Chapter 31 Epidural Opioids for Postoperative Pain

Question 1

An opioid administered into the epidural space will diffuse

into

Answer 1

the surrounding tissues including epidural fat and
veins. Opioids that diffuse into epidural fat are no longer available to bind to opioid receptors and thus cannot produce analgesia.

Question 2

Opioids administered into the epidural space generally produce analgesia via two mechanisms:

Answer 2

spinal and supraspinal/systemic analgesia

Question 3

supraspinally mediated analgesia produced by

Answer 3

epidural opioids may be
absorbed into plasma and redistributed to the brainstem opioid receptors
via the bloodstream

Question 4

spinally mediated analgesia produced by

Answer 4

epidural opioids must diffuse through the spinal meninges into the cerebrospinal fluid

Question 5

Once inside the CSF, epidural opioids interact with

Answer 5

spinal opioid receptors
located in lamina II of the dorsal horn of the spinal cord
and achieve antinociception via presynaptic reduction of
afferent neurotransmitter release and postsynaptic hyperpolarization
of dorsal horn neurons

Question 6

One of the key pharmacologic properties of an epidurally
administered opioid that determines its analgesic and
side effect profile is

Answer 6

the extent of its lipophilicity

Question 7

lipophilic opioids

Answer 7

such as fentanyl and sufentanil, generally have a relatively faster onset but shorter duration of action

Question 8

hydrophilic opioids

Answer 8

morphine and hydromorphone

Question 9

The relatively rapid clearance from the CSF of lipophilic opioids may limit the

Answer 9

development of certain side effects such as delayed respiratory depression

Question 10

the primary analgesic site of

action for hydrophilic opioids

Answer 10

selectively spinal

Question 11

Once the epidurally administered hydrophilic opioid has penetrated the dural membrane into the CSF

Answer 11

the opioid will remain within the CSF to produce spinal analgesia and spread cephalad or rostrally in the CSF (due in part to its
low lipid solubility) to act at the brainstem.

Question 12

The rostral spread of hydrophilic opioid to the brainstem may be associated with what side effects

Answer 12

facial pruritus, nausea, and sedation.

Question 13

the analgesic profile (duration of analgesia and side effects) is dependent primarily on the

Answer 13

degree of lipophilicity (vs. hydrophilicity) with hydrophilic agents such as morphine and hydromorphone
producing a longer duration of analgesia versus
lipophilic agents such as fentanyl and sufentanil

Question 14

single injection of a hydrophilic opioid like morphine typically last

Answer 14

provides 12 to 18 hr of analgesia at the risk of
delayed respiratory depression and would be useful for postoperative analgesia in surgical inpatients with appropriate
monitoring or regular assessments

Question 15

A single epidural bolus of a lipophilic opioid like fentanyl last

Answer 15

a rapid (onset within 5–10 min) but relatively transient (up to 4 hr) postoperative analgesia.

Question 16

Diluting the epidural dose of fentanyl (typically 50–100 mg)

in at least 10 ml of preservative-free normal saline will

Answer 16

hasten onset and prolong the duration of analgesia possibly as a result of an increase in the initial spread and diffusion of fentanyl

Question 17

Combining a hydrophilic

opioid (e.g., morphine) and a lipophilic opioid (e.g., sufentanil) in a single epidural injection

Answer 17

combines the short onset

time produced by the lipophilic opioid and the long duration of analgesia produced by the hydrophilic opioid

Question 18

The doses of epidural morphine may need to be decreased for

Answer 18

elderly patients and thoracic catheter sites

Question 19

Fentanyl Epidural Dose

Answer 19

Single Dose: 50–100 mcg

Continuous Infusion: 25–100 mcg/hr

Question 20

Sufentanil Epidural Dose

Answer 20

Single Dose: 10–50 mcg

Continuous Infusion: 10–20 mcg/hr

Question 21

Alfentanil Epidural Dose

Answer 21

Single Dose: 0.5–1 mg

Continuous Infusion: 0.2 mg/hr

Question 22

Morphine Epidural Dose

Answer 22

Single Dose: 1–5 mg

Continuous Infusion: 0.1–1 mg/hr

Question 23

Diamorphine Epidural Dose

Answer 23

Single Dose: 4–6 mg

Continuous Infusion: —–

Question 24

Hydromorphone Epidural Dose

Answer 24

Single Dose: 0.5–1 mg

Continuous Infusion: 0.1–0.2 mg/hr

Question 25

Meperidine Epidural Dose

Answer 25

Single Dose: 20–60 mg | Continuous Infusion: 10–60 mg/hr

Question 26

Methadone Epidural Dose

Answer 26

Single Dose: 4–8 mg | Continuous Infusion: 0.3–0.5 mg/hr

Question 27

epidural infusions of lipophilic opioids produce analgesia primarily via

Answer 27

a supraspinal/systemic mechanism

Question 28

continuous epidural infusions of hydrophilic opioids produce analgesia primarily

Answer 28

a spinal mechanism

Question 29

SIDE EFFECTS OF EPIDURAL OPIOIDS

Answer 29

respiratory depression, | pruritus, nausea, and vomiting.

