doi: 10.1016/j.bja.2019.08.017 Advance Access Publication Date: xxx Special Article
Christopher C. Young1,2,*, Erica M. Harris2, Charles Vacchiano1,3, Stephan Bodnar3,
Brooks Bukowy3, R. Ryland D. Elliott2, Jaclyn Migliarese3, Chad Ragains2, Brittany Trethewey3, Amanda Woodward4, Marcelo Gama de Abreu5, Martin Girard6, Emmanuel Futier7, Jan P. Mulier8, Paolo Pelosi9,10 and Juraj Sprung11
1Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA, 2Duke University Medical Center, Durham, NC, USA, 3Duke University School of Nursing, Durham, NC, USA, 4Duke University Medical Center Library, Durham, NC, USA, 5Pulmonary Engineering Group Dresden, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany, 6Department of Anesthesiology, Centre Hospitalier de l’Universite de Montre al, Montreal, QC, Canada, 7Department of Perioperative Medicine, Anesthesiology, and Critical Care Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France, 8Department of Anesthesiology, Intensive Care and Reanimation, AZ Sint Jan Brugge-Oostende, Bruges, Belgium, 9Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy, 10Anaesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy and 11Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
*Corresponding author. E-mail: email@example.com
Postoperative pulmonary complications (PPCs) occur frequently and are associated with substantial morbidity and mortality. Evidence suggests that reduction of PPCs can be accomplished by using lung-protective ventilation strategies intraoperatively, but a consensus on perioperative management has not been established. We sought to determine recommendations for lung protection for the surgical patient at an international consensus development conference. Seven experts produced 24 questions concerning preoperative assessment and intraoperative mechanical ventilation for patients at risk of developing PPCs. Six researchers assessed the literature using questions as a framework for their review. The modified Delphi method was utilised by a team of experts to produce recommendations and statements from study questions. An expert consensus was reached for 22 recommendations and four statements. The following are the highlights: (i) a dedicated score should be used for preoperative pulmonary risk evaluation; and (ii) an individualised mechanical ventilation may improve the mechanics of breathing and respiratory function, and prevent PPCs. The ventilator should initially be set to a tidal volume of 6e8 ml kg 1 predicted body weight and positive end-expiratory pressure (PEEP) 5 cm H2O. PEEP should be individualised thereafter. When recruitment manoeuvres are performed, the lowest effective pressure and shortest effective time or fewest number of breaths should be used.
Keywords: anaesthesia; adverse effects; Delphi method; intraoperative care; lung injury; perioperative; posititve end- expiratory pressure; positive-pressure respiration; postoperative pulmonary complications; tidal volume
Editorial decision: 04 August 2019; Accepted: 4 August 2019
© 2019 The Authors. Published by Elsevier Ltd on behalf of British Journal of Anaesthesia. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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British Journal of Anaesthesia, xxx (xxx): xxx (xxxx)
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Young et al.
Editor’s key points
Expert consensus-based recommendations were pro- duced to reduce pulmonary complications after surgery.
Low tidal ventilation (6e8 ml kg 1) and PEEP (5 cm H2O) should be used initially.
Alveolar recruitment manoeuvres are beneficial in reopening collapsed alveoli and improving lung mechanics.
Postoperative pulmonary complications (PPCs) account for substantial morbidity and mortality. The incidence of PPCs varies according to definition and type of surgery, and has been reported to range from 5% to 33%.1,2 The 30 day mortality rate for patients who develop PPCs can be as high as 20%.1 Recent reviews have highlighted the growing evidence that lung-protective ventilation, consisting of low tidal volumes (VT), application of PEEP, and use of alveolar recruitment ma- noeuvres (ARMs), can reduce PPCs.3,4 More recently, high ventilator driving pressure (DP1⁄4plateau pressure [Pplat]ePEEP) has been recognised as a significant determinant of lung injury5 and is linked to PPCs.6 Despite evidence of harm, a large proportion of patients continue to receive high VT me- chanical ventilation with a wide range of PEEP and frequently elevated DP.7,8
Many factors may play a role in lung-protective ventilation, yet a consensus in the literature concerning the key clinical question of how to best provide lung protection during me- chanical ventilation in surgical patients is lacking. For this reason, a multidisciplinary panel with expertise in periopera- tive care of mechanically ventilated patients was convened with the aim of developing consensus-based recommenda- tions. As the practice of intraoperative mechanical ventilation varies widely in the published literature and amongst practi- tioners, a consensus-building approach from experts repre- senting six countries in both Europe and North America was thought to best identify areas of agreement. The panel sought to first produce questions regarding preoperative pulmonary risk assessment and characteristics of intraoperative lung- protective ventilation. The current literature was then reviewed to provide evidence-based guidance in response to the identified questions and, in the absence of sufficient clin- ical data, an expert opinion was solicited. Subsequently, the panel convened and established consensus-based recom- mendations using the modified Delphi method. The Delphi method is a consensus-building method that is based upon a structured, iterative communication amongst content experts. The modified method allows for an expert discussion during the final round. Their combined contributions can help resolve complex clinical issues. It was used as a decision tool to effi- ciently identify best practices in protective lung ventilation whilst allowing for the experts to contribute their distinct perspectives.
Research/expert teams and main topics
The president of the coordinating team (CCY) discussed the development of lung-protective-ventilation practice recom- mendations with the meeting sponsor (GE Healthcare). The meeting sponsor agreed to assist with establishing a consensus conference. The president and sponsor identified
individuals who were subsequently invited to participate in the consensus meeting. The selection criteria for the experts included previous publications in the field of intraoperative ventilation, demonstrated knowledge and interest in lung- protective strategies, and ability to participate in all pre- meeting teleconferences and a 1 day face-to-face meeting.
