Original Article
577
Tidal Volume in Infants with Congenital Diaphragmatic Hernia Supported with Conventional Mechanical Ventilation Saumya Sharma, MD1
Kabir M. Abubakar, MD1
Martin Keszler, MD2
1 Division of Neonatology, Department of Pediatrics, Georgetown
University Hospital, Washington, District of Columbia 2 Department of Pediatrics, Brown University, Providence, Rhode Island
Address for correspondence Kabir M. Abubakar, MD, Division of Neonatology, Department of Pediatrics, M3400, Georgetown University Hospital, 3800 Reservoir Road, NW, WA 20007 (e-mail: [email protected]).
Abstract
Keywords
► congenital diaphragmatic hernia ► tidal volume ► minute ventilation ► mechanical ventilation
Objective This study aims to test the hypothesis that the tidal volume (V T) required for maintaining eucapnia in infants with congenital diaphragmatic hernia (CDH) is not reduced to the same degree as their lung mass. Study Design Records of infants with CDH admitted to our hospital from 1997 to 2009 managed with conventional ventilation were reviewed. Demographics, ventilator settings, observed V T, respiratory rate (RR), and blood gas values pre- and postsurgery were recorded. Minute ventilation (MV) was calculated as a product of RR V T. Only V T values with corresponding PaCO2 between 35 and 60 mm Hg were included. Mean V T/kg and MV/kg were calculated for each patient. Forty term/late preterm infants ventilated for lung disease other than CDH or pulmonary hypoplasia served as controls. Results Birth weights of the 19 patients with CDH and 40 control infants were similar (3,360 480 g and 3,300 640 g). Mean gestational age was 38.5 2 and 37.4 1.5 week, p ¼ 0.02. Infants with CDH required similar V T and MV as controls to maintain equal PaCO2. Conclusions Infants with CDH require similar V T to clear their CO2 production compared with infants of similar size without pulmonary hypoplasia. These are the first reference values to guide selection of V T in infants with CDH.
Congenital diaphragmatic hernia (CDH) is a complex congenital disorder with an incidence of 1 in every 2,500 live born infants with a male preponderance.1 It is an important cause of morbidity and mortality in neonates with an overall survival of 79% (range, 69–93%).2 CDH is characterized by variable degrees of pulmonary hypoplasia. Both ipsilateral and contralateral lungs exhibit decreased alveolar numbers with increase in arterial wall thickness in the intra-acinar arteries.3,4 The degree of pulmonary hypoplasia is an important determinant of morbidity and mortality and absolute fetal lung volume has been shown to predict neonatal survival.5
With the advent of delayed repair of CDH, the importance of preoperative stabilization is being increasingly recognized.6 The goal is to use ventilatory strategies that achieve acceptable ventilation and optimize oxygenation with minimal lung injury to the highly susceptible hypoplastic lungs. In this regard, gentle ventilation with permissive hypercapnia has been shown to improve survival.7 It has been observed that volume, rather than pressure is the most important determinant of lung injury and volume targeted ventilation is being increasingly used to ventilate newborn infants.8,9 The optimal tidal volume (VT) to be used in volume-targeted ventilation has been studied extensively in preterm infants
received September 12, 2014 accepted after revision December 5, 2014 published online January 21, 2015
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0034-1543985. ISSN 0735-1631.
Downloaded by: Florida International University. Copyrighted material.
Am J Perinatol 2015;32:577–582.
V T in Infants with CDH Supported with Conventional Mechanical Ventilation and has been found to be between 4 and 6 mL/kg.10–13 However, the setting to be used in patients with pulmonary hypoplasia such as in CDH has not been defined. The V T setting in volume-targeted ventilation is usually based on the infant’s size. However, infants with CDH have a substantially smaller lung volume than unaffected infants of the same birth weight, so the appropriate V T in these infants may be different. We undertook to retrospectively analyze data from infants with CDH managed on volume guarantee ventilation in the Georgetown University Hospital Neonatal Intensive Care Unit and to determine the actual V T/kg needed to achieve adequate ventilation. Based on empiric observations, we hypothesized that the V T required to maintain eucapnia in infants with CDH is not reduced to the same degree as their lung mass, because they require similar minute ventilation (MV) to meet their metabolic carbon dioxide (CO2) production as infants of similar size without lung hypoplasia.
Data were compared with 40 term and late preterm infants ventilated during the same time period for severe uniform lung disease such as respiratory distress syndrome (RDS) or pneumonia. Patients with meconium aspiration syndrome, other causes of pulmonary hypoplasia or significant congenital anomalies were excluded. We collected data on patient demographics, primary diagnosis, ventilator settings, observed (exhaled) V T, and respiratory rate (RR) at the time that a blood gas was obtained and the PaCO2 on that blood gas. At each time point, MV was calculated as a product of RR V T. Mean V T/kg and MV/kg were calculated for each patient and these mean values were subjected to descriptive statistical analysis. Because the data were normally distributed, the two groups were compared by means of an unpaired t-test. The study was approved by the Georgetown University Institutional Review Board.
