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This article explores the question of the implementation of lung protective ven-tilation in the OR. The discussion on how to ventilate surgical patients intraope-ratively to minimise postoperative pulmonary complications has been lively in the past years. In the whitepaper we will provide an overview of the challenge of implementing protective ventilation and we will give some recommendations based on actual literature.

Protective Ventilation in the OR

Implementation into daily clinical routine may be a challenge

IMPLEMENTATION INTO DAILY CLINICAL ROUTINE MAY BE A CHALLENGE

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Vt in patients undergoing abdominal surgery and spinal surgery. Tidal volumes in these trials were as low as 6 - 7 ml/kg predic-ted bodyweight (PBW) 9. The two large European trials, known as IMPROVE and PROVHILO, have both advocated that lung pro-tective ventilation in the OR should include low Vt, but showed contradicting results with respect to other components of lung pro-tection, namely PEEP and recruitment manoeuvres (RM) 12, 13. A recent meta-analysis stated the harmful effects of high Vt even under short-term ventilation for general anaesthesia for surgery ad-vocating relatively low Vt of 6 - 8 ml/kg PBW14. A very recent RCT on lung protective ventilation further suggests this approach for healthy patients undergoing laparoscopic surgery15.

TIDAL VOLUME AND PREDICTED BODY WEIGHT It is well known that tidal volumes should not be calculated based on actual but on predicted or ideal body weight, as suggested. This is important as the application of tidal vo-lumes as low as 6 – 8 ml/kg result in tidal volumes that may appear very low, probably lower than many would expect. In addition, there seems to be no agreement on a uniform way to calculate the PBW. The equations found in literature are inconsistent and result in markedly different tidal volumes. An actual article listed and compared various equations and recommended the NIH/NHLBI ARDSNet definition16:

• Women: 45.5 + 0.905 x ([height in cm] – 152.4)• Men: 50.0 + 0,905 x ([height in cm] – 152.4)

PEEP Whereas most research seems to be unambiguous with respect to tidal volumes, the use and the benefit of PEEP appears to be still controversial. For patients with moderate to severe ARDS, a meta-analysis has suggested a benefit from higher PEEP levels. But three independent RCTs failed to demonstrate definitive benefit. In critically ill patients without ARDS one study showed a benefit of a PEEP of 5 - 8 cmH2O compared to zero PEEP (ZEEP) with regards to the incidence of ventilator-associated pneumonia and the risk of hypoxemia, but not with respect to outcomes. Another trial could not demonstrate a positive effect of a PEEP of 8 cmH2O on

Various randomized controlled trials (RTCs) and reviews have been conducted to bring light into the dark about the ongoing discussion, on how to ventilate surgical patients intraoperatively to minimise postoperative pulmonary complications. However, re-search has not fully restored clinical balance. Some parameters of ventilation are proven as levers for protecting patients’ lungs during surgery, some remain unclear and require further research. However, all in all it seems to be common sense that general anaesthesia impairs lung function and ventilation plays a significant role in causing these impairments. Although results from research conducted on this topic are ambiguous the evidence gained during the past years mandate the use of lung protective strategies in sur-gical patients even though not all questions have been sufficient-ly answered yet.

The question is how current approaches can be implemented ef-fectively. Various other clinical procedures have shown that, al-though striking evidence is in place, recommendations and even guidelines are not fully applied on a routine basis in clinical practice.

Discussion on protective ventilation in the ORIn the discussion on intraoperative lung protection, research focus-ses on specific parameters that are expected to have an influence on the incidence of postoperative pulmonary complications, either individually or in conjunction with each other. Under discussion is the size of tidal volumes (Vt), the use and the level of positive end-expiratory pressure (PEEP), the applied oxygen fraction9, recruit-ment manoeuvres and recently the plateau- and driving pressures10.

Tidal volumeHigh Vt has already been described for quite some time to be particularly dangerous for ARDS patients and low Vt ventilation has become a standard of care for these patients in ICU as evidence demonstrated a clear reduction of mortality. But evidence has not only demonstrated the benefits of low Vt for ARDS patients, but also for critically ill patients without lung injury. But for these pa-tients, low Vt strategies have not yet become a standard of care9.In the OR, clinical trials have suggested that lung protective strate-gies encompassing reduced Vt have a positive effect on lung func-tion and the incidence of postoperative pulmonary complications (PPCs). Three RCTs have demonstrated positive effects of low

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the occurrence of ARDS or other associated complications. But another RCT found an independent association between higher PEEP levels and the development of lung injury when comparing Vt of 6 and 10 ml/kg PBW in the critically ill patient without ARDS9,

31, 32, 33, 34, 35, 36, 37.

