Intraoperative Mechanical Ventilation Strategies in Patients Undergoing One-Lung Ventilation: A Meta-Analysis
Intraoperative Mechanical Ventilation Strategies in Patients Undergoing One-Lung Ventilation: A Meta-Analysis
Intraoperative Mechanical Ventilation Strategies in Patients Undergoing One-Lung Ventilation: A Meta-Analysis
Abstract
Background: Postoperative pulmonary complications (PPCs), which are not uncommon in one-lung ventilation, are
among the main causes of postoperative death after lung surgery. Intra-operative ventilation strategies can influence
the incidence of PPCs. High tidal volume (VT) and increased airway pressure may lead to lung injury, while pressure-
controlled ventilation and lung-protective strategies with low VT may have protective effects against lung injury. In
this meta-analysis, we aim to investigate the effects of different ventilation strategies, including pressure-controlled
ventilation (PCV), volume-controlled ventilation (VCV), protective ventilation (PV) and conventional ventilation (CV),
on PPCs in patients undergoing one-lung ventilation. We hypothesize that both PV with low VT and PCV have protec-
tive effects against PPCs in one-lung ventilation.
Methods: A systematic search (PubMed, EMBASE, the Cochrane Library, and Ovid MEDLINE; in May 2015) was
performed for randomized trials comparing PCV with VCV or comparing PV with CV in one-lung ventilation. Meth-
odological quality was evaluated using the Cochrane tool for risk. The primary outcome was the incidence of PPCs.
The secondary outcomes included the length of hospital stay, intraoperative plateau airway pressure (Pplateau), oxygen
index (PaO2/FiO2) and mean arterial pressure (MAP).
Results: In this meta-analysis, 11 studies (436 patients) comparing PCV with VCV and 11 studies (657 patients) com-
paring PV with CV were included. Compared to CV, PV decreased the incidence of PPCs (OR 0.29; 95 % CI 0.15–0.57;
P < 0.01) and intraoperative Pplateau (MD −3.75; 95 % CI −5.74 to −1.76; P < 0.01) but had no significant influence on
the length of hospital stay or MAP. Compared to VCV, PCV decreased intraoperative Pplateau (MD −1.46; 95 % CI −2.54
to −0.34; P = 0.01) but had no significant influence on PPCs, PaO2/FiO2 or MAP.
Conclusions: PV with low VT was associated with the reduced incidence of PPCs compared to CV. However, PCV and
VCV had similar effects on the incidence of PPCs.
Keywords: Protective ventilation, Conventional ventilation, One lung ventilation, Pressure-controlled ventilation,
Volume-controlled ventilation
© 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
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Liu et al. SpringerPlus (2016) 5:1251 Page 2 of 12
at end-inspiration (Guldner et al. 2015). Protective ven- was defined as ventilation using VT ≥ 7 ml/kg predicted
tilation with low VT is thought to result in less ventilator- body weight with or without PEEP and without recruit-
induced lung injury and has become a routine strategy in ment maneuvers in one-lung ventilation (Lohser 2008;
patients with ARDS (Petrucci and De Feo 2013). Recent Della Rocca and Coccia 2013).
studies have reported similar results in that low VT pre- The included studies met the following criteria: rand-
vents postoperative complications in surgical patients omized controlled trials of patients aged 18 years or older
(Serpa Neto et al. 2015a, b). However, the effect of low who were undergoing one-lung ventilation during a sur-
VT on patients undergoing one-lung ventilation remains gical procedure. Randomized clinical trials (RCTs) were
unclear. In some studies, PV has been associated with a excluded if they did not involve a surgical procedure, if
decreased oxygenation index and more dead space ventila- they included patients undergoing cardiac surgery, if they
tion without decreases in the incidence of PPCs (Maslow included patients with cardiac diseases, sepsis or ARDS
et al. 2013; Jung et al. 2014; Blank et al. 2016; Neto et al. before surgery, if they were conference abstracts or if full-
2016). In other studies, PV was associated with a lower text articles could not be obtained, if they did not focus
incidence of PPCs and satisfactory gas exchange (Schil- on the comparisons of different ventilation strategies in
ling et al. 2005; Yang et al. 2011; Serpa Neto et al. 2015a, b). the dependent lung, if the intervention group and con-
VCV and PCV are also used in one-lung ventilation. PCV trol group had different ventilation settings during two-
may result in lower airway pressure and a more homoge- lung ventilation (TLV), or if the RCTs did not report any
neous distribution of the tidal volume; PCV also has less outcomes mentioned above. Animal studies were also
of an effect on cardiac function than VCV (Al Shehri et al. excluded.
