inpatient vs. outpatient), drug

allergies, previous experience with medications, and concurrent

drug therapy. The ASA physical status classification system classifies patients as I through V. ASA-I patients are healthy with

little medical risk, whereas ASA-V patients have little chance of

survival. Severe systemic disorders (e.g., uncontrolled diabetes

mellitus, coronary artery disease) are present in ASA-III through

ASA-V patients. Selection of preoperative medications in this

group of patients will be more difficult. These patients generally have limited physiological reserve; thus, administration of

a cardiovascular depressant agent, for example, can be harmful.

Furthermore, these patients will be taking a significant number of

medications; hence, chances for drug interactions are increased.

The patient’s other medical conditions are important to consider

to prevent the administration of contraindicated medications. For

example, the benzodiazepines are contraindicated in pregnancy.

A patient’s age will play a role in the response seen with premedicant administration. The elderly are often more sensitive

to preoperative opioids and benzodiazepines, as well as to the

central nervous system (CNS) effects of anticholinergic agents.

Familiarity with the surgery to be performed will aid in selecting appropriate premedicants. In surgical cases in which painful

procedures (e.g., vascular cannulation, peripheral nerve block)

will be performed on the patient, an analgesic premedicant may

be warranted. The length and type of the procedure is important to consider when selecting premedicants. For example, a

patient undergoing emergency surgery who has not fasted is

often administered a nonparticulate antacid because of the risk

for aspiration of gastric contents. In outpatient surgery, agents

with a long duration of action should be avoided because residual

150 Section 1 General Care

effects can prolong discharge time. Finally, it is important to

review the patient’s current drug therapy before selecting an

agent to prevent potentially harmful drug interactions.

Timing and Routes of Administration

The timing and route of administration is almost as important

as the choice of the agent. As a general rule, agents administered

by the IV route produce the fastest onset of action and are often

given after the patient arrives in the OR, whereas medications

administered via the oral route are usually administered 30 to

60 minutes before the patient arrives in the OR. If possible, the

intramuscular (IM) route should be avoided because it is painful

and undesirable for the patient.

Administration of Chronic Medications

Before Surgery

CASE 8-1

QUESTION 1: K.J., a 61-year-old man, is scheduled to

undergo a carotid endarterectomy under general anesthesia. K.J.’s past medical history is significant for diabetes,

hypertension, hyperlipidemia, and coronary artery disease.

His current medications are enalapril 20 mg once daily,

metoprolol XL 50 mg once daily, metformin XR 1,000 mg

once daily, atorvastatin 40 mg once daily, aspirin EC 325 mg

once daily, and clopidogrel 75 mg once daily. What medications should K.J. take the morning of surgery?

Consequences of stopping a chronic medication before, or

failing to restart that medication after surgery, can be significant. For example, abrupt discontinuation of a β-blocker during

the perioperative period in a patient who has been on chronic

β-blocker therapy can increase the risk of death in the intraoperative and postoperative period. The American College of

Cardiology/American Heart Association (ACC/AHA) recommends continuation of β-blocker therapy in patients undergoing surgery who are receiving a β-blocker for treatment of

conditions with ACC/AHA Class I guideline indications for the

drugs (e.g., angina, symptomatic arrhythmia, postmyocardial

infarction).5 Angiotensin-converting enzyme inhibitors (ACEIs)

and angiotensin receptor blockers (ARBs) increase the risk of

hypotension after induction of anesthesia when these agents are

not withheld 24 hours before surgery.6 In general, this hypotension is not responsive to conventional vasopressors (ephedrine,

phenylephrine) but will respond to vasopressin.7 Stopping the

ACEI before surgery, however, can result in adverse postoperative effects such as rebound hypertension and atrial fibrillation.

Therefore, the decision to continue or stop the ACEI or ARB

before surgery is made on an individual basis, taking into consideration the indication for the ACEI or ARB and the type of surgery.

