Juliann M. DiFiore

Persistence of the biphasic ventilatory response to hypoxia in preterm infants

OBJECTIVE To characterize postnatal maturation of the biphasic ventilatory response to hypoxia in order to determine whether it persists beyond the first weeks of life in preterm infants, and the contributions of respiratory frequency and tidal volume to this response. METHODS Stable preterm infants were studied at two postnatal ages, 2 to 3 weeks (n = 12) and 4 to 8 weeks (n = 12), before hospital discharge at 35 weeks (range, 33 to 38 weeks) of postconceptional age. Infants were exposed to 5 minutes of 15% (or 13%) inspired oxygen; ventilation, oxygen saturation, end-tidal partial pressure of carbon dioxide, and heart rate were simultaneously recorded. RESULTS Minute ventilation exhibited a characteristic biphasic response to hypoxia at both postnatal ages, regardless of the development of periodic breathing. At both ages there was a transient increase in tidal volume, which peaked at 1 minute, accompanied by a sustained decrease in respiratory frequency as a result of significant prolongation of expiratory time. CONCLUSION The characteristic biphasic ventilatory response to hypoxia persists into the second month of postnatal life in preterm infants. We speculate that this finding is consistent with the prolonged vulnerability of such infants to neonatal apnea.

Cup-Feeding for Preterm Infants: Mechanics and Safety:

Cup-feedingis recommended for breastfed preterm infants to avoid artificial nipples. However, the oral mechanisms used in cup-feeding, or its safety and efficacy, have not been described. The authors measured sipping, breathing, Sa0 2,band volume of intake during15 cupfeeding sessions for 8 infants (mean gestational age at birthwas 30.6 weeks). Mean duration of sippingb ursts and pauseswas 3.6 seconds and 28.1 seconds, respectively. Mean breathingrate duringb ursts and pauses was similar (46.2 ± 24.3 vs 45.7 ± 17.7, respectively), with Sa02 = 90% duringall bursts. Mean duration of cup-feedings was 15.2 ± 3.9 minutes (range, 11.0-23.3), whereas mean volume of intake was only 4.6 ± 2.2 mL (range, 1.5-8). For the 15 sessions, 38.5% of milk taken from the cup was recovered on the bib. Although infants remain physiologically stable, cup-feeding has questionable efficacy and efficiency. Differentiating between actual intake versus spillage of milk merits attention.

Vulnerability of respiratory control in healthy preterm infants placed supine

OBJECTIVE We tested the hypothesis that healthy preterm infants have attenuated ventilatory responses to hypercapnia, associated with a decreased rib cage contribution to ventilation, in the supine versus prone position. STUDY DESIGN We elicited hypercapnic ventilatory responses from 19 healthy preterm infants (postconceptional age 35 +/- 1 weeks) who were being prepared for hospital discharge. The O2 saturation was continuously monitored. Before and during CO2 rebreathing, ventilation was measured with a nasal mask pneumotachygraph and was derived from chest wall motion as determined by respiratory inductance plethysmograph. This measuring method allowed us to compare both ventilation and the percentage rib cage contribution to ventilation between supine and prone positions. Statistical analysis employed analysis of variance with repeated measures. RESULTS The supine position was associated with a higher respiratory rate (p < 0.02) and lower O2 saturation (p < 0.007) than the prone position. The increase in ventilation in response to hypercapnia was lower in the supine than in the prone position. This was statistically significant for the respiratory inductance plethysmograph (p < 0.008) but not the pneumotachygraph (p = 0.077), and was associated with a smaller rib cage contribution to ventilation in the supine than in the prone position (p < 0.0001). CONCLUSION Respiratory control may be vulnerable when healthy preterm infants are placed supine. Widespread avoidance of the prone position may not be appropriate for such patients.