Seven experts (MGA, EF, MG, EMH, JPM, PP, and JS) from six countries agreed to serve on the panel for this consensus meeting. It has been suggested that between 5 and 10 experts are required for content validation,9 and that a ‘suitable min- imum size’ for an expert panel is seven.10
The coordinating team (CCY and CV) and experts gener- ated, reviewed, and approved 24 questions on perioperative mechanical ventilation (Supplementary Table S1). A content- validity universal agreement was not directly measured. However, the use of participants who have knowledge and interest in the topic increases the content validity of the Del- phi method, and the use of successive rounds in the devel- opment of the questionnaire likewise improves validity.11
A team of six researchers (SB, BB, RRDE, JM, CR, and BT) evaluated the existing literature for each question. A literature search was conducted in order to identify any additional topics of interest.
Research questions were used as guidance for literature searches conducted by a research librarian (AW). The search strategy combined subject headings and keywords for anaes- thesia, surgery or perioperative care, and lung-protective ventilation in adults. A systematic literature search on each subject was performed by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 18, 2018 (Supplementary Table S2). Observational and experimental studies, and also literature reviews, systematic reviews, and meta-analyses written in English were included. The authors chose to include a clinically important, late- breaking randomised trial in the discussion even though it was not published until June 2019.12
All articles were screened and reviewed by teams of two for eligibility based on title and abstract (Fig. 1). Rayyan software (https://rayyan.qcri.org) was used as a screening tool to facil- itate blind screening within the teams.13 Every citation was reviewed by two members of the research team using the same inclusion criteria. Any conflicts in including or excluding articles were resolved through a discussion within the research teams.
Eligible full-text articles were obtained and categorised according to sub-questions developed for each topic. They were summarised and evaluated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system,14 which systematically evaluates the avail- able literature and focuses on the level of evidence based upon the types of studies included.
Each research team worked with one of the experts to formulate recommendations for their sub-questions based on the available literature and the input of their assigned expert. The quality of the evidence was evaluated according to the GRADE system, and assigned as ‘high’ (⊠⊠⊠⊠), ‘moderate’ (⊠⊠⊠), ‘low’ (⊠⊠), or ‘very low’ (⊠). The strength of the recommendation was based on judgement of the level of evi- dence, and reported as weak or strong. Expert and researcher teams produced recommendations for presentation at the face-to-face meeting. When the literature was insufficient to
Lung-protective ventilation – 3
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Fig 1. PRISMA flow diagram. Each search term underwent a systematic review using PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 18, 2018. Then, 651 eligible full-text articles were obtained and categorised. After question development for each topic, the relevant full-text articles were summarised and evaluated according to the GRADE system; 221 articles were included in the final development of the lung-protective ventilation recommendations. PRISMA, preferred reporting items for sys- tematic reviews and meta-analyses.
provide a recommendation, the expert was asked to provide an opinion (Fig. 2).
Throughout the article, recommendations or statements are referred to by their main topic and sub-question. For example, Topic 1 (pulmonary risk assessment) and Question 1 (factors that increase risk of PPCs) are denoted as (Q1.1). The results of every question are displayed in Tables 1e3.
The consensus meeting, held in Frankfurt, Germany on October 1, 2018, was organised according to a modified Delphi methodology referred to as the ‘Amsterdam Delphi method’.15 The key components of the Delphi method include iteration
(two rounds), controlled acquisition of feedback, and aggre- gation of responses. The modified Delphi method was chosen because it allowed for expert interaction in the final round. This allowed members of the panel to provide further clarifi- cation on some matters and present arguments in order to justify their viewpoints. Anonymity, which is a component of the original Delphi method, was not feasible in this setting, and hence the ‘modified’ method was implemented. After displaying the recommendations, the experts voted their agreement or disagreement. Refraining from voting was not allowed. No discussion was allowed between the experts at this point. If 100% consensus was reached during the first round of voting, the recommendation was accepted without further voting or discussion. When the experts were not in full
Young et al.
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Fig 2. Initial development of recommendations flow chart. Ex- perts developed preliminary questions and expert/researcher teams produced recommendations based upon literature review and quality assessment using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The resulting recommendations were used as the basis of dis- cussion at the face-to-face modified Delphi meeting.
agreement, the research team was given 2 min to present the underlying considerations. After this, 5 min of discussion amongst the experts was allowed and the recommendation could be reformulated. A given question could result in a statement rather than a recommendation at the discretion of the expert panel. A final round of voting was conducted using the revised recommendation or statement (Fig. 3). The ‘consensus’ level during the second round of voting was set at
70% agreement amongst experts. This level of agreement was validated and accepted at previous guideline development conferences, including the 2015 European Association for Endoscopic Surgery consensus meeting on appendicitis16 and the 2016 American Society for Metabolic and Bariatric Surgery consensus meeting on perioperative management of obstructive sleep apnoea in bariatric surgery.15
Preoperative risk assessment
Preoperative assessment should include a dedicated score for pulmonary risk evaluation in order to identify patients with greater risk for PPCs (Table 1; Q1.1). Many scoring systems exist to quantify PPC risk, but most are too complex to be clinically useful or lack external validation confirming the accuracy of the score. Although the definition of PPCs was revisited recently with the goal of standardising the criteria, the consensus achieved in that publication does not differ substantially from previous ones.17 Despite the lack of evi- dence for the use of a specific prediction score, the patient factors and perioperative characteristics associated with increased PPC risk are well established. The panel agreed that the intraoperative ventilation strategy should be guided by an awareness of the factors that pose the greatest risk: age >50 yr, BMI >40 kg m 2, ASA physical status >2, obstructive sleep apnoea, preoperative anaemia, preoperative hypoxaemia, emergency or urgent surgery, and ventilation duration >2 h (Table 1; Q1.1).
