Neonatal pain management: still in search for the Holy Grail

Allegaert, Karel; Anker, John N. van den

doi:10.5414/cp202561

Cited by 37 publications

(35 citation statements)

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“…Alcanza su pico máximo de analgesia en el primer minuto de su administración, tres a cuatro veces más rápido que el fentanilo. Su metabolismo es por medio de esterasas plasmáticas y tisulares inespecíficas, mismas presentes y con actividad madura al nacimiento, por lo que su aclaramiento es predecible a pesar de la inmadurez del resto de los órganos (5,7,15) .…”

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“…Durante el procedimiento es aconsejable mantener al paciente con ventilación espontánea para la valoración dinámica de la respiración y la movilidad de las estructuras. Lo anterior, sumado a las características anatomofisiológicas del neonato, nos obliga a planear nuestro manejo anestésico en el cual debemos considerar el grado de inmadurez hepática, renal, cardiovascular, respiratoria, sistema nervioso central, así como de los sistemas enzimáticos y de unión a las proteínas, que impactan la farmacocinética en este grupo (5,6) . A pesar de que el sistema nervioso central no está desarrollado en su totalidad al nacimiento, es de vital importancia considerar que las vías del dolor están integradas desde momentos tempranos en la gestación (6) .…”

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“…Dentro de las opciones farmacológicas con las que contamos están los opioides, y de éstos, los de vida media corta, rápida eliminación y metabolismo por esterasas plasmáticas como el remifentanyl; éste es una buena opción en el neonato, ya que las esterasas están presentes al nacimiento, por lo que se puede predecir su aclaramiento a pesar de las diferencias anatomofisiológicas importantes en el neonato (5,7,8) .…”

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Sedoanalgesia en neonato a base de remifentanyl. En relación con un caso para epiglotopexia

Madriz-Godoy¹,

Sánchez-Hernández²,

Ortiz-Hernández³

2020

Revista Mexicana De Anestesiología

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Sedoanalgesia en neonato a base de remifentanyl. En relación con un caso para epiglotopexia

Madriz-Godoy¹,

Sánchez-Hernández²,

Ortiz-Hernández³

2020

Revista Mexicana De Anestesiología

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“…Recognized side effects of opioids are hypotension, respiratory depression, prolonged ileus, ventilator dependence and depression of the immune system in a dose-dependent response [11,12] , whereas ketorolac may decrease platelet aggregation, increase bleeding events and cause renal insufficiency [9,13] . Thus, studies examining non-pharmacological strategies or ways to combine with other treatments or balance these treatments for neonatal patients to achieve optimal pain relief with less prolonged exposure are needed [4,14].…”

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confidence: 99%

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery

et al. 2016

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Background: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. Methods: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. Results: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 μg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (β = -27 μg/kg, p = 0.028; R² model = 0.90) for shorter duration (β = -9 days, p = 0.003; R² model = 0.94). No differences in fentanyl or ketorolac were detected. Conclusions: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.

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“…Pharmacogenetics, considered as a tool for precision medicine also in neonates, may play a role in this search. However, the usefulness of genetic variants as covariates is limited to periods in development where genotype-phenotype correlation is already present [12]. Furthermore, early life is characterized by isoenzyme-specific maturation of activity.…”

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Biomarkers of Propofol Metabolism in Neonates: The Quest Beyond Ontogeny

2017

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" We anticipate that the contribution of genetic variants will be different in neonates comparedwith adults, since ontogeny of the metabolizing enzymes has to be taken into account "First draft submitted: 1 June 2017; Accepted for publication: 11 July 2017; Published online: 23 October 2017The use of propofol, a short-acting sedative, for procedural sedation in neonates is increasing. In early life, a remarkable variability in propofol clearance has been documented. At present, two-third of this variability can be explained by age [1]. Although the impact of indirect hyperbilirubinemia as biomarker of reduced propofol clearance in neonates was explored, it was not retained as relevant clinical predictor [2]. Since in the last few years, no additional covariates of propofol pharmacokinetics (PK) and/or pharmacodynamics (PD) have been documented in neonates, it might be useful to determine whether covariates defined in other populations are relevant to be explored in neonates or not. Starting with a summary of covariates contributing to propofol PK/PD variability in adults, we reflect on the current knowledge of propofol disposition in neonates, and on future challenges to further explore covariates explaining neonatal propofol disposition.As a highly lipophilic compound, propofol immediately distributes to the subcutaneous fat and central nervous system after intravenous administration. In adults, 90% of the propofol dose is metabolized in the liver, and the metabolites are excreted in urine. Both Phase I (hydroxylation) and Phase II (glucuronidation) processes contribute to propofol metabolism. In adults, 70% is converted to propofol glucuronide by uridine diphosphate UGT1A9, while the CYP2B6 and to a lesser extent, CYP2C9 are responsible for the hydroxylation of propofol to 1-and 4-quinol metabolites. These metabolites subsequently undergo glucuronidation or sulfation [3]. The large intersubject variability in propofol biotransformation in adults is in part attributed to patient-related characteristics (i.e., age, weight, height, lean body mass, gender and genetic polymorphisms), disease state and environmental factors.Choong et al. documented the impact of gender in adults receiving propofol by target-controlled infusion for elective surgery. Significantly higher area under the curve values of the hydroxyl and glucuronide metabolites were observed in women [4]. This suggests a dimorphic propofol metabolism in vivo, with higher metabolic turnover in female compared with male subjects. Their findings confirmed results of a previous pilot study as well as in vitro data [5]. In their pilot study, higher (i.e., 1.7 to 2.1-fold difference) weight-corrected area under the curve for all propofol glucuronides after a single propofol bolus were found in women compared with men [5]. Also in an elderly cohort (65-91 years), the impact of gender on propofol PK was observed by Vuyk et al. Predicted propofol concentrations during continuous infusion (i.e., 1.5 mg/kg propofol bolus in 1 min followed by 7 mg/kg/h for 89 min) w...

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Neonatal pain management: still in search for the Holy Grail

Cited by 37 publications

References 66 publications

Sedoanalgesia en neonato a base de remifentanyl. En relación con un caso para epiglotopexia

Sedoanalgesia en neonato a base de remifentanyl. En relación con un caso para epiglotopexia

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery

Biomarkers of Propofol Metabolism in Neonates: The Quest Beyond Ontogeny

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