Opioids are a class of drug that promotes decreased pain perception and decreases the reaction to pain; the drug class that includes morphine or morphine sulfate, methadone, and fentanyl or fentanyl citrate. As demonstrated in Figure 5.1, opioids work by binding with specific proteins and opioid receptors found in the brain, spinal cord, gastrointestinal tract, and other organs throughout the body. When the opioid attaches to any one of the receptors, as shown in Figure 5.2, the stimulus of pain to the brain is slowed or blocked, thus reducing the perception of pain. The types of opioids commonly used in neonates include morphine, fentanyl, methadone, and meperidine.
Morphine and morphine sulfate are similar opioid compounds; morphine sulfate is a salt compound of morphine. Morphine works by stimulating opioid receptors within the posterior amygdala, hypothalamus, thalamus, spinal column, gastrointestinal tract, and the spinal nucleus of the trigeminal nerve. Morphine binds very strongly to the receptor sites, generating an increased sense of pain relief, but also generating a greater sense of sedation and respiratory depression, which contributes to a quicker tolerance and greater dependence. The recommended use for morphine in the neonate is for analgesia, sedation, treatment of opioid withdrawal, and abstinence withdrawal. The recommended dosage is dependent on the purpose or use. Recommendations appear in Table 5.1.
FIGURE 5.1. Path of opioids.
CNS, central nervous system.
FIGURE 5.2. The brain has many, many receptors for opioids. An overdose occurs when too much of an opioid, such as heroin or oxycodone, fits in too many receptors slowing and then stopping the breathing.
Side effects of morphine include marked respiratory depression, hypotension, bradycardia, ileus and delayed gastric emptying, and urine retention. The receptor sites that morphine has a binding affinity for are found along the dorsal roots innervating the respiratory muscles and gastrointestinal tract, contributing to the relaxation of the smooth muscles of these organs; the side effects are frequently seen after administration. Care must be practiced when administering to provide careful assessment and monitoring to ensure adequate and effective ventilation occurs and is provided if necessary. Frequent monitoring of gastrointestinal function and urine output is necessary.
TABLE 5.1 Opioids for Neonates
Withdrawal of morphine must be done carefully and gradually. Tolerance and dependence are common with morphine use and withdrawal must be attempted slowly to avoid central nervous system irritation and seizure activity. Weaning should occur at 10% of original dose once each day as tolerated (Bio, Siu, & Poon, 2011). Discontinuation of medication can be safely done when the infant’s dose reaches 0.12 to 0.016 mg/kg/day.
When assessing risks of use in comparison to benefits of use, it is necessary to understand the difference. The risk of use of morphine includes respiratory depression, decreased gastrointestinal motility, and urinary retention, whereas benefits include a deep, effective sedative, and analgesic response for mild to moderate pain. Studies suggest that infants who receive morphine to manage moderate pain tend to require less pain management as adults and are less likely to be resistant to the effects of morphine as adults (Georgia State University, 2008). Studies suggest morphine may have a negative effect on cell life when used without caution or in absence of noxious stimulus (Attarian et al., 2014). Studies also suggest managing neonatal pain appropriately with morphine provides more long-term benefits for healthy neurodevelopmental and adult pain responses than not medicating appropriately.
Limitations of use of morphine when considering the gestational age, weight, and diagnosis of the neonate are controversial and variable. Morphine has a slow onset of analgesic effect—up to 5 minutes, with a peak effectiveness within 15 minutes. Painful procedures or interventions that are emergent should not be managed with morphine. Gestational age considerations focus on organ maturity and enzymatic availability for metabolism. The lower the gestational age, the less mature the neonatal liver—the site of morphine metabolism. Lower gestational age infants tend to develop tolerance much quicker than their term counterparts, thus creating a need for increasing dosing, which can contribute to increased risk of respiratory depression and hypotension. Use of morphine for management of chronic pain related to mechanical ventilation is controversial as well (Hall & Shbarou, 2009), with use primarily limited to moderate postoperative pain.
FENTANYL AND FENTANYL CITRATE