Results
Methods At Georgetown University Hospital we have used volume guarantee ventilation with the Dreger Babylog 8000 þ ventilator (Draeger, Luebeck, Germany) for over 10 years for nearly all infants supported with conventional mechanical ventilation. Our clinical practice has been to start volumetargeted ventilation with V T of 4.5 to 5 mL/kg in most infants, with adjustments of 0.5 mL/kg to achieve target blood gases. However, in view of the known pulmonary hypoplasia in infants with CDH, lower initial V T was typically chosen by the clinical team with subsequent adjustment based on blood gas measurement and assessment of the V T generated spontaneously by the infant. The general approach to mechanical ventilation at our institution for patients with CDH included the use of the lowest V T consistent with adequate ventilation, targeting pulse oximetry values of 94 to 98% and using moderate level of positive end-expiratory pressure (PEEP) designed to promote gentle lung volume recruitment but avoid overexpansion of the hypoplastic lungs that might worsen pulmonary hypertension and increase the risk of air leak. Infants who required inflation pressure greater than 25 to 30 cm H2O were usually switched to high-frequency ventilation (HFV). Surfactant was not routinely used. Extracorporeal membrane oxygenation (ECMO) was available at our institution for rescue in infants unresponsive to maximal respiratory support. We reviewed medical records of all infants with CDH admitted to Georgetown University Hospital from January 1997 to December 2009 who were managed on conventional ventilation during at least a portion of their acute illness and had arterial access for blood gas analysis. Data were collected while the infants were managed with assist/ control (AC) with volume guarantee or pressure support ventilation (PSV) with volume guarantee during the first 5 days of life. Only V T values with corresponding PaCO2 in the range of 35 to 60 mm Hg were included, as this was our arbitrary definition of “eucapnia” in this population and roughly corresponds to the target range used clinically. American Journal of Perinatology
Sharma et al.
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No. 6/2015
Overall, 40 patients with CDH were admitted to Georgetown University Hospital from January 2000 to December 2009. A total of 21 patients were managed solely with HFV; 19 patients were managed with conventional ventilation during at least a portion of their acute illness and had adequate data available for analysis. Overall, 40 term and late preterm infants who were managed on conventional ventilation for RDS or pneumonia served as controls. Some CDH infants were on conventional ventilation only before or after surgery, some on both occasions. For this reason, the respiratory variables are analyzed and presented separately for the two periods. The mean birth weight of the 19 patients with CDH and the 40 control infants was 3,360 480 g and 3,300 640 g, respectively (p ¼ nonsignificant). The mean gestational age was 38.5 2.0 and 37.4 1.5 weeks, respectively, p ¼ 0.02. Baseline ventilator settings and blood gas values are shown in ►Table 1. Measured inflation pressure, FIO2, PaO2, and arterial/Alveolar oxygen tension ratio (a/A) ratio were not different, indicating a comparable degree of disease severity at the outset, while PEEP was significantly lower, reflecting a disease-specific strategy. While both groups had a mean pH well within an acceptable range, the pH was significantly lower in the CDH group partially due to a nonsignificantly higher PaCO2 in the CDH group, with a likely contribution of a slightly higher base deficit. Compared with the control group, infants with CDH required similar VT and MV to achieve adequate PaCO2 values both before and after the surgical repair. The V T tended to be slightly lower (but still > 4.5 mL/kg) and RR slightly higher in the CDH infants, resulting in a virtually identical MV. The mean PaCO2 values were statistically significantly higher in the CDH infants, reflecting an attempt at permissive hypercapnia, but both were well within the normal range (►Table 2). In the CDH group five patients required ECMO in the preoperative period for severe pulmonary hypertension. Survival in this group was 89.4%. In the control group two patients required ECMO for severe persistent pulmonary hypertension of the newborn (PPHN) and all patients survived.
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578
V T in Infants with CDH Supported with Conventional Mechanical Ventilation
Sharma et al.
579
Table 1 Baseline respiratory variables for CDH and control groups. The values are mean SD CDH group (n ¼ 19)
Control group (n ¼ 40)
p-Value
Measured PIP (cm H2O)
22.2 4.8
23.0 7.3
0.685
PEEP (cm H2O)
5.5 0.8
6.2 0.9
0.007
FIO2
0.60 0.30
0.67 0.29
0.403
pH
7.31 0.08
7.38 0.05
0.0001
PaCO2 (mm Hg)
44.8 9.3
41.3 4.7
0.067
PaO2 (mm Hg)
84.4 40.5
90.4 43.9
0.632
a/A ratio
0.29 0.19
0.25 0.15
0.424
Abbreviations: a/A, arterial/Alveolar oxygen tension ratio; CDH, congenital diaphragmatic hernia; PIP, peak inspiratory pressure; PEEP, positive endexpiratory pressure; SD, standard deviation.
