Perioperative Medication Management

Routinely used medications have many potential interactions with drugs used during surgery, but few situations prohibit concurrent administration. The half-life of routinely used medications and adjustment of the dose according to the perioperative schedule must be considered. Many medications must be continued through the perioperative period, with the last dose taken with a sip of clear liquid up to 2 hours prior to the procedure, and resumed during recovery.

Other drugs must be stopped, replaced, or temporarily administered by another route. Obtain advice on selecting alternative treatments from clinical or drug information pharmacists. Additional monitoring of the patient or plasma drug concentrations may be required when different treatments or formulations are used perioperatively. Heightened awareness and diligent documentation of patient medications from admission to discharge can reduce serious problems in the perioperative management of society's increasingly elderly and frail population.

The perioperative period extends from the preoperative day through the operation and into the postoperative recovery. Proper perioperative management helps to prevent or minimize complications, to reduce postoperative pain, and to accelerate recovery. The components of perioperative medication management are as follows:

• Accurate documentation of preoperative medication

• Established decisions on stopping medications prior to surgery

• Monitoring of appropriate chemistry study results to determine dosages and the occurrence of adverse effects

• Appropriate management of pain

• Administration of adjunctive medications

• Use of appropriate formulations and alternative products when needed

• Review of discharge medications to ensure discontinuation of surgery-specific drugs (eg, anticoagulants, analgesics) to avoid polypharmacy

Some drugs (eg, beta-blockers) have potential adverse effects when discontinued abruptly and should be given parenterally in the perioperative period. Switching to an alternative formulation of the same drug may involve a change in dose due to differing bioavailability of the active drug.

Kluger et al showed that 44% of surgical patients took medications prior to surgery, with an average of 2.1 drugs per patient. ^[1] Cardiac medications accounted for the largest proportion of prescriptions (41%). Almost 50% of the drugs were omitted on the day of surgery, while on the first day after the operation, 33% of the medications were withheld. The reasons for this pattern included the following:

• Fasting (49%)

• Failure of the admitting doctor to prescribe (29%)

• Drug withheld on order of medical staff (10%)

• Drug unavailable in pharmacy or not delivered to the ward (1%)

• Gastrointestinal tract operation with prolonged ileus (3%)

• Unknown (8%)

Overnight fasting reduces the risk for aspiration of stomach contents when the patient is placed under general anesthesia. However, liquids are cleared from the stomach within 2 hours of ingestion, and no differences in the volume or pH of gastric contents is noted in those patients taking clear fluids 2 hours before surgery compared to those taking clear fluids 9 hours before surgery. Therefore, patients can be given their routine medications with sips of water up to 2 hours before anesthesia.

For excellent patient education resources, see eMedicineHealth's patient education article Pain After Surgery.

Ischemic heart disease

Patients with known coronary artery disease undergoing surgery should be monitored for evidence of myocardial ischemia and provided therapy to prevent and treat ischemia in the perioperative period.

Monitoring techniques during the perioperative period include surveillance of electrocardiographic ST-changes, echocardiographic assessment of the regional and global wall motion, and invasive measurement of pulmonary arterial and capillary wedge pressures. If ischemia is detected, medication should be titrated to specific endpoints of heart rate and blood pressure or until the ischemia resolves.

Beta-blockers provide the single best therapy for prevention of ischemia during the perioperative period. Postoperative myocardial infarction (MI) and angina have a peak incidence during the first 3 postoperative days but may occur for up to 5 days. Recent studies suggest that postoperative cardiac events may be decreased by use of perioperative beta-blocker regimens. In an excellent randomized, double-blind, placebo-controlled trial, Mangano et al showed that for patients who have or are at high risk for coronary artery disease and undergo noncardiac surgery, treatment with atenolol during hospitalization can reduce mortality and the incidence of cardiac complications for at least 2 years after the surgery. ^[2] Most hospitals now have clinical practice guidelines regarding perioperative beta-blockers.

Ischemia frequently presents atypically, with chest pain occurring only 50% of the time. In the event of possible signs of ischemia, following up the ECG with serial enzyme measurements, echocardiography, or nuclear perfusion studies may be required. If no evidence of perioperative ischemia or infarction is present, then using a simple 12-lead ECG immediately after surgery and for the first 2 postoperative days is sufficient to evaluate any change from baseline. The following chart indicates the perioperative drug management of patients with coronary artery disease.

Table 1. Outline of Perioperative Drug Management of Patients With Coronary Artery Disease (Open Table in a new window)

Hypertension

Hypertension is a risk factor for coronary artery disease. Patients with elevated blood pressure seem more likely to experience significant fluctuations in intraoperative blood pressure and associated MI. Adequate blood pressure control is essential prior to elective surgeries because this reduces perioperative ischemia and subsequent cardiac morbidity. ^[3]

Continue antihypertensive medications throughout the perioperative period, with a change of formulation or substitution if needed. Abrupt withdrawal of beta-blocking agents may adversely affect the heart rate and blood pressure and may precipitate MI.