Intraoperative atelectasis, related changes in lung mechanics, and postoperative pulmonary complications
Atelectasis occurs in roughly 90% of all patients undergoing general anaesthesia and can persist for weeks after opera- tion.18,19 Intraoperative atelectasis results in decreased func- tional residual capacity (FRC), increased heterogeneity of lung expansion, cyclic lung overstress, and increased DP. DP is the pressure difference that generates VT, and can be expressed as the ratio between VT and respiratory system compliance (CRS).20 Lower intraoperative DP values have been associated with a reduction in PPCs,21,22 and high DP is considered a key mediator of lung injury during positive-pressure ventilation.23 Therefore, intraoperative ventilation that avoids de- recruitment without causing over-distension of alveoli may decrease postoperative pulmonary risk by improving periop- erative oxygenation and respiratory mechanics,3,24,25 and reducing oxidative stress, inflammatory response, and lung injury.26,27
Induction of anaesthesia
Supine positioning during induction of anaesthesia causes cephalad displacement of abdominal contents, thereby forc- ing the diaphragm upwards and compressing dependent lung regions. These changes are attenuated by placing patients in a head-up or ramped position (Table 1; Q3.1). During induction of anaesthesia, particularly in obese individuals, the head-up method produces a longer non-hypoxic apnoea time compared with supine, allowing more time for laryngos- copy.28,29 The supine position should be avoided during
Lung-protective ventilation – 5
Table 1 Recommendations and statements concerning pulmonary risk assessment, case set-up, and ventilation management during anaesthesia induction. CPAP, continuous positive airway pressure; FIO2, fraction of inspired oxygen; HOB, head of bed; I:E, inspir- atory:expiratory; NIPPV, non-invasive positive-pressure ventilation; OSA, obstructive sleep apnoea; PBW, predicted body weight; PPC, postoperative pulmonary complication; Pplat, plateau pressure; SpO2, peripheral oxygen saturation; VT, tidal volume; ZEEP, zero end- expiratory pressure.
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. 1.1 A dedicated score should be used for risk evaluation.
The greatest risk factors for PPCs include age >50 yr, BMI >40
kg m 2, ASA >2, OSA, preoperative anaemia, preoperative hypoxaemia, emergency or urgent surgery, ventilation duration >2 h, and intraoperative factors (such as haemodynamic impairment and low oxyhaemoglobin saturation).
. 1.2 Use a low-tidal-volume protective-ventilation strategy (6e8 ml kg 1 PBW). ZEEP is not recommended. Appropriate PEEP and recruitment manoeuvres may improve intraoperative
respiratory function and prevent PPCs.
. 1.3 The formation of perioperative clinically significant
atelectasis may be an important risk factor for the
development of PPCs.
. 2.1 Individualised mechanical ventilation should be used and
may improve intraoperative respiratory function, but the
beneficial effects are likely to disappear after extubation.
. 2.2 The ventilator should initially be set to deliver VT 6e8 ml
kg 1 PBW and PEEP1⁄45 cm H2O. Evidence regarding I:E ratio
settings is lacking.
. 2.3 PEEP should be individualised to the patient in order to avoid
increases in driving pressure (PplatePEEP) whilst maintaining a low VT. To optimise intraoperative respiratory function in obese patients, during pneumoperitoneum insufflation, and during prone or Trendelenburg positioning, PEEP adjustment may be required.
. 3.1 Before induction of anaesthesia, position the patient with the HOB elevated ! 30 deg (i.e. ‘beach chair’); avoid flat supine
position. If not contraindicated, before the loss of spontaneous ventilation, use NIPPV or CPAP to attenuate anaesthesia-induced respiratory changes.
. 3.2 During induction, monitor for an obstructive breathing pattern and use a combination of appropriate techniques,
including positioning, application of NIPPV or CPAP, or placement of a nasopharyngeal airway to avoid upper airway obstruction.
. 3.3 After intubation, FIO2 should be set to 0.4. Thereafter, use the lowest possible FIO2 to achieve SpO2 !94%.
. 3.4 No specific mode of controlled mechanical ventilation is recommended.
Consensus Quality of (%) evidence
100 ⊠⊠,, 100 ⊠⊠,,
100 ⊠⊠⊠⊠ 100 ⊠⊠,, 86 ⊠⊠⊠, 100 ⊠⊠,,
100 ⊠,,, 100 ⊠,,,
Strength of recommendation
Statement Strong Strong Strong
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anaesthesia induction, as 30 degree head-up and reverse Trendelenburg position is associated with less reduction of FRC.30
Non-invasive ventilation during induction
Non-invasive positive-pressure ventilation (NIPPV) or contin- uous positive airway pressure (CPAP) should be considered as useful adjuncts during anaesthesia induction. Contraindica- tions, such as altered mental status, certain procedures (face/ nose/oesophageal resection), or emergency procedures, should be considered before applying NIPPV or CPAP (Table 1; Q3.1). Head-up positioning combined with NIPPV/CPAP30 further attenuates FRC decrease with anaesthesia induction. Using NIPPV/CPAP during induction increases PaO2 and dura- tion of non-hypoxic apnoea.29,31e33 Two meta-analyses of obese patients corroborated the finding that NIPPV/CPAP
during induction improved duration of non-hypoxic apnea34 and improved oxygenation.35 A single study failed to demon- strate positive effects of NIPPV/CPAP on non-hypoxic apnoeic time.36 NIPPV/CPAP was also noted to decrease venous admixture when compared with spontaneous breathing.31 Other methods, including monitoring of obstructive breath- ing, head positioning, and naso- or oropharyngeal airway insertion should be used to avoid upper airway obstruction during induction (Table 1; Q3.2).
Optimal intraoperative ventilator settings
Low VT ventilation, 6e8 ml kg 1 predicted body weight (PBW), is a fundamental component of lung-protective ventilation (Table 1; Q1.2). Multiple studies have demonstrated a signifi- cant reduction in PPCs associated with low (<8 ml kg 1) vs high
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Table 2 Recommendations and statements concerning respiratory system monitoring and ventilation management during anaes- thesia maintenance/surgery. ESA, European Society of Anaesthesiology; Pplat, plateau pressure; FIO2, fraction of inspired oxygen.