Genioglossus Response to Airway Occlusion in Apneic Versus Nonapneic Infants

ABSTRACT. The ability to maintain pharyngeal patency is compromised in infants who have apneic episodes associated with airway obstruction. Since the genioglossus (GG) muscle is thought to be important in maintaining pharyngeal patency, we measured the GG EMG with sublingual surface electrodes during unobstructed breathing and in response to end-expiratory airway occlusion. Studies were performed in nine premature infants with mixed and obstructive apnea and in eight nonapneic control infants. Phasic GG EMG was usually absent during normal tidal breathing in both groups of infants, however, GG activity typically appeared during airway occlusion. The response of the GG muscle during airway occlusion differed between control and apneic infants. During the first three occluded inspiratory efforts, control infants had 42 ± 5, 74 ± 5, and 80 ± 5% (mean ± SEM) of their occlusions associated with a GG EMG response, respectively. In contrast, apneic infants had significantly fewer (13 ± 4, 38 ± 9, and 52 ± 9%) occlusions associated with a GG EMG response. There was a delay in onset of the GG EMG when compared to the onset of the diaphragm EMG and initial negative esophageal pressure swing, but this delay decreased with each subsequent appearance of the GG EMG in both infant groups. Infants with mixed and obstructive apnea thus have decreased activation of their GG in response to occlusion which may reflect their inability to recruit dilating muscles of the upper airway during spontaneous airway obstruction.

Nasogastric tube placement: Effects on breathing and sucking in very-low-birth-weight infants

Eighteen very-low-birth-weight (VLBW) infants who met study criteria were observed during routinely scheduled feedings, twice in one day, once with a nasogastric (NG) tube and once without, in random order. Breathing and sucking measurements were compared with and without NG tube placement. During the prefeed period, minute ventilation and tidal volume were significantly lower with an NG tube than without the tube. During the continuous sucking (CS) period after commencement of oral feeding, minute ventilation, tidal volume, pulse rate, and oxygen saturation were also lower with the tube. During both CS and subsequent intermittent sucking periods, infants sucked less forcefully and took less formula with the tube. Based on these findings, if VLBW infants have an NG tube in place, clinicians are urged to monitor for breathing compromise, oxygen desaturation, and bradycardia during oral feeding.

A Comparison of Swallowing During Apnea and Periodic Breathing in Premature Infants

ABSTRACT: Periodic breathing and apnea are two forms of ventilatory instability which are commonly observed in premature infants. This study was undertaken to characterize the pattern of swallowing during apnea and compare this pattern to that present during periodic breathing. We assessed the frequency and distribution of swallows during the respiratory pauses of apnea and periodic breathing in 22 premature infants birth weight 1.2 ± 0.2 kg, postconceptional age 34 ± 2 wk. Twelve infants had apnea and 10 exhibited periodic breathing. During sleep the pharyngeal phase of swallowing was detected by a catheter in the pharynx and esophageal peristalsis by an esophageal pressure catheter. Nasal airflow was monitored by a pneumotachometer. During apnea, the frequency of swallows was significantly greater than during the respiratory pauses of periodic breathing (15.9 ± 8.2 versus 0.72 ± 0.73 swallows/min, respectively, p < 0.0001) and also much higher than the rate of spontaneous swallows during sleep in either group (0.66 ± 0.66 and 0.58 ± 1.08 swallows/min, respectively). We conclude that an increased rate of swallowing is characteristic of apnea in premature infants, and distinguishes apnea from the respiratory pauses of periodic breathing.

Increased respiratory drive as an inhibitor of oral feeding of preterm infants

This study was designed to determine whether increased respiratory drive induced by inhalation of carbon dioxide would alter the reflex and voluntary components of feeding. For 10 preterm infants (mean +/- SD: postconceptional age at study, 34 +/- 2 weeks; weight, 2.1 +/- 0.2 kg), four trials of nutritive feeding were offered: two while the infants were inhaling a gas mixture containing 40% oxygen and two while the infants were breathing 40% oxygen and 7% carbon dioxide. Nasal airflow was monitored with a pneumotachygraph. Pressure-sensitive catheters in the esophagus and in the feeding nipple were used to detect swallowing and sucking. Sucking frequency and pattern, rate of swallowing, end-tidal carbon dioxide, and minute ventilation were recorded for 30-second epochs during feeding. When the inhaled gas mixture was switched from 40% oxygen to 40% oxygen and 7% carbon dioxide, sucking frequency decreased from 53 +/- 10 to 48 +/- 12 and from 54 +/- 12 to 40 +/- 19 sucks/min, respectively (p < 0.005). Frequency of swallowing also fell during the two feeding epochs on 7% carbon dioxide, from 45 +/- 15 to 40 +/- 15 and from 43 +/- 14 to 31 +/- 16 swallows/min (p < 0.003). Thus acute hypercapnea was accompanied by a decrease in rate of both sucking and swallowing during nutritive feeding. Increased ventilatory drive may directly inhibit nutritive feeding behavior in premature infants.

