Intraoperative mechanical ventilation practice in thoracic surgery patients and its association with postoperative pulmonary complications: results of a multicenter prospective observational study

The present work is a post hoc analysis of the ‘Local assessment of ventilatory management during general anesthesia for surgery and effects on postoperative pulmonary complications’ (LAS VEGAS trial) [3]. The LAS VEGAS trial protocol was first approved by the institutional review board of the Academic Medical Center, Amsterdam, The Netherlands (W12_190#12.17.0227) and registered at clinicaltrials.gov (NCT01601223). The protocol of this trial was published elsewhere [9].

Consecutive adult patients receiving invasive ventilation during general anesthesia for elective or non–elective surgery were eligible for participation in the study, which ran for seven predefined days in each country, selected by the national coordinator, in the period between January 14th and March 4th, 2013. Patients were excluded from participation if they were aged < 18 years, or scheduled for pregnancy related surgery, surgical procedures outside the operating room, or procedures involving cardio-pulmonary bypass.

The patient database of the LAS VEGAS trial was searched for eligible patients who received either open thoracic surgery, thoracoscopic or thoracoscopy assisted surgery (both summarized as endoscopic surgery), with or without OLV. These data have not been considered in previous analyses.

Reasonable parameters of baseline characteristics, intraoperative data and preoperative risk factors for PPCs were identified from previous studies [10‐13]. During the intraoperative period, data describing ventilation settings and vital parameters, as well as episodes of hypoxia (SpO₂ < 92%), use of recruitment maneuvers, airway pressure reduction, presence of expiratory flow limitation, hypotension (mean arterial pressure < 60 mmHg), use of vasoactive drugs, and new arrhythmias, was collected. Postoperative residual curarisation with neuromuscular blocking agents (NMBAs), defined as train–of–four stimulation (TOF) ratio <  0.9, was documented.

The definition of protective mechanical ventilation is still under debate. For this analysis it was based on recent recommendations [8, 14‐16]. Patients were considered to be have been protectively ventilated “as recommended” if PEEP ≥5 cmH₂O and V_T ≤ 8 ml/kg PBW during TLV [8, 14, 17], and PEEP ≥5 cmH₂O and V_T ≤ 5 ml/kg PBW during OLV [18‐20].

The occurrence of PPCs is presented as a collapsed composite of PPCs in the first five postoperative days. The following PPCs were scored daily from the day of surgery until hospital discharge or postoperative day 5: 1) need for supplementary oxygen (due to PaO₂ < 60 mmHg or SpO₂ < 90% in room air, excluding oxygen supplementation given as standard care or as continuation of preoperative therapy), 2) respiratory failure (PaO₂ < 60 mmHg or SpO₂ < 90% despite oxygen therapy, or need for non-invasive mechanical ventilation), 3) unplanned new or prolonged invasive or non–invasive mechanical ventilation, 4) acute respiratory distress syndrome, 5) pneumonia. Severe PPCs were defined as the occurrence of one or more of the complications 2–5. Patient data were anonymized before entry onto a password secured, web–based electronic case record form (OpenClinica, Boston, MA, USA).

Patients were stratified into groups based on: 1) use or not of OLV (OLV vs. only TLV); 2) use or not of an endoscopic approach (endoscopic vs. open); and 3) risk for PPC according to ARISCAT (low risk [ARISCAT < 26] vs. moderate-to-high risk [ARISCAT ≥26] Supplemental Table 2, Additional file 1). The ventilatory data, which were collected hourly, were first averaged for each patient according to the number of observations (median of the value). In a longitudinal analysis, this data is presented for the first, second, third, fourth and last hour of surgery. All data are presented for the whole population and for the subgroups. In-hospital length of stay (LOS) and in-hospital mortality was censored at postoperative day 28. Proportions are compared using χ² or Fisher exact tests and continuous variables are compared using the Mann-Whitney U Test, as appropriate.

The distributions of combinations of tidal volume size and PEEP level are presented in scatter plots. Cut-offs of 6 ml/kg PBW for tidal volume, and 5 cmH₂O for PEEP were chosen to form the matrices. These cut-offs were based on widely accepted values of each variable, or according to normal daily practice. The driving pressure was defined as plateau pressure (Pplat) minus the PEEP level.