2014). However, tidal volumes in PCV are highly variable The primary outcome of interest was the development
(Della Rocca and Coccia 2013). The benefits of PCV in of PPCs during follow up, defined as the development of
terms of oxygenation and protection against lung damage atelectasis, lung infiltration, pneumonia or ARDS. The
should be balanced. secondary outcomes included the length of hospital stay,
This meta-analysis aims to investigate the association intraoperative Pplateau, PaO2/FiO2 and MAP. PaO2/FiO2 at
between ventilation strategies and PPCs; the length of 20–40 min in one-lung ventilation in randomized parallel
hospital stay, intraoperative Pplateau, PaO2/FiO2 and MAP studies was included in the analysis of PaO2/FiO2. Cross-
were compared as the secondary outcomes. We hypothe- over studies were not used to evaluate the effect of ven-
size that PV with low VT and PCV have protective effects tilation strategies on PPCs, the length of hospital stay or
on PPCs in one-lung ventilation. PaO2/FiO2.
sis by removing trials and reanalyzing the remaining studies. 21 studies included in qualitative synthesis
Quality assessment
A Measure Tool to Assess Systematic Reviews 21 studies (22 comparisons) were included in the
meta-analysis
(AMSTAR) was applied to assess the methodologi- 11, comparisons testing pressure controlled ventilation vs
volume controlled ventilation
cal quality. Grading of Recommendations Assessment, 11, comparisons testing protective ventilation vs
conventional ventilation
Development and Evaluation (GRADE) system was used
to assess the evidence quality. Fig. 1 Study flow diagram
Table 1 Characteristics of included studies
Author Year No. of Study Details of VT Age (year), Type of surgery Duration of one- Outcomes Time point Preopera-
patients intervention (ml/kg) and mean (SD) lung ventilation of measure- tive FEV1 (%
PEEP (cmH2O) in each mode ment of out- of predicted)
(min), mean (SD) comes (SD)
PEEP = 0
Qutubet al. 2014 (1) 13 (1) PV 4 (1) VT = 4 (1) 42 (32–54) VATS Not reported Extravascular lung 15, 45 min after (1) 87.1 (3.0)
(2) 13 (2) PV 6 PEEP = 5 (2) 39.5 (31–51) water content OLV; 48 h, 30d (2) 88.4 (2.9)
(3) 13 (3) CV (2) VT = 6 (3) 36 (29–48) index, respiratory post operation (3) 85.8 (4.1)
PEEP = 5 parameters, gas
(3) VT = 8 exchange, clinical
PEEP = 5 outcomes
Jung et al. 2014 (1) 30 (1) PV (1) VT = 6 (1) 35.2 (10.2) VATS Not reported Respiratory param- 5, 15, 30, 45 min Not reported
(2) 30 (2) CV PEEP = 8 (2) 36.3 (9.5) eters after OLV
(2) VT = 10
PEEP = 0
Shen et al. 2013 (1) 53 (1) PV (1) VT = 5 (1) 60.5 (7.3) MIE (1) 72.2 (23.6) Clinical outcomes, 18 h post opera- (1) 92.8 (14.6)
(2) 48 (2) CV PEEP = 5 (2) 57.2 (9.1) (2) 75.0 (18.8) gas exchange, tion, 30d post (2) 87.1 (16.9)
(2) VT = 8 cytokines expres- operation
PEEP = 0 sion
Maslow et al. 2013 (1) 16 (1) PV (1) VT = 5 (1) 62 (14.4) Thoracic surgery (1) 42 (8.3) Respiratory 5, 10, 15, 20, (1) 85.8 (21.7)
