Epidural analgesia should be chosen based on the need for good

postoperative pain relief and reduced perioperative physiological

responses. Postoperative pain should be localized at an appropriate level for catheter placement in the lumbar or thoracic location

of the epidural space. Patients undergoing abdominal, gynecologic, obstetric, colorectal, urologic, lower limb (e.g., major vascular), or thoracic surgery are excellent candidates for epidural

pain management. Absolute contraindications to epidural analgesia include severe systemic infection or infection in the area

of catheter insertion, known coagulopathy, clinically significant

abnormal platelet count or function, increased intracranial pressure, patient refusal, and anatomical abnormalities that make

epidural catheter placement difficult or impossible.121 T.M. is

a good candidate for epidural analgesia based on the severity of

pain associated with his surgery and the location and invasiveness

of the surgical procedure.

CHOICE OF AGENT AND MECHANISMS OF ACTION

CASE 8-15, QUESTION 2: What drug or drug combination

can be used for T.M.’s epidural infusion? What are the mechanisms of action of the analgesics commonly administered

in the epidural space?

Most commonly, an opioid and a local anesthetic are administered in combination in the epidural analgesic infusion. Opioids

in the epidural space are transported by passive diffusion and the

vasculature to the spinal cord, where they act at opioid receptors in the dorsal horn. After epidural administration, opioids can

reach brainstem sites by cephalad movement in the cerebrospinal

fluid. In addition, lipophilic opioids (fentanyl, sufentanil) have

substantial systemic absorption from the epidural space.113,122

Opioids selectively block pain transmission and have no effect on

nerve transmission responsible for motor, sensory, or autonomic

function.123 Local anesthetics, however, spread within the epidural space to anesthetize nerve roots as they exit the neural foramina (openings in the spinal column) and block nerve transmission.

Depending on the drug, concentration, and depth of nerve penetration, local anesthetics produce sensory, motor, or autonomic

blockade (see Local Anesthetics section). Table 8-13 describes the

spinal actions, efficacy, and adverse effects of opioids and local

anesthetics administered by the epidural route.114,121,122,124

As previously mentioned, opioids and local anesthetics are

combined in the same solution because these two classes of

drugs act synergistically at two different sites to produce analgesia, allowing the administration of lower doses of each drug

to reduce the risk of adverse effects while providing effective

analgesia. Table 8-14 lists the drugs, concentrations, and typical

infusion rates for epidural administration.115,122,123,125 Bupivacaine is commonly chosen as the local anesthetic agent. Because

pain fibers are on the outer aspect of the nerve and are not heavily

myelinated, a low concentration of bupivacaine (≤0.125%) can

be administered to block these fibers without significantly blocking motor fibers. The choice of opioid is based on pharmacokinetic differences among the available agents. Onset, duration,

spread of agent in the spinal fluid (dermatomal spread), and systemic absorption are affected by the lipophilicity of the drug.124

Highly lipophilic opioids such as fentanyl and sufentanil have

a faster onset of action, a shorter duration of action (from a

TABLE 8-13

A Comparison of the Spinal Actions, Efficacy, and Adverse Effects of Opioids and Local Anestheticsa,114,121,122,124

Opioids Local Anesthetics

Actions

Site of action Substantia gelatinosa of dorsal horn of spinal cordb Spinal nerve roots

Modalities blocked “Selective” block of pain conduction Blockade of pain nerve fibers; can block sensory or motor fibers

Efficacy

Surgical pain Partial relief Complete relief possible

Labor pain Partial relief Complete relief

Postoperative pain Fair or good relief Complete relief

Adverse effects Nausea, vomiting, sedation, pruritus, constipation or

ileus, urinary retention, respiratory depression

Hypotension, urinary retention, loss of sensation, loss of motor

function (patient may not be able to bear weight and ambulate)

a Epidurally administered morphine and local anesthetics exert their effects mainly by a spinal mechanism of action; lipophilic opioids such as fentanyl and sufentanil achieve

therapeutic plasma concentrations when administered epidurally and therefore exert their effects by a systemic mechanism of action.

b Other sites where opioid receptor binding sites are present.

171Perioperative Care Chapter 8

TABLE 8-14

Adult Analgesic Dosing Recommendations for Epidural Infusion115,122,123,125

Drug Combinationa Infusion Concentrationb Usual Infusion Rateb

Morphine + bupivacaine 12.5–25 mcg/mL (M) 4–10 mL/h

0.5–1.25 mg/mL (B)

Hydromorphone + bupivacaine 3–10 mcg/mL (H) 4–10 mL/h

0.5–1.25 mg/mL (B)

Fentanyl + bupivacaine 2–5 mcg/mL (F) 4–10 mL/h

0.5–1.25 mg/mL (B)

Sufentanil + bupivacaine 1 mcg/mL (S) 4–10 mL/h

0.5–1.25 mg/mL (B)

aUse only preservative free products and preservative free 0.9% sodium chloride as the admixture solution.

b Exact concentrations and rates are institution specific. Initial concentration and rate often depend on the age and general condition

of the patient and the location of the catheter.