For the perioperative ventilation, the available research does not give a clear answer on what the ideal PEEP is. The above menti-oned three RCTs compared bundles of lung protective measures, also including different levels of PEEP. This made it almost im-possible to draw any conclusion about the individual effect of this parameter9. PEEP was also the controversial point when comparing the two big European trials, PROVHILO and IMPROVE12, 13. While IMPROVE recommended a moderate PEEP level to keep recruited lungs open and to prevent further collapse, the PROVHILO trial could not demonstrate any benefit from higher PEEP levels of 12 cmH2O compared to low PEEP levels of 2 cmH2O, but high PEEP levels produced more intraoperative hypotension and a higher need for vasoactive drugs12, 13. The above mentioned meta-analysis cites recent findings that also suggest that higher levels of PEEP (10 - 12 cmH2O) do not protect against PPCs and may even cause harm, at least in the non-obese patient14. The above mentioned recent RCT on lung protective ventilation in patients undergoing laparoscopic surgery found that low Vt with a moderate PEEP of 5 cmH2O was associated with less incidences of pulmonary complications com-pared to conventional ventilation approaches with high Vt with RM and no PEEP15. So the discussion currently appears to tend toward moderate to low PEEPs10, 30.

Some authors mention, that an appropriate PEEP has to be cho-sen, but leave the question open what an appropriate PEEP is. In a recent commentary, Pelosi and Ball have asked the question as to whether it is time to talk about tailored protective ventilation, and demand further studies in particular on the role of patient-tailored PEEP settings10. This is also backed by a recent comprehensive re-view stating that PEEP should be chosen according to the patient’s particular characteristics, to specifics of the surgical approach and the patients’ position30. From a clinical routine perspective, Dr. Chris Thompson, Senior Staff Specialist at Royal Prince Alfred Hospital, Clinical Lecturer at the University of Sydney, Australia, has com-mented on this topic in his lecture at the ANZCA Congress 2015 in Australia. In his lecture, he gave practical insights into his ap-

proaches to protective ventilation including patient individual PEEP titration26.

TIP: You can watch the lecture on youtube (Link).

Plateau pressure and driving pressureTwo parameters have seldom appeared in the discussion on pro-tective ventilation: plateau pressure and driving pressure, which is defined as plateau pressure minus PEEP. A recent hospital based registry study analyzing 69.265 consecutive patients undergoing non-cardiac surgery (2007 – 2014) with general anaesthesia and endotracheal intubation found, that there is a moderate, statistically significant dose dependent relation between the risk of respiratory complications and the level of plateau pressure. The driving pres-sure was stated to have an effect on the occurrence of respiratory complication comparable to the plateau pressure. A median plateau pressure of less than 16cmH2O was identified as being protective and resulting in no increased risk of ventilator associated postope-rative respiratory complications. A very interesting finding was, that there was no significant statistical association between Vt and the incidence of PPCs17.

Ball and Pelosi, whose earlier mentioned comment refers to this study, stated that this finding suggests that the harmful effect of tidal volume dynamic strain might be mediated by an increase in plateau pressure linked to lung compliance, possibly reflecting lung stress10.

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RecruitmentMost studies cited herein have not specifically studied how, when and for which patients to best apply recruitment. However, PEEP has been described as being most effective when a recruitment manoeuvre has been carried out before. Güldner et al recommend to do so during tidal ventilation using an incremental approach with pressure controlled ventilation keeping plateau pressure constant at 15 – 20 cmH2O and gradually increasing PEEP to 20 cmH2O in steps of 5 cmH2O at 30-60 seconds per step. PEEP and tidal volu-me are adjusted to desired levels after up to 5 breaths at the PEEP level that achieves the targeted inspiratory pressure. Recruitment of atelectatic lung areas may require airway pressures of 40 mbar or even higher30. This approach shows similarities with the above men-tioned approach to PEEP titration suggested by Chris Thompson26.

