Chapter 30 Intrathecal Opioid Injections for Postoperative Pain Flashcards
KEY POINTS 1. The pharmacologic properties of IT 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 duration of action (and certain side effects such as delayed respiratory depression). 2. Like opioids administered by other routes, IT opioids may result in widely recognized opioid-related side effects such as nausea, vomiting, pruritus, sedation, and
Common uses
of IT opioids for postoperative analgesia
obstetric and gynecologic surgery, orthopedic joint and spine procedures,
thoracic and vascular procedures, cardiac bypass, pediatric surgery, urologic procedures, and abdominal procedures.
Fibers that play a major role in the transmission of pain
Nociceptive information is transmitted by multiple afferent
neurons with small-diameter unmyelinated and thinly
myelinated fibers (C-fibers and Ad-fibers, respectively)
Central terminals of small unmyelinated fibers are located in
Rexed’s laminae I, II, and III
What provides the anatomic basis for selective analgesia by opioids injected into the cerebrospinal fluid (CSF)
Opioid receptors exist in
Rexed’s laminae I, II, and V in the dorsal horn of the spinal cord.
Spinal cord analgesia is likely mediated by what receptors?
mu- and k-receptors.
substance P
substance P is released into the CSF by electrical stimulation. This release is inhibited by the administration of morphine
into the CSF and possibly mediated by gammaaminobutyric
acid (GABA) presynaptically and glycine postsynaptically
Lipophilicity
Lipophilicity (versus hydrophilicity) is the key property affecting the speed of onset and duration of action. Highly lipid-soluble drugs such as fentanyl and
sufentanil have a faster onset but shorter duration of action when used intrathecally
Highly lipid-soluble drugs have shorter duration of action when used intrathecally
Shortly after injection,
CSF levels are barely detectible as the drug is quickly distributed to the spinal cord. This may result in a more
segmental spread of analgesia and a lower concentration reaching the brain, decreasing the risk of delayed respiratory
depression (e.g., 12 to 24 hr after injection)
Hydrophilic opioids
Hydrophilic opioids, such as morphine, have a slower onset and longer duration of action, and remain detectable
in the CSF long after injection. Delayed respiratory depression may be more likely with morphine than other
lipophilic drugs, as morphine remains in the CSF long enough to circulate rostrally to the brainstem and respiratory
centers
Only opioid has strong enough local anesthetic
properties to be used as a sole agent for surgery.
meperidine. IT injection of meperidine produces spinal anesthesia that
is qualitatively similar to that achieved with conventional local anesthetics.
Why can meperidine be used as the sole agent in
spinal anesthesia?
It is likely the combined action of its local anesthetic properties and its opioid receptor binding
meperidine vs. fentanyl
The onset of action for meperidine is similar to that of fentanyl despite being significantly less
lipid soluble; however, its duration is longer than fentanyl
meperidine vs. morphine
Meperidine has a shorter duration of action than
morphine, as meperidine dissipates from the CSF four times faster than morphine.
IT opioids dose vs. IV or epidural
Equianalgesic doses
of IT opioids are typically a small fraction of those used for intravenous or epidural use
The duration of analgesia for a hydrophilic opioid compared to IV or epidural
The duration of analgesia for a hydrophilic opioid
such as morphine is greater compared to intravenous or
epidural administration
A single IT injection of morphine 0.04 to 0.5 mg will provide analgesia up to
15 to 24 hr of analgesia.
