shorter than the duration of an

intubating dose of rocuronium. Because this procedure will last

longer than the duration of muscle relaxation provided by the

intubating dose of rocuronium, this is not a concern.

Routes of Elimination

CASE 8-10

QUESTION 1: M.M., a 70-year-old woman, ASA-IV, is scheduled to undergo a 2-hour GI procedure. Pertinent laboratory

findings are as follows:

Aspartate aminotransferase, 272 units/L

Alanine aminotransferase, 150 units/L

Blood urea nitrogen, 40 mg/dL

Serum creatinine, 1.8 mg/dL

Albumin, 2.6 g/dL

Which neuromuscular blocking agent would you recommend for M.M.?

When selecting a neuromuscular blocking agent, one of the

factors that must be considered is the patient’s renal and hepatic

function. Neuromuscular blocking agents often depend on the

kidneys and liver for varying amounts of their metabolism and

excretion (Table 8-8).54,55,58 Some agents, however, are primarily

metabolized by plasma cholinesterase (pseudocholinesterase),

Hofmann elimination (a nonbiological process that does not

require renal, hepatic, or enzymatic function), or nonspecific

esterases.

Hofmann elimination is a pH- and temperature-dependent

process unique to atracurium and cisatracurium. One of the

products produced by Hofmann elimination is laudanosine,

a CNS stimulant in high concentrations. Laudanosine undergoes renal and hepatic elimination. Because of the short-term

use of atracurium and cisatracurium in the OR, accumulation of laudanosine with resultant seizure activity is not a concern, even in patients with end-stage renal failure.63 Because

plasma cholinesterase levels may be decreased in patients with

160 Section 1 General Care

TABLE 8-8

Elimination of Neuromuscular Blocking Agents54,55,58

Agent Renal Hepatic Biliary Plasma

Atracurium 10% NS Hofmann elimination, ester hydrolysis

Cisatracurium NS NS Hofmann elimination

Pancuronium 80% 10% 5%–10%

Rocuronium 10%–25% 10%–20% 50%–70%

Succinylcholine Plasma cholinesterase

Vecuronium 15%–25% 20%–30% 40%–75%

NS, not significant.

renal or hepatic dysfunction, the duration of action of succinylcholine could be prolonged. The increased duration of action

of succinylcholine in patients with low levels of normal plasma

cholinesterase is generally not clinically significant. Patients with

atypical plasma cholinesterase, however, cannot hydrolyze the

ester bonds in succinylcholine. This results in a significantly

increased duration of action in these patients.64

Unchanged neuromuscular blocking agents and their metabolites are excreted by the renal or biliary routes. The duration of

action of the renally eliminated agent, pancuronium, will be

increased in patients with renal failure. Vecuronium’s duration

of action can be increased in patients with liver disease, reflecting impaired metabolism or excretion rather than termination

of effect by redistribution.65 Although the main route of elimination of rocuronium is hepatobiliary, the duration of action

of rocuronium can be significantly prolonged in chronic renal

failure.66

Because M.M. has evidence of both significant renal and hepatic impairment, cisatracurium or atracurium would be appropriate choices for a neuromuscular blocking agent because their

properties are not altered significantly by renal and hepatic failure. Furthermore, because these agents have an intermediate

duration of action, they can easily be used in a 2-hour procedure. The availability of generic atracurium makes this agent

a more economical choice; however, the greater propensity of

atracurium to cause histamine release with resultant hypotension makes cisatracurium the most appropriate choice in this

70-year-old, ASA-IV patient.