However, as we believe recruitment is a quite important topic in the discussion on intraoperative lung protection, we will provide you with a separate review of literature at a later point in time.

RECOMMENDATIONS FROM LITERATUREBased on current evidence, Ball & Pelosi suggest the following parameters to be included into a protective ventilation strategy which is largely backed by recom-mendations by Filho and Serpa Neto published in a recent commentary 10, 8 and Güldner et al published in their recent Review30:– Low tidal volumes of 6 - 8 ml/kg PBW10, 8, 30

– Plateau pressure (<16 cmH2O) and low driving pres-sure, whenever possible 10, 8

– low PEEP ≤ 5 cmH2O 10 or even ≤ 2 cmH2O30

without recruitment 10, 30

– PEEP between 5 - 10 cmH2O to be considered in obese patients and for patients undergoing laparo-scopic surgery in Trendelenburg position for > 4h 10

– FiO2 ≥ 0.4 to keep SpO2 ≥ 92 %30– No recruitment manoeuvre as initial measure30

– In case of hypoxemia (if other causes are ruled out and if not contraindicated), FiO2 should be increa-sed first, followed by increase of PEEP and incre-mental recruitment manoeuvre30.

Fraction of inspired oxygen (FiO2) Traditionally a high FiO2 was expected to improve oxygenation and reduce the incidence of PONV as well as surgical site infections. But in the past years a more critical discussion has developed around the fraction of inspired oxygen that puts a question mark behind the afore mentioned traditional opinion. Part of this dis-cussion is the assumption that high FiO2 may induce pulmonary dysfunction, e.g. by induction of resorption atelectasis in unstable aveoli, and pulmonary injury, at least in part caused by oxidative stress via increased levels of reactive oxygen-derived free radicals that can overcharge natural antioxidant defenses and injure cellu-lar structures. Furthermore, evidence suggests that high FiO2 in conjunction with high blood oxygen is associated with increased mortality in critically ill patients9.

For intraoperative ventilation, Güldner et al recommend to use an FiO2 of ≥ 0.4 to keep SpO2 ≥ 92% and increase FiO2 first in case of hypoxemia (if other reasons are ruled out)30. This applies to non-obese, healthy patients. There may be good reasons for higher oxygen fractions depending on the patient or the surgical procedure.

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This also applies to both, anaesthetised patients with healthy lungs and patients with substantial pulmonary dysfunction. The reason for this supposedly lies in the role of the diaphragm. When phar-macologically relaxed, the intra-abdominal hydrostatic pressure will push against the diaphragm and move it more cranially – with in-creasing the pressure from anterior to posterior. This counters or even prevents diaphragm movement in the dependent lung regions resulting into ventilation being shifted to the nondependent lung re-gions and leaving dorsal lung regions close to the diaphragm being less ventilated or atelectatic. In due course mechanically administe-red tidal volume goes primarily into the anterior, nondependent and less perfused parts of the lung leading to the aforementioned V/Q mismatch24.

… getting even While breathing spontaneously, the posterior parts of the dia-phragm move more than the anterior tendon plate resulting in bet-ter ventilation of the dependent lung regions even when supine. This results in a better V/Q matching as the diaphragm is able to oppose alveolar compression20, 24 The improved aeration of the juxtadiaphragmatic lung regions is the reason for the improved functional residual capacity (FRC) associated with spontaneous breathing20, 24.

Fig. 2: CT image (C) from a patient with normally aerated lungs, representing the regional distribution of air content; EIT image (D) representing a homogeneous dis-tribution of ventilation.

Spontaneous breathing - another aspect of intraoperative protective ventilation?Various aspects of lung protection during general anesthesia ven-tilation have been discussed in the past years. We have gathered evidence insights and recommendations from literature for you. This discussion mainly concentrated on controlled mechanical ventilation, which is quite clear as many surgical procedures require neuromus-cular relaxation and consequently call for protective methods of me-chanical ventilation.

But it should be considered that neuromuscular relaxation and sub-sequent (mandatory) positive pressure ventilation appears to be a significant factor itself leading to respiratory impairment and poten-tially to the above cited postoperative pulmonary complications that protective ventilation intends to counteract. Therefore, it seem not too far-fetched to ask, whether spontaneous breathing either as ear-ly as possible towards the end of general anesthesia or even soon after securing the airway may be more beneficial. The following shall briefly highlight what the literature says and what the opinion of clini-cians is who have worked on this topic for the past years.