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Question Statement/recommendation Consensus (%)
. 4.1 In addition to standard monitoring (ASA/ESA), 100 dynamic compliance, driving pressure (PplatePEEP),
and Pplat should be monitored on all controlled
mechanically ventilated patients.
. 4.2 Decreasing compliance caused by surgical/ 86
anaesthesia factors (i.e. pneumoperitoneum, positioning, and circuit disconnect) should be treated by appropriate interventions. Individualised PEEP can prevent progressive alveolar collapse. Recruitment manoeuvres can reverse alveolar collapse, but have limited benefit without sufficient PEEP.
Statement: Increasing FIO2 may be effective in increasing the oxygenation, but is not an effective intervention to improve dynamic compliance of the respiratory system.
. 4.3 The effectiveness of interventions aimed at optimising 100 respiratory system mechanics should be evaluated
by measuring an improvement of the respiratory system compliance under a constant tidal volume.
. 5.1 High-quality supportive evidence is lacking to recommend a routine ARM for all patients after tracheal intubation. However, an ARM may be considered according to an
individual riskebenefit assessment.
. 5.2 The bag-squeezing ARM should be avoided in favour of a
. 5.3 ARMs should be performed using the lowest effective Pplat (30
e40 cm H2O in non-obese; 40e50 cm H2O in obese) and
shortest effective time or fewest number of breaths.
. 5.4 Continuous haemodynamic and oxygen saturation
monitoring is recommended before and during an ARM. Ensure adequate haemodynamic stability before performing an ARM. Avoid ARMs when contraindicated.
. 5.5 PEEP should be individualised after an ARM to avoid both alveolar overdistention and collapse.
. 6.1 Optimise patient positioning and avoid ZEEP during emergence. Avoid tracheal tube suctioning immediately
before tracheal extubation.
. 6.2 Avoid apnoea with ZEEP before extubation.
. 6.3 In the appropriate clinical scenario, the use of low FIO2 (<0.4) during emergence from general anaesthesia can improve
pulmonary function in the postoperative period.
. 6.4 When high FIO2 (>0.8) is used during emergence, the use of
low FIO2 (<0.3) CPAP immediately after tracheal extubation
may reduce the risk of resorption atelectasis.
. 6.5 Administration of postoperative supplemental oxygen is
recommended when room air SpO2 decreases below 94%. Avoid routine application of supplemental oxygen without investigating and treating the underlying cause.
. 6.6 Prophylactic NIPPV/CPAP should be considered after operation for patients with prior routine use of NIPPV/
Quality of evidence
Strength of recommendation
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Table 3 Recommendations and statements concerning recruitment manoeuvres and ventilation management during anaesthesia emergence. ARM, alveolar recruitment manoeuvre; CPAP, continuous positive airway pressure; FIO2, fraction of inspired oxygen; HOB, head of bed; NIPPV, non-invasive positive-pressure ventilation; Pplat, plateau pressure; SpO2, peripheral oxygen saturation; ZEEP, zero end-expiratory pressure. *Consensus level <70%.
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Consensus Quality (%) of
100 ⊠,,, 100 ⊠⊠,,
71 ⊠⊠,, 100 ⊠,,,
100 ⊠,,, 71 ⊠,,,
29* ⊠,,, 100 ⊠,,,
Strength of recommendation
Lung-protective ventilation – 7
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Fig 3. Modified Delphi process flow chart. After the development of recommendations, the experts met in a face-to-face meeting to develop a consensus. All recommendations and statements underwent two rounds of voting as no recommendation achieved 100% consensus during the first round. The final round of voting was conducted using the revised recommendation or statement.
(>8 ml kg 1) VT ventilation.26,37,38 However, the use of a low VT without adequate PEEP may increase the risk of atelectrauma as a result of cyclic lung de-recruitment.37,39
A number of studies have suggested the negative effects associated with mechanical ventilation with zero end- expiratory pressure (ZEEP).4,40e43 These effects include a pro- found reduction in end-expiratory lung volume (EELV) after anaesthesia induction and an increased area of atelectasis. Loss of EELV and atelectasis contribute to decreased CRS in de- recruited areas, and increase the propensity for overinflation of aerated lung tissue (volutrauma).40,41 Therefore, allowing airway/alveolar pressure to achieve ZEEP is not recommended (Table 1; Q1.2).
Individualised PEEP improves oxygenation, EELV, and res- piratory system mechanics during ventilation; however, these improvements may disappear soon after extubation.44e51 Whilst the panel noted that many measurable effects of lung-protective ventilation may dissipate after extubation,
they agreed that mechanical ventilation should be targeted to optimise the respiratory function (Table 1; Q2.1), and that more studies are needed to quantify whether these positive intraoperative effects on ventilatory mechanics have a clini- cally meaningful impact on postoperative respiratory outcomes.
Although several studies of low VT (6e8 ml kg 1) have consistently shown improvement in pulmonary function and reduction of PPCs, the optimal level of PEEP remains a matter of debate.4,25,52,53 The panel agreed that lung-protective ventilation requires a combination of low VT and some de- gree of PEEP (Table 1; Q2.2). Multiple studies demonstrate that the use of PEEP improves EELV; increases oxygenation; and improves dependent lung ventilation, CRS, and postoperative pulmonary function when compared with ZEEP.39,54e58 More- over, several large RCTs showed that intraoperative ventila- tion with reduced VT (6e8 ml kg 1) and increased levels of PEEP (6e10 cm H2O) prevents PPCs38,59,60; reduces atelectasis and recruitment/de-recruitment injury; and improves CRS, EELV, PaO2, and dependent lung ventilation with little-to-no over- distension.43,57 However, one large trial protective ventilation
8 – Young et al.
