Chapter 31 Epidural Opioids for Postoperative Pain Flashcards Preview

Essentials of Pain Medicine > Chapter 31 Epidural Opioids for Postoperative Pain > Flashcards

Flashcards in Chapter 31 Epidural Opioids for Postoperative Pain Deck (47):

An opioid administered into the epidural space will diffuse

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.


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

spinal and supraspinal/systemic analgesia


supraspinally mediated analgesia produced by

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


spinally mediated analgesia produced by

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


Once inside the CSF, epidural opioids interact with

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


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

the extent of its lipophilicity


lipophilic opioids

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


hydrophilic opioids

morphine and hydromorphone


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

development of certain side effects such as delayed respiratory depression


the primary analgesic site of
action for hydrophilic opioids

selectively spinal


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

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.


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

facial pruritus, nausea, and sedation.


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

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


single injection of a hydrophilic opioid like morphine typically last

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


A single epidural bolus of a lipophilic opioid like fentanyl last

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


Diluting the epidural dose of fentanyl (typically 50–100 mg)
in at least 10 ml of preservative-free normal saline will

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


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

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


The doses of epidural morphine may need to be decreased for

elderly patients and thoracic catheter sites


Fentanyl Epidural Dose

Single Dose: 50–100 mcg
Continuous Infusion: 25–100 mcg/hr


Sufentanil Epidural Dose

Single Dose: 10–50 mcg
Continuous Infusion: 10–20 mcg/hr


Alfentanil Epidural Dose

Single Dose: 0.5–1 mg
Continuous Infusion: 0.2 mg/hr


Morphine Epidural Dose

Single Dose: 1–5 mg
Continuous Infusion: 0.1–1 mg/hr


Diamorphine Epidural Dose

Single Dose: 4–6 mg
Continuous Infusion: -----


Hydromorphone Epidural Dose

Single Dose: 0.5–1 mg
Continuous Infusion: 0.1–0.2 mg/hr


Meperidine Epidural Dose

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


Methadone Epidural Dose

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


epidural infusions of lipophilic opioids produce analgesia primarily via

a supraspinal/systemic mechanism


continuous epidural infusions of hydrophilic opioids produce analgesia primarily

a spinal mechanism



respiratory depression,
pruritus, nausea, and vomiting.


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

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


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

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.


mechanism of respiratory depressant of epidural lipophilic and hydrophilic opioids.

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


Cephalad spread of
hydrophilic opioids typically occurs within

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


Treatment in reversing respiratory depression

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


Nausea and vomiting from epidural opioids
result from

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


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

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


Treatment of epidural opioid-induced nausea and vomiting may include

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


etiology of epidural opioid-induced pruritus

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


treatment of of epidural opioid-induced pruritus

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


mechanism of epidural opioids induced urinary

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


treatment of epidural opioids induced urinary

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


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

transmission of nociceptive information through the central nervous system.


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

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


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

48 hr after a single dose.


extended-release epidural
morphine (EREM)

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


Local Anesthetic with EREM

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


Continuous infusions of hydrophilic opioid vs Continuous infusions of lipophilic opioid

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

Decks in Essentials of Pain Medicine Class (80):