Tip: For further technical background information, see our “tech-nology insights” e-book. Uneven distribution…Imaging studies in animals have demonstrated that ventilation is not physiologically distributed during continuous mandatory ventilation (CMV). During CMV, ventilation is being shifted to the anterior, nondependent and less perfused lung regions leading to the well described ventilation/perfusion (V/Q) mismatch20.

Fig. 1: CT image (A) from a patient with dorsal lung collapse, representing the regio-nal distribution of air content. EIT image (B) from a patient with a comparable lung condition, representing the regional distribution of ventilation.

A. Lung collapse as displayed by CT B. Lung collapse as displayed by EIT

10 %

40 %

41 %

9 %

C. Normally aerated lung as displayed by CT

D. Normally aerated lung as displayed by EIT

10 %

40 %

41 %

9 %

6 %,

38 %

54 %

2 %

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Diaphragmatic Excursion The above was also confirmed in a research studying diaphragmatic excursion by diaphragmatic fluoroscopy during spontaneous brea-thing and during positive pressure ventilation. The diaphragm was divided into three segments: top (ventral, nondependent), middle and bottom (dorsal, dependent) in order to analyse differences. During normal spontaneous breathing, total diaphragmatic excursi-on was significantly greater compared to positive pressure breaths. The data from this study clearly show, that when breathing spon-taneously, most diaphragmatic excursion is being observed in the bottom, dependent region, no matter if it was a normal breath or a deep breath.

During positive pressure ventilation, excursion of the diaphragm was less in the bottom, dependent part but rather at the top, non-dependent part when lower tidal volumes were applied. Only when having applied larger tidal volumes, diaphragmatic excursion was more or less equal in top and the bottom part of the diaphragm21. This may be remarkable having the discussion on lung protective ventilation in mind which demands for low tidal volumes.

Support neededIt appears that spontaneous breathing potentially leads to better ventilator conditions compared to CMV. But during surgery, anaest-hetic drugs – especially opioids – impair spontaneous breathing by causing respiratory depression27. When comparing general anaes-thesia using Isoflurane or Sevoflurane with either positive pressure ventilation (PPV) or spontaneous breathing, it was found that PPV produced better respiratory results compared to spontaneous brea-thing, specifically with respect to oxygenation and etCO2. No diffe-rences were observed with regards to haemodynamic parameters. However, in this study, spontaneous breathing attempts were not actively supported by any means28.

Brimacombe et al tested if pressure support ventilation (PSV) with PEEP would achieve better results compared to the application of CPAP only, without any tidal support. The results clearly show that PSV results in higher oxygenation saturation, lower etCO2 values and higher expired tidal volumes compared to CPAP without tidal support thus providing more effective gas exchange22. In another trial, Bosek et al found that a PSV with a pressure titrated to pro-duce a near normal (physiological) Vt improves the efficiency of spontaneous breathing during inhalational anaesthesia by lowering respiratory rate (RR) and PaCO2 while preserving haemodynamic homeostasis23.

But there is another aspect to intraoperative spontaneous breathing that extends into the postoperative period. The above mentioned trial by Keller et al also found that time to emerge from general anaesthesia using Sevoflurane shortened from 12 minutes down to 6 minutes when patients were breathing spontaneously during ge-neral anaesthesia28. This finding was just recently confirmed by an RCT by Capdevilla et al suggesting that intra-operative PSV in pa-tients with laryngeal mask (LMA) reduces anaesthesia emergence time and Propofol consumption compared to continuous mandatory ventilation. In addition they found, that PSV improved respiratory function and did not cause adverse effects25.

Position of the diaphragmafter expiration

Position of the diaphragmafter inspiration

Fig. 3: Diaphragmic activity during spontaneous breathing favours redistribution of gas to dependent, well perfused areas

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When combining the above with the concepts of distraction and mental workload that anaesthetists are exposed to, there is a po-tentially negative impact on patient care.

