PEDIATRICS Vol. 122 No. 5 November 2008, pp. e1086-e1090 (doi:10.1542/peds.2008-1193)
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ARTICLE |
Hemodynamic Changes During Weaning From Nasal Continuous Positive Airway Pressure
a Neonatal Care Unit
b Pediatric Cardiology Unit, Mansoura University Children's Hospital, Egypt
c Department of Neonatology, The George Washington University and the Children's National Medical Center, Washington, DC
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ABSTRACT |
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 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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BACKGROUND. Nasal continuous positive airway pressure is frequently used to support preterm infants with respiratory distress syndrome. Little is known about the hemodynamic changes that occur, particularly during the weaning phase when lung compliance has improved and most of the airway pressure can be transmitted to the heart and major blood vessels.
METHODS. We conducted a prospective study on preterm infants (gestational age 
32 weeks) with resolving respiratory distress syndrome, who were receiving nasal continuous positive airway pressure of 5 cm H2O and 21% oxygen. While cycling nasal continuous positive airway pressure, we performed 2-dimensional M-mode and pulsed Doppler echocardiography on all infants during nasal continuous positive airway pressure and 1 hour after being off nasal continuous positive airway pressure.
RESULTS. A total of 25 preterm infant were studied. The use of nasal continuous positive airway pressure significantly decreased right ventricular output (320 ± 22.7 vs 410.5 ± 44.1 mL/kg per min); right ventricular end diastolic diameter (6 ± 0.7 vs 6.4 ± 0.4 mm), left ventricular end diastolic diameter (11.6 ± 0.9 vs 13.6 ± 0.7 mm), left ventricular end systolic diameter (7.1 ± 0.6 vs 8.3 ± 0.4 mm), left atrial diameter (6.3 ± 0.5 vs 8 ± 0.5 mm), aortic root diameter (6.4 ± 0.3 vs 6.6 ± 0.4 mm), superior vena cava flow (70.2 ± 8.5 vs 91.1 ± 4 mL/kg per minute), and pulmonary maximum velocity (0.6 ± 0.1 vs 0.7 ± 0.1 m/seconds). It significantly increased mean inferior vena cava diameter (4.3 ± 0.5 vs 3.5 ± 0.6 mm), whereas nasal continuous positive airway pressure did not influence left ventricular output, aortic maximum velocity, fractional shortening, heart rate, or mean arterial blood pressure. Changes associated with nasal continuous positive airway pressure were similar in infants with (n = 8) and without (n = 17) patent ductus arteriosus.
CONCLUSIONS. In infants with resolving respiratory distress syndrome, nasal continuous positive airway pressure can impede systemic and pulmonary venous return, but it does not compromise systemic arterial pressure or heart rate. It is not clear whether the degree of these hemodynamic changes can affect the success of weaning off nasal continuous positive airway pressure.
Key Words: CPAP • cardiac output • preterm infants • echocardiography
Abbreviations: nCPAP—nasal continuous positive airway pressure • RDS—respiratory distress syndrome • CO—cardiac output • PDA—patent ductus arteriosus • SPO2—transcutaneous oxygen saturation • LVDD—left ventricular cavity dimensions at end-diastole • RVO—right ventricular output • LVO—left ventricular output • SVC—superior vena cava • IVCD—mean inferior vena cava diameter
There has been recent interest in using nasal continuous positive airway pressure (nCPAP) for the management of respiratory distress syndrome (RDS) in preterm infants.1,2 The application of nCPAP allows alveolar distention, even during expiration, that subsequently increases functional residual capacity and decreases the work of breathing.3 In addition, nCPAP decreases the resistance of the airway and reduces the risk for obstructive apnea.4 The effect of the increased intrathoracic pressure, caused by nCPAP, on venous return to the right heart and cardiac output (CO) has not been adequately studied. These hemodynamic effects are particularly significant during the weaning phase when lung compliance has improved and most of the airway pressure can potentially be transmitted to the heart and major blood vessels. Therefore, we aimed in this prospective study to measure hemodynamic changes in preterm infants while weaning off nCPAP. We hypothesized that nCPAP can impede venous return without compromising CO in preterm infants.
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SUBJECTS AND METHODS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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We conducted a prospective study in the NICU at Mansoura University Children's Hospital between February 2007 and October 2007. Our study included 25 preterm infants born at
32 weeks’ gestation, with resolving RDS, stable on nCPAP pressure of 5 cm H2O and 21% oxygen concentration. During nCPAP, we ensured mouth closure by using a pacifier to prevent any fluctuation in nCPAP pressure.5 Newborn infants who had congenital heart disease apart from patent ductus arteriosus (PDA) were excluded from the study. The decision to wean from nCPAP was made by the attending physician, who was not involved in the trial.
