Invasive ventilation modes in children: a systematic review and meta-analysis.

0.33 MB·English

by  Duyndam, Anita

Duyndametal.CriticalCare2011,15:R24
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RESEARCH Open Access
Invasive ventilation modes in children:
a systematic review and meta-analysis
Anita Duyndam, Erwin Ista*, Robert Jan Houmes, Bionda van Driel, Irwin Reiss, Dick Tibboel
Abstract
Introduction: The purpose of the present study was to critically review the existing body of evidence on
ventilation modes for infants and children up to the age of 18 years.
Methods: The PubMed and EMBASE databases were searched using the search terms ‘artificial respiration’,
‘instrumentation’, ‘device’, ‘devices’, ‘mode’, and ‘modes’. The review included only studies comparing two
ventilation modes in a randomized controlled study and reporting one of the following outcome measures: length
of ventilation (LOV), oxygenation, mortality, chronic lung disease and weaning. We quantitatively pooled the results
of trials where suitable.
Results: Five trials met the inclusion criteria. They addressed six different ventilation modes in 421 children: high-
frequency oscillation (HFO), pressure control (PC), pressure support (PS), volume support (VS), volume diffusive
respirator (VDR) and biphasic positive airway pressure. Overall there were no significant differences in LOV and
mortality or survival rate associated with the different ventilation modes. Two trials compared HFO versus
conventional ventilation. In the pooled analysis, the mortality rate did not differ between these modes (odds ratio =
0.83, 95% confidence interval = 0.30 to 1.91). High-frequency ventilation (HFO and VDR) was associated with a better
oxygenation after 72 hours than was conventional ventilation. One study found a significantly higher PaO /FiO ratio
2 2
with the use of VDR versus PC ventilation in children with burns. Weaning was studied in 182 children assigned to
either a PS protocol, a VS protocol or no protocol. Most children could be weaned within 2 days and the weaning
time did not significantly differ between the groups.
Conclusions: The literature provides scarce data for the best ventilation mode in critically ill children beyond the
newborn period. There is no evidence, however, that high-frequency ventilation reduced mortality and LOV.
Longer-term outcome measures such as pulmonary function, neurocognitive development, and cost-effectiveness
should be considered in future studies.
Introduction more sensitive indicator of the effects of clinical ventila-
Ventilator-induced lung injury in critically ill children tion interventions than would mortality or duration of
suffering from acute respiratory failure should be coun- ventilation [1].
teracted by adapting ventilation management to the Pediatric intensive care units worldwide use a wide
cause of respiratory failure [1]. Ideally, management variety of ventilation modes: high-frequency oscillation
should be based on proven effective strategies. In a mul- (HFO), pressure control (PC), synchronized intermittent
ticenter study, bronchiolitis was the most frequent cause mandatory ventilation, pressure support (PS), pressure-
of respiratory failure in infants (43.6%); pneumonia the regulated volume control and, more recently, neurally
most frequent cause in older children (24.8%) [2]. Mor- adjusted ventilator assist [3,4]. The ventilation mode is
tality in that study was rare (1.6%); the median duration often not targeted specifically to the underlying disease
of ventilation was 7 days. Randolph suggested that in but rather is determined by the intensive care physi-
pediatric clinical trials long-term morbidity would be a cian’s experience, local pediatric intensive care unit pol-
icy and protocols, or outcomes of studies in adults
*Correspondence:[email protected] [1,2,5]. An unambiguous international guideline is still
IntensiveCareUnit,ErasmusMC-SophiaChildren’sHospital,POBox2060,
lacking [1,5].
3000CBRotterdam,TheNetherlands
©2011Duyndametal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.
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The objective of the present article is to systematically effect size? Consensus between the authors on the inter-
review the randomized controlled trials (RCTs) compar- pretation of the extracted data was achieved.
ing ventilation modes used in critically ill children (from
term born up to 18 years of age) on the following out- Data abstraction
come measures: length of ventilation, oxygenation, mor- Authors AD and EI each independently recorded patient
tality, chronic lung disease and weaning. We aimed to characteristics (sample size, age, respiratory failure),
determine whether there is sufficient evidence to decide details of the ventilation mode and the period over
on the better mode. which outcome variables were measured. Outcome vari-
ables considered were the following: length of ventila-
Materials and methods tion (LOV), oxygenation, chronic lung disease, mortality
Search and selection and weaning.