Administer all antihypertensive medications (with a sip of water) except diuretics and ACE inhibitors until the day of surgery. Diuretics should not be administered on the day of surgery because of the potential adverse interaction of diuretic-induced volume depletion, potassium derangement, and the use of anesthetic agents. The renin-angiotensin-aldosterone system (RAAS) is involved in maintaining normal blood pressure during anesthesia. Hemodynamic instability, including refractory hypotension, has been described in RAAS-blocked patients. Therefore, ACE inhibitors should be discontinued the day before surgery. ^{[4, 5, 6]}

Appropriate perioperative management of pain, anxiety, hypoxia, and hypothermia with rewarming are key to maintaining normotension. Patients with a history of preoperative hypertension are predisposed to postoperative hypertension and to intraoperative blood pressure lability. Restarting the patient's oral medications and minimizing oral and intravenous sodium when possible are important therapies.

For those patients unable to take oral medications who require treatment, parenteral alternatives must be used. Intravenous beta-blockers, including propranolol, atenolol, and metoprolol, are particularly attractive because of their previously discussed antiischemic benefits in the perioperative period. Other alternatives are intravenous enalapril, verapamil, or diltiazem and the transdermal clonidine patch. For more serious hypertension, labetalol, nitroglycerin, and nitroprusside are appropriate. In general, avoidance of parenteral hydralazine is warranted in patients with ischemic heart disease because the reflex tachycardia produced may lead to ischemia. Use of sublingual nifedipine is associated with strokes, MI, and death. Also, keep in mind that the clonidine patch is not fully active until 48 hours after placement.

For many patients with only mild postoperative elevations of blood pressure, withholding parenteral antihypertensives until they can take oral medications, while limiting sodium and aggressively controlling pain and anxiety, is appropriate. Clonidine and similar drugs may result in severe rebound hypertension when discontinued abruptly before surgery. Administer with a sip of water on the day of surgery, and continue with transdermal administration (therapeutic systemic levels of transdermal clonidine are not reached for 48 h) or substitute with intravenous methyldopa, nitroprusside, or phentolamine.

Although not commonly used, methyldopa may be discontinued in the perioperative period if needed. Reserpine and prazosin must be given until the day before surgery, then resumed postoperatively. Hydralazine is typically used in combination with beta-blockers. Observe caution with intravenous formulations because the dose required is less than the oral dose.

Table 2. Perioperative Drug Management for Patients With Hypertension (Open Table in a new window)

Congestive heart failure, valvular heart disease, arrhythmia, and conduction system disease

Patients with congestive heart failure (CHF) need stabilization with diuretics, digoxin, ACE inhibitors, and nitroglycerides prior to surgery. Preoperative CHF is the strongest predictor of postoperative pulmonary edema.

Hemodynamic monitoring with a pulmonary artery catheter is recommended for patients with severe CHF requiring emergency surgery. This should extend at least 48 hours postoperatively to guide fluid management. Loss of cardiac pump function leading to CHF significantly increases perioperative risk.

Although postoperative CHF occurs in only approximately 1-6% of patients, the associated mortality rate is 15-20%. During surgery, volume changes, other intraoperative stressors, and the myocardial depressant actions of anesthetic agents can lead to a significant decrease in cardiac output.

Following surgery, most sequestered fluid is mobilized within the first 48 hours, placing an increased load on the heart. This is also a period of greatly increased metabolic and neurohumoral stress. Most postoperative CHF occurs within 1 hour following surgery, and, in 50% of these cases, inappropriate fluid administration is a major factor.

Heart valve prostheses

For those patients with heart valve prostheses, anticoagulant management is an important component of perioperative care. ^[7]

For major surgeries, substituting warfarin with heparin is recommended to maintain anticoagulation until the time of surgery. The short half-life of heparin allows the patient to safely undergo surgery within a few hours after discontinuation. Heparin should be discontinued 6 hours prior to surgery and then restarted 12-24 hours after surgery, when postoperative hemorrhage is no longer a threat. Monitor heparin by maintaining an activated partial thromboplastin time (aPTT) of 1.5- to 2-times normal. For patients on warfarin, checking the prothrombin time 1 day prior to the day of the operation and administering vitamin K (1-3 mg is generally sufficient), if necessary, is recommended.

Therapeutic anticoagulation is typically not reestablished for several days after warfarin is initiated; therefore, the patient should again receive heparin in the postoperative period until oral anticoagulation is fully therapeutic. Start warfarin and adjust to an International Normalized Ratio (INR) based on the underlying reason for the long-term anticoagulation.

For minor surgery (eg, cataract removal, most dental surgeries), Coumadin does not need to be discontinued, although many surgeons still request it.

When substituting warfarin with heparin, low molecular weight heparin (LMWH) generally can be used. Widespread anecdotal experience among cardiologists and internists suggests that Lovenox in a dose of 1 mg/kg bid can be used safely instead of unfractionated heparin, but double-blind studies have not been conducted. The exception to this is prosthetic valves requiring an INR of 3-3.5. Because of the lack of experience with LMWH in this setting, conventional heparin should still be used.

When using LMWH, the last dose should be 12 hours before surgery. However, if spinal anesthesia is anticipated, the last dose should be 24 hours before surgery.

For patients taking warfarin for atrial fibrillation, warfarin can be stopped safely without interim use of heparin. The exception to this is the high-risk patient with atrial fibrillation (eg, history of prior embolization, known atrial thrombus).