LOCAL ANESTHETICS

Local and Regional Anesthesia

Some surgical procedures can be performed under regional anesthesia (anesthesia selective for part of the body, such as the

area near the surgical site) rather than general anesthesia (total

body anesthesia with the patient rendered unconscious). Epidural, spinal (intrathecal), peripheral nerve block, or local infiltration anesthesia can be chosen, depending on the location of the

surgical site, extent of the surgery, patient health and physical

characteristics, coagulation status, duration of surgery, and the

desires and cooperativeness of the patient. For epidural anesthesia, the local anesthetic is administered into the epidural space,

which is located between the dura and the ligament covering the

spinal vertebral bodies and discs. To provide spinal anesthesia,

the local anesthetic is injected into the cerebrospinal fluid within

the subarachnoid (intrathecal) space. By injecting a local anesthetic in the tissue near a specific nerve or nerve plexus (peripheral

nerve block), certain types of surgery can be performed under

regional anesthesia rather than general anesthesia. Examples

include carotid endarterectomy (cervical plexus), upper extremity surgery (brachial plexus), and hand surgery (ulnar, median,

or radial nerve). Regional anesthesia can be selected to reduce

or avoid the likelihood of complications such as postoperative

pain, nausea, vomiting, laryngeal irritation, or dental complications, all of which are associated with general anesthesia. Potential advantages of spinal or epidural anesthesia include reduction

of the stress response to surgery, improvement in cardiac function in patients with ischemic heart disease, fewer postoperative

pulmonary complications, and the ability to continue epidural

analgesia into the postoperative period.67 Potential advantages

of peripheral nerve block include continued analgesia into the

postoperative period and fewer side effects or technical problems

than epidural analgesia.68 Disadvantages of spinal, epidural, or

peripheral nerve block include the additional time and manipulations required to perform it, possible complications or pain from

invasive catheter placements or injections, slow onset of effect,

possible failure of technique, and potential toxicity from absorption of the drugs administered. Finally, local infiltration anesthesia can be used to provide localized anesthesia to allow a minor

procedure (e.g., a deep laceration repair) to be performed or to

provide postoperative analgesia at the site of surgical incision.

Uses of Local Anesthetic Agents

Local anesthetics are a mainstay of analgesia because they prevent

the initiation or propagation of the electrical impulses required

for peripheral and spinal nerve conduction. These agents can be

administered by all routes previously discussed, depending on

the drug chosen. Table 8-9 lists the common uses of currently

available local anesthetics.69,70 Local anesthetics are often given

in combination with other agents, such as sodium bicarbonate

(to increase the speed of onset and reduce pain on local infiltration), epinephrine (to prolong the duration of action and to

delay vascular absorption of the local anesthetic, thereby minimizing plasma concentration and systemic toxicity), or opioids

(to provide analgesia by a different mechanism of action).

TABLE 8-9

Clinical Uses of Local Anesthetic Agents69,70

Agent Primary Clinical Use

Esters

Chloroprocaine Epidural

Cocaine Topical

Tetracaine Topical

Amides

Bupivacaine Local infiltration, nerve block, epidural, spinal

Lidocaine Local infiltration, nerve block, spinal, epidural,

topical, intravenous regional

Mepivacaine Local infiltration, nerve block, epidural

Ropivacaine Local infiltration, nerve block, epidural

161Perioperative Care Chapter 8

Mechanism of Action

The two structural classes of local anesthetics are characterized

by the linkage between the molecule’s lipophilic aromatic group

and hydrophilic amine group: amides and esters. Both amide and

ester classes provide anesthesia and analgesia by reversibly binding to and blocking the sodium channels in nerve membranes,

thereby decreasing the rate of rise of the action potential such that

threshold potential is not reached. As a result, propagation of the

electrical impulses required for nerve conduction is prevented.

The axonal membrane blockade that results is selective depending on the drug, the concentration and volume administered,

and the depth of nerve penetration. C fibers (pain transmission

and autonomic activity) appear to be the most easily blocked,

followed by fibers responsible for touch and pressure sensation

(A-α,A-β, and A-δ), and finally, those responsible for motor function (A-α and A-β). At the most commonly used doses and concentrations, some non–pain-transmitting nerve fibers are also

blocked. The blockade of sensory, motor, or autonomic (sympathetic, parasympathetic) fibers may result in adverse effects

such as paresthesia, numbness and inability to move extremities, hypotension, and urinary retention. Systemic effects (e.g.,

seizures or cardiac arrhythmias) are related to the inherent cardiac and CNS safety margins of these drugs.69,70

Ropivacaine, like bupivacaine, has a long duration of action.

