5Lung Recruitment Maneuver During Proportional Assist Ventilation of Preterm Infants With Acute Respiratory Distress Syndrome

8/11/2019 5Lung Recruitment Maneuver During Proportional Assist Ventilation of Preterm Infants With Acute Respiratory Distress Syndrome

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ORIGINAL ARTICLE

Lung recruitment maneuver during proportional assist

ventilation of preterm infants with acute respiratory distress

syndromeR Wu1,4, S-B Li2,4, Z-F Tian3,4, N Li1, G-F Zheng1, Y-X Zhao1, H-L Zhu1, J-H Hu1, L Zha1, M-Y Dai1 and W-Y Xu1

OBJECTIVE:To investigate the effect of lung recruitment maneuver (LRM) with positive end-expiratory pressure (PEEP) on

oxygenation and outcomes in preterm infants ventilated by proportional assist ventilation (PAV) for respiratory distress

syndrome (RDS).

STUDY DESIGN: Preterm infants on PAV for RDS after surfactant randomly received an LRM (group A, n = 12) or did not

(group B,n = 12). LRM entailed increments of 0.2 cm H2O PEEP every 5 min, until fraction of inspired oxygen (FiO2) = 0.25. Then PEEP

was reduced and the lung volume was set on the deation limb of the pressure/volume curve. When saturation of peripheral

oxygen fell and FiO2 rose, we reincremented PEEP until SpO2 became stable.

RESULT:Group A and B infants were similar: gestational age 29.5 1.0 vs 29.4 0.9 weeks; body weight 1314 96 vs

1296 88 g; Silverman Anderson score for babies at start of ventilation 8.6 0.8 vs 8.2 0.7; initial FiO20.56 0.16 vs 0.51 0.14,respectively. The less doses of surfactant administered in group A than that in group B (Po0.05). Groups A and B showed

different max PEEP during the rst 12 h of life (8.4 0.5 vs 6.7 0.6 cm H2O,P= 0.00), time to lowest FiO2(101 18 versus 342 128

min;P= 0.000) and O2 dependency (7.83 2.04 vs 9.92 2.78 days;P= 0.04). FiO2 levels progressively decreased (F= 43.240,

P= 0.000) and a/AO2 ratio gradually increased (F= 30.594,P= 0.000). No adverse events and no differences in the outcomes

were observed.

CONCLUSION:LRM led to the earlier lowest FiO2 of the rst 12 h of life and a shorter O2 dependency.

Journal of Perinatology(2014) 34, 524527; doi:10.1038/jp.2014.53; published online 3 April 2014

INTRODUCTION

Respiratory distress syndrome (RDS) is the most commoncondition of preterm infants in neonatal intensive care unit (NICU)with complications due to RDS constituting the most signicantcause of mortality and long-term morbidity. Neonatal mechanicalventilator is considered a valuable tool to manage RDS in preterminfants. Several types of ventilation modes and strategieshave been explored in clinical practice to optimize mechanicalventilation, so as to reduce the risk of ventilator-induced lunginjury.

There are several mechanisms that may underlie lung protec-tion from lung recruitment maneuver (LRM). First, recruitingcollapsed alveoli may temporarily improve gas exchange and thusreduce the FiO2. Second, with an open lung, a lower pressure canexpand the lungs through the tidal range. Third, if applied withpositive end-expiratory pressure (PEEP), an LRM may reducerepetitive opening and closing that causes shear stress that candamage terminal lung units.1 In summary, LRM that achieves anopen lung may reduce the risk of oxygen toxicity, overdistentioninjury and shear-stress injury. Open-lung ventilation uses LRM toopen alveoli and optimize lung volume and avoids excessive lungination. There is evidence that open-lung ventilation with LRMcan also reduce ventilator-induced lung injury and may be an

important adjunct to limiting tidal volume (VT) and applying

adequate PEEP.2,3Proportional assist ventilation (PAV) is a mode in which the

ventilator guarantees a percentage of work regardless of changesin pulmonary compliance and resistance. Consequently, the VTand pressure of the ventilator are varied based on the patient swork of breathing and the amount it deliversis proportional to thepercentage of assistance it is set to provide.4

In this pilot study, we prospectively collected data on venti-latory parametersFiO2 requirements, gas exchange and respira-tory outcomesto investigate the effect of an LRM in preterminfants who received LRM plus PAV versus those who receivedPAV only during the acute phase of RDS, using saturation ofperipheral oxygen (SpO2) to guide the maneuver.

