Analgosedation in neonates: do we still need additional tools after 30 years of clinical research?

Abstract

Approximately 30 years ago, the myth that nervous system immaturity precluded neonates from pain perception and its negative effects was rejected. Neurobiologists further explored neurodevelopmental nociception. These observations strongly suggest that early pain experience contributes to neurodevelopmental outcome, pain thresholds, pain or stress-related behaviour and physiological responses in later life. Effective management of pain therefore remains an important indicator of the quality of care provided to neonates, not only from an ethical, but also from a short and long-term outcome perspective. Simultaneously, neonatal care itself has changed and data on neuro-apoptosis and impaired synaptogenesis following exposure to analgosedatives emerged. When developmental pharmacology concepts are applied to neonatal analgosedation, this means that this should be based on systematic assessment, followed by titrated administration of the most appropriate analgesic(s) with subsequent re-assessment to adapt treatment. This review will focus on the limitations of the available assessment tools, newly emerging analgosedatives in neonates to illustrate how these compounds can be integrated into the changing concepts of neonatal care.

Sedation in the Neonatal Intensive Care Unit: International Practice

“…Neonates treated with dexmedetomidine require a shorter time to reach full enteral feeds compared to neonates treated with fentanyl. Finally, in vitro and animal experimental studies suggest neuroprotective effects [13,160,161]. Unfortunately, dexmedetomidine has the potential for significant adverse drug reactions.…”

“…Ideal analgo-sedation should be rapid in its onset of action, be predictable in its duration and depth of action, not depending on active metabolites (effects or side effects), have rapid dissipation of effects on discontinuation of the agent, be nonaddictive (physical dependence or withdrawal on discontinuation), without drug tolerance, nor have adverse effects on cardiopulmonary function [13]. Preferably, this should be combined with a wide therapeutic index, absence of drug interactions and incompatibilities with other drugs, and without influence of underlying comorbidities, like renal or hepatic disease.…”

“…Preferably, this should be combined with a wide therapeutic index, absence of drug interactions and incompatibilities with other drugs, and without influence of underlying comorbidities, like renal or hepatic disease. We are unaware of such an ideal compound for neonates, but dexmedetomidine may become a potential useful asset to attain these objectives in neonates [13]. Dexmedetomidine is a potent lipophilic α(alpha)2-adrenoreceptor agonist with a α(alpha)2/α(alpha)1 activity ratio of 1,620/1.…”

“…Effective pain management therefore remains an important indicator of the quality of care provided to neonates, not only from an ethical, but also from an outcome perspective [12,13].…”

“…These shifts in clinical care induced a shift in pharmacokinetic covariates and pharmacodynamic endpoints [13].…”