Calcium-channel blockers, clonidine, amiodarone, digoxin, and

statins should be continued. Preoperative withdrawal of a statin

in a patient undergoing major vascular surgery, for example,

increases the risk of myocardial infarction and cardiovascular

death after surgery.8 Diuretics are typically held the morning

of surgery to minimize the risk of hypovolemia and electrolyte

abnormalities.

Oral antidiabetic agents and noninsulin injectable agents are

typically held the morning of surgery and not restarted until normal food intake resumes. In patients with renal dysfunction and

those who may receive IV contrast media, metformin should be

discontinued 24 to 48 hours before surgery to reduce the risk

of perioperative lactic acidosis. For patients on insulin therapy,

a portion of the morning dose of intermediate- or long-acting

insulin is generally administered on the day of surgery after a

check of the patient’s blood glucose. Close blood glucose monitoring guides subsequent insulin doses to avoid hypoglycemia.9

Antiepileptics, antipsychotics, benzodiazepines, lithium,

selective serotonin and norepinephrine reuptake inhibitors

(SSRIs and SNRIs), tricyclic antidepressants (TCAs), and carbidopa/levodopa have a greater risk for withdrawal or disease

decompensation than for perioperative complications. These

medications should therefore be continued up to and including

the morning of surgery.

Monoamine oxidase inhibitors (MAOIs) can interact with certain drugs used during anesthesia to produce cardiovascular instability. However, administration of an MAOI-safe anesthetic avoids

the need to stop the MAOI before surgery (and relapse of the

underlying disease) in a patient requiring an MAOI for refractory psychiatric illness.10

Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs)

reversibly inhibit platelet aggregation and are often stopped 1 to

3 days before surgery, depending on the duration of action of

the drug. Celecoxib does not affect platelet aggregation and may

be continued up to and including the day of surgery. Nonselective

NSAIDs and celecoxib should be held if there is a concern for

impaired renal function during or after surgery.

For patients on anticoagulant or antiplatelet therapy, the risks

for thromboembolism must be balanced with the risk for bleeding during and after the surgical procedure. For patients on

warfarin who are at high risk for perioperative thromboembolism, bridging anticoagulation therapy with IV heparin or

low-molecular-weight heparin (LMWH) before surgery is recommended. Warfarin may not need to be discontinued if the

patient is undergoing minor surgery (e.g., certain ophthalmic,

dental, or dermatologic procedures). For patients who have had

coronary stents recently placed, discontinuing antiplatelet therapy prematurely can significantly increase the risk of perioperative stent thrombosis and have catastrophic consequences.11

Traditionally, it was thought that patients who have been taking long-term corticosteroid therapy before surgery will experience adrenal insufficiency in the perioperative period and should

receive a supplemental stress-dose of hydrocortisone or methylprednisolone during and up to 2 to 3 days after surgery.12 A

recent review of the literature, however, found that patients on

long-term corticosteroid therapy only require continuation of

their normal daily dose of corticosteroid in the perioperative

period. These patients are generally able to increase their endogenous adrenal function above their baseline corticosteroid dose

to meet the increased demand from surgery; a supplemental

stress dose of corticosteroid is not necessary. These patients can

be closely monitored, and if hypotension that is refractory to

volume replacement does develop, a stress dose of a corticosteroid should be administered at that time. Patients who have

a known dysfunctional hypothalamic-pituitary-adrenal axis deficiency (e.g., Addison disease), on the other hand, will require

supplemental corticosteroid doses in the perioperative period as

they cannot increase endogenous cortisol production to meet

the increased demand from surgery.13

Opioid-dependent chronic pain patients who undergo surgery

often experience more severe acute pain after surgery. These

patients should receive either their chronic opioid medication or

a comparable dose of an IV opioid the morning of surgery to meet

their daily requirements to avoid uncontrolled pain and opioidwithdrawal symptoms. Opioid-dependent patients being treated