Question 30

Factors that may increase the risk of respiratory depression developing in patients who have received epidural opioids include:

Answer 30

thoracic surgery, presence of comorbidities, age, an opioid-naive state, and concomitant use of systemic opioids and sedatives

Question 31

differences in time of respiratory depressant | between epidural lipophilic and hydrophilic opioids.

Answer 31

``` Lipophilic opioids (e.g., fentanyl) administered in the epidural space are associated with early (typically within 2–4 hr of administration). the onset of respiratory depression after epidural administration of hydrophilic opioids (e.g., morphine) is generally slower. ```

Question 32

mechanism of respiratory depressant of epidural lipophilic and hydrophilic opioids.

Answer 32

Lipophilic opioids are rapidly absorbed systemically from the epidural venous plexus and delivered to the brain and respiratory centers, Hydrophilic epidural opioids are primarily delivered to the brain via relatively slower rostral migration in the CSF

Question 33

Cephalad spread of | hydrophilic opioids typically occurs within

Answer 33

12 hr following injection. Respiratory depression from epidural administration of hydrophilic opioids can therefore occur later, typically within 6 to 12 hr after injection

Question 34

Treatment in reversing respiratory depression

Answer 34

Administration of naloxone (0.1–0.4-mg increments) is generally effective in reversing respiratory depression; however, a continuous infusion of naloxone (0.5–5 mg/kg/hr) may be needed since the duration of action of naloxone is shorter than the respiratory depressant effect of epidural opioids

Question 35

Nausea and vomiting from epidural opioids | result from

Answer 35

interactions with opioid receptors in the area | postrema and chemotactic trigger zone of the medulla

Question 36

For epidurally administered hydrophilic opioids, nausea and vomiting may be related to

Answer 36

the cephalad migration of opioid within the CSF to the area postrema in the medulla

Question 37

Treatment of epidural opioid-induced nausea and vomiting may include

Answer 37

the use of naloxone, droperidol, metoclopramide, | dexamethasone, transdermal scopolamine, and even a small dose of propofol

Question 38

etiology of epidural opioid-induced pruritus

Answer 38

activation of an “itch center” in the medulla, interaction with opioid receptors in the trigeminal nucleus or nerve roots, or changes in the sensory modulation of the trigeminal and upper cervical spinal cord due to cephalad migration of the opioid; however, opioid-induced pruritus does not appear to be associated with peripheral histamine release

Question 39

treatment of of epidural opioid-induced pruritus

Answer 39

Naloxone, naltrexone, nalbuphine, and droperidol appear to be effective in the treatment of epidural opioid-induced pruritus

Question 40

mechanism of epidural opioids induced urinary | retention

Answer 40

related to a decrease in detrusor muscle | strength contraction secondary to spinal opioid receptor activation.

Question 41

treatment of epidural opioids induced urinary | retention

Answer 41

Low-dose naloxone may be effective in treating epidural opioid-induced urinary retention but at the risk of reversing analgesia.

Question 42

Unlike what occurs | with local anesthetics, use of epidural morphine will still allow

Answer 42

transmission of nociceptive information through the central nervous system.

Question 43

Because of the inability to completely suppress the neuroendocrine stress response, epidural opioids do not consistently prevent

Answer 43

the perioperative increases in cortisol, epinephrine, or glucose but may attenuate increases in levels of norepinephrine

Question 44

extended-release epidural | morphine (EREM) may provide analgesia for

Answer 44

48 hr after a single dose.

Question 45

extended-release epidural | morphine (EREM)

Answer 45

The current clinically available formulation utilizes microscopic lipid-based particles with numerous internal vesicles containing morphine. Each vesicle is separated from the adjacent chambers by synthetic analogs of naturally occurring lipid membranes

Question 46

Local Anesthetic with EREM

Answer 46

``` Local anesthetic (e.g., test dose) should not be administered immediately after injection of a dose of EREM; however, preliminary data indicate that any interaction may be minimized by waiting 15 min after a local anesthetic dose before injecting the EREM ```

Question 47

Continuous infusions of hydrophilic opioid vs Continuous infusions of lipophilic opioid

Answer 47

Continuous infusions of hydrophilic opioid alone provide effective postoperative analgesia even when the catheter insertion site is not congruent to the incision site. Continuous infusions of lipophilic opioid alone will not provide a selective spinal site of action; but because of their titratability, lipophilic opioid infusions are most commonly seen as part of a local anesthetic–opioid solution in patientcontrolled epidural analgesia