A systematic search was performed in the PubMed and
EMBASE databases in September 2010. MeSH terms Statistical methods
and keywords searched for in the titles, abstracts and We quantitatively pooled the results of individual trials,
keywords areas were ‘artificial respiration’, ‘instrumenta- where suitable. We expressed the treatment effect as an
tion’, ‘device’, ‘devices’, ‘mode’, and‘ modes’, combined odds ratio (OR) for dichotomous outcomes and as a
with the Boolean operators AND, OR. (Additional file 1 weighted mean difference (WMD) for continuous out-
provides the complete search strategy.) The search was comes with 95% confidence intervals (CIs). The pooled
limited to RCTs or quasi-experimental studies, with age OR was estimated with the Mantel-Haenszel method,
limit >28 days until 18 years. Only articles comparing at which is generally the most robust model [7]. Differ-
least two ventilation modes were selected for review. ences were considered statistically significant if P < 0.05
Articles on non-invasive ventilation, studies in prema- or if the 95% confidence interval did not include the
®
ture neonates (< 37 weeks) and articles in other lan- value 1. The analyses were performed with Microsoft
guages than English or Dutch were excluded. No limits Excel, Office 2007 for Windows.
were imposed on the publication date.
Two authors (AD, EI) independently reviewed Results
abstracts and full-text articles to identify eligible studies. Search and selection
Reference lists of retrieved studies were hand-searched After filtering out duplicate studies, the titles and
for additional articles. abstracts of 461 potentially relevant articles were
screened (Figure 1). The reference lists yielded one
Quality assessment other study that had been missed because the keywords
The study quality and level of evidence were assessed on were not in the title or abstract. Eventually, nine full-
criteria established by the Dutch Institute for Healthcare text articles were retrieved and assessed for eligibility.
Improvement CBO in collaboration with the Dutch Four RCTs were excluded for any of the following rea-
Cochrane library (see Additional file 2 and Table 1) [6]. sons: focus on triggering instead of ventilation, inclusion
The major criteria were as follows: Was assignment to of infants below 37 weeks of gestational age, or not
the study group randomized? Were investigators comparing two ventilation modes [8-11]. The present
blinded? Was it an intention-to-treat analysis? Were the review therefore includes five RCTs [12-16].
study groups comparable? Was there appropriate report Tabulated details of these five RCTs are presented in
of outcome results for each group and the estimated Tables 2 and 3.
Table 1Level ofevidence
Level Descriptionofevidence
1++ High-qualitymeta-analyses,systematicreviewsofRCTs,orRCTswithaverylowriskofbias
1+ Well-conductedmeta-analyses,systematicreviewsofRCTs,orRCTswithalowriskofbias
1- Meta-analyses,systematicreviewsofRCTs,orRCTswithahighriskofbias
2++ High-qualitysystematicreviewsofcase-controlorcohortstudies;orhigh-qualitycase-controlorcohortstudieswithaverylowriskof
confounding,bias,orchanceandahighprobabilitythattherelationshipiscausal
2+ Well-conductedcase-controlorcohortstudieswithalowriskofconfounding,bias,orchanceandamoderateprobabilitythatthe
relationshipiscausal
2- Case-controlorcohortstudieswithahighriskofconfounding,biasorchance,andasignificantprobabilitythattherelationshipisnotcausal
3 Non-analyticstudies;forexample,casereports,caseseries
4 Expertopinion
RCT,randomizedcontrolledtrial.
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Figure1Searchresults.RCT,randomizedcontrolledtrial.
