Predicting severity of adverse cardiorespiratory effects of morphine in premature infants: a post hoc analysis of Procedural Pain in Premature Infants trial data

Hartley, Caroline; Baxter, Luke; Moultrie, Fiona; Purdy, Ryan; Bhatt, Aomesh; Rogers, Richard; Patel, Chetan K.; Adams, Eleri; Slater, Rebeccah

doi:10.1016/j.bja.2020.10.034

Cited by 13 publications

(16 citation statements)

References 10 publications

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“…Additionally, analysis of vital signs may be useful to develop predictive models to tailor individualised care 27,28 . We recently showed in a post-hoc analysis of the morphine-treated infants in the Poppi trial that we could predict the risk of adverse cardiorespiratory effects in individual infants from their baseline physiological stability 29 . To date, measures of respiration are often not included in the development of predictive tools, which is likely due to the relatively poor quality of the currently-available measurement tools 28 .…”

Section: Discussionmentioning

confidence: 99%

A new method to measure inter-breath intervals in infants for the assessment of apnoea and respiratory dynamics

Purdy

Jorge

Adams

et al. 2021

Preprint

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Background Respiratory disorders, including apnoea, are common in preterm infants due to their immature respiratory control and function compared with term-born infants. However, our inability to accurately measure respiratory rate in hospitalised infants results in unreported episodes of apnoea and an incomplete picture of respiratory dynamics. Methods We develop, validate and use a novel algorithm to identify inter-breath intervals (IBIs) and apnoeas in infants. In 42 infants (a total of 1600 hours of recordings) we assess IBIs from the chest electrical impedance pneumograph using an adaptive amplitude threshold for the detection of individual breaths. The algorithm is refined by comparing its accuracy with clinically-observed breaths and pauses in breathing. We also develop an automated classifier to differentiate periods of true central apnoea from artefactually low amplitude signal. We use this algorithm to explore its ability to identify morphine-induced respiratory depression in 15 infants. Finally, in 22 infants we use the algorithm to investigate whether retinopathy of prematurity (ROP) screening alters the IBI distribution. Findings 88% of the central apnoeas identified using our algorithm were missed in the clinical notes. As expected, morphine caused a shift in the IBI distribution towards longer IBIs, with significant differences in all IBI metrics assessed. Following ROP screening, there was a shift in the IBI distribution with a significant increase in the proportion of pauses in breathing that lasted more than 10 seconds (t-statistic=1.82, p=0.023). This was not reflected by changes in the monitor- derived respiratory rate or episodes of apnoea recorded on clinical charts. Interpretation Better measurement of infant respiratory dynamics is essential to improve care for hospitalised infants. Use of the novel IBI algorithm demonstrates that following ROP screening increased instability in respiratory dynamics can be detected in the absence of clinically-significant apnoeas. Funding Wellcome Trust and Royal Society

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Section: Discussionmentioning

confidence: 99%

A new method to measure inter-breath intervals in infants for the assessment of apnoea and respiratory dynamics

Purdy

Jorge

Adams

et al. 2021

Preprint

Self Cite

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“… 30 31 We recently showed in a post-hoc analysis of the morphine-treated infants in the Poppi trial that we could predict the risk of adverse cardiorespiratory effects in individual infants from their baseline physiological stability. 32 To date, measures of respiration are often not included in the development of predictive tools, which is likely due to the relatively poor quality of the currently available measurement tools. 31 Here we provide a more accurate measure of IBIs, which will allow for more complex metrics, such as respiratory rate variability, to be computed.…”

Section: Discussionmentioning

confidence: 99%

New method to measure interbreath intervals in infants for the assessment of apnoea and respiration

et al. 2021

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BackgroundRespiratory disorders, including apnoea, are common in preterm infants due to their immature respiratory control compared with term-born infants. However, our inability to accurately measure respiratory rate in hospitalised infants results in unreported episodes of apnoea and an incomplete picture of respiratory activity.MethodsWe develop, validate and use a novel algorithm to identify interbreath intervals (IBIs) and apnoeas in preterm infants. In 42 preterm infants (1600 hours of recordings), we assess IBIs from the chest electrical impedance pneumograph using an adaptive amplitude threshold for the detection of breaths. The algorithm is refined by comparing its accuracy with clinically observed breaths and pauses in breathing. We develop an automated classifier to differentiate periods of true apnoea from artefactually low amplitude signal. We assess the performance of this algorithm in the detection of morphine-induced respiratory depression. Finally, we use the algorithm to investigate whether retinopathy of prematurity (ROP) screening alters the IBI distribution.ResultsIndividual breaths were detected with a false-positive rate of 13% and a false-negative rate of 12%. The classifier identified true apnoeas with an accuracy of 93%. As expected, morphine caused a significant shift in the IBI distribution towards longer IBIs. Following ROP screening, there was a significant increase in pauses in breathing that lasted more than 10 s (t-statistic=1.82, p=0.023). This was not reflected by changes in the monitor-derived respiratory rate and no episodes of apnoea were recorded in the medical records.ConclusionsWe show that our algorithm offers an improved method for the identification of IBIs and apnoeas in preterm infants. Following ROP screening, increased respiratory instability can occur even in the absence of clinically significant apnoeas. Accurate assessment of infant respiratory activity is essential to inform clinical practice.

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“…However, very recently, Hartley et al 60 electronically captured vital signs of 15 newborn infants who were treated with 0.1 mg/kg morphine orally ≈1 hour before their clinical procedure for the duration of 24 hours before and after a clinical procedure. These authors showed that there was a wide variation in the baseline physiologic stability of these infants, even in an already relatively simple clinical scenario of a planned diagnostic intervention.…”

Section: Appropriate Dose Adjustments In Premature Infants Based On Novel Ways To Evaluate the Effects Of Their Pharmacotherapymentioning

confidence: 99%

Considerations for Drug Dosing in Premature Infants

Anker

Allegaert

2021

The Journal of Clinical Pharma

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In premature infants, effective and safe drug therapy depends on optimal dose selection and requires a thorough understanding of the underlying disease(s) of these fragile infants as well as the pharmacokinetics and pharmacodynamics of the drugs selected to treat their diseases. Differences in gestational and postnatal age or weight are the major determinants of the observed variability in drug disposition and effect in these infants. This article presents an outline on how to translate the results of a population pharmacokinetic/pharmacodynamic study into rational dosing regimens, and how physiologically based pharmacokinetic modeling, electronic health records, and the abundantly available data of vital functions of premature infants during their stay in the neonatal intensive care unit for evaluation of their pharmacotherapy can be used to tailor the most safe and effective dose in these infants.

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Predicting severity of adverse cardiorespiratory effects of morphine in premature infants: a post hoc analysis of Procedural Pain in Premature Infants trial data

Cited by 13 publications

References 10 publications

A new method to measure inter-breath intervals in infants for the assessment of apnoea and respiratory dynamics

A new method to measure inter-breath intervals in infants for the assessment of apnoea and respiratory dynamics

New method to measure interbreath intervals in infants for the assessment of apnoea and respiration

Considerations for Drug Dosing in Premature Infants

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