Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study

Abstract

Background: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality.

Methods: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model.

Results: From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59-78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57-77] vs 74 [64-80] years, p < 0.001) and had lower driving (12 [8-16] vs 15 [11-17] cmH₂O, p < 0.001), plateau (20 [15-23] vs 22 [19-26] cmH₂O, p < 0.001) and peak (21 [17-27] vs 26 [20-32] cmH₂O, p < 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60-1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16-2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06-1.18], p < 0.001) and tidal volume after day 7 (HR 0.69 [0.52-0.93], p = 0.015) were related to survival.

Conclusions: Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury. Trial registration Clinicaltrials.gov NCT02010073.

Keywords: Cardiogenic pulmonary edema; Driving pressure; Mechanical ventilation; Ventilator-induced lung injury.

Fig. 1

A Patient flowchart. B Intensive care unit (ICU) survival and mortality. C Hospital survival and mortality

Fig. 2

A Profile plot of two patient classes identified according to several ventilatory variables at first day of invasive mechanical ventilation using a latent mixture analysis. Values show means in each variable used for classification for each class (after normalization, Z-scores). The largest differences are observed in airway pressures, whereas there are no differences in respiratory rate. B Discharge from the intensive care unit (ICU) alive and spontaneously breathing for each patient class. C Hospital mortality for each patient class. D Hazard ratios for mortality obtained from a marginal structural model addressing the time-dependent changes in each variable

Fig. 3

Time course of ventilatory settings and gas exchange over the first 10 days, according to the previously identified latent classes. A Driving pressures. B Positive end-expiratory pressure (PEEP). C Tidal volumes, expressed as milliliters per predicted body weight (PBW). D PaO₂/FiO₂ ratio. E PaCO₂. F Arterial pH. Values were compared between classes using a repeated measurements analysis of the variance (ANOVA)

Fig. 4

Distribution of values of ventilatory settings (A Peak inspiratory pressure; B Plateau pressure; C Driving pressure; D Positive end-expiratory pressure [PEEP]; E Tidal volume) according to the hemodynamic item of the SOFA score (0: mean arterial pressure ≥ 70 mmHg; 1: mean arterial pressure < 70 mmHg, 2: dopamine ≤ 5 μg/kg/min or dobutamine; 3: dopamine 5–15 μg/kg/min or norepinephrine ≤ 0.1 μg/kg/min or epinephrin ≤ 0.1 μg/kg/min; 4: dopamine > 15 μg/kg/min or norepinephrine > 0.1 μg/kg/min or epinephrin > 0.1 μg/kg/min). Spearman’s coefficients (ρ) were calculated to assess the correlation between these parameters and the score