Length of ventilation inspiratory time to increase the mean airway pressure
The LOV served as the outcome measure in four studies and to limit peak inspiratory pressure increases. Cross-
(Table 2). First, Arnold and colleagues in a multicenter over to the alternate ventilator was required if the
trial compared HFO and conventional ventilation (CV) patient met defined criteria for treatment failure. LOV
in 58 children with either diffuse alveolar disease and/or did not significantly differ between the CV and HFO
air leak syndrome; 29 had been randomized to HFO, groups (WMD = 2.0 days, 95% CI = -9.61 to 13.61).
and 29 to CV [12]. During the first 72 hours of study, Second, Dobyns and colleagues in a multicenter study
the mean airway pressure was significantly (P < 0.001) compared HFO and CV in 99 children with acute
higher in the HFO group. The HFO strategy entailed hypoxemic respiratory failure [14]. Seventy-three children
aggressive increases in mean airway pressure to attain were treated with CV (38 without inhaled nitric oxide
the ideal lung volume and to achieve an arterial oxygen (iNO), 35 with iNO), and 26 with HFO (12 without iNO,
saturation >90% with FiO < 0.6. The CV strategy 14 with iNO). Mechanical ventilation and FiO were
2 2
entailed stepping up the end-expiratory pressure and adjusted to maintain SaO at 90% and pCO between 45
2 2
Table 2Includedrandomized controlled trials -ventilation hD
ttpuy
Reference Studypopulation Intervention/mode Outcomemeasures eLevvideelnocfe ://ccfondam
Mortality/survival LOV(days) Oxygenation CLD rum eta
Arnoldand 58children(age:HFO Multicenterstudy(five Numberofsurvivorsat30days- Total-CV:22± PaO2/PAO2increaseovertime(72hours)in CV:n=10(59%); 1+ .co.lC
c[1o2ll]eagues 23..35y±ea2r.5s)vws.itChVd3if.f1us±e centers) C29V:(6167%o)f(2N9S)(59%);HFO:19of 1277;HFO:20± HFOcomparedwithCV(P<0.001) H=F0O.0:3n9;=O4R(=215%.4)(P m/c ritic
o a
alveolardiseaseand/or 95%CI=1.2to n l
airleaksyndrome Comparisoneffectivenessof Death(ranked)-CV:40%,CVto Survivors(at30 PaO2/PAO2-HFO:0.13(0hours)upto0.26 23.2)(O2at30days) tent/1520Care
2H9F)O-(cnro=ss2o9v)erwithCV(n= H82F%O:(4P2≤%0,.0H0F1O):6%,HFOtoCV: d18a;ysH)F-OC:V2:72±9± (h7o2uhrso)urs);CV:0.13(0hours)upto0.22(72 /1/R211,1
31. 45:R
2
Crossover:CVtoHFO(n= Nonsurvivors(at Aftercrossover-PaO/PAO increaseover 4
2 2
19),HFOtoCV(n=11) 30days)-CV:11 time(72hours)inCVtoHFOgroup
±9;HFO:8±6 comparedwithHFOtoCVgroup(P=
(NS) 0.003)
Dobyns 99children(age0to Multicenterstudy(seven Trendofimprovedsurvivalin CV:22±4;CV+ PaO/FiO (PF)ratio-after4hours:HFO+ 1+
2 2
and 23years)withAHRF, centers) HFO+iNO-CV:22of38(58%); iNO:21±3; iNO136±21vs.CV96±6(P=0.2);after
colleagues oxygenationindex>15 CV+iNO:20of35(53%);HFO: HFO:52±28; 12hours:HFO+iNO184±45vs.CV107±
[14] 7of12(58%);HFO+iNO:10of HFO+iNO:17 8andCV+iNO115±9,HFO136±32(P
14(71%)(P=0.994) ±4(P=0.098) =0.023);after24hours:treatmentboth
HFO+iNOandHFOresultedingreater
improvementinPFratiothanCVorCV+
iNO(P=0.005);after72hours:HFO259±
60vs.CV148±15andCV+iNO150±19;
HFO+iNO213±29(P=0.027)
Comparisonsbetween
patientstreatedwithHFO+
iNO(n=14),HFOalone(n
=12),CV+iNO(n=35),
andCValone(n=38)
Jaarsma 18children(age0to Single-centerstudy ND BIPAP:9.8±9.2; ND 1-
and 10years)with PS:6.4±5.8(P
colleagues respiratoryfailurefor =0.27)
[13] ventilation
CompareBIPAP(n=11)
withPS(n=7),determining
whichmodeiseffective,
safeandeasy
Carman 64children(age7.4± Single-centerstudy VDR:2/32(6%);PC:5/32(16%) VDR:12±2; PFratio-VDR:563±16;PC:507±13(P< 1-
and 0.7years)with (NS) PCV:11±2(NS) 0.05)
colleagues inhalationinjury
[16]
CompareVDR(n=32)with
PC(n=32) P
a
g
Datapresentedasnumber/total(percentage)ormean±standarddeviation.AHRF,acutehypoxemicrespiratoryfailure;BIPAP,biphasicpositiveairwaypressure;CI,confidenceinterval;CLD,chroniclungdisease;CV, e