Non-CDH (n ¼ 40)
p-Value control versus presurgery
p-Value control versus postsurgery
4.53 0.79
4.86 0.8
0.49
0.139
56.6 4.6
54.0 6.6
0.05
0.109
276.6 44.0
250 46.1
262.4 41.5
0.77
0.121
43.7 2.2
44.8 2.9
41.55 3.1
0.0095
0.0002
CDH Before surgery (n ¼ 14)
After surgery (n ¼ 17)
Tidal volume (mL/kg)
4.69 0.78
Respiratory rate (per minute)
58.1 6.0
Minute ventilation (mL/kg/min) PaCO2 (mm Hg)
Note: Data are expressed as mean standard deviation. Some congenital diaphragmatic hernia infants were on conventional ventilation only before or after surgery, some on both occasions, hence the n of 14 and 17. The mean values in the table represent 229 paired observations of tidal volume and PaCO2 in 14 infants before surgery, 272 in 17 infants after surgery, and 603 in the 40 control patients.
Discussion CDH is a rare and complex congenital disorder associated with high morbidity and mortality. Despite recent advances in our understanding and management of this disorder, CDH infants remain some of the most challenging patients to manage. The underlying pathophysiology is that of hypoplastic and dysplastic lungs, invariably associated with some degree of vascular hypoplasia and PPHN. Delayed surgery after initial stabilization has now become standard, placing even more emphasis on the importance of minimizing ventilator-induced lung injury. The optimal ventilatory strategy during this crucial period has not been established, but lung injury secondary to mechanical ventilation has been shown to play an important role in mortality rate of patients with CDH14 emphasizing the importance of carefully choosing the ventilatory parameters. Over the past decade, there has been increased recognition of the importance of volutrauma in lung injury with volumetargeted ventilation being increasingly used to support newborn infants requiring mechanical ventilation. The appropriate V T target has been reasonably well established for preterm infants with RDS a disorder characterized by low lung volume.10–13 However, till date, there are no evidence-based recommendations to guide the clinician to select appropriate V T targets in certain populations whose pathophysiology may result in a different V T requirement. At present there are no well controlled randomized trials comparing the different
ventilatory modes in the management of CDH. Evidence suggests that use of “gentle” ventilatory strategies with permissive hypercapnia appear to improve outcome.7 While many centers use HFV as a first-line therapy or as a rescue mode when conventional ventilation fails, the superiority of HFV has never been established in a controlled trial. In our center we use volume guarantee ventilation as the initial mode of support for patients with CDH. In the absence of published data on appropriate V T for infants with CDH, most clinicians assume that due to pulmonary hypoplasia, lower V T would be appropriate, typically starting at values of 3 to 3.5 mL/kg. In our practice, we often found this to be inadequate and noted that the infants were generating spontaneously V T above the set value. Subsequent adjustments were made in response to blood gas results and thus the V T that was ultimately used for the majority of the ventilation period was the result of adjustments made in response to blood gas measurements and the infant’s own respiratory effort, which often resulted spontaneous breathing above the target V T set initially. Our data are consistent with those of te Pas et al, who measured V T in infants with CDH during initial resuscitation in the delivery room. They noted that the spontaneously generated V T was 3.8 1.9 mL/kg with V T of 4.7 2.5 mL/kg when positive pressure inflation coincided with spontaneous effort of the infant. Positive pressure inflations not coordinated with a spontaneous effort generated only 2.6 1.6 mL/kg with a peak inspiratory pressure of 25 cm H2O. This level of support translated into neonatal American Journal of Perinatology
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Table 2 Tidal volume and PaCO2 values