The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) study included 3007 patients with nonvalvular atrial fibrillation who were receiving long-term therapy with dabigatran, rivaroxaban, or apixaban. The direct oral anticoagulant was stopped before and then resumed after elective surgery or procedures without heparin bridging. The investigators reported only about a 2% rate of perioperative major bleeding and less than 1% rate of thromboembolic events among the study’s participants. ^[8]

Arrhythmia

Treat life-threatening arrhythmia in the perioperative period.

Continue digoxin for control of atrial fibrillation and supraventricular tachycardia in the perioperative period. Bioavailabilities differ with oral and parenteral preparations; therefore, carefully administer appropriate dosages.

Because a risk of digitalis toxicity and perioperative arrhythmia exists, some clinicians prefer to withhold the medication 12 hours before surgery.

Patients on quinidine should receive their dose on the night before surgery. Intravenous lidocaine may be used for ventricular arrhythmia, and intravenous propranolol or verapamil can be used for supraventricular arrhythmias. Quinidine is restarted as soon as patient is on oral sips.

Patients on procainamide, similar to those on quinidine, should receive their dose on the night before surgery. To control arrhythmia in the intraoperative period, intravenous procainamide or lidocaine may be used. Poorly tolerated supraventricular arrhythmia may be treated with propranolol and verapamil.

Disopyramide has a negative inotropic effect with adverse anticholinergic effects of urinary retention and constipation; therefore, it is discontinued on the night prior to surgery and substituted with intravenous lidocaine in the perioperative period.

Tocainide is an oral agent similar to lidocaine and may be used for the treatment of ventricular arrhythmia. Administer the night before surgery, and use intravenous lidocaine until the patient resumes oral tocainide.

Discontinue amiodarone, used in life-threatening arrhythmia, on the night before surgery. It has a long half-life (30-60 d); therefore, it can be restarted safely after the patient is on oral feedings. If arrhythmia develops in the perioperative period, the intravenous preparation can be used in conjunction with conventional intravenous drugs (eg, procainamide, lidocaine).

A rare postoperative reaction in patients on amiodarone is acute respiratory distress syndrome, but the exact inciting anesthetic drug or intraoperative event is not understood.

Verapamil (for arrhythmia) is given with a sip of water on the morning of surgery, and an intravenous formulation can be used to cover the perioperative period.

To summarize, those patients on long-term therapy for supraventricular tachycardia should receive their usual medication in the perioperative period. Supplemental rate control can be achieved with calcium channel blockers, beta-blockers, or cautious use of digoxin. Treatment of sustained ventricular arrhythmia with oral medication should occur until the day of surgery, when substitution with intravenous procainamide or lidocaine is used.

Drugs in hypotension

Hypotension can occur at any time during surgery as a result of blood or fluid loss and from the effects of vasoactive anesthetic drugs. Medications used to treat coexisting cardiovascular disorders may also exacerbate hypotension.

Phenylephrine is a selective alpha-1 adrenergic agent that causes peripheral vasoconstriction. It is useful in the treatment of hypotension associated with spinal anesthesia, as well as in patients with coronary artery disease or aortic stenosis to increase coronary perfusion pressure. It can be administered in bolus doses of 40-100 mcg through a peripheral intravenous line or an infusion of 10-20 mcg/min. It has a rapid onset of action and short duration of action (5-10 min).

Serum calcium levels are decreased with the administration of heparin and albumin or after a transfusion of blood preserved with citrate. Low serum concentrations of ionized calcium are associated with myocardial depression and decreased peripheral vascular resistance. Calcium ions increase myocardial contractility and have a variable effect on systemic vascular resistance. However, calcium is best used in the treatment of hyperkalemia and hypotension in patients who are hypocalcemic and are receiving calcium channel blockers. Calcium should be administered as a slow intravenous bolus of 0.5-1 g.

Dopamine is used in the treatment of cardiogenic shock, CHF, and following cardiac surgery. It has 3 different actions at 3 pharmacologic doses. When administering in the range of 0.5-2 mcg/kg/min, it increases renal blood flow and urine output via DA₁ receptors, which are postsynaptic and act on renal, mesenteric, splenic, and coronary vascular smooth muscle to mediate vasodilation through stimulation of adenylate cyclase and increased production of cAMP. ^[9] At 3-10 mcg/kg/min, it increases inotropy and chronotropy, augmenting cardiac output. Finally, at more than 10 mcg/kg/min, it increases total peripheral resistance.

Dobutamine is a β-adrenergic receptor agonist with minimal α-adrenergic receptor agonist activity. It is a positive chronotropic and inotropic agent with pulmonary and systemic vasodilatory effect. It decreases total peripheral resistance and increases cardiac output, without the tendency to cause tachycardia that may be evident with dopamine. It is useful in low cardiac output states when an increase in left ventricular end-diastolic volume and pulmonary vascular resistance is not desirable. It is administered as an infusion of 5-15 mcg/kg/min.

Epinephrine is a naturally occurring catecholamine found in the adrenal medulla. It is an α- and β-adrenergic receptor agonist (β-adrenergic receptor predominance at lower doses) that increases cardiac contractility and the heart rate, accentuates systolic and mean blood pressures, and serves as an effective bronchodilator. It should be used as an infusion, starting at 1-4 mcg/min, and then titrated to cardiac output and blood pressure.

Norepinephrine causes vasoconstriction and has positive inotropic action without increasing the heart rate. It has primarily α-, with minimal β₂ -receptor, activity. It should be used as an infusion, starting at 1-4 mcg/min and titrated to blood pressure.