with buprenorphine present a unique challenge for postoperative pain management. Buprenorphine is a partial mu-agonist

and kappa antagonist that tightly binds to these receptors for a

very long time. If buprenorphine is continued up to the morning

151Perioperative Care Chapter 8

of surgery, it prevents a pure mu-agonist such as morphine from

providing effective analgesia. Although buprenorphine produces

analgesia, it only partially stimulates the mu-receptor, resulting

in a ceiling effect for analgesia. Increasing the dose of buprenorphine does not usually provide enough analgesia. In patients

expected to have moderate to severe pain after surgery (requiring the use of an opioid), it is recommended that buprenorphine be discontinued 5 to 7 days before surgery. These patients

may be transitioned to nonopioid pain medications and possibly

methadone, which would then be continued up to and including the morning of surgery. The use of nonopioid analgesics

or analgesic techniques (e.g., acetaminophen, peripheral nerve

blockade, epidural analgesia) for perioperative analgesia should

be maximized, regardless of whether or not buprenorphine is

discontinued prior to surgery.14

For K.J., metformin should be discontinued 24 to 48 hours

before surgery to minimize the risk for lactic acidosis during or

after surgery. Metoprolol, on the other hand, should be taken up

to and including the morning of surgery. K.J. has coronary artery

disease and is undergoing a carotid endarterectomy, which is

a vascular surgical procedure with a high risk of serious cardiovascular complications (such as stroke or myocardial infarction). Based on the ACC/AHA practice guidelines,5 perioperative

β-blocker therapy is recommended for K.J. The decision for K.J.

to take enalapril and atorvastatin the morning of surgery is made

by the anesthesia care provider. For K.T., it is likely that he will

be asked to take his atorvastatin but hold his morning dose of

enalapril to ensure hemodynamic stability during induction of

general anesthesia. The decision for K.J. to take or hold aspirin

and clopidogrel is made by the surgeon, based on risk of bleeding versus the benefit of cardiovascular protection. For K.T., it is

likely that the surgeon will ask him to take the aspirin up to and

including the morning of surgery but hold the clopidogrel for

7 days before surgery.

Aspiration Pneumonitis Prophylaxis

CASE 8-2

QUESTION 1: D.W., a 5-foot 4-inch, 95-kg, 38-year-old

woman, ASA-II, is scheduled to undergo a laparoscopic

cholecystectomy under general anesthesia. D.W. has type

2 diabetes. Physical examination is normal except for an

abnormal airway, which is anticipated to complicate intubation. Her medications include glipizide and an antacid

for dyspepsia. The procedure is scheduled as a same-day

surgery. What factors predispose D.W. to aspiration, and

what premedication, if any, should D.W. receive for aspiration prophylaxis?

DEFINITION

Aspiration pneumonitis, although uncommon, is a potentially

fatal condition that occurs as a result of regurgitation and aspiration of gastric contents. Aspiration of undigested or semidigested

gastric contents into the respiratory tract can cause obstruction

and an inflammatory response. Acute chemical pneumonitis and

subsequent acute lung injury (aspiration pneumonitis) can result

from aspiration of acidic gastric secretions.15 For adult patients,

it is believed that aspiration of more than 25 mL of gastric fluid

with a pH of less than 2.5 places them at greater risk for severe

pneumonitis and pulmonary sequelae should aspiration occur.1

RISK FACTORS

Patients at greatest risk for regurgitation and aspiration include

those with increased gastric acid, elevated intragastric pressure,

gastric or intestinal hypomotility, digestive structural disorders,

neuromuscular incoordination, and depressed sensorium. These

can include pregnant women, obese patients, and patients with

diabetes, as well as patients with a hiatal hernia, gastroesophageal

reflux, esophageal motility disorders, or peptic ulcer disease.1,16

Diabetic patients with reflux symptoms or poor glucose control

may also benefit from pharmacologic prophylaxis. In addition

to having delayed gastric emptying, obese patients will often

present with increased abdominal pressure and an abnormal airway; both factors predispose these individuals to aspiration. Hormonal changes in pregnant women account for delayed gastric

emptying and relaxation of the lower esophageal sphincter. An

increase in intra-abdominal pressure is also seen during pregnancy. Labor can increase gastrin levels, increasing gastric volume and acidity as well as delaying gastric emptying. Patients

undergoing emergency surgery frequently have full stomachs

because they have not had time to fast appropriately.