METHODS

Patient population

This study was performed at the NICU of Huaian Maternity and ChildHealthcare Hospital, after the local ethical committees approval. Westudied infants with gestational age (GA) 2830 weeks and birth weigh(BW) 10001500 g who received at least one course of prenatal gluco-corticoids and required tracheal intubation and mechanical ventilation in

1Neonatal Medical Center, Huaian Maternity and Child Healthcare Hospital, Anhui Medical University, Huaian, China; 2Anhui Medical University, Hefei, China and 3Huaian First

People's Hospital, Nanjing Medical University, Huaian, China. Correspondence: Professor R Wu, Neonatal Medical Center, Huaian Maternity and Child Healthcare Hospital,

Anhui Medical University, No.104, South Renmin Road, Huaian, Jiangsu Province 223002, China.

E-mail: [email protected] authors contributed equally to this work.

Received 7 October 2013; revised 18 February 2014; accepted 18 February 2014; published online 3 April 2014

Journal of Perinatology (2014) 34, 524527

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the rst six hours of life due to severe RDS, with written parental consent.Exclusion criteria included lethal congenital anomalies, severe intraven-tricular hemorrhage (above grade II), no spontaneous breathing orspontaneous breathing weak and absence of parental consent. Thesample size was determined by the number of early preterm infantsadmitted to our hospital in 1 year.

Study design

This study is a randomized trial. The enrolled infants were randomlyassigned to receive an LRM in the second 2 h of life (group A) or not (groupB), using sequentially numbered, sealed opaque envelopes. RDS diagnosiswas based on the clinical presentation, such as early respiratory distress,which includes cyanosis, grunting, sternal and intercostal recession andtachypnoea. Clinical diagnosis was conrmed with chest X-ray changesthat included a ground glass appearance and air bronchograms.5 SevereRDS was dened as arterial-to-alveolar oxygen ratio o0.2. All neonatesunderwent the same management in the delivery room according to ourNICU protocols and as recommended by European consensus guidelines.6

From the delivery room, all infants were transferred to the NICU in T-piecedevices (set background continuous positive airways pressure (PEEPlevel=5cm H2O level) with a measured peak inspiratory pressure duringocclusion of the T-piece). All the patients received the rst dose ofendotracheal porcine natural surfactant (200 mg/kg; Curosurf, Chiesi, Italy)immediately after tracheal intubation according to our standard protocolfor infants of GA 2830 weeks. During the rst 6 h of life, intubated infants

were supported with PAV (Stephanie infant ventilator, Gackenbach,Germany) with the following starting parameters: VT = 46 ml/kg, and aninitial PEEP = 5 cm H2O. The elastic unloading and resistive unloading wasset to maintain VT in 46 ml/kg. Backup conventional mechanicalventilation (SIMV mode) automatically initiated 10 s after cessation ofspontaneous breathing. When spontaneous breath recurred, backupventilation automatically suppressed and PAV resumed. During mechanicalventilation, the FiO2level was chosen to maintain a preductal SpO2of 85 to93%,6 the range of the peak inspiratory pressure was 1020cm H2O, andPEEP was 59cm H2O.