V T in Infants with CDH Supported with Conventional Mechanical Ventilation intensive care unit admission pH of 7.19 0.23 and PaCO2 of 53 mm Hg (range, 34–161 mm Hg). Because these observations were made during the first minutes of life when the lungs may still be partially fluid filled, these values may underestimate the V T that would be seen at a later point in time.15 Our findings that the V T in infants with CDH is comparable to V T in infants without pulmonary hypoplasia may seem counterintuitive at first glance in view of the presence of pulmonary hypoplasia. However, upon careful analysis, this finding should not be surprising, because the CO2 production in these infants is unlikely to be different from infants without pulmonary hypoplasia and thus they would be expected to need similar MV. While it is possible to achieve the same MV with the use of smaller V T and faster RR, the proportion of dead space ventilation increases and rapid shallow breathing with high dead space to V T ratio becomes increasingly inefficient. It is important to note that the infants in this study were ventilated with modalities that support every breath (PSV or AC) and therefore the infants determined their own ventilator rate. The CDH infants did have higher RR, but still required nearly the same V T/kg and achieved the same MV/kg, as would be expected based on the expectation that their CO2 production would not differ from other infants. Our study has some limitations. It represents a single center experience and thus may reflect specific local practices. The V T data were not downloaded prospectively from the ventilator’s communication port, but rather were collected retrospectively from bedside flow sheets. The V T value displayed by the ventilator fluctuates in actively breathing infants, which could lead to random inaccuracy. Our nurses are taught to observe the V T values for a period of time and write down an average value, a practice that should minimize this problem. In addition, since there were hundreds of individual observations, any such random variation would not be expected to lead to a systematic bias. Target PaCO2 values were not explicitly defined by unit policy, but the mean values observed in our patients were well within the normal range and did not differ between the two groups. Although we intended to tolerate mild degrees of hypocapnia, the use of advanced synchronized ventilation modes, such as AC or PSV allows the infant to drive the ventilator rate and provides sufficient support to allow these term infants to achieve the level of ventilation dictated by their respiratory control center. The MV was not directly recorded, but rather was calculated from the recorded RR and V T. All our patients were managed on AC or PSV. As implemented on the Babylog 8000 þ, PSV is identical to AC, with the exception that onset of expiration is flow cycled, rather than time cycled. As a result, every inflation was a machine supported breath with relatively uniform V T. The RR displayed by the device is the total RR, unlike when synchronized intermittent mandatory ventilation is used. Therefore, we believe that this value should be quite accurate. The V T data obtained from the Babylog ventilator represent exhaled V T measured at the airway opening (proximal airway), which more accurately reflects the true V T in the presence of a leak around the endotracheal tube. However, this value may be slightly American Journal of Perinatology
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Sharma et al.
different from the set V T on other types of ventilators. Nonetheless, these results should be generalizable to other devices, irrespective of how V T is regulated, provided the V T is measured in the same way. The V T values we found in the control infants are very similar to those previously documented in preterm infants with RDS.10–13 This fact should increase confidence in the findings of the present study. It is likely that this cohort of patients does not include infants with the most severe degree of pulmonary hypoplasia. Some of the CDH patients could not be supported with conventional ventilation or were electively changed to HFV because relatively high inflation pressures were needed. However, all patients were severely symptomatic soon after birth and suffered from respiratory failure. Many required HFV at some point in their hospital course and some required ECMO. Therefore, they were likely to have at least moderate degree of pulmonary hypoplasia. In conclusion, our findings support the hypothesis that with conventional mechanical ventilation infants with CDH, despite their pulmonary hypoplasia, require V T very similar to other infants with respiratory failure. This is consistent with the need for similar MV to meet their normal level of CO2 production. While the conclusion itself is not surprising, this conclusion implies that, given the decreased number of alveoli present, the volume of gas entering each alveolus is proportionately larger and would thus be expected to result in volutrauma. This would be a theoretical argument in favor of using HFV in the more severely affected infants. Nonetheless, when conventional ventilation is to be used, we provide the first normative data to guide selection of V T in infants with CDH.
