Chapter 30 Intrathecal Opioid Injections for Postoperative Pain

Question 1

Common uses

of IT opioids for postoperative analgesia

Answer 1

obstetric and gynecologic surgery, orthopedic joint and spine procedures,
thoracic and vascular procedures, cardiac bypass, pediatric surgery, urologic procedures, and abdominal procedures.

Question 2

Fibers that play a major role in the transmission of pain

Answer 2

Nociceptive information is transmitted by multiple afferent
neurons with small-diameter unmyelinated and thinly
myelinated fibers (C-fibers and Ad-fibers, respectively)

Question 3

Central terminals of small unmyelinated fibers are located in

Answer 3

Rexed’s laminae I, II, and III

Question 4

What provides the anatomic basis for selective analgesia by opioids injected into the cerebrospinal fluid (CSF)

Answer 4

Opioid receptors exist in

Rexed’s laminae I, II, and V in the dorsal horn of the spinal cord.

Question 5

Spinal cord analgesia is likely mediated by what receptors?

Answer 5

mu- and k-receptors.

Question 6

substance P

Answer 6

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

Question 7

Lipophilicity

Answer 7

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

Question 8

Highly lipid-soluble drugs have shorter duration of action when used intrathecally

Answer 8

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)

Question 9

Hydrophilic opioids

Answer 9

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

Question 10

Only opioid has strong enough local anesthetic

properties to be used as a sole agent for surgery.

Answer 10

meperidine. IT injection of meperidine produces spinal anesthesia that
is qualitatively similar to that achieved with conventional local anesthetics.

Question 11

Why can meperidine be used as the sole agent in

spinal anesthesia?

Answer 11

It is likely the combined action of its local anesthetic properties and its opioid receptor binding

Question 12

meperidine vs. fentanyl

Answer 12

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

Question 13

meperidine vs. morphine

Answer 13

Meperidine has a shorter duration of action than

morphine, as meperidine dissipates from the CSF four times faster than morphine.

Question 14

IT opioids dose vs. IV or epidural

Answer 14

Equianalgesic doses

of IT opioids are typically a small fraction of those used for intravenous or epidural use

Question 15

The duration of analgesia for a hydrophilic opioid compared to IV or epidural

Answer 15

The duration of analgesia for a hydrophilic opioid
such as morphine is greater compared to intravenous or
epidural administration

Question 16

A single IT injection of morphine 0.04 to 0.5 mg will provide analgesia up to

Answer 16

15 to 24 hr of analgesia.

Question 17

hemodynamic changes of opioids when

applied intrathecally

Answer 17

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)

Question 18

effect of opioids on motor blockade or sensory

Answer 18

opioids do not cause motor blockade or sensory loss,

potentially allowing earlier ambulation

Question 19

benefit of IT opioids when used with local anesthetics

Answer 19

IT opioids do provide a sparing effect for local anesthetics, allowing lower doses to be used intrathecally or epidurally while still maintaining adequate analgesia

Question 20

SIDE EFFECTS OF INTRATHECAL

OPIOIDS

Answer 20

most feared complications are respiratory depression

and arrest

Question 21

Respiratory depression typically occurs when

Answer 21

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

Question 22

Common Side Effects of Intrathecal Opioids

Answer 22

Mild respiratory depression
Pruritus
Sedation
Nausea
Vomiting
Urinary retention

Question 23

Uncommon Side Effects of Intrathecal Opioids

Answer 23

Respiratory arrest
Generalized muscle rigidity
Nystagmus
Epileptic seizure
Myoclonus
Hyperalgesia
Neurotoxicity
Water retention

Question 24

The risk of respiratory depression increases with

Answer 24

the addition of systemic opioids or sedatives, increasing age, lack of opioid tolerance (i.e., opioid-naive state), obesity, and sleep apnea

Question 25

mechanism of hydrophilic opioids causing respiratory

depression

Answer 25

the migration of opioid
within the CSF to and reaction with opioid receptors in
the ventral medulla

Question 26

treatment of respiratory

depression due to opioids

Answer 26

Naloxone has been used effectively

to treat respiratory depression from IT opioids,

Question 27

Morphine

Answer 27

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

Question 28

Meperidine

Answer 28

Oil–Water Partition
Coefficient*: 39 
Typical Adult 
Intrathecal Dose: 10-100mg
Onset of Analgesia
(minutes) : 2-12
Duration of Analgesia
(minutes: 60-400

Question 29

Fentanyl

Answer 29

Oil–Water Partition
Coefficient: 816
Typical Adult
Intrathecal Dose: 10-50mcg
Onset of Analgesia
(minutes) : 5-10
Duration of Analgesia
(minutes): 30-120

Question 30

Sufentanil

Answer 30

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

Question 31

Advantages of Intrathecal Opioids

Answer 31

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

Question 32

IT opioid-induced

pruritus is likely due to

Answer 32

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;

Question 33

IT opioid-induced

pruritus treatment

Answer 33

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

Question 34

unconventional IT opioid-induced pruritus treatment

Answer 34

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

Question 35

The presumed mechanism of IT opioid-induced n/v

Answer 35

the cephalad migration of drug and subsequent interaction

with opioid receptors in the area postrema

Question 36

Treatment of IT opioid-induced n/v

Answer 36

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.

Question 37

mechanism of IT opioid-induced Urinary retention

Answer 37

related to opioid receptor–induced inhibition of sacral

parasympathetic nervous system outflow, resulting in detrusor relaxation and an increase in bladder capacity

Question 38

Treatment of IT opioid-induced Urinary retention

Answer 38

Naloxone may be effective in treatment, although bladder

catheterization is frequently required

Question 39

Relationship between IT morphine and Herpes

Answer 39

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

Question 40

IT Sufentanil for Postop Analgesia

Answer 40

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

Question 41

IT morphine doses

Answer 41

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

Question 42

pediatric patients IT morphine doses

Answer 42

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

Question 43

Clonidine

Answer 43

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