Clinical and Physiological Responses to Prolonged Nasogastric Administration of Doxapram for Apnea of Prematurity

Abstract

We hypothesized that enteral doxapram would effectively treat apnea of prematurity without the appearance of major side effects. Of 16 infants, 10 (BW 1,520 ± 102 g) received doxapram alone and 6 (BW 1,020 ± 35 g) received doxapram plus theophylline. Apneas decreased from 16.7 ± 1.9 to 2.1 ± 0.6 in infants receiving doxapram alone, and from 38.2 ± 4.4 to 7.9 ± 2.2 apneas/24 h in those receiving doxapram plus theophylline. This was associated with an increase in alveolar ventilation, a shift of the ventilatory response to CO₂ to the left, and no change in the immediate ventilatory response to 100% oxygen. Side effects included premature teeth buds corresponding to the lower central incisors, prevalence of occult blood in stool and necrotizing enterocolitis. The findings suggest that doxapram effectively controls apnea when given enterally, but should be used cautiously because of potentially harmful side effects.

Long-Term Neurodevelopmental Outcome after Doxapram for Apnea of Prematurity

“…Many clinicians are reluctant to use doxapram in preterm infants because of possible gastrointestinal side effects [7,8]. In line with previous reports, we did not observe more cases of NEC or spontaneous intestinal perforation in the doxapram group [5,9].…”

“…Doxapram has also been associated with short-term adverse effects, such as hypertension, QT interval prolongation and gastrointestinal disturbances [6,7,8,9,10]. Furthermore, a case-control study in preterm patients with isolated mental developmental delay [11] and a follow-up (telephone interviews) study [12] reported a possible association between doxapram treatment and long-term neurodevelopmental delay (ND).…”

Doxapram Treatment for Apnea of Prematurity: A Systematic Review

“…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].…”

“…Sixteen case series were included, reporting a total of 324 preterm infants treated with doxapram (table 1) [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]. One study was a pilot study described in a letter to the editor [29], and one study was only available in abstract form [38].…”

“…All studies reporting on apnea frequency showed a significant reduction after starting doxapram therapy [27,28,29,30,31,34,37,39,41,42]. Four of the 9 studies reporting on blood pressure showed hypertension in patients treated with a doxapram dose exceeding 1.5 mg·kg -1 ·h -1 (table 1) [30,31,32,42].…”