Association of Continuous Opioids and/or Midazolam During Early Mechanical Ventilation with Survival and Sensorimotor Outcomes at Age 2 Years in Premature Infants: Results from the French Prospective National EPIPAGE 2 Cohort

Tristan, Marie-Amélie de; Martin-Marchand, Laetitia; Roué, Jean‐Michel; Anand, Kanwaljeet J. S.; Pierrat, Véronique; Tourneux, P.; Kuhn, Pierre; Milési, Christophe; Benhammou, Valérie; Ancel, Pierre–Yves; Carbajal, Ricardo; Durrmeyer, Xavier

doi:10.1016/j.jpeds.2020.12.069

Cited by 7 publications

(5 citation statements)

References 54 publications

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“…A strength of our study is its detailed description of the doses used, unlike previous multicenter cohorts reporting sedation and analgesia ( Carbajal et al, 2015 ; Borenstein-Levin et al, 2017 ; Zimmerman et al, 2017 ). Clinical studies do not currently provide definitive conclusion about neurodevelopmental outcomes and analgesic/sedative use ( Rozé et al, 2008 ; Loepke, 2010 ; Lammers et al, 2014 ; McPherson and Grunau, 2014 ; Valkenburg et al, 2015 ; Ancora et al, 2017 ; de Tristan et al, 2021 ), but it seems likely that the doses used influence this outcome, as suggested by the possible negative association between treatment duration and neurodevelopmental outcomes ( Puia-Dumitrescu et al, 2021 ). The follow-up study of a randomized controlled trial found that morphine use did not appear to affect cognition and behavior at 8 or 9 years and might even have had a positive effect on executive functions ( de Graaf et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Frequencies, Modalities, Doses and Duration of Computerized Prescriptions for Sedative, Analgesic, Anesthetic and Paralytic Drugs in Neonates Requiring Intensive Care: A Prospective Pharmacoepidemiologic Cohort Study in 30 French NICUs From 2014 to 2020

et al. 2022

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Objectives: No consensus exists about the doses of analgesics, sedatives, anesthetics, and paralytics used in critically ill neonates. Large-scale, detailed pharmacoepidemiologic studies of prescription practices are a prerequisite to future research. This study aimed to describe the detailed prescriptions of these drug classes in neonates hospitalized in neonatal intensive care units (NICU) from computerized prescription records and to compare prescriptions by gestational age.Materials and Methods: We included all neonates requiring intensive care in 30 French level III units from 2014 through 2020 with a computerized prescription for an analgesic, sedative, anesthetic, or paralytic agent. We described frequencies of prescription, methods of administration, concomitant drug prescriptions, and dosing regimen, and compared them across gestational ages.Results: Among 65,555 neonates, 29,340 (44.8%) were prescribed at least one analgesic (acetaminophen in 37.2% and opioids in 17.8%), sedative (9.8%), anesthetic (8.5%), and/or paralytic agent (1%). Among preterm infants born before 28 weeks, 3,771/4,283 (88.0%) were prescribed at least one of these agents: 69.7% opioids, 41.2% sedatives, 32.5% anesthetics, and 5.8% paralytics. The most frequently prescribed agents were sufentanil (in 10.3% of neonates) and morphine (in 8.0% of neonates) for opioids, midazolam (9.3%) for sedatives, ketamine (5.7%) and propofol (3.3%) for anesthetics. In most neonates, opioids and sedatives were prescribed as continuous infusion, whereas anesthetics were prescribed as single doses. Opioids, sedatives and paralytics were mostly prescribed in association with another agent. Doses varied significantly by gestational age but within a limited range. Gestational age was inversely related to the frequency, cumulative dose and duration of prescriptions. For example, morphine prescriptions showed median (IQR) cumulative doses of 2601 (848–6750) vs. 934 (434–2679) µg/kg and median (IQR) durations of 7 (3–15) vs. 3 (2–5) days in infants born <28 vs. ≥ 37 weeks of gestation, respectively (p-value<0.001).Conclusion: The prescriptions of analgesic, sedative, anesthetic, or paralytic agent were frequent and often combined in the NICU. Lower gestational age was associated with higher frequencies, longer durations and higher cumulative doses of these prescriptions. Dose-finding studies to determine individualized dosing regimens and studies on long-term neurodevelopmental outcome according to received cumulative doses are required.

