Drug utilisation in neonatal units in England and Wales: a national cohort study

Al-Turkait, Asma; Szatkowski, Lisa; Choonara, Imti; Ojha, Shalini

doi:10.1007/s00228-021-03267-x

Cited by 15 publications

(14 citation statements)

References 27 publications

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“…Caffeine is the most frequently prescribed medicine in neonates 1. The Caffeine for Apnea of Prematurity (CAP) trial showed that, in very low birthweight infants, caffeine reduces the risk of bronchopulmonary dysplasia (BPD), and improves the rate of survival without neurodevelopmental impairment at 18–21 months of age 2.…”

Section: Introductionmentioning

confidence: 99%

Observational cohort study of use of caffeine in preterm infants and association between early caffeine use and neonatal outcomes

Szatkowski

Fateh

Abramson

et al. 2023

Arch Dis Child Fetal Neonatal Ed

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ObjectiveTo quantify trends in caffeine use in infants born at <32 weeks’ gestational age (GA), and to investigate the effects of early vs late caffeine on neonatal outcomes.Study designRetrospective propensity score matched cohort study using routinely recorded data from the National Neonatal Research Database of infants born at <32 weeks’ GA admitted to neonatal units in England and Wales (2012–2020).Results89% (58 913/66 081) of infants received caffeine. In 70%, caffeine was started early (on the day of birth or the day after), increasing from 55% in 2012 to 83% in 2020. Caffeine was given for a median (IQR) of 28 (17–43) days starting on day 2 (1–3) and continued up to 34 (33–34) weeks postmenstrual age.In the propensity score matched cohort of 13 045 pairs of infants, the odds of preterm brain injury (early caffeine, 2306/13 045 (17.7%) vs late caffeine, 2528/13 045 (19.4%), OR=0.89 (95% CI 0.84 to 0.95)) and bronchopulmonary dysplasia (BPD) (early caffeine, 4020/13 045 (32.8%) vs late caffeine, 4694/13 045 (37.7%), OR=0.81 (95% CI 0.76 to 0.85)) were lower in the group that received early caffeine compared with those who received it later.ConclusionsEarly use of caffeine has increased in England and Wales. This is associated with reduced risks of BPD and preterm brain injury. Randomised trials are needed to find the optimal timing of caffeine use and the groups of infants who will benefit most from early administration of caffeine.

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Section: Introductionmentioning

confidence: 99%

Observational cohort study of use of caffeine in preterm infants and association between early caffeine use and neonatal outcomes

Szatkowski

Fateh

Abramson

et al. 2023

Arch Dis Child Fetal Neonatal Ed

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“…Caffeine citrate is one of the most widely prescribed drugs in neonatology ( 106 ) and reduces the rates of BPD, intraventricular hemorrhage, and neurodevelopmental impairment among preterm infants ( 107 ). The Caffeine for Apnea of Prematurity trial for the use of caffeine citrate in preterm infants attributed the increased incidence of BPD among its control group to the extended time this group required positive pressure ventilator support ( 108 ).…”

Section: Impact Of Bpd Therapies On Tgf-β Signalingmentioning

confidence: 99%

Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia

Calthorpe

Poulter

Smyth

et al. 2023

American Journal of Physiology-Lung Cellular and Molecular Phys

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As survival of extremely preterm infants continues to improve, there is also an associated increase in bronchopulmonary dysplasia (BPD), one of the most significant complications of preterm birth. BPD development is multifactorial resulting from exposure to multiple antenatal and postnatal stressors. BPD has both short-term health implications and long-term sequelae including increased respiratory, cardiovascular and neurological morbidity. Transforming growth factor beta (TGF-b) is an important signaling pathway in lung development, organ injury and fibrosis and is implicated in the development of BPD. This review provides a detailed account on the role of TGF-b in antenatal and postnatal lung development, the effect of known risk factors for BPD on the TGF-b signaling pathway, and how medications currently in use or under development, for the prevention or treatment of BPD, affect TGF-b signaling.

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“…In the UK, the percentage of very preterm infants who receive intravenous morphine increased from 32% in 2010 to 37% in 2017. 13…”

Section: Pain In Preterm Infantsmentioning

confidence: 99%

“…36 37 In an update of medication prescribing patterns in the US NICUs, Stark et al reported that between 2010 and 2018, dexmedetomidine was ninth in the list of drugs that had the greatest relative increase in use and had become the 90th most frequently prescribed medication 38 although its use was not reported, at least until 2017, in neonatal care in the UK. 13 Dexmedetomidine is used for sedation and analgesia on its own or in combination with other agents with the aim of reducing cumulative exposure to opioids and benzodiazepines. Comparing 48 infants with a mean GA of 25 weeks who received either fentanyl or dexmedetomidine, O'Mara et al found that the dexmedetomidine group required less adjunctive sedation.…”

Section: Clinical Reports Of the Use Of Dexmedetomidine In Preterm In...mentioning

confidence: 99%

Sedation and analgesia from prolonged pain and stress during mechanical ventilation in preterm infants: is dexmedetomidine an alternative to current practice?

Ojha

Abramson

Dorling

2022

bmjpo

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Mechanical ventilation is an uncomfortable and potentially painful intervention. Opioids, such as morphine and fentanyl, are used for analgesia and sedation but there is uncertainty whether they reduce pain in mechanically ventilated infants. Moreover, there may be short-term and long-term adverse consequences such as respiratory depression leading to prolonged mechanical ventilation and detrimental long-term neurodevelopmental effects. Despite this, opioids are widely used, possibly due to a lack of alternatives.Dexmedetomidine, a highly selective alpha-2-adrenergic agonist with analgesic and sedative effects, currently approved for adults, has come into use in newborn infants. It provides analgesia and simulates natural sleep with maintenance of spontaneous breathing and upper airway tone. Although data on pharmacokinetics–pharmacodynamics in preterm infants are scant, observational studies report that using dexmedetomidine in conjunction with opioids/benzodiazepines or on its own can reduce the cumulative exposure to opioids/benzodiazepines. As it does not cause respiratory depression, dexmedetomidine could enable quicker weaning and extubation. Dexmedetomidine has also been suggested as an adjunct to therapeutic hypothermia in hypoxic ischaemic encephalopathy and others have used it during painful procedures and surgery. Dexmedetomidine infusion can cause bradycardia and hypotension although most report clinically insignificant effects.The increasing number of publications of observational studies and clinical use demonstrates that dexmedetomidine is being used in newborn infants but data on safety and efficacy are scant and not of high quality. Importantly, there are no data on long-term neurodevelopmental impact on preterm or term-born infants. The acceptance of dexmedetomidine in routine clinical practice must be preceded by clinical evidence. We need adequately powered and well-designed randomised controlled trials investigating whether dexmedetomidine alone or with opioids/benzodiazepines in infants on mechanical ventilation reduces the need for opioids/benzodiazepine and improves neurodevelopment at 24 months and later as compared with the use of opioids/benzodiazepines alone.

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Drug utilisation in neonatal units in England and Wales: a national cohort study

Cited by 15 publications

References 27 publications

Observational cohort study of use of caffeine in preterm infants and association between early caffeine use and neonatal outcomes

Observational cohort study of use of caffeine in preterm infants and association between early caffeine use and neonatal outcomes

Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia

Sedation and analgesia from prolonged pain and stress during mechanical ventilation in preterm infants: is dexmedetomidine an alternative to current practice?

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