Milrinone is a noncatecholamine inotropic agent (phosphodiesterase inhibitor) with hemodynamic properties similar to those of dobutamine. Inhibition of myocardial type III phosphodiesterase leads to an increase in myocardial cAMP, which increases the influx of intracellular Ca²⁺ and has a positive inotropic effect independent of β-adrenergic receptor stimulation. It increases cardiac inotropy and slightly decreases total peripheral resistance, thereby improving cardiac output. It causes pulmonary and coronary vasodilation.

(See also the pill identifier tool.)

In the perioperative period, beta-agonists and bronchodilators should not be discontinued in patients with asthma, and beta-agonists and atropine analogs should not be discontinued in patients with chronic obstructive pulmonary disease. The patient should take the usual inhaled medication or tablet until the day of surgery and also on the morning of the operation.

During the procedure, while the patient is under anesthesia, these drugs are usually not needed. Following surgery, if the endotracheal tube is still present, the inhaled medication can be continued. Optimization of treatment for chronic obstructive pulmonary disease is critical, and some patients require an increase in their steroid dose for 1-2 weeks preoperatively.

Consider preoperative bronchodilator therapy in those with a forced vital capacity of less than 1 L or a forced expiratory volume in 1 second of less than 500 cm³, especially if improvement occurs after treatment. In the case of productive cough, reschedule an elective surgery and treat the patient with a course of antibiotics to reduce the risk of bronchospasm.

Postoperative analgesia also plays an important role. Judicious use of narcotics and diligent monitoring for respiratory depression is important in patients with respiratory compromise. Instruct patients to breathe deeply and cough to avoid atelectasis. Counsel patients on the effects of smoking and urge them to stop. Patients should be advised to stop smoking 2 months prior to elective operations to maximize the effect of smoking cessation, ^[10] or for at least 4 weeks to benefit from improved mucociliary function and some reduction in postoperative pulmonary complication rate. ^[11] When a person who smokes stops for a short time before surgery, the use of transdermal nicotine replacement is helpful to alleviate symptoms of withdrawal.

For patients on long-term steroid therapy, increase the dose on the day of surgery (hydrocortisone 100 mg q8h for 24 h), then decrease the dose by 50% every day until back to the usual dose (prednisone is 4 times stronger than hydrocortisone).

Diabetes

Patients with diabetes are at higher risk for perioperative complications. In a study of 1042 patients who underwent total hip replacement, researchers compared the incidence rate of postoperative infection in persons with diabetes (11%) and in persons without diabetes (2%). This increased incidence rate may be accounted for by delayed wound healing or an alteration in leukocyte function in patients with poorly controlled diabetes.

Diabetes is a predictor of cardiac morbidity in patients undergoing vascular surgery. adequate glycemic control is essential prior to an elective surgery. The blood glucose level on the morning of surgery ideally should be lower than 200 mg. Postpone elective surgery in patients who have glucose levels greater than 300 mg. For emergency surgery, achieve optimal control rapidly, and direct attention toward optimization of volume status.

The primary goal of perioperative control is to avoid ketosis and to maintain glucose levels of 100-200 mg/dL. If the procedure is short and can be performed early in the morning and the patient is expected to eat shortly after the procedure, then the patient's diabetic regimen can be shifted to a few hours later in the day.

Persons with type 1 diabetes always require insulin perioperatively, even if the addition of glucose is needed to allow the administration of insulin without hypoglycemia. Persons with type 2 diabetes require insulin perioperatively, especially if their diabetes is usually controlled with insulin and they are undergoing major surgery. Administer insulin either subcutaneously at approximately 50% of the patient's usual morning human insulin isophane suspension dose on the morning of surgery or by an intravenous infusion at approximately 1 U/h. To avoid hypoglycemia, dextrose must be given along with insulin while the patient is not eating or drinking (ie, while NPO). Restart the usual regimen when patient is eating.

Monitor serum glucose levels every 1-2 hours during surgery and every 2-4 hours while NPO, then administer supplemental short-acting insulin as dictated by the blood sugar level. In states of peripheral vasoconstriction in which the subcutaneous compartment is suboptimally perfused, intravenous insulin administration (either bolus or infusion) ensures more controlled and effective tissue delivery than subcutaneous administration.

For patients controlled on oral agents, discontinue drugs 1 day before surgery. Discontinue biguanides (metformin) on the day of surgery because alterations in renal function arising intraoperatively may potentiate the risk of the patient developing lactic acidosis. Sulfonylureas are routinely continued on the day before surgery and withheld on the operative day.

Measure glucose levels every 4 hours. Regular insulin can be administered as needed to patients with glucose levels greater than 250 mg/dL. Resume the oral agent when patients return to their baseline diet. For patients undergoing outpatient surgery, reinstitute their preoperative regimen when they resume eating.

A study by Garg et al that included 3909 diabetes patients undergoing surgery who had preoperative and inpatient diabetes management reported improved glycemic control on the surgical date and decreased hypoglycemia incidence postoperatively. On the day of surgery, mean blood glucose was 146.4 ± 51.9 mg/dL before and 139.9 ± 45.6 mg/dL after the program (P = 0.0028). ^[12]

Table 3. Perioperative Medication Management for Patients With Diabetes and Hypothyroidism (Open Table in a new window)

 

Thyroid drugs

Advise patients using a replacement thyroxine to take the medication in the perioperative period. Start the drug postoperatively as soon as the patient is on oral liquids. One can withhold this medication for as long as a week because of its long half-life (ie, 7 d).