during general anesthesia for open abdominal surgery: high versus low positive end-expiratory pressure (PROVHILO) showed no difference in the development of PPCs with low VT and either high or low levels of PEEP ( 2 cm H2O vs 12 cm H2O).61 Whilst ZEEP is not recommended, the precise level of PEEP remains controversial.42,43,57,58,61e67
Individualised PEEP has demonstrated many benefits to pulmonary function, and is especially important in obese pa- tients, during abdominal insufflation, and during prone or Trendelenburg positioning (Table 1; Q2.2). One RCT of obese patients (BMI >35 kg m 2) undergoing laparoscopic surgery found that the average calculated individualised PEEP was 18.5 cm H2O.45 This trial also found that individualised PEEP decreased DP and increased PaO2/FIO2 ratios, EELV, CRS, and ventilation to dependent lung regions. A recent large inter- national trial, however, showed that, although higher PEEP with recruitment manoeuvres results in improved pulmonary function intraoperatively compared with a low PEEP without recruitment manoeuvres, it does not reduce the incidence of PPCs in obese surgical patients.12
The importance of individualised PEEP was further high- lighted in a meta-analysis of individual patient data from RCTs comparing intraoperative protective ventilation with conven- tional ventilation, which found that the benefits of protective ventilation were related to reductions in DP rather than to changes in VT or level of PEEP.6 The authors reported that only CRS and DP were significantly associated with PPCs, and that their incidence was not affected by the level of PEEP unless it resulted in an increase in DP. Therefore, the panel recom- mends an initial PEEP setting of 5 cm H2O and thereafter PEEP levels should be individualised (Table 1; Q2.2 and 2.3).
Several studies have compared prolonged inspiratory-to- expiratory (I:E) ratios to the 1:2 ratio commonly used during mechanical ventilation. An I:E ratio of 1:1, which has been characterised as providing a ‘balanced stress to time product’,4 was associated with attenuation of lung damage. Prolonged I:E ratio increases mean airway pressure and concomitantly re- duces peak airway pressure. Studies using prolonged inspira- tory times have described beneficial effects, including increased CRS and PaO2, lower alveolarearterial gradient, and reduced inflammatory markers.6,67e72 Given the lack of evi- dence for a clear benefit of a specific I:E ratio, no recommen- dation was offered by the panel (Table 1; Q2.2). However, the panel noted that optimisation of inspiratory time for individ- ual patients can be achieved by monitoring parameters, such as oxygenation, CRS, and DP.
Increased FIO2 during mechanical ventilation is administered to prevent or correct hypoxaemia, but may result in hyper- oxia.73,74 The negative effects of hyperoxia are not clear, but it has been suggested that it may increase oxidative stress, pe- ripheral vascular and coronary artery vasoconstriction, decrease cardiac output, increase resorption atelectasis, and increase the rate of PPCs.75e81
Recommendations for optimal use of oxygen and current evidence regarding the association between hyperoxaemia and clinically relevant outcomes during intraoperative me- chanical ventilation are lacking. Few studies have revealed a protective effect of hyperoxaemia,82 some report an
association with mortality,83 whilst others show no associa- tion with clinically relevant outcomes.83 Therefore, in the absence of evidence, the most prudent course of action during mechanical ventilation is to maintain normoxaemia. SpO2 monitoring can assist in the detection of hypoxaemia, but during oxygen therapy SpO2 cannot detect hyperoxia.84 Whilst SpO2 monitoring reduces the incidence of hypoxaemia, it does not improve the overall patient outcomes and does not reduce morbidity and mortality.85 Therefore, once the airway is secured, FIO2 should be set to 0.4 with the goal of using the lowest possible FIO2 to achieve normoxia (or SpO2 !94%) (Table 1; Q3.3). Unnecessarily high FIO2 should be avoided. Administering lower FIO2 will not only decrease the risk of hyperoxia, but will also reduce the masking effect of oxygen therapy and allow for earlier diagnosis of gas-exchange impairment.84
Modes of mechanical ventilation
A number of studies explored whether one mode of mechan- ical ventilation is better than others at reducing PPCs. When assessing pressure-controlled ventilation (PCV) vs volume- controlled ventilation (VCV), the results are mixed. VCV was associated with lower maximal plateau pressures, greater VT, and less dead-space ventilation.86 In an observational study, the risk of PPC was higher in patients who received PCV compared with VCV, particularly with PEEP <5 cm H2O.87 A meta-analysis regarding intraoperative ventilation mode in obese patients found VCV to be superior to PCV.88
Pressure-controlled ventilation was superior to VCV on the basis of lower peak inspiratory pressure (PIP) or improved arterial blood gas (ABG) results in several studies. Four studies showed lower PIP with no change in arterial oxygenation.89e92 Another demonstrated improved ABG results in patients ventilated with PCV compared with VCV, with no change in airway pressures.93 No significant differences between PCV and VCV were found in one randomised trial when assessing airway pressures, ABG results, or oxygenation.94 VCV with an inspiratory pause does allow for measurement of Pplat, there- fore allowing for a more accurate determination of DP. Given the heterogeneity of the published trials, no specific mode of controlled mechanical ventilation is recommended (Table 1; Q3.4).
Alveolar recruitment manoeuvres
General anaesthesia promotes the formation of atelectasis, which negatively impacts respiratory function and may be associated with subsequent PPCs.18,44 ARMs are beneficial in reopening collapsed alveoli and improving lung mechanics, suggesting that performing an ARM after intubation can combat anaesthesia-induced FRC changes.45,95e100 Even after an ARM, normal alveoli filled with 100% oxygen have a rapid tendency to collapse and form shunt.101 Therefore, resorption atelectasis can be attenuated with an ARM performed with FIO2 <1.0.18 After an ARM, CRS and PaO2 improved.24,60,102e104 ARMs are effective when applied after intubation and during any episodes of oxyhaemoglobin desaturations or release of positive pressure from the breathing circuit.