References 1 Downard CD. Congenital diaphragmatic hernia: an ongoing clini-
cal challenge. Curr Opin Pediatr 2008;20(3):300–304 2 Logan JW, Rice HE, Goldberg RN, Cotten CM. Congenital diaphrag-
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matic hernia: a systematic review and summary of best-evidence practice strategies. J Perinatol 2007;27(9):535–549 Bohn D, Tamura M, Perrin D, Barker G, Rabinovitch M. Ventilatory predictors of Pulmonary hypoplasia in CDH, confirmed by morphologic assessment. J Pediatr 1987;111:423 Thibeault DW, Haney B. Lung volume, pulmonary vasculature, and factors affecting survival in congenital diaphragmatic hernia. Pediatrics 1998;101(2):289–295 Büsing KA, Kilian AK, Schaible T, Endler C, Schaffelder R, Neff KW. MR relative fetal lung volume in congenital diaphragmatic hernia: survival and need for extracorporeal membrane oxygenation. Radiology 2008;248(1):240–246 Wung JT, Sahni R, Moffitt ST, Lipsitz E, Stolar CJ. Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatr Surg 1995; 30(3):406–409 Boloker J, Bateman DA, Wung JT, Stolar CJ. Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/elective repair. J Pediatr Surg 2002;37(3):357–366 Keszler M, Abubakar KM. Volume guarantee ventilation. Clin Perinatol 2007;34(1):107–116, vii Keszler M. Volume-targeted ventilation. J Perinatol 2005;25 (Suppl 2):S19–S22
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13 Nassabeh-Montazami S, Abubakar KM, Keszler M. The impact of
and incidence of hypocarbia. Pediatr Pulmonol 2004;38(3): 240–245 11 Lista G, Castoldi F, Fontana P, et al. Lung inflammation in preterm infants with respiratory distress syndrome: effects of ventilation with different tidal volumes. Pediatr Pulmonol 2006;41(4): 357–363 12 Dawson C, Davies MW. Volume-targeted ventilation and arterial carbon dioxide in neonates. J Paediatr Child Health 2005;41(9-10): 518–521
instrumental dead-space in volume-targeted ventilation of the extremely low birth weight (ELBW) infant. Pediatr Pulmonol 2009; 44(2):128–133 14 Sakurai Y, Azarow K, Cutz E, Messineo A, Pearl R, Bohn D. Pulmonary barotrauma in congenital diaphragmatic hernia: a clinicopathological correlation. J Pediatr Surg 1999;34(12):1813–1817 15 te Pas AB, Kamlin CO, Dawson JA, et al. Ventilation and spontaneous breathing at birth of infants with congenital diaphragmatic hernia. J Pediatr 2009;154(3):369–373
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10 Keszler M, Abubakar K. Volume guarantee: stability of tidal volume
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577
Tidal Volume in Infants with Congenital Diaphragmatic Hernia Supported with Conventional Mechanical Ventilation Saumya Sharma, MD1
Kabir M. Abubakar, MD1
Martin Keszler, MD2
1 Division of Neonatology, Department of Pediatrics, Georgetown
University Hospital, Washington, District of Columbia 2 Department of Pediatrics, Brown University, Providence, Rhode Island
Address for correspondence Kabir M. Abubakar, MD, Division of Neonatology, Department of Pediatrics, M3400, Georgetown University Hospital, 3800 Reservoir Road, NW, WA 20007 (e-mail: [email protected]).
Abstract
Keywords
► congenital diaphragmatic hernia ► tidal volume ► minute ventilation ► mechanical ventilation
Objective This study aims to test the hypothesis that the tidal volume (V T) required for maintaining eucapnia in infants with congenital diaphragmatic hernia (CDH) is not reduced to the same degree as their lung mass. Study Design Records of infants with CDH admitted to our hospital from 1997 to 2009 managed with conventional ventilation were reviewed. Demographics, ventilator settings, observed V T, respiratory rate (RR), and blood gas values pre- and postsurgery were recorded. Minute ventilation (MV) was calculated as a product of RR V T. Only V T values with corresponding PaCO2 between 35 and 60 mm Hg were included. Mean V T/kg and MV/kg were calculated for each patient. Forty term/late preterm infants ventilated for lung disease other than CDH or pulmonary hypoplasia served as controls. Results Birth weights of the 19 patients with CDH and 40 control infants were similar (3,360 480 g and 3,300 640 g). Mean gestational age was 38.5 2 and 37.4 1.5 week, p ¼ 0.02. Infants with CDH required similar V T and MV as controls to maintain equal PaCO2. Conclusions Infants with CDH require similar V T to clear their CO2 production compared with infants of similar size without pulmonary hypoplasia. These are the first reference values to guide selection of V T in infants with CDH.
Congenital diaphragmatic hernia (CDH) is a complex congenital disorder with an incidence of 1 in every 2,500 live born infants with a male preponderance.1 It is an important cause of morbidity and mortality in neonates with an overall survival of 79% (range, 69–93%).2 CDH is characterized by variable degrees of pulmonary hypoplasia. Both ipsilateral and contralateral lungs exhibit decreased alveolar numbers with increase in arterial wall thickness in the intra-acinar arteries.3,4 The degree of pulmonary hypoplasia is an important determinant of morbidity and mortality and absolute fetal lung volume has been shown to predict neonatal survival.5
With the advent of delayed repair of CDH, the importance of preoperative stabilization is being increasingly recognized.6 The goal is to use ventilatory strategies that achieve acceptable ventilation and optimize oxygenation with minimal lung injury to the highly susceptible hypoplastic lungs. In this regard, gentle ventilation with permissive hypercapnia has been shown to improve survival.7 It has been observed that volume, rather than pressure is the most important determinant of lung injury and volume targeted ventilation is being increasingly used to ventilate newborn infants.8,9 The optimal tidal volume (VT) to be used in volume-targeted ventilation has been studied extensively in preterm infants
received September 12, 2014 accepted after revision December 5, 2014 published online January 21, 2015
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0034-1543985. ISSN 0735-1631.
Downloaded by: Florida International University. Copyrighted material.
