Pharmacological management of pain in the neonatal intensive care unit

Effective and consistent management of neonatal pain remains a controversial issue. In fact, premature infants are repeatedly subjected to painful tests and procedures or suffer painful conditions. In particular, sources of infant pain can be summarized as acute pain (caused by various diagnostic and therapeutic procedures), established pain (associated with post-operative pain, inflammatory pain, thermal orchemical burns), and prolonged or disease-related pain (resulting from contractures, nerve injury, or other pathological conditions). Moreover, the complexity of infants inability to verbalize pain and the inherent variability of pain make an appropriate identification of this condition very difficult. Therefore, with different mechanisms transducing various types of pain the practice of 'one-drug fits all' becomes questionable.

It is advisable that clinicians use the latest non-pharmacologic and pharmacologic therapies for effective management of neonatal pain, distress, or agitation. For what concerns pharmacologic strategies, most important treatments currently in use are opioid therapies and other options including ketamine and midazolam.

Opioid therapy was in past considered the mainstay for neonatal analgesia. Among these drugs, morphine is the most commonly used. However, there is an open controversy in its dosing and clinical usage. In fact, it is established that morphine is associated to a ceiling effect: after a certain therapeutic level has been reached, higher doses will produce more adverse effects rather than increased analgesia. Clinical experience suggests that a ceiling effect may be reached by using doses up to 0.5 mg/kg. Moreover, morphine has a slow onset of analgesia owing to lower lipid solubility, especially in premature infants. It has also been suggested that, for those infants on fluid restriction for patent ductus arteriosus (PDA) and those on diuretics, morphine will produce some degree of hypotension; caution should be used when prescribing morphine in patients with asthma or bronchopulmonary dysplasia. For what concern efficacy, there is accumulating evidence that morphine may not be effective in the treatment of acute pain, even if results are still controversal. Alternative approaches with methadone, ketamine, or local anesthetics could also be considered.

An appropriate approach to the management of pain needs to assess the type of pain the neonate is experiencing. For acute physiological pain, avoiding invasive procedures, utilizing sucrose pacifiers, and topical/local anesthetics can be useful. For post-operative pain, a short duration (24 to 48 h) of opioid therapy, positioning, removing drains, and considering adjuvant therapies would be appropriate. For inflammatory pain, anti-inflammatory agents should be considered. For visceral or neuropathic pain, Specific therapies for underlying condition might be useful, as well as epidural or spinal analgesia. Opioids can be used in this setting if the pain is severe or extensive. A comprehensive knowledge base and familiarity with current research related to pain assessment and management are paramount, to help the clinician treating neonates in the NICU.

Future research must define efficacy of specific therapeutic approaches, applicability to specific neonatal populations, combination approaches, and comparative studies between analgesic drugs.

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