Rapid sequence induction, effective application of cricoid pressure, maintaining a patent upper airway, avoiding inflation of

the stomach with anesthetic gases, and inserting a large-bore

gastric tube once the airway has been secured, as well as the

use of regional anesthesia when possible, are probably the most

important measures the anesthesia provider can take to reduce

the patient’s risk of aspiration.17 Routine administration of pharmacologic aspiration prophylaxis is not cost-effective and does

not reduce morbidity in healthy patients undergoing elective

surgery.18 Administration of pharmacologic aspiration prophylaxis should, however, be considered to prevent morbidity in

patients at risk for aspiration.

D.W. has several factors that place her at risk for aspiration.

She is obese with an abnormal airway. She also has diabetes

and reports symptoms of dyspepsia that are relieved by antacids.

These conditions will predispose D.W. to increased abdominal

pressure, delayed gastric emptying, and increased risk of regurgitation. Her abnormal airway may delay intubation, increasing

the amount of time D.W. is susceptible to aspiration. Therefore,

aspiration prophylaxis with medications that buffer gastric acid

and reduce gastric volume is prudent for D.W.

MEDICATIONS

Many medications (e.g., antacids, gastric motility stimulants,

H2-receptor antagonists) can reduce the risk of pneumonitis if

aspiration occurs. These drugs, with the possible exception of

metoclopramide, are relatively free of adverse effects and have a

favorable risk-benefit profile.

ANTACIDS

Antacids, effective in raising gastric pH to greater than 2.5, should

be given as a single dose (30 mL) approximately 15 to 30 minutes

before induction of anesthesia. Nonparticulate antacids (e.g., citric acid and sodium citrate) are the agents of choice because

the suspension particles in particulate antacids can act as foci

for an inflammatory reaction if aspirated and increase the risk

of pulmonary damage.1 Antacids have two major advantages

when used for aspiration pneumonitis prophylaxis; there is no

“lag time” for onset of activity, and antacids are effective on the

fluid already in the stomach. Their major disadvantages are (a)

a short-acting buffering effect that is not likely to last as long as

the surgical procedure (citric acid and sodium citrate must be

administered no more than 1 hour before induction of anesthesia, with its duration possibly dependent on gastric emptying);

(b) the potential for emesis (owing to their lack of palatability);

(c) the possibility of incomplete mixing in the stomach; and (d)

their administration adds fluid volume to the stomach.1,18

152 Section 1 General Care

GASTRIC MOTILITY STIMULANTS

The gastric motility stimulant, metoclopramide, has no effect

on gastric pH or acid secretion. This agent reduces gastric volume in predisposed patients (e.g., parturients, obese patients)

by promoting gastric emptying. Preoperative metoclopramide

increases lower esophageal sphincter pressure and reduces gastric

volume.1,18 Metoclopramide should be administered 60 minutes

before induction of anesthesia when given orally. When given

by the IV route, metoclopramide should be slowly (3–5 minutes)

administered 15 to 30 minutes before induction of anesthesia.

