Opening pressures and atelectrauma in acute respiratory distress syndrome

Purpose

Open lung strategy during ARDS aims to decrease the ventilator-induced lung injury by minimizing the atelectrauma and stress/strain maldistribution. We aim to assess how much of the lung is opened and kept open within the limits of mechanical ventilation considered safe (i.e., plateau pressure 30 cmH₂O, PEEP 15 cmH₂O).

Methods

Prospective study from two university hospitals. Thirty-three ARDS patients (5 mild, 10 moderate, 9 severe without extracorporeal support, ECMO, and 9 severe with it) underwent two low-dose end-expiratory CT scans at PEEP 5 and 15 cmH₂O and four end-inspiratory CT scans (from 19 to 40 cmH₂O). Recruitment was defined as the fraction of lung tissue which regained inflation. The atelectrauma was estimated as the difference between the intratidal tissue collapse at 5 and 15 cmH₂O PEEP. Lung ventilation inhomogeneities were estimated as the ratio of inflation between neighboring lung units.

Results

The lung tissue which is opened between 30 and 45 cmH₂O (i.e., always closed at plateau 30 cmH₂O) was 10 ± 29, 54 ± 86, 162 ± 92, and 185 ± 134 g in mild, moderate, and severe ARDS without and with ECMO, respectively (p < 0.05 mild versus severe without or with ECMO). The intratidal collapses were similar at PEEP 5 and 15 cmH₂O (63 ± 26 vs 39 ± 32 g in mild ARDS, p = 0.23; 92 ± 53 vs 78 ± 142 g in moderate ARDS, p = 0.76; 110 ± 91 vs 89 ± 93, p = 0.57 in severe ARDS without ECMO; 135 ± 100 vs 104 ± 80, p = 0.32 in severe ARDS with ECMO). Increasing the applied airway pressure up to 45 cmH₂O decreased the lung inhomogeneity slightly (but significantly) in mild and moderate ARDS, but not in severe ARDS.

Conclusions

Data show that the prerequisites of the open lung strategy are not satisfied using PEEP up to 15 cmH₂O and plateau pressure up to 30 cmH₂O. For an effective open lung strategy, higher pressures are required. Therefore, risks of atelectrauma must be weighted versus risks of volutrauma.

Trial registration

Clinicaltrials.gov identifier: NCT01670747 (www.clinicaltrials.gov).

     

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study

Introduction

While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.

Aim

This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).

Methods

The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st–3rd quartiles).

Results

Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16–23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO₂/F_IO₂ increased from 101 (76–136) to 171 (118–220) mmHg (P = 0.0001) driving pressure decreased from 14 [11–17] to 13 [10–16] cmH₂O (P = 0.001), and Pplat decreased from 26 [23–29] to 25 [23–28] cmH₂O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).

Conclusions

In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

     

Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis

Purpose

Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate associations between ventilatory settings during ECMO for refractory hypoxemia and outcome in ARDS patients.

Methods

In this individual patient data meta-analysis of observational studies in adult ARDS patients receiving ECMO for refractory hypoxemia, a time-dependent frailty model was used to determine which ventilator settings in the first 3 days of ECMO had an independent association with in-hospital mortality.

Results

Nine studies including 545 patients were included. Initiation of ECMO was accompanied by significant decreases in tidal volume size, positive end-expiratory pressure (PEEP), plateau pressure, and driving pressure (plateau pressure ? PEEP) levels, and respiratory rate and minute ventilation, and resulted in higher PaO₂/FiO₂, higher arterial pH and lower PaCO₂ levels. Higher age, male gender and lower body mass index were independently associated with mortality. Driving pressure was the only ventilatory parameter during ECMO that showed an independent association with in-hospital mortality [adjusted HR, 1.06 (95 % CI, 1.03–1.10)].

Conclusion

In this series of ARDS patients receiving ECMO for refractory hypoxemia, driving pressure during ECMO was the only ventilator setting that showed an independent association with in-hospital mortality.