Am J Perinatol 2015;32:577–582.
V T in Infants with CDH Supported with Conventional Mechanical Ventilation and has been found to be between 4 and 6 mL/kg.10–13 However, the setting to be used in patients with pulmonary hypoplasia such as in CDH has not been defined. The V T setting in volume-targeted ventilation is usually based on the infant’s size. However, infants with CDH have a substantially smaller lung volume than unaffected infants of the same birth weight, so the appropriate V T in these infants may be different. We undertook to retrospectively analyze data from infants with CDH managed on volume guarantee ventilation in the Georgetown University Hospital Neonatal Intensive Care Unit and to determine the actual V T/kg needed to achieve adequate ventilation. Based on empiric observations, we hypothesized that the V T required to maintain eucapnia in infants with CDH is not reduced to the same degree as their lung mass, because they require similar minute ventilation (MV) to meet their metabolic carbon dioxide (CO2) production as infants of similar size without lung hypoplasia.
Data were compared with 40 term and late preterm infants ventilated during the same time period for severe uniform lung disease such as respiratory distress syndrome (RDS) or pneumonia. Patients with meconium aspiration syndrome, other causes of pulmonary hypoplasia or significant congenital anomalies were excluded. We collected data on patient demographics, primary diagnosis, ventilator settings, observed (exhaled) V T, and respiratory rate (RR) at the time that a blood gas was obtained and the PaCO2 on that blood gas. At each time point, MV was calculated as a product of RR V T. Mean V T/kg and MV/kg were calculated for each patient and these mean values were subjected to descriptive statistical analysis. Because the data were normally distributed, the two groups were compared by means of an unpaired t-test. The study was approved by the Georgetown University Institutional Review Board.
Results
Methods At Georgetown University Hospital we have used volume guarantee ventilation with the Dreger Babylog 8000 þ ventilator (Draeger, Luebeck, Germany) for over 10 years for nearly all infants supported with conventional mechanical ventilation. Our clinical practice has been to start volumetargeted ventilation with V T of 4.5 to 5 mL/kg in most infants, with adjustments of 0.5 mL/kg to achieve target blood gases. However, in view of the known pulmonary hypoplasia in infants with CDH, lower initial V T was typically chosen by the clinical team with subsequent adjustment based on blood gas measurement and assessment of the V T generated spontaneously by the infant. The general approach to mechanical ventilation at our institution for patients with CDH included the use of the lowest V T consistent with adequate ventilation, targeting pulse oximetry values of 94 to 98% and using moderate level of positive end-expiratory pressure (PEEP) designed to promote gentle lung volume recruitment but avoid overexpansion of the hypoplastic lungs that might worsen pulmonary hypertension and increase the risk of air leak. Infants who required inflation pressure greater than 25 to 30 cm H2O were usually switched to high-frequency ventilation (HFV). Surfactant was not routinely used. Extracorporeal membrane oxygenation (ECMO) was available at our institution for rescue in infants unresponsive to maximal respiratory support. We reviewed medical records of all infants with CDH admitted to Georgetown University Hospital from January 1997 to December 2009 who were managed on conventional ventilation during at least a portion of their acute illness and had arterial access for blood gas analysis. Data were collected while the infants were managed with assist/ control (AC) with volume guarantee or pressure support ventilation (PSV) with volume guarantee during the first 5 days of life. Only V T values with corresponding PaCO2 in the range of 35 to 60 mm Hg were included, as this was our arbitrary definition of “eucapnia” in this population and roughly corresponds to the target range used clinically. American Journal of Perinatology
Sharma et al.
Vol. 32
No. 6/2015
Overall, 40 patients with CDH were admitted to Georgetown University Hospital from January 2000 to December 2009. A total of 21 patients were managed solely with HFV; 19 patients were managed with conventional ventilation during at least a portion of their acute illness and had adequate data available for analysis. Overall, 40 term and late preterm infants who were managed on conventional ventilation for RDS or pneumonia served as controls. Some CDH infants were on conventional ventilation only before or after surgery, some on both occasions. For this reason, the respiratory variables are analyzed and presented separately for the two periods. The mean birth weight of the 19 patients with CDH and the 40 control infants was 3,360 480 g and 3,300 640 g, respectively (p ¼ nonsignificant). The mean gestational age was 38.5 2.0 and 37.4 1.5 weeks, respectively, p ¼ 0.02. Baseline ventilator settings and blood gas values are shown in ►Table 1. Measured inflation pressure, FIO2, PaO2, and arterial/Alveolar oxygen tension ratio (a/A) ratio were not different, indicating a comparable degree of disease severity at the outset, while PEEP was significantly lower, reflecting a disease-specific strategy. While both groups had a mean pH well within an acceptable range, the pH was significantly lower in the CDH group partially due to a nonsignificantly higher PaCO2 in the CDH group, with a likely contribution of a slightly higher base deficit. Compared with the control group, infants with CDH required similar VT and MV to achieve adequate PaCO2 values both before and after the surgical repair. The V T tended to be slightly lower (but still > 4.5 mL/kg) and RR slightly higher in the CDH infants, resulting in a virtually identical MV. The mean PaCO2 values were statistically significantly higher in the CDH infants, reflecting an attempt at permissive hypercapnia, but both were well within the normal range (►Table 2). In the CDH group five patients required ECMO in the preoperative period for severe pulmonary hypertension. Survival in this group was 89.4%. In the control group two patients required ECMO for severe persistent pulmonary hypertension of the newborn (PPHN) and all patients survived.
