Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort studyResearch in context

Summary: Background: Preterm infants often require mechanical ventilation (MV), which can be a painful experience. Opioids (such as morphine) are used to provide analgesia, despite conflicting evidence about their impact on the developing brain. We aimed to quantify the use of opioids during MV in...

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Main Authors: Lisa Szatkowski, Don Sharkey, Helen Budge, Shalini Ojha
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:EClinicalMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S258953702300473X
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author Lisa Szatkowski
Don Sharkey
Helen Budge
Shalini Ojha
author_facet Lisa Szatkowski
Don Sharkey
Helen Budge
Shalini Ojha
author_sort Lisa Szatkowski
collection DOAJ
description Summary: Background: Preterm infants often require mechanical ventilation (MV), which can be a painful experience. Opioids (such as morphine) are used to provide analgesia, despite conflicting evidence about their impact on the developing brain. We aimed to quantify the use of opioids during MV in infants born at <32 weeks' gestational age and to investigate the association between opioid use and evidence of brain injury. Methods: In this retrospective propensity score-matched cohort study, we used routinely recorded data from the National Neonatal Research Database to study infants born at 22–31 weeks gestational age who were admitted to neonatal units in England and Wales (between Jan 1, 2012, and Dec 31, 2020) and who were mechanically ventilated on one or more days during their hospital stay. We used propensity score matching to identify pairs of infants (one who received opioids during MV and one who did not) with similar demographic and clinical characteristics. The pre-specified primary outcome was preterm brain injury assessed in all infants who received MV for more than two days and had evidence of preterm brain injury at or before discharge from neonatal care. Adjusted analyses accounted for differences in infants’ characteristics, including illness severity and painful/surgical conditions. Findings: Of 67,206 infants included, 45,193 (67%) were mechanically ventilated for one or more days and 26,201 (58% of 45,193) received an opioid whilst ventilated. Opioids were given for a median of 67% of ventilated days (IQR 43–92%) and the median exposure was 4 days (2–11). The percentage of mechanically ventilated infants who received opioids while ventilated increased from 52% in 2012 to 60% in 2020 (morphine, 51%–56%; fentanyl, 6%–18%). In the propensity score-matched cohort of 3608 pairs who were ventilated for >2 consecutive days, the odds of any preterm brain injury (adjusted odds ratio 1.22, 95% CI 1.10–1.35) were higher in those who received opioids compared with those who did not (received opioids, 990/3608 (27.4%) vs. did not receive opioids, 855/3608 (23.7%). The adjusted odds of these adverse outcomes increased with increasing number of days of opioid exposure. Interpretation: Use of opioids during mechanical ventilation of preterm infants increased during the study period (2012–2020). Although causation cannot be determined, among those ventilated for >2 consecutive days, these data suggest that opioid use is associated with an increased risk of preterm brain injury and the risk increases with longer durations of exposure. Funding: University of Nottingham Impact Fund.
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spelling doaj.art-a083b2bf69974ed5909037190c448a4a2023-11-28T07:26:51ZengElsevierEClinicalMedicine2589-53702023-11-0165102296Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort studyResearch in contextLisa Szatkowski0Don Sharkey1Helen Budge2Shalini Ojha3Centre for Perinatal Research, Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UKCentre for Perinatal Research, Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UKCentre for Perinatal Research, Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UKCentre for Perinatal Research, Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK; Neonatal Unit, University Hospitals of Derby and Burton NHS Trust, Derby, UK; Corresponding author. Lifespan and Population Health, School of Medicine, University of Nottingham, Room 4117, Medical School Building, Royal Derby Hospital, Derby, DE22 3NE, UK.Summary: Background: Preterm infants often require mechanical ventilation (MV), which can be a painful experience. Opioids (such as morphine) are used to provide analgesia, despite conflicting evidence about their impact on the developing brain. We aimed to quantify the use of opioids during MV in infants born at <32 weeks' gestational age and to investigate the association between opioid use and evidence of brain injury. Methods: In this retrospective propensity score-matched cohort study, we used routinely recorded data from the National Neonatal Research Database to study infants born at 22–31 weeks gestational age who were admitted to neonatal units in England and Wales (between Jan 1, 2012, and Dec 31, 2020) and who were mechanically ventilated on one or more days during their hospital stay. We used propensity score matching to identify pairs of infants (one who received opioids during MV and one who did not) with similar demographic and clinical characteristics. The pre-specified primary outcome was preterm brain injury assessed in all infants who received MV for more than two days and had evidence of preterm brain injury at or before discharge from neonatal care. Adjusted analyses accounted for differences in infants’ characteristics, including illness severity and painful/surgical conditions. Findings: Of 67,206 infants included, 45,193 (67%) were mechanically ventilated for one or more days and 26,201 (58% of 45,193) received an opioid whilst ventilated. Opioids were given for a median of 67% of ventilated days (IQR 43–92%) and the median exposure was 4 days (2–11). The percentage of mechanically ventilated infants who received opioids while ventilated increased from 52% in 2012 to 60% in 2020 (morphine, 51%–56%; fentanyl, 6%–18%). In the propensity score-matched cohort of 3608 pairs who were ventilated for >2 consecutive days, the odds of any preterm brain injury (adjusted odds ratio 1.22, 95% CI 1.10–1.35) were higher in those who received opioids compared with those who did not (received opioids, 990/3608 (27.4%) vs. did not receive opioids, 855/3608 (23.7%). The adjusted odds of these adverse outcomes increased with increasing number of days of opioid exposure. Interpretation: Use of opioids during mechanical ventilation of preterm infants increased during the study period (2012–2020). Although causation cannot be determined, among those ventilated for >2 consecutive days, these data suggest that opioid use is associated with an increased risk of preterm brain injury and the risk increases with longer durations of exposure. Funding: University of Nottingham Impact Fund.http://www.sciencedirect.com/science/article/pii/S258953702300473XInfantPretermMechanical ventilationOpioidNeurodevelopment
spellingShingle Lisa Szatkowski
Don Sharkey
Helen Budge
Shalini Ojha
Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort studyResearch in context
EClinicalMedicine
Infant
Preterm
Mechanical ventilation
Opioid
Neurodevelopment
title Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort studyResearch in context
title_full Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort studyResearch in context
title_fullStr Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort studyResearch in context
title_full_unstemmed Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort studyResearch in context
title_short Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort studyResearch in context
title_sort association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury a propensity score matched cohort studyresearch in context
topic Infant
Preterm
Mechanical ventilation
Opioid
Neurodevelopment
url http://www.sciencedirect.com/science/article/pii/S258953702300473X
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