After setting a starting PEEP level of 5 cm H2O, we applied repeatedincrements of 0.2 cm H2O of PEEP every 5 min, monitoring the FiO2requirements and SpO2levels. During the 5 min of monitoring, SpO2 levelwas the signal to proceed with the Fio2 requirements and the PEEP level.We adjusted infant's PEEP and Fio2 in accordance with SpO2. SpO2 rosegradually with increasing PEEP. As soon as SpO2 approached 93%, we

began decreasing FiO2, which resulted in a slow drop in SpO2. When SpO2approached 85%, we stop decreasing FiO2. When FiO2reached 0.25, a slowstepwise PEEP reduction was started while monitoring the SpO2 levels.When oxygenation levels fell and FiO2 administration rose consequently,we reincreased the PEEP level until stable oxygenation was achieved andthe FiO2 level reached levels prior to the fall in oxygenation. CO 2 levels(monitored with N-85 handheld detecter, Pleasanton, CA; Non-dispersiveinfrared and Microstream capnography technology, Nellcor PuritanBennett, US)7 and cardiovascular status (heart rate, systemic bloodpressure) were monitored as well; the rise in CO2 levels and changes ofthe cardiovascular status were considered signals of stress and over-distention and we interrupted the maneuver if necessary.

Mechanical ventilation was stopped when FiO2 was 0.30, PEEP= 5 c mH2O, MAP was 6 cm H2O, and partial pressure of oxygen in arterial bloodand PaCO2were 50mm Hg and o65 mm Hg, respectively. The manage-ment after the extubation was balanced between the groups. In bothgroups, following NICU protocols, the extubation of mechanically

ventilated infants was mandatory within 2 h after they reached extubationcriteria. After extubation, the decision as to whether to begin nasalcontinuous positive airways pressure to prevent the need for reintubation,to offer oxygen supplementation only, or to put the patient directly intoroom air was completely up to the neonatologist on duty. Nasalcontinuous positive airways pressure was stopped when neonates withadequate spontaneous respiratory effort had FiO2 0.30, CDP 5 cm H2O,PaO2 50mm Hg and PaCO2 o65 mm Hg. Oxygen saturation-SpO2,arterial/alveolar oxygen ratio, FiO2 requirements and cardiovascular statuswere monitored during the procedure, after LRM, or within 12 h of life.All infants were evaluated before respiratory support by the SilvermanAnderson score.8 The following data were also recorded for each infant:GA, BW, sex, need for additional surfactant, length of oxygen therapy,duration of mechanical ventilation and of ventilatory assistance (non-invasive plus mechanical ventilation), air leak/pneumothorax, extubationfailure occurred, BPD, grade 3 or 4 intraventricular hemorrhage and greater

than grade 2 retinopathy of prematurity (ROP). BPDwas dened as oxygenrequirement at 36 weeks of postconceptional age.9 We calculated BPD ratein survivors. Follow-up for BPD denition was completed before discharge.Intraventricular hemorrhage was classied according to Papile et al.10 andROP was graded according to the international classication of ROP.11

Data processing and statistical analysis

Clinical characteristics of infants in the two groups were described usingmean values and s.d. or rate and percentage. The Student s t-test was

performed for parametric continuous variables and the Fishers exact testfor categorical variables. KolmogorovSmirnov tests on population in totaland on the two groups conrmed the normal distribution of the variablesduration of ventilation and length of oxygen exposure and appropriate-ness of Student's t-test. The linear change of PEEP, FiO2 and a/AO2 ratioduring the LRM application to infants of group A were analyzed byrepeated measures analysis of variance. Po0.05 was consideredstatistically signicant.

RESULTS

Twenty four infants were included in the study. Clinicalcharacteristics of infants in the two groups were similar (groupA,n = 12, GA 29.5 1.0 weeks, BW 1314 96 g,Silverman Andersonscore 8.6 0.8, females 7/12; group B,n = 12, GA 29.4 0.9 weeks;

