Effects of a divided high loading dose of caffeine on circulatory variables in preterm infants

Hoecker, Christina; Nelle, Mathias; Beedgen, B.; Rengelshausen, Jens; Linderkamp, Otwin

doi:10.1136/adc.2005.073866

Cited by 34 publications

(36 citation statements)

References 34 publications

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“…Hoecker et al 4,6 examined the effect of caffeine loading in two regimens in two groups of 16 infants and showed no change in left ventricular CO (LVCO), HR or BP when measured 1 and 2 h after in one regimen and 1, 2 and 20 h later in the second regimen. Walther et al 5 showed an increase in LVCO and HR in 11 infants treated with aminophylline, however postaminophylline determinations were made 4 h after maintenance dose.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] However, caffeine has other physiologic effects, including stimulating the central nervous and cardiovascular system, 4 enhancing catecholamine secretion, 4 and increasing basal metabolic rate. 4 At the pharmacologic level, caffeine acts by blocking adenosine receptors A1 and A2a, increasing cyclic 3, 5 adenosine monophosphate by inhibiting phosphodiesterase, and translocating intracellular calcium. 5 At least plausibly, some of these pharmacologic actions might interact with regulation of systemic hemodynamics.…”

Section: Introductionmentioning

confidence: 99%

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Acute hemodynamic effects of caffeine administration in premature infants

et al. 2008

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Objective: Administration of caffeine citrate (caffeine) has been a central component of the treatment of apnea of prematurity. However, given its multiple pharmacologic effects, caffeine might be expected to produce hemodynamic changes in heart rate, stroke volume, cardiac output and vascular resistance.Study Design: In this prospective observational study, we report the hemodynamic effects of intravenous caffeine administration in a population of premature infants who received caffeine to correct or prevent apnea of prematurity.Methods: Hemodynamic effects of caffeine were determined in 31 infants. Stroke volume was measured via echocardiogram, using velocity time integral at the aortic root diameter. Statistically univariate analyses were performed parametrically using paired t-test and nonparametrically (sign test). Multivariate linear regression models were used to identify subgroup covariate effects.Results: After intravenous caffeine, cardiac index increased in 31 of 31 trials, by an average of 14.6 ± 16.3% (s.d.); stroke volume increased in 24 of 31 trials, by 7.8±12.2%; heart rate increased in 28 of 31 trials by 7.7 ± 7.2 beats per min; and blood pressure increased in 25 of 31 trials, by 4.1±5.8 mm Hg (all P<0.001). Multivariate linear regression revealed no significant effect of dose, birth weight, gestational age or postnatal age.Conclusions: Intravenous caffeine consistently increases cardiac output and blood pressure in relatively stable premature infants, when given to treat or prevent apnea of prematurity. We speculate that there may be a role for caffeine in the hemodynamic treatment of hypotensive/ hypoperfused infants.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acute hemodynamic effects of caffeine administration in premature infants

et al. 2008

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“…Furthermore, Hoecker et al (27) reported an increase in arterial pressure in preterm infants, 1 and 20 h after day 2 of caffeine administration, and an increase in heart rate 20 h after day 2 of caffeine exposure. However, these increases were compared with measurements taken just prior to caffeine administration and not to a control group.…”

Section: C)mentioning

confidence: 99%

Impact of daily high-dose caffeine exposure on developing white matter of the immature ovine brain

et al. 2014

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Background: Caffeine is widely used to treat apnea of prematurity, but the standard dosing regimen is not always sufficient to prevent apnea. Before higher doses of caffeine can be used, their effects on the immature brain need to be carefully evaluated. Our aim was to determine the impact of daily highdose caffeine administration on the developing white matter of the immature ovine brain. Methods: High-dose caffeine (25 mg/kg caffeine base loading dose; 20 mg/kg daily maintenance dose; n = 9) or saline (n = 8) were administered to pregnant sheep from 0.7 to 0.8 of term, equivalent to approximately 27-34 wk in humans. At 0.8 of term, the white and gray matter were assessed histologically and immunohistochemically. results: Daily caffeine administration led to peak caffeine concentration of 32 mg/l in fetal plasma at 1 h, followed by a gradual decline, with no effects on mean arterial pressure and heart rate. Initial caffeine exposure led to transient, mild alkalosis in the fetus but did not alter oxygenation. At necropsy, there was no effect of daily high-dose caffeine on brain weight, oligodendrocyte density, myelination, axonal integrity, microgliosis, astrogliosis, apoptosis, or neuronal density. conclusion: Daily high-dose caffeine administration does not appear to adversely affect the developing white matter at the microstructural level.

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“…The decrease in blood flow velocity in cerebral and intestinal arteries following a high caffeine loading dose has been attributed to vasoconstriction, which may increase the risk of periventricular leukomalacia, hemorrhage, and necrotizing enterocolitis [38]. Owing to concern over the risk of cerebral and intestinal ischemia, Hoecker et al [40] investigated the use of a divided loading dose of two 25 mg/kg caffeine citrate doses separated by 4 h, and reported a decrease in cerebral blood flow velocity following the second dose, although blood flow velocity in intestinal arteries and left ventricular output were unaffected. It is well appreciated that high loading doses are more effective in the treatment of neonatal apnea, although further research is needed to develop an optimal loading-dose regimen.…”

Section: Resultsmentioning

confidence: 99%

Use of Methylxanthine Therapies for the Treatment and Prevention of Apnea of Prematurity

et al. 2014

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Apnea of prematurity (AOP) is a common complication of preterm birth, which affects more than 80 % of neonates with a birth weight less than 1,000 g. Methylxanthine therapies, including caffeine and theophylline, are a mainstay in the treatment and prevention of AOP. Despite their frequent use, little is known about the long-term safety and efficacy of these medications. In this review, we systematically evaluated the literature on neonatal methylxanthine therapies and found that caffeine is associated with fewer adverse effects and a wider therapeutic window when compared with theophylline. When used as a therapeutic agent, larger doses of caffeine citrate have been shown to improve acute neonatal outcomes when administered promptly, although further studies are needed to assess the long-term neurological consequences associated with the use of large loading doses. In a secondary analysis of data obtained from a randomized controlled trial, the prophylactic use of caffeine was associated with substantial cost savings and improved clinical outcomes. However, there remains a paucity of well-controlled, randomized clinical trials that have examined the use of caffeine as a prophylactic agent, and further prospective trials are needed to determine if caffeine is a safe and effective prophylactic agent. Additionally, measuring plasma concentrations longitudinally as a marker of therapeutic efficacy and/or toxicity has not been shown to be clinically useful in neonates who are responsive to treatment and exhibit no signs or symptoms of toxicity. However, in cases where toxicity is of concern or for neonates with congenital or pathophysiologic process that may alter the pharmacokinetics of these drugs, therapeutic drug monitoring may be warranted to monitor for methylxanthine toxicity.

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Effects of a divided high loading dose of caffeine on circulatory variables in preterm infants

Cited by 34 publications

References 34 publications

Acute hemodynamic effects of caffeine administration in premature infants

Acute hemodynamic effects of caffeine administration in premature infants

Impact of daily high-dose caffeine exposure on developing white matter of the immature ovine brain

Use of Methylxanthine Therapies for the Treatment and Prevention of Apnea of Prematurity

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