Monitoring for hypothermia, hypoventilation, hyponatremia, and hypoglycemia is mandatory. Do not defer urgent surgery in a newly diagnosed patient with hypothyroidism. In patients with severe hypothyroidism, intravenous L-thyroxine, with an initial dose of 500 mcg, followed by 50-100 mcg/d, may be given. Elective surgery should be delayed in patients with symptomatic hypothyroidism.

One should also assess for pituitary-adrenal hypofunction, and treat the patient with steroids if needed. Patients with a hypothyroidism or thyrotoxicosis should be under good control prior to surgery. In a case of nonthyroid surgery, patients should receive their antithyroid drug with propranolol on the day of surgery with a sip of water. Resume postoperatively by oral or nasogastric routes within 24 hours after surgery, if possible. Patients with significant hypothyroidism requiring surgery should receive perioperative hydrocortisone for possible adrenal insufficiency.

In the case of a patient undergoing thyroidectomy for thyrotoxicosis, perioperative medication includes iodine for 10 days prior to surgery in addition to the antithyroid drug and propranolol. This reduces intraoperative bleeding from the thyroid gland. Propranolol may be administered for a few days after thyroidectomy and then discontinued.

Contraceptives

Patients taking oral contraceptives have an increased risk of postoperative venous thromboembolism because of the combined effects of hormones and the hypercoagulable state, which accompanies surgical stress and postoperative immobility. Controversy focuses on whether to stop or continue combined oral contraceptive pills (OCPs).

The recommendation of the British National Formulary and manufacturers of combined OCPs is that for major surgeries, the patient should switch to alternative contraceptive methods 4-6 weeks prior to surgery and then restart OCPs after the first menses occurs at least 2 weeks after regaining full mobility following surgery. Other groups suggest that insufficient evidence is available to recommend interrupting the routine schedule for elective major procedures and that this places the patient at risk of unwanted pregnancy. Thus, the patient is faced with a choice of continuing combined OCPs and receiving thromboprophylaxis in the perioperative period (ie, subcutaneous LMWH and graduated elastic compression stockings) or stopping the pill 4-6 weeks prior to surgery and using another form of contraception (eg, a progesterone-only pill).

In case of unprotected intercourse during this period, pregnancy must be excluded before the operation.

Hormone replacement therapy (HRT) in postmenopausal women may increase the risk of postoperative venous thromboembolism. A similar controversy exists as with OCPs. Most women on HRT are likely to have additional risk factors for thromboembolism because of their age; hence, perioperative thromboprophylaxis is prudent, rather than subjecting the patient to the risk of provoking postmenopausal symptoms by stopping HRT.

In the event of an emergency surgery in patients on combined OCPs or HRT, perioperative thromboprophylaxis is warranted.

Perioperative steroids

A common issue that arises in patients who are on long-term corticosteroid therapy is the perioperative supplementation with stress doses. Several studies have shown that a stress dose is needed only when the hypothalamic-pituitary-adrenal axis (HPAA) is suppressed.

The corticosteroid dose below which HPAA suppression is unlikely is difficult to predict. Many patients take supraphysiologic doses of prednisone (5 mg/d long term, 7.5-10 mg/d for 1 mo, more than 20 mg/d for 1 wk, or high doses of other inhaled corticosteroids) for a variety of conditions and may show evidence of HPAA suppression.

The time to recovery of normal adrenal function after stopping corticosteroids varies from a few days to several months. The best plan is to assume that patients receiving corticosteroids within 3 months of surgery have some degree of HPAA suppression and should receive perioperative supplementation.

When using perioperative corticosteroid supplementation, doses should parallel the physiologic response of the normal adrenal gland to surgical stress, providing only very short-term supplementation. Depending on the dose the patient is taking prior to surgery and the type of operative procedure, the following schedule can be used:

• In the case of a minor surgery, in a patient on more than 10 mg/d of prednisone (or equivalent), 25-100 mg of hydrocortisone at induction is sufficient. Postoperatively, patients resume the usual dose of corticosteroid the next day.

• In the case of a major operation, 100 mg of hydrocortisone every 8 hours for 24 hours should be used, on the day of surgery, then the dose of prednisone should be decreased rapidly (ie, 50% per day, down to the usual steroid dose). Oral corticosteroid therapy should be resumed when GI function returns.

• In the case of ambulatory procedures, administer hydrocortisone (100 mg IV/IM) at discharge, along with a prescription for a rapid taper of prednisone or resumption of the previous steroid dose.

• A patient taking a high dose of steroids for immunosuppression should be maintained during the perioperative period. For example, for a patient taking 60 mg of prednisone per day, hydrocortisone at 250-300 mg/d parenterally is recommended until the patient can resume the normal oral dose.

• Remember that when calculating the hydrocortisone dose, prednisone is 4 times stronger.

Grand mal seizures can substantially increase the risks of surgery. Considerable morbidity may follow grand mal seizures in the perioperative period (eg, pulmonary aspiration, wound dehiscence, disruption of reduced fractures and prostheses). Identifying patients with preexisting seizure disorders assures that their anticonvulsant medications can be continued. On the other hand, neither absence nor focal seizures appreciably increase the risk of surgery and anesthesia.