conventionalmechanicalventilation;HFO,high-frequencyoscillationventilation;iNO,inhalednitricoxide;LOV,lengthofventilation;ND,nodata;NS,notsignificant;OR;oddsratio;VDR,volumediffusiverespirator 4
o
(high-frequencytime-cycledpressureventilator);PC,pressure-controlledventilation;PS,pressuresupportventilation. f
8
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Table 3Included randomized controlled trials-weaning
Reference Studypopulation Intervention/mode Outcomemeasures Levelof
evidence
Durationof Extubationfailurerate Oxygenation
weaning
(days)a
Randolph 182children(age0to17 Multicenterstudy(10centers) PS:1.6(0.9to PS(15%),VS(24%);no ND 1++
and years)withweaningof toevaluateweaning 4.1);VS:1.8(1.0 protocol(17%)(P=0.44).
colleagues ventilationsupportformore protocolscomparingVS to3.2);no Malechildrenmore
[15] than24hoursandwho (continuousautomated protocol:2.0 frequentlyfailedextubation
failedatestforextubation adjustmentofPSbythe (0.9to2.9)(P (OR=7.8695%CI=2.36to
readinessonminimalPS ventilator)(n=59)andPS =0.75) 26.2;P<0.001)
(adjustmentbyclinicians)(n=
61)withstandardcare(no
protocol)(n=59)
aDatapresentedasmedian(interquartilerange).CI,confidenceinterval;ND,nodata;OR,oddsratio;PS,pressuresupport;VS,volumesupport.
and 55 mmHg. Higher pCO values were tolerated as aiming at a pCO of 4 to 5 kPa and a pO of 8 to
2 2 2
long as the arterial pH was 7.20. In the CV strategy, the 11 kPa. The LOV did not significantly differ between
positive end-expiratory pressure was increased incremen- biphasic positive airway pressure (9.8 ± 9.2 days) and PS
tally to improve oxygenation while avoiding clinical and (6.4 ± 5.8 days).
radiographic signs of lung hyperinflation. The peak air- Pooled analysis of these trials resulted in a signifi-
way pressure was maintained at <35 to 40 cmH O by cantly shorter LOV after CV in comparison with HFO
2
limiting the level of tidal volume and positive end-expira- (WMD = -2.3 days, 95% CI = -3.63 to -1.04) (Table 4).
tory pressure. The initial HFO settings were: FiO of 1.0,
2
33% inspiratory time, frequency of 10 Hz, and mean air- Oxygenation
way pressure set at 2 to 4 cmH O above that used on Three studies addressed the effects of different ventila-
2
CV. The pressure amplitude was set to achieve percepti- tion modes on oxygenation.
ble chest wall motion and was adjusted if possible to In the study by Dobyns and colleagues, the PaO /FiO
2 2
optimize ventilation. In this study HFO did not lead to a (PF) ratio improved most in the HFO mode with iNO
significantly shorter LOV (Table 2). For the two ventila- after 4 hours (136 ± 21 mmHg vs. CV 96 ± 6 mmHg;
tion groups without iNO, however, the LOV significantly P = 0.2) and after 12 hours (HFOV + iNO 184 ± 45
differed between CV and HFO (WMD = -30.0 days, 95% mmHg vs. CV 107 ± 8 mmHg and CV + iNO 115 ± 9
CI = -45.89 to -14.11). mmHg, P = 0.023; HFOV 136 ± 32 mmHg) [14]. After
Third, Carman and colleagues compared the volume 24 hours, HFO treatment both with and without iNO
diffusive respirator (VDR) with PC ventilation in burned provided better oxygenationthan CVboth with and with-
children with inhalation injury [16]. The VDR is a high- out iNO (P < 0.05). After 72 hours, HFO treatment was
frequency, time-cycled pressure ventilator that can ven- associated with the best improvement in PF ratio (HFO
tilate, oxygenate and promote secretion removal. SaO 259 ± 60 mmHg vs. CV 148 ± 15 mmHg and CV + iNO
2
was maintained at or above 90%; PaCO was maintained 150 ± 19 mmHg, P = 0.027; HFOV + iNO 213 ±
2
at <55 mmHg. Thirty-two children with a mean ± stan- 9 mmHg). The two therapies did not differ in failure rate.