B, bupivacaine; F, fentanyl; H, hydromorphone; M, morphine; S, sufentanil.

single dose), less dermatomal spread, and much greater systemic absorption. After several hours of epidural infusion, the

dermatomal (regional) effect of fentanyl is lost, and analgesia

is achieved because of a therapeutic plasma concentration. Morphine, which is relatively hydrophilic, has a slower onset of action,

longer duration of action, greater dermatomal spread and migration to the brain, and less systemic absorption.122,124 Morphine,

unlike fentanyl, retains its spinal site of action.122 The lipophilicity

of hydromorphone is intermediate between fentanyl and morphine. Clinically, hydromorphone has a faster onset and shorter

duration than morphine. Its site of action is likely in the spinal

cord.126 A comparison of the pharmacokinetic properties important to epidural opioids is found in Table 8-15.115,116,124,125 T.M.

should receive a combination of opioid and local anesthetic, such

as hydromorphone and bupivacaine, as an epidural infusion for

postoperative pain management.

CASE 8-15, QUESTION 3: Hydromorphone–bupivacaine is

chosen for T.M. How should this be prepared, and what infusion rate should be chosen?

Hydromorphone and bupivacaine are commonly admixed

in 0.9% sodium chloride (usual concentration ranges are found

in Table 8-14). Concentrations are often institution-specific and

depend on the rate of administration. Preservative free preparations of each drug should be used because neurologic effects

are possible with inadvertent subdural administration of large

amounts of benzyl alcohol or other preservatives. Strict aseptic

technique should be used when admixing and administering an

epidural solution.

The rate of administration is chosen empirically based on the

anticipated analgesic response, the concentration of opioid in the

admixture, and the potential for adverse effects. Usually, a rate of

4 to 10 mL/hour is adequate; the epidural space can safely handle

up to approximately 20 mL/hour of fluid. An initial infusion rate

of 8 mL/hour would be reasonable for T.M., with titration based

on efficacy and adverse effects.

ADVERSE EFFECTS

CASE 8-15, QUESTION 4: Two hours after initiation of his

hydromorphone–bupivacaine epidural infusion, T.M. experiences discomfort in the form of an itchy feeling on his nose,

torso, and limbs. Is this related to his epidural infusion?

Adverse effects of the epidural infusion may be caused by

the opioid or the local anesthetic. Pruritus has been associated

with almost all opioids, with a significantly greater frequency

when the opioid is administered as an epidural infusion rather

than by IV administration.127 This effect is usually seen within

2 hours and is probably dose-related. It generally subsides as the

opioid effect wears off and can be more of a problem with continuous epidural administration of opioids or when opioids are

administered via PCA. Although pruritus from opioids is probably mu-receptor mediated and not histamine mediated, antihistamines (e.g., diphenhydramine) are commonly used with equivocal effectiveness. A better approach is to administer very small

doses of a mu-antagonist (e.g., naloxone 0.04 mg or nalbuphine

2.5 mg) to effectively reverse opioid adverse effects, such as pruritus, but not analgesia. Because of naloxone’s short duration

of action, nalbuphine is often preferred. Ondansetron has also

shown some efficacy for managing itching from an intrathecal

or epidural opioid.128

Other adverse effects possible with epidural opioids include

nausea, vomiting, constipation, ileus, urinary retention, sedation, and respiratory depression. Although rare, respiratory

depression from epidural opioids is the most dangerous adverse

effect. Respiratory depression can occur as long as 12 to

24 hours after a single bolus of morphine122,124 or within hours

after beginning a continuous infusion of fentanyl–bupivacaine

TABLE 8-15

Pharmacokinetic Comparison of Common Epidural Opioid Analgesics115,116,124,125

Agent Partition Coefficienta

Onset of Action of

Bolus (minutes)

Duration of Action

of Bolus (hours) Dermatomal Spread

Fentanyl 955 5 2–4 Narrow

Hydromorphone 525 15 6–12 Intermediate

Morphine sulfate (Duramorph) 1 30 12–24 Wide

Sufentanil 1,737 5 2–4 Narrow

aOctanol–water partition coefficient; used to assess lipophilicity; higher numbers indicate greater lipophilicity.

172 Section 1 General Care

or hydromorphone–bupivacaine. Sedation level, as well as respiratory rate and effort, must be assessed every hour for the first

12 hours, then every 2 hours for the next 12 hours, then if stable,

every 4 hours until removal of the catheter.129 As with parenteral

opioids, particular attention must be paid to patients at high

risk for respiratory depression from an opioid. These risk factors include age older than 65 years, obesity, pulmonary disease

or other conditions that reduce ventilatory capacity, and known

or suspected history of sleep apnea.114 In a patient with known

obstructive sleep apnea, for example, the anesthesia provider may

prescribe an epidural analgesic solution containing bupivacaine

only (no opioid).

Adverse effects of epidural local anesthetics include hypotension, urinary retention, lower limb paresthesias or numbness,

and lower limb motor weakness. Depending on the degree of

numbness and motor weakness, the patient may have difficulty

ambulating. In a patient prone to hypotension or