As a general principle, if control of epilepsy has been adequate during the year before surgery, measuring blood levels of antiepileptic medications or repeating an electroencephalogram evaluation is not necessary.

Phenytoin and phenobarbital should be continued in the perioperative period with parenteral formulations, if needed. However, carbamazepine and valproic acid are not available in parenteral form. ^[13]

Patients taking these drugs must be loaded with phenytoin at 18 mg/kg and maintained on 4-8 mg/kg in 3 divided doses until they resume eating. Those who are intolerant of or allergic to phenytoin may be loaded with phenobarbital in a dose of 6 mg/kg.

If a patient is allergic to both and the risk of major seizure is high, premedication with prednisone in a dose of 60 mg/d for 2 days usually prevents allergic reactions. Loading the patient with oral dosages and then giving intravenous maintenance doses is better. However, in emergency cases, the loading may be performed intravenously using the same doses. Maintaining the serum levels in the upper half of the therapeutic range (ie, 15-20 mcg/mL for phenytoin, 30-40 mcg/mL for phenobarbital) minimizes the risk of intraoperative seizures.

Phenytoin and phenobarbital are usually effective for all types of seizures except true absences, which require ethosuximide or valproic acid (not available in parenteral form). However, pure absence seizures pose little threat, and their treatment can be safely interrupted until after surgery.

Table 4: Perioperative Medication Management in Patients With Epilepsy (Open Table in a new window)

Patients with Parkinson disease who take dopamine (combination of L-dopa and carbidopa) must stay on their usual medication schedule as much as possible perioperatively because no parenteral form of Sinemet is available and withholding the drug can cause a parkinsonian crisis. Anticholinergics, such as benztropine mesylate in a dose of 0.5-1 mg twice daily, may be given intramuscularly during the perioperative period without serious cardiovascular risk. L-dopa should be resumed postoperatively as soon as possible, and the patient should be carefully monitored for hypotension. ^[14]

Psychotropic agents

Psychotropic agents demand close attention in the perioperative period. Their complex effects on cardiovascular and autonomic nervous system function warrant careful consideration.

Patients treated with psychotropic drugs may have altered responses to other medications. With proper precautions, psychotropic drugs can be managed safely in surgical patients.

• Antidepressants

  • No drug interactions between selective serotonin reuptake inhibitors and anesthetics are known.

  • Tricyclic antidepressants (TCAs) manifest a number of important drug interactions. TCAs should be administered until just before surgery and resumed when the patient is able to take oral fluids. In cases in which the drug is to be discontinued, tapering should occur over 1-2 weeks to minimize sleep disturbances.

  • Although rarely used, controversy exists with discontinuing monoamine oxidase inhibitors (MAOIs) before surgery and with the safety of using narcotic-based anesthesia in patients taking them. Use of meperidine in patients taking MAOIs is contraindicated because of a possible life-threatening reaction similar to neuroleptic malignant syndrome (characterized by fever, hallucinations, and rigidity).

• Neuroleptic drugs

  • This group of drugs is used primarily to treat psychotic symptoms and constitutes a chemically heterogeneous group of major tranquilizers, such as the phenothiazines, butyrophenones, thioxanthenes, indolones, and dibenzoxazepines.

  • Most adverse effects of these drugs are easily managed. Given the complications associated with untreated psychosis in the perioperative period, continued treatment with antipsychotic drugs is warranted throughout the perioperative period.

• Lithium

  • Lithium is used to treat bipolar affective disorders. It may potentiate the effect of depolarizing and competitive neuromuscular blocking agents. The clearance of lithium can be reduced and its toxicity increased by factors that cause negative fluid balance, negative sodium balance, and decreased glomerular filtration rate.

  • Lithium should be discontinued 2-3 days before major surgery and resumed when renal function and electrolyte levels are stable. If serum levels are not in a toxic range, renal function is normal, and fluid electrolyte status is stable, lithium can be continued before minor surgery.

• Benzodiazepines

  • Benzodiazepines (BZs) are the most commonly prescribed class of anxiolytic drugs and play a major role in anesthesia. They can be used throughout the perioperative period to treat anxiety and agitation. They can also be used with opiates for premedication or analgesia.

  • Patients who have been on BZs for a long time develop tolerance and have an increased risk of serious withdrawal symptoms. Maintaining these patients on BZs in adequate doses and appropriate formulations at timely intervals is indicated to avert withdrawal in the perioperative period.

  • The use of phenothiazines, butyrophenones, and BZs can lead to problems with hypotension and myocardial depression in the perioperative period in patients with heart disease. The recommendation is to discontinue tranquilizing agents several days before surgery and resume as needed on the second or third postoperative day.

Deep vein thrombosis (DVT) is prevalent in major surgery, especially in pelvic and lower limb surgery. Thus, for all major urologic, gynecologic, and rectal operations or surgery for malignancy, preventing this complication is warranted.

Prophylaxis for DVT after hip surgery has developed greatly. Prior to LMWH, an adjusted dose of heparin was administered subcutaneously (5000 U q8h) before surgery and continued until the patient was ambulatory. Maintaining an aPTT outside of the reference range was the goal.

