Pharmacological treatment of neonatal pain: in search of a new equipoise

Abstract

Inadequate management of pain in early human life contributes to impaired neurodevelopmental outcome and alters pain thresholds, pain or stress-related behavior and physiological responses. However, there are also emerging animal experimental data on the impact of exposure to analgo-sedatives on the incidence and extent of neuro-apoptosis. Since this association has also been suggested in humans, the pharmacological treatment of neonatal pain is in search of a new equipoise since these 'conflicting' observations are the main drivers to further reconsider our current treatment regimens. This review focuses on new data concerning clinical pharmacology of morphine, followed by data on more recently introduced opioids like remifentanil and tramadol, locoregional anesthesia and minimally invasive techniques in neonates, and finally with data on intravenous paracetamol. Since the available data are still incomplete, priorities for both clinical management and future research will be proposed.

Figure 1

Plasma log₁₀ values of tramadol (M) on O-demethyl tramadol (M1) (log₁₀ M/M1) reflect CYP2D6 activity in early life. The lower the log₁₀ value, the higher the metabolite concentration (i.c. M1). The phenotypic plasma log value (log₁₀ M/M1) depends on both postmenstrual age (PMA) as well as on the CYP2D6 activity score (either CYP2D6 activity score <2, ×; or ≥2, ○).