Downloaded by: Florida International University. Copyrighted material.
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V T in Infants with CDH Supported with Conventional Mechanical Ventilation
Sharma et al.
579
Table 1 Baseline respiratory variables for CDH and control groups. The values are mean SD CDH group (n ¼ 19)
Control group (n ¼ 40)
p-Value
Measured PIP (cm H2O)
22.2 4.8
23.0 7.3
0.685
PEEP (cm H2O)
5.5 0.8
6.2 0.9
0.007
FIO2
0.60 0.30
0.67 0.29
0.403
pH
7.31 0.08
7.38 0.05
0.0001
PaCO2 (mm Hg)
44.8 9.3
41.3 4.7
0.067
PaO2 (mm Hg)
84.4 40.5
90.4 43.9
0.632
a/A ratio
0.29 0.19
0.25 0.15
0.424
Abbreviations: a/A, arterial/Alveolar oxygen tension ratio; CDH, congenital diaphragmatic hernia; PIP, peak inspiratory pressure; PEEP, positive endexpiratory pressure; SD, standard deviation.
Non-CDH (n ¼ 40)
p-Value control versus presurgery
p-Value control versus postsurgery
4.53 0.79
4.86 0.8
0.49
0.139
56.6 4.6
54.0 6.6
0.05
0.109
276.6 44.0
250 46.1
262.4 41.5
0.77
0.121
43.7 2.2
44.8 2.9
41.55 3.1
0.0095
0.0002
CDH Before surgery (n ¼ 14)
After surgery (n ¼ 17)
Tidal volume (mL/kg)
4.69 0.78
Respiratory rate (per minute)
58.1 6.0
Minute ventilation (mL/kg/min) PaCO2 (mm Hg)
Note: Data are expressed as mean standard deviation. Some congenital diaphragmatic hernia infants were on conventional ventilation only before or after surgery, some on both occasions, hence the n of 14 and 17. The mean values in the table represent 229 paired observations of tidal volume and PaCO2 in 14 infants before surgery, 272 in 17 infants after surgery, and 603 in the 40 control patients.
Discussion CDH is a rare and complex congenital disorder associated with high morbidity and mortality. Despite recent advances in our understanding and management of this disorder, CDH infants remain some of the most challenging patients to manage. The underlying pathophysiology is that of hypoplastic and dysplastic lungs, invariably associated with some degree of vascular hypoplasia and PPHN. Delayed surgery after initial stabilization has now become standard, placing even more emphasis on the importance of minimizing ventilator-induced lung injury. The optimal ventilatory strategy during this crucial period has not been established, but lung injury secondary to mechanical ventilation has been shown to play an important role in mortality rate of patients with CDH14 emphasizing the importance of carefully choosing the ventilatory parameters. Over the past decade, there has been increased recognition of the importance of volutrauma in lung injury with volumetargeted ventilation being increasingly used to support newborn infants requiring mechanical ventilation. The appropriate V T target has been reasonably well established for preterm infants with RDS a disorder characterized by low lung volume.10–13 However, till date, there are no evidence-based recommendations to guide the clinician to select appropriate V T targets in certain populations whose pathophysiology may result in a different V T requirement. At present there are no well controlled randomized trials comparing the different
ventilatory modes in the management of CDH. Evidence suggests that use of “gentle” ventilatory strategies with permissive hypercapnia appear to improve outcome.7 While many centers use HFV as a first-line therapy or as a rescue mode when conventional ventilation fails, the superiority of HFV has never been established in a controlled trial. In our center we use volume guarantee ventilation as the initial mode of support for patients with CDH. In the absence of published data on appropriate V T for infants with CDH, most clinicians assume that due to pulmonary hypoplasia, lower V T would be appropriate, typically starting at values of 3 to 3.5 mL/kg. In our practice, we often found this to be inadequate and noted that the infants were generating spontaneously V T above the set value. Subsequent adjustments were made in response to blood gas results and thus the V T that was ultimately used for the majority of the ventilation period was the result of adjustments made in response to blood gas measurements and the infant’s own respiratory effort, which often resulted spontaneous breathing above the target V T set initially. Our data are consistent with those of te Pas et al, who measured V T in infants with CDH during initial resuscitation in the delivery room. They noted that the spontaneously generated V T was 3.8 1.9 mL/kg with V T of 4.7 2.5 mL/kg when positive pressure inflation coincided with spontaneous effort of the infant. Positive pressure inflations not coordinated with a spontaneous effort generated only 2.6 1.6 mL/kg with a peak inspiratory pressure of 25 cm H2O. This level of support translated into neonatal American Journal of Perinatology
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Table 2 Tidal volume and PaCO2 values
