Caffeine therapy in preterm infants.
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ABSTRACT:
SUBMITTER: Abdel-Hady H
PROVIDER: S-EPMC4637812 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Publications
Caffeine therapy in preterm infants.
Abdel-Hady Hesham H Nasef Nehad N Shabaan Abd Elazeez AE Nour Islam I
World journal of clinical pediatrics 20151108 4
Caffeine is the most commonly used medication for treatment of apnea of prematurity. Its effect has been well established in reducing the frequency of apnea, intermittent hypoxemia, and extubation failure in mechanically ventilated preterm infants. Evidence for additional short-term benefits on reducing the incidence of bronchopulmonary dysplasia and patent ductus arteriosus has also been suggested. Controversies exist among various neonatal intensive care units in terms of drug efficacy compare ...[more]
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Project description:AimsCaffeine concentrations in preterm infants are usually measured in the blood. However, salivary assays may provide a valid and practical alternative. The present study explored the validity and clinical utility of salivary caffeine concentrations as an alternative to blood concentrations and developed a novel plasma/salivary caffeine distribution model.MethodsPaired salivary and plasma samples were obtained in 29 infants. Salivary samples were obtained using a commercially available salivary collection system. Caffeine concentrations in the saliva and plasma were determined using high-performance liquid chromatography. A population pharmacokinetic (PK) model was developed using NONMEM 7.3.ResultsThe mean (± standard deviation) gestational age (GA) at birth and birth weight were 27.9 ± 2.1 weeks and 1171.6 ± 384.9 g, respectively. Paired samples were obtained at a mean postmenstrual age (PMA) of 35.5 ± 1.1 weeks. The range of plasma caffeine concentrations was 9.5-54.1 μg ml(-1) , with a mean difference (95% confidence interval) between plasma and salivary concentrations of -0.18 μg ml(-1) (-1.90, 1.54). Salivary and plasma caffeine concentrations were strongly correlated (Pearson's correlation coefficient = 0.87, P < 0.001). Caffeine PK in plasma and saliva was simultaneously described by a three-compartment recirculation model. Current body weight, birth weight, GA, PMA and postnatal age were not significantly correlated with any PK parameter.ConclusionsSalivary sampling provides an easy, non-invasive method for measuring caffeine concentrations. Salivary concentrations correlate highly with plasma concentrations. Caffeine PK in saliva and plasma are well described by a three-compartment recirculation model.
| S-EPMC5338118 | biostudies-literature
Project description:Standard-dose caffeine improves white matter microstructural development assessed by diffusion magnetic resonance imaging (MRI). We hypothesized that early high-dose caffeine would result in further improvement in white matter microstructural development.Seventy-four preterm infants (?30?wk gestational age) were randomly assigned to either a high (80?mg/kg i.v.) or standard (20?mg/kg i.v.) loading dose of caffeine citrate in the first 24?h of life. MRI and neurobehavioral testing were undertaken at term equivalent age. Infants returned at 2 y of age for developmental testing.Clinical characteristics were similar between groups, with the exception of higher maternal age in the high-dose caffeine group. There was an increased incidence of cerebellar hemorrhage in infants randomized to high-dose caffeine (36 vs. 10%, P = 0.03). Infants in the high-dose caffeine group also demonstrated more hypertonicity (P = 0.02) and more deviant neurologic signs (P = 0.04) at term equivalent age. Diffusion measures at term equivalent age and developmental outcomes at 2 y of age did not differ between groups.Preterm infants randomized to early high-dose caffeine had a higher incidence of cerebellar injury with subsequent alterations in early motor performance. The results of this pilot trial discourage a larger randomized controlled trial.
| S-EPMC4928641 | biostudies-literature
Project description:The incidence of preterm birth is increasing, leading to a growing population with potential long-term pulmonary complications. Apnoea of prematurity (AOP) is one of the major challenges when treating preterm infants; it can lead to respiratory failure and the need for mechanical ventilation. Ventilating preterm infants can be associated with severe negative pulmonary and extrapulmonary outcomes, such as bronchopulmonary dysplasia (BPD), severe neurological impairment and death. Therefore, international guidelines favour non-invasive respiratory support. Strategies to improve the success rate of non-invasive ventilation in preterm infants include pharmacological treatment of AOP. Among the different pharmacological options, caffeine citrate is the current drug of choice. Caffeine is effective in reducing AOP and mechanical ventilation and enhances extubation success; it decreases the risk of BPD; and is associated with improved cognitive outcome at 2?years of age, and pulmonary function up to 11?years of age. The commonly prescribed dose (20?mg·kg-1 loading dose, 5-10?mg·kg-1 per day maintenance dose) is considered safe and effective. However, to date there is no commonly agreed standardised protocol on the optimal dosing and timing of caffeine therapy. Furthermore, despite the wide pharmacological safety profile of caffeine, the role of therapeutic drug monitoring in caffeine-treated preterm infants is still debated. This state-of-the-art review summarises the current knowledge of caff-eine therapy in preterm infants and highlights some of the unresolved questions of AOP. We speculate that with increased understanding of caffeine and its metabolism, a more refined respiratory management of preterm infants is feasible, leading to an overall improvement in patient outcome.