(2) 16 (2) CV PEEP = 5 (2) 69.6 (12.9) (2) 46 (9.5) parameters, gas 30 min after (2) 75.4 (16.4)
(2) VT = 10 exchange, hemo- OLV
PEEP = 0 dynamics, clinical
outcomes
Ye and Li 2011 (1) 10 (1) PCV (1) VT = 8 20–65 Thoracic surgery Not reported Respiratory 20, 45 and Not reported
(2) 10 (2) VCV PEEP = 0 parameters, gas 70 min after
(3) 10 (3) PV (2) VT = 8 exchange OLV
PEEP = 0
(3) VT = 6
PEEP = 5
Yang et al. 2011 (1) 50 (1) PV (1) VT = 6 (1) 58 (12) Thoracic surgery (1) 120 (41) Clinical outcomes, 15, 60 min after (1) 105 (9)
(2) 50 (2) CV PEEP = 5 (2) 60 (10) (2) 126 (53) gas exchange, OLV; 2, 72 h (2) 104 (17)
(2) VT = 10 hemodynamics post operation
PEEP = 0
Boules and 2011 (1) 18 (1) PCV-VG (1) VT = 6 (1) 33.4 (6.4) Thoracic surgery (1) 88.7 (42.1) Respiratory 30 min after (1) 73.4 (11.7)
Ghobrial (2) 19 (2) VCV PEEP = 0 (2) 34.7 (7.6) (2) 75.6 (34.7) parameters, gas OLV;72 h post (2) 74.3 (12.5)
(2) VT = 6 exchange, hemo- operation
PEEP = 0 dynamics, clinical
outcomes
Page 4 of 12
Table 1 continued
Author Year No. of Study Details of VT Age (year), Type of surgery Duration of one- Outcomes Time point Preopera-
patients intervention (ml/kg) and mean (SD) lung ventilation of measure- tive FEV1 (%
PEEP (cmH2O) in each mode ment of out- of predicted)
(min), mean (SD) comes (SD)
Pardos et al. 2009 (1) 55 (1) PCV +PEEP (1) VT = 8 (1) 59.5 (13) Thoracic surgery Not reported Respiratory 20, 30 and (1) 91.2 (24)
(2) 55 (2) VCV + PEEP PEEP = 0; (2) 63.9 (11) parameters, gas 40 min after (2) 87.9 (21)
20 min after OLV exchange, clinical OLV; 24 h post
PEEP = 5 outcomes operation; 30d
(2) VT = 8 post operation
Liu et al. SpringerPlus (2016) 5:1251
PEEP = 0;
20 min after OLV
PEEP = 5
Lin et al. 2008 (1) 20 (1) PV (1) VT = 5–6 (1) 55 Thoracic surgery Not reported Cytokines expres- 120 min after Not reported
(2) 20 (2) CV PEEP = 3–5 (2) 54 sion, respiratory OLV, 24 h post
(2) VT = 10 PEEP parameters, gas operation
unclear exchange
Michelet et al. 2006 (1) 26 (1) PV (1) VT = 5 (1) 61 (10) Thoracic surgery (1) 85 (29) Cytokines expres- 15 min after OLV; (1) 93 (19)
(2) 26 (2) CV PEEP = 5 (2) 60 (8.5) (2) 89 (29) sion, respiratory at the end of (2) 96 (18)
(2) VT = 9 parameters, gas OLV; 1,18 h
PEEP = 0 exchange, clinical post operation
outcomes
Randomized cross-over study
Song et al. 2014 27 (1) PCV-VG (1) VT = 8 63.6 (9.7) Thoracic surgery (1) 30 Respiratory 30 min after OLV 107.3 (33.1)
(2) VCV PEEP = 0 (2) 30 parameters, gas in each mode
(2) VT = 8 exchange, hemo-
PEEP = 0 dynamics
Pu et al. 2014 20 (1) PCV-VG (1) VT = 8–10 PEEP 59.8 (unclear) Thoracic surgery (1) 30 Respiratory 30 min after OLV Not reported
(2) VCV unclear (2) 30 parameters, gas in each mode
(2) VT = 8–10 PEEP exchange, hemo-
unclear dynamics
Al Shehri et al. 2014 28 (1) PCV (1) VT = 6 (1) 37.4 (11.51) Thoracic surgery (1) 30 Right ventricular 30 min after OLV 84.5 (10.8)