DistractionDistractions are cited as contributory to healthcare-associated er-rors in a large portion of incidents including or involving the anaes-thetistt1. The safe administration of anaesthesia requires vigilance, time-sharing among multiple tasks and the ability to rapidly make decisions and take actions7. It is well recognised in other industries, such as aviation, that distraction increases the risk of error. Within anaesthesia, distraction has been implicated in the development of critical incidences2. Another aspect has the potential to make the entire mixture quite delicate.

Looking into literature, distraction of the anaesthetist has already been researched. One observational study has found that on ave-rage 34 distracting events were observed in cases with a mean duration of 103 minutes. Sources of distraction included other anaesthetists, the circulating nurse, visitors and the surgeon. But events with the highest level of distraction requiring immediate at-tention originated from OR equipment (alarms, noises) and other anaesthetists. The spread of distractions across the phases of

CONCLUSIONThe above intends to raise spontaneous breathing as a potentially interesting component of lung protective ventilation in the OR resulting in a better ventilation distribution. However, although there is also good re-ason and absolute necessity for mechanical ventilation for various patients and surgical procedures, sponta-neous breathing might be a good option in the future for even more indications as anticipated today. Further research is required to determine these indications and provide evidence for the effectiveness of sponta-neous breathing in intraoperative ventilation.

A distracting thought on difficulties deploying protective ventilationThe current, lively discussion on lung protective ventilation in the OR stresses the importance of this topic and the question may be raised on how implementation into daily clinical routine can be achieved. Looking at other procedures, such as active warming of patients in the OR, evidence is clear and even guidelines demand respective measures. But deployment into daily clinical routine ap-pears to be hampered for various reasons. We eagerly await the results of an international, prospective, observational, multicenter cohort study intending to research the current mechanical ventilati-on practices during general anaesthesia to get solid insights into the degree of protective ventilation deployment in the OR29. However, clinicians may need to consider a growing number of guidelines and standardised procedures in their daily clinical routine to fulfil the so-called standard of care in the future. That specifically applies to the fairly complex topic of ‛Ventilation in the OR‘.

Complexity The workplace of anaesthetists in the OR is very complex and over-loaded with information and multitasking necessities. The number of tasks, anaesthesiologists have to perform daily has increased substantially over the past decades, also demanding to continuous-ly multitask under difficult conditions. In an article by Thomas M. Hemmerling he referred to the anaesthetist as the pilot in the phy-siological biosphere of modern acute care medicine18.

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anaesthesia was equal. Another study found that one distracting event happened every 4 minutes and 23 seconds, most frequently during emergence with one event every 2 minutes2. In the first stu-dy mentioned above, approximately 8 distracting events per case were judged to be detrimental to current patient care1. The second study judged 22% of all observed distracting events to have a ne-gative effect2.

Distracting events during key anaesthetic interventions were ob-served relatively frequently, with about 2 events per case. The role of general background noise in the OR is controversial. General background theatre noise has been associated with deterioration in mental efficiency and short-term memory. But looking into the nature of different tasks, noise does not always have a negative effect. Low demand tasks may be performed better with increasing levels of external stimulation (conversations, noise and music) up to a certain point, but higher demand tasks may suffer with the same degree of external stimulation1.

Our perspective and moreFrom our perspective, the administration of a general anaesthesia, including protective ventilation needs to be considered as a high demand task that requires vigilance and close monitoring of all parameters that can be compromised by distractions as described above. Reported incidences may underline this thought. In one case in Germany, an anaesthetist forgot to switch on the anaest-hesia device while the patient was intubated. The reported reasons were distraction and ambient noise level in the OR3. In another case, the anaesthetist forgot to re-start the ventilation after deli-berately suspending ventilation during cardiac surgery. Among the reasons reported: many distractions4.

The abovementioned events can surely not only be attributed to inattention of the anaesthetist or other inadequate behaviour. But they may be a result of the abovementioned contributing factors: complex work environment meets information overload meets con-stant multitasking meets frequent distraction. Another factor that has been studied but apparently not yet clearly proven to be a factor contributing to human error in anaesthesiology is the mental workload6. Methods to measure mental workload have been re-searched and further research is desirable6. However, all this calls for the medical device industry to come up with devices that redu-

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IMPRINTGERMANYDrägerwerk AG & Co. KGaAMoislinger Allee 53–5523542 Lübeck

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ce information overload, are being used intuitively and assist with tasks that can be carried out following evidence based rule sets. Maybe assistance systems that take over those tasks but leave the anaesthetist in the drivers seat, easing the compliance with the standard of care, freeing up cognitive resources of the anaesthetist and reducing the potential negative effects of distractions in the OR may help reduce errors and gain importance.

