Effect of maturation stability of infants
on the extrathoracic
SHAHNAZ DUARA, GALDINO AND EDUARDO BANCALARI Division of Neonutology, Miami, Florida 33101
SILVA
NETO,
of Pediatrics,
Department
DUARA,SHAHNAZ,GALDINOSILVANETO,NELSONCLAURE, TILT GERHARDT,ANDEDUARDOBANCALARI.E~~~&~~ maturution on the extruthoracic airway stability of infants. J. Appl. Physiol. 73(6): 2368-2372, 1992.-The influence of maturation on extrathoracic airway (ETA) stability during quiet sleepwasdetermined in 13 normal preterm infants of 1.41 t 0.14 (SD) kg birth weight and 32 t 2 wk estimated gestational age. Studies beganin the first week of life and were performed three times at weekly intervals. A drop in intraluminal pressurewithin the ETA was producedby external inspiratory flow-resistive loading (60 cmH,O l 1-l. s at 1 Urnin); an increasein intrinsic resistance, indicating airway narrowing, wassought asa measureof ETA instability. Baseline total pulmonary resistancewas not significantly different between weeksI, 2, and 3 (88 t 35,65 t24, and 61& 17cmH,O l s,respectively) but increasedmarkedly abovebaselinewith loading to 144_t 45 cmH,O 1-l s during week 1 (P < O.OOl),89 t 28 cmH,O 1-l s at week2 (P < O.Ol), and 74 t 25 cmH,O 1-l s at week 3 (n = 10). The increment with loading was significantly greater during week 1 than during weeks 2 or 3 (P -C0.02). Similar studieswere alsodonein seven full-term infants in the first week of life to evaluate the influence of gestational maturity on ETA stability. Despite a relatively greater drop in intraluminal pressurewithin the ETA of term vs. preterm infants with loading (P -c O.OOl), total pulmonary resistance failed to increase (68 t 21 to 71 k 32 cmH,O 1-l s). These data reveal that ETA instability is present in preterm infants at birth and decreaseswith increasing postnatal age. Full-term neonates, by comparison, display markedly greater ETA stability in the immediate neonatal period. l-l
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l
l
l
l
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l
l
upper airway mechanics;loading; newborn airway
PREVIOUS STUDIES have shown that preterm
infants develop multiple episodes of apnea, and the frequency of these events is inversely related to gestational age (6). Also, the same study showed that the number of days that the apneic episodes persisted were inversely related to gestational age, with the majority of infants resolving their apnea by 40 wk of postconceptional age. Our previous work has shown that inspiratory flow-resistive loading may be utilized to decrease the intraluminal pressure within the extrathoracic airway (ETA) of preterm infants and result in local narrowing, which is demonstrable by an increase in intrinsic resistance (4). Although the ETA extends from the nares to the thoracic inlet and includes multiple potential sites for narrowing, the most common site in preterm infants is the orophar2368
0161-7567192
$2.00 Copyright
NELSON University
airway
CLAURE,
TILO
of Miami School
GERHARDT,
of Medicine,
ynx (8). In an earlier study of preterm infants, studied at postnatal ages that ranged from 3 to 4 wk, it was found that the ETA was relatively stable in the presence of small changes in intraluminal pressure, whereas significantly larger changes produced airway narrowing (5). Because upper airway obstruction has been found to occur in many apneic episodes (14), we hypothesized that ETA instability would be elicitable in preterm infants shortly after birth and that this propensity would decrease with advancing postnatal age. We further hypothesized that full-term infants would display ETA stability shortly after birth. At the present time, it is not known whether the ETA stability of neonates increases in relation to maturational events. If the partial stability of the ETA in the preterm infants evaluated in our previous study (4) reflected a transitional phase in the development of mechanical stability within this region, it may be possible to demonstrate changes in ETA stability with increasing postnatal age in the preterm infants and to detect differences between the ETA stability of less mature preterm and more mature full-term infants. The purpose of this study was to determine the role of postnatal maturation on ETA stability in the preterm infant and to compare the findings with those obtained in full-term infants. MATERIAL AND METHODS
Thirteen preterm infants were studied after informed parental consent was obtained in accordance with the Guidelines for Human Research at the University of Miami School of Medicine. All infants were healthy at the time of study, and none of the infants had apnea or was receiving methylxanthines at the time of study. The pret%erm infants weighed 1.41 t 0.14 (SD) kg at birth. Their gestational age was 32 t 2 wk, and their postnatal age was 5 t 2 days when first studied. Repeat studies were performed at weekly intervals, with the postnatal age averaging 13 t 3 days at the second study and 20 t 2 days at the third study. A separate group of seven fullterm infants, who weighed 3.7 t 0.4 kg and were 2.3 t 1.1 days of age at study, were evaluated once in the first week after birth. Infants were evaluated in the neonatal pulmonary laboratory. Gas flow was measured by a Fleisch no. 00 pneumotachograph with a resistance of 2.3 cmH,O l a s, which was attached to nasal prongs (Novametrix, Wal-
0 1992 the American
Physiological
Society
Downloaded from www.physiology.org/journal/jappl at Karolinska Institutet University Library (130.237.122.245) on February 12, 2019.