dard deviation age of 5.5 ± 0.9 years were treated with Arnold and colleagues reported a significant (P = 0.001)
VDR, and 32 children with a mean ± standard deviation relationship between time and a decreasing oxygenation
age of 9.4 ± 1.0 years were treated with PC ventilation index in the HFO group but not in the CV group [12].
(P = 0.04 for mean age). The LOV was significantly dif- After crossover (19 patients crossed over from CV to
ferent between the study groups (WMD = -1.0 days, HFO and 11 patients crossed over from HFO to CV) this
95% CI = -1.98 to -0.02). relationship was significant in both crossover groups (P =
Fourth, Jaarsma and colleagues randomized 18 chil- 0.03 crossover to CV; P = 0.02 crossover to HFO).
dren with respiratory failure to either biphasic positive Carman and colleagues reported a significantly higher
airway pressure (n = 11) or pressure support ventilation PF ratio in the VDR mode compared with PC (563 ±
(n = 7); their median age was 4 months (range 4 weeks 15 mmHg vs. 507 ± 13 mmHg, P < 0.05) but did not
to 10 years) [13]. Initial ventilator settings depended on specify the time point at which the best PF ratio was
age and the cause of respiratory failure, and were measured [16]. As the oxygenation parameters in these
adjusted according to thoracic excursions and the mea- three studies were not uniform it was not possible to
sured tidal volume. Adjustments were made afterwards pool the data.
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Table 4Meta-analysis oftrials comparing high-frequency ventilation withconventional ventilation: lengthof
ventilation
Study CV HFOV WMD(95%CI) Zvalue(Pvalue)
Mean(SD) n Mean(SD) n
Arnoldandcolleagues[12] 22(17) 29 20(27) 29 2(-9.61to13.61) -0.338(0.74)
Dobynsandcolleagues[14] 22(4) 38 52(28) 12 -30(-45.89to-14.11) 3.699(0.0002)
Subtotal 67 41 -11.51(-15.14to-7.88) -6.221(<0.0001)
Carmanandcolleagues(VDR)[16] 11(2) 32 12(2) 32 -1(-1.98to-0.02) -2.0(0.046)
Overall 99 73 -2.34(-3.63to-1.04) -3.542(0.0004)
CI,confidenceinterval;CV,conventionalventilation;HFOV,High-frequencyoscillationventilation;SD,standarddeviation;VDR,volumediffusiverespirator
(high-frequencytime-cycledpressureventilator);WMD,weightmeandifference.
Mortality and survival discretion of the physician (n = 60) (Table 3) [15]. The
Three studies focused on the outcome measure of mor- VS and PS protocols dictated that FiO and positive
2
tality or survival. end-expiratory pressure be adjusted to maintain SpO at
2
None found a significant difference in mortality 95% or higher. In the PS protocol, the amount of pres-
between patients treated with HFO and those treated sure support was adjusted to achieve an exhaled tidal
with CV. Arnold and colleagues reported a mortality volume goal of 5 to 7 ml/kg. In the VS protocol, the
rate of 34% (10/29) for HFO versus 41% (12/29) for CV ventilator automatically adjusted the level of PS to
(OR = 0.75, 95% CI = 0.26 to 2.16) [12]. The mortality achieve an exhaled tidal volume of 5 to 7 ml/kg.