The period immediately after induction can often be a time of haemodynamic instability caused by medication and positive-pressure ventilation effects. Whilst ARMs are considered safe and effective,105 some patients, such as those with hypovolaemia, severe emphysema, or chronic
obstructive lung disease, may be prone to hypotension during an ARM; therefore, the risk to benefit ratio of ARMs should be carefully considered. High-quality supportive evidence is lacking to recommend a routine ARM for all patients after tracheal intubation. However, an ARM may be considered ac- cording to an individual riskebenefit assessment (Table 3; Q5.1). Further research is needed to identify which patients would benefit from an ARM immediately after induction.
ARMs should be performed after a disconnection from the circuit and whenever the patient’s SpO2 is consistently 94%. The two primary methods are manual ARM and ventilator- driven ARM.
Manual alveolar recruitment manoeuvres
A manual ARM is performed by sustained lung inflation using the reservoir bag on the anaesthesia machine with the adjustable pressure-limiting valve set to the desired inflation pressure. The manual ARM can lead to brief loss of positive pressure when switching back to the ventilator circuit, which results in recollapse of alveoli. For this reason, the ventilator- driven ARM is favoured (Table 3; Q5.2).
Ventilator-driven alveolar recruitment manoeuvres
Ventilator-driven ARMs can be divided into three types: vital capacity, pressure-controlled, or volume-controlled cycling manoeuvres. The vital-capacity ARM resembles the manual ARM except that the VT is delivered through the ventilator circuit. This requires a ventilator capable of providing CPAP or an inspiratory hold of 7e8 s.106 The panel concurs that 7e8 s is an appropriate inspiratory time in patients with healthy lungs, but that individual patient characteristics (elevated BMI, Trendelenburg position, and abdominal insufflation) may require longer times and higher PIP. Studies that have evalu- ated intraoperative alveolar collapse have found that, in healthy patients with BMIs <35 kg m 2, a PIP hold of 40 cm H2O is required to improve PaO2 and lung compliance.107 For pa- tients with BMIs >35 kg m 2, pressures of up to 50 cm H2O or multiple, successive ARMs have been recom- mended.51,62,90,102,108e113 The recently published effect of intraoperative high positive end-expiratory pressure (PEEP) with recruitment maneuvers vs low PEEP on postoperative pulmonary complications in obese patients (PROBESE) trial showed no reduction of PPCs when an ARM was performed after intubation and each hour afterwards as part of a non- individualised ventilator protocol in obese surgical patients.12
In pressure-controlled-mode ARM, recruitment airway pressure should be based upon patient BMI, as discussed previously, and this ‘opening’ pressure should be maintained for 10 breaths.21,45,114e118 The panel was unanimous in urging caution when using PIP >50 cm H2O. When using volume- controlled mode for ARM,60 one should start with a VT of 6e8 ml kg 1 PBW and I:E ratio of 1:1, and increase the VT by 4 ml kg 1 every three to six breaths until Pplat of 30e40 cm H2O is reached. After an additional three to six breaths at this level, sufficient recruitment occurs and VT settings can be reduced. PEEP adjustment after an ARM may be required to maintain alveolar recruitment. The panel further recommends that one should evaluate change in CRS and DP after an ARM, and repeat the ARM with a longer inspiratory hold or higher pressure if recruitment is assessed as ineffective.
The panel recommends using the lowest FIO2 during ARMs to aid in identifying the patient’s opening and closing pres- sures, and sustain recruited alveoli by reducing the occurrence of resorption atelectasis.119,120 They also state that the method used to produce an ARM through the ventilator circuit is not as important as avoiding the use of manual ARMs. ARMs should be performed using the lowest effective PIP and shortest effective time or fewest number of breaths (Table 3; Q5.3). ARM effectiveness can be measured by improved oxygenation, CRS, or DP. Further research is required, as there is currently little evidence linking ARMs to pulmonary outcomes.
Complications related to alveolar recruitment manoeuvres
Hypoxaemia and haemodynamic instability are reported
complications of ARMs. No adverse effects of performing
an ARM were found in 26 of 33 stud- ies.24,51,57,59,60,62,65,95e100,102,104,108,111e114,116e118,121e123 Six
studies identified transient haemodynamic instability requiring vasopressor treatment during ARMs.21,45,46,52,61,103 One study found more oxyhaemoglobin desaturation in the ARM group.124 The panellists recommend continuous hae- modynamic and SpO2 monitoring before and during the ARM.125 It is essential to ensure adequate haemodynamic stability before performing an ARM and avoid ARMs when contraindicated (Table 3; Q5.4).
Intraoperative monitoring of lung mechanics and oxygenation
Because the lung is a dynamic system, altered by both anaesthesia and surgery, the components of the mechanical breath should be continuously evaluated.20 CRS, DP, and Pplat should be monitored on all mechanically ventilated patients (Table 2; Q4.1), and interventions aimed at optimising respi- ratory system mechanics should be evaluated by measuring CRS under constant VT6 (Table 2; Q4.3).
Current monitoring standards focus primarily on detecting hypoxaemia using SpO2. Interventions tend to focus more on improving SpO2, often by increasing FIO2, rather than improving the underlying pulmonary system derangement. Whilst increasing FIO2 may be effective in increasing oxygenation, it does not improve the underlying ventilationeperfusion mismatch (Table 2; Q4.2).