POSTNATAL
03
0.5
1.0
FIG.
Pressure-flow
1.
1.5 FLOW I/min
a-@L, characteristics
of 2
MATURATION
2.0 o-OL2
2.5
resistors used in preterm
and term infants (L, and L, , respectively).
lingford, CT) that had a resistance of 5 cmH,O 1-l s at 2 l/min gas flow, and dead space was 0.3 ml. Differential pressure from the pneumotachograph was measured by a pressure transducer (model MP45-14, Validyne, Northridge, CA), and the signal was linear up to a flow rate of 6 l/min. The flow signal from the pneumotachograph was electronically integrated to determine tidal volume. Esophageal pressure was measured by a fluidfilled 8-Fr catheter positioned in the lower one-third of the esophagus and attached to a Gould PM23 pressure transducer. Satisfactory placement of the fluid-filled esophageal tube and validity of its signal were verified by an airway occlusion maneuver dune before each study (1). Infants were studied in the supine position, with the head turned to the right side. Head position was maintained by a sandbag behind the infant’s back and a support roll under the chin. Proximal airway pressure was measured at a side port in the nasal prongs using a Gould PM23 press ure transducer and was used a.s an overall indicator of intraluminal pressu re changes, since negative pressure is likely to be greater distal to downstream sites of narrowing within the ETA. All signals were recorded on a Gould eight-channel recorder. Petroleum jelly was used at the nasal junction to prevent air leak. Inadvertent air leak was recognized by the onset of drift in the volume signal, and those portions of the tracing were excluded from calculations. In addition, the investigator applying the nosepiece held the infant’s lips gently apposed during the study. A low-magnitude resistor (60 cmH,O 1-l. s at 1 l/mini L,) was used in all three studies in the preterm infants, and its pressure-flow characteristics are displayed in Fig. 1. The load was applied to the inspiratory limb of a low dead space nonrebreathing valve (internal dead space 1.45 ml, Hans Rudolph, Kansas City, MO), which was then connected to the pneumotachograph. Short-term loading was performed and usually did not exceed 20 consecutively loaded breaths. The full-term infants were studied under similar laboratory conditions. The only difference from the protocol employed for the preterm infants was that larger custorn-made nasal prongs (dead space 1 ml) were used and the inspiratory flow-resistive load was of a greater magnitude (125 cmH,O +1-l. s at 1 Umin; L, in Fig. 1) to prol
l
l
2369
OF ETA IN NEWBORNS
duce a greater drop in intraluminal pressure within the ETA. The transmural pressure changes caused by a load of this size had previously resulted in ETA narrowing in preterm infants during studies of airway stability (5). Studies were performed during quiet sleep, using Prechtl’s (12) criteria. Runs complicated by arousal or by recognizable changes in sleep state were repeated later in the same day or on the following day. For quiet sleep to be diagnosed, the infants were required to breathe regularly, with no eye movements, facial movements, or limb jerking other than occasional startles. Total pulmonary resistance was calculated by the method of Mead and Whittenberger (9) as the ratio of the difference in transpulmonary pressure measured between the points of half tidal volume in inspiration and expiration and related to the sum of inspiratory and expiratory flows at the same points. An average of 10 contiguous breaths of similar tidal volume were analyzed. Transpulmonary pressure was measured as the difference between the esophageal pressure and proximal airway pressure. Esophageal pressure values were measured from peak-to-peak changes. Statistical analysis was performed by a one-factor repeated measures analysis of variance (ANOVA) for the comparison between the