| S-EPMC7049734 | biostudies-literature
Project description:The paper aimed to evaluate the efficacy of different therapies in improving survival among preterm infants.PubMed and Embase were searched from inception to 2017. We assessed studies for eligibility and extracted data. A Bayesian random-effects model was used to evaluate different therapies combined direct comparisons with indirect evidence. Consistency analysis was achieved using node-splitting plots. Surface under the cumulative ranking curve (SUCRA) was calculated to rank different therapies. Rankings of the competing therapies were also performed.A total of 42 randomized controlled trials (RCTs) were included for the network meta-analysis. Forest plots demonstrated that dexamethasone (OR = 10.13, 95% CrI: 5.11 to 17.89) and vitamin A (OR = 28.44, 95% CrI: 14.66 to 42.11) is superior to placebo in duration of oxygen supplementation while vitamin A (OR = -29.76, 95% CrI: -57.66 to -1.75) is inferior to placebo with regard to duration of hospitalization. Also, dexamethasone (OR = 0.42, 95% CrI: 0.24 to 0.68) showed lower incidence rate of BPD.SUCRA results showed the superiority of Budesonide based on primary efficacy outcomes. In addition, dexamethasone also showed high efficacy ranking in duration of ventilation, duration of oxygen supplementation, and occurrence of BPD. Hydrocortisone was effective in reducing neonatal mortality. No significant difference was found among these drugs.No significant heterogeneity was found among these drugs. In general, budesonide might have the potential to be the optimal drug for its efficacy in reducing neonatal mortality and BPD, the two most essential outcome measures. Dexamethasone might be the suboptimal drug.
| S-EPMC5655271 | biostudies-literature
Project description:IntroductionRespiratory distress syndrome (RDS) or surfactant deficiency occurs primarily in premature infants resulting in composite outcomes of death or bronchopulmonary dysplasia. Initial management strategies for preterm infants with RDS includes early initiation of continuous positive airway pressure (CPAP) and titration of fractional inspired oxygen (FiO2), and may include the use of less invasive surfactant administration (LISA) to avoid the need for mechanical ventilation. In order to optimise success of non-invasive support, the use of early caffeine therapy may be critical to the success of LISA. The objective of our trial is to evaluate whether infants that receive early caffeine, CPAP and surfactant via the LISA method compared with infants that receive caffeine and CPAP alone, have a decreased need for invasive mechanical ventilation in the first 72 hours of life.Methods and analysisCaLI is an unblinded multicentre, randomised controlled, trial of 180 preterm infants (24+0-29+6 weeks corrected GA). Criteria for intubation/treatment failure will follow guidelines for the management of RDS, including: (1) CPAP level of 6-8 cmH20 and FiO2 >0.40 required to maintain saturations 90%-95% for 2?hours after randomisation; (2) a pH of 7.15 or less or a paCO2 >65?mm Hg on any (2) blood gases (arterial/capillary/or venous) at least 2?hours after randomisation and in the first 72 hours of life; (3) continued apnoea/bradycardia/desaturation events despite nasal intermittent minute ventilation mode of ventilation. Infants will be randomised by 1?hour of life and caffeine/LISA treatments administered by 2?hour of life. Caffeine will be administered prior to surfactant in the LISA arm and before 2?hours of life in the control arm.Ethics and disseminationChiesi Farmaceutici, S.p.A is the sponsor of CaLI. Ethical approval has been obtained. Results will be submitted for publication in peer reviewed journals.Trial registration numberwww.Clinicaltrials.gov: NCT04209946; Pre-results.
| S-EPMC7825253 | biostudies-literature
Project description:16S rRNA gene profiling of preterm infants
| PRJEB34372 | ENA
Project description:AimsThis study evaluated the therapeutic outcomes of early versus late caffeine therapy in preterm neonates.MethodsWe performed a systematic literature search in PubMed, Embase, CINAHL and CENTRAL from inception to 30 June 2016 to identify studies investigating the use of early caffeine therapy (initiated at less than 3 days of life) in preterm infants. Effect estimates were combined using random-effects meta-analysis. The primary outcomes for this study were bronchopulmonary dysplasia and mortality.ResultsThe initial search found 4066 citations, of which 14 studies enrolling a total of 64?438 participants were included. The time of initiation of early caffeine therapy varied from the first 2 h to 3 days postnatal. Early caffeine therapy reduced the risk of bronchopulmonary dysplasia in both cohort studies (RR: 0.80, 95% CI: 0.66 to 0.96) and randomized controlled trials (RR: 0.67, 95% CI: 0.56 to 0.81). In cohort studies, neonates treated early with caffeine also showed decreased risks of patent ductus arteriosus, brain injury, retinopathy of prematurity and postnatal steroid use. However, the mortality rate was increased.ConclusionsThe findings suggest that early caffeine therapy is associated with reduced incidence of bronchopulmonary dysplasia and may help decrease the burden of morbidities in preterm infants.