LMWH prevents DVT in patients undergoing abdominal or hip surgery. It has greater efficacy and a lower incidence of bleeding than conventional heparin and produces less inhibition of platelet function.

One of the regimens used in orthopedic surgery is enoxaparin, 30 mg every 12 hours subcutaneously, starting the night before the surgery and postoperatively until the patient is ambulatory.

In cases in which prophylaxis is warranted (eg, abdominal surgery, orthopedic surgery), the following drugs can be used:

• Enoxaparin (approved in Canada and the United States) is administered at 20 mg subcutaneously 1-2 hours before surgery and once daily postoperatively for moderate-risk patients. A dose of 40 mg with the same schedule is administered to high-risk patients.

• Dalteparin (approved in Canada and the United States) is administered at 2500 U subcutaneously 1-2 hours before surgery and once daily postoperatively for moderate-risk patients. A dose of 5000 U with the same schedule is administered to high-risk patients.

• Nadroparin (approved in Canada) is administered at 2850 U subcutaneously 2-4 hours before surgery and once daily postoperatively for moderate-risk patients.

• Tinzaparin (approved in Canada and the United States) is administered at 3500 U subcutaneously 2 hours before surgery and once daily postoperatively for moderate-risk patients.

• Fondaparinux sodium (approved in Canada and the United States) is administered at 2.5 mg subcutaneously starting 6 hours postoperatively and once daily thereafter for moderate- and high-risk patients.

Laboratory monitoring of LMWH is only needed in those receiving prolonged treatment or in high-risk patients with a propensity for bleeding or recurrent thrombosis. Its effect can be monitored by heparin assay (antifactor Xa heparin assay, reference range 0.35-0.7 U/mL). Both agents are safe and efficacious in randomized clinical trials, but bleeding still occurs in 3-5% of these patients, especially when heparin is given in concert with nonsteroidal anti-inflammatory drugs (NSAIDs).

When the diagnosis of DVT is made postoperatively, begin full-dose heparinization (bolus of 5000-10,000 IU, followed by continuous infusion of 1000-1500 IU/h) if surgical hemostasis is achieved. If a risk is still present, an inferior vena cava filter must be placed. Once on therapeutic heparin (aPTT of 1.5-2), warfarin should be initiated and the dose adjusted to maintain an appropriate INR (ie, 2-3). Heparin and a therapeutic level of warfarin should overlap for at least 48 hours before discontinuing heparin.

If edema is present, the patient should remain on bed rest with the affected limb elevated above the level of the heart for several days. The patient should remain on bed rest for 2-3 days even if no pain or edema is present and even if the aPTT is at a therapeutic range to allow fixation of the clot to the vessel wall. Administer 3-6 months of therapy in the case of proximal DVT, assuming that surgery was the only predisposing risk factor. LMWH may also be used in conjunction with warfarin for therapy of DVT.

• Dalteparin sodium (approved in Canada) is administered at 200 anti-Xa IU/kg/d subcutaneously, with a single dose not to exceed 18,000 IU.

• Enoxaparin sodium (approved in Canada and the United States) is administered at 1 mg/kg q12h subcutaneously or at 1.5 mg/kg/d subcutaneously. The single daily dose should not exceed 150 mg.

• Nadroparin calcium (approved in Canada) is administered at 86 anti-Xa IU/kg bid subcutaneously for 10 days or at 171 anti-Xa IU/kg subcutaneously daily. The single daily dose should not exceed 17,000 IU.

• Tinzaparin sodium (approved in Canada and the United States) is administered at 175 anti-Xa IU/kg/d subcutaneously daily.

NSAIDs are often prescribed for patients with rheumatic diseases. NSAIDs that inhibit platelet cyclooxygenase-1 (COX-1) block the formation of thromboxane A2, which impairs thromboxane-dependent platelet aggregation and variably prolongs the bleeding time. Because aspirin irreversibly blocks cyclooxygenase, the inhibition persists for the circulating lifetime of the platelet. Most nonaspirin NSAIDs inhibit cyclooxygenase reversibly; therefore, their duration of action depends on the specific drug, dose, serum level, and half-life. Those NSAIDs with limited activity against platelet COX-1 include nonacetylated salicylates and nabumetone. The highly selective cyclooxygenase-2 (COX-2) inhibitors (eg, celecoxib [Celebrex]) have no effect on platelet aggregation and bleeding time, even when given at supratherapeutic doses.

Conflicting data exist regarding the use of NSAIDs and perioperative bleeding. However, the general consensus is to withhold aspirin and platelet active–nonaspirin NSAIDs before surgery. Because the inhibitory effect of aspirin on platelet aggregation may persist for 7-10 days, discontinuing aspirin at least 1 week before surgery is prudent.

Because nonaspirin NSAIDs act in a reversible fashion, the function of cyclooxygenase returns as the drug clears from the circulation. Therefore, the rate of return of normal platelet function varies with the terminal drug half-life.

Withholding nonaspirin NSAIDs several days before surgery is reasonable, especially in surgical procedures in which bleeding complications could be catastrophic. In urgent cases, COX-2 selective NSAIDs can likely be used without increased risk of bleeding. Their effect on mucosal wound healing has not been studied in humans.

In those patients with inflammatory arthritis who are dependent on their NSAID therapy for control of their symptoms, withholding therapy in the perioperative period may result in increased pain and stiffness. This effect should be anticipated, and alternative therapy, such as analgesics or low-dose corticosteroids, should be considered to prevent pain, which may result in delayed postoperative rehabilitation.