Assessment of tidal volume over time in preterm infants using respiratory inductance plethysmography

Non‐invasive techniques for monitoring ventilation in infants are widely used in short‐term laboratory studies but have not been evaluated in routine clinical settings. To determine whether respiratory inductance plethysmography (RIP) can provide reproducible measurements of tidal volume (VT) in premature infants over an extended period of time, we monitored respiration in eight healthy preterm infants over 4.9 ± 1.0 hours (mean ± SD). The algebraic sum (Sum) of rib cage (RC) and abdominal (AB) motion signals (obtained by RIP) was calculated and presented over the entire recording period as percent of an initial 5 minute calibration period. VT was simultaneously measured with a nasal mask pneumotachometer with infants in prone and supine positions during active and quiet sleep. Infants were studied in the morning (am) and again in the afternoon (pm). Between these studies they were returned to the nursery wearing the RIP in a continuous record mode.

Recurrent hypoxic exposure and reflex responses during development in the piglet.

The effects of recurrent hypoxia on cardiorespiratory reflexes were characterized in anesthetized piglets at 2-10 d (n=15), 2-3 weeks (n=11) and 8-10 weeks (n=8). Responses of phrenic and hypoglossal electroneurograms (ENG(phr) and ENG (hyp)) to hypoxia (8% 0(2), bal N(2), 5 min), hypercapnia (7% CO(2) bal O(2), 5 min) and intravenous capsaicin were tested before and after recurrent exposure to 11 episodes of hypoxia (8% O(2) bal N(2), 5 min). In piglets 2-10 d, ENG(phr) response to hypoxia declined in proportion to the number of hypoxic exposures; however, ENG (hyp) response to hypoxia was unchanged. In piglets at 2-10 d, intracisternal injection of bicuculline (GABA(A) receptor antagonist) reversed effects of recurrent hypoxia on ENG(phr) hypoxic response, eliminated apnea during hypoxia, as well as the delay in appearance of ENG(phr) after hypoxia. The ENG(phr) response to 7% CO(2) inhalation also decreased after recurrent hypoxia; however, the ENG(phr) response to C-fiber stimulation by capsaicin was unaltered. Piglets at 2-3 and 8-10 weeks were resistant to the depressive effects of recurrent hypoxia on respiratory reflex responses. We conclude that the response of the anesthetized newborn piglet to recurrent hypoxia is dominated by increasing inhibition of phrenic neuroelectrical output during successive hypoxic exposures. Central GABAergic inhibition may contribute significantly to the cumulative effects of repeated hypoxia in the newborn piglet experimental model.

Genioglossus and Diaphragm Activity during Obstructive Apnea and Airway Occlusion in Infants

ABSTRACT: To document mechanisms contributing to upper airway collapse, we compared the electromyographic activity of the genioglossus (GG) and diaphragm (DIA) during spontaneous mixed and obstructive apnea and during induced end-expiratory airway occlusion in 11 premature infants. In addition to ventilation and esophageal pressure measurements, we obtained DIA and GG electromyograms (EMG) from subcostal and sublingual surface electrodes, respectively. Amplitude of the DIA EMG and the frequency of occurrence of the GG EMG were determined for:1) the breath preceding apnea or occlusion, 2) the initial and last obstructed inspiratory efforts, and 5) the first breath at resolution of both apnea and occlusion. During spontaneous apnea with airway obstruction amplitude of the DIA, EMG decreased on the initial obstructed inspiratory effort and did not exceed that of the breath preceding apnea until reestablishment of flow. In contrast, during end-expiratory airway occlusion, the amplitude of the DIA EMG increased both during and at release of occlusion. In 18 ± 6% of the spontaneous apneic episodes, GG EMG was present with the breath preceding apnea and this frequency did not increase significantly until resolution of the apnea. During induced airway occlusion, GG EMG was not present with the breath preceding occlusion but its frequency did increase to 58 ± 8 and 42 ± 8% with the last occluded inspiratory effort and the first breath after release of occlusion, respectively. The decreased presence of the GG EMG from the last occluded effort to the breath at release of occlusion (58 ± 8 versus 42 ± 8%, p<0.05) was probably due to the greater mechanoreceptormediated inhibition associated with reestablishment of flow. This study thus demonstrates markedly different respiratory muscle responses to spontaneously occurring obstructed inspiratory efforts during apnea as compared to experimentally induced airway occlusion in preterm infants.