Predicting severity of adverse cardiorespiratory effects of morphine in premature infants: a post hoc analysis of Procedural Pain in Premature Infants trial data.
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SUBMITTER: Hartley C
PROVIDER: S-EPMC8767644 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundInfant pain has immediate and long-term effects but is undertreated because of a paucity of evidence-based analgesics. Although morphine is often used to sedate ventilated infants, its analgesic efficacy is unclear. We aimed to establish whether oral morphine could provide effective and safe analgesia in non-ventilated premature infants for acute procedural pain.MethodsIn this single-centre masked trial, 31 infants at the John Radcliffe Hospital, Oxford, UK, were randomly allocated using a web-based facility with a minimisation algorithm to either 100 μg/kg oral morphine sulphate or placebo 1 h before a clinically required heel lance and retinopathy of prematurity screening examination, on the same occasion. Eligible infants were born prematurely at less than 32 weeks' gestation or with a birthweight lower than 1501 g and had a gestational age of 34-42 weeks at the time of the study. The co-primary outcome measures were the Premature Infant Pain Profile-Revised (PIPP-R) score after retinopathy of prematurity screening and the magnitude of noxious-evoked brain activity after heel lancing. Secondary outcome measures assessed physiological stability and safety. This trial is registered with the European Clinical Trials Database (number 2014-003237-25).FindingsBetween Oct 30, 2016, and Nov 17, 2017, 15 infants were randomly allocated to morphine and 16 to placebo; one infant assigned placebo was withdrawn from the study before monitoring began. The predefined stopping boundary was crossed, and trial recruitment stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy. None of the co-primary outcome measures differed significantly between groups. PIPP-R score after retinopathy of prematurity screening was mean 11·1 (SD 3·2) with morphine and 10·5 (3·4) with placebo (mean difference 0·5, 95% CI -2·0 to 3·0; p=0·66). Noxious-evoked brain activity after heel lancing was median 0·99 (IQR 0·40-1·56) with morphine and 0·75 (0·33-1·22) with placebo (median difference 0·25, 95% CI -0·16 to 0·80; p=0·25).InterpretationAdministration of oral morphine (100 μg/kg) to non-ventilated premature infants has the potential for harm without analgesic efficacy. We do not recommend oral morphine for retinopathy of prematurity screening and strongly advise caution if considering its use for other acute painful procedures in non-ventilated premature infants.FundingWellcome Trust and National Institute for Health Research.
| S-EPMC6294828 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-04-06 | GSE129460 | GEO
Project description:IntroductionInfants and children are frequently exposed to painful medical procedures such as immunisation, blood sampling and intravenous access. Over 40 scales for pain assessment are available, many designed for neonatal or postoperative pain. What is not well understood is how well these scales perform when used to assess procedural pain in infants and children.AimThe aim of this study was to test the psychometric and practical properties of the Face, Legs, Activity, Cry and Consolability (FLACC) scale, the Modified Behavioural Pain Scale (MBPS) and the Visual Analogue Scale (VAS) observer pain scale to quantify procedural pain intensity in infants and children aged from 6-42 months to determine their suitability for clinical and research purposes.Methods and analysisA prospective observational non-interventional study conducted at a single centre. The psychometric and practical performance of the FLACC scale, MBPS and the VAS observer pain scale and VAS observer distress scale used to assess children experiencing procedural pain will be assessed. Infants and young children aged 6-42 months undergoing one of four painful and/or distressing procedures were recruited and the procedure digitally video recorded. Clinicians and psychologists will be recruited to independently apply the scales to these video recordings to establish intrarater and inter-rater reliability, convergent validity responsiveness and specificity. Pain score distributions will be presented descriptively; reliability will be assessed using the intraclass correlation coefficient and Bland-Altman plots. Spearman correlations will be used to assess convergence and linear mixed modelling to explore the responsiveness of the scales to pain and their capacity to distinguish between pain and distress.Ethics and disseminationEthical approval was provided by the Royal Children's Hospital Human Research Ethics Committee, approval number 35220B. The findings of this study will be disseminated via peer-reviewed journals and presented at international conferences.
| S-EPMC5589003 | biostudies-literature
Project description:BackgroundContinuous intravenous (IV) morphine is commonly used in ventilated neonates. Oral route is theoretically feasible but data on oral morphine in ventilated premature infants are lacking.ObjectiveTo assess the efficacy, efficiency, and tolerability of a continuous intravenous to oral morphine switch protocol.DesignRetrospective study.SettingSingle level III center's neonatal intensive care unit.PatientsVentilated premature infants hospitalized in the NICU in 2016 and 2017, receiving continuous IV morphine with an expected ventilation course of at least 72 more hours. We excluded patients treated for withdrawal syndrome or palliative care.InterventionsContinuous IV to oral morphine switch with the same initial cumulated daily dose.Main outcome measuresPain scores (ComfortNeo scale) and morphine doses were analyzed over time using Friedman's test in the 24 hours preceding and the 48 hours following the oral switch. Adverse effects attributable to opioids were collected.ResultsSeventeen infants were included with a median [IQR] gestational age at birth of 25.9 [24.6-26.9] weeks and a median postnatal age at oral switch of 30 [22-36] days. One patient's intravenous treatment had to be resumed because of a high ComfortNeo score. All others remained on oral morphine. No significant change over time was observed for ComfortNeo scores (P = .15). Median [IQR] doses were 13.5 [10-20] µg/kg/h in the IV period and significantly increased to 15 [10-25] µg/kg/h in the oral period (P = .009). No short-term respiratory, digestive, or urinary adverse event was observed. After a median [IQR] duration of 13 [4-20] days of oral morphine treatment, 11 (65%) patients showed signs of withdrawal. Upon hospital discharge, 16 infants (94%) had bronchopulmonary dysplasia and none had severe cerebral abnormality on brain imaging.ConclusionOral morphine might be useful in ventilated neonates in the NICU but deserves further studies and additional safety assessment.