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Section: Discussionmentioning

confidence: 99%

Frequencies, Modalities, Doses and Duration of Computerized Prescriptions for Sedative, Analgesic, Anesthetic and Paralytic Drugs in Neonates Requiring Intensive Care: A Prospective Pharmacoepidemiologic Cohort Study in 30 French NICUs From 2014 to 2020

et al. 2022

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“…Мидазолам является одним из самых распространенных препаратов, используемых для седации новорожденных, находящихся на ИВЛ [51]. Применение мидазолама рассматривается в рамках стратегии краткосрочной терапии при неэффективности опиоидных анальгетиков, уменьшении их дозы и при невозможности путем подбора параметров ИВЛ синхронизировать дыхание пациента с респиратором [77]. Важно отметить, что мидазолам не обладает анальгетическим действием, что может привести к недооценке поведенческих проявлений боли…”

Section: мидазоламunclassified

“…у новорожденного [77]. Мидазолам так же, как и кетамин, имеет интраназальную форму выпуска, применяемую для процедурной седации и премедикации у детей перед оперативным вмешательством [73,75].…”

Section: мидазоламunclassified

“…Мидазолам так же, как и кетамин, имеет интраназальную форму выпуска, применяемую для процедурной седации и премедикации у детей перед оперативным вмешательством [73,75]. В обсервационном исследовании было показано, что применение опиоидов и/или мидазолама у недоношенных до 32 нед гестации на ИВЛ ассоциировалось с повышением выживаемости без каких-либо различий в отношении умеренных или тяжелых сенсомоторных нарушений в возрасте 2 лет [77]. Также не отмечено отрицательного влияния непрерывной инфузии мидазолама в дозах, соответствующих гестационному возрасту ребенка [78].…”

Section: мидазоламunclassified

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Analgesia and Sedation in Newborns with Long-Term Mechanical Ventilation

Shestak

Ковтун

2023

Vopr. sovr. pediatr.

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Relevant data on drugs used for analgesia and sedation in newborns in the intensive care units during mechanical ventilation is presented. The overview of studies on the most common sedatives and analgesics (opioids, acetaminophen, ketamine, midazolam, dexmedetomidine, propofol) is provided. Analysis of their efficacy and risk of short-term and long-term adverse effects is presented, including those associated with the child’s nervous system development. The use of drugs both as monotherapy and in combination with other medications for analgesia and sedation is being discussed.

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“…Similarly, in a large national cohort study examining the association of early continuous infusions of opioids and/or midazolam with survival and sensorimotor outcomes at age two years in very premature infants who were ventilated, infants either received continuous opioid and/or midazolam infusion in the first week of life ( n = 450) or no treatment ( n = 472). Infants in the treated group had improved survival without any difference in moderate or severe sensorimotor impairments at age two years [ 170 ]. More research is needed to determine the best practices for safe and effective administration of opioids for pain management in neonates.…”

Section: Management Of Neonatal Painmentioning

confidence: 99%

Assessment and Management of Pain in Preterm Infants: A Practice Update

2022

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Infants born preterm are at a high risk for repeated pain exposure in early life. Despite valid tools to assess pain in non-verbal infants and effective interventions to reduce pain associated with medical procedures required as part of their care, many infants receive little to no pain-relieving interventions. Moreover, parents remain significantly underutilized in provision of pain-relieving interventions, despite the known benefit of their involvement. This narrative review provides an overview of the consequences of early exposure to untreated pain in preterm infants, recommendations for a standardized approach to pain assessment in preterm infants, effectiveness of non-pharmacologic and pharmacologic pain-relieving interventions, and suggestions for greater active engagement of parents in the pain care for their preterm infant.

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Association of Continuous Opioids and/or Midazolam During Early Mechanical Ventilation with Survival and Sensorimotor Outcomes at Age 2 Years in Premature Infants: Results from the French Prospective National EPIPAGE 2 Cohort

Cited by 7 publications

References 54 publications

Frequencies, Modalities, Doses and Duration of Computerized Prescriptions for Sedative, Analgesic, Anesthetic and Paralytic Drugs in Neonates Requiring Intensive Care: A Prospective Pharmacoepidemiologic Cohort Study in 30 French NICUs From 2014 to 2020

Frequencies, Modalities, Doses and Duration of Computerized Prescriptions for Sedative, Analgesic, Anesthetic and Paralytic Drugs in Neonates Requiring Intensive Care: A Prospective Pharmacoepidemiologic Cohort Study in 30 French NICUs From 2014 to 2020

Analgesia and Sedation in Newborns with Long-Term Mechanical Ventilation

Assessment and Management of Pain in Preterm Infants: A Practice Update

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