Discover more on our website– more about protective ventilation in recovery/emergence– more about protective ventilation in maintenance– more about protective ventilatin in induction– overview about protective ventilation

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1 Jothiraj H, Howland-Harris J, Evley R, Moppett IK. Distractions and the anaesthetist: a qualitative study of context and direction of distraction. Br J Anaesth. 2013

Sep;111(3):477-82. Link

2 Campbell G1, Arfanis K, Smith AF. Distraction and interruption in anaesthetic practice. Br J Anaesth. 2012 Nov;109(5):707-15. Link

3 CIRSmedical / CIRS AINS, Case No. 28440; URL: https://www.cirsmedical.ch/AINS/m_files/cirs.php?seitennr=cpFBeri; viewed 14.05.2016

4 CIRSmedical / CIRS AINS, Case No. 110537; URL: https://www.cirsmedical.ch/AINS/m_files/cirs.php?seitennr=cpFBeri; viewed 14.05.2016

5 CIRSmedical / CIRS AINS, Case No. 1292; URL: https://www.cirsmedical.ch/AINS/m_files/cirs.php?seitennr=cpFBeri; viewed 14.05.2016

6 Byrne AJ1, Murphy A, McIntyre O, Tweed N. The relationship between experience and mental workload in anaesthetic practice: an observational study. Anaesthesia. 2013

Dec;68(12):1266-72. Link

7 Weinger MB, Slagle J. Human factors research in anesthesia patient safety. Proc AMIA Symp. 2001:756-60. Link

8 Filho RR, Serpa Neto A. One more brick in the wall of protective ventilation in surgical patients. Ann Transl Med. 2015 Dec;3(21):339. Link

9 Serpa Neto A, Schultz MJ, Slutsky AS. Current concepts of protective ventilation during general anaesthesia. Swiss Med Wkly. 2015 Nov 12;145:w14211. Link

10 BallL,PelosiP.Intraoperativemechanicalventilationinpatientswithnon-injuredlungs:timetotalkabouttailoredprotectiveventilation?AnnTranslMed.2016

Jan;4(1):17. Link

11 Levin MA, McCormick PJ, Lin HM, Hosseinian L, Fischer GW. Low intraoperative tidal volume ventilation with minimal PEEP is associated with increased mortality. Br

J Anaesth. 2014 Jul;113(1):97-108. Link

12 Hemmes SN, Gama de Abreu M, Pelosi P, et al. on behalf oft he PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology.

High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial.

Lancet. 2014 Aug 9;384(9942):495-503 Link

13 Futier E, Constantin JM, Paugam-Burtz C, et al; IMPROVE Study Group. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013

Aug 1;369(5):428-37. Link

14 Serpa Neto A, Schultz MJ, Gama de Abreu M. Intraoperative ventilation strategies to prevent postoperative pulmonary complications: Systematic review, meta-analysis,

and trial sequential analysis. Best Pract Res Clin Anaesthesiol. 2015 Sep;29(3):331-40. Link

15 ParkSJ,KimBG,OhAH,etal.Effectsofintraoperativeprotectivelungventilationonpostoperativepulmonarycomplicationsinpatientswithlaparoscopicsurgery:

prospective, randomized and controlled trial. Surg Endosc. 2016 Feb 19. Link

16 Linares-Perdomo O, East TD, Brower R, Morris AH. Standardizing Predicted Body Weight Equations for Mechanical Ventilation Tidal Volume Settings. Chest. 2015

Jul;148(1):73-8. Link

17 Ladha K, Vidal Melo MF, McLean DJ, et al. Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry

study. BMJ. 2015 Jul 14;351:h3646. Link

18 Hemmerling TM. Automated anesthesia. Curr Opin Anaesthesiol. 2009 Dec;22(6):757-63. Link

19 ECRI Institute, 2016 Top 10 Health Technology Hazards, 2016, URL: https://www.ecri.org/Pages/2016-Hazards.aspx; viewed 14.05.2016