| S-EPMC8975237 | biostudies-literature
Project description:The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) μM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.
| S-EPMC11144121 | biostudies-literature
Project description:BackgroundMachine learning has been attracting increasing attention for use in healthcare applications, including neonatal medicine. One application for this tool is in understanding and predicting neurodevelopmental outcomes in preterm infants. In this study, we have carried out a systematic review to identify findings and challenges to date.MethodsThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases were searched in February 2022, with articles then screened in a non-blinded manner by two authors.ResultsThe literature search returned 278 studies, with 11 meeting the eligibility criteria for inclusion. Convolutional neural networks were the most common machine learning approach, with most studies seeking to predict neurodevelopmental outcomes from images and connectomes describing brain structure and function. Studies to date also sought to identify features predictive of outcomes; however, results varied greatly.ConclusionsInitial studies in this field have achieved promising results; however, many machine learning techniques remain to be explored, and the consensus is yet to be reached on which clinical and brain features are most predictive of neurodevelopmental outcomes.ImpactThis systematic review looks at the question of whether machine learning can be used to predict and understand neurodevelopmental outcomes in preterm infants. Our review finds that promising initial works have been conducted in this field, but many challenges and opportunities remain. Quality assessment of relevant articles is conducted using the Newcastle-Ottawa Scale. This work identifies challenges that remain and suggests several key directions for future research. To the best of the authors' knowledge, this is the first systematic review to explore this topic.
| S-EPMC9153218 | biostudies-literature
Project description:Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the LV function as measured by tissue Doppler imaging (TDI) and its association with BPD-PH. We retrospectively assessed prospectively acquired clinical and echocardiographic data from 77 preterm infants born between 2011 and 2013. We characterized the LV function by measuring systolic and diastolic myocardial velocities (s', e', a'), isovolumetric relaxation time (IVRT), and myocardial performance index with TDI at three time periods from 32 and 36 weeks, postmenstrual age through one year of age. We also measured post systolic motion (PSM), a marker of myocardial dysfunction that results from asynchronous movement of the ventricular walls, and not previously described in preterm infants. Patients were stratified into groups according to BPD severity and the presence of PH and compared over time. Conventional TDI measures of the LV function were similar between groups, but the septal PSM was significantly prolonged over the first year of age in patients with BPD-PH. PSM provides a novel objective way to assess the hemodynamic impact of lung and pulmonary vascular disease severity on LV function in preterm infants with BPD and PH.
| S-EPMC8160781 | biostudies-literature
Project description:Accurate evaluation of retinopathy of prematurity (ROP) severity is vital for screening and proper treatment. Current deep-learning-based automated AI systems for assessing ROP severity do not follow clinical guidelines and are opaque. The aim of this study is to develop an interpretable AI system by mimicking the clinical screening process to determine ROP severity level. A total of 6100 RetCam Ⅲ wide-field digital retinal images were collected from Guangdong Women and Children Hospital at Panyu (PY) and Zhongshan Ophthalmic Center (ZOC). A total of 3330 images of 520 pediatric patients from PY were annotated to train an object detection model to detect lesion type and location. A total of 2770 images of 81 pediatric patients from ZOC were annotated for stage, zone, and the presence of plus disease. Integrating stage, zone, and the presence of plus disease according to clinical guidelines yields ROP severity such that an interpretable AI system was developed to provide the stage from the lesion type, the zone from the lesion location, and the presence of plus disease from a plus disease classification model. The ROP severity was calculated accordingly and compared with the assessment of a human expert. Our method achieved an area under the curve (AUC) of 0.95 (95% confidence interval [CI] 0.90-0.98) in assessing the severity level of ROP. Compared with clinical doctors, our method achieved the highest F1 score value of 0.76 in assessing the severity level of ROP. In conclusion, we developed an interpretable AI system for assessing the severity level of ROP that shows significant potential for use in clinical practice for ROP severity level screening.
| S-EPMC11351924 | biostudies-literature
Project description:AbstractPreterm infants show a higher incidence of cognitive, social, and behavioral problems, even in the absence of major medical complications during their stay in the neonatal intensive care unit (NICU). Several authors suggest that early-life experience of stress and procedural pain could impact cerebral development and maturation resulting in an altered development of cognition, behavior, or motor patterns in later life. However, it remains very difficult to assess this impact of procedural pain on physiological development. This study describes the maturation of electroencephalogram (EEG) signals and heart rate variability in a prospective cohort of 92 preterm infants (<34 weeks gestational age) during their NICU stay. We took into account the number of noxious, ie, skin-breaking, procedures they were subjected in the first 5 days of life, which corresponded to a median age of 31 weeks and 4 days. Using physiological signal modelling, this study shows that a high exposure to early procedural pain, measured as skin-breaking procedures, increased the level of discontinuity in both EEG and heart rate variability in preterm infants. These findings have also been confirmed in a subset of the most vulnerable preterm infants with a gestational age lower than 29 weeks. We conclude that a high level of early pain exposure in the NICU increases the level of functional dysmaturity, which can ultimately impact preterm infants' future developmental outcome.
| S-EPMC8054544 | biostudies-literature