In our practice, infants are not routinely intubated in the delivery room and are primarily supported by nCPAP. Tracheally intubated infants are considered candidates for extubation whenever intermittent mandatory ventilation is weaned to 15 beats per minute and fraction of inspired oxygen is weaned to <40%, while they maintain hemodynamic stability. Our NICU policy does not specify an extubation value for peak inspiratory pressure; however, extubation usually occurs at peak inspiratory pressure 20 mm Hg. There is no standardized method for weaning preterm infants off nCPAP. Some practices include the following: to trial an infant off nCPAP once they are stable, to cycle the infant through periods on and off nCPAP before stopping, and to gradually wean to lower pressure settings.6–8 In this study, we used the cycling method. While cycling nCPAP, we performed 2-dimensional M-mode and pulsed Doppler echocardiography on all infants during nCPAP immediately before and 1 hour after being off nCPAP. When the infants were off nCPAP, they were maintained under a head box and oxygen was offered when needed to maintain their oxygen saturation at 88% to 92%. During this period of 60 minutes fluid management remained unchanged. None of the infants received inotropic support during the study. At study entry and after 60 minutes of being off nCPAP; heart rate, blood pressure, transcutaneous oxygen saturation (SPO2), and blood gases were recorded. nCPAP was delivered by the Arabella CPAP system (Hamilton Medical AG, CH-7402 Bonaduz, Switzerland) using binasal prongs. Informed written consent was obtained from the parents before enrollment in the study. The study was approved by the institutional review board at Mansoura University Children's Hospital.
Echocardiographic Data Collection
Echocardiographic measurements were done (SONOS-5500, Hewlett Packard, Andover, MA) with 12 MHz probe incorporating color flow, pulsed wave, and continuous wave Dopplers. Images were recorded on videotapes and each scan was given a random number that was drawn from a sealed envelope. That number was the only identifier displayed on the ultrasound screen. All hemodynamic measurements were performed away from bedside by a single investigator (MM) who was masked to whether an infant had been on or off nCPAP.
Structural normality of the heart was established on the initial scan. In each study, the following measurements were taken: (a) 2-dimensional M-mode measurements, obtained from a parasternal short-axis view according to the guidelines for M-mode echocardiography of the American Society of Echocardiography.9 Aortic diameter at the level of the valvular annulus, left ventricular cavity dimensions at end-diastole (LVDD) and left ventricular cavity dimensions at end-systole, left atrial size, and right ventricular cavity dimension at end-diastole were assessed. Fractional shortening was calculated as (FS%) = (LVDD– left ventricular cavity dimensions at end-systole)/LVDD x 100. (b) Pulse wave Doppler measurements of maximum flow velocities across aortic and pulmonary valve were obtained from both apical 5-chamber view and parasternal short-axis view. (c) Doppler volumetric measurement of right ventricular output (RVO) and left ventricular output (LVO); LVO was assessed with internal aortic diameter measured from the parasternal long-axis view immediately distal to the valve orifice at end systole using the M-mode trailing edge-leading edge technique, and aortic flow velocity assessed from a modified apical view.10 RVO was assessed with pulmonary diameter measured from either the parasternal short axis or the tilted parasternal long-axis view at the hinge-points of the pulmonary valve by frame-by frame analysis of the 2-dimensional image during cardiac systole, and pulmonary flow velocity assessed from the parasternal short axis view at the level of the tips of the pulmonary valve leaflets.11 Measurements from 4–6 cardiac cycles were averaged to determine the fractional shortening, LVO, and RVO. (d) Superior vena cava (SVC) flow was measured as previously described.12 The flow was imaged from a low subcostal view. The Doppler sample volume was placed at the junction of the SVC and right atrium. The flow consists of 3 waves: systolic, diastolic, and atrial. The diameter of the SVC was imaged by M mode, from the right or left parasternal long-axis view, at the junction of the SVC and right atrium. Because of the variation in vessel diameter throughout the cardiac cycle, a mean of the maximum and minimum diameter during the cardiac cycle was used for calculation of the flow. (e) Mean inferior vena cava diameter (IVCD) was expressed as [(IVCD in inspiration + IVCD in expiration)/2].13 (f) Color Doppler diameter of ductus arteriosus shunt and size.14 Clinically significant PDA was diagnosed when there was color Doppler echocardiographic evidence of left to right ductal shunt associated with at least 2 of the following clinical signs: heart murmur (systolic or continuous), persistent tachycardia (heart rate >160/min), hyperactive precordial pulsation, bounding pulses, and radiographic evidence of cardiomegaly or pulmonary congestion.15 Because all subjects were clinically stable, patients diagnosed with a clinically significant PDA did not receive indomethacin or ibuprofen; although they underwent fluid restriction (130 mL/kg per day).