(2)VCV PEEP = 5 (2) 39.1 (13.93) (2) 30 function, gas in each mode
(2) VT = 6 exchange, hemo-
PEEP = 5 dynamics
Végh et al. 2013 100 (1) PV (1) VT = 5 (1) 64 (12) Thoracic surgery (1) 30 Respiratory 30 min after OLV 91.5
(2) CV PEEP = 5 (2) 63 (12) (2) 30 parameters, gas in each mode (14.0)
(2) VT = 10 exchange, hemo-
PEEP = 0 dynamics
Roze et al. 2012 82 (1) PV (1) VT = 5 (1) 62 (10) Thoracic surgery (1) 10 Respiratory 10 min after OLV Not reported
(2) CV PEEP = 9 (1) (2) 60 (10) (2) 10 parameters, Gas in each mode
(2) VT = 8 exchange, hemo-
PEEP = 5 dynamics
Sungur Ulke 2011 31 (1) PV (1) VT = 6 58.3 (7.2) Thoracic surgery (1) 20 Respiratory 20 min after OLV 75 (14.7)
et al. (2) CV PEEP = 5 (2) 20 parameters, gas in each mode
(2) VT = 8 exchange, hemo-
PEEP = 0 dynamics
Page 5 of 12
Liu et al. SpringerPlus (2016) 5:1251
Table 1 continued
Author Year No. of Study Details of VT Age (year), Type of surgery Duration of one- Outcomes Time point Preopera-
patients intervention (ml/kg) and mean (SD) lung ventilation of measure- tive FEV1 (%
PEEP (cmH2O) in each mode ment of out- of predicted)
(min), mean (SD) comes (SD)
Montes et al. 2010 41 (1) PCV (1) VT = 6 (1) 59.1 (16) Thoracic surgery (1) 30 Respiratory 30 min after OLV 91.2 (19.3)
(2)VCV PEEP = 5 (2) 56.1 (17) (2) 30 parameters, gas in each mode
(2) VT = 6 exchange
PEEP = 5
Choi et al. 2009 18 (1) PCV (1) VT = 8 61.4 (10.3) Robot-assisted (1) 30 Respiratory 30 min after OLV 109.1 (21.2)
(2) VCV PEEP = 0 esophagectomy (2) 30 parameters, gas in each mode
(2) VT = 9 exchange, hemo-
PEEP = 0 dynamics
Unzueta et al. 2007 57 (1) PCV (1) VT = 9 (1) 58.25 (15.15) Thoracic surgery (1) 30 Respiratory 30 min after OLV 82.2 (17.5)
(2) VCV PEEP = 0 (2) 54.75 (13.91) (2) 30 parameters, gas in each mode
(2) VT = 9 exchange
PEEP = 0
Tugrul et al. 1997 48 (1) PCV (1) VT = 10 PEEP 56.4 Thoracic surgery (1) 30 Respiratory 30 min after OLV 76.8 (14)
(2) VCV unclear (2) 30 parameters, gas in each mode
(2) VT = 10 PEEP exchange, hemo-
unclear dynamics
ARS alveolar recruitment strategy, CV conventional ventilation, MIE minimally invasive esophagectomy, PCV pressure-controlled ventilation, PCV-VG volume guaranteed pressure-controlled ventilation, PV protective
ventilation, VATS video-assisted thoracoscopic surgery, VCV volume-controlled ventilation
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Liu et al. SpringerPlus (2016) 5:1251 Page 7 of 12
found that PCV did not have any advantages over VCV in et al. 1997; Unzueta et al. 2007; Choi et al. 2009; Par-
terms of decreased incidence of PPCs (OR 1.05; 95 % CI dos et al. 2009; Montes et al. 2010; Boules and Ghobrial
0.25–4.34; I2 = 0; P = 0.95) (Fig. 2a). 2011; Al Shehri et al. 2014; Pu et al. 2014). PCV showed
Four of the 12 studies including 285 patients compar- decreased Pplateau compared to VCV (MD −1.46; 95 % CI
ing PV with CV reported PPCs as an outcome (Michelet −2.58 to −0.34; I2 = 72 %; P = 0.01) (Fig. 4a).