three baseline values in the preterm infants and the percent change in resistance with loading between weeks and by a two-factor (baby and week) repeated model ANOVA for comparison of the increase in resistance with loading in the separate studies done in preterm infants. A paired t test determined significance between increased resistance with loading and baseline values at each study, and an unpaired t test was used for comparison of esophageal and mouth pressures between the term and preterm infants. Correlation analysis was used to determine whether the percent change in resistance with loading at each study was related to birth weight, gestational age, postnatal age, or the study weight. Post hoc determination of significance for the difference between the means by ANOVA was done by the Duncan’s multiple range test. Significance was accepted at co.05 level (13). RESULTS
All infants tolerated the study protocol. Three preterm infants were not evaluated on the third occasion because of the onset of intercurrent illnesses, which prevented timely evaluations. The preterm infants gained weight steadily throughout the study period, increasing from 1.33 t 0.18 kg at the first study, to 1.43 t 0.20 kg at the second study, and to 1.62 t 0.16 kg at the third study (P < 0.01, zueeK 1 vs. 2 and uleeh 2 vs. 3). In this group of infants, the baseline value of total pulmonary resistance increased significantly with loading at zueek 1 (88 t 35 to 144 t 45 cmH,O 1-l s, P < 0.001) and week 2 (65 t 24 to 89 t 28 cmH,O 1-l s, P < 0.01) but failed to do so at zueek 3 (61 t 17 to 74 t 25 cmH,O 1-l s). Although the baseline resistances appeared to decline over time, this difference was not significant. The absolute increment in total pulmonary resistance with loading at uleek 1 was 56 t 31 cmH,O 1-l s, which l
l
l
l
l
l
l
l
Downloaded from www.physiology.org/journal/jappl at Karolinska Institutet University Library (130.237.122.245) on February 12, 2019.
2370
POSTNATAL
4
OF ETA IN NEWBORNS
was demonstrable between the least mature (28-30 wk) and the most mature (40-41 wk) groups of infants (P
on the extrathoracic
SHAHNAZ DUARA, GALDINO AND EDUARDO BANCALARI Division of Neonutology, Miami, Florida 33101
SILVA
NETO,
of Pediatrics,
Department
DUARA,SHAHNAZ,GALDINOSILVANETO,NELSONCLAURE, TILT GERHARDT,ANDEDUARDOBANCALARI.E~~~&~~ maturution on the extruthoracic airway stability of infants. J. Appl. Physiol. 73(6): 2368-2372, 1992.-The influence of maturation on extrathoracic airway (ETA) stability during quiet sleepwasdetermined in 13 normal preterm infants of 1.41 t 0.14 (SD) kg birth weight and 32 t 2 wk estimated gestational age. Studies beganin the first week of life and were performed three times at weekly intervals. A drop in intraluminal pressurewithin the ETA was producedby external inspiratory flow-resistive loading (60 cmH,O l 1-l. s at 1 Urnin); an increasein intrinsic resistance, indicating airway narrowing, wassought asa measureof ETA instability. Baseline total pulmonary resistancewas not significantly different between weeksI, 2, and 3 (88 t 35,65 t24, and 61& 17cmH,O l s,respectively) but increasedmarkedly abovebaselinewith loading to 144_t 45 cmH,O 1-l s during week 1 (P < O.OOl),89 t 28 cmH,O 1-l s at week2 (P < O.Ol), and 74 t 25 cmH,O 1-l s at week 3 (n = 10). The increment with loading was significantly greater during week 1 than during weeks 2 or 3 (P -C0.02). Similar studieswere alsodonein seven full-term infants in the first week of life to evaluate the influence of gestational maturity on ETA stability. Despite a relatively greater drop in intraluminal pressurewithin the ETA of term vs. preterm infants with loading (P -c O.OOl), total pulmonary resistance failed to increase (68 t 21 to 71 k 32 cmH,O 1-l s). These data reveal that ETA instability is present in preterm infants at birth and decreaseswith increasing postnatal age. Full-term neonates, by comparison, display markedly greater ETA stability in the immediate neonatal period. l-l
