Coanalgesics, or adjuvant medications, are a group of pharmaceuticals with pharmacological characteristics that were not primarily intended for pain relief but were found to have therapeutic properties when used independently or in conjunction with opioids (Khan, Walsh, & Brito-Dellan, 2011). The list of coanalgesics includes a variety of classes, such as topical medications, anticonvulsants, muscle relaxers, anxiolytics, and sedatives. Specific medications include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), EMLA, midazolam, dexmedetomidine, phenobarbital, lorazepam, thiopental, chloral hydrate, and lidocaine. Each medication has recommended usages, dosages, side effects, risks, benefits, and limitations based on gestational age, weight, and diagnosis.
Body composition at birth is a special consideration with coanalgesic use. At birth, infants have high body water content in the extracellular space. This, combined with their low body fat and muscle content, this places the infant at higher risk for prolonged duration of action of medications that are redistributed to fat or muscle after first pass (Haidon & Cunliffe, 2010). Renal function is immature at birth, which causes delayed renal drug excretion, contributing to longer half-life of medications. Also contributing to delayed drug excretion and increasing half-life is the immaturity of the liver and the limited availability of liver enzymes. Lastly, the blood–brain barrier is immature at birth, which allows easier passage of medications to the brain, particularly morphine. These considerations are for the term infant; premature infants are at a higher risk because of their decreased physiological capacity to metabolize and excrete medications, therefore, they require more intense monitoring and dosage modifications.
Acetaminophen is an analgesic and an antipyretic used to treat mild pain. The exact mechanism of action of acetaminophen is unknown, but is believed to reduce the level of the inflammatory chemical prostaglandin in the brain.
Acetaminophen helps reduce pain by increasing the pain threshold, which means the pain has to be more severe before the infant actually perceives it. The benefits of using acetaminophen include its ability to reduce pain with nonopioid treatment with little sedative or neurological effects. Side effects of acetaminophen are very rare; however, rash, itch, swelling, thrombocytopenia, leukopenia, and neutropenia have been documented. Close monitoring of vital signs and lab values is necessary if any concerns of side effects exist. Withdrawal of acetaminophen has no contraindications or concerns.
Risks of use of acetaminophen are relative to gestational age, weight, and diagnosis. Infants less than 32 weeks gestation have a longer half-life elimination and require dosing modification. Infants with liver dysfunction have a decreased capacity to metabolize acetaminophen and require dosing modification. Assessment of liver function and consideration of gestational age are necessary before dosing and administration. The recommended use for acetaminophen in the neonate is for mild to moderate pain, especially circumcision pain, and for fever reduction. The recommended dosage is dependent on purpose or use. Recommendations appear in Table 6.1.
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
NSAIDs are a class of drugs that provide analgesia and antipyretic effects. NSAIDs include aspirin, ibuprofen, and naproxen. NSAIDs work by inhibiting enzymatic development of molecules responsible for supporting inflammatory responses in the body. NSAIDs are not typically used in the neonatal population for pain management, although ibuprofen has been used for closure of patent ductus arteriosis. Side effects of NSAIDs include renal dysfunction and interruption of platelets’ adhesive properties; these have limited the use of NSAIDs for pain or antipyretic purposes. Although some studies suggest NSAIDs can promote cerebral circulation in neonates, regular use of NSAIDs is still limited.
TABLE 6.1 Coanalgesics for Neonates