Methylxanthines for the treatment of apnea associated with bronchiolitis and anesthesia

McNamara, David; Nixon, Gillian M.; Anderson, Brian J.

doi:10.1111/j.1460-9592.2004.01351.x

Cited by 14 publications

(3 citation statements)

References 96 publications

(134 reference statements)

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“…20 Caffeine is a respiratory stimulant that is effective in the prevention and treatment of apnoea of prematurity and intermittent hypoxaemia and also reduces the incidence of chronic lung disease, cerebral palsy and cognitive delay in very preterm infants. [21][22][23] Follow-up to 11 years of age has recently shown that caffeine treatment reduces the risk of motor dysfunction by a third infants born very preterm. 24 25 While some of the long-term beneficial effects of caffeine may be due to its effect in reducing the incidence of bronchopulmonary dysplasia, 26 there is also benefit from reducing the amount of time that infants are hypoxic, independent of the effect on bronchopulmonary dysplasia.…”

Section: Introductionmentioning

confidence: 99%

(Rad 8)Caffeine prophylaxis to improve intermittent hypoxaemia in infants born late preterm: a randomised controlled dosage trial (Latte Dosage Trial)

et al. 2020

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IntroductionInfants born late preterm (34+0 to 36+6 weeks’ gestational age) have frequent episodes of intermittent hypoxaemia compared with term infants. Caffeine citrate reduces apnoea and intermittent hypoxaemia and improves long-term neurodevelopmental outcomes in infants born very preterm and may have similar effects in late preterm infants. Clearance of caffeine citrate increases with gestational age and late preterm infants are likely to need a higher dose than very preterm infants. Our aim is to determine the most effective and best-tolerated dose of caffeine citrate to reduce transient intermittent hypoxaemia events in late preterm infants.Methods and analysisA phase IIB, double-blind, five-arm, parallel, randomised controlled trial to compare the effect of four doses of oral caffeine citrate versus placebo on the frequency of intermittent hypoxaemia. Late preterm infants will be enrolled within 72 hours of birth and randomised to receive 5, 10, 15 or 20 mg/kg/day caffeine citrate or matching placebo daily until term corrected age. The frequency of intermittent hypoxaemia (events/hour where oxygen saturation concentration is ≥10% below baseline for ≤2 min) will be assessed with overnight oximetry at baseline, 2 weeks after randomisation (primary outcome) and at term corrected age. Growth will be measured at these timepoints, and effects on feeding and sleeping will be assessed by parental report. Data will be analysed using generalised linear mixed models.Ethics and disseminationThis trial has been approved by the Health and Disability Ethics Committees of New Zealand (reference 18/NTA/129) and the local institutional research review committees. Findings will be disseminated to peer-reviewed journals to clinicians and researchers at local and international conferences and to the public. The findings of the trial will inform the design of a large multicentre trial of prophylactic caffeine in late preterm infants, by indicating the most appropriate dose to use and providing information on feasibility.Trial registration numberACTRN12618001745235; Pre-results.

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Section: Introductionmentioning

confidence: 99%

(Rad 8)Caffeine prophylaxis to improve intermittent hypoxaemia in infants born late preterm: a randomised controlled dosage trial (Latte Dosage Trial)

et al. 2020

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“…18 Caffeine is effective in the prevention and treatment of apnoea of prematurity and IH, and reduces the incidence of chronic lung disease, cerebral palsy and cognitive delay in very preterm infants. [19][20][21] Due to hepatic immaturity, caffeine elimination is slow in extremely preterm infants. 22 With increasing gestational age the elimination of caffeine increases, 22 23 requiring larger doses to maintain a therapeutic effect.…”

Section: Introductionmentioning

confidence: 99%

“…Caffeine is effective in the prevention and treatment of apnoea of prematurity and IH, and reduces the incidence of chronic lung disease, cerebral palsy and cognitive delay in very preterm infants 19–21. Due to hepatic immaturity, caffeine elimination is slow in extremely preterm infants 22.…”

Section: Introductionmentioning

confidence: 99%

Caffeine to prevent intermittent hypoxaemia in late preterm infants: randomised controlled dosage trial

Oliphant

McKinlay

McNamara

et al. 2022

Arch Dis Child Fetal Neonatal Ed

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ObjectiveTo establish the most effective and best tolerated dose of caffeine citrate for the prevention of intermittent hypoxaemia (IH) in late preterm infants.DesignPhase IIB, double-blind, five-arm, parallel, randomised controlled trial.SettingNeonatal units and postnatal wards of two tertiary maternity hospitals in New Zealand.ParticipantsLate preterm infants born at 34+0–36+6 weeks’ gestation, recruited within 72 hours of birth.InterventionInfants were randomly assigned to receive a loading dose (10, 20, 30 or 40 mg/kg) followed by 5, 10, 15 or 20 mg/kg/day equivolume enteral caffeine citrate or placebo daily until term corrected age.Primary outcomeIH (events/hour with oxygen saturation concentration ≥10% below baseline for ≤2 min), 2 weeks postrandomisation.Results132 infants with mean (SD) birth weight 2561 (481) g and gestational age 35.7 (0.8) weeks were randomised (24–28 per group). Caffeine reduced the rate of IH at 2 weeks postrandomisation (geometric mean (GM): 4.6, 4.6, 2.0, 3.8 and 1.7 events/hour for placebo, 5, 10, 15 and 20 mg/kg/day, respectively), with differences statistically significant for 10 mg/kg/day (GM ratio (95% CI] 0.39 (0.20 to 0.76]; p=0.006) and 20 mg/kg/day (GM ratio (95% CI] 0.33 (0.17 to 0.68]; p=0.003) compared with placebo. The 20 mg/kg/day dose increased mean (SD) pulse oximetry oxygen saturation (SpO2) (97.2 (1.0) vs placebo 96.0 (0.8); p<0.001), and reduced median (IQR) percentage of time SpO2 <90% (0.5 (0.2–0.8) vs 1.1 (0.6–2.4); p<0.001) at 2 weeks, without significant adverse effects on growth velocity or sleeping.ConclusionCaffeine reduces IH in late preterm infants at 2 weeks of age, with 20 mg/kg/day being the most effective dose.Trial registration numberACTRN12618001745235.

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Anesthesia and Ancillary Drugs and the Neonate

Anderson

Larsson

Lerman

2014

Neonatal Anesthesia

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Methylxanthines for the treatment of apnea associated with bronchiolitis and anesthesia

Cited by 14 publications

References 96 publications

(Rad 8)Caffeine prophylaxis to improve intermittent hypoxaemia in infants born late preterm: a randomised controlled dosage trial (Latte Dosage Trial)

(Rad 8)Caffeine prophylaxis to improve intermittent hypoxaemia in infants born late preterm: a randomised controlled dosage trial (Latte Dosage Trial)

Caffeine to prevent intermittent hypoxaemia in late preterm infants: randomised controlled dosage trial

Anesthesia and Ancillary Drugs and the Neonate

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