To minimise the risk associated with mechanical ventila- tion, the ventilator should be set to maintain the DP as low as possible.6 Appropriately set PEEP can maintain FRC without causing gross over-distension, and is evidenced by the lowest DP that achieves the desired VT.126 Surgical or anaesthesia factors that cause changes in CRS or DP should be treated by interventions that restore physiological lung volume whilst avoiding both over- and under-distention (Table 2; Q4.2). During controlled mechanical ventilation, if the circuit is disconnected or switched from the ventilator to the manual mode, loss of lung volume will occur immediately, accompa- nied by a decrease in CRS and an increase in DP.127 In order to restore CRS and prevent lung over-distension, FRC must be re- established by an increase in pressure sufficient to overcome the degree of lung collapse.50,127
The FRC is maintained, not restored, by PEEP. Therefore, in order to prevent lung over-distension related to PEEP, FRC should be restored with an ARM before any increase in the
Lung-protective ventilation – 9
10 – Young et al.
level of set PEEP.127 Likewise, ARMs can reverse alveolar collapse, but the benefit will be of short duration without sufficient PEEP (Table 2; Q4.2). PEEP should be individualised after an ARM to avoid alveolar over-distension or collapse (Table 3; Q. 5.5).
Emergence from anaesthesia
Consideration should be given to avoiding conditions during emergence that negate the intraoperative efforts to recruit and maintain an open lung. Recommendations similar to those applied during induction include optimising patient posi- tioning (head elevated !30 deg) and avoiding ZEEP (Table 3; Q6.1). Reduction of lung volume by routine suctioning of the tracheal tube just before extubation should be avoided. Other interventions likely beneficial include prevention of coughing and bucking on the tracheal tube, and avoiding upper airway obstruction after extubation. The common practice of turning off the ventilator allowing carbon dioxide to accumulate to stimulate spontaneous ventilation should also be avoided, as the period of apnoea is associated with ZEEP and collapse of alveoli (Table 3; Q6.2). Atelectasis that develops during general anaesthesia persists into the postoperative period. This finding argues for some methods of keeping recruited alveoli open, such as application of CPAP during the transition be- tween mechanical ventilation and spontaneous breathing. However, applying an ARM followed by PEEP, and then main- taining positive airway pressure using CPAP from return of spontaneous breathing until extubation did not improve postoperative oxygenation.122
FIO2 during emergence
FIO2 >0.8 during emergence significantly increases atelectasis formation.128e131 If clinically appropriate, FIO2 0.4 during emergence may be used to reduce atelectasis. Lower FIO2 during emergence can improve postoperative pulmonary function130 (Table 3; Q6.3). CPAP with low FIO2 (<0.3) after extubation may decrease the area of atelectasis.31,123,130,132 However, current evidence regarding efficacy of this tech- nique is lacking and cannot presently be universally recom- mended (Table 3; Q6.4). After extubation, supplemental oxygen should be administered for SpO2 <94%; however, the underlying cause should be investigated and appropriate in- terventions should be used (Table 3; Q6.5).
Non-invasive ventilator support
A systematic review of CPAP administered after a major abdominal surgery found weak evidence that CPAP may reduce atelectasis, the rate of pneumonia, and the frequency of reintubation.133 Prophylactic postoperative CPAP reduced the incidence of PPCs in patients undergoing abdominal sur- gery; however, the authors noted that the optimum CPAP in this setting is unknown and the administration of CPAP should be individualised.134 Postoperative CPAP of 7.5 cm H2O vs 6 L min 1 flow of 50% oxygen by the Venturi mask may reduce reintubation rate, pneumonia, infection, and sepsis after a major abdominal surgery.135 CPAP of 10 cm H2O after thor- acoabdominal surgery reduced PPCs and decreased the dura- tion of ICU and hospital stay.136
Administration of CPAP immediately post-extubation in the obese population has been shown to reduce atelectasis,
improve oxygenation and pulmonary function, and may minimise the risk of developing PPCs.66,137 The early post- operative use of NIPPV in obese patients promoted a more rapid recovery of lung function and improved oxygenation when compared with a 6 L min 1 flow of 50% oxygen via Venturi mask.138 In addition, the PaO2 and PaO2/FIO2 ratio were significantly improved up to 24 h after operation when CPAP was applied immediately upon extubation in obese pa- tients.139 In obese patients undergoing laparoscopic surgery, NIPPV administration post-extubation improved pulmonary function and reduced the risk of respiratory complications; however, it did not reduce the risk of reintubation or un- planned ICU admission.35
The postoperative prophylactic use of NIPPV or CPAP should be considered for patients who use these modalities to maintain adequate ventilation before operation (Table 3; Q6.6).
A panel of experts produced consensus recommendations for intraoperative protective ventilation for the surgical patient. Those statements and recommendations that were of mod- erate to high quality and received strong support from the expert panel are presented in Table 4. We need to reiterate that two study questions did not achieve the consensus level of 70%. First, high-quality supportive evidence is lacking to recommend a routine ARM for all patients after tracheal intubation; however, 57% agreement was achieved that an ARM may be considered according to an individual riskebenefit assessment. Second, only 29% agreement was achieved that low FIO2 (<0.3) with CPAP immediately after tracheal extubation may reduce the risk of resorption atelec- tasis. In both cases, published evidence was weak or non- existent, and the non-agreeing experts expressed concern about supporting potentially harmful interactions without more robust evidence.
Whilst these are the first published recommendations for the management of intraoperative mechanical ventilation, practice guidelines for mechanical ventilation in adult pa- tients with acute respiratory distress syndrome (ARDS) strongly support the use of low VT ventilation (4e8 ml kg 1 PBW) and limiting Pplat to less than 30 cm H2O.140 The recom- mendations presented here are similar except for the use of DP instead of Pplat, as this appears better correlated with out- comes.5,6 In surgical patients, PEEP titration in conjunction with ARM is likely to be beneficial particularly during times when CRS changes rapidly, such as during insufflation and steep Trendelenburg positioning. The use of higher levels of PEEP and ARM is only conditionally recommended in ARDS patients.140 These differences likely reflect the different un- derlying pathophysiologies occurring in ARDS (inflammatory pulmonary oedema and cellular debris accumulation in alveoli) vs in the operating room (healthy lungs with a high degree of atelectasis). Whilst atelectatic alveoli during surgery can be reopened with ARM and incremental PEEP, the ‘baby lung’ of ARDS may not have a similar recruitable alveolar volume, and therefore, may not respond as favourably to ARM and PEEP.141
The modified Delphi method is recommended to determine a consensus for a defined clinical problem in the healthcare setting, and is an effective process for determining expert group consensus where there is little or no definitive evidence,
Moderate- to high-quality recommendations with strong expert support:
The ventilator should initially be set to deliver VT 6e8 ml kge1 PBW and PEEP1⁄45 cm H2O. ZEEP is not recommended.
