This Invited Commentary accompanies the following original article:
Cohen B, Ruetzler K, Kurz A, et al. Intra-operative high inspired oxygen fraction does not increase the risk of postoperative respiratory complications: Alternating intervention clinical trial. Eur J Anaesthesiol 2019; 36:320–326.
High intra-operative fraction of inspired oxygen (FIO2) has been proposed to increase the tissue O2 tension during surgery with the aim to reduce surgical-wound infection.1 However, an FIO2 of 0.60 to 0.90 does not reduce the relative risk (RR) of surgical site infection [RR 0.86 (95% confidence interval (CI) 0.63 to 1.1)] and all-cause mortality [RR 1.12 (95% CI 0.93 to 1.36)] more than an FIO2 of 0.40 or less.2 Trial sequential analysis estimates a required study size of 10 736 patients to detect a risk increase of 20% in all-cause mortality.2 The cumulative Z-curve does not reach the conventional boundary for significance and monitoring boundary for harm/benefit suggesting insufficient evidence with high FIO2.2
In a large observationnal study, an intraoperative FIO2 of at least 0.6 was used in 41% of patients without increasing the risk of postoperative pulmonary complications measured by a composite score.3 Reactive oxygen species induced by high O2 administration can worsen lung function during prolonged ventilation.1 An alternating interventional trial during abdominal surgery lasting more than 2 h compared FIO2 of 0.80 and 0.30.4 No difference was observed in the primary outcomes (30-day surgical-wound infection and mortality) which concerned 10.8 and 11.0% of patients, respectively.4 In this issue of the European Journal of Anaesthesiology, a posthoc analysis5 of that study,4 including 5056 patients assigned to the two FIO2 regimens, is presented. The main outcome was the ratio between arterial oxygen saturation estimated by pulse oximetry (SpO2) and the inspired oxygen fraction (SpO2:FIO2 ratio) in the post anaesthesia care unit (PACU). The use of an FIO2 of 0.80 did not worsen the lowest SpO2:FIO2 ratio (P = 0.91).5 No difference was noted in postoperative pulmonary complications [17.6 vs. 16.3%, RR 1.07 (95% CI 0.95 to 1.21, P = 0.25)] nor its components.5 In contrast, postoperative pulmonary complications were increased in a registry study in noncardiothoracic procedures 7 days after surgery [adjusted odds ratio 1.99 (95% CI 1.72 to 2.31)] with FIO2 of 0.79 (range 0.64 to 1.0) compared with 0.31 (range 0.16 to 0.34).6 However, when compared with the results of Cohen et al.5 the frequency of postoperative pulmonary complications was four times less, the duration of surgery was 36% shorter and patients were sicker in the high FIO2 group.6 Despite multivariate adjustments, this study was limited by residual confounding variables and the choice of high FIO2 was mainly influenced by unfavourable pre-operative conditions of patients. The SpO2:FIO2 ratio is a continuous available surrogate marker closely correlated to the ratio of arterial partial pressure of oxygen (PaO2) to the inspired oxygen fraction (PaO2:FIO2 ratio). Validated predominantly in nonsurgical patients,7 the SpO2:FIO2 ratio is frequently used to guide O2 supplementation in PACU. High FIO2 promoted atelectasis in 90% of patients when maintained after intubation and is related to an increase in low ventilation:perfusion ratio in the dependant juxta-diaphragmatic lung regions and by gas resorption phenomena.8 Combined with the impact of anaesthesia on respiratory muscle tone and airway closure, the repeating opening/closing of alveoli can facilitate the occurrence of postoperative pulmonary complications. However, despite an intra-operative FIO2 less than 0.35, an FIO2 of 0.30 during recovery did not reduce the atelectatic area when compared with an FIO2 of 1.0.8 When a washout was performed after intubation to stabilise FIO2 between 0.30 and 0.35, atelectasis was similar in patients who did not receive the washout.9 In a meta-analysis, an FIO2 more than 0.50 did not increase atelectasis [RR 0.93 (95% CI 0.59 to 1.46)] but postoperative pulmonary complications were not defined accurately and the absence of trial sequential analysis downgraded the relevance of the results.10
In the study of Cohen et al.5 the SpO2 was extracted from patients’ electronic records and the FIO2 calculated from the reported O2 enrichment device. Although patients’ characteristics were well balanced, no arterial blood samples were obtained, positive end-expiratory pressure (PEEP) was not controlled, the tidal volume was not detailed [predictive body weight (PBW) or not] and nor was the use of recruitment manoeuvres. PEEP, recruitment manoeuvre, low tidal volume based on PBW and enhanced recovery programme are implemented methods with the aim to reduce lung injury during ventilation and to enhance oxygenation parameters.5 In a meta-analysis, a tidal volume of 8 ml kg−1 or less of PBW with or without PEEP at least 5 cmH2O and with or without recruitment manoeuvres reduced the risk of postoperative pulmonary complications [odds ratio (OR) 0.64 (95% CI 0.46 to 0.88)] compared with a tidal volume more than 8 ml kg−1 without PEEP and recruitment manoeuvres.11 No association was observed between different levels of PEEP or recruitment manoeuvres and the risk of postoperative pulmonary