l
l
l
l
l
l
l
l
l
upper airway mechanics;loading; newborn airway
PREVIOUS STUDIES have shown that preterm
infants develop multiple episodes of apnea, and the frequency of these events is inversely related to gestational age (6). Also, the same study showed that the number of days that the apneic episodes persisted were inversely related to gestational age, with the majority of infants resolving their apnea by 40 wk of postconceptional age. Our previous work has shown that inspiratory flow-resistive loading may be utilized to decrease the intraluminal pressure within the extrathoracic airway (ETA) of preterm infants and result in local narrowing, which is demonstrable by an increase in intrinsic resistance (4). Although the ETA extends from the nares to the thoracic inlet and includes multiple potential sites for narrowing, the most common site in preterm infants is the orophar2368
0161-7567192
$2.00 Copyright
NELSON University
airway
CLAURE,
TILO
of Miami School
GERHARDT,
of Medicine,
ynx (8). In an earlier study of preterm infants, studied at postnatal ages that ranged from 3 to 4 wk, it was found that the ETA was relatively stable in the presence of small changes in intraluminal pressure, whereas significantly larger changes produced airway narrowing (5). Because upper airway obstruction has been found to occur in many apneic episodes (14), we hypothesized that ETA instability would be elicitable in preterm infants shortly after birth and that this propensity would decrease with advancing postnatal age. We further hypothesized that full-term infants would display ETA stability shortly after birth. At the present time, it is not known whether the ETA stability of neonates increases in relation to maturational events. If the partial stability of the ETA in the preterm infants evaluated in our previous study (4) reflected a transitional phase in the development of mechanical stability within this region, it may be possible to demonstrate changes in ETA stability with increasing postnatal age in the preterm infants and to detect differences between the ETA stability of less mature preterm and more mature full-term infants. The purpose of this study was to determine the role of postnatal maturation on ETA stability in the preterm infant and to compare the findings with those obtained in full-term infants. MATERIAL AND METHODS
Thirteen preterm infants were studied after informed parental consent was obtained in accordance with the Guidelines for Human Research at the University of Miami School of Medicine. All infants were healthy at the time of study, and none of the infants had apnea or was receiving methylxanthines at the time of study. The pret%erm infants weighed 1.41 t 0.14 (SD) kg at birth. Their gestational age was 32 t 2 wk, and their postnatal age was 5 t 2 days when first studied. Repeat studies were performed at weekly intervals, with the postnatal age averaging 13 t 3 days at the second study and 20 t 2 days at the third study. A separate group of seven fullterm infants, who weighed 3.7 t 0.4 kg and were 2.3 t 1.1 days of age at study, were evaluated once in the first week after birth. Infants were evaluated in the neonatal pulmonary laboratory. Gas flow was measured by a Fleisch no. 00 pneumotachograph with a resistance of 2.3 cmH,O l a s, which was attached to nasal prongs (Novametrix, Wal-
0 1992 the American
Physiological
Society
Downloaded from www.physiology.org/journal/jappl at Karolinska Institutet University Library (130.237.122.245) on February 12, 2019.
POSTNATAL
03
0.5
1.0
FIG.
Pressure-flow
1.
1.5 FLOW I/min
a-@L, characteristics
of 2
MATURATION
2.0 o-OL2
2.5
resistors used in preterm
and term infants (L, and L, , respectively).