Higher plasma concentrations of ropivacaine are required to produce mild CNS toxicity (lightheadedness, tinnitus, numbness of

the tongue) in volunteers when compared with bupivacaine. In

animal studies, ropivacaine was found to be less cardiotoxic than

bupivacaine. As a result, some practitioners believe that ropivacaine is safer than bupivacaine. However, once plasma concentrations reach higher levels, all local anesthetics are capable of

producing severe myocardial depression.71 Prevention of local

anesthetic systemic toxicity (LAST) is key, with attention paid

to early detection of intravascular needle or catheter placement

as well as predictors of local anesthetic plasma levels (e.g., dose,

block site, patient factors, etc.) that will be discussed further in

the Toxicity section.

Allergic Reaction

Localized skin hypersensitivity reactions (e.g., localized rash,

itching, edema, burning) to local anesthetics are the most common types of allergic reactions. Ester-type local anesthetic agents

(e.g., chloroprocaine) produce most of the allergic reactions,

owing to their metabolite, para-aminobenzoic acid (PABA). True

(systemic immunologic) allergy to amide-type local anesthetics

is extremely rare. However, allergic reactions may occur to a

preservative (methylparaben or other substances that are structurally similar to PABA) in the product. Because amide-type local

anesthetics do not undergo metabolism to a PABA metabolite,

a patient with a known allergy to an ester-type local anesthetic

can safely receive an amide-type agent.69,70,72 When selecting a

product, it is best to administer a preservative free, epinephrinefree preparation to a patient with a known allergy to a local

anesthetic.

Toxicity

Factors that influence the toxicity of local anesthetics include

the total amount of drug administered, presence or absence of

epinephrine, vascularity of the injection site, extremities of age

(e.g., <4 months or >70 years of age), and presence of cardiac, renal, or hepatic dysfunction.71 Systemic absorption of the

local anesthetic is positively correlated with the vascularity of the

injection site (IV > epidural > brachial plexus > subcutaneous).

End-stage pregnancy, extremities of age, significant hepatic or

renal dysfunction, and advanced heart failure can result in either

higher peak levels or accumulation of local anesthetic with continued or repeated dosing. In general, local anesthetic doses

should be reduced in patients with these conditions.73

Toxic levels of local anesthetics are most often achieved by

unintentional intravascular injection, which results in excessive

plasma concentrations. Systemic toxicity of local anesthetics

involves the CNS and cardiovascular systems. Patients may initially complain of tinnitus, lightheadedness, metallic taste in the

mouth, tingling, numbness, and dizziness. Hypotension may

occur. These symptoms can quickly be followed by tremors,

seizures, arrhythmias, unconsciousness, and cardiac or respiratory arrest as plasma levels rise.69,74 If signs and symptoms of

LAST occur, treatment includes airway management, benzodiazepines for seizure management, and if a cardiac arrest occurs,

standard Advanced Cardiac Life Support should be initiated

with minor modifications. Small (10–100 mcg) initial epinephrine

doses are preferred, vasopressin is not recommended, calciumchannel blockers and β-blockers should be avoided, and ventricular arrhythmias should be treated with amiodarone. After

airway management, 20% lipid emulsion therapy may be considered at the first signs of LAST (initial IV bolus dose of 1.5

mL/kg followed by 0.25 mL/kg/minute for at least 10 minutes

after circulatory stability is achieved).71

Physicochemical Properties

Affecting Action

The potency of a local anesthetic is primarily determined by the

degree of lipid solubility. Local anesthetics such as bupivacaine

are highly lipid soluble and can be given in concentrations of

0.25% to 0.5%. Less lipid-soluble agents, such as lidocaine, require

concentrations of 1% to 2% for many anesthetic techniques.

