Chapter 31 Epidural Opioids for Postoperative Pain Flashcards
KEY POINTS 1. As is seen with intrathecal opioids, the pharmacologic properties of epidurally administered opioids reflect the extent of the hydro- versus lipophilicity of the specific opioid: lipophilic opioids (fentanyl and sufentanil) have a shorter onset and duration of action whereas hydrophilic opioids (morphine, hydromorphone) have a delayed onset and prolonged duration of action (and certain side effects such as delayed respiratory depression). 2. Epidural opioids exhibit the same sid
An opioid administered into the epidural space will diffuse
into
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
SIDE EFFECTS OF EPIDURAL OPIOIDS
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
retention
related to a decrease in detrusor muscle
strength contraction secondary to spinal opioid receptor activation.
treatment of epidural opioids induced urinary
retention
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
