Physiologic effects of doxapram in idiopathic apnea of prematurity

Barrington, Keith J.; Finer, Neil N.; Peters, Kathrine L.; Barton, Joanne

doi:10.1016/s0022-3476(86)80786-7

Cited by 72 publications

(60 citation statements)

References 25 publications

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“…In addition, 130 studies were excluded for the reasons mentioned in figure 1. This left 32 studies for the final analyses, 4 RCTs [13,14,15,16], 1 prospective crossover study [17], 2 case-control studies [18,19], and 25 cohort, case series or case reports studies [20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44]. Four studies were only available in abstract form [19,23,24,38].…”

Section: Resultsmentioning

confidence: 99%

Doxapram Treatment for Apnea of Prematurity: A Systematic Review

et al. 2016

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Background: Apnea of prematurity (AOP) is a common complication of preterm birth, for which caffeine is the first treatment of choice. In case of persistent AOP, doxapram has been advocated as an additional therapy. Objective: To identify and appraise all existing evidence regarding efficacy and safety of doxapram use for AOP in infants born before 34 weeks of gestational age. Methods: All studies reporting on doxapram use for AOP were identified by searching electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research. Two reviewers independently assessed study eligibility and quality, and extracted data on study design, patient characteristics, efficacy and safety outcomes. Results: The randomized controlled trials showed less apnea during doxapram treatment when compared to placebo, but no difference in treatment effect when compared to theophylline. No serious adverse effects were reported. We identified 28 observational studies consisting mainly of cohort studies and case series (n = 1,994). There was considerable heterogeneity in study design and quality. Most studies reported a positive effect of doxapram on apnea rate. A few studies reported on long-term outcomes with conflicting results. A range of possible doxapram-related short-term adverse effects were reported, sometimes associated with the use of higher doses. Conclusion: Based on the limited number of studies and level of evidence, no firm conclusions on the efficacy and safety of doxapram in preterm infants can be drawn. For this reason, routine use cannot be recommended. A large multicenter randomized controlled trial is urgently needed to provide more conclusive evidence.

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Section: Resultsmentioning

confidence: 99%

Doxapram Treatment for Apnea of Prematurity: A Systematic Review

et al. 2016

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“…After obtaining consent, airway occlusions were performed as previously described (5). A face mask was applied and the absence of leaks was confirmed.…”

Section: Methodsmentioning

confidence: 99%

The Natural History of the Appearance of Apnea of Prematurity

Barrington

Finer

1991

Pediatr Res

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ABSTRACT. Twenty healthy preterm infants of less than 34 wk gestation were studied with continuous recordings, commencing within 8 h of birth, for up to 1 wk of age to determine the usual time course of the appearance of apnea and to classify apnea types. Airway occlusion studies were also performed on a regular basis to determine whether apneic spells were preceded or followed by a reduction in central respiratory drive. Apneic spells of greater than 15 s duration accompanied by hypoxia or bradycardia occurred in all infants before 24 h of age. The frequency of apneic spells was highest in the first 24 h after birth with a mean frequency of 0.9/h and gradually reduced thereafter, falling to 0.2/h by 5 d of age ( p < 0.01). Apneic spells were more likely to be obstructive in the first 2 d of life than thereafter ( p < 0.05). Central apnea was proportionately significantly less frequent during this time period. Reduced respiratory drive, as demonstrated by airway occlusion pressures, was associated with more frequent apnea and was evident at the first occlusion study, which frequently preceded the first significant apnea. (Pediatr Res 29: 372-375,1991) Abbreviations SpOz, pulse oximeter-derived saturation Po.,, airway pressure 0.1 s after initiation of first occluded breath ANOVA, analysis of variance It is commonly stated that idiopathic apnea of prematurity develous after the first 24 to 72 h of life and amea that is noted early requires vigorous investigation (1). The factual basis of this statement is uncertain. Henderson-Smart (2) previously demonstrated that apnea (more than three spells of greater than 20 s duration) developed on the 1st or 2nd postnatal d in 77% of preterm infants. He appears to have used impedance monitoring only and it is uncertain whether any recordings were made for independent confirmation of apnea (3). Carlo et al. (4), utilizing 60-min recordings, showed that apneic spells of greater than 5 s duration occurred on d 1 in eight of 10 preterm infants without lung disease.There appears to be no published information regarding the usual frequency and nature of significant apneic spells in an unselected population of healthy newborn preterm infants who have undergone prolonged recordings.Our main objective was to ascertain the usual age of the appearance of apneic spells and the relative frequency of obstructive, mixed, and central apnea during the 1 st wk of life in preterm infants without respiratory disease. Our secondary objective was to describe the development of respiratory drive, by determining the postnatal progression of occlusion pressures, in infants with and without apnea. SUBJECTS AND METHODSTwenty infants of less than 34 wk gestation with birth weights above the 5th percentile for gestational age were studied. Infants were all born in the Royal Alexandra Hospitals and were entered into the study as soon after birth as possible. We entered consecutive infants who were clinically determined to be free of acute medical problems; in particular, they were without significan...

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“…In these smaller doses doxapram increases tidal volume and minute ventilation in the newborn. 86 These effects are mediated through stimulation of peripheral chemoreceptors because denervation of peripheral chemoreceptors eliminated the increase in ventilation by doxapram at doses <6 mg kg -1 (Mitchell and Herbert 87 ). Several studies have shown the effectiveness of doxapram in reducing apnea refractory to methylxanthines.…”

Section: Doxapram and Peripheral Chemoreceptorsmentioning

confidence: 99%

“…Several studies have shown the effectiveness of doxapram in reducing apnea refractory to methylxanthines. 86,88 In a blinded, placebo-controlled trial Peliowski et al 89 found no significant difference between theophylline and doxapram. As a result of its poor absorption, it is typically used as a continuous intravenous infusion.…”

Section: Doxapram and Peripheral Chemoreceptorsmentioning

confidence: 99%

Apnea of prematurity: pathogenesis and management strategies

Mathew

2010

J Perinatol

105

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Apnea of prematurity (AOP) is a significant clinical problem manifested by an unstable respiratory rhythm reflecting the immaturity of respiratory control systems. This review will address the pathogenesis of and treatment strategies for AOP. Although the neuronal mechanisms leading to apnea are still not well understood, recent decades have provided better insight into the generation of the respiratory rhythm and its modulation in the neonate. Ventilatory responses to hypoxia and hypercarbia are impaired and inhibitory reflexes are exaggerated in the neonate. These unique vulnerabilities predispose the neonate to the development of apnea. Treatment strategies attempt to stabilize the respiratory rhythm. Caffeine remains the primary pharmacological treatment modality and is presumed to work through blockade of adenosine receptors A 1 and A 2 . Recent evidences suggest that A 2A receptors may have a greater role than previously thought. AOP typically resolves with maturation suggesting increased myelination of the brainstem.

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Physiologic effects of doxapram in idiopathic apnea of prematurity

Cited by 72 publications

References 25 publications

Doxapram Treatment for Apnea of Prematurity: A Systematic Review

Doxapram Treatment for Apnea of Prematurity: A Systematic Review

The Natural History of the Appearance of Apnea of Prematurity

Apnea of prematurity: pathogenesis and management strategies

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