Amide-type local anesthetics are metabolized primarily by

microsomal enzymes in the liver. The cytochrome P-450 enzyme

system is involved in the metabolism of lidocaine (CYP3A4)

and ropivacaine (CYP3A2, CYP3A4, and CYP1A2). Agents that

induce or inhibit these enzymes could affect the metabolism,

and therefore the plasma concentration, of these drugs. Estertype local anesthetics are hydrolyzed by plasma cholinesterase

and, to a lesser extent, cholinesterase in the liver.69,70

Differences in the clinical activity of local anesthetics are

explained by other physicochemical properties such as protein

binding and pKa (the pH at which 50% of the drug is present in

the unionized form and 50% in the ionized form). Agents that are

highly protein bound typically have a longer duration of action.

Agents with a lower pKa typically have a faster onset of action.70

Choice of local anesthetic is based on the duration of the surgical procedure (e.g., the duration of analgesia required). Usually,

a local anesthetic that will, at least minimally, outlast the duration

of surgery with a single injection is chosen; a continuous infusion

can also be administered for titration of effect with shorter-acting

agents. Important physicochemical and pharmacokinetic properties of local anesthetics are shown in Table 8-10.69,70

Regional Anesthesia in

High-Risk Patients

CASE 8-11

QUESTION 1: M.S., a 52-year-old, 5-foot 9-inch, 105-kg

black man, is undergoing an emergent minor hand repair

procedure after a fall-related injury. His medical history is

positive for type 1 diabetes mellitus for 41 years, angina,

162 Section 1 General Care

TABLE 8-10

Physicochemical and Pharmacokinetic Properties of Local Anesthetic Agents69,70

Maximum Recommended Doseb

Agent pKa Potency Toxicity Onset Durationa Plain (mg) With Epinephrine (mg)

Esters

Cocainec – – – – – 1.5 mg/kg –

Chloroprocaine 9.1 Low Very low Very fast Short 800 1,000

Tetracaine 8.4 High Moderate Slow Very long 100 (topical) 200

Amides

Bupivacaine 8.1 High High Slow Long 175 225

Lidocaine 7.8 Moderate Moderate Fast Moderate 300 500

Mepivacaine 7.7 Moderate Moderate Moderate Moderate 300 500

Ropivacaine 8.1 High Moderate Slow Long 300 –

aDepends on factors such as injection site, dose, and addition of epinephrine. In general, a short duration is <1 hour, a moderate duration is 1–3 hours, and a long or very

long duration of action is 3–12 hours when the local anesthetic is administered without epinephrine.

b Maximum recommended single dose for infiltration or peripheral nerve block in 70-kg adults.

cTopical use only; concentrations >4% are not recommended owing to increased risk for systemic adverse effects.

and hypertension. On OR admission, laboratory values of

note are plasma glucose, 240 mg/dL, and BP, 145/92 mm

Hg. His sister tells the anesthesia provider that he has been

having increasing difficulty walking up stairs and, of late, is

often short of breath. The anesthesia provider chooses to

provide regional anesthesia via an axillary block; the anticipated duration of surgery is 2 hours. M.S. agrees with this

plan. Why is this a good plan for M.S., and which local anesthetic should be chosen?

With his medical conditions of diabetes, angina, and hypertension, M.S. is at risk for complications from general anesthesia.

General anesthesia is not absolutely necessary in this localized

surgery. Regional anesthesia would be beneficial in M.S. because

it does not disrupt autonomic function. In addition, his diabetes

and obesity, and possibly full stomach (emergency surgery, diabetic gastroparesis), place him at significant risk for aspiration

during both induction and emergence from general anesthesia.

An axillary block with a local anesthetic could provide M.S. with

adequate anesthesia and analgesia during and after his procedure.

The local anesthetic of choice is one with a duration at least

that of the anticipated surgery and with a good safety profile

should systemic absorption inadvertently occur. A local anesthetic containing epinephrine would increase the agent’s duration of action and reduce the systemic absorption; however, such

an agent is not indicated in M.S. because of his diabetes (peripheral vascular effects) and hypertension (added effect from catecholamine administration). Lidocaine as a single injection without epinephrine has a duration of action that may be too short

for M.S.’s procedure. Mepivacaine, an intermediate-acting local

anesthetic, or ropivacaine, a long-acting agent to provide longerlasting postoperative analgesia, would be appropriate choices to

use in M.S.