     

Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome

Purpose

Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV).

Methods

A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (P_high) set at the last plateau airway pressure (P_plat), not to exceed 30 cmH₂O) and low airway pressure ( P_low) set at 5 cmH₂O; the release phase (T_low) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10–14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; P_plat not exceeding 30 cmH₂O; positive end-expiratory pressure (PEEP) guided by the PEEP–FiO₂ table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, P_plat, respiratory system compliance, and patient outcomes.

Results

Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8–22] vs. 2 (IQR 0–15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower P_plat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance).

Conclusions

Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased P_plat and reduced the duration of both mechanical ventilation and ICU stay.

     

Adult ICU ventilators to provide neonatal ventilation: a lung simulator study

Background

Traditionally, specific ventilators have been manufactured to only provide neonatal mechanical ventilation. However, many of the current generation of ICU ventilators also include a neonatal mode.

Methods

Using the IngMar ASL5000 lung simulator the Puritan Bennett 840, the Maquet Servo i, the Viasys AVEA, the GE Engström, the Drager Evita XL and Babylog 8000 Plus were evaluated during assisted ventilation in the pressure assist/control mode. Three lung mechanics were set: resistance 50 cmH₂O/L/s, compliance 2 mL/cmH₂O; resistance 100 cmH₂O/L/s, compliance 1 mL/cmH₂O; and resistance 150 cmH₂O/L/s, compliance 0.5 mL/cmH₂O. A maximum negative pressure drop of 4 and 7 cmH₂O was achieved during simulated inspirations. Each ventilator was evaluated with PEEP 5 cmH₂O, peak pressure 20 cmH₂O and inspiratory time 0.3 s and with PEEP 10 cmH₂O, peak pressure 30 cmH₂O and inspiratory time 0.4 s. Each ventilator setting was then repeated with a leak of 0.3 L/min at a constant pressure of 5 cmH₂O.

Results

Overall each of the 5 ICU ventilators responded faster or greater than the Babylog with respect to: pressure to trigger (except the Servo i), time to trigger (except the Evita XL), time between trigger and return of pressure to baseline, time from start of breath to 90% of peak pressure (except the Avea) and pressure time product of breath activation. Expiratory tidal volume was also greater with all ICU ventilators except the Avea. Variation in mechanics, leak, PEEP and muscular effort had little effect on these differences.

Conclusion

All ICU ventilators tested were able to at least equal the performance of the Babylog 8000 Plus on all variables evaluated.

     

Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome

Purpose

To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).

Patients and methods

We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.

Main outcomes

We included 1899 patients with ARDS in this study. The relationship between maximum PaCO₂ in the first 48 h and mortality suggests higher mortality at or above PaCO₂ of ≥50 mmHg. Patients with severe hypercapnia (PaCO₂ ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO₂/FiO₂ ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04–2.41; p = 0.032).

Conclusions

Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.

Trial registration

Clinicaltrials.gov identifier, NCT01093482.

     

Mortality and pulmonary mechanics in relation to respiratory system and transpulmonary driving pressures in ARDS

Purpose

The driving pressure of the respiratory system has been shown to strongly correlate with mortality in a recent large retrospective ARDSnet study. Respiratory system driving pressure [plateau pressure?positive end-expiratory pressure (PEEP)] does not account for variable chest wall compliance. Esophageal manometry can be utilized to determine transpulmonary driving pressure. We have examined the relationships between respiratory system and transpulmonary driving pressure, pulmonary mechanics and 28-day mortality.

Methods

Fifty-six patients from a previous study were analyzed to compare PEEP titration to maintain positive transpulmonary end-expiratory pressure to a control protocol. Respiratory system and transpulmonary driving pressures and pulmonary mechanics were examined at baseline, 5 min and 24 h. Analysis of variance and linear regression were used to compare 28 day survivors versus non-survivors and the intervention group versus the control group, respectively.