BW 1296 88 g; Silverman Anderson score 8.2 0.7, females 6/12).Group A received the LRM at 96 25 min of age and the maneuverlasted for 70 12 min. Ventilatory and gas analysis changesduring the maneuver are described in Tables 13. There wereno statistically signicant differences between the two groups inFiO2, PEEP, a/AO2ratio and PaO2at the start of LRM and number ofextubation failure (P>0.05). The maximum PEEP level at the endof the incremental increase was higher in group A (Po0.05). Thenal PEEP level after decrementing PEEP and completing theentire process was lower (Po0.05). Moreover, the a/AO2 ratio inthe rst 12 h of life was signicantly higher (Po0.05). A shorterneed for mechanical ventilation (Po0.05) and duration of oxygentherapy (Po0.05) in the treated group was observed. The numberof surfactant doses used in group A were signicantly lower thanthat of group B (Po0.05). Group A and B showed differences

in max PEEP during the

rst 12h of life (8.4 0.5 cm versus6.7 0.6 cm H2O, P= 0.000) and time to lowest FiO2(101 18minversus 342 128 min; P= 0.000). FiO2 levels progressively decrea-sed (F= 43.240, P= 0.000) and a/AO2 ratio gradually increased(F= 30.594, P= 0.000) during the LRM application to infants ofgroup A. No differences were observed in extubation failure, BPD,ROP and death between the two groups. InFigure 1,step-by-stepchanges in SpO2 and FiO2 related to PEEP levels during the LRM

Table 1. Ventilatory and gas analysis changes during the LRM and in

the rst 12 h of life

Group A(n =12)

Group B(n = 12)

P

FiO2 at the start fo LRM 0.55 0.16 0.51 0.14 0.744Lowest FiO2

a 0.27 0.02 0.39 0.06 0.000Time to the lowest FiO2 (min) 101 18 342 128 0.000PEEP at the start of LRM (cm H2O) 6.6 0.5 6.5 0.5 0.698Max PEEP during LRM (cm H2O) 8.4 0.5 6.7 0.6 0.000Final PEEP at the end of LRM(cm H2O)

6.4 0.4 6.6 0.4 0.293

a/AO2ratio at the start of LRM 0.24 0.06 0.25 0.06 0.817a/AO2ratio at the end of LRM

a 0.45 0.10 0.35 0.08 0.013

Abbreviations: a/AO2, arterial/alveolar oxygen ratio; FiO2, fraction of

inspired oxygen; LRM, lung recruitment maneuver; PaO2, partial pressure

of oxygen in arterial blood; PEEP, positive end-expiratory pressure.aIn the rst 12h of life.

Lung recruitment maneuver

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application in the group A are shown. FiO2 levels progressively

decreased with the LRM for the growing SpO2 levels. When thePEEP level reached 5 cm H2O, a reduction of SpO2 was recordedand the PEEP level was reincreased to achieve prior SpO 2 levels.During the LRM application, no adverse events occurred,circulatory parameters were stable, and the maneuver was welltolerated.

DISCUSSION

LRM can be dened as a transient increase of transpulmonarypressure with the goal of opening or recovering alveolar units withhigh critical opening pressure, thus increasing end-expiratory lungvolume.12These effects may be temporary, but, over time, alveolarstability may be preserved with maintenance of an adequate PEEP

after RM administration.

1315

In the NICU, LRM have been limited primarily to increasingmean airway pressure during high frequency ventilation. Once theventilation mode is determined, the most important factor isselecting a ventilation strategy that optimizes lung volume. Thereis evidence that optimization of the lung volume is critical tolungprotection, regardless of what ventilation mode is used.1618

PEEP was used mainly as an adjunct to improve oxygenationand decrease work of breathing by shifting tidal breathing to amore compliant portion of the pressurevolume curve.19 PEEP isnow considered a means to recruit the lung and minimize injuryassociated with repeated opening and closure of an atelectaticlung.20 There is potential to prevent recollapse of alveoli if PEEP isapplied after recruitment.21 Clinical studies are required todetermine whether setting the right level of PEEP should be

performed according to ination or deation PV curves; in otherwords, should PEEP be systematically implemented after arecruitment maneuver. An optimal PEEP may be dened as thelevel of continuous pressure that, after an LRM, prevents alveolarcollapse and avoids overination with optimal lung volume.22

There is no evidence that starting the maneuver with a differentlevel of PEEP changes the effects of the practice. The settings wechosen in this study are all according to the referencedliterature.23 Castoldi F et al.23 found that the adequate PEEP,added to VG ventilation, can improve the effect of volume-targeted ventilation in acute neonatal RDS .