Alkalinization of Local Anesthetics

CASE 8-12

QUESTION 1: T.F., a 22-year-old man, is scheduled for a hernia repair. He has never undergone surgery and is very anxious. In the preoperative area, the nurse chooses to locally

infiltrate 1% lidocaine to reduce the pain and discomfort

from IV catheter placement. She injects a small amount of

lidocaine under the skin. T.F. flinches and complains of pain

from the injection. Can anything be done to reduce the pain

from injection of lidocaine?

The onset of action of local anesthetics depends on their pKa.

Drugs with pKas closest to body pH (7.4) will have the fastest

onset because a high percentage of the local anesthetic molecules

will be unionized and therefore will be able to cross the nerve

membranes to their intracellular site of action. Local anesthetics are formulated in solutions with acidic pH to optimize their

shelf-lives. When sodium bicarbonate is added to local anesthetic

solutions, the pH is increased, the percentage of unionized drug

is increased, and the onset of local anesthetic action can be shortened considerably. The amount of bicarbonate added to the solution depends on the pH of the local anesthetic agent. Because too

much sodium bicarbonate will precipitate the local anesthetic,

a dose of 0.1 mEq (0.1 mL of a 1-mEq/mL concentration) of

sodium bicarbonate is added to 10 mL of bupivacaine, whereas

1 mEq (1 mL of a 1-mEq/mL concentration) is added to 10 mL of

lidocaine. More importantly, alkalinized lidocaine can be significantly less painful for subcutaneous injection before IV catheter

placement when compared with lidocaine at pH 5 (its pH in

the commercially available vial).75 However, if the lidocaine contains epinephrine, the addition of bicarbonate to the solution

will destroy the activity of epinephrine (which is stable only in

an acidic pH).

ANTIEMETIC AGENTS AND

POSTOPERATIVE NAUSEA AND

VOMITING

Impact of Postoperative Nausea and

Vomiting

The two most common complications after surgery are postoperative pain and PONV. Patients who experience PONV are

greatly dissatisfied with their surgical experience, and require

additional resources such as nursing time, and medical and surgical supplies. Furthermore, vomiting can provoke the rupture

of surgical sutures and cause wound pain and hematomas, and,

if severe, more serious adverse events can occur (e.g., aspiration pneumonitis, increased intraocular pressure leading to loss

of vision). PONV typically lasts less than 24 hours; however,

symptom distress can continue at home, thereby preventing the

163Perioperative Care Chapter 8

patient from resuming normal activities or returning to work.

It is important to remember that nausea is a separate subjective

sensation and is not always followed by vomiting. Nausea can be

more distressing to patients than vomiting.76

Mechanisms of and Factors Affecting

Postoperative Nausea and Vomiting

The vomiting center is reflex activated through the chemoreceptor trigger zone (CTZ). Input from other sources can also

stimulate the vomiting center. Afferent impulses from the periphery (e.g., manipulation of the oropharynx or GI tract), the cerebral cortex (e.g., unpleasant sights or smells, emotions, anxiety,

hypotension, pain), and the endocrine environment (e.g., female

sex) can also stimulate the vomiting center. In addition, disturbances in vestibular function (e.g., movement after surgery, middle ear surgery) can stimulate the vomiting center via direct

central pathways and the CTZ. Neurotransmitter receptors that

play an important role in impulse transmission to the vomiting

center include dopamine type 2 (D2), serotonin (5-HT3), muscarinic cholinergic (M1), histamine type 1 (H1), and neurokinin

type 1 (NK1) (Fig. 8-1).76–80 Opioid analgesics can activate the

CTZ, as well as the vestibular apparatus, to produce nausea and

vomiting.76–80

PONV is probably not caused by a single event, entity, or

mechanism; instead, the cause is likely to be multifactorial. Factors that place adults at risk for developing PONV include female

sex, history of PONV or motion sickness, nonsmoking status,

use of postoperative opioids, duration of anesthesia, and general

anesthesia with inhalation anesthetic agents.81,82 A commonly

used tool for determining an adult patient’s risk of developing

PONV has been developed; one point is assigned to each of the

following risk factors: female sex, nonsmoker, history of PONV,

and postoperative use of opioids.83 The level of risk for developing PONV is low (<20%) for patients with zero or one risk factor

and increases significantly with the presence of each additional

risk factor (2 risk factors, 40%; 3 risk factors, 60%; and 4 risk factors, 80%).83 For children, risk factors for postoperative vomiting

include duration of surgery 30 minutes or longer, age 3 years or

older, strabismus surgery, and a history of postoperative vomiting in the child or PONV in the mother, father, or siblings.84