Table 5. Perioperative Management of NSAIDs (Open Table in a new window)

Drugs in rheumatic disease

Whether perioperative methotrexate increases the risk of postoperative complications (eg, infections, poor wound healing) remains unclear. Because the drug is predominantly cleared from the body by the kidneys, withholding the drug 48 hours before surgery or any other procedure (eg, contrast dye study) that may be associated with even transient renal insufficiency is prudent. Some surgeons also prefer to withhold the drug for 2 weeks postoperatively to ensure appropriate wound healing.

Similarly, withholding cyclophosphamide (also excreted renally) a few days prior to surgery is recommended. Other antirheumatic drugs (eg, hydroxychloroquine, colchicine, gold, sulfasalazine, azathioprine) should be discontinued prior to surgery, although very little data exist regarding their use in the perioperative period.

Depending on the severity of the rheumatologic condition, methotrexate should be started as soon as possible after surgery to avoid a rebound flare in arthritis. Discuss restarting all antirheumatic medications with the patient's rheumatologist.

Many patients who come to the operating room are at risk for aspiration pneumonitis. Examples include patients with large gastric fluid volumes, such as parturients, nonfasting patients scheduled for emergency surgery, obese patients, patients with trauma, and patients with hiatal hernia or history of gastroesophageal reflux. Many different agents have been used to alter gastric volume and increase the pH of gastric fluid. Anticholinergics, H₂ receptor antagonists, antacids, and gastrokinetic agents have all been used to reduce the possibility of aspiration pneumonitis. Regardless of pharmacotherapy used, clinicians should maintain a low threshold for placement of a nasogastric tube prior to induction while patient has intact airway reflexes to ensure proper gastric emptying prior to induction of anesthesia.

Anticholinergics are ineffective in increasing gastric fluid pH or reducing gastric fluid volume. ^[15] In fact, intravenous doses of anticholinergics may cause relaxation of the gastroesophageal junction and increase risk of aspiration.

The histamine receptor antagonists cimetidine, ranitidine, famotidine, and nizatidine reduce gastric acid secretion via competitive antagonism of the histamine receptor, thereby increasing gastric fluid pH. These agents may be used for the allergic patient or in preparing a patient for exposure to an allergenic trigger, such as radiologic dye.

Antacids are used 20-30 minutes before induction to increase gastric fluid pH higher than 2.5. The nonparticulate antacid, 0.3 M sodium citrate, is used because aspiration of gastric contents containing these antacids will not cause damage to lungs. In contrast, aspiration of gastric fluid containing particulate antacids may lead to pulmonary damage, despite the increase in gastric fluid pH.

Proton-pump inhibitors suppress gastric acid secretion in a dose-dependent manner by binding to the proton pump of the parietal cell. Intravenous doses of 40 mg 30 minutes before induction are commonly used. Unfortunately, investigators have found increases in gastric pH and inconsistent effects on gastric volume with administration of omeprazole and ranitidine. ^[16]

Gastrokinetic agents are used to reduce gastric fluid volume. Metoclopramide is a dopamine antagonist that stimulates upper gastrointestinal motility, increases gastroesophageal sphincter tone, and relaxes the pyloric sphincter. It has no effect on gastric acid secretion. An intravenous dose of 5-10 mg is usually given 15-30 minutes before induction over 3-5 minutes to prevent abdominal cramping. An oral dose of 10 mg achieves onset within 30-60 minutes. Use is contraindicated in patients with bowel obstruction.

A summary of fasting recommendations to reduce the risk of pulmonary aspiration includes the ingested material and the minimum fasting time for all age groups. These recommendations apply only to healthy patients who are undergoing elective procedures and are not intended for women in labor. Following the guidelines does not guarantee complete gastric emptying. See the following ^{[17, 18]} :

• Clear liquids (eg, water, fruit juices without pulp, carbonated beverages, clear tea, black coffee) - 2 hours

• Breast milk - 4 hours

• Infant formula - 6 hours

• Nonhuman milk - 6 hours

• Light meal (toast and clear liquids) - 6 hours

Patient populations at risk for postoperative nausea and vomiting include those scheduled for ophthalmologic surgery, patients with a prior history of nausea and vomiting or motion sickness, patients scheduled for laparoscopic surgery or gynecologic procedures, and patients who are obese.

A risk score for predicting postoperative nausea and vomiting after inhalation anesthesia identified 4 risk factors: female sex, nonsmoking, prior history of motion sickness or postoperative nausea, and the use of postoperative opioids. One study suggests prophylactic antiemetic therapy when 2 or more of the risk factors are present when using volatile anesthetics. Ondansetron (4 mg IV), dexamethasone (4 mg IV), droperidol (0.625 mg IV), diphenhydramine (Benadryl) (25 mg IV), and scopolamine transdermal patch (1.5 mg) singly or in combination, are agents in common usage. ^[19]

Most anesthesiologists believe antiemetics should be administered 30 minutes prior to the end of the case (except dexamethasone on induction and scopolamine patch preoperatively). As always, clinicians should consider reduction of baseline risks, including avoidance/minimization of nitrous oxide, volatile anesthetics, high-dose neostigmine, and postoperative opioids.