Appropriate PEEP and recruitment manoeuvres may improve intraoperative respiratory function and prevent PPCs.
Before the induction of anaesthesia, position the patient with the HOB elevated !30 deg (i.e. ‘beach chair’); avoid flat supine
position. If not contraindicated, before the loss of spontaneous ventilation, use NIPPV or CPAP to attenuate anaesthesia-
induced respiratory changes.
In addition to standard monitoring (ASA/ESA), dynamic compliance, driving pressure (PplatePEEP), and Pplat should be monitored
on all controlled mechanically ventilated patients.
Continuous haemodynamic and oxygen saturation monitoring is recommended before and during an ARM. Ensure adequate
haemodynamic stability before performing an ARM. Avoid ARMs when contraindicated. Moderate- to high-quality statements with strong expert support:
The formation of perioperative clinically significant atelectasis may be an important risk factor for the development of PPCs.
Decreasing compliance caused by surgical/anaesthesia factors (i.e. pneumoperitoneum, positioning, and circuit disconnect)
should be treated by appropriate interventions.
Individualised PEEP can prevent progressive alveolar collapse. Recruitment manoeuvres can reverse alveolar collapse, but have
limited benefit without sufficient PEEP.
of the respiratory system.
and where opinion is important.11 The strengths of this method include the ability to bring a geographically dispersed and diverse group of expert panellists together, having an organised communication process in place, refining the con- tent through repeated review, and the ability to condense expert opinion into clearly defined practice recommendations. Recognised limitations include the time required for expert participation and lack of anonymity during the face-to-face meeting. A limitation of our recommendations is that most of the literature focuses on surrogate endpoints, such as oxygenation or respiratory mechanics, and that relatively little published data support improvements in morbidity or mor- tality. By the same token, the recommendations are inde- pendent from the recently revised definition of PPCs.17 Interventions with associated costs or potential complica- tions with no proven benefit in hard endpoints could not be recommended. Whilst the focus of this consensus conference was specifically to provide guidance for preoperative risk assessment and intraoperative mechanical ventilation for patients undergoing surgery, other factors not addressed in our review that may contribute to PPCs, such as incomplete reversal of neuromuscular block, postoperative opioid use, and surgical inflammation suppression, deserve further investigation. Future studies should continue to evaluate the roles of PEEP and ARM in the surgical patient. New imaging modalities, such as ultrasound and electrical impedance to- mography, may help further elucidate their roles. Good- quality data on lung de-recruitment during emergence and possible mitigating methods are also needed. Finally, the role of FIO2 in the development of PPCs requires further study.
In conclusion, this consensus meeting resulted in 26 recom- mendations and statements concerning the use of lung- protective ventilation in patients undergoing mechanical ventilation in the operating theatre. As the basic and clinical research focused on the application of mechanical ventilation in the surgical setting continues to emerge, it is likely that best practices to reduce or eliminate PPCs will likewise evolve. The
panel urges continued investigations and the adoption of proven interventions that will help optimise the perioperative care and safety of surgical patients. Further studies are needed to definitively confirm the beneficial effects of these in- terventions and manoeuvres on meaningful clinical outcomes.
Study design: CCY, EMH, CV
Literature search: AW
Literature review/compilation: SB, BB, RRDE, JM, CR, BT Review of studies with research team: MGA, MG, EF, JPM, PP, JS, EMH
Writing of first draft: CCY, EMH, CV
Formatting of references: AW
Revising of final draft: all authors
CCY was the consensus conference president (coordinating team). CV was the consensus conference moderator (coordi- nating team). EMH, MGA, MG, EF, JPM, PP, and JS were the consensus conference experts. SB, BB, RRDE, JM, CR, and BT were the consensus conference participants.
GE Healthcare provided financial and logistical support for the development and implementation of the consensus panel meeting, including travel, lodging, and meals for the partici- pants. GE Healthcare was not involved in the study data collection, analysis and interpretation of data, consensus panel deliberations, writing the report, or the decision to submit the report for publication. These were solely the de- cisions of the authors.
Declarations of interest
EF reports consulting fees from Dra€ger Medical, Edwards Lifesciences, GE Healthcare, and Orion Pharma, and lecture fees from Fresenius Kabi, Getinge, and Fisher & Paykel Healthcare. MGA has received financial support for research
Lung-protective ventilation – 11
Table 4 Recommendations and statements with moderate-to high-quality and strong expert support. ARM, alveolar recruitment manoeuvre; CPAP, continuous positive airway pressure; ESA, European Society of Anaesthesiology; FIO2, fraction of inspired oxygen; HOB, head of bed; I:E, inspiratory-to-expiratory ratio; NIPPV, non-invasive positive-pressure ventilation; PBW, predicted body weight; PPC, postoperative pulmonary complication; Pplat, plateau pressure; VT, tidal volume; ZEEP, zero end-expiratory pressure.
￼ ￼ ￼ ￼ ￼ ￼
￼ ￼ ￼ ￼
12 – Young et al.
and lecture fees from Dra€ger Medical AG, Ambu, Glax- oSmithKline, and GE Healthcare. MG and CCY are paid con- sultants for GE Healthcare. There are no other relationships or activities that could appear to have influenced the submitted work.
GE Healthcare (Anaesthesia and Respiratory Care)
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.org/10.1016/j.bja.2019.08.017.
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