Kaplan–Meier estimates of the cumulative probability of development of PPC and hospital discharge were performed. Cox proportional hazard models without adjustment for covariates were used to assess the effect of the subgroups on outcome. The proportionality assumption was tested with scaled Schoenfeld residuals. Adjustments for multiple comparisons were not performed and no assumption for missing data was done. Statistical significance was considered to be at two-sided p <  0.05. All analyses were performed with R version 3.4.1 (http://​www.​R-project.​org/​).

Patients operated under OLV received more often double-lumen tubes and had more frequently lung or pleural surgery than those operated under TLV (Table 1). Use of epidural anesthesia was less and duration of surgery shorter in endoscopic compared to non-endoscopic surgery (Table 1).

Patients at moderate-to-high risk for PPC received more frequently antibiotic prophylaxis and epidural anesthesia, and had longer duration of surgery as well as anesthesia, compared with patients at low risk (Table 1).

The amounts of crystalloids, colloids, albumin and packed red blood cells was higher in open vs. endoscopic surgery, and in patients at moderate-to-high vs. low risk for PPC (Table 2).

Patients were ventilated with V_T of 7.4 ± 1.6 ml/kg PBW, PEEP of 3.5 ± 2.4 cmH₂O, and driving pressure of 14.4 ± 4.6 cmH₂O (Table 2). Compared to patients operated solely under TLV, patients receiving OLV had lower V_T, higher peak, plateau and driving pressures, as well as PEEP and respiratory rate, and received higher number of recruitment maneuvers (Table 2). Protective ventilation was used in 14.8% (41/302) of all patients, mainly during TLV. The ventilatory management of patients undergoing endoscopic and non-endoscopic procedures did not differ significantly. Patients at moderate-to-high risk for PPC had higher levels of PEEP, and received more recruitment maneuvers than patients at low risk (Table 2).

Values of ventilator settings along time are shown in Supplemental Figures 2 through 4 (Additional file 1). Patients operated under OLV had higher FiO₂ compared with patients operated under TLV (Supplemental Figure 2, Additional file 1). The combinations of V_T and PEEP according to subgroups are shown in Supplemental Figures 5 through 7 (Additional file 1).

The overall incidence of PPCs in this population was 45.7% (138/302), and did not differ significantly between OLV vs. TLV (82/168 vs. 56/134, 48.8% vs. 41.8%, p = 0.223, total number and percentage respectively), and endoscopic vs. open procedures (16/46 vs. 122/256, 34.8% vs. 47.7%, p = 0.106, total number and percentage respectively, Table 3, Fig. 1). Patients at moderate-to-high risk showed an increased incidence of PPC compared to patients at lower risk (48.1% vs. 28.9%; hazard ratio, 1.95; 95% CI 1.05–3.61; p = 0.033), mainly due to unplanned need for supplemental oxygen (Table 3, Fig. 1).

The incidence of severe PPCs, unplanned ICU admission and hospital mortality did not differ among groups (Table 3). The incidence of hypotension was decreased in endoscopic compared to open procedures, and in patients at lower compared to moderate-to-high risk of PPCs (Table 3).

The LOS was increased in patients who developed PPCs (Supplemental Figure 8, Additional file 1), and shorter in patients operated under OLV vs. TLV, endoscopic vs. open, and those with low vs. moderate-to-high risk for PPC (Table 3, Fig. 2).

This study has several limitations. First, a one-week inclusion period was relatively short in order to include a high number of patients per center. However, this fact was counterbalanced by the multicenter design. Second, a short inclusion period might have resulted in selection bias, since fluctuation of the severity of cases cannot be ruled out. Nevertheless, the benefits of avoiding changes in therapy during the observation period as a potential confounder should not be underestimated. Third, the definition of protective mechanical ventilation was based on recommendations that are still under debate. Fourth, most study sites included less than 10 patients. This number, however, does not imply lack of experience with the procedure, since thoracic anesthesia per se already requires a substantial degree of expertise. Fifth, the duration of OLV was not investigated and, therefore, the exact contribution of OLV to PPCs cannot be separated from the period under TLV in this sub-population. Sixth, the design of this study precludes the possibility of determining cause-effect relationships, and results must be seen from a hypothesis-generating perspective. Seventh, the fact that data was collected prospectively might have interfered with clinical practice itself, and biased towards the use of protective ventilation. Still, non-protective ventilation was used in a vast majority of patients. Eighth, the total number of patients enrolled allowed analyses of three subgroups only. Potential confounders could be the type of anesthesia (total intravenous anesthesia vs. volatile anesthetics), the type of postoperative analgesia (epidural anesthesia vs. opioids) or the ASA status, which should be subject of future trials.