rate in patients not crossed over to CV from HFO or to Two outcome measures were assessed: weaning time
HFO from CV, however, was significantly better (P = andextubationfailure(thatis,anyinvasiveornon-invasive
0.003) than that in patients managed with CV only. ventilator support within 48 hours of extubation). The
Dobyns and colleagues showed that the survival rate authors hypothesized that VS would result in a shorter
for patients treated with HFO in combination with iNO weaning time as the inspiratory pressures automatically
was higher than that for patients treated with HFO only decrease with improvement of lung compliance. Most
or with CV (71% vs. 58% in CV, 53% in CV + iNO and childrencouldbeweaned within2days andthe weaning
58% in HFO) [14]. These differences did not achieve sta- timedidnotsignificantlydifferfortheprotocolsused:PS,
tistical significance. These authors speculated that the 1.6days;VS,1.8days;andno protocol,2.0days.Extuba-
improved lung recruitment by HFO enhances the effects tion failure rates were not significantly different for PS
of low-dose iNO on gas exchange. The mortality rate (15%),VS(24%)andnoprotocol(17%).
for HFO without iNO was 42% (5/12) versus 42% (16/
38) for CV without iNO (OR = 0.98, 95% CI = 0.26 to Quality of studies
3.66) [14]. In the study by Carman and colleagues, five These five studies compared six different ventilation
out of 32 (16%) patients in the PCV group died versus modes in 421 children [12-14,16]. Two studies, based on
two out of 32 (6%) in the VDR group (OR = 0.36, 95%
CI = 0.06 to 2.01) [16].
Table 5Meta-analysis oftrials comparing high-frequency
In the pooled analysis, the mortality rates in the HFO ventilation withconventional ventilation: mortality
mode and in CV did not differ (OR = 0.70, 95% CI =
Study Conventional High-frequency Oddsratio(95%
0.33 to 1.47) (Table 5). ventilation oscillation confidence
ventilation interval)
Chronic lung disease Arnoldand 12/29 10/29 0.75(0.26to2.16)
colleagues[12]
Chronic lung disease was examined only in the study by
Dobynsand 6/38 5/12 0.98(0.26to3.66)
Arnold and colleagues [12]. The proportion of patients
colleagues[14]
treated with HFO and requiring supplemental oxygen at
Subtotal 67 41 0.83(0.30to1.91)
30 days was lower than that of patients managed with Mantel-
CV (P = 0.039; OR = 5.4, 95% CI = 1.2 to 23.2). Haenszel
Carmanand 5/32 2/32
colleagues
Weaning
(VDR)[16]
Randolph and colleagues randomized 182 children aged
OverallMantel- 99 73 0.70(0.33to1.47)
from 0 to 17 years to either a PS protocol (n = 62), a Haenszel
volume support (VS) protocol (n = 60) or a no ventila-
Datapresentedasnumber/total.VDR,volumediffusiverespirator(high-
tion weaning protocol in which weaning was at the frequencytime-cycledpressureventilator).
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an intention-to-treat analysis, met all CBO quality cri- The level of evidence proved moderate to good in three
teria [14,15]. Blinding was not possible in any of these studies [12,14,15]. The study by Jaarsma and colleagues
studies, because ventilator displays cannot be masked. In was stopped halfway through as both physicians and
four studies, patient characteristics and prognostic vari- nurses preferred biphasic positive airway pressure [13].
ables did not differ between the intervention groups. In This was designated level 1 evidence because of the high
the study by Carman and colleagues, the mean age dif- risk of bias. Likewise, the study by Carman and collea-
fered significantly [16]. Only one study calculated the gues was designated level 1 evidence because the rando-
estimated effect sizes (relative risk of OR) for continu- mization failed for the demographic variable age [16].