Results

At baseline and 5 min there was no difference in respiratory system or transpulmonary driving pressure. By 24 h, survivors had lower respiratory system and transpulmonary driving pressures. Similarly, by 24 h the intervention group had lower transpulmonary driving pressure. This decrease was explained by improved elastance and increased PEEP.

Conclusions

The results suggest that utilizing PEEP titration to target positive transpulmonary pressure via esophageal manometry causes both improved elastance and driving pressures. Treatment strategies leading to decreased respiratory system and transpulmonary driving pressure at 24 h may be associated with improved 28 day mortality. Studies to clarify the role of respiratory system and transpulmonary driving pressures as a prognosticator and bedside ventilator target are warranted.

     

Effects of neuromuscular blockers on transpulmonary pressures in moderate to severe acute respiratory distress syndrome

Purpose

To investigate whether neuromuscular blocking agents (NMBA) exert beneficial effects in acute respiratory distress syndrome (ARDS) by reason of their action on respiratory mechanics, particularly transpulmonary pressures (P _L).

Methods

A prospective randomised controlled study in patients with moderate to severe ARDS within 48 h of the onset of ARDS. All patients were monitored by means of an oesophageal catheter and followed up for 48 h. Moderate ARDS patients were randomised into two groups according to whether they were given a 48-h continuous infusion of cisatracurium besylate or not (control group). Severe ARDS patients did not undergo randomisation and all received cisatracurium besylate per protocol. The changes during the 48-h study period in oxygenation and in respiratory mechanics, including inspiratory and expiratory P _L and driving pressure, were assessed and compared. Delta P _L (?P _L) was defined as inspiratory P _L minus expiratory P _L.

Results

Thirty patients were included, 24 with moderate ARDS and 6 with severe ARDS. NMBA infusion was associated with an improvement in oxygenation in both moderate and severe ARDS, accompanied by a decrease in both plateau pressure and total positive end-expiratory pressure. The mean inspiratory and expiratory P _L were higher in the moderate ARDS group receiving NMBA than in the control group. In contrast, there was no change in either driving pressure or ?P _L related to NMBA administration.

Conclusions

NMBA could exert beneficial effects in patients with moderate ARDS, at least in part, by limiting expiratory efforts.

     

Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study

Purpose

To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification.

Methods

Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24 h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification.

Results

Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01–1.13), P?=?0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both resolved and confirmed ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal.

Conclusions

ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population.

Trial Registration

ClinicalTrials.gov NCT02010073.

     

Apnoeic oxygenation via high-flow nasal cannula oxygen combined with non-invasive ventilation preoxygenation for intubation in hypoxaemic patients in the intensive care unit: the single-centre,blinded, randomised controlled OPTINIV trial

Purpose

High-flow nasal cannula oxygen (HFNC) has the potential to provide apnoeic oxygenation. We decided to assess in a proof-of-concept study whether the addition of HFNC to non-invasive ventilation (NIV) could reduce oxygen desaturation during intubation, compared with NIV alone for preoxygenation, in severely hypoxaemic intensive care unit (ICU) patients with respiratory failure.

Methods

We conducted a randomised, controlled, single-centre trial with assessor-blinded outcome assessment in patients admitted to the ICU. Hypoxaemic patients requiring orotracheal intubation for respiratory failure were randomised to receive preoxygenation using HFNC [flow = 60 L/min, fraction of inspired oxygen (FiO₂) = 100 %] combined with NIV (pressure support = 10 cmH₂O, positive end-expiratory pressure = 5 cmH₂O, FiO₂ = 100 %) in the intervention group or NIV alone in the reference group prior to intubation. The primary outcome was the lowest oxygen saturation (SpO₂) during the intubation procedure. Secondary outcomes were intubation-related complications and ICU mortality.

Results

Between July 2015 and February 2016, we randomly assigned 25 and 24 patients to the intervention and reference groups, respectively. In both groups the main reasons for respiratory failure were pneumonia and ARDS. During the intubation procedure, the lowest SpO₂ values were significantly higher in the intervention group than in the reference group [100 (95–100) % