional study compared renal and hepatic function after the administration of sevoflurane

and isoflurane in patients undergoing surgery who had normal baseline renal function. There were

no differences between the anesthetic agents (37).

Rationale

• Various medications and hypotension may alter renal blood flow and thereby warrant dosage

alterations in the postoperative period.

• Various anesthetics and hypotension may alter hepatic blood flow, particularly in patients with

underlying hepatic dysfunction, and thereby warrant medication adjustments postoperatively.

Comments

• The etiology of postoperative renal and hepatic dysfunction is multifactorial and often related to

factors other than a specific anesthetic agent. Hypotension, preexisting renal or hepatic

dysfunction, aminoglycosides, and type of surgery have all been implicated as risk factors.

7.2 Use alternative agents or routes of administration as necessary.

Recommendations

• Consider alternatives to oral or enteral medications in patients who are NPO or have decreased

bowel function postoperatively.

• Use intravenous preparations of the medication, if available, or a different drug in the same class.

Evidence

• Consensus.

Rationale

• Patients may not be able to take their usual medications postoperatively.

• Postoperative ileus may result in decreased absorption of medication.

• After GI or major abdominal surgery, patients are unable to take medications orally and may

require a parenteral substitute until GI function returns.





of 74

• The patient may experience decompensation or exacerbation of various cardiovascular conditions if

medications (or substitutes) are not continued.

7.3 Continue prophylactic medication (such as anticoagulants), β-blockers,

and antibiotics postoperatively as appropriate.

Recommendations

• Continue DVT prophylaxis until the patient is ambulatory or discharged, or no longer depending on

the procedure.

• Continue perioperative β-blockers, if used, beyond discharge in most patients.

• Consider giving an additional dose of antibiotics for surgical wound prophylaxis for a long surgical

procedure.

Evidence

• A 2012 guideline from the American College of Chest Physicians recommended DVT prophylaxis

until the patient is ambulatory and, in major orthopedic surgery, for a minimum of 10 to 14 days

and possibly extended prophylaxis for up to 35 days (38).

• A 2012 review from The Medical Letter on antimicrobial prophylaxis for surgery recommended

intraoperative repeat antibiotic dosing during procedures lasting longer than 3 hours, at intervals of

one to two times the half-life of the antibiotic (35).

Rationale

• Ongoing risk for DVT is based on patient and procedural factors.

• Patients who are candidates for perioperative β-blockers also have indications for long-term

therapy.

• If the duration of surgery was longer than 4 hours, the initial dose of antibiotics may be insufficient

prophylaxis.

7.4 Remember to restart necessary medications that were stopped

preoperatively to minimize potential complications.

Recommendations

• Watch for:

Hyperglycemia if insulin or hypoglycemic medications were stopped before surgery, and slowly reintroduce them as the patient resumes oral feeding

Evidence of thromboembolism if anticoagulation was stopped or reduced preoperatively, and restart anticoagulants and antiplatelet agents when the surgeon feels there is no significant risk for bleeding

Evidence of heart failure if diuretics or ACE inhibitors were discontinued preoperatively, and restart them as soon as possible postoperatively

• Restart medications for underlying conditions as soon as possible after surgery, substituting

parenteral dosage forms if needed if the patient cannot take oral medications.

Evidence

• Consensus.

Rationale

• Glucose levels will increase due to the stress of surgery, dextrose-containing intravenous fluids,

and increasing oral intake.

• The risk for an embolic or thrombotic event will decrease if the “unprotected period” off

anticoagulation or antiplatelet therapy is minimized; however, the risk for postoperative bleeding

may be increased if anticoagulation is resumed too quickly.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278063/



of 74

• Without their usual medications, some patients with left ventricular dysfunction may decompensate

in the perioperative period.

new



of 74

References Top

1. Lau HS, Florax C, Porsius AJ, De Boer A. The completeness of medication histories in hospital medical records of patients

admitted to general internal medicine wards. Br J Clin Pharmacol. 2000;49:597-603. (PMID: 10848724)

2. Bedell SE, Jabbour S, Goldberg R, Glaser H, Gobble S, Young-Xu Y, et al. Discrepancies in the use of medications: their extent and predictors in an outpatient practice. Arch Intern Med. 2000;160:2129-34. (PMID: 10904455)

3. Yang JC, Tomlinson G, Naglie G. Medication lists for elderly patients: clinic-derived versus in-home inspection and interview. J Gen Intern Med. 2001;16:112-5. (PMID: 11251762)

new

4. Ma X, Ma C, Yun Y, Zhang Q, Zheng X. Safety and efficacy outcomes of preoperative aspirin in patients undergoing coronary artery bypass grafting: a systematic review and meta-analysis. J Cardiovasc Pharmacol Ther. 2014;19:97-113. (PMID: 24212980)

5. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA. 2001;286:208-16. (PMID: 11448284)

6. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61:2163-75. (PMID: 11772128)

new

7. Lee A, Chui PT, Aun CS, Lau AS, Gin T. Incidence and risk of adverse perioperative events among surgical patients taking traditional Chinese herbal medicines. Anesthesiology. 2006;105:454-61. (PMID: 16931976)

8. Leung JM, Dzankic S, Manku K, Yuan S. The prevalence and predictors of the use of alternative medicine in presurgical patients in five California hospitals. Anesth Analg. 2001;93:1062-8. (PMID: 11574384)

9. Tsen LC, Segal S, Pothier M, Bader AM. Alternative medicine use in presurgical patients. Anesthesiology. 2000;93:148-51. (PMID: 10861158)

10. Skinner CM, Rangasami J. Preoperative use of herbal medicines: a patient survey. Br J Anaesth. 2002;89:792-5. (PMID: 12393786)

11. Adusumilli PS, Ben-Porat L, Pereira M, Roesler D, Leitman IM. The prevalence and predictors of herbal medicine use in surgical patients. J Am Coll Surg. 2004;198:583-90. (PMID: 15051013)

12. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57:1221-7; quiz 1228-30. (PMID: 10902065)

new

13. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof EL, Chaikof E, et al.; Society for Vascular Surgery. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. J Am Coll Cardiol. 2007;50:e159-241. (PMID: 17950140)

new

14. Bangalore S, Wetterslev J, Pranesh S, Sawhney S, Gluud C, Messerli FH. Perioperative beta blockers in patients having non-cardiac surgery: a meta-analysis. Lancet. 2008;372:1962-76. (PMID: 19012955)

new

15. McColl RJ, Dixon E. ACP Journal Club. Review: Perioperative beta-blockers provide no clear benefit in patients having noncardiac surgery. Ann Intern Med. 2009;150:JC3-4. [Full Text] (PMID: 19306485)

16. Shammash JB, Trost JC, Gold JM, Berlin JA, Golden MA, Kimmel SE. Perioperative beta-blocker withdrawal and mortality in vascular surgical patients. Am Heart J. 2001;141:148-53. (PMID: 11136500)

new

17. Wilson SJ, Sexton DJ. Elevated preoperative fasting serum glucose levels increase the risk of postoperative mediastinitis in patients undergoing open heart surgery. Infect Control Hosp Epidemiol. 2003;24:776-8. (PMID: 14587944)

http://www.ncbi.nlm.nih.gov/pubmed?term=10848724














http://annals.org/article.aspx?volume=150&issue=6&page=JC3






of 74

new

18. Desai SP, Henry LL, Holmes SD, Hunt SL, Martin CT, Hebsur S, et al. Strict versus liberal target range for perioperative glucose in patients undergoing coronary artery bypass grafting: a prospective randomized controlled trial. J Thorac Cardiovasc Surg. 2012;143:318-25. (PMID: 22137804)

new

19. Lazar HL, McDonnell MM, Chipkin S, Fitzgerald C, Bliss C, Cabral H. Effects of aggressive versus moderate glycemic control on clinical outcomes in diabetic coronary artery bypass graft patients. Ann Surg. 2011;254:458-63; discussion 463-4. (PMID: 21865944)

new

20. Wahr JA, Parks R, Boisvert D, Comunale M, Fabian J, Ramsay J, et al. Preoperative serum potassium levels and perioperative outcomes in cardiac surgery patients. Multicenter Study of Perioperative Ischemia Research Group. JAMA. 1999;281:2203-10. (PMID: 10376573)

21. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:7S-47S. (PMID: 22315257)

new

22. Gupta PK, Gupta H, Sundaram A, Kaushik M, Fang X, Miller WJ, et al. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circulation. 2011;124:381-7. (PMID: 21730309)

23. Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287:236-40. (PMID: 11779267)

24. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med. 1997;336:1506-11. (PMID: 9154771)

25. Goldstein S, Amar D. Pharmacotherapeutic considerations in anesthesia. Heart Dis. 2003;5:34-48. (PMID: 12549987)

new

26. Gillaizeau F, Chan E, Trinquart L, Colombet I, Walton RT, Rège-Walther M, et al. Computerized advice on drug dosage to improve prescribing practice. Cochrane Database Syst Rev. 2013;(11):CD002894. (PMID: 24218045)

new

27. Hart GR, Anderson RJ. Withdrawal syndromes and the cessation of antihypertensive therapy. Arch Intern Med. 1981;141:1125-7. (PMID: 6114720)

new

28. Geyskes GG, Boer P, Dorhout Mees EJ. Clonidine withdrawal. Mechanism and frequency of rebound hypertension. Br J Clin Pharmacol. 1979;7:55-62. (PMID: 760743)

new

29. Neusy AJ, Lowenstein J. Blood pressure and blood pressure variability following withdrawal of propranolol and clonidine. J Clin Pharmacol. 1989;29:18-24. (PMID: 2708545)

new

30. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165:1095-106. (PMID: 15911722)

new

31. Baradari AG, Habibi MR, Khezri HD, Aarabi M, Khademloo M, Jalali Z, et al. Does high-dose metformin cause lactic acidosis in type 2 diabetic patients after CABG surgery? A double blind randomized clinical trial. Heart Int. 2011;6:e8. (PMID: 21977308)

new

















of 74

32. American Society of Anesthesiologists Committee. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures: an updated

report by the American Society of Anesthesiologists Committee on Standards and Practice Parameters. Anesthesiology. 2011;114:495-511. (PMID: 21307770)

new

33. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof EL, Fleischmann KE, et al.; Society for Vascular Surgery. 2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. J Am Coll Cardiol. 2009;54:e13-e118. (PMID: 19926002)

new

34. Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD, et al.; American College of Cardiology/American Heart Association Task Force. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008;118:e523-661. (PMID: 18820172)

new

35. Antimicrobial prophylaxis for surgery. Treat Guidel Med Lett. 2012;10:73-8; quiz 79-80. (PMID: 22996382)

36. Burchardi H, Kaczmarczyk G. The effect of anaesthesia on renal function. Eur J Anaesthesiol. 1994;11:163-8. (PMID: 8050420)

37. Kharasch ED, Frink EJ Jr, Artru A, Michalowski P, Rooke GA, Nogami W. Long-duration low-flow sevoflurane and isoflurane effects on postoperative renal and hepatic function. Anesth Analg. 2001;93:1511-20, table of contents. (PMID: 11726433)

new

38. Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al.; American College of Chest Physicians. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e278S-325S. (PMID: 22315265)

new

39. Dai N, Xu D, Zhang J, Wei Y, Li W, Fan B, et al. Different β-blockers and initiation time in patients undergoing noncardiac surgery: a meta-analysis. Am J Med Sci. 2014;347:235-44. (PMID: 23588263)

new

40. Landoni G, Turi S, Biondi-Zoccai G, Bignami E, Testa V, Belloni I, et al. Esmolol reduces perioperative ischemia in noncardiac surgery: a meta-analysis of randomized controlled studies. J Cardiothorac Vasc Anesth. 2010;24:219-29. (PMID: 19800816)

new

41. Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med. 2005;353:349-61. (PMID: 16049209)

new

42. Ashes C, Judelman S, Wijeysundera DN, Tait G, Mazer CD, Hare GM, et al. Selective β1-antagonism with bisoprolol is associated with fewer postoperative strokes than atenolol or metoprolol: a single-center cohort study of 44,092 consecutive patients. Anesthesiology. 2013;119:777-87. (PMID: 23820187)

new

43. Wallace AW, Au S, Cason BA. Perioperative β-blockade: atenolol is associated with reduced mortality when compared to metoprolol. Anesthesiology. 2011;114:824-36. (PMID: 21372680)

new

44. Flu WJ, van Kuijk JP, Chonchol M, Winkel TA, Verhagen HJ, Bax JJ, et al. Timing of pre-operative Beta-blocker treatment in vascular surgery patients: influence on post-operative outcome. J Am Coll Cardiol. 2010;56:1922-9. (PMID: 21109115)
















of 74

new

45. Wijeysundera DN, Beattie WS. Calcium channel blockers for reducing cardiac morbidity after noncardiac surgery: a meta-analysis. Anesth Analg. 2003;97:634-41. (PMID: 12933374)

new

46. Malhotra R, Mishra M, Kler TS, Kohli VM, Mehta Y, Trehan N. Cardioprotective effects of diltiazem infusion in the perioperative period. Eur J Cardiothorac Surg. 1997;12:420-7. (PMID: 9332921)

new

47. Seitelberger R, Hannes W, Gleichauf M, Keilich M, Christoph M, Fasol R. Effects of diltiazem on perioperative ischemia, arrhythmias, and myocardial function in patients undergoing elective coronary bypass grafting. J Thorac Cardiovasc Surg. 1994;107:811-21. (PMID: 8127110)

new

48. Donegani E, Costa P, De Paulis R, di Summa M, Poletti GA, Pignatelli MG, et al. Myocardial protection by perioperative diltiazem drip: a clinical evaluation. Thorac Cardiovasc Surg. 1986;34:168-71. (PMID: 2426830)

new

49. Hannes W, Fasol R, Zajonc H, Schindler M, Schumacher B, Schlosser V, et al. Diltiazem provides anti-ischemic and anti-arrhythmic protection in patients undergoing coronary bypass grafting. Eur J Cardiothorac Surg. 1993;7:239-45. (PMID: 8517952)

new

50. el-Sadek M, Krause E. Postoperative antiarrhythmic effects of diltiazem in patients undergoing coronary bypass grafting. Cardiology. 1994;85:290-7. (PMID: 7850818)

new

51. Zanardo G, Michielon P, Rosi P, Teodori T, Antonucci F, Caenaro G, et al. Effects of a continuous diltiazem infusion on renal function during cardiac surgery. J Cardiothorac Vasc Anesth. 1993;7:711-6. (PMID: 8305662)

new

52. Seitelberger R, Zwölfer W, Huber S, Schwarzacher S, Binder TM, Peschl F, et al. Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. Circulation. 1991;83:460-8. (PMID: 1899365)

new

53. Jenkins LC, Scoates PJ. Anaesthetic implications of calcium channel blockers. Can Anaesth Soc J. 1985;32:436-47. (PMID: 2862980)

new

54. Engelman RM, Hadji-Rousou I, Breyer RH, Whittredge P, Harbison W, Chircop RV. Rebound vasospasm after coronary revascularization in association with calcium antagonist withdrawal. Ann Thorac Surg. 1984;37:469-72. (PMID: 6732337)

new

55. Gottlieb SO, Ouyang P, Achuff SC, Baughman KL, Traill TA, Mellits ED, et al. Acute nifedipine withdrawal: consequences of preoperative and late cessation of therapy in patients with prior unstable angina. J Am Coll Cardiol. 1984;4:382-8. (PMID: 6376596)

new

56. Sear JW, Howell SJ, Sear YM, Yeates D, Goldacre M, Foex P. Intercurrent drug therapy and perioperative cardiovascular mortality in elective and urgent/emergency surgical patients. Br J Anaesth. 2001;86:506-12. (PMID: 11573623)

new















of 74

57. Dodds TM, Stone JG, Coromilas J, Weinberger M, Levy DG. Prophylactic nitroglycerin infusion during noncardiac surgery does not reduce perioperative ischemia. Anesth Analg. 1993;76:705-13. (PMID: 8466005)

new

58. Yousif H, Davies G, Westaby S, Prendiville OF, Sapsford RN, Oakley CM. Preoperative myocardial ischaemia: its relation to perioperative infarction. Br Heart J. 1987;58:9-14. (PMID: 3304371)

new

59. Wijeysundera DN, Naik JS, Beattie WS. Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: a meta-analysis. Am J Med. 2003;114:742-52. (PMID: 12829201)

new

60. Nishina K, Mikawa K, Uesugi T, Obara H, Maekawa M, Kamae I, et al. Efficacy of clonidine for prevention of perioperative myocardial ischemia: a critical appraisal and meta-analysis of the literature. Anesthesiology. 2002;96:323-9. (PMID: 11818763)

new

61. Yacoub R, Patel N, Lohr JW, Rajagopalan S, Nader N, Arora P. Acute kidney injury and death associated with renin angiotensin system blockade in cardiothoracic surgery: a meta-analysis of observational studies. Am J Kidney Dis. 2013;62:1077-86. (PMID: 23791246)

new

62. Rosenman DJ, McDonald FS, Ebbert JO, Erwin PJ, LaBella M, Montori VM. Clinical consequences of withholding versus administering renin-angiotensin-aldosterone system antagonists in the preoperative period. J Hosp Med. 2008;3:319-25. (PMID: 18698608)

new

63. Hasija S, Makhija N, Choudhury M, Hote M, Chauhan S, Kiran U. Prophylactic vasopressin in patients receiving the angiotensin-converting enzyme inhibitor ramipril undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth.

2010;24:230-8. (PMID: 19875309)

new

64. Kheterpal S, Khodaparast O, Shanks A, O’Reilly M, Tremper KK. Chronic angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy combined with diuretic therapy is associated with increased episodes of hypotension in noncardiac surgery. J Cardiothorac Vasc Anesth. 2008;22:180-6. (PMID: 18375317)

new

65. Drenger B, Fontes ML, Miao Y, Mathew JP, Gozal Y, Aronson S, et al.; Multicenter Study of Perioperative Ischemia Research Group. Patterns of use of perioperative angiotensin-converting enzyme inhibitors in coronary artery bypass graft surgery with cardiopulmonary bypass: effects on in-hospital morbidity and mortality. Circulation. 2012;126:261-9. (PMID: 22715473)

new

66. Behnia R, Molteni A, Igić R. Angiotensin-converting enzyme inhibitors: mechanisms of action and implications in anesthesia

practice. Curr Pharm Des. 2003;9:763-76. (PMID: 12570793)

new

67. Khan NA, Campbell NR, Frost SD, Gilbert K, Michota FA, Usmani A, et al. Risk of intraoperative hypotension with loop diuretics: a randomized controlled trial. Am J Med. 2010;123:1059.e1-8. (PMID: 21035594)

new

68. Polanczyk CA, Goldman L, Marcantonio ER, Orav EJ, Lee TH. Supraventricular arrhythmia in patients having noncardiac surgery: clinical correlates and effect on length of stay. Ann Intern Med. 1998;129:279-85. [Full Text] (PMID: 9729180)

new












http://annals.org/article.aspx?volume=129&issue=4&page=279




of 74

69. Amar D, Roistacher N, Burt ME, Rusch VW, Bains MS, Leung DH, et al. Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy. Ann Thorac Surg. 1997;63:1374-81; discussion 1381-2. (PMID: 9146330)

new

70. Parker FB, Greiner-Hayes C, Bove EL, Marvasti MA, Johnson LW, Eich RH. Supraventricular arrhythmias following coronary artery bypass. The effect of preoperative digitalis. J Thorac Cardiovasc Surg. 1983;86:594-600. (PMID: 6353078)

new

71. Yazicioglu L, Eryilmaz S, Sirlak M, Inan MB, Aral A, Tasoz R, et al. The effect of preoperative digitalis and atenolol combination on postoperative atrial fibrillation incidence. Eur J Cardiothorac Surg. 2002;22:397-401. (PMID: 12204730)

new

72. Böhm M, Maack C, Wehrlen-Grandjean M, Erdmann E. Effect of bisoprolol on perioperative complications in chronic heart failure after surgery (Cardiac Insufficiency Bisoprolol Study II (CIBIS II)). Z Kardiol. 2003;92:668-76. (PMID: 12955414)

new

73. Karachalios GN, Charalabopoulos A, Papalimneou V, Kiortsis D, Dimicco P, Kostoula OK, et al. Withdrawal syndrome following cessation of antihypertensive drug therapy. Int J Clin Pract. 2005;59:562-70. (PMID: 15857353)

new

74. Ryu JH, Apfel CC, Whelan R, Jeon YT, Hwang JW, Do SH, et al. Comparative prophylactic and therapeutic effects of intravenous labetalol 0.4 mg/kg and nicardipine 20 μg/kg on hypertensive responses to endotracheal intubation in patients undergoing elective surgeries with general anesthesia: a prospective, randomized, double-blind study. Clin Ther. 2012;34:593-604. (PMID: 22364823)

new

75. Kaukinen S, Kaukinen L, Eerola R. Preoperative and postoperative use of clonidine with neurolept anaesthesia. Acta Anaesthesiol Scand. 1979;23:113-20. (PMID: 442942)

new

76. Bruce DL, Croley TF, Lee JS. Preoperative clonidine withdrawal syndrome. Anesthesiology. 1979;51:90-2. (PMID: 453602)

77. Ulchaker JC, Goldfarb DA, Bravo EL, Novick AC. Successful outcomes in pheochromocytoma surgery in the modern era. J Urol. 1999;161:764-7. (PMID: 10022680)

new

78. Chatziralli IP, Sergentanis TN. Risk factors for intraoperative floppy iris syndrome: a meta-analysis. Ophthalmology. 2011;118:730-5. (PMID: 21168223)

new

79. Cantrell MA, Bream-Rouwenhorst HR, Steffensmeier A, Hemerson P, Rogers M, Stamper B. Intraoperative floppy iris syndrome associated with alpha1-adrenergic receptor antagonists. Ann Pharmacother. 2008;42:558-63. (PMID: 18364408)

80. Davies MJ, Cronin KD, Cowie RW. The prevention of hypertension at intubation. A controlled study of intravenous hydrallazine on patients undergoing intracranial surgery. Anaesthesia. 1981;36:147-51. (PMID: 7011085)

new

81. Brown OW, Brown M. Control of hypertension following carotid endarterectomy. Am Surg. 1986;52:581-4. (PMID: 3777700)

new

82. Aasbo JD, Lawrence AT, Krishnan K, Kim MH, Trohman RG. Amiodarone prophylaxis reduces major cardiovascular morbidity and length of stay after cardiac surgery: a meta-analysis. Ann Intern Med. 2005;143:327-36. [Full Text] (PMID: 16144891)

new


















of 74

83. Mitchell LB, Exner DV, Wyse DG, Connolly CJ, Prystai GD, Bayes AJ, et al. Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial.

JAMA. 2005;294:3093-100. (PMID: 16380589)

new

84. Liberman BA, Teasdale SJ. Anaesthesia and amiodarone. Can Anaesth Soc J. 1985;32:629-38. (PMID: 4075214)

new

85. Wurdeman RL, Mooss AN, Mohiuddin SM, Lenz TL. Amiodarone vs. sotalol as prophylaxis against atrial fibrillation/flutter after heart surgery: a meta-analysis. Chest. 2002;121:1203-10. (PMID: 11948054)

new

86. Sanjuán R, Blasco M, Carbonell N, Jordá A, Núñez J, Martínez-León J, et al. Preoperative use of sotalol versus atenolol for atrial fibrillation after cardiac surgery. Ann Thorac Surg. 2004;77:838-43. (PMID: 14992883)

new

87. Sanders RD, Nicholson A, Lewis SR, Smith AF, Alderson P. Perioperative statin therapy for improving outcomes during and after noncardiac vascular surgery. Cochrane Database Syst Rev. 2013;(7):CD009971. (PMID: 23824754)

new

88. Liakopoulos OJ, Kuhn EW, Slottosch I, Wassmer G, Wahlers T. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev. 2012;:CD008493. (PMID: 22513959)

new

89. Winchester DE, Wen X, Xie L, Bavry AA. Evidence of pre-procedural statin therapy a meta-analysis of randomized trials. J Am Coll Cardiol. 2010;56:1099-109. (PMID: 20825761)

new

90. Neilipovitz DT, Bryson GL, Taljaard M. STAR VaS--Short Term Atorvastatin Regime for Vasculopathic Subjects: a randomized placebo-controlled trial evaluating perioperative atorvastatin therapy in noncardiac surgery. Can J Anaesth. 2012;59:527-37. (PMID: 22528165)

new

91. Redelmeier DA, Thiruchelvam D, Daneman N. Delirium after elective surgery among elderly patients taking statins. CMAJ. 2008;179:645-52. (PMID: 18809895)

new

92. Fallouh N, Chopra V. Statin withdrawal after major noncardiac surgery: risks, consequences, and preventative strategies. J Hosp Med. 2012;7:573-9. (PMID: 22744758)

93. Farmer JA, Gotto AM Jr. Antihyperlipidaemic agents. Drug interactions of clinical significance. Drug Saf. 1994;11:301-9. (PMID: 7873090)

new

94. Strebel N, Prins M, Agnelli G, Büller HR. Preoperative or postoperative start of prophylaxis for venous thromboembolism with low-molecular-weight heparin in elective hip surgery? Arch Intern Med. 2002;162:1451-6. (PMID: 12090880)

new

95. Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med. 2004;164:1319-26. (PMID: 15226166)

new
















of 74

96. Jafri SM. Periprocedural thromboprophylaxis in patients receiving chronic anticoagulation therapy. Am Heart J. 2004;147:3-15. (PMID: 14691412)

new

97. Dunn AS, Turpie AG. Perioperative management of patients receiving oral anticoagulants: a systematic review. Arch Intern Med. 2003;163:901-8. (PMID: 12719198)

new

98. Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med. 2002;162:1833-40. (PMID: 12196081)

new

99. Siegal D, Yudin J, Kaatz S, Douketis JD, Lim W, Spyropoulos AC. Periprocedural heparin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation. 2012;126:1630-9. (PMID: 22912386)

new

100. Weitz JI, Eikelboom JW, Samama MM; American College of Chest Physicians. New antithrombotic drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e120S-51S. (PMID: 22315258)

new

101. Ortel TL. Perioperative management of patients on chronic antithrombotic therapy. Hematology Am Soc Hematol Educ Program. 2012;2012:529-35. (PMID: 23233630)

102. Harder S, Klinkhardt U, Alvarez JM. Avoidance of bleeding during surgery in patients receiving anticoagulant and/or antiplatelet therapy: pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet. 2004;43:963-81. (PMID: 15530128)

103. Merritt JC, Bhatt DL. The efficacy and safety of perioperative antiplatelet therapy. J Thromb Thrombolysis. 2004;17:21-7. (PMID: 15277784)

new

104. Tanguay JF, Bell AD, Ackman ML, Bauer RD, Cartier R, Chan WS, et al.; Canadian Cardiovascular Society. Focused 2012 update of the Canadian Cardiovascular Society guidelines for the use of antiplatelet therapy. Can J Cardiol. 2013;29:1334-45. (PMID: 23978596)

new

105. Hall R, Mazer CD. Antiplatelet drugs: a review of their pharmacology and management in the perioperative period. Anesth Analg. 2011;112:292-318. (PMID: 21212258)

new

106. Fitchett D, Mazer CD, Eikelboom J, Verma S. Antiplatelet therapy and cardiac surgery: review of recent evidence and clinical implications. Can J Cardiol. 2013;29:1042-7. (PMID: 23642333)

new

107. Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e89S-119S. (PMID: 22315278)

108. Stein PD, Schunemann HJ, Dalen JE, Gutterman D. Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:600S-608S. (PMID: 15383486)

new
















of 74

109. Oscarsson A, Gupta A, Fredrikson M, Järhult J, Nyström M, Pettersson E, et al. To continue or discontinue aspirin in the perioperative period: a randomized, controlled clinical trial. Br J Anaesth. 2010;104:305-12. (PMID: 20150346)

new

110. Gerstein NS, Schulman PM, Gerstein WH, Petersen TR, Tawil I. Should more patients continue aspirin therapy perioperatively?: clinical impact of aspirin withdrawal syndrome. Ann Surg. 2012;255:811-9. (PMID: 22470078)

new

111. Au AG, Majumdar SR, McAlister FA. Preoperative thienopyridine use and outcomes after surgery: a systematic review. Am J Med. 2012;125:87-99.e1. (PMID: 22079019)

new

112. Saadeh C, Sfeir J. Discontinuation of preoperative clopidogrel is unnecessary in peripheral arterial surgery. J Vasc Surg. 2013;58:1586-92. (PMID: 23891491)

new

113. Chernoguz A, Telem DA, Chu E, Ozao-Choy J, Tammaro Y, Divino CM. Cessation of clopidogrel before major abdominal procedures. Arch Surg. 2011;146:334-9. (PMID: 21422366)

new

114. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al.; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001-15. (PMID: 17982182)

115. Kałuza GL, Joseph J, Lee JR, Raizner ME, Raizner AE. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol. 2000;35:1288-94. (PMID: 10758971)

116. Becquemin JP. Effect of ticlopidine on the long-term patency of saphenous-vein bypass grafts in the legs. Etude de la Ticlopidine après Pontage Fémoro-Poplité and the Association Universitaire de Recherche en Chirurgie. N Engl J Med. 1997;337:1726-31. (PMID: 9392698)

117. Ohtake H, Urayama H, Kimura K, Yokoi K, Tsunezuka Y, Kawakami T, et al. Comparison of cilostazol with warfarin as antithrombotic therapy after femoro-popliteal bypass surgery using an ePTFE graft. Minerva Cardioangiol. 1997;45:527-30. (PMID: 9549283)

118. Sanz G, Pajarón A, Alegría E, Coello I, Cardona M, Fournier JA, et al. Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Español para el Seguimiento del Injerto Coronario (GESIC). Circulation. 1990;82:765-73. (PMID: 2203555)

119. Straube S, Derry S, McQuay HJ, Moore RA. Effect of preoperative Cox-II-selective NSAIDs (coxibs) on postoperative outcomes: a systematic review of randomized studies. Acta Anaesthesiol Scand. 2005;49:601-13. (PMID: 15836672)

120. Fischer LM, Schlienger RG, Matter CM, Jick H, Meier CR. Discontinuation of nonsteroidal anti-inflammatory drug therapy and risk of acute myocardial infarction. Arch Intern Med. 2004;164:2472-6. (PMID: 15596638)

121. Souter AJ, Fredman B, White PF. Controversies in the perioperative use of nonsterodial antiinflammatory drugs. Anesth Analg. 1994;79:1178-90. (PMID: 7978444)

new

122. Ott E, Nussmeier NA, Duke PC, Feneck RO, Alston RP, Snabes MC, et al.; Ischemia Research and Education Foundation (IREF) Investigators. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2003;125:1481-92. (PMID: 12830070)

123. Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis. 2001;60:214-7. (PMID: 11171680)

new

124. Kasdan ML, June L. Postoperative results of rheumatoid arthritis patients on methotrexate at the time of reconstructive surgery of the hand. Orthopedics. 1993;16:1233-5. (PMID: 8290397)

125. Carpenter MT, West SG, Vogelgesang SA, Casey Jones DE. Postoperative joint infections in rheumatoid arthritis patients on methotrexate therapy. Orthopedics. 1996;19:207-10. (PMID: 8867548)




















of 74

126. Bridges SL Jr, Lopez-Mendez A, Han KH, Tracy IC, Alarcon GS. Should methotrexate be discontinued before elective orthopedic surgery in patients with rheumatoid arthritis? J Rheumatol. 1991;18:984-8. (PMID: 1920333)

new

127. Härle P, Straub RH, Fleck M. Perioperative management of immunosuppression in rheumatic diseases--what to do? Rheumatol Int. 2010;30:999-1004. (PMID: 20033813)

new

128. Pieringer H, Danninger K, Tzaribachev N, Böhler N, Pohanka E, Herold M. Patients with arthritis undergoing surgery: how should we manage tumour necrosis factor blocking agents perioperatively? A systematic literature review. Yonsei Med J. 2013;54:253-7. (PMID: 23225828)

129. Dilworth JP, Warley AR, Dawe C, White RJ. The effect of nebulized salbutamol therapy on the incidence of postoperative chest infection in high risk patients. Respir Med. 1994;88:665-8. (PMID: 7809438)

new

130. Silvanus MT, Groeben H, Peters J. Corticosteroids and inhaled salbutamol in patients with reversible airway obstruction

markedly decrease the incidence of bronchospasm after tracheal intubation. Anesthesiology. 2004;100:1052-7. (PMID: 15114199)

new

131. Licker M, Schweizer A, Ellenberger C, Tschopp JM, Diaper J, Clergue F. Perioperative medical management of patients with COPD. Int J Chron Obstruct Pulmon Dis. 2007;2:493-515. (PMID: 18268924)

132. Kil HK, Rooke GA, Ryan-Dykes MA, Bishop MJ. Effect of prophylactic bronchodilator treatment on lung resistance after tracheal intubation. Anesthesiology. 1994;81:43-8. (PMID: 8042809)

133. Su FW, Beckman DB, Yarnold PA, Grammer LC. Low incidence of complications in asthmatic patients treated with preoperative corticosteroids. Allergy Asthma Proc. 2004;25:327-33. (PMID: 15603206)

134. Taitelman U, Reece EA, Bessman AN. Insulin in the management of the diabetic surgical patient: continuous intravenous infusion vs subcutaneous administration. JAMA. 1977;237:658-60. (PMID: 576296)

135. González-Michaca L, Ahumada M, Ponce-de-León S. Insulin subcutaneous application vs. continuous infusion for postoperative blood glucose control in patients with non-insulin-dependent diabetes mellitus. Arch Med Res. 2002;33:48-52. (PMID: 11825631)

136. Furnary AP, Wu Y, Bookin SO. Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project. Endocr Pract. 2004;10 Suppl 2:21-33. (PMID: 15251637)

137. Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, et al. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003;125:1007-21. (PMID: 12771873)

138. Zimmerman CR, Mlynarek ME, Jordan JA, Rajda CA, Horst HM. An insulin infusion protocol in critically ill cardiothoracic surgery patients. Ann Pharmacother. 2004;38:1123-9. (PMID: 15150382)

new

139. Rosenblatt SI, Dukatz T, Jahn R, Ramsdell C, Sakharova A, Henry M, et al. Insulin glargine dosing before next-day surgery:

comparing three strategies. J Clin Anesth. 2012;24:610-7. (PMID: 23122972)

140. McCartney MM, Gilbert FJ, Murchison LE, Pearson D, McHardy K, Murray AD. Metformin and contrast media—a dangerous combination? Clin Radiol. 1999;54:29-33. (PMID: 9915507)

141. Weinberg AD, Brennan MD, Gorman CA, Marsh HM, O’Fallon WM. Outcome of anesthesia and surgery in hypothyroid patients. Arch Intern Med. 1983;143:893-7. (PMID: 6679233)

142. Adlerberth A, Stenström G, Hasselgren PO. The selective beta 1-blocking agent metoprolol compared with antithyroid drug and thyroxine as preoperative treatment of patients with hyperthyroidism. Results from a prospective, randomized study. Ann Surg. 1987;205:182-8. (PMID: 3545108)

143. Vickers P, Garg KM, Arya R, Godha U, Mathur P, Jain S. The role of selective beta 1-blocker in the preoperative preparation of thyrotoxicosis: a comparative study with propranolol. Int Surg. 1990;75:179-83. (PMID: 2242971)

144. Feek CM, Sawers JS, Irvine WJ, Beckett GJ, Ratcliffe WA, Toft AD. Combination of potassium iodide and propranolol in preparation of patients with Graves' disease for thyroid surgery. N Engl J Med. 1980;302:883-5. (PMID: 6892650)






















of 74

new

145. Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. Arch Surg. 2008;143:1222-6. (PMID: 19075176)

146. Kemmeren JM, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. BMJ. 2001;323:131-4. (PMID: 11463678)

new

147. Nelson HD, Walker M, Zakher B, Mitchell J. Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations. Ann Intern Med. 2012;157:104-13. [Full Text] (PMID: 22786830)

new

148. Nelson HD, Smith ME, Griffin JC, Fu R. Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013;158:604-14. [Full Text] (PMID: 23588749)

149. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999;281:2189-97. (PMID: 10376571)

150. Campisi P, Badhwar V, Morin S, Trudel JL. Postoperative hypocalcemic tetany caused by fleet phospho-soda preparation in a patient taking alendronate sodium: report of a case. Dis Colon Rectum. 1999;42:1499-501. (PMID: 10566542)

new

151. Wichards WS, Schobben AF, Leijten FS. Perioperative substitution of anti-epileptic drugs. J Neurol. 2013;260:2865-75. (PMID: 23996127)

152. Evans DE. Anaesthesia and the epileptic patient. A review. Anaesthesia. 1975;30:34-45. (PMID: 1115340)

153. Baker CJ, Prestigiacomo CJ, Solomon RA. Short-term perioperative anticonvulsant prophylaxis for the surgical treatment of low-risk patients with intracranial aneurysms. Neurosurgery. 1995;37:863-70; discussion 870-1. (PMID: 8559333)

154. Franceschetti S, Binelli S, Casazza M, Lodrini S, Panzica F, Pluchino F, et al. Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Acta Neurochir (Wien). 1990;103:47-51. (PMID: 2360466)

155. Yen DJ, Chen C, Shih YH, Guo YC, Liu LT, Yu HY, et al. Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring. Epilepsia. 2001;42:251-5. (PMID: 11240598)

156. DeToledo JC, Ramsay RE, Lowe MR, Greiner M, Garofalo EA. Increased seizures after discontinuing carbamazepine: results from the gabapentin monotherapy trial. Ther Drug Monit. 2000;22:753-6. (PMID: 11128246)

157. Ward MM, Barbaro NM, Laxer KD, Rampil IJ. Preoperative valproate administration does not increase blood loss during temporal lobectomy. Epilepsia. 1996;37:98-101. (PMID: 8603633)

158. Friedman JH, Feinberg SS, Feldman RG. A neuroleptic malignantlike syndrome due to levodopa therapy withdrawal. JAMA. 1985;254:2792-5. (PMID: 4057489)

159. Kas J, Kiss D, Simon V, Svastics E, Major L, Szobor A. Decade-long experience with surgical therapy of myasthenia gravis: early complications of 324 transsternal thymectomies. Ann Thorac Surg. 2001;72:1691-7. (PMID: 11722066)

160. Eisenkraft JB, Book WJ, Mann SM, Papatestas AE, Hubbard M. Resistance to succinylcholine in myasthenia gravis: a dose-response study. Anesthesiology. 1988;69:760-3. (PMID: 3189923)

161. Baraka A, Taha S, Yazbeck V, Rizkallah P. Vecuronium block in the myasthenic patient. Influence of anticholinesterase therapy. Anaesthesia. 1993;48:588-90. (PMID: 8102223)

162. Baraka A. Anaesthesia and myasthenia gravis. Can J Anaesth. 1992;39:476-86. (PMID: 1596973)

163. Feldman S, Karalliedde L. Drug interactions with neuromuscular blockers. Drug Saf. 1996;15:261-73. (PMID: 8905251)

164. Walker C, Perks D. Do you know about donepezil and succinylcholine? [Letter]. Anaesthesia. 2002;57:1041. (PMID: 12358980)

new

165. Huyse FJ, Touw DJ, van Schijndel RS, de Lange JJ, Slaets JP. Psychotropic drugs and the perioperative period: a proposal for a guideline in elective surgery. Psychosomatics. ;47:8-22. (PMID: 16384803)


























of 74

166. Kroenke K, Gooby-Toedt D, Jackson JL. Chronic medications in the perioperative period. South Med J. 1998;91:358-64. (PMID: 9563428)

167. Smith MS, Muir H, Hall R. Perioperative management of drug therapy, clinical considerations. Drugs. 1996;51:238-59. (PMID: 8808166)

168. Wolfe RM. Antidepressant withdrawal reactions. Am Fam Physician. 1997;56:455-62. (PMID: 9262526)

new

169. Krings-Ernst I, Ulrich S, Adli M. Antidepressant treatment with MAO-inhibitors during general and regional anesthesia: a review and case report of spinal anesthesia for lower extremity surgery without discontinuation of tranylcypromine. Int J Clin Pharmacol Ther. 2013;51:763-70. (PMID: 23993253)

170. el-Ganzouri AR, Ivankovich AD, Braverman B, McCarthy R. Monoamine oxidase inhibitors: should they be discontinued preoperatively? Anesth Analg. 1985;64:592-6. (PMID: 4003777)

171. Noble WH, Baker A. MAO inhibitors and coronary artery surgery: a patient death. Can J Anaesth. 1992;39:1061-6. (PMID: 1464133)

172. Michaels I, Serrins M, Shier NQ, Barash PG. Anesthesia for cardiac surgery in patients receiving monoamine oxidase inhibitors. Anesth Analg. 1984;63:1041-4. (PMID: 6333833)

173. O’Hara JF Jr, Maurer WG, Smith MP. Sufentanil-isoflurane-nitrous oxide anesthesia for a patient treated with monoamine oxidase inhibitor and tricyclic antidepressant. J Clin Anesth. 1995;7:148-50. (PMID: 7598924)

174. Sprung J, Distel D, Grass J, Bloomfield EL, Lavery IC. Cardiovascular collapse during anesthesia in a patient with preoperatively discontinued chronic MAO inhibitor therapy. J Clin Anesth. 1996;8:662-5. (PMID: 8982896)

175. Browne B, Linter S. Monoamine oxidase inhibitors and narcotic analgesics. A critical review of the implications for treatment. Br J Psychiatry. 1987;151:210-2. (PMID: 2891392)

176. Meyer D, Halfin V. Toxicity secondary to meperidine in patients on monoamine oxidase inhibitors: a case report and critical review. J Clin Psychopharmacol. 1981;1:319-21. (PMID: 7334144)

177. Michelson D, Fava M, Amsterdam J, Apter J, Londborg P, Tamura R, et al. Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, placebo-controlled trial. Br J Psychiatry. 2000;176:363-8. (PMID: 10827885)

new

178. Auerbach AD, Vittinghoff E, Maselli J, Pekow PS, Young JQ, Lindenauer PK. Perioperative use of selective serotonin reuptake inhibitors and risks for adverse outcomes of surgery. JAMA Intern Med. 2013;173:1075-81. (PMID: 23699725)

179. Movig KL, Janssen MW, de Waal Malefijt J, Kabel PJ, Leufkens HG, Egberts AC. Relationship of serotonergic antidepressants and need for blood transfusion in orthopedic surgical patients. Arch Intern Med. 2003;163:2354-8. (PMID: 14581256)

new

180. Schalekamp T, Klungel OH, Souverein PC, de Boer A. Increased bleeding risk with concurrent use of selective serotonin reuptake inhibitors and coumarins. Arch Intern Med. 2008;168:180-5. (PMID: 18227365)

new

181. Serebruany VL. Selective serotonin reuptake inhibitors and increased bleeding risk: are we missing something? Am J Med. 2006;119:113-6. (PMID: 16443409)

182. Wilbur R, Kulik AV. Abstinence syndrome from therapeutic doses of oxazepam. Can J Psychiatry. 1983;28:298-300. (PMID: 6871816)

183. Buczko GB. Sedation in critically ill patients: a review. Med Health R I. 2001;84:321-3. (PMID: 11693048)

184. Kain ZN, Sevarino F, Pincus S, Alexander GM, Wang SM, Ayoub C, et al. Attenuation of the preoperative stress response with midazolam: effects on postoperative outcomes. Anesthesiology. 2000;93:141-7. (PMID: 10861157)

185. Shafer A, White PF, Urquhart ML, Doze VA. Outpatient premedication: use of midazolam and opioid analgesics. Anesthesiology. 1989;71:495-501. (PMID: 2478048)

186. Johnson MA, Ogorman J, Golembiewski GH, Paluzzi MW. Nephrogenic diabetes insipidus secondary to lithium therapy in the postoperative patient: a case report. Am Surg. 1994;60:836-9. (PMID: 7978676)

187. Gray EJ, Dierks EJ. Lithium-induced diabetes insipidus in a surgical patient: report of a case and review of the literature. J Oral Maxillofac Surg. 1996;54:909-12. (PMID: 8676240)

























of 74

188. Constandis DD, Schriever HG. Severe lithium-induced diabetes insipidus in a surgical patient treated with hydrochlorothiazide. Am J Surg. 1981;141:741-3. (PMID: 7246868)

189. Rosner TM, Rosenberg M. Anesthetic problems in patients taking lithium. J Oral Surg. 1981;39:282-5. (PMID: 6937625)

190. Takami H. Lithium in the preoperative preparation of Graves' disease. Int Surg. 1994;79:89-90. (PMID: 8063564)

191. Mochinaga N, Eto T, Maekawa Y, Tsunoda T, Kanematsu T, Izumi M. Successful preoperative preparation for thyroidectomy in Graves' disease using lithium alone: report of two cases. Surg Today. 1994;24:464-7. (PMID: 8054820)

192. Tsunoda T, Mochinaga N, Eto T, Yamaguchi M, Tsuchiya R, Izumi M. Lithium carbonate in the preoperative preparation of Graves' disease. Jpn J Surg. 1991;21:292-6. (PMID: 1713279)

193. Nishina K, Mikawa K, Takao Y, Shiga M, Maekawa N, Obara H. A comparison of rabeprazole, lansoprazole, and ranitidine for improving preoperative gastric fluid property in adults undergoing elective surgery. Anesth Analg. 2000;90:717-21. (PMID: 10702463)

194. Nishina K, Mikawa K, Maekawa N, Takao Y, Shiga M, Obara H. A comparison of lansoprazole, omeprazole, and ranitidine for reducing preoperative gastric secretion in adult patients undergoing elective surgery. Anesth Analg. 1996;82:832-6. (PMID: 8615506)

195. Levack ID, Bowie RA, Braid DP, Asbury AJ, Marshall RL, Slawson KB, et al. Comparison of the effect of two dose schedules of oral omeprazole with oral ranitidine on gastric aspirate pH and volume in patients undergoing elective surgery. Br J Anaesth. 1996;76:567-9. (PMID: 8652333)

196. Chan KH, Lai EC, Tuen H, Ngan JH, Mok F, Fan YW, et al. Prospective double-blind placebo-controlled randomized trial on the use of ranitidine in preventing postoperative gastroduodenal complications in high-risk neurosurgical patients. J Neurosurg. 1995;82:413-7. (PMID: 7861219)

197. Moesgaard F, Jensen LS, Christiansen PM, Thorlacius-Ussing O, Nielsen KT, Rasmussen NR, et al. The effect of ranitidine on postoperative infectious complications following emergency colorectal surgery: a randomized, placebo-controlled, double-blind trial. Inflamm Res. 1998;47:12-7. (PMID: 9495581)

198. Lamothe PH, Rao E, Serra AJ, Castellano J, Woronick CL, McNicholas KW, et al. Comparative efficacy of cimetidine, famotidine, ranitidine, and mylanta in postoperative stress ulcers. Gastric pH control and ulcer prevention in patients undergoing coronary artery bypass graft surgery. Gastroenterology. 1991;100:1515-20. (PMID: 2019357)

199. Cook DJ, Fuller HD, Guyatt GH, Marshall JC, Leasa D, Hall R, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994;330:377-81. (PMID: 8284001)

200. Colombel JF, Loftus EV Jr, Tremaine WJ, Pemberton JH, Wolff BG, Young-Fadok T, et al. Early postoperative complications are not increased in patients with Crohn's disease treated perioperatively with infliximab or immunosuppressive therapy. Am J Gastroenterol. 2004;99:878-83. (PMID: 15128354)

201. Tay GS, Binion DG, Eastwood D, Otterson MF. Multivariate analysis suggests improved perioperative outcome in Crohn's disease patients receiving immunomodulator therapy after segmental resection and/or strictureplasty. Surgery. 2003;134:565-72; discussion 572-3. (PMID: 14605616)

202. Aberra FN, Lewis JD, Hass D, Rombeau JL, Osborne B, Lichtenstein GR. Corticosteroids and immunomodulators: postoperative infectious complication risk in inflammatory bowel disease patients. Gastroenterology. 2003;125:320-7. (PMID: 12891531)

new

203. Kumar A, Auron M, Aneja A, Mohr F, Jain A, Shen B. Inflammatory bowel disease: perioperative pharmacological considerations. Mayo Clin Proc. 2011;86:748-57. (PMID: 21803957)

new

204. Subramanian V, Pollok RC, Kang JY, Kumar D. Systematic review of postoperative complications in patients with inflammatory bowel disease treated with immunomodulators. Br J Surg. 2006;93:793-9. (PMID: 16710880)

new

205. Pinna-Pintor M, Arese P, Bona R, Falletto E, Schieroni R, Villata E, et al. Severe steroid-unresponsive ulcerative colitis: outcomes of restorative proctocolectomy in patients undergoing cyclosporin treatment. Dis Colon Rectum. 2000;43:609-13; discussion 613-4. (PMID: 10826419)

new

206. Hyde GM, Jewell DP, Kettlewell MG, Mortensen NJ. Cyclosporin for severe ulcerative colitis does not increase the rate of perioperative complications. Dis Colon Rectum. 2001;44:1436-40. (PMID: 11598471)






















of 74

new

207. Melendez JA, Delphin E, Lamb J, Rose E. Noncardiac surgery in heart transplant recipients in the cyclosporine era. J Cardiothorac Vasc Anesth. 1991;5:218-20. (PMID: 1830819)

new

208. Yee J, Petsikas D, Ricci MA, Guerraty A. General surgical procedures after heart transplantation. Can J Surg. 1990;33:185-8. (PMID: 2350741)

209. Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK, . Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV. MMWR Recomm Rep. 2002;51:1-55. (PMID: 12027060)

210. Kaplan JE, Masur H, Holmes KK; USPHS; Infectious Disease Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons—2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. 2002;51:1-52. (PMID: 12081007)

211. Palkama VJ, Ahonen J, Neuvonen PJ, Olkkola KT. Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clin Pharmacol Ther. 1999;66:33-9. (PMID: 10430107)

new

212. Liu B, Zhang L, Guo R, Su J, Li L, Si Y. Anti-infective treatment in HIV-infected patients during perioperative period. AIDS Res Ther. 2012;9:36. (PMID: 23181440)

213. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. Acute heart transplant rejection due to Saint John's wort [Letter]. Lancet. 2000;355:548-9. (PMID: 10683008)

214. Breidenbach T, Hoffmann MW, Becker T, Schlitt H, Klempnauer J. Drug interaction of St John's wort with cyclosporin [Letter]. Lancet. 2000;355:1912. (PMID: 10866469)

215. Yue QY, Bergquist C, Gerdén B. Safety of St John's wort (Hypericum perforatum) [Letter]. Lancet. 2000;355:576-7. (PMID: 10683030)

216. Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol. 1999;12:7-10. (PMID: 10447148)

217. Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology. 1996;46:1775-6. (PMID: 8649594)

218. Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba [Letter]. Lancet. 1998;352:36. (PMID: 9800751)

219. Gilbert GJ. Ginkgo biloba [Letter]. Neurology. 1997;48:1137. (PMID: 9109922)

220. Matthews MK Jr. Association of Ginkgo biloba with intracerebral hemorrhage [Letter]. Neurology. 1998;50:1933-4. (PMID: 9633781)

221. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract [Letter]. N Engl J Med. 1997;336:1108. (PMID: 9091822)

222. Fessenden JM, Wittenborn W, Clarke L. Gingko biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy. Am Surg. 2001;67:33-5. (PMID: 11206893)

223. Vuksan V, Sievenpiper JL, Koo VY, Francis T, Beljan-Zdravkovic U, Xu Z, et al. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med. 2000;160:1009-13. (PMID: 10761967)

224. Kuo SC, Teng CM, Lee JC, Ko FN, Chen SC, Wu TS. Antiplatelet components in Panax ginseng. Planta Med. 1990;56:164-7. (PMID: 2353062)

225. Yuan CS, Wei G, Dey L, Karrison T, Nahlik L, Maleckar S, et al. Brief communication: American ginseng reduces warfarin's effect in healthy patients: a randomized, controlled trial. Ann Intern Med. 2004;141:23-7. [Full Text] (PMID: 15238367)

226. Srivastava KC. Evidence for the mechanism by which garlic inhibits platelet aggregation. Prostaglandins Leukot Med. 1986;22:313-21. (PMID: 3088604)

227. Rose KD, Croissant PD, Parliament CF, Levin MB. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurgery. 1990;26:880-2. (PMID: 2352608)

228. Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava and alprazolam [Letter]. Ann Intern Med. 1996;125:940-1. [Full Text] (PMID: 8967683)

229. Pepping J. Echinacea. Am J Health Syst Pharm. 1999;56:121-2. (PMID: 10030527)



















http://annals.org/article.aspx?articleid=717566









of 74

230. Boullata JI, Nace AM. Safety issues with herbal medicine. Pharmacotherapy. 2000;20:257-69. (PMID: 10730682)

231. Cheema P, El-Mefty O, Jazieh AR. Intraoperative haemorrhage associated with the use of extract of Saw Palmetto herb: a

case report and review of literature. J Intern Med. 2001;250:167-9. (PMID: 11489067)

232. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med. 2000;343:1833-8. (PMID: 11117974)

233. Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol. 1999;51:505-12. (PMID: 10411208)

234. Hendriks H, Bos R, Allersma DP, Malingré TM, Koster AS. Pharmacological screening of valerenal and some other components of essential oil of Valeriana officinalis. Planta Med. 1981;42:62-8. (PMID: 7255569)

235. Garges HP, Varia I, Doraiswamy PM. Cardiac complications and delirium associated with valerian root withdrawal [Letter]. JAMA. 1998;280:1566-7. (PMID: 9820254)

new

236. Nurmohamed MT, Rosendaal FR, Büller HR, Dekker E, Hommes DW, Vandenbroucke JP, et al. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet. 1992;340:152-6. (PMID: 1352573)

new

237. Hoenig H, Rubenstein LV, Sloane R, Horner R, Kahn K. What is the role of timing in the surgical and rehabilitative care of community-dwelling older persons with acute hip fracture? Arch Intern Med. 1997;157:513-20. (PMID: 9066455)

new

238. Butson AR. Intermittent pneumatic calf compression for prevention of deep venous thrombosis in general abdominal surgery. Am J Surg. 1981;142:525-7. (PMID: 7025675)

new

239. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med. 1988;318:1162-73. (PMID: 3283548)

new

240. Eikelboom JW, Quinlan DJ, Douketis JD. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials. Lancet. 2001;358:9-15. (PMID: 11454370)

new

241. Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, et al.; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358:2765-75. (PMID: 18579811)

new

242. Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, et al.; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008;372:31-9. (PMID: 18582928)

new

243. Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, et al.; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776-86. (PMID: 18579812)

new

244. Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, et al.; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373:1673-80. (PMID: 19411100)

new


















of 74

245. Nieto JA, Espada NG, Merino RG, González TC. Dabigatran, rivaroxaban and apixaban versus enoxaparin for thomboprophylaxis after total knee or hip arthroplasty: pool-analysis of phase III randomized clinical trials. Thromb Res.

2012;130:183-91. (PMID: 22425218)

new

246. Turpie AG, Levine MN, Hirsh J, Carter CJ, Jay RM, Powers PJ, et al. A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med. 1986;315:925-9. (PMID: 3531851)

new

247. Colwell CW, Collis DK, Paulson R, McCutchen JW, Bigler GT, Lutz S, et al. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am. 1999;81:932-40. (PMID: 10428124)

new

248. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP)

trial. Lancet. 2000;355:1295-302. (PMID: 10776741)

new

249. Mesko JW, Brand RA, Iorio R, Gradisar I, Heekin R, Leighton R, et al. Venous thromboembolic disease management patterns in total hip arthroplasty and total knee arthroplasty patients: a survey of the AAHKS membership. J Arthroplasty. 2001;16:679-88. (PMID: 11547365)

new

250. Prandoni P, Bruchi O, Sabbion P, Tanduo C, Scudeller A, Sardella C, et al. Prolonged thromboprophylaxis with oral anticoagulants after total hip arthroplasty: a prospective controlled randomized study. Arch Intern Med. 2002;162:1966-71. (PMID: 12230419)

new

251. Samama CM, Vray M, Barré J, Fiessinger JN, Rosencher N, Lecompte T, et al.; SACRE Study Investigators. Extended venous thromboembolism prophylaxis after total hip replacement: a comparison of low-molecular-weight heparin with oral anticoagulant. Arch Intern Med. 2002;162:2191-6. (PMID: 12390061)

new

252. Best AJ, Williams S, Crozier A, Bhatt R, Gregg PJ, Hui AC. Graded compression stockings in elective orthopaedic surgery. An assessment of the in vivo performance of commercially available stockings in patients having hip and knee arthroplasty. J Bone Joint Surg Br. 2000;82:116-8. (PMID: 10697326)

new

253. Maxwell GL, Synan I, Dodge R, Carroll B, Clarke-Pearson DL. Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial. Obstet Gynecol. 2001;98:989-95. (PMID: 11755543)

new

254. Goldhaber SZ, Dunn K, Gerhard-Herman M, Park JK, Black PM. Low rate of venous thromboembolism after craniotomy for brain tumor using multimodality prophylaxis. Chest. 2002;122:1933-7. (PMID: 12475829)

new

255. Sawczuk IS, Williams D, Chang DT. Low molecular weight heparin for venous thromboembolism prophylaxis in urologic oncologic surgery. Cancer Invest. 2002;20:889-92. (PMID: 12449719)

new

256. Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, et al. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996;335:701-7. (PMID: 8703169)















of 74



of 74

Glossary Top

ACC American College of Cardiology

ACE angiotensin-converting enzyme

AHA American Heart Association

ARB angiotensin receptor blocker

BP blood pressure

BUN

blood urea nitrogen

CABG coronary artery bypass graft(ing)

CAD coronary artery disease

CI

confidence interval

CNS central nervous system

COPD chronic obstructive pulmonary disease

DVT deep venous thrombosis

ECG electrocardiography

GI gastrointestinal

HIV human immunodeficiency virus

INR

international normalized ratio

LMWH low-molecular-weight heparin

MAO monoamine oxidase

MI

myocardial infarction

NNH number needed to harm

NNT number needed to treat

NPO nothing by mouth



of 74

NSAID

nonsteroidal anti-inflammatory drug

OR odds ratio

OTC over the counter

PTT

partial thromboplastin time

RCRI Revised Cardiac Risk Index

RR risk ratio

T4 thyroxine

TSH thyrotropin

VTE venous thromboembolism



of 74

Tables Top

Laboratory and Other Studies for Drug Prescribing in the Surgical Patient

Test In Whom to Order Notes

Drug levels (e.g., digoxin, antiarrhythmics, antiepileptics,

theophylline)

Patients on antiepileptics (phenytoin, phenobarbital, valproic acid),

antiarrhythmics (digoxin, quinidine), theophylline, and other drugs

with a narrow therapeutic range.

Obtain if toxicity suspected or if levels have not recently been

checked.

Some postoperative patients may need levels of aminoglycosides or

vancomycin

Drug levels may vary perioperatively due to interactions with

anesthetic and analgesic agents

Glucose All patients with diabetes.

Patients with prediabetic states (impaired glucose tolerance,

impaired fasting glucose)

Evaluate diabetic control and adjust medications based on risk for

perioperative hypoglycemia or hyperglycemia in diabetics

Electrolytes (potassium) Patients on diuretics, ACE inhibitors, or ARBs; patients with CKD or

hyporenin-hypoaldosteronism

Assess for possible hypokalemia (diuretics) or hyperkalemia (ACE

inhibitors, renal insufficiency, hyporenin-hypoaldosteronism)

BUN/Creatinine Patients with CKD or acute kidney injury, patients taking potentially

nephrotoxic drugs, patients with risk factors for renal disease

Renal function may be unstable after intra- or postoperative

hypotension, which may lead to renal insufficiency.

Renal function may affect drug dosing

Liver function tests Patients on hepatotoxic drugs, patients with history of liver disease Dosing adjustments may be necessary for certain drugs

metabolized by the liver

CBC Patients on drugs with bone marrow toxicity or drugs that cause

hemolysis or thrombocytopenia

Heparin can commonly cause thrombocytopenia

Thyroid function tests (free T4, TSH) Patients with known hyperthyroidism or hypothyroidism in whom

levels have not recently been checked, or in whom medication

doses have changed

Uncontrolled hyperthyroidism may increase surgical risk

PT/INR/PTT Patients on warfarin or heparin Assess level of anticoagulation, both preoperatively and postoperatively.

Drug interactions and altered diet can interact with warfarin and

affect the INR

Bleeding time Patients on antiplatelet agents who are undergoing certain high-risk

surgeries. Not needed in most patients

Assess only if the patient has been on antiplatelet agents (ASA or

NSAIDs) and risk for bleeding would be a factor (neurosurgery,

surgery without direct access to the bleeding site) (rarely used)

ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; ASA = acetylsalicylic acid (aspirin); BUN = blood urea nitrogen; CBC = complete blood count; CKD = chronic kidney disease; INR =

international normalized ratio; NSAID = nonsteroidal anti-inflammatory drug; PT = prothrombin time; PTT = partial thromboplastin time; T4 = thyroxine; TSH = thyrotropin.



of 74

Perioperative Cardiovascular Medication Management

β-blockers (propranolol, metoprolol, atenolol, bisoprolol)

Recommendation: Continue in patients already receiving. Consider starting in high-risk patients undergoing vascular or high-risk noncardiac surgery

Comments: To avoid withdrawal symptoms. To prevent perioperative cardiac events (target heart rate 55-65 beats/min), although while ischemia and nonfatal MI are reduced, stroke risk and overall mortality

may be increased

Evidence:

A 2014 systematic review of the effect of perioperative β-blockers compared with placebo in patients with at least one risk factor for heart disease who were undergoing noncardiac surgery included eight

trials. Overall, patients receiving β-blockers had a lower risk for MI (RR, 0.73 [CI, 0.61 to 0.86]), an increased risk for stroke (RR, 2.17 [CI, 1.35 to 3.50]), and no difference in mortality (RR, 0.91 [CI, 0.60 to

1.36]) (39)

A 2010 systematic review of esmolol in patients undergoing noncardiac surgery included 32 randomized trials. Patients receiving esmolol had fewer episodes of cardiac ischemia (OR, 0.16 [CI, 0.05 to 0.54])

but similar rates of MI (OR, 0.23 [CI, 0.01 to 6.09]), arrhythmias (OR, 0.52 [CI, 0.23 to 1.18]), hypotension (OR, 0.41 [CI, 0.22 to 0.79]), and bradycardia (OR, 1.42 [CI, 0.74 to 2.74]) (40)

A 2008 systematic review of the effect of perioperative β-blockers on mortality included 33 trials with 12,306 patients and found that treatment with β-blockers did not lead to improved all-cause or

cardiovascular mortality. Treatment was associated with a decrease in nonfatal MI (NNT, 63) and an increase in nonfatal stroke (NNH, 293) (14)

A retrospective, multicenter, cohort study evaluated the impact of perioperative β-blocker therapy on patients who underwent noncardiac surgery. The impact on mortality varied according to cardiac risk. In

very low-risk patients (RCRI score, 0), β-blockers increased the risk for in-hospital mortality (adjusted OR, 1.43, [CI, 1.29 to 1.58]), and in those with an RCRI score of 1, there was a trend toward increased

mortality with β-blockers (adjusted OR, 1.13 [CI, 0.99 to 1.30]). There was no impact on mortality in patients with RCRI scores of 2 (adjusted OR, 0.90 [CI, 0.75 to 1.08]). In patients at higher risk, β-

blockers prevented mortality, with an adjusted OR of 0.71 (CI, 0.56 to 0.91) in patients with an RCRI score of 3, and 0.57 (CI, 0.42 to 0.76) in patients with an RCRI score of 4 (41)

A retrospective cohort study compared outcomes in patients who received bisoprolol with those who received β1-selective β-blockers (metoprolol or atenolol) in the perioperative setting. In the multivariate

analysis, bisoprolol was associated with fewer perioperative strokes than atenolol or metoprolol (OR, 0.20 [CI, 0.04 to 0.99]) (42)

A retrospective cohort study compared outcomes in 1011 patients who received perioperative atenolol with outcomes in 2776 who received perioperative metoprolol at the San Francisco Veterans Affairs

hospital. Patients receiving metoprolol had higher 1-year mortality in the propensity-matched analysis than those receiving atenolol (OR, 2.1 [CI, 1.5 to 2.9]) (43)

A retrospective cohort study evaluated the impact of the timing of perioperative β-blocker initiation on 940 vascular surgery patients. Perioperative β-blockers, when started at least 1 week before surgery,

were more beneficial than when started less than 1 week preoperatively (44; 39)

A retrospective cohort study evaluated the impact of β-blocker discontinuation in 140 patients who underwent vascular surgery. In the multivariate analysis, discontinuation after surgery was associated with

increased mortality (adjusted OR, 17.0; P=0.01) and postoperative MI (adjusted OR, 17.7; P=0.003) (16)

Calcium-channel blockers (nifedipine, amlodipine, diltiazem, verapamil)

Recommendation: Continue. Consider starting diltiazem prophylactically for CABG

Comments: Rare withdrawal syndrome, potential effects on anesthetic agents; potential antiarrhythmic, anti-ischemic, and renal protective effects with CABG

Evidence:

A 2003 systematic review of the impact of calcium-channel blockers on patients undergoing noncardiac surgery included 11 studies. Calcium-channel blockers reduced ischemia (RR, 0.49 [CI, 0.30 to 0.80])

and SVT (RR, 0.52 [CI, 0.37 to 0.72]); most benefit was with diltiazem (45)

Small studies have evaluated the effect of diltiazem in patients undergoing CABG and have documented anti-ischemic and antiarrhythmic protection (46; 47; 48; 49; 50) and prevention of decrease in renal

function (51)

A randomized trial compared nifedipine with nitroglycerine in 104 patients undergoing CABG. The nifedipine group had fewer MIs (4% vs. 12%, P<0.001) (52)

A 1985 narrative review stated that calcium-channel blockers may potentiate hemodynamic and MAC depressive effects of inhalation anesthetics and neuromuscular blockers (53)

Two of 16 patients on diltiazem and 2 of 100 patients on nifedipine experienced life-threatening coronary vasospasm following discontinuation of the drug at the time of coronary revascularization (54), but 0

of 81 patients on nifedipine in another study had no adverse effects after acute withdrawal (55)


http://journals.lww.com/anesthesia-analgesia/Fulltext/2003/09000/Calcium_Channel_Blockers_for_Reducing_Cardiac.6.aspx



of 74

Nitrates

Recommendation: Continue. May start iv nitrates intra- or postoperatively. Do not use prophylactically during surgery

Comments: May be a marker for in-hospital mortality; intraoperatively may reduce ischemia or have no benefit in noncardiac surgery

Evidence:

A retrospective cohort study used the Oxford Record Linkage Study to examine relationships between intercurrent cardiovascular drug therapy and cardiac death within 30 days of surgery under general

anesthesia. Nitrates were associated with increased cardiac death (adjusted OR, 4.79 [CI, 1.01 to 22.72]) (56)

A randomized trial compared prophylactic intraoperative nitroglycerin infusion vs. placebo in 45 patients undergoing noncardiac surgery. There was no difference in incidence of perioperative ischemia between

the groups (57)

A randomized trial compared preoperative isosorbide dinitrate infusion vs. placebo in 100 patients undergoing CABG. The rate of perioperative MI did not differ between the groups (22% vs. 18%) (58)

Sympatholytics; α2-agonists for perioperative prophylaxis

Evidence:

A 2003 systematic review of the effect of α2-agonists on perioperative complications included 23 trials with 3395 patients. Perioperative α2-agonists reduced mortality overall (RR, 0.64 [CI, 0.42 to 0.99]) and

also reduced myocardial infarction (RR, 0.66 [CI, 0.46 to 0.94]) and mortality (RR, 0.47 [CI, 0.25 to 0.90]) during vascular surgery (59)

A 2002 systematic review of clonidine for the prevention of perioperative myocardial ischemia included seven studies. Clonidine reduced perioperative ischemia, with a pooled OR of 0.49 (CI, 0.34 to 0.71)

(60)

ACE inhibitors (captopril, enalapril, lisinopril, ramipril)

Recommendation: Controversial—continue with caution (avoid hypovolemia)

Comments: Potential for hypotension with induction of anesthesia and increased vasoconstrictor requirements; many anesthesiologists recommend withholding it on the morning of surgery; other physicians

base recommendations on indication for the drug and current BP (continue for HF and uncontrolled hypertension; otherwise, discontinue)

Evidence:

A 2013 systematic review of the effects of ACE inhibitors and ARBs in patients undergoing cardiothoracic surgery included 29 studies. Perioperative use of ACE inhibitors or ARBs was associated with mortality

(OR, 1.20 [CI, 1.06 to 1.35]) and acute kidney injury (OR, 1.17 [CI, 1.01 to 1.36]), although there was heterogeneity in the kidney-injury outcome (61)

A 2008 systematic review of withholding or administering ACE inhibitors and ARBs in the perioperative period included five studies with 434 participants. The preoperative administration of ACE inhibitors or

ARBs increased intraoperative hypotension requiring vasopressors (RR, 1.50 [CI, 1.15 to 1.96]), but there were insufficient data to assess other outcomes (62)

A randomized trial compared discontinuation of ramipril, continuation of ramipril, and continuation of ramipril with prophylactic low-dose vasopressin in 47 patients on ramipril who were undergoing CABG.

Patients who continued ramipril had lower BP with anesthesia induction which stayed low; those who received vasopressin had a drop in BP followed by recovery (63)

A prospective observational study evaluated the effect of ACE-inhibitor or ARB therapy in patients undergoing noncardiac surgery. Patients on ACE-inhibitor or ARB therapy did not have increased rates of

perioperative MI or renal failure, although those who were also receiving diuretics had more frequent hypotension (64)

A prospective observational study evaluated the impact of perioperative ACE inhibitors in 4224 patients undergoing CABG. Compared with no ACE-inhibitor treatment, continuous therapy (OR, 0.64 [CI, 0.46

to 0.88]) and the addition of a postoperative ACE inhibitor (OR, 0.63 [CI, 0.40 to 0.97]) were associated with lower risks for cardiovascular events. Compared with continuous therapy, withdrawal of ACE

inhibitors was associated with cardiac (OR, 1.27) and renal (OR, 1.15) events (65)

A 2003 narrative review stated that induction of anesthesia in a patient with preoperative fasting, volume depletion, sympathetic blockade, and reduced venous capacitance may cause hypotension in patients

on ACE inhibitors whose angiotensin II response to hypotension is blocked. Vasopressors and fluids should be readily available (66)

Angiotensin II receptor blockers/antagonists (losartan, valsartan, candesartan, irbesartan)

Recommendation: Uncertain, although they are usually continued

Comments: Potential for hypotension with induction of anesthesia and decreased responsiveness to pressors

http://www.amjmed.com/article/S0002-9343%2803%2900165-7/fulltext

http://journals.lww.com/anesthesiology/Fulltext/2002/02000/Efficacy_of_Clonidine_for_Prevention_of.16.aspx

http://www.ajkd.org/article/S0272-6386%2813%2900821-4/fulltext



of 74

Evidence:

A 2013 systematic review of the effects of ACE inhibitors and ARBs in patients undergoing cardiothoracic surgery included 29 studies. Perioperative use of ACE inhibitors or ARBs was associated with mortality

(OR, 1.20 [CI, 1.06 to 1.35]) and acute kidney injury (OR, 1.17 [CI, 1.01 to 1.36]), although there was heterogeneity in the kidney injury outcome (61)

A 2008 systematic review of withholding or administering ACE inhibitors and ARBs in the perioperative period included five studies with 434 participants. The preoperative administration of ACE inhibitors or

ARBs increased intraoperative hypotension requiring vasopressors (RR, 1.50 [CI, 1.15 to 1.96]), but there were insufficient data to assess other outcomes (62)

Diuretics (furosemide, spironolactone, hydrochlorothiazide)

Recommendation: Optional (can continue on morning of surgery or stop, either on morning of surgery or day before)

Comments: Avoid hypokalemia and hypovolemia acutely (although these problems are less likely once steady-state has been reached); check K+, BUN/Cr

Evidence:

A randomized trial compared continued furosemide with placebo on the day of surgery in 193 patients on chronic furosemide undergoing noncardiac surgery. Rates of intraoperative hypotension (49.0% vs.

51.9%, P=0.78) and postoperative cardiac events (4.8% vs. 2.8%, P=0.49) were similar in the furosemide and placebo groups (67)

A nested case-control study evaluated predictors of perioperative outcomes in 2402 patients undergoing CABG. Serum potassium level of less than 3.5 mmol/L was independently associated with serious

perioperative arrhythmias (OR, 2.2 [CI, 1.2 to 4.0]) and postoperative atrial fibrillation or flutter (OR, 1.7 [CI, 1.0 to 2.7]) (20)

Digoxin (digoxin)

Recommendation: Continue. May be used prophylactically for arrhythmias (pre- or postoperatively) in cardiothoracic surgery

Comments: Check serum level to avoid toxicity (which is enhanced by other drugs, stress, acidosis, hypoxia, electrolyte abnormalities, catecholamines); unclear effect on supraventricular arrhythmias

Evidence:

A prospective cohort study evaluated predictors of supraventricular arrhythmias in 4181 patients undergoing noncardiac surgery who were initially in sinus rhythm. Among patients who underwent

intrathoracic surgery, digoxin was associated with a lower risk for arrhythmias (OR, 0.20 [CI, 0.04 to 0.80]) (68)

A randomized trial compared digoxin to diltiazem in 70 patients after pneumonectomy. The diltiazem group had fewer supraventricular arrhythmias (0% vs. 32%, P<0.005) (69)

A randomized trial compared digitalis with control in 120 patients on propranolol who were undergoing CABG. The digitalis group had a lower rate of postoperative supraventricular arrhythmias (3.1% vs.

21.4%, P<0.005) (70)

A randomized trial compared the combination of digitalis plus atenolol vs. digitalis alone, atenolol alone, or neither in 160 patients undergoing CABG. The rate of postoperative atrial fibrillation was 5% in the

combination group, 17.9% in the digitalis group, 15.4% in the atenolol group, and 25% in the control group; the difference between combination therapy and control was statistically significant (71)

β-blockers/α-β blockers

Recommendation: Continue. Do not start for acute HF

Comments: To avoid withdrawal symptoms

Evidence:

A randomized trial compared perioperative bisoprolol with placebo in 165 patients with HF undergoing noncardiac surgery. There was no difference in mortality between the groups (34.5% with bisoprolol and

24.4% with placebo, P=0.17) (72)

Antihypertensives

Evidence: A 2005 narrative review discussed symptoms associated with withdrawal of antihypertensive medications (73)

Diuretics

Recommendation: Optional

http://www.ajkd.org/article/S0272-6386%2813%2900821-4/fulltext



of 74

Comments: Avoid hypokalemia and hypovolemia acutely (although these problems are less likely once steady-state has been reached); check K+, BUN/Cr

β-blockers

Recommendation: Continue

Comments: To avoid withdrawal symptoms. To prevent perioperative cardiac events

α-β blockers (labetalol)

Recommendation: Continue. May be started intra- or postoperatively for perioperative hypertension

Comments: May attenuate hemodynamic responses to intubation; also used for pheochromocytomas, perioperative hypertension, and deliberately induced hypotension, an anesthetic technique usually for

neurosurgery

Evidence:

A randomized trial compared labetalol to nicardipine before intubation or for treatment of hypertension in 130 patients undergoing general anesthesia. Mean arterial BP was higher in the labetalol groups than

in the nicardipine groups. The rate of tachycardia was lower in the labetalol groups, but there were no differences in other adverse events (74)

Calcium blockers


Comments: Rare withdrawal syndrome; potential effects on anesthetic agents; potential antiarrhythmic, anti-ischemic, and renal protective effects with CABG

ACE inhibitors/ARBs

Recommendation: Uncertain

Comments: Potential for hypotension with induction of anesthesia and increased vasoconstrictor requirements

Sympatholytics (centrally acting α2-agonists—clonidine)

Recommendation: Continue. May start prophylactically in high-risk cardiac patients with contraindications to β-blockers

Comments: To avoid withdrawal syndrome (rebound hypertension, tachycardia); may decrease ischemia, shivering, anesthesia-analgesia requirement, sedative hypnotic effect, decrease sympathetic tone

Evidence:

Case reports have described a withdrawal syndrome after perioperative cessation of clonidine (75; 76)

α-blockers (doxazosin, terazosin)

Recommendation: Continue. Start treatment for pheochromocytoma at least 5 days preoperatively. Consider stopping before cataract surgery

Comments: May be used for pheochromocytoma (with or without β-blockade, depending on type); may be associated with floppy iris syndrome

Evidence:

A case series reviewed 113 patients undergoing surgical excision of pheochromocytoma. Patients receiving preoperative α-blockade required more intra- and postoperative fluids and that calcium-channel

blockers were as effective and safer when used as the primary mode of antihypertensive therapy (77)

Intraoperative floppy iris syndrome is a clinical syndrome observed during cataract surgery reported in patients taking systemic α1 adrenergic receptor antagonists. It has been most strongly linked to the use

of tamsulosin (78). Medication washout periods of up to 2 weeks and specific surgical procedures have been attempted to reduce risk of complications from α1 adrenergic receptor antagonists in the setting of

cataract surgery (79)

Vasodilators (hydralazine)

Recommendation: Continue. May be started intraoperatively or postoperatively to treat hypertension. Indicated for treatment of preeclampsia/eclampsia



of 74

Comments: May reduce intraoperative and postoperative hypertension

Evidence:

Hydralazine pretreatment in 10 patients reduced the incidence of intubation hypertension (80)

A case series described the effect of the combination of hydralazine and propranolol in 110 patients undergoing carotid endarterectomy. All patients receiving the therapy had good control of postoperative

hypertension (81)

Antiarrhythmics

Recommendation: Continue (except for EPS/mapping)

Class Ia (quinidine, procainamide, disopyramide, lidocaine)

Recommendation: Continue; can substitute iv lidocaine or procainamide perioperatively

Comments: Check levels; negative inotropes, can prolong QT and prolong neuromuscular blockade

Evidence: Consensus

Class Ic (flecainide, encainide, propafenone, moricizine)


Comments: Negative inotropic effect

Evidence: Consensus

Class III

Amiodarone

Recommendation: Continue. May be started prophylactically for arrhythmias in cardiac surgery

Comments: Check level; long half-life; may cause bradycardia, atrioventricular dissociation, and vasodilation. May prevent atrial arrhythmias post-CABG

Evidence:

A 2005 systematic review of amiodarone prophylaxis in patients undergoing cardiac surgery included 10 trials with 1744 participants. Amiodarone decreased postoperative atrial fibrillation or flutter (RR,

0.64 [CI, 0.55 to 0.75]), ventricular tachyarrhythmias (RR, 0.42 [CI, 0.28 to 0.63]), and stroke (RR, 0.39 [CI, 0.21 to 0.76]) (82)

The PAPABEAR study was a randomized, controlled trial comparing amiodarone with placebo in 601 patients undergoing cardiac surgery. The amiodarone group had fewer atrial tachyarrhythmias (16.1% vs.

29.5%, P<0.001) overall, with a similar effect in various subgroups, including younger as well as older patients, patients undergoing CABG alone or with valve surgery, and patients taking or not taking β-blockers (83)

A review of 17 anesthetics administered to 16 patients on amiodarone found dangerous interactions in patients undergoing CABG and hemodynamically significant bradyarrhythmias in patients undergoing

noncardiac surgery (84)

Sotalol

Recommendation: Continue or can start prophylactically

Comments: Prophylactically may decrease atrial arrhythmias after CABG

Evidence:

A 2002 systematic review of amiodarone compared with sotalol for the prevention of atrial fibrillation in patients undergoing cardiac surgery included 10 studies. Both active drugs were superior to placebo,

and there was no significant difference between them (85)

A randomized trial compared sotalol with atenolol in 253 patients undergoing cardiac surgery. Postoperative atrial fibrillation occurred in fewer patients taking sotalol (10% vs. 22%, P=0.13) (86)





of 74

Digoxin


Comments: Check serum level to avoid toxicity (which is enhanced by other drugs, stress, acidosis, hypoxia, electrolyte abnormalities, catecholamines); equivocal results in decreasing supraventricular

arrhythmias

β-blocker


Comments: To avoid withdrawal symptoms. To prevent perioperative cardiac events

Calcium blockers (nondihydropyridine)


Comments: Rare withdrawal syndrome; potential effects on anesthetic agents; potential antiarrhythmic, anti-ischemic, and renal protective effects with CABG

Lipid-lowering agents

Statins

Recommendation: Continue, as recommended by ACC/AHA guidelines (33), or start prophylactically, especially in patients undergoing cardiovascular procedures and vascular surgery, despite manufacturer's

recommendation to discontinue preoperatively

Comments: Potential benefits to continuing: may prevent perioperative MI, atrial fibrillation, death. Potential theoretical benefits: plaque stabilization, rebound, may reduce inflammatory response to bypass

surgery. Potential theoretical reasons to discontinue: may increase risk for myopathy and hepatotoxicity, may be associated with delirium in the elderly

Evidence:

A 2013 Cochrane review of perioperative statins in statin-naïve patients undergoing vascular surgery included six studies. Statins had no effect on mortality (RR, 0.73, [CI, 0.31 to 1.75]), although though

there were few patients in the analysis (87)

A 2012 Cochrane review of preoperative statins in patients undergoing cardiac surgery included 11 trials with 984 participants. Preoperative statin therapy was associated with a lower risk for postoperative

atrial fibrillation (OR, 0.40 [CI, 0.29 to 0.55]) but had no effect on mortality (OR, 0.98 [CI, 0.14 to 7.10]) or stroke (OR, 0.70 [CI, 0.14 to 3.63]) (88)

A 2010 systematic review of the effect of preprocedural statins on outcomes included 21 trials with 4805 participants. Preprocedural statin therapy significantly reduced postprocedural MI overall (RR, 0.57

[CI, 0.46 to 0.70]) and after percutaneous coronary intervention and noncardiac surgery, but not after CABG. Statin therapy did not reduce all-cause mortality (RR, 0.66 [CI, 0.37 to 1.17]) but did reduce

post-CABG atrial fibrillation (RR, 0.54 [CI, 0.43 to 0.68]) (89)

Although statins are thought to have a beneficial effect on inflammation, a small placebo-controlled trial failed to show that atorvastatin, initiated within 7 days preoperatively, was associated with clinically

significant reductions in levels of C-reactive protein (90)

A retrospective cohort analysis of 284,158 patients aged 65 and older undergoing elective surgery found that statin use was associated with an increased risk for postoperative delirium (91)

A 2012 narrative review based on a literature review suggested that statin withdrawal is associated with worse outcomes in acute coronary syndrome, ischemic stroke, and noncardiac surgery, emphasizing

the importance of resumption of statins after surgery (92)

Bile sequestrants (colestipol)

Recommendation: Discontinue the day before or morning of surgery

Comments: May decrease bioavailability of other drugs and fat-soluble vitamins

Evidence:

A 1994 narrative review noted that bile sequestrants result in decreased bioavailability of thiazide diuretics, digitalis preparations, β-blockers, coumarin anticoagulants, thyroid hormones, fibric acid

derivatives, and certain oral hypoglycemic agents (93)





of 74

Niacin

Recommendation: Unknown

Comments: May cause liver enzyme elevations

Evidence:

No data in perioperative period

Fibric acid derivatives (gemfibrozil)

Recommendation: Unknown

Comments: May cause myopathy, especially in combination with statins

Evidence:

No data in perioperative period

Anticoagulants

Heparin (unfractionated)

Recommendation: Discontinue on morning of surgery (4-6 hours before) if full anticoagulation and restart at least 12 hours postoperatively if adequate hemostasis (or as per surgeon and type of procedure).

Continue or start if for prophylaxis (mini-dose 5000 IU sc q8-12h)

Comments: Minimize risk for perioperative bleeding as well as period of time without full anticoagulation protection; check PTT preoperatively if on full-dose anticoagulation. If used prophylactically, it should

not interfere significantly with the coagulation mechanism

Evidence:

Based on recommendations from the 2012 ACCP guideline on antithrombotic therapy and prevention of thrombosis, 9th ed. (21)

LMWH (enoxaparin, dalteparin)

Recommendation: Continue or start for prophylaxis: can start 12 hours before, 2 hours before, 6 hours after, or the following morning. Discontinue 24 hours preoperatively if on full-dose anticoagulation. If

neuraxial anesthesia is planned, do not give LMWH for at least 12 hours before surgery or at least 2 hours after removal of a spinal needle or epidural catheter

Comments: Discontinue before neuraxial anesthesia due to potential risk for perispinal hematoma. Effective for prophylaxis, particularly in orthopedic surgery and high-risk to very high-risk patients. Consider

extended prophylaxis for 3-5 weeks postoperatively after total-hip arthroplasty and surgery for abdominal or pelvic cancer

Evidence:


A 2002 systematic review evaluated preoperative compared with postoperative treatment with LMWH in patients undergoing elective hip surgery. The rate of postoperative DVT was 19.2% in patients who

received preoperative LMWH, 12.4% in those who received perioperative LMWH, and 14.4% in those who received postoperative LMWH. Rates of bleeding were higher in the perioperative group (6.3%) than

in the other groups (94)

Several studies have addressed LMWH as bridging anticoagulation (95; 96; 97)

Pentasaccharides (fondaparinux)

Recommendation: Start 6 hours after total hip or knee replacement or hip fracture surgery for DVT prophylaxis. Watch for postoperative bleeding; inhibits factor Xa and has a 15-hour half-life

Comments: Effective DVT prophylaxis for major orthopedic surgery

Evidence:








of 74

A 2002 systematic review of fondaparinux compared with enoxaparin in patients undergoing total hip or knee replacement and hip-fracture surgery included four trials with 7344 participants. Patients

receiving fondaparinux had a lower risk of VTE by day 11 (6.8% vs 13.7%, P<0.001), with higher rates of major bleeding but similar rates of clinically relevant bleeding (98)

Warfarin

Recommendation: Discontinue preoperatively depending on indication:

Stop 3-5 days before elective surgery (depending on INR) to minimize bleeding.

Check INR preoperatively; ideally ≤1.5.

For urgent procedures, can use low-dose oral or sc vitamin K to reduce INR within 24-36 hours; if emergency, use fresh frozen plasma or prothrombin complex concentrate.

If high risk for embolic event, use bridging therapy with unfractionated or LMWH.

Restart after procedure when deemed safe by surgeon.

Start the night before orthopedic surgery if for DVT prophylaxis; goal is INR 2-3 by postoperative day 3-5

Comments: Minimize risk for perioperative bleeding as well as period of time without full anticoagulation protection. Consider the indication for anticoagulation and risk for an embolic event when not

anticoagulated. Check PT/INR preoperatively

Evidence:


A 2012 systematic review of periprocedural heparin bridging therapy included 34 studies, of which 1 was a randomized trial. The rate of thromboembolic events did not differ between bridged and nonbridged

patients (OR, 0.80 [CI, 0.32 to 1.54]), but bridged patients had a higher rate of major bleeding (OR, 3.60 [CI, 1.52 to 8.50]) (99)

Novel Oral Anticoagulants

Evidence: Based on recommendations regarding new antithrombotic drugs (100) from the 2012 ACCP guideline on antithrombotic therapy and prevention of thrombosis, 9th ed.

Oral thrombin inhibitors (dabigatran)

Recommendation: If discontinuing anticoagulation preoperatively, stop dabigatran 1-4 days before surgery: 24 hours before surgery with normal renal function and for procedures with low bleeding risk; add

an additional day if there is impaired renal function and an additional 1-2 days for procedures with high bleeding risk or spinal/epidural anesthesia

Evidence: Consensus; manufacturer's recommendations; review (101)

Oral Xa inhibitors (rivaroxaban, apixaban)

Recommendation: If discontinuing anticoagulation preoperatively, stop rivaroxaban and apixaban at least 1 day before surgery if renal function is normal and for procedures with low bleeding risk. Add an

additional day if there is impaired renal function or if the procedure has a high bleeding risk

Evidence: Consensus; manufacturer's recommendations; review (101)

Antiplatelet agents

Evidence: Reviews of perioperative management of anticoagulant and antiplatelet therapy (102; 103; 104; 105; 106; 107) and use in CABG (108)

Comment: The role of preoperative platelet function testing is controversial

Aspirin

Recommendation: Uncertain; often discontinued but depends on indication (TIA, CAD/ACS), procedure (risk for bleeding and access to the site), and surgeon's preference. If discontinuing, usually stop 5-10

days before surgery and consider restarting 24-48 hours postoperatively. Before elective surgery, dual antiplatelet therapy with aspirin and clopidogrel, prasugrel, or ticagrelor is recommended for at least 4-6 weeks after placement of a bare metal stent and at least 12 months after a drug-eluting stent, if possible, to minimize the chance of stent thrombosis postoperatively

Comments: Consider indication for therapy and risk for bleeding:

Irreversible platelet inhibitor

Prolongs bleeding time but not necessarily correlated with bleeding complications



http://circ.ahajournals.org/content/126/13/1630.long




of 74

It may have beneficial effects

Discontinuation may be associated with a rebound effect

Evidence:

A randomized trial compared low-dose aspirin with placebo in high-risk patients undergoing noncardiac surgery. Rates of major adverse cardiac events were lower in the aspirin group (1.8% vs. 9.0%,

P=0.02) with no difference in bleeding complications, although the study was not powered to evaluate bleeding complications (109)

A 2012 narrative review based on a literature review advised individualizing the plan for perioperative aspirin but suggested continuation if used for secondary prevention, noting that the risk for withdrawal and thromboembolic events was probably greater than the risk for bleeding (except in specific surgeries) (110)

Clopidogrel

Recommendation: Discontinue. Usually stop 5-7 days preoperatively

Comments: Inhibitor of ADP-induced platelet aggregation; irreversible platelet inhibitor

Evidence:

A 2012 systematic review of the impact of thienopyridines on patients undergoing surgery included 37 studies (31 cardiac surgery and 6 noncardiac surgery). Exposure to thienopyridines within the 5 days

before surgery was not associated with postoperative MI (OR, 0.98 [CI, 0.72 to 1.34]) but was associated with stroke (OR, 1.54 [CI, 1.08 to 2.20]) and mortality (OR, 1.38 [CI, 1.13 to 1.69]) (111)

Data on 647 major arterial procedures revealed that combined therapy with clopidogrel and aspirin up to the day of surgery was not associated with increased bleeding complications or transfusion

requirements (112)

A review of 104 patients receiving clopidogrel before abdominal surgery found that while clopidogrel use within 7 days of surgery increased the risk for postoperative bleeding, most bleeding episodes were

successfully managed by transfusion, and there was no increase in bleeding-related mortality or reoperation (113)

Prasugrel

Recommendation: Discontinue. Usually stop 7 days preoperatively

Comments: Inhibits P2Y12 ADP-induced platelet aggregation; irreversible platelet inhibitor

Evidence:

Consensus, manufacturer's recommendation

CABG-related TIMI major bleeding was greater in patients taking prasugrel than in patients taking clopidogrel (13.4% vs. 3.2%; HR, 4.73) (114)

Ticagrelor

Recommendation: Discontinue. Usually stop 5 days preoperatively

Comments: Even though ticagrelor is a reversible platelet inhibitor, the package insert recommends stopping it 5 days before surgery rather than earlier

Evidence:

Consensus, manufacturer's recommendation

A 2013 narrative review of antiplatelet therapy and cardiac surgery stated that patients who have received ticagrelor should wait 5 days after the last dose before undergoing surgery, although it is likely that

surgery can be safely performed 3 days after discontinuing ticagrelor (106)

Ticlopidine

Recommendation: Discontinue. Usually stop 10-14 days preoperatively. Can start postoperatively to improve graft patency in vascular surgery

Comments: Irreversibly inhibits ADP-induced platelet-fibrinogen binding and subsequent platelet-platelet interactions. Postponing elective noncardiac surgery for 2-4 weeks after coronary stenting should

permit completion of the mandatory antiplatelet regimen (aspirin and ticlopidine), thereby reducing the risk for stent thrombosis and bleeding complications; otherwise one must balance the risk for

thrombosis with premature discontinuation with the risk of bleeding if the drugs are continued (this drug is rarely used)

http://www.amjmed.com/article/S0002-9343%2811%2900677-2/fulltext



of 74

Evidence:

In 40 consecutive patients undergoing noncardiac surgery within 6 weeks of coronary stent placement, there were 7 MIs, 11 major bleeding episodes, and 8 deaths, most occurring within 2 weeks of stent

placement (115). Of 6 patients with major bleeding who died, 3 did not have ticlopidine withheld

A randomized trial compared ticlopidine with placebo after saphenous vein bypass surgery. The ticlopidine group had better long-term graft patency, with no significant difference in overall mortality or major

ischemic events (116)

Cilostazol

Recommendation: Discontinue. Usually stop 3-5 days preoperatively (half-life 12 hours)

Comments: Reversible cAMP PDE III inhibitor

Evidence:

In a study of 16 patients, cilostazol was considered to be as effective as warfarin and suitable for postoperative antithrombotic therapy after ePTFE bypass surgery (117)

Dipyridamole


Comments: Reversible platelet adhesion inhibitor (half-life 10 hours); may increase risk for bleeding when combined with aspirin

Evidence:

A randomized trial compared aspirin, aspirin plus dipyridamole, and placebo in 1112 patients undergoing CABG. Aspirin plus dipyridamole decreased rates of early saphenous vein aortocoronary occlusion

compared with placebo (12.9% vs. 18%), with a trend toward reduction with aspirin alone (118)

ACC = American College of Cardiology; ACCP = American College of Chest Physicians; ACE = angiotensin-converting enzyme; ACS = acute coronary syndrome; ADP = adenosine diphosphate; AHA = American

Heart Association; ARB = angiotensin receptor blocker; BP = blood pressure; BUN = blood urea nitrogen; CABG = coronary artery bypass graft(ing); CAD = coronary artery disease; cAMP = cyclic adenosine

monophosphate; CI = confidence interval; Cr = creatinine; DVT = deep venous thrombosis; EPS = extrapyramidal symptoms; ePTFE = expanded polytetrafluoroethylene; HF = heart failure; HR = hazard ratio;

iv = intravenous; INR = international normalized ratio; IU = international unit; LMWH = low-molecular-weight heparin; MAC = minimum alveolar concentration; MI = myocardial infarction; NNH = number

needed to harm; NNT = number needed to treat; OR = odds ratio; PAPABEAR = Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve

Replacement, or Repair (trial); PDE = phosphodiesterase; PT = prothrombin time; PTT = partial thromboplastin time; q8-12h = every 8-12 hours; RCRI = Revised Cardiac Risk Index; RR = risk ratio; sc = subcutaneous; SVT = supraventricular tachycardia; TIA = transient ischemic attack; TIMI = thrombolysis in myocardial infarction; VTE = venous thromboembolism.



of 74

Perioperative Rheumatologic Medication Management

NSAIDs

Recommendation: Controversial

If discontinuing, stop 1-3 days before, depending on half-life

May start postoperatively for pain relief

Comments: Reversible platelet inhibitors. Disadvantages—potential for bleeding and renal insufficiency. Advantages—may decrease requirement for opioids and improve early postoperative analgesia

Evidence:

A 2005 systematic review of the effect of preoperative coxibs on clinical outcomes included 22 studies with 2246 participants. Preoperative coxibs reduced postoperative pain, analgesic consumption, and

patient satisfaction compared with placebo in the majority of studies. There was no significant difference in intraoperative blood loss (119)

A large case-control analysis found that the risk for acute MI was 1.52 for patients who stopped taking NSAIDs 1-29 days before the index date compared with nonusers. Current and past NSAID use

(discontinued ≥60 days before) was not associated with an increased risk for acute MI (120)

A 1994 narrative review highlighted controversies in the perioperative use of NSAIDs and recommended the selective use of NSAIDs in combination with opioid analgesics and local anesthetics for

perioperative management of pain (121)

COX-2 inhibitors

Recommendation: Uncertain; discontinue valdecoxib

Comments: No effect on platelets but potential for renal dysfunction as with NSAIDs

Evidence:

A 2005 systematic review of the effect of preoperative coxibs on clinical outcomes included 22 studies with 2246 participants. Preoperative coxibs reduced postoperative pain, analgesic consumption, and

patient satisfaction compared with placebo in the majority of studies. There was no significant difference in intraoperative blood loss (119)

A randomized trial compared the combination of parecoxib and valdecoxib with placebo in 462 patients undergoing CABG. Pain control was better in the coxib group than in the placebo group, but there was

an increased incidence of serious adverse events (19% vs. 9.9%, P=0.015) (122)

Opioids (codeine, oxycodone, methadone)

Recommendation: Continue until morning of surgery; then decision is up to the anesthesiologist to determine narcotic use intraoperatively

Comments: Need to continue adequate pain management and prevent withdrawal symptoms; however, if given immediately preoperatively, will alter analgesic/narcotic dose requirement intraoperatively

Evidence:

Consensus

Methotrexate (methotrexate)


Comments: Caution with renal insufficiency; mixed results but most likely no problems with wound healing or postoperative infections

Evidence:

A randomized trial compared continuation of methotrexate with cessation of methotrexate in 388 patients with RA on methotrexate who were undergoing elective orthopedic surgery. Results were also

compared with outcomes in surgical patients who were not on methotrexate. Patients who continued methotrexate had a lower risk of surgical complication or postoperative infection than patients who

discontinued (2% vs. 15%, P<0.003) or patients who were not on methotrexate (10.5%) (123)

A retrospective case series reported outcomes in 15 patients with RA taking methotrexate who underwent 39 surgeries. No postoperative complications related to methotrexate were observed (124)



of 74

Two small studies of 32 (125) and 38 (126) patients with RA undergoing orthopedic procedures suggested that methotrexate may increase postoperative infections, and it should be temporarily discontinued

before surgery

A 2010 narrative review of the perioperative management of medication for RA recommended continuing methotrexate perioperatively (127)

Biologic response modifiers (etanercept, infliximab, anakinra, rituximab, adalimumab)

Recommendation: Hold for two half-lives or at least one administration interval

Comments: Potentially increased risk for infection

Evidence:

A 2013 systematic review of infectious risk in patients treated with TNF blocking agents and undergoing surgery included 14 studies, of which 13 were retrospective. There was an increased risk for infection in

4 of 6 studies in which patients received TNF blocking agents compared with not receiving them. However, none of the other studies that compared continued vs. discontinued treatment at surgery found an

increased risk for infection when the medication was continued perioperatively (128)

A 2010 narrative review of the perioperative management of immunosuppressive medication suggested waiting four to five half-lives before surgery and restarting treatment after recovery from surgery (127)

CABG = coronary artery bypass graft(ing); COX-2 = cyclo-oxygenase 2; MI = myocardial infarction; NSAID = nonsteroidal anti-inflammatory drug; RA = rheumatoid arthritis; TNF = tumor necrosis factor.




of 74

Perioperative Pulmonary Medication Management

Inhaled β-agonists

Recommendation: Continue or start if bronchospasm is present

Comments: To maintain bronchodilator effect

Evidence:

A randomized trial compared nebulized salbutamol with saline in 53 patients at high risk for postoperative infection who were undergoing upper abdominal surgery. There was no difference in the rate of

postoperative chest infection between the salbutamol group and saline group (129)

A randomized trial compared salbutamol with salbutamol plus corticosteroids in 31 patients with partially reversible airway obstruction. Patients in the combination-therapy group were less likely to have

wheezing after intubation (77% to 80% vs. 6.7%, P=0.0058) (130)

A 2007 narrative review discussed the perioperative management of patients with COPD (131)

Inhaled anticholinergics


Comments: To maintain bronchodilator effect

Evidence:

A randomized trial compared prophylactic treatment with either an inhaled β-2 adrenergic agonist or an inhaled cholinergic antagonist or a placebo inhalation in 42 patients undergoing intubation for surgery.

Both bronchodilators resulted in lower lung resistance after intubation compared with placebo (132)

Inhaled steroids

Recommendation: Continue or consider starting if bronchospasm is present

Comments: To maintain anti-inflammatory and bronchodilator effects

Leukotriene antagonists (montelukast, zafirlukast) and lipoxygenase inhibitors (zileuton)

Recommendation: Continue?

Comments: No data in perioperative setting

Systemic steroids for asthma/COPD

Recommendation: Continue/increase; may start prophylactically if patient had been on steroids in the recent past

Comments: Give stress doses of hydrocortisone if suspected suppression of hypothalamic-pituitary-adrenal axis

Evidence:

A retrospective cohort study evaluated risks associated with preoperative corticosteroids in 172 patients with asthma. Overall, 5.2% of patients developed postoperative bronchospasm and 3.6% had

postoperative infections (133)

COPD = chronic obstructive pulmonary disease.



of 74

Perioperative Endocrine Medication Management

Insulin

Recommendation: Modify and follow fingersticks: options include 1/2-2/3 NPH dose, or iv regular insulin infusion

Comments: Type 1 diabetics require perioperative insulin to prevent ketoacidosis. Hypoglycemia is more dangerous than hyperglycemia. Tight control perioperatively is not clearly defined, and it may or may

not result in better outcome

Evidence:

A prospective, randomized study of insulin-requiring diabetic patients undergoing orthopedic surgery found better diabetic control in those receiving an infusion of 2 U/h of regular insulin than those receiving

two thirds of their daily maintenance dose of NPH; however, two of eight patients receiving the infusion needed a reduction in dose and increased dextrose infusion to avoid hypoglycemia (134)

A study of 65 NIDDM patients undergoing major surgery showed that those receiving sc or continuous iv insulin had better glucose control than those in the routinely managed group. The iv insulin group also

required a smaller insulin dose and only had one hypoglycemic event (135)

A cohort study evaluated the impact of continuous insulin infusion with tighter glucose control on surgical outcomes in patients undergoing cardiac surgery. Continuous insulin therapy was associated with

lower rates of hospital mortality (57% reduction) and deep sternal wound infections (66% reduction) after CABG (136)

A cohort study compared outcomes in diabetic patients undergoing cardiac surgery who were treated with sc insulin or continuous insulin infusion. In the multivariate analysis, continuous insulin infusion was

associated with a lower risk for death (OR, 0.43; P=0.001) (137)

A pre-post study evaluated the impact of an insulin-infusion protocol with a target glucose level of 80-150 mg/dL in postoperative cardiothoracic surgery patients. The protocol resulted in significantly

improved glycemic control without significantly increasing the risk for hypoglycemia (138)

A prospective, randomized trial divided 401 patients taking evening insulin glargine into two groups according to absence of short-acting insulin and then randomly assigned them to three evening glargine

strategies: take 80% of the usual dose; call a physician for dose; or refer to a dosing table based on self-reported usual fasting blood glucose. The achievement of target preoperative fasting blood glucose

levels was similar among all three strategies in both insulin-glargine groups, but fewer patients following the dosing table had glucose levels above 249 mg/dL. The authors concluded that a strategy based on

usual glycemic control may better prevent hyperglycemia (139)

Sulfonylureas

Recommendation: Discontinue

Comments: Stop 12-72 hours before surgery depending on half-life of drug and type of procedure to minimize possibility of hypoglycemia

Evidence:

Consensus

Meglitinides (repaglinide, nateglinide)

Recommendation: Probably discontinue, although uncertain

Comments: Minimize possibility of postoperative hypoglycemia (although unlikely as a single agent)

Evidence:

Consensus; no specific data in perioperative period

Biguanides (metformin)

Recommendation: Discontinue 24-48 hours before major surgery; can stop on morning of radiologic procedure using iv contrast media

Comments: To minimize the rare possibility of lactic acidosis; less risk with iv contrast procedures, especially with normal renal function

Evidence:

A 1999 systematic review of metformin-associated lactic acidosis found that almost all reported cases occurred in patients with decreased renal function or other contraindications to the drug (140)



of 74

Thiazolidinediones (rosiglitazone, pioglitazone)

Recommendation: Probably discontinue on morning of surgery although uncertain

Comments: Insulin sensitizers; possibility of postoperative hypoglycemia; potential for liver dysfunction (based on problems with troglitazone)

Evidence:

Consensus

α-glucosidase inhibitors (acarbose, miglitol)


Comments: Probably minimal risk for hypoglycemia based on mechanism that minimizes increase in postprandial glucose

Evidence:

Consensus

Thyroxine

Recommendation: Continue (or start preoperatively, although hypothyroid patients tolerate surgery well in most cases)

Comments: Has long half-life, iv preparation available; risk of surgery with mild-moderate hypothyroidism is low

Evidence:

A retrospective cohort study compared surgical outcomes in 59 patients with mild to moderate hypothyroidism and matched controls. There were no differences in outcomes (141)

Antithyroid drugs (propylthiouracil, methimazole)

Recommendation: Continue or start preoperatively

Comments: Inhibit synthesis of thyroxine, prevent conversion from T4 to T3

Evidence:

A randomized study of 30 untreated hyperthyroid patients showed that methimazole and thyroxine normalized T3 and decreased risk for postoperative hypothyroidism compared with metoprolol alone (142)

β-blockers

Recommendation: Continue or start preoperatively

Comments: Decrease adrenergic activity, decrease peripheral conversion of T4 to T3

Evidence:

In 130 patients undergoing subtotal thyroidectomy, preoperative propranolol and metoprolol both prevented thyroid storm. Metoprolol offered additional advantages of shortened preoperative preparation

time, simplicity of dosage, and shorter postoperative stay compared with propranolol (143)

Preoperative treatment with metoprolol alone compared favorably to methimazole and thyroxine in preventing thyroid storm and perioperative complications (142)

Potassium iodide (potassium iodide)

Recommendation: Continue or start preoperatively for clinical hyperthyroidism

Comments: Prevent release of T4 and T3

Evidence:

An observational study reported outcomes in 10 patients who were undergoing surgery for Grave's disease. Potassium iodide and propranolol for 10 days normalized T3 and T4 better than either drug alone



of 74

had done historically (144)

Glucocorticoids

Recommendation: Continue/increase

Comments: Give stress doses of hydrocortisone if suspected suppression of hypothalamic-pituitary-adrenal axis. Adrenal suppression secondary to glucocorticoid therapy is variable and may last 9-12 months.

ACTH stimulation test results may not correlate with clinical outcome

Evidence:

A 2008 systematic review of perioperative stress-dose steroids included nine studies. Hemodynamics did not differ between patients on stress-dose steroids and those on chronic doses (145)

Oral contraceptives

Recommendation: Continue (with DVT prophylaxis) or discontinue several weeks before surgery and use alternative method for contraception

Comments: Possible risk for pregnancy may outweigh risk for DVT. Oral contraceptives increase DVT risk, although absolute risk is low in young, healthy women. Oral contraceptives reduced antithrombin III

and anti-Xa levels

Evidence:

A 2001 systematic review evaluated the risk for VTE associated with third-generation oral contraceptive pills. Third-generation oral contraceptive pills were associated with a higher risk for VTE than second-

generation oral contraceptive pills (adjusted OR, 1.7 [CI, 1.4 to 2.0]) (146)

Postmenopausal HT

Recommendation: Discontinue at least 30 days before surgery (if possible)

Comments: Increases risk for VTE and CAD

Evidence:

A 2012 systematic review for the U.S. Preventive Services Task Force included nine fair-quality trials with most of the results reported from the Women's Health Initiative, which had 11 years of follow-up. The

results of this analysis included the finding that estrogen plus progestin therapy increased the number of cases of invasive breast cancer (8 more per 10,000 women-years), stroke (9 more per 10,000

women-years), and DVT (12 more per 10,000 women-years). This analysis reported risks for both combined estrogen and progestin therapy as well as for estrogen-only therapy (147)

Tamoxifen (tamoxifen)

Recommendation: Consult oncologist before any decision to discontinue

Comments: Increased DVT risk but need to clarify risk-benefit ratio

Evidence:

A 2013 systematic review for the U.S. Preventive Services Task Force of medications to reduce the risk for primary breast cancer included seven studies. Tamoxifen increased thromboembolic events more

than raloxifene (NNH, 250) (148)

Raloxifene (raloxifene)

Recommendation: Discontinue at least 3 days preoperatively

Comments: Increased DVT risk similar to HT and greatest in first 4 months of use; selective estrogen-receptor modulator

Evidence:

The MORE trial was a randomized trial comparing raloxifene with placebo in over 7000 women with osteoporosis. Raloxifene increased the risk for DVT (RR, 3.1) (149)

Alendronate (alendronate)

Recommendation: Discontinue at least 1 day before surgery

http://archsurg.jamanetwork.com/article.aspx?articleid=402330






of 74

Comments: Stop due to specific administration guidelines: unable to remain NPO; bisphosphonate that inhibits osteoclast-mediated bone resorption

Evidence:

Must be taken with at least 6-8 oz of water and patient should not lie down for at least 30 minutes and until after the first food of the day (as per manufacturer's recommendations)

A case report of a patient developing hypocalcemic tetany after bowel prep with Fleet Phospho-Soda suggested that patients taking bone metabolism regulators may not be able to respond appropriately to

hypocalcemic stressors (150)

ACTH = adrenocorticotropic hormone; CABG = coronary artery bypass graft(ing); CAD = coronary artery disease; CI = confidence interval; DVT = deep venous thrombosis; HT = hormone therapy; iv =

intravenous; MORE = Multiple Outcomes of Raloxifene Evaluation; NIDDM = non-insulin-dependent diabetes mellitus; NNH = number needed to harm; NPH = neutral protamine Hagedorn (insulin); NPO =

nothing by mouth; OR = odds ratio; RR = risk ratio; sc = subcutaneous; T3 = triiodothyronine; T4 = thyroxine; VTE = venous thromboembolism.



of 74

Perioperative Neurologic Medication Management

Recommendation: Continue (except before neurosurgery aimed at removing epileptic foci); may start prophylactically before intracranial surgery

Comments:

To prevent perioperative seizures; may be useful for short-term prophylaxis with intracranial aneurysms or cerebral tumors

Non-oral formulations may be substituted perioperatively (151):

Commercial alternatives are available for clonazepam, diazepam, lacosamide, levetiracetam, lorazepam, midazolam, nitrazepam, phenobarbital, phenytoin, and valproic acid.

Alternatives requiring preparation are available for carbamazepine, clobazam, lamotrigine, oxcarbazepine, primidone, and topiramate.

There are no alternatives for ethosuccimide, felbamate, retigabine, stiripentol, tiagabine, vigabatrin, and zonisamide

Evidence:

A review discusses numerous drug interactions between anticonvulsants and anesthetic agents (152)

A retrospective analysis of 387 neurosurgical patients at low risk for seizures with intracranial aneurysms found that postoperative anticonvulsant medication given for an average of 3 days controlled seizures

(153)

A study of 128 patients undergoing craniotomy for intracerebral tumors recommended short-term preventive treatment with antiepileptic drugs in patients without preoperative seizures (154)

Acute withdrawal of various antiepileptic drugs provoked seizures in temporal lobe epilepsy patients undergoing presurgical video-EEG monitoring (155)

Phenytoin


Comments: Check level; CNS depressant; may reduce requirement for general anesthetics

Evidence: Consensus

Phenobarbital


Comments: Check level; CNS depressant; avoid rebound; may reduce requirement for general anesthetics

Evidence: Consensus

Carbamazepine


Comments: Check level

Evidence:

Discontinuation of carbamazepine was associated with increased frequency of seizures (maximal increase in the first 2 weeks) in patients with a history of epilepsy and incompletely controlled seizures (156)

Valproic acid


Comments: Check level; CNS depressant; may reduce requirement for general anesthetics

Evidence:

Valproic acid did not increase complications of hemostasis during therapeutic resections for epilepsy, and it should not be discontinued before craniotomy (157)



of 74

Carbidopa/levodopa

Recommendation: Uncertain; either continue or discontinue the night before surgery

Comments: Withdrawal may worsen symptoms of Parkinsonism or precipitate a neuroleptic malignant-like syndrome; may have drug interactions; can cause arrhythmias (treated with β-blockers), hypo- or

hypertension

Evidence:

Three patients with Parkinson's disease developed a neuroleptic malignant-like syndrome after discontinuation of carbidopa-levodopa or on a drug holiday (158)

For myasthenia gravis ( pyridostigmine , neostigmine )

Recommendation: Continue (may reduce dose if not severe)

Comments: Despite potential medication side effects (bradycardia, salivation), withdrawal may worsen muscle weakness and increase risk for respiratory complications

Evidence:

In a review of 324 thymectomies, excessive incidence of respiratory insufficiency and airway-associated morbidity was potentially related to prolonged mechanical ventilation and withdrawal of

anticholinesterase medication (159)

Myasthenia gravis patients treated with pyridostigmine show a resistance to the effects of succinylcholine (160) and vecuronium (161)

Myasthenic patients are sensitive to nondepolarizing relaxants, but intermediate-acting nondepolarizing relaxants (atracurium and vecuronium) are eliminated rapidly and can be titrated and reversed (162)

For Alzheimer's disease (tacrine, donepezil)


Comments: Intravenous administration of tacrine may prolong action of succinylcholine; po use may cause resistance to nondepolarizing muscle relaxants

Evidence:

Tacrine depresses cholinesterase activity and prolongs the duration of the neuromuscular block (163)

Donepezil has a possible synergistic effect with succinylcholine-type muscle relaxants; discontinue 2-3 weeks before surgery due to its long half-life (164)

CNS = central nervous system; EEG = electroencephalogram; po = oral.



of 74

Perioperative Psychiatric Medication Management

Overview: Based on a 2006 systematic review (165), a multidisciplinary group of clinicians made the following recommendations:

Patients who use lithium, MAO inhibitors, tricyclics, and clozapine have serious drug-drug interactions and qualify for American Society of Anesthesiologists Physical Status 3. From the perspective of physical

risk, they require discontinuation; however, from the perspective of withdrawal risk and psychiatric relapse, they need intensive, integrated anesthetic/psychiatric management.

For ASA Physical Status 2 patients on SSRIs who are physically and mentally stable, the risk of withdrawal seems to justify their continuation. Patients with higher physical or psychiatric risks should be seen

in consultation.

Physical and psychiatric risks of patients using antipsychotics and other antidepressants are enhanced and should be considered to be ASA Physical Status 2 from a physical perspective. From a withdrawal

perspective, they should be seen by their psychiatrists

TCAs (amitriptyline, nortriptyline, imipramine, desipramine)

Recommendation: Uncertain; continue or taper and discontinue at least several days before elective surgery

Comments: Anticholinergic effects, widened QRS and QT, arrhythmias, drug interactions, withdrawal syndrome

Evidence:

Most anesthesiologists surveyed continued TCAs despite theoretical concerns. Reported complications in surgical patients are extremely rare (166)

Because effects of long-term TCAs last several days after cessation of the drug and the mechanisms for interactions have been identified, continuation of therapy perioperatively is reasonable provided due

caution is used (167)

TCA withdrawal syndromes are characterized by GI or somatic distress, sleep disturbances, mood fluctuations, and movement disorders, most likely due to rebound excess cholinergic activity (168)

MAO inhibitors (pargyline, phenelzine)

Recommendation: Usually stop 10-14 days before surgery (although some anesthesiologists feel they can be continued with precautions)

Comments: Potential drug interactions. The newer class (RIMA) allows selective rapidly reversible inhibition of type A-MAO. If continued perioperatively, avoid foods with high amounts of tyramine

Evidence:

Newer studies found the risk for pharmacokinetic drug reactions to be lower for tranylcypromine than for phenelzine, and anesthesia without discontinuation of MAO inhibitors may be safe after careful

evaluation of the patient's perioperative and psychiatric risk (169)

There were no differences in hemodynamics or complications in 27 patients undergoing ECT or elective surgery while on MAO inhibitors (170)

Surgical case reports include a death after cardiac surgery with MAO inhibitors and fentanyl plus midazolam (171), two cases of urgent cardiac surgery using fentanyl without adverse effects (172), a

successful case in a patient refusing to stop an MAO inhibitor and TCA (173), and cardiovascular collapse in a patient who discontinued an MAO inhibitor 20 days before surgery (174)

Nonsurgical case report and reviews: Interactions with sympathomimetics can cause hypertension and with meperidine result in hyperpyrexia, hallucinations, coma (175; 176)

SSRIs (fluoxetine, sertraline, paroxetine, citalopram, fluvoxamine)

Recommendation: Continue with caution

Comments: Associated with withdrawal syndrome if stopped; inhibit cytochrome P450 enzymes; can increase INR; may be associated with increased risk for bleeding

Abrupt discontinuation can result in a syndrome characterized by specific physical and psychological symptoms. Incidence, timing, and severity of symptoms vary related to plasma elimination and clinical

characteristics (177)

Evidence:

A retrospective study of 72,540 patients on SSRIs compared with 457,876 not taking SSRIs found that receiving SSRIs in the perioperative period was associated with a higher risk for adverse events

(mortality, readmission at 30 days, transfusions); however, an unmeasured covariate may have explained the result (178)

A retrospective cohort study evaluated the association between the use of SSRIs and bleeding. SSRIs were associated with an increased risk for transfusion (adjusted OR, 3.71 [CI, 1.35 to 10.18]) in patients



of 74

undergoing orthopedic surgery (179)

In users of coumarins and antiplatelet agents, use of SSRIs was associated with increased bleeding risks (180; 181)

Phenothiazines, butyrophenones,risperidone, ziprasidone, olanzapine


Comments: Can enhance CNS depression, lower seizure threshold, cause ECG abnormalities, arrhythmias, hypotension, neuroleptic malignant syndrome; discontinuation associated with withdrawal dyskinesia

and rebound agitation

Evidence:

Consensus

Benzodiazepines

Recommendation: Continue; may be started preoperatively (by the anesthesiologist) or postoperatively for sedation

Comments: May decrease anesthetic requirement. Chronic use may increase requirement for opiates. Abrupt discontinuation may cause a withdrawal syndrome

Evidence:

An abstinence syndrome with anxiety, mood swing, depression, and thinking disorder developed 24 hours after abruptly stopping oxazepam, which the patient had been taking for 2 months (182)

Abrupt withdrawal of sedation with midazolam, propofol, or lorazepam in critically ill patients may precipitate withdrawal symptoms (183)

Subjects treated with midazolam preoperatively self-report improved postoperative psychological and pain recovery (184)

Preoperatively, midazolam premedication was associated with a significantly lower anxiety level and higher sedation level but did not prolong the discharge time (185)

Lithium (lithium)

Recommendation: Uncertain; continue or stop 2-3 days before surgery

Comments: Check level; can cause ECG changes, prolonged action of muscle relaxants, NDI

Evidence:

Case reports of NDI in surgical patients (186; 187; 188) and other potential difficulties with lithium and anesthesia (189)

Case reports of patients treated with lithium carbonate in preoperative preparation of Grave's disease showed successful surgical outcome with no significant adverse effects (190; 191; 192)

ASA = American Society of Anesthesiologists; CI = confidence interval; CNS = central nervous system; ECG = electrocardiography; ECT = electroconvulsive therapy; GI = gastrointestinal; INR = international

normalized ratio; MAO = monoamine oxidase; NDI = nephrogenic diabetes insipidus; OR = odds ratio; QRS = electrocardiographic complex; QT = electrocardiographic interval; RIMA = reversible inhibition of

monoamine oxidase; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.



of 74

Perioperative Gastrointestinal Medication Management

H2 blockers

Recommendation: Continue or start prophylactically

Comments: May be protective for stress ulcers and aspiration

Evidence:

See PPIs for aspiration protection (193; 194; 195)

Prophylactic ranitidine prevented postoperative gastroduodenal complications in high-risk neurosurgical patients (196)

Prophylactic iv ranitidine had a beneficial effect on postoperative infectious complications in patients following acute colorectal surgery (197)

PPIs

Recommendation: Continue or start prophylactically

Comments: May be protective for stress ulcers and aspiration

Evidence:

Two consecutive doses of rabeprazole, lansoprazole, or omeprazole or a single dose of ranitidine on the morning of surgery reduced gastric volume and acidity, potentially protecting against aspiration

pneumonitis (193; 194; 195)

In CABG patients in postoperative intensive care, better gastric pH control and potential prevention of gastric stress ulcers was achieved with famotidine or ranitidine compared with cimetidine or antacids

(198)

A study of 2252 ICU patients found mechanical ventilation and coagulopathy to be the most important risk factors for stress-induced GI bleeding; in the absence of these two risk factors, clinically important

GI bleeding was rare (0.1%), and prophylaxis can be safely withheld (199)

Immunomodulators/Immunosuppressants

Purine analogues: azathioprine, 6-mercaptopurine

Recommendation: Continue or hold on day of surgery

Comments: Theoretical risk for perioperative myelotoxicity (thiopurines—renal elimination)

Evidence:

The use of azathioprine, 6-mercaptopurine, or infliximab did not increase postoperative infections in several studies of patients with IBD undergoing abdominal surgery (200; 201; 202); however, one study

of 343 patients reported an increased risk of postoperative intra-abdominal septic complications, primarily in patients with known risk factors (203)

Cyclosporine (cyclosporine)


Comments: Minimize graft rejection

Evidence:

A 2006 systematic review including five studies with azathioprine, five with cyclosporine, and three with infliximab showed no increased risk for total or infectious complications (204)

Several studies found no significant increase in perioperative complications in patients on cyclosporine (205; 206)

Chronic cyclosporine therapy in postcardiac transplant patients undergoing noncardiac surgery did not clinically prolong the anesthetic effect (207)



of 74

Fourteen patients with cardiac transplants undergoing noncardiac surgery received cyclosporine alone or with azathioprine or prednisone. There were no deaths and two cases of wound infection (208)

CABG = coronary artery bypass graft(ing); GI = gastrointestinal; H2 = histamine-2; iv = intravenous; IBD = inflammatory bowel disease; ICU = intensive care unit; PPI = proton-pump inhibitor.



of 74

Perioperative HIV Medication Management

Antiretroviral agents

Recommendation: Continue up to surgery, stop together, then restart together

Comments: Theoretical advantage to minimize emergence of resistant viral strains; may affect cytochrome P450 system

Evidence:

Consensus (209; 210)

Midazolam should be avoided or used at a reduced dosage with saquinavir, which significantly decreases its clearance (211)

HIV patients with CD4 counts <200 cells/μL were more likely to get sepsis postoperatively (despite antibiotics and antiretrovirals) than patients with higher CD4 counts (212)

CD4 = cluster of differentiation 4; HIV = human immunodeficiency virus.



of 74

Perioperative Herbal Medication Management

St. John's wort

Recommendation: Discontinue at least 5 days before surgery

Comments: Inhibits serotonin, norepinephrine, and dopamine reuptake; long half-lives of active ingredients: hypericin (43.1 hours), hyperforin (9 hours); induces cytochrome P450 enzymes, alters

metabolism of other drugs

Evidence:

Cyclosporine levels were decreased in transplant recipients (213; 214)

Anticoagulant effect of warfarin was reduced (215)

May create a syndrome of central serotonin excess (216)

Ginkgo biloba

Recommendation: Discontinue at least 36 hours before surgery

Comments: Inhibits platelet aggregation; active ingredient, terpenoids, have half-lives of 3-10 hours

Evidence:

Ginkgo has been associated with spontaneous intracranial bleeding (217; 218; 219; 220), hyphema (221), and postoperative bleeding following laparoscopic cholecystectomy (222)

Ginseng

Recommendation: Discontinue at least 24 hours before surgery (based on half-life) or 7 days before due to platelet inhibition

Comments: Inhibits platelet aggregation; alters coagulation cascade; may cause hypoglycemia; ginsenosides have half-lives of 0.8-7.4 hours

Evidence:

Ginseng lowered postprandial glucose levels in both diabetics and nondiabetics (223)

Ginsenosides inhibited platelet release reaction while panaxynol in addition inhibited aggregation and thromboxane formation (224)

American ginseng reduced warfarin's anticoagulant effect in a small group of healthy patients (225)

Garlic

Recommendation: Discontinue at least 7 days before surgery

Comments: Inhibits platelet aggregation

Evidence:

Components of garlic exerted their effects at various stages in the process of platelet aggregation (226)

An elderly man developed a spontaneous spinal epidural hematoma causing paraplegia secondary to a qualitative platelet disorder from excessive garlic ingestion (227)

Kava

Recommendation: Discontinue at least 24 hours before surgery

Comments: Dose-dependent CNS effects including sedation; may be associated with liver injury; kavalactone half-life is 9 hours

Evidence:



of 74

Case report of coma attributed to an alprazolam-kava interaction (228)

Echinacea

Recommendation: Discontinue (as far in advance of surgery as possible)

Comments: Short-term immunostimulatory effects but long-term use has potential for immunosuppression; pharmacokinetics not studied

Evidence:

Expert opinion warned against concomitant use of echinacea and immunosuppressive drugs because of the probability of decreased effectiveness, especially in patients awaiting transplants (229)

Long-term use (>8 weeks), however, has the potential for immunosuppression and the possibility of impaired wound healing and opportunistic infections (5; 230)

Saw palmetto


Comments: Increases bleeding time

Evidence:

Case report of intraoperative hemorrhage with a prolonged bleeding time that normalized after stopping the herb (231)

Ma huang (ephedra)


Comments: Sympathomimetic effects

Evidence:

Reports to the FDA of adverse effects of ephedra alkaloids included hypertension, palpitations, tachycardia, stroke, seizure, and death (232)

Valerian

Recommendation: Taper and discontinue slowly weeks before surgery (if physically dependent) or continue until the day of surgery

Comments: May potentiate sedative effects of anesthetics and adjuvants; may be associated with withdrawal symptoms; pharmacokinetics not studied but probably short-lived

Evidence:

Inhibits breakdown of GABA and produces dose-dependent sedation and hypnosis (233; 234)

Case report of valerian withdrawal: a patient presenting with delirium and cardiac complications after surgery, responding to benzodiazepine treatment (235)

CNS = central nervous system; FDA = Food and Drug Administration; GABA = γ-aminobutyric acid.



of 74

Surgical Risk Stratification and Associated VTE Incidence

Patient Risk Risk Factor Stratification VTE Incidence without Prophylaxis

Low Minor surgery in patients under age 40 with no additional risk

factors

Calf vein DVT: 2%

Proximal vein DVT: 0.4%

Clinical PE: 0.2%

Fatal PE: 0.002%

Moderate Nonmajor surgery in patients aged 40-60 with no clinical risk

factors

Minor surgery lasting <30 minutes in patients with clinical risk

factors

Major surgery in patients under age 40 with no clinical risk factors

Calf vein DVT: 10%-20%

CellTxtL::Proximal DVT: 2%-4%

CellTxtL::Clinical PE: 1%-2%

CellTxtL::Fatal PE: 0.1%-0.4%

High Nonmajor surgery in patients over age 60 or with clinical risk factors

Major surgery in patients over age 40 or with clinical risk factors




CellTxtL::Fatal PE: 0.4%-1%

Very high Major surgery in patients over age 40 with history of VTE, cancer,

or certain hypercoagulable states

Hip or knee arthroplasty

Hip fracture surgery

Major trauma

Spinal cord injury




CellTxtL::Fatal PE: 0.2%-5%

DVT = deep venous thrombosis; PE = pulmonary embolism; VTE = venous thromboembolism.



of 74

VTE Prophylaxis Regimens by Surgical Procedure

General Surgery

Low risk (A)*

Early ambulation postoperatively (adequate for patients at very low risk)

IPC sleeves

Graduated elastic stockings

Moderate risk (A)

Graduated elastic stockings

IPC sleeves (preferable), or

Enoxaparin, 40 mg sc qd, or

Dalteparin, 5000 IU sc, or

Unfractionated heparin, 5000 IU sc q12h

High risk (A)

Unfractionated heparin, 5000 IU sc q8h, or


Dalteparin, 5000 IU sc qd

Very high risk (C)

Unfractionated heparin, 5000 IU sc q8h, plus graduated elastic stockings and/or IPC sleeves, or

Enoxaparin, 40 mg sc qd (extended duration), plus graduated elastic stockings and/or IPC sleeves, or

Dalteparin, 5000 IU sc qd (extended duration), plus graduated elastic stockings and/or IPC sleeves

Rivaroxaban, 10 mg po qd

Comments

IPC sleeves alone are best reserved for patients at high risk for hemorrhage (e.g., trauma patients, patients undergoing procedures with a high incidence of bleeding such as radical prostatectomy, patients

with factor deficiencies, craniotomy)

Graduated elastic stockings and IPC sleeves must be placed before surgery and worn continuously through the intraoperative and postoperative period until the patient is ambulatory

The rate for symptomatic or asymptomatic total VTE in general surgery is ~25% without prophylaxis

Evidence

A 2012 guideline from the American College of Chest Physicians provided guidance based on pooled VTE prophylaxis data on surgical and trauma patients (21; 38)

A 1992 meta-analysis of studies from 1984 to 1991 compared LMWH vs. unfractionated heparin for postoperative VTE prophylaxis. Among general-surgery patients there was no improvement in the benefit-

to-risk ratio for LMWH compared with unfractionated heparin. In orthopedic surgery, the absolute risk reduction for VTE was significant for LMWH vs. unfractionated heparin (236)

Hip fracture patients who were repaired within 2 days of hospitalization and had more than 5 physical or occupational therapy sessions had a shorter length of stay, fewer medical complications, and were more likely to return to the community (237)




of 74

A prospective randomized trial compared intermittent pneumatic calf compression with no treatment in patients undergoing major abdominal surgery. There was no difference in the incidence of VTE between

the two groups (238)

In a review of VTE prophylaxis with unfractionated heparin in two specific surgical populations, unfractionated heparin was effective in reducing the incidence of fatal PE and proximal DVT (239)

Orthopedic Surgery

Total hip or knee replacement (A) (treat for at least 10-14 days)

LMWH (preferred)

Enoxaparin, 30 mg sc q12h or 40 mg sc qd, or

Dalteparin, 5000 IU sc qd, or

Fondaparinux, 2.5 mg qd

Warfarin adjusted to a target INR of 2-3

Rivaroxaban 10 mg, po qd1

Apixaban 2.5 mg bid1

Dabigatran 110 mg qd1

Unfractionated heparin

Aspirin (may be less effective than other options)

Adjuvant prophylaxis with IPC (with or without graduated elastic stockings) may provide additional benefit (C)

Hip fracture surgery

LMWH

Enoxaparin, 30 mg sc q12h (C), or

Fondaparinux, 2.5 mg qd (A)

Unfractionated heparin

Warfarin adjusted to a target INR of 2-3

Aspirin (may be less effective than other options)

Extended prophylaxis (A)

LMWH (preferred)



Warfarin with a goal INR of 2-3

Comments

Dextran or IPC alone is not recommended

Enoxaparin 40 mg qd has not been approved for prophylaxis for total knee replacement, but may be as effective and is less costly than 30 mg q12h



of 74

The risk for VTE extends beyond the hospital stay; extended prophylaxis for 4-6 weeks may reduce the incidence of clinically important VTE events

Without prophylaxis, the rates for symptomatic and asymptomatic VTE in total hip replacement include total DVT, 45%-57%; proximal DVT, 23%-36%; total PE, 0.7%-30%; and fatal PE, 0.1%-0.4%. In total

knee replacement, rates are total DVT, 40%-84%; proximal DVT, 9%-20%; total PE, 1.8%-7%; and fatal PE, 0.2%-0.7%. In hip fracture patients without prophylaxis, rates are total DVT, 36%-60%; proximal DVT, 17%-36%; total PE, 4.3%-24%; and fatal PE, 3.6%-12.9%

Evidence

A 2012 guideline from the American College of Chest Physicians evaluated pooled VTE prophylaxis data on surgical and trauma patients and provided recommendations on VTE prophylaxis (21)

A 2002 meta-analysis of four randomized controlled trials found that fondaparinux significantly reduced the incidence of VTE by day 11 (182/2682 = 6.8%) compared with enoxaparin (371/2703 = 13.7%)

with an odds ratio of 0 ([CI, 0.458- 0.631] P<0.001) among patients undergoing major orthopedic surgery. This beneficial effect was consistent across all types of surgery and all subgroups. Major bleeding occurred more frequently in the fondaparinux-treated group (2.7%) than in the enoxaparin group (1.7%) (P=0.008) (98)

A 2001 systematic review and meta-analysis demonstrated that among patients undergoing total hip or knee replacement, extended-duration prophylaxis (for 3042 days) significantly reduced the frequency of symptomatic VTE. The reduction in risk is equivalent to about 20 symptomatic events per 1000 patients treated (240)

The four RECORD trials (241; 242; 243; 244) evaluated the efficacy and safety of rivaroxaban compared with enoxaparin in over 12,000 patients undergoing hip or knee arthroplasty. In the RECORD 1 trial,

which included 4541 patients undergoing hip arthroplasty, a 31- to 39-day course of rivaroxaban significantly reduced the total event rate compared with an equal duration of treatment with enoxaparin (1.1%

and 3.7%, respectively; P<0.001) (241). In the RECORD 2 trial involving 2509 patients undergoing total hip arthroplasty, a 31- to 39-day course of rivaroxaban significantly reduced the total event rate

compared with a 10- to 14-day course of enoxaparin followed by 21 to 25 days of placebo (2.0% and 9.3%, respectively; P<0.0001) (242). The

RECORD 3 trial included 2531 patients undergoing knee arthroplasty. A 10- to 14-day course of treatment with rivaroxaban significantly reduced the total event rate compared with an equal duration of treatment with enoxaparin (9.6% and 18.9%, respectively, P<0.001) (243). In the RECORD 4 trial involving 3148 patients undergoing knee arthroplasty, a 10- to 14-day course of treatment with rivaroxaban significantly reduced the total event rate compared with an equal duration of enoxaparin at the higher 30-mg twice-daily dose (6.9% and 10.1%, respectively; P<0.012) (244). In both the RECORD 2 and 3 trials, rivaroxaban significantly reduced the incidence of symptomatic VTE compared with enoxaparin. Rivaroxaban did not increase major bleeding in any of the trials, but a pooled analysis of all four trials revealed a small but significant increase in major plus clinically relevant nonmajor bleeding with rivaroxaban

A pooled analysis compared newer agents (apixaban, rivaroxaban and dabigatran) with enoxaparin for the prevention of VTE after total hip or knee replacement. The study found that rivaroxaban was superior to enoxaparin for the prevention of major VTE with RR, 0.32 [CI, 0.15-0.67] and that apixaban and dabigatran were equivalent. There were no statistically significant differences in major bleeding when

comparing newer drugs with enoxaparin (245)

Patients undergoing total hip replacement were randomly assigned to enoxaparin vs. placebo. Venography was the endpoint for DVT. Four patients (10.8%) receiving enoxaparin developed DVT, whereas 20

(51.3%) had DVT in the placebo group. The observed major bleeding rate was 4% in both groups. This showed the efficacy of enoxaparin for preventing DVT in this patient group (246)

Investigators compared enoxaparin and warfarin for the prevention of VTE after total hip arthroplasty. Inpatient programs providing treatment with either enoxaparin, 30 mg sc q12h, or adjusted-dose

warfarin for a mean of 7.3 days afforded protection against VTE, with overall rates of morbidity and mortality of 3.7% and 0.6%, respectively, and a very low rate of major bleeding complications (0.9%) for 3

months after total hip arthroplasty. During the hospitalization, the patients managed with enoxaparin had a lower rate of VTE than those managed with adjusted-dose warfarin (P=0.008). This benefit was lost

after the medication was discontinued, with no difference in the prevalence of VTE between the two groups at 3 months after discharge from hospital (247)

A large, randomized trial compared aspirin, 160 mg, vs. placebo until post-op day 35 in patients undergoing repair of fractured hips. The group assigned to aspirin had lower rates of VTE (DVT or PE), with a

number needed to treat of 111 after 35 days. Patients were allowed to have other forms of VTE prophylaxis, which makes the results difficult to interpret and apply (248)

In a survey of members in the American Association of Hip and Knee Surgeons, warfarin was the most common drug treatment used for total hip and total knee arthroplasties, followed by IPC sleeves and

LMWH (249)

A consecutive patient study of 360 patients undergoing total hip arthroplasty showed that continuing warfarin (0.5%) after discharge for 4 weeks was more effective than placebo (9.4%) in the incidence of

VTE (250)

In another study of prolonged out-of-hospital prophylaxis after total hip replacement, the LMWH reviparin was compared with an adjusted dose oral anticoagulant (acenocoumarol). Symptomatic

thromboembolic events occurred in 2.3% (15/643) of the reviparin group and 3.3% (21/636) of those receiving acenocoumarol. Major bleeding was reported in 1.4% (9/643) of the reviparin group and 3.7%

(24/643) in those on the adjusted-dose oral therapy (251)

In a trial of 89 patients undergoing total hip or knee replacement, investigators evaluated the efficacy of graded compression stockings. All patients had the pressure gradient generated by the compression

stockings evaluated, and 98% of the stockings failed to produce the ideal pressure gradient. Reversed gradient was observed in 54%, and this resulted in a higher incidence of DVT. The overall rate of DVT

was 16.7% by venography (252)





of 74

Gynecologic Surgery

Low risk (C)

Early mobilization alone is recommended for low-risk patients undergoing short procedures for benign disease

Moderate to high risk (surgery for benign disease without additional risk factors)

Unfractionated heparin, 5000 IU sc q12h (A), or

LMWH

Enoxaparin, 40 mg sq qd, or

Dalteparin, 5000 IU sc qd (C)

IPC (C)

Very high risk (malignancy) (C)

IPC and/or unfractionated heparin, 5000 IU sc q8h, or

LMWH



Comments

IPC sleeves must be placed before surgery and worn continuously through the intraoperative period and postoperative period until the patient is ambulatory; IPC may be combined with LMWH

Extended prophylaxis after discharge may be considered for select very high-risk patients who are not ambulating or are considered to still be at risk for development of VTE. LMWH: enoxaparin (40 mg sc qd), dalteparin (5000 IU sc qd), or warfarin (goal INR 2-3) is suggested but has not been studied in clinical trials in this patient population

The rate for symptomatic or asymptomatic total VTE in gynecologic surgery is ~16%

Evidence

LMWH and IPC appear to be similarly effective in the postoperative prophylaxis of VTE in high-risk gynecologic-oncology patients. The use of LMWH is not associated with an increased risk for bleeding

complications when compared with IPC (253)

Neurosurgery

Craniotomy (A)

IPC alone (preferred except in high-risk patients), or

IPC plus

Unfractionated heparin, 5000 IU sc q12h, or enoxaparin, 40 mg sc qd

Spinal cord injury (C)

IPC plus

Enoxaparin, 30 mg sc q12h, or

Heparin, 5000 IU sc q8h for 2 weeks, then

Enoxaparin, 40 mg sc qd, or warfarin (goal INR 2-3) continued during the rehabilitation phase



of 74

Comments

Continuing prophylaxis into the rehabilitation phase is indicated in spinal cord injury but the duration has not been established

The rate for symptomatic or asymptomatic total VTE in neurologic surgery is ~22%

Evidence

A randomized, prospective, double-blind trial of 150 patients undergoing craniotomy for brain tumor compared enoxaparin, 40 mg sc qd, with unfractionated heparin, 5000 IU sc q12h. All patients wore

graduated compression stockings plus IPC devices and had compression ultrasonography to evaluate VTE at discharge. The overall rate of asymptomatic VTE was 9.3% and there were no significant

differences between the groups (254)

Urologic Surgery

Transurethral prostatectomy (C)

Early ambulation alone is recommended for patients undergoing transurethral prostatectomy or other low-risk procedures

Moderate risk (major open urologic procedures, e.g., nephrectomy) (B)

Unfractionated heparin, 5000 IU sc q12h

LMWH



IPC

Very high risk (e.g. radical prostatectomy) (C)

IPC and or graduated elastic stockings plus

Unfractionated heparin, 5000 IU q8h, or

Enoxaparin, 40 mg sc qd, or dalteparin, 5000 IU sc qd

Evidence

A 2012 guideline from the American College of Chest Physicians evaluated pooled VTE prophylaxis data on surgical and trauma patients and provided recommendations on VTE prophylaxis (21)

A review of VTE prophylaxis with unfractionated heparin in general, orthopedic, and urologic surgery found that it was effective in reducing the incidence of fatal PE and proximal DVT (239)

In a prospective study of 36 patients undergoing urologic surgery for malignancy, patients received dalteparin for 3-7 days and no clinically evident VTE developed (255)

Major Trauma

LMWH


Dalteparin, 5000 IU sc qd, or

Unfractionated heparin, 5000 IU q8h

Patients at high risk for bleeding:

Initial IPC and elastic stockings followed by

LMWH when possible (C)




of 74

Comments

Patients with clinical risk factors for VTE should receive prophylaxis, if possible (A)

Enoxaparin is preferred if no contraindication for use such as intracranial bleeding, incomplete spinal cord injury with paraspinal hematoma, continued uncontrolled bleeding, or coagulopathy

Continue prophylaxis until patient is ambulatory

If VTE risk continues after discharge, consider extended prophylaxis with LMWH or warfarin

Evidence

Among 344 randomly assigned major trauma patients, 136 who received low-dose heparin (5000 IU sc q12h) and 129 who received enoxaparin (30 mg sc q12h) had venograms adequate for analysis. Sixty

patients given heparin (44%) developed DVT, and 40 patients given enoxaparin (31%) had DVT. The rates of proximal DVT were 15% and 6%, respectively. LMWH was more effective than low-dose heparin

in preventing VTE after major trauma (256)

*Letters in parentheses indicate strength of recommendation:

A = Strength of recommendation based on preponderance of data derived from level 1 studies, which meet all of the evidence criteria for that study type;

B = Strength of recommendation based on preponderance of data derived from level 2 studies, which meet all of the evidence criteria for that study type;

C = Strength of recommendation based on preponderance of data derived from level 3 studies, which meet all of the evidence criteria for that study type. 1U.S. FDA approval for this indication pending

bid = twice daily; CI = confidence interval; DVT = deep venous thrombosis; FDA = Food and Drug Administration; INR = international normalized ratio; IPC = intermittent pneumatic compression; LMWH =

low-molecular-weight heparin; PE = pulmonary embolism; po = orally; q8h = every 8 hours; q12h = every 12 hours; qd = every day; RR = risk ratio; sc = subcutaneous; VTE = venous thromboembolism.

perioperative medication management - cecity · perioperative medication management pier is...

Documents