Statistical Analysis
Based on previous studies on hemodynamic changes associated with nCPAP, we used a convenient sample size of 25 infants. Data are presented as mean ± SD. Data were plotted to ensure normal distribution, and the paired-sample t test was used to compare echocardiographic data during nCPAP and off nCPAP. The independent samples t test was used for group comparisons of data in patients with and without PDA. Significance was defined as a 2-tailed P value of <.05. Data were statistically analyzed with the use of the Statistical Package for Social Science program (SPSS version 15.0 for windows, Chicago, IL).
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RESULTS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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A total of 25 preterm infants were studied (11 males and 14 females); mean gestational age was 30.4 ± 1.6 weeks, and birth weight was 1.8 ± 0.2 kg. Median (IQ range) postnatal age at study entry was 7 (4–18) days. All infants were put on nCPAP because of RDS; 9 (36%) were ventilated before nCPAP, and 2 (8%) received 1 dose of early rescue surfactant therapy (Survanta, Abbott Laboratories, North Chicago, IL). Eleven infants (44%) received antenatal steroids, and 12 (48%) were inborn. None of the enrolled infants received inotropic support during the study period, whereas 3 infants received methylxanthines. Eight infants (32%) had PDA; the mean duct diameter was 2.2 mm; in 5 patients (62.5%), the PDA was hemodynamically significant; these infants were fluid restricted (130 mL/kg per day), and none of them received indomethacin or ibuprofen. For all other infants without significant PDA, the total maintenance fluid was kept at 150 mL/kg. There were no significant changes in physiologic measurements while on and off nCPAP (Table 1). Blood gas analysis during nCPAP showed a mean PaCO2 of 47.6 ± 6.6 mm Hg compared with 48.6 ± 4.5 mmHg, whereas off nCPAP; P = .41. Only 6 infants received supplemental oxygen via head box to achieve the preset goal SPO2 of 88% to 92%.
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Echocardiographic measurements are shown in Table 1 and Fig 1. nCPAP significantly reduced RVO, pulmonary venous return (decrease in left atrial and left ventricular diameters), and systemic venous return (decreased SVC flow and increased mean IVCD), but it did not influence systemic circulation (LVO and aortic maximum velocity) or myocardial contractility (fractional shortening). Individual patient changes in key hemodynamic measurements are shown Fig 2.
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on nCPAP; 
off nCPAP; a P
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On subgroup analyses, infants with PDA (n = 8) had similar hemodynamic changes compared with those without PDA while on nCPAP, whereas PDA was associated with a significant increase in RVO and left atrial diameter, and decrease in aortic root diameter (Table 2).
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DISCUSSION |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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We demonstrated that nCPAP at a pressure of 5 cm H2O led to significant hemodynamic changes in preterm infants with resolving RDS because it significantly decreased RVO and systemic and pulmonary blood venous returns. However, it did not change any of the vital signs and had no influence on LVO, systemic blood flow, and myocardial contractility.
Blood flow in the SVC decreased with the use of nCPAP. Although statistically significant, the amount of decrease in SVC flow was not clinically important. In our study, the SVC flow decreased during the use of nCPAP to 70.2 ± 8.5 mL/kg per minute, whereas pathologically low measures of SVC are defined when less than 40 mL/kg per minute.12 Blood flow in the SVC is a surrogate for upper-body systemic perfusion.12 Low SVC flow in the neonatal period has been linked to periventricular hemorrhage.16
LVO was not affected by nCPAP in our population. Previous studies reported compromises in LVO in preterm infants when using more aggressive nCPAP pressure (up to 10 cm H2O).17 Depressed CO was even more demonstrable with CPAP when animals were in a state of hypovolemia.18 Other studies related the use of nCPAP with changes in regional blood flow evidenced by attenuation in superior mesenteric artery flow19 and decrease in urine output.20 However, nCPAP did not affect cerebral perfusion or oxygenation.21 It is important to note that any hemodynamic effects for nCPAP are dependant on the status of lung parenchyma. When lung compliance is reduced, the amount of pressure transmitted to the vascular system decreases to only one fourth,22 whereas when pressure is set too low, blood is shunted away from collapsed alveoli, which produces a regional increase in pulmonary vascular resistance. With optimal lung volume, lung vascular resistance will be at its lowest point, thus maximizing RVO and cardiac input.