et al. 2006; Yang et al. 2011; Maslow et al. 2013; Shen Eight of the 12 studies including 497 patients compar-
et al. 2013). PV showed a protective effect over CV on ing PV with CV reported Pplateau as an outcome (Michelet
respiratory complications after one-lung ventilation (OR et al. 2006; Lin et al. 2008; Sungur Ulke et al. 2011;
0.29; 95 % CI 0.15–0.57; I2 = 0; P < 0.01) (Fig. 2b). Yang et al. 2011; Roze et al. 2012; Maslow et al. 2013;
Végh et al. 2013; Jung et al. 2014). PV decreased Pplateau
Length of hospital stay compared to CV (MD −3.57; 95 % CI −5.74 to −1.76;
Four studies including 272 patients comparing PV with I2 = 94 %; P < 0.01) (Fig. 4b).
CV reported the length of hospital stay as an outcome
(Yang et al. 2011; Maslow et al. 2013; Shen et al. 2013; PaO2/FiO2
Qutub et al. 2014). No advantages in terms of the length Three randomized parallel trials including 167 patients
of hospital stay were found in the PV group (MD −0.65; comparing PCV and VCV reported PaO2/FiO2 at
95 % CI −1.59 to 0.30; I2 = 27 %; P = 0.18) (Fig. 3). 20–30 min after OLV as an outcome (Pardos et al. 2009;
Boules and Ghobrial 2011; Ye and Li 2011). No differ-
Plateau airway pressure ences in PaO2/FiO2 were found in those 2 groups (MD
Eight of the 11 studies including 359 patients comparing 47.56; 95 % CI −7.67 to 102.79; I2 = 91 %; P = 0.09)
PCV with VCV reported Pplateau as an outcome (Tugrul (Fig. 5).
Liu et al. SpringerPlus (2016) 5:1251 Page 8 of 12
Fig. 2 Effect of ventilation strategies on postoperative pulmonary complications. a PCV versus VCV; b PV versus CV
Fig. 4 Effect of ventilation strategies on plateau airway pressure. a PCV versus VCV; b PV versus CV
on the final result. Heterogeneity in PaO2/FiO2 could be that PCV-VG (but not traditional PCV) can decrease
resolved by excluding the study by Pardos et al. (Pardos Pplateau. Currently available data are insufficient to iden-
et al. 2009) (MD 74.01; 95 % CI 60.04–87.98; I2 = 0 %; tify differences between PV and CV or PCV and VCV on
P < 0.01). This change affected the final result and showed the length of hospital stay, PaO2/FiO2 or MAP.
PCV benefited PaO2/FiO2 in comparison with VCV. In Our result suggesting that PV with low VT can protect
the comparison of PV with CV on Pplateau, heterogeneity surgical patients from PPCs is consistent with recently pub-
and the final result could not be resolved by the exclusion lished studies (Hemmes et al. 2015, Serpa Neto et al. 2015a,
of any study involved in this meta-analysis. b). However, the definition of PV in these studies is venti-
lation with VT ≤ 8 ml/kg, and they also include all surgi-
Discussion cal patients under general anesthesia (Hemmes et al. 2015).