Similarly to adults, the level of risk for developing postoperative

vomiting is low for children with zero or one risk factor and

increases significantly with the presence of each additional risk

factor (2 risk factors, 30%; 3 risk factors, 55%; and 4 risk factors,

70%).83 In children, nausea is not easily measured and hence not

routinely assessed.

CASE 8-13

QUESTION 1: J.E., a 34-year-old, 55-kg woman, is scheduled to undergo a gynecologic laparoscopy under general inhalation anesthesia on an outpatient basis. She has

had one previous surgery, has no known medication allergies, and is a nonsmoker. On questioning, she reports that

she experienced PONV after her first surgery. Her physical

D2, 5-HT3, M1,

Mu–opioid, NK1

Vestibular center

(movement after surgery,

middle ear surgery)

H1, M1 Endocrine environment

(female sex, pregnancy)

Increased ICP (tumor,

CSF obstruction)

Cerebral cortex (anxiety,

emotions, sights, smells)

Vagal afferents from the

periphery (distension of GI

tract, gastroparesis,

insufflation of the

abdomen during

laparoscopic surgery, early

ingestion of fluids or food)

5-HT3, D2, NK1

D2, 5-HT3, M1,

H1, NK1

Chemoreceptor

Trigger Zone

Nucleus Tractus

Solitarius

Vomiting Center

Upper GI Tract

Motor Response –

Emesis

Hypotension,

hypoxia

FIGURE 8-1 Mechanisms and neurotransmitters of postoperative nausea and vomiting. The chemoreceptor

trigger zone (CTZ) is located in the area postrema of the midbrain. The vomiting center is also located in the

midbrain, close to the nucleus tractus solitarius (NTS) and the area postrema. The CTZ, NTS, and area postrema

are rich in 5-HT3, H1, M1, D2, and mu-opioid receptors. Antiemetic agents used to manage postoperative

nausea and vomiting block one or more of these receptors. 5-HT3, serotonin type 3 receptor; CSF, cerebral

spinal fluid; D2, dopamine type 2 receptor; GI, gastrointestinal; H1, histamine type 1 receptor; ICP, intracranial

pressure; M1, muscarinic cholinergic type 1 receptor; NK1, substance P neurokinin type 1 receptor.

164 Section 1 General Care

examination is unremarkable. Is J.E. a candidate for prophylactic antiemetic therapy?

J.E. has several risk factors that make her susceptible to experiencing PONV. Adult women are two to three times more likely

than adult men to develop PONV. Previous PONV also increases

the likelihood of developing PONV threefold. In addition, a nonsmoking status increases the risk of developing PONV. Using

the simplified risk score for PONV, J.E. has four risk factors,

anticipating that she will require postoperative opioids for pain

management. In addition, the type of procedure J.E. is undergoing (gynecologic laparoscopy) may further increase her risk for

developing PONV. Because of the presence of four risk factors,

J.E. is at very high risk and should be administered at least two

prophylactic antiemetic agents.

Prevention of Postoperative Nausea and

Vomiting: Choice of Agent

CASE 8-13, QUESTION 2: Which antiemetic drugs would be

most appropriate for J.E., and when should they be administered?