hemodynamic changes of opioids when
applied intrathecally
Unlike neuraxially administered local anesthetics, which
may result in vasodilation and hypotension, opioids do not per se cause adverse hemodynamic changes when applied intrathecally and may not significantly attenuate
the neuroendocrine stress response even when administered
in extremely large doses (4.0 mg)
effect of opioids on motor blockade or sensory
opioids do not cause motor blockade or sensory loss,
potentially allowing earlier ambulation
benefit of IT opioids when used with local anesthetics
IT opioids do provide a sparing effect for local anesthetics, allowing lower doses to be used intrathecally or epidurally while still maintaining adequate analgesia
SIDE EFFECTS OF INTRATHECAL
OPIOIDS
most feared complications are respiratory depression
and arrest
Respiratory depression typically occurs when
within minutes to hours for the lipophilic opioids (fentanyl, sufentanil) with early respiratory depression (minutes) not being reported with a hydrophilic opioid such as morphine
Common Side Effects of Intrathecal Opioids
Mild respiratory depression Pruritus Sedation Nausea Vomiting Urinary retention
Uncommon Side Effects of Intrathecal Opioids
Respiratory arrest Generalized muscle rigidity Nystagmus Epileptic seizure Myoclonus Hyperalgesia Neurotoxicity Water retention
The risk of respiratory depression increases with
the addition of systemic opioids or sedatives, increasing age, lack of opioid tolerance (i.e., opioid-naive state), obesity, and sleep apnea
mechanism of hydrophilic opioids causing respiratory
depression
the migration of opioid
within the CSF to and reaction with opioid receptors in
the ventral medulla
treatment of respiratory
depression due to opioids
Naloxone has been used effectively
to treat respiratory depression from IT opioids,
Morphine
Oil–Water Partition Coefficient*: 1.4 Typical Adult Intrathecal Dose: 0.05- 0.6mg Onset of Analgesia (minutes): 30-60 Duration of Analgesia (minutes: 480-1440
Meperidine
Oil–Water Partition Coefficient*: 39 Typical Adult Intrathecal Dose: 10-100mg Onset of Analgesia (minutes) : 2-12 Duration of Analgesia (minutes: 60-400
Fentanyl
Oil–Water Partition Coefficient: 816 Typical Adult Intrathecal Dose: 10-50mcg Onset of Analgesia (minutes) : 5-10 Duration of Analgesia (minutes): 30-120
Sufentanil
Oil–Water Partition Coefficient: 1727 Typical Adult Intrathecal Dose: 2.5- 12.5mcg Onset of Analgesia (minutes): 3-6 Duration of Analgesia (minutes: 60-180
Advantages of Intrathecal Opioids
Long duration of action
Small doses required for equianalgesic effect
Almost undetectable vascular absorption
Ease of cannulating the intrathecal space
Minimal hemodynamic changes
No motor blockade
No sensory loss
IT opioid-induced
pruritus is likely due to
cephalad migration of the drug and interaction with opioid receptors in the trigeminal nucleus located superficially in the medulla, the exact etiology is not clear. Itching does not appear to be histamine mediated
nor is it related to systemic absorption of the drug. Antihistamines are minimally effective as a treatment;
IT opioid-induced
pruritus treatment
Opioid receptor antagonists, such as
naloxone, and opioid agonists–antagonists are effective in the treatment for pruritus. Low-dose intravenous naloxone may be effective in attenuating pruritus
but does not generally decrease the analgesic efficacy of IT opioids
unconventional IT opioid-induced pruritus treatment
Propofol in a 2-mg dose may relieve pruritus without affecting analgesia, but is less effective than μ receptor antagonists. Ondansetron may be an effective agent for treating spinal or epidural morphine induced pruritus. Prophylactic ondansetron 0.1 mg/kg
intravenous (IV) has also been shown to reduce the incidence of pruritus after IT morphine
The presumed mechanism of IT opioid-induced n/v
the cephalad migration of drug and subsequent interaction
with opioid receptors in the area postrema
Treatment of IT opioid-induced n/v
Naloxone is generally effective in the treatment of nausea and vomiting induced by IT opioids. Long-acting opioid antagonists may not be as
effective in treating nausea, but there may be a benefit if given prophylactically.
mechanism of IT opioid-induced Urinary retention
related to opioid receptor–induced inhibition of sacral
parasympathetic nervous system outflow, resulting in detrusor relaxation and an increase in bladder capacity
Treatment of IT opioid-induced Urinary retention
Naloxone may be effective in treatment, although bladder
catheterization is frequently required
Relationship between IT morphine and Herpes
Herpes simplex labialis virus reactivation has been reported following IT morphine. Epidural
morphine has also been postulated to cause reactivation of herpes. Opioids reach the sensory ganglia where the herpes virus lies dormant and may reactivate the virus
through an unknown interaction
IT Sufentanil for Postop Analgesia
Sufentanil (10 mg) improves and prolongs the duration of surgical
analgesia in patients undergoing cesarean section but at the cost of increased hypotension and pruritus
IT morphine doses
IT morphine is clearly beneficial in reducing additional opioid requirements in patients undergoing
orthopedic surgery, but the optimal dose is not clear.
For patients who are opioid-tolerant, higher doses are probably acceptable while doses of less than 0.3 mg may be ideal for opioid-naive individuals
pediatric patients IT morphine doses
in pediatric patients,
IT morphine in doses less than 10 mg/kg has been demonstrated
to be effective in children 6 months of age
or older
Clonidine
Clonidine, an alpha-2 receptor agonist, has been used to improve analgesia in combination with IT opioids as
well as with IT local anesthetics. Clonidine increases the
duration of sensory and motor blockade from bupivicaine
spinal anesthesia through several mechanisms. Alpha-2
adrenergic agonists administered intrathecally may increase the antinociceptive threshold by activating descending noradrenergic pathways in the spinal cord