To achieve an effective nCPAP system, clinicians should ensure that pressure is transmitted down the airways.5 We recommend having a clear policy in the NICU with a checklist at the bedside for nurses to use every 3 to 4 hours while providing care.6 The check list can include the following: (a) ensure nCPAP application device is well sealed at the nose without causing trauma to the nasal septum; (b) clear secretions off the nose, mouth, and pharynx using an 8F suction catheter; because the use of smaller catheters is usually not effective in clearing thick secretions; (c) maintain the mouth closed using an appropriate size pacifier; and (d) maintain the neck slightly extended to prevent floppy airways from collapse. Without ensuring these key points, nCPAP pressure may not reach alveoli, and the devise is possibly useless. The absence of these key points can explain the inconsistent findings on hemodynamic changes associated with the use of nCPAP. For instance, Mortiz et al23 did not observe hemodynamic changes with nCPAP, whereas de Waal et al24 observed significant changes after increasing the PEEP pressure in tracheally intubated infants. Therefore, the lack of hemodynamic changes reported in previous studies need to be cautiously interpreted as to whether it is related to the absence of airway seal or that truly nCPAP does not affect circulation. It is important to note that the hemodynamic changes that we observed could not be explained by changes in PaCO2 values, because we did not observe any significant variations in PaCO2 while infants were on and off nCPAP. In our study, hemodynamic measurements were performed whenever infants were ready for weaning off nCPAP, regardless of their postnatal age. Pulmonary vascular resistance gradually decreases during the early postnatal life. Therefore, the wide range of postnatal age (4–18 days) in our subjects could theoretically affect our findings. However, to eliminate any impact for postnatal age on our data, we were particularly careful in obtaining the 2 readings in each subject while on and off nCPAP within 1 hour.
To our knowledge, the circulatory impact of nCPAP in preterm infants with PDA was not addressed previously. While off nCPAP, PDA was associated with significant increase in RVO and left atrial diameter, and decrease in aortic root diameter. These PDA-associated hemodynamic changes were completely abolished when infants were supported with nCPAP. Meanwhile, nCPAP did not influence duct diameter or shunt severity. Our findings support and provide explanation for the previous report that demonstrated nCPAP treatment to relieve signs of cardiac decompensation associated with left-to-right shunt in infants with PDA.25 In adult patients with congestive heart failure,26 nCPAP improved stroke volume suggesting improved inotropic function of the left ventricle by optimizing FRC and thereby reducing pulmonary vascular resistance.
We were surprised to detect PDA with significant shunting in almost one third of our study population, despite the fact that their degree of prematurity was not extreme (gestational age = 30 weeks) and none of them required oxygen supplementation. We did not administer any medication to close their PDA, and follow-up echocardiography demonstrated its closure in all infants. Our finding may fuel the debate of whether and/or when PDA should be treated in preterm infants.27,28
We conclude that nCPAP can impede systemic and pulmonary venous return, but does not compromise systemic blood pressure or vital signs in preterm infants with resolving RDS. Our finding that hemodynamic effects in infants with PDA were abolished while on nCPAP should be interpreted with caution, because that study was not powered to test this finding with such small number of infants with PDA. This study does not bring relief on whether similar or more exaggerated hemodynamic changes occur in very preterm infants, whether these changes continue beyond the-1-hour measurement, and surely whether the decreased hemodynamic variability across PDA in nCPAP supported preterm infants can influence ductal closure.
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FOOTNOTES |
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Accepted Jul 24, 2008.
Address correspondence to Hany Aly, MD, 900 23rd Street, NW, Suite G2092, Washington, DC, 20037. E-mail: haly{at}mfa.gwu.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
| What's Known on This Subject Continuous positive airway pressure is often used in the NICU. It has multiple beneficial effects to the lungs. The relation of continuous positive airway pressure to pulmonary physiology is well studied.
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| What This Study Adds The study provides echographic data and measurements of cardiac chambers and the flow into the great vessels during periods off and on continuous positive airway pressure.
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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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