Antiemetic drugs can be classified as antimuscarinics (scopolamine, promethazine, diphenhydramine), serotonin antagonists (ondansetron, dolasetron, granisetron, palonosetron),

benzamides (metoclopramide), butyrophenones (droperidol),

phenothiazines (prochlorperazine), and NK1 antagonists (aprepitant). These drugs exert their antiemetic effects primarily

by blocking one central neurotransmitter receptor and exert

their antiemetic effect independently of one another. The

higher a patient’s baseline risk for experiencing PONV, the

more antiemetic agents and interventions must be combined. Dopamine antagonists include the benzamides, butyrophenones, and phenothiazines. Ondansetron, granisetron,

dolasetron, and palonosetron block 5-HT3 receptors of vagal

afferent nerves in the GI tract and in the CTZ. Antimuscarinics

such as scopolamine and diphenhydramine likely exert their

antiemetic effect by blocking Ach in the vestibular apparatus,

vomiting center, and CTZ. The proposed site of action, usual

adult dose, and select adverse effects of the commonly used

antiemetic drugs for prevention and treatment of PONV are

summarized in Table 8-11.3,76,78,81,82,85

BUTYROPHENONES

Droperidol possesses significant antiemetic activity. It effectively

prevents PONV at IV doses of 0.625 to 1.25 mg, with a rapid onset

and short duration of action.86 Therefore, droperidol is most

effective when administered near the end of surgery. Adverse

effects include sedation (especially at doses ≥2.5 mg), hallucinations, hypotension, and, rarely, restlessness or other extrapyramidal (EP) reactions. Because of its effectiveness and cost, droperidol has historically been used extensively as a first-line agent.

However, in December 2001, the FDA strengthened warnings

regarding adverse cardiac events after droperidol administration.

With the new warning to perform continuous 12-lead electrocardiographic monitoring before and for 2 to 3 hours after administration of droperidol, it became an issue, from both expense and

logistical viewpoints, to administer droperidol to an outpatient,

a patient in the PACU (recovery room), or a patient in an unmonitored bed. Because low-dose droperidol has been used for more

than 30 years to prevent PONV, several studies were undertaken

to examine the effect of low-dose droperidol on the QTc interval.

When compared with placebo (saline), low-dose droperidol did

not produce QTc prolongation after surgery.87 When compared

with ondansetron, droperidol produced similar QTc prolongation, and it was concluded that serotonin antagonists may not

be safer than low-dose droperiol.88 Finally, Nuttall et al.89 retrospectively examined whether low-dose droperidol administration increased the incidence of torsades de pointes in patients

undergoing general surgery. Of the 16,791 patients exposed to

droperidol, no patient experienced torsades de pointes. These

authors concluded that the FDA’s black-box warning for lowdose droperidol is excessive and unnecessary.

BENZAMIDES

Metoclopramide, in doses of 10 to 20 mg, has been used in the

prevention and treatment of PONV. However, variable results

have been seen with this agent at these doses.90 For maximal

benefit, metoclopramide should be administered in a dose of

25 mg IV near the end of surgery (secondary to its rapid redistribution after IV administration); 10 mg IV administered at the

beginning of surgery is not effective.91 Adverse effects of metoclopramide include drowsiness and EP reactions, such as anxiety and restlessness. Metoclopramide should be administered

by slow IV injection for at least 2 minutes to minimize the risk

of EP reactions and cardiovascular effects such as hypotension,

bradycardia, and supraventricular tachycardia.

SEROTONIN ANTAGONISTS

Ondansetron (4 mg IV) was the first 5-HT3 antagonist to receive

an indication for PONV. Dolasetron (12.5 mg IV) and granisetron

(1 mg IV) are also approved for preventing and treating PONV.

Palonosetron (0.075 mg IV) is approved for the prevention of

PONV for up to 24 hours after surgery. In general, serotonin

antagonists are consistently more effective in reducing vomiting

rather than nausea.82,92 Ondansetron and dolasetron are equally

efficacious in preventing PONV.93 A single dose of ondansetron,

dolasetron, or granisetron provides acute relief and can protect

against nausea and vomiting for up to 24 hours after administration. Palonosetron is effective when compared with placebo,

but it has not been compared with the older, first-generation

agents (ondansetron, granisetron, dolasetron). For optimal efficacy, serotonin antagonists should be administered near the end

of surgery. Adverse effects are generally minimal and include

headache and constipation; prolongation of the QTc interval can

occur.