Our results suggest that, in the LRM group, we more rapidlyobtained an optimal lung volume (proved by a signicantlyreduced time to achieve a good oxygen saturation with minimalFiO2 and a better nal a/AO2 ratio. Furthermore, the duration ofmechanical ventilation and oxygen therapy in the LRM group wassignicantly reduced, which is consistent with the ndings ofCastoldi F et al.23 group.

Surfactant is now often given shortly after birth as prophylaxisagainst RDS. In preterm lambs, surfactant spreads less homo-geneously in a ventilated lung than when given before the rstbreath.24 In premature infants, whose clinical condition requiresemergency intubation or in whom elective intubation has beenchosen, it is good practice to administer exogenous surfactant asearly as possible.25,26 If given later, the clinical effect of surfactantis so far insufcient for treating RDS. In our study, surfactant wasgiven as soon as possible after tracheal intubation.

Our study has several limitations. First, the sample size is small.Further, larger studies of the similar experiments are warranted.Second, we did not measure intrinsic PEEP. Many preterm infantswith RDS can have intrinsic PEEP and it is possible that intrinsicPEEP may have affected both gas exchange and lung mechanics

parameters of study. Third, this study only observed the short-term effects on oxygenation and ventilator parameters. Long-termclinical effects need to be studied to adequately address the issueof safety.

In conclusion, early LRM in preterm infants with RDS resulted inan earlier achievement of the lowest FiO2 for the rst 12 h of life,which was signicantly lower than the FiO2 previously necessaryto obtain adequate arterial oxygenation, and a shorter O2dependency. These results suggest that the LRM is a reasonablepractice to improve the effect of premature RDS.

CONFLICT OF INTEREST

The authors declare no conict of interest.

75

80

85

90

95

100

105

5 6 7 8 7 6 5 6

PEEP (cm H2O)

SpO2(%)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

FiO2

SpO2

FiO2

Figure 1. Changes of fraction of inspired oxygen (FiO2) andsaturation of peripheral oxygen (SpO2) related to positive end-expiratory pressure (PEEP) levels during lung recruitment maneuverin the group A.

Table 2. Respiratory and clinical outcomes

Group A(n = 12)

Group B(n = 12)

P

Surfactant doses (n) 1.1 0.3 1.5 0.5 0.027Extubation failure (n) 1 1 NSLength of respiratory support (d) 5.6 1.4 6.1 2.0 0.026Length of tracheal intubation (d) 4.8 1.0 5.8 1.0 0.026

BPD (n) 0 1 NSPDA occurrence (n) 3/12 3/12 NSSepsis (n) 2/12 2/12 NSROP grade >2 (n) 0 0 NSModerate or severe BPD (n) 0 0 NSDeath (n) 0 0 NSO2 dependency (d) 7.83 2.04 9.92 2.78 0.049

Abbreviations: BPD, bronchopulmonary dysplasia; NS, not signicant; PDA,

patent ductus arteriosus; ROP, retinopathy of prematurity.

Table 3. Changes of PEEP, FiO2 and a/AO2ratio in the course of lung

recruitment maneuver in the group A (n=12)

Different time point PEEP (cm H2O) Fi O2 a/AO2 ratio

The start of LRM 6.6 0.5 0.55 0.16 0.24 0.06Max PEEP of LRM 8.4 0.5 0.27 0.02 0.34 0.06

The end of LRM 6.4 0.4a 0.29 0.03a 0.45 0.10a

F 257.552 43.240 30.594P 0.000 0.000 0.000

Abbreviations: a/AO2 ratio, alveolar/Arterial oxygen ratio; FiO2, fraction of

inspired oxygen; PEEP, positive end-expiratory pressure.aPo0.05 versus start level.


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ACKNOWLEDGEMENTS

We thank all the neonatal units and staff who responded to our survey. This research

was funded by grants from Jiangsu Province Health Department (Project no:

F201233).

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5Lung Recruitment Maneuver During Proportional Assist Ventilation of Preterm Infants With Acute Respiratory Distress Syndrome