complications.11 A PEEP of at least 5 cmH2O appeared beneficial only with a tidal volume of 7 ml kg−1 or less [OR 0.40 (95% CI 0.21 to 0.78)] compared with 10 ml kg−1 in improving re-aeration of the collapsed lung.11 A dose–response effect was observed between the probability of postoperative pulmonary complications and tidal volume (R2 0.39) but not with PEEP.11 The threshold of PEEP to reduce postoperative pulmonary complications remains unknown but levels of 10 cmH2O or less are commonly sufficient in nonobese patients. The risk of airway distension with high level of PEEP is established and recruitment manoeuvres can induce transient haemodynamic perturbance by an increase in transpulmonary pressure reducing stroke volume.11,12 In the PROVHILO study, despite a better dynamic respiratory compliance, postoperative pulmonary complications was similar in patients ventilated with PEEP of 12 cmH2O associated with recruitment manoeuvres and in patients receiving no PEEP and no recruitment manoeuvres with an increased risk of arterial hypotension [RR 1.29 (95% CI 1.1 to 1.5)].12
PEEP titration was evaluated during abdominal surgery using electrical impedance tomography.13 The titrated-PEEP patients had higher PEEP values (13.2 ± 4 and 10.1 ± 2 cm H2O during laparoscopy and laparotomy respectively) than those treated conventionally (PEEP of 4 cm H2O) with, in the latter, worsening of oxygenation by less aeration in dependent lung zones.13 The titration enhanced the PaO2:FIO2 ratio (FIO2 0.50) and decreased the postoperative proportion of nonaerated lung (6.2 ± 4.1 vs. 10.8 ± 7.1%).12 Postoperative pulmonary complications were reduced [RR 0.8 (95% CI 0.65 to 0.99)] after abdominal surgery in patients ventilated with repeated recruitment manoeuvres associated with PEEP individualised according to dynamic compliance and SpO2 (PEEP 10.3 ± 2.7 cmH2O) combined with postoperative continuous positive airway pressure (CPAP) only when SpO2 was 96% or less compared with patients randomised to a constant PEEP of 5 cmH2O and no CPAP.14 In this study, FIO2 was set at 0.80 for induction and recovery, tidal volume was fixed at 8 ml kg−1 of PBW and titration was adapted during surgery. Titration improved the PaO2:FIO2 ratio14 despite higher PEEP levels than those previously validated.11
The driving pressure (ΔP = difference between the plateau pressure and the level of PEEP) estimates the proportion of tidal volume delivered to the aerated lung.15 Using PEEP levels of 2, 7 and 12 cmH2O, ΔP decreased when PEEP increased from 2 to 7 cmH2O and was related to dynamic strain only if the aerated lung volume remained lower than the predicted functional residual capacity.15 In an animal study, low tidal volume with moderate PEEP reduced ΔP, provoked less lung collapse, less cell injuries and less TNF-α release regardless of the use of a single or repeated recruitment manoeuvres.16 ΔP was independently associated with a reduction in postoperative pulmonary complications during surgery, its reduction better protecting the lung than low PBW-based tidal volume or nontitrated PEEP alone.17 Any increase in ΔP during PEEP elevation can worsen the risk of postoperative pulmonary complications [RR 3.11 (95% CI 1.39 to 6.96)].17 A PEEP setting strategy lowered ΔP during abdominal surgery as well as the proportion of collapsed lung during ventilation.13 Routine recruitment manoeuvres, regardless of the level of FIO2 and PEEP, can be harmful when carried out inappropriately without using a ventilator-based recruitment manoeuvre in obese patients.18 The performance of pressure-support ventilation, although rarely used,3,18 can be altered in anaesthesia ventilators, particularly in low fresh gas flow techniques, reducing tidal volume and O2 delivery.19 In the study of Cohen et al.5 the median time-weighted average of FIO2 were 43 and 81% in patients assigned to the 30 and 80% groups, respectively. The augmentation of FIO2 is frequent when using low tidal volume with fixed PEEP, essentially through lung collapse below the resting lung volume leading to the use of FIO2 of at least 0.8 in 12% of patients.3 The choice of FIO2 may be influenced by higher baseline patients’ risk factors for postoperative pulmonary complications.6 Finally, the use of a high inspired O2 after surgery with high-flow nasal canulae, increasing FIO2 from 0.21 to 1.0, remains to be clarified even if its benefit seems to be associated with the use of recruitment manoeuvres during surgery.20 In the light of recent evolution in ventilation settings12–17 and the sparse data from meta-analyses,2,10 the causal link between SpO2:FIO2 and postoperative pulmonary complications in surgical patients has not yet been determined. However, the findings of Cohen et al.5 reinforce the necessity to evaluate prospectively the impact of an individualised FIO2 with PEEP titration, low tidal volume and repeated recruitment manoeuvres to lower ΔP and peak pressure associated with the occurrence of postoperative pulmonary complications in nonobese patients.3
Acknowledgements relating to this article
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Comment from the Editor: This article was checked and accepted by the Editors, but was not sent for external peer-review.
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