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Project description:OBJECTIVE: To investigate if antenatal glucocorticoid treatment has an effect on hippocampal histology of the human preterm newborn. PATIENTS AND METHODS: Included were consecutive neonates with a gestational age between 24 and 32 weeks, who were born between 1991 to 2009, who had died within 4 days after delivery and underwent brain autopsy. Excluded were neonates with congenital malformations and neonates treated postnatally with glucocorticoids. The brains were routinely fixed, samples of the hippocampus were stained with haematoxylin and eosin and sections were examined for presence or absence of large and small neurons in regions of the hippocampus. Additional staining with GFAP, neurofilament and vimentin was performed to evaluate gliosis and myelination. The proliferation marker Ki67 was used to evaluate neuronal proliferation. Staining with acid fuchsin-thionin was performed to evaluate ischemic damage. RESULTS: The hippocampi of ten neonates who had been treated with antenatal glucocorticoids showed a lower density of large neurons (p?=?0.01) and neurons irrespective of size (p?=?0.02) as compared to eleven neonates who had not been treated with glucocorticoids. No difference was found in density of small neurons, in myelination, gliosis, proliferation or ischemic damage. CONCLUSION: We found a significantly lower density of neurons in the hippocampus of neonates after antenatal glucocorticoid treatment. Although the pathophysiological and clinical interpretations of these findings are not clear, they are consistent with those from experiments in mice and rhesus monkeys.
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Project description:BackgroundGastro-oesophageal reflux is prevalent in preterm infants. Despite widespread use in clinical practice, there is still much controversy over the efficacy and safety of drug interventions, particularly antacid therapy.ObjectiveTo systematically review the effects of antacid therapy on preterm infants with symptoms of gastro-oesophageal reflux, and to assess the safety of these interventions.MethodsWe carried out an electronic search of the Cochrane central register of controlled trials (CENTRAL, The Cochrane Library), MEDLINE (1966-present), EMBASE (1980-present) and CINAHL (1982-present) as well as other online sources. Participants were preterm infants (<37 weeks gestation) with gastro-oesophageal reflux disease who were receiving care on a neonatal unit. We assessed the effects of histamine-2 receptor antagonists, proton pump inhibitors and alginates against placebo, primarily to see if they reduced the symptoms of reflux.ResultsSix studies were included in this review. Meta-analysis could not be carried out due to a lack of studies assessing the same intervention with the same outcomes. Omeprazole therapy significantly reduced the oesophageal acid exposure percentage time with pH<4 (p<0.01) and sodium alginate significantly decreased gastro-oesophageal reflux episodes (p=0.024). Metoclopramide and ranitidine showed a significant increase in gastro-oesophageal reflux disease symptoms versus placebo (p<0.04). No significant results were found for the use of esomeprazole or lansoprazole versus placebo.ConclusionsThere is insufficient evidence available to conclude whether antacid therapy is effective or safe when treating gastro-oesophageal reflux disease in preterm infants. Further research is needed into this topic and caution should be taken when administering antacids to preterm infants.Trial registration numberCRD42017078778.
| S-EPMC6045735 | biostudies-literature
Project description:ObjectiveHigh-flow nasal cannula (HFNC) therapy is increasingly used in preterm infants despite a paucity of physiological studies. We aimed to investigate the effects of HFNC on respiratory physiology.Study designA prospective randomised crossover study was performed enrolling clinically stable preterm infants receiving either HFNC or nasal continuous positive airway pressure (nCPAP). Infants in three current weight groups were studied: <1000 g, 1000-1500 g and >1500 g. Infants were randomised to either first receive HFNC flows 8-2 L/min and then nCPAP 6 cm H2O or nCPAP first and then HFNC flows 8-2 L/min. Nasopharyngeal end-expiratory airway pressure (pEEP), tidal volume, dead space washout by nasopharyngeal end-expiratory CO2 (pEECO2), oxygen saturation and vital signs were measured.ResultsA total of 44 preterm infants, birth weights 500-1900 g, were studied. Increasing flows from 2 to 8 L/min significantly increased pEEP (mean 2.3-6.1 cm H2O) and reduced pEECO2 (mean 2.3%-0.9%). Tidal volume and transcutaneous CO2 were unchanged. Significant differences were seen between pEEP generated in open and closed mouth states across all HFNC flows (difference 0.6-2.3 cm H2O). Infants weighing <1000 g received higher pEEP at the same HFNC flow than infants weighing >1000 g. Variability of pEEP generated at HFNC flows of 6-8 L/min was greater than nCPAP (2.4-13.5 vs 3.5-9.9 cm H2O).ConclusionsHFNC therapy produces clinically significant pEEP with large variability at higher flow rates. Highest pressures were observed in infants weighing <1000 g. Flow, weight and mouth position are all important determinants of pressures generated. Reductions in pEECO2 support HFNC's role in dead space washout.
| S-EPMC6951230 | biostudies-literature