V T in Infants with CDH Supported with Conventional Mechanical Ventilation intensive care unit admission pH of 7.19 0.23 and PaCO2 of 53 mm Hg (range, 34–161 mm Hg). Because these observations were made during the first minutes of life when the lungs may still be partially fluid filled, these values may underestimate the V T that would be seen at a later point in time.15 Our findings that the V T in infants with CDH is comparable to V T in infants without pulmonary hypoplasia may seem counterintuitive at first glance in view of the presence of pulmonary hypoplasia. However, upon careful analysis, this finding should not be surprising, because the CO2 production in these infants is unlikely to be different from infants without pulmonary hypoplasia and thus they would be expected to need similar MV. While it is possible to achieve the same MV with the use of smaller V T and faster RR, the proportion of dead space ventilation increases and rapid shallow breathing with high dead space to V T ratio becomes increasingly inefficient. It is important to note that the infants in this study were ventilated with modalities that support every breath (PSV or AC) and therefore the infants determined their own ventilator rate. The CDH infants did have higher RR, but still required nearly the same V T/kg and achieved the same MV/kg, as would be expected based on the expectation that their CO2 production would not differ from other infants. Our study has some limitations. It represents a single center experience and thus may reflect specific local practices. The V T data were not downloaded prospectively from the ventilator’s communication port, but rather were collected retrospectively from bedside flow sheets. The V T value displayed by the ventilator fluctuates in actively breathing infants, which could lead to random inaccuracy. Our nurses are taught to observe the V T values for a period of time and write down an average value, a practice that should minimize this problem. In addition, since there were hundreds of individual observations, any such random variation would not be expected to lead to a systematic bias. Target PaCO2 values were not explicitly defined by unit policy, but the mean values observed in our patients were well within the normal range and did not differ between the two groups. Although we intended to tolerate mild degrees of hypocapnia, the use of advanced synchronized ventilation modes, such as AC or PSV allows the infant to drive the ventilator rate and provides sufficient support to allow these term infants to achieve the level of ventilation dictated by their respiratory control center. The MV was not directly recorded, but rather was calculated from the recorded RR and V T. All our patients were managed on AC or PSV. As implemented on the Babylog 8000 þ, PSV is identical to AC, with the exception that onset of expiration is flow cycled, rather than time cycled. As a result, every inflation was a machine supported breath with relatively uniform V T. The RR displayed by the device is the total RR, unlike when synchronized intermittent mandatory ventilation is used. Therefore, we believe that this value should be quite accurate. The V T data obtained from the Babylog ventilator represent exhaled V T measured at the airway opening (proximal airway), which more accurately reflects the true V T in the presence of a leak around the endotracheal tube. However, this value may be slightly American Journal of Perinatology
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different from the set V T on other types of ventilators. Nonetheless, these results should be generalizable to other devices, irrespective of how V T is regulated, provided the V T is measured in the same way. The V T values we found in the control infants are very similar to those previously documented in preterm infants with RDS.10–13 This fact should increase confidence in the findings of the present study. It is likely that this cohort of patients does not include infants with the most severe degree of pulmonary hypoplasia. Some of the CDH patients could not be supported with conventional ventilation or were electively changed to HFV because relatively high inflation pressures were needed. However, all patients were severely symptomatic soon after birth and suffered from respiratory failure. Many required HFV at some point in their hospital course and some required ECMO. Therefore, they were likely to have at least moderate degree of pulmonary hypoplasia. In conclusion, our findings support the hypothesis that with conventional mechanical ventilation infants with CDH, despite their pulmonary hypoplasia, require V T very similar to other infants with respiratory failure. This is consistent with the need for similar MV to meet their normal level of CO2 production. While the conclusion itself is not surprising, this conclusion implies that, given the decreased number of alveoli present, the volume of gas entering each alveolus is proportionately larger and would thus be expected to result in volutrauma. This would be a theoretical argument in favor of using HFV in the more severely affected infants. Nonetheless, when conventional ventilation is to be used, we provide the first normative data to guide selection of V T in infants with CDH.
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