This meta-analysis suggests that PV but not PCV can The definition of VT and the conclusions from these studies
decrease the incidence of PPCs. Although both PV and might not be suitable in one-lung ventilation. Our results
PCV can decrease the Pplateau, subgroup analyses show suggest that PV with VT ≤ 6 ml/kg can benefit surgical
Liu et al. SpringerPlus (2016) 5:1251 Page 10 of 12
Fig. 6 Effect of ventilation strategies on mean arterial pressure. a PCV versus VCV; b PV versus CV
Table 3 Subgroup analyses of patients undergoing one-lung ventilation with PCV and VCV
Volume of VT Type of PCV
≤6 ml/kg ≥7 ml/kg Traditional PCV PCV-VG
Plateau airway pressure [MD (95 % CI)] −2.58 (−4.74, −0.43) −0.58 (−1.37, 0.20) −1.06 (−2.37, 0.24) −2.78 (−4.21, −1.35)
Mean arterial pressure [MD (95 % CI)] −2.17 (−7.25, 2.91) 1.06 (−1.87, 3.99) 0.04 (−3.12, 3.20) 0.64 (−3.62, 4.91)
patients in one-lung ventilation. A high quality retrospec- identify any difference between PCV and VCV on PPCs.
tive study published recently found that low VT does not It should be noted that Pplateau in PV is lower than Pplateau
prevent PPCs, which contradicts our results (Blank et al. in PCV on average (Choi et al. 2009; Sungur Ulke et al.
2016). In this retrospective study, fewer than half (47 %) of 2011). Differences in Pplateau may be caused by the differ-
the patients received PEEP ≥ 5 cmH2O (Blank et al. 2016). ences in VT. The VT in PCV is usually 8 ml/kg or higher,
Atelectasis should be considered in all general anesthe- while the VT in PV is no more than 6 ml/kg (Michelet
tized patients. And it is of great importance to avoiding the et al. 2006; Jung et al. 2014; Pu et al. 2014). PCV-VG is a
occurrence of atelectasis during OLV (Lohser and Slinger novel mode of ventilation which has been used in recent
2015). Low VT with low PEEP can cause increased amounts years. Although present data suggest that PCV-VG can
of atelectasis (Guldner et al. 2015). Only one study with a decrease Pplateau, more studies are still needed.
sample size of 40 patients used PV with PEEP ≤ 5 cmH2O A combination of low VT and PEEP is generally used in
(Lin et al. 2008). In this study performed by Lin et al., PPCs PV. PEEP can cause cardiac compromise, which can be
were not included in the outcomes (Lin et al. 2008). To reflected by MAP. Low VT may induce hypoxemia. In this
achieve a protective effect on PPCs, PEEP ≥ 5 cmH2O may meta-analysis, the effects of different ventilation strate-
be necessary when PV is used in surgical patients undergo- gies on PaO2/FiO2 and MAP were compared. Decreasing
ing one-lung ventilation. alveolar oxygen tension could induce HPV and resulted
Pplateau is part of the driving pressure and contributes in the redistribution of pulmonary blood flow (Moudgil
to ventilator-induced lung injury (Neto et al. 2016). Our et al. 2005). HPV had a rapid-onset phase and a delayed
results suggest that PV has lower Pplateau compared to CV, phase in response to alveolar hypoxia. The rapid-onset
which might explain the mechanism of decreased PPCs phase reached a plateau at 20–40 min. The delayed phase
in the PV group. Although PCV can also decrease the begins at 40 min and takes more than 2 h to reverse
Pplateau compared to VCV, current data are insufficient to (Lumb and Slinger 2015). PaO2/FiO2 can be affected by
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