ous outcome variables such as LOV, survival or weaning The strengths of the present review include a compre-
failure [15]. The study by Dobyns and colleagues [14] is hensive search strategy, broad inclusion criteria (result-
of limited quality because it is a secondary analysis of ing in a representative, heterogeneous population) and
data obtained from a previous multicenter, randomized assessment of clinically important outcomes. In addition,
trial on iNO treatment in pediatric acute hypoxemic we pooled the data. This statistical approach is also
respiratory failure [8]. The mode of ventilation was allowed for quasi-experimental, nonrandomized studies -
determined by the attending physician with the guidance such as the study by Dobyns and colleagues [14] - in
of guidelines to maximize oxygenation. The patient was which randomization of groups was not possible or failed
then randomized to treatment with or without iNO [23]. Meta-analytic techniques in the analysis of nonran-
[14]. Levels of evidence for the different studies are pre- domized studies have been criticized for their potential to
sented in Tables 2 and 3. perpetuate the individual biases of each study and to give
a false impression of cohesion in the literature, thus dis-
Discussion couraging further research [24]. The counter-argument is
The present review aimed at identifying the various ven- that statistical quantification and pooling of results from
tilation modes used in children over the past three dec- many studies helps to identify reasons for variability,
ades, searching for any data that would favor a inconsistency or heterogeneity in the literature, and thus
particular mode for pediatric ventilation. The five RCTs may encourage further research [23,25]. Nevertheless, the
included in this review varied in the investigated modes pooled results of the present study should be interpreted
of ventilations, in outcomes and in patient groups. cautiously in view of the diversity in patient groups, sam-
High-frequency ventilators may use different ventila- ple sizes, randomization methods, types of ventilators and
tion modes. Two studies included in the present review ventilation strategies.
concerned HFO ventilation [12,14]; a third concerned The reviewed RCTs cannot easily be compared owing
the VDR (high-frequency, time-cycled pressure ventila- to the heterogeneity in age, underlying disease and
tor) [16]. The evidence from these studies does not study outcomes. We would therefore recommend setting
allow making a recommendation on the preferred type up studies investigating the best ventilation strategy for
of high-frequency ventilator. Two RCTs compared HFO specific age categories or underlying pathology [1].
with CV on the outcomes oxygenation, LOV and mor- Furthermore, as mortality is rather low, longer-term
tality. Neither study found significant differences in outcome measures others than the short-term outcome
mortality and LOV. Analysis of the pooled data, how- measures studied in the present review should be con-
ever, revealed a significantly lower LOV for the CV sidered, such as pulmonary function, neurocognitive
groups. A confounding factor for this finding is the development and cost-effectiveness. Internationally con-
threefold sample size of conventionally ventilated sensus on the most appropriate outcome measures
patients in the study by Dobyns and colleagues [14]. On should be reached.
the other hand, this analysis only concerned patients
treated with HFO and CV without iNO. Conclusions
In all studies, oxygenation significantly improved The available literature does not provide sufficient evi-
over 72 hours for patients treated with high-frequency denceonthebestventilationmodeincriticallyillchildren
oscillators [12,14,16]. A lack of uniform data on oxyge- beyond the newborn period. High-frequency ventilation
nation, however, prevented analysis of pooled data. (HFO and VDR) provided better oxygenation after
This finding is in contrast with that reported for pre- 72 hours than did CV. There is no evidence that high-
term neonates. The systematic reviews and meta- frequencyventilationwouldreducemortalityandLOV.
analyses overall provide no evidence that HFO as the
initial ventilation strategy offers important advantages Key messages
over CV in terms of preventing chronic lung disease in (cid:129) There is no evidence for the best ventilation mode
preterm infants with acute pulmonary dysfunction in critically ill children beyond the newborn period
[17-22]. up to 18 years.
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(cid:129) The different modes have not yet been investigated 9. GuthrieSO,LynnC,LafleurBJ,DonnSM,WalshWF:Acrossoveranalysisof
in (large) groups of children. mandatoryminuteventilationcomparedtosynchronizedintermittent
mandatoryventilationinneonates.JPerinatol2005,25:643-646.
(cid:129) Oxygenation significantly improved over 72 hours
10. ThiagarajanRR,ColemanDM,BrattonSL,WatsonRS,MartinLD:Inspiratory
for patients treated with high-frequency oscillators. workofbreathingisnotdecreasedbyflow-triggeredsensingduring
(cid:129) Longer-term outcome measures such as pulmonary spontaneousbreathinginchildrenreceivingmechanicalventilation:a
preliminaryreport.PediatrCritCareMed2004,5:375-378.
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lengthofventilation;OR:oddsratio;PC:pressurecontrol;pCO:partial LuckettPM,ForbesP,LilleyM,ThompsonJ,CheifetzIM,HibberdP,
2
arterialpressureofcarbondioxide;PF:PaO/FiO ratio;pO:partialpressure WetzelR,CoxPN,ArnoldJH:Effectofmechanicalventilatorweaning
2 2 2
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2
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