Intrathecal Opioids


Intrathecal administration of opioids is a commonly used practice among anesthesiologists to treat intraoperative and postoperative pain. Historically, the primary concern with this method is the potential for causing respiratory depression. Though serious, this is a relatively rare side effect, occurring in less than 0.5% of cases. Conversely, pruritus can occur in up to 100% of patients, and though often dismissed as a simple annoyance, it can significantly impact patient comfort and satisfaction. Here we present a typical case in which spinal opioids are used and discuss the possible mechanisms by which pruritus (and other adverse effects) develop, how to risk stratify patients, and how best to manage them.


analgesia, intrathecal opioids, naloxone, nausea, nociception, pruritis, respiratory depression, spinal, urinary retention, vomiting


Case Synopsis

An otherwise healthy 26-year-old woman undergoes cesarean section for delivery of a breech infant. Spinal anesthesia is used, consisting of 1.6 mL of 0.75% hyperbaric bupivacaine (12 mg) with preservative-free morphine (0.3 mg). The surgery is uneventful, and the infant has Apgar scores of 9 and 9 at 5 and 10 minutes, respectively. The patient remains in the recovery room for 2 hours and is then transferred to the floor. She is treated with diphenhydramine 50 mg intravenously (IV) for generalized pruritus 6 hours after surgery and promethazine 25 mg IV for vomiting 7 hours after surgery. Ten hours after surgery, she complains of persistent pruritus, noting that the diphenhydramine had no effect.

Problem Analysis


Intrathecal administration of opioids is an effective means of providing analgesia both intraoperatively and postoperatively. A combination of opioids and local anesthetics is often coadministered in an effort to reduce doses of both classes, thereby limiting the side effects. Morphine is commonly chosen for intrathecal administration, as a single dose may provide analgesia for up to 24 hours. Side effects of intrathecal opioids include early and late respiratory depression, nausea and vomiting, pruritus, sedation, and urinary retention ( Table 88.1 ).

TABLE 88.1

Cause and Treatment of Complications of Intrathecal Medications

Complication Cause Treatment
Early respiratory depression Rapid vascular uptake and redistribution Ventilatory support, naloxone
Late respiratory depression Rostral CSF spread to brainstem respiratory center Ventilatory support, naloxone
Pruritus Unknown (unlikely due to histamine release) Naloxone, antihistamines (controversy), mixed opioid agonist-antagonists
Nausea, vomiting Rostral CSF spread to vomiting center or chemoreceptor trigger zone in fourth ventricle Naloxone, antiemetics, droperidol, transdermal scopolamine
Urinary retention Inhibited sacral parasympathetic outflow Naloxone (large doses), urinary catheterization
Sedation Rostral spread in CSF to thalamus, limbic system, or cortex; hypercarbia Naloxone

CSF, Cerebrospinal fluid.

Early respiratory depression occurs in the first 2 hours after intrathecal administration of opioids and is believed to be due to vascular uptake and redistribution. Delayed respiratory depression, which occurs 6 to 12 hours after intrathecal administration, is thought to be due to the rostral spread of opioid in the cerebrospinal fluid (CSF). Similarly, nausea and vomiting is due to the rostral spread of the opioid in the CSF with stimulation of the area postrema in the fourth ventricle. Sedation is related to the spread of opioids through the CSF to the thalamus, limbic system, or cerebral cortex. Sedation may be exacerbated by hypercarbia with carbon dioxide narcosis. Urinary retention is due to the inhibition of sacral parasympathetic outflow with relaxation of the bladder detrusor muscle and concomitant inability to relax the sphincter.

Pruritus, either generalized or localized, can occur frequently in patients receiving intrathecal opioids. Pruritus is defined as an unpleasant sensation that results in the desire or reflex to scratch. It typically first occurs in the area of the nose, eyes, and face, likely related to the relatively high concentration of opioid receptors at the spinal nucleus of the trigeminal nerve. Notably, this effect occurs more commonly after epidural and spinal administration than with systemic administration. Although the mechanism is not fully understood, histamine release is not postulated to be a causative factor.


Although the most serious complication of intrathecal opioid administration is respiratory depression, respiratory depression of clinical significance occurs in less than 0.5% of cases. Though not life threatening, pruritus remains the most common patient complaint, occurring in 83% of postpartum patients and 69% of nonpregnant patients. This can lead to significant patient discomfort. In some cases, the resulting pruritus can be more unpleasant for the patient than the pain itself.

Although the true mechanism of pruritus induced by intrathecal administration of opioids is not fully understood, there are several theories. One theory points to the relationship between nociception and pruritus and the method by which these signals are transmitted. Both nociception and pruritus are transmitted by C fibers, whose signaling is potentiated by prostaglandins. Given the small unmyelinated nature of C fibers, both pruritus and nociceptive sensations can be attenuated by “rubbing.” This is consistent with the gate theory of pain, which asserts that increased activity of large myelinated Aβ sensory fibers diminishes transmission of nociceptive (and potentially pruritic) stimuli carried by small unmyelinated C fibers, by modulation of thalamic projection neurons. Another theory suggests that nociception-specific neurons in the dorsal horn inhibit pruritus-specific neurons in the spinothalamic tract. This can be observed by the decrease in pruritus that occurs with an increase in nociception, however slight, in the form of scratching. The addition of opioids may weaken this inhibition, resulting in an increased sensation of pruritus. There are additional theories involving serotonergic pathways, but the exact mechanisms are unknown. What is known is that there is a high concentration of μ and serotonin receptors in the dorsal horn of the spinal cord and the spinal tract of the trigeminal nerve in the medulla. The spinal trigeminal nucleus is thought to be an integrative “itch center” for sensory input from the face. Supporting this are studies demonstrating reduction in pruritus with ondansetron and propofol, which has strong noncompetitive inhibition of serotonin channel activity. However, no single unifying theory can fully explain opioid-induced pruritus.

Though effectively preventing and addressing pruritus remains a challenge, a careful understanding of treatment options and known mechanisms of action is important to ensuring maximum patient satisfaction in the perioperative period.

Risk Assessment

Careful selection of patients for the administration of intrathecal opioids is important. Discussion should be had with the patient regarding the potential for pruritus and the patient’s level of tolerance for this side effect. The parturient is at higher risk for pruritus after neuraxial administration of opioids, with an incidence of 60% to 100%. By comparison, orthopedic patients have an incidence of 30% to 60%.

Lipid-soluble opioids such as fentanyl have a shorter duration of pruritus compared with opioids such as intrathecal morphine, likely due to the increased systemic uptake of the former. Not surprisingly, the incidence of pruritus also increases with escalating doses of intrathecal opioids. Utilization of concomitant local anesthetics in the intrathecal bolus may result in a decreased severity of pruritus by reducing the dose of intrathecal opioid necessary to achieve appropriate analgesia. However, utilization of epinephrine in the intrathecal bolus may potentially result in worsening pruritus by reducing systemic uptake of the opioid via local vasoconstriction, resulting in increased peak CSF concentrations.

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Feb 18, 2019 | Posted by in ANESTHESIA | Comments Off on Intrathecal Opioids
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