The effects of metoclopramide on gastric emptying have been

variable, especially when used with other agents. For example,

the concomitant administration of anticholinergics (e.g., glycopyrrolate, atropine) or prior administration of opioids can reduce

lower esophageal sphincter pressure, which can offset the effects

of metoclopramide on the upper gastrointestinal (GI) tract.1,19

H2-RECEPTOR ANTAGONISTS

H2-receptor antagonists reduce gastric acidity and volume by

decreasing gastric acid secretion. Unlike antacids, the H2-receptor

antagonists do not produce immediate effects. Onset time for

these agents when administered orally is 1 to 3 hours; good effects

will be seen in 30 to 60 minutes when administered IV.3 Duration

of action of H2-receptor antagonists is also important because

the risk of aspiration pneumonitis extends through emergence

from anesthesia. After IV administration, the cimetidine dose

should be repeated in 6 hours if necessary, whereas therapeutic

concentrations of ranitidine and famotidine persist for 8 and

12 hours, respectively.3

PROTON-PUMP INHIBITORS

Proton-pump inhibitors (PPIs; e.g., omeprazole) act at the final

site of gastric acid secretion, making these agents very effective

in suppressing acid secretion. When the effects of preoperative

IV pantoprazole on gastric pH and volume were compared with

IV ranitidine and placebo, both pantoprazole and ranitidine significantly reduced the volume and increased the pH of gastric

contents when compared with placebo (saline). There was no

difference, however, between the pantoprazole and ranitidine

groups.20 Therefore, there appears to be no need to use the

more-expensive PPIs in patients at risk for pulmonary aspiration.

Because D.W.’s surgery is scheduled as a same-day surgery,

D.W. will arrive at the hospital or surgical center approximately

90 minutes before the start of the procedure. A nonparticulate

antacid such as citric acid and sodium citrate solution 30 mL

orally can be administered to D.W. immediately before entering

the OR. The anesthesia care provider may also administer an

H2-receptor antagonist instead of, or in addition to, the nonparticulate antacid.

INTRAVENOUS ANESTHETIC AGENTS

General Anesthesia

General anesthesia is a state of drug-induced unconsciousness.

Other components of general anesthesia include amnesia, analgesia, immobility, and attenuation of autonomic responses to

noxious stimuli.21 Drugs used to induce general anesthesia

should produce unconsciousness rapidly and smoothly while

minimizing any cardiovascular changes. An IV induction agent is

commonly administered for initiation of general anesthesia. The

most common drug used for IV induction is propofol. Methohexital, etomidate, remifentanil, midazolam, and ketamine are

less frequently used. Propofol can also be used to maintain general anesthesia, as drugs that do not accumulate during repeat

or continuous dosing are ideal choices for maintenance therapy.

Mechanisms of Action

Most IV anesthetic agents produce CNS depression by action

on the γ -aminobutyric acid (GABA) benzodiazepine chloride

ion channel receptor. GABA is the principal inhibitory neurotransmitter in the CNS. The barbiturates (methohexital) bind

to a receptor site on the GABA–receptor complex, reducing the

rate of dissociation of GABA from its receptor. This results in

increased chloride conductance through the ion channel, nerve

cell hyperpolarization, and inhibition of nerve impulse transmission. Barbiturates can directly activate the chloride channels by

mimicking the action of GABA. Benzodiazepines (midazolam)

also bind to this GABA–receptor complex, and their subsequent

potentiation of the inhibitory action of GABA is well described.

At large doses, most of the benzodiazepine receptors will be

occupied, and hypnosis (unconsciousness) will occur. The site of

action of etomidate—and propofol—is also at the GABA receptor, with etomidate augmenting GABA-gated chloride currents

and propofol enhancing the activity of the GABA-activated chloride channel. Ketamine acts at a different site than other induction agents. At anesthetic doses, ketamine produces dissociation

between the cortex and the thalamus within the limbic system,

resulting in a dissociative state; that is, the patient appears to be

detached from his or her surroundings. Ketamine also produces

analgesia and amnesia at these doses.22

Pharmacokinetics

The onset and duration of effect are the most important pharmacokinetic properties of IV anesthetic agents when used for induction of anesthesia. In general, the commonly used IV induction

agents have a rapid onset of action and short clinical duration.