20 NeumannP,WriggeH,ZinserlingJ,etal.Spontaneousbreathingaffectsthespatialventilationandperfusiondistributionduringmechanicalventilatorysupport.Crit

Care Med. 2005 May;33(5):1090-5. Link

21 Kleinman BS, Frey K, VanDrunen M, et al. Motion of the diaphragm in patients with chronic obstructive pulmonary disease while spontaneously breathing versus during

positive pressure breathing after anesthesia and neuromuscular blockade. Anesthesiology. 2002 Aug;97(2):298-305. Link

22 Brimacombe J, Keller C, Hörmann C. Pressure support ventilation versus continuous positive airway pressure with the laryngeal mask airway: a randomized crossover

study of anesthetized adult patients. Anesthesiology. 2000 Jun;92(6):1621-3. Link

23 BosekV1,RoyL,SmithRA.Pressuresupportimprovesefficiencyofspontaneousbreathingduringinhalationanesthesia.JClinAnesth.1996Feb;8(1):9-12.Link

24 Putensen C, Muders T, Varelmann D, Wrigge H. The impact of spontaneous breathing during mechanical ventilation. Curr Opin Crit Care. 2006 Feb;12(1):13-8. Link

REFERENCE:

IMPLEMENTATION INTO DAILY CLINICAL ROUTINE MAY BE A CHALLENGE

© Drägerwerk AG & Co. KGaA 10

25 CapdevilaX,JungB,BernardN,etal.Effectsofpressuresupportventilationmodeonemergencetimeandintra-operativeventilatoryfunction:arandomizedcontrolled

trial. PLoS One. 2014 Dec 23;9(12):e115139. Link

26 Dr.ChrisThompson,SeniorStaffSpecialistatRoyalPrinceAlfredHospital,ClinicalLecturerattheUniversityofSydney,Australia,lectureattheANZCACongress2015in

Australia, “Ventilation Techniques – A Practical Workshop”; ”; URL: https://www.youtube.com/watch?v=sU7sgTH2seA&feature=youtu.be; viewed 14.05.2016. Link

27 Dahan A, Aarts L, Smith TW. Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression. Anesthesiology. 2010 Jan;112(1):226-38. Link

28 Keller C, Sparr HJ, Luger TJ, Brimacombe J. Patient outcomes with positive pressure versus spontaneous ventilation in non-paralysed adults with the laryngeal mask. Can

J Anaesth. 1998 Jun;45(6):564-7. Link

29 Hemmes SN, de Abreu MG, Pelosi P, et al. ESA Clinical Trials Network 2012: LAS VEGAS--Local Assessment of Ventilatory Management during General Anaesthesia

forSurgeryanditseffectsonPostoperativePulmonaryComplications:aprospective,observational,international,multicentrecohortstudy.EurJAnaesthesiol.2013

May;30(5):205-7. Link

30 Güldner A, Kiss T, Serpa Neto A, et al. Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review

of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers. Anesthesiology. 2015 Sep;123(3):692-713. Link

31 Determann RM, Royakkers A, Wolthuis EK, et al. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung inju-

ry: a preventive randomized controlled trial. Crit Care. 2010;14(1):R1. Link

32 Brower RG1, Lanken PN, MacIntyre N, et al; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressu-

res in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36. Link

33 Mercat A, Richard JC, Vielle B, et al. Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respi-

ratory distress syndrome: a randomized controlled trial. JAMA. 2008 Feb 13;299(6):646-55. Link

34 Meade MO, Cook DJ, Guyatt GH, et al. Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive

end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008 Feb 13;299(6):637-45. Link

35 Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic

review and meta-analysis. JAMA. 2010 Mar 3;303(9):865-73. Link

36 Manzano F, Fernández-Mondéjar E, Colmenero M, et al. Positive-end expiratory pressure reduces incidence of ventilator-associated pneumonia in nonhypoxemic patients.

Crit Care Med. 2008 Aug;36(8):2225-31. Link

37 Pepe PE, Hudson LD, Carrico CJ. Early application of positive end-expiratory pressure in patients at risk for the adult respiratory-distress syndrome. N Engl J Med. 1984

Aug 2;311(5):281-6. Link

REFERENCE F.F. :