lingford, CT) that had a resistance of 5 cmH,O 1-l s at 2 l/min gas flow, and dead space was 0.3 ml. Differential pressure from the pneumotachograph was measured by a pressure transducer (model MP45-14, Validyne, Northridge, CA), and the signal was linear up to a flow rate of 6 l/min. The flow signal from the pneumotachograph was electronically integrated to determine tidal volume. Esophageal pressure was measured by a fluidfilled 8-Fr catheter positioned in the lower one-third of the esophagus and attached to a Gould PM23 pressure transducer. Satisfactory placement of the fluid-filled esophageal tube and validity of its signal were verified by an airway occlusion maneuver dune before each study (1). Infants were studied in the supine position, with the head turned to the right side. Head position was maintained by a sandbag behind the infant’s back and a support roll under the chin. Proximal airway pressure was measured at a side port in the nasal prongs using a Gould PM23 press ure transducer and was used a.s an overall indicator of intraluminal pressu re changes, since negative pressure is likely to be greater distal to downstream sites of narrowing within the ETA. All signals were recorded on a Gould eight-channel recorder. Petroleum jelly was used at the nasal junction to prevent air leak. Inadvertent air leak was recognized by the onset of drift in the volume signal, and those portions of the tracing were excluded from calculations. In addition, the investigator applying the nosepiece held the infant’s lips gently apposed during the study. A low-magnitude resistor (60 cmH,O 1-l. s at 1 l/mini L,) was used in all three studies in the preterm infants, and its pressure-flow characteristics are displayed in Fig. 1. The load was applied to the inspiratory limb of a low dead space nonrebreathing valve (internal dead space 1.45 ml, Hans Rudolph, Kansas City, MO), which was then connected to the pneumotachograph. Short-term loading was performed and usually did not exceed 20 consecutively loaded breaths. The full-term infants were studied under similar laboratory conditions. The only difference from the protocol employed for the preterm infants was that larger custorn-made nasal prongs (dead space 1 ml) were used and the inspiratory flow-resistive load was of a greater magnitude (125 cmH,O +1-l. s at 1 Umin; L, in Fig. 1) to prol
l
l
2369
OF ETA IN NEWBORNS
duce a greater drop in intraluminal pressure within the ETA. The transmural pressure changes caused by a load of this size had previously resulted in ETA narrowing in preterm infants during studies of airway stability (5). Studies were performed during quiet sleep, using Prechtl’s (12) criteria. Runs complicated by arousal or by recognizable changes in sleep state were repeated later in the same day or on the following day. For quiet sleep to be diagnosed, the infants were required to breathe regularly, with no eye movements, facial movements, or limb jerking other than occasional startles. Total pulmonary resistance was calculated by the method of Mead and Whittenberger (9) as the ratio of the difference in transpulmonary pressure measured between the points of half tidal volume in inspiration and expiration and related to the sum of inspiratory and expiratory flows at the same points. An average of 10 contiguous breaths of similar tidal volume were analyzed. Transpulmonary pressure was measured as the difference between the esophageal pressure and proximal airway pressure. Esophageal pressure values were measured from peak-to-peak changes. Statistical analysis was performed by a one-factor repeated measures analysis of variance (ANOVA) for the comparison between the three baseline values in the preterm infants and the percent change in resistance with loading between weeks and by a two-factor (baby and week) repeated model ANOVA for comparison of the increase in resistance with loading in the separate studies done in preterm infants. A paired t test determined significance between increased resistance with loading and baseline values at each study, and an unpaired t test was used for comparison of esophageal and mouth pressures between the term and preterm infants. Correlation analysis was used to determine whether the percent change in resistance with loading at each study was related to birth weight, gestational age, postnatal age, or the study weight. Post hoc determination of significance for the difference between the means by ANOVA was done by the Duncan’s multiple range test. Significance was accepted at co.05 level (13). RESULTS
All infants tolerated the study protocol. Three preterm infants were not evaluated on the third occasion because of the onset of intercurrent illnesses, which prevented timely evaluations. The preterm infants gained weight steadily throughout the study period, increasing from 1.33 t 0.18 kg at the first study, to 1.43 t 0.20 kg at the second study, and to 1.62 t 0.16 kg at the third study (P < 0.01, zueeK 1 vs. 2 and uleeh 2 vs. 3). In this group of infants, the baseline value of total pulmonary resistance increased significantly with loading at zueek 1 (88 t 35 to 144 t 45 cmH,O 1-l s, P < 0.001) and week 2 (65 t 24 to 89 t 28 cmH,O 1-l s, P < 0.01) but failed to do so at zueek 3 (61 t 17 to 74 t 25 cmH,O 1-l s). Although the baseline resistances appeared to decline over time, this difference was not significant. The absolute increment in total pulmonary resistance with loading at uleek 1 was 56 t 31 cmH,O 1-l s, which l
l
l
l
l
l
l
l
Downloaded from www.physiology.org/journal/jappl at Karolinska Institutet University Library (130.237.122.245) on February 12, 2019.
2370
POSTNATAL
4
OF ETA IN NEWBORNS
was demonstrable between the least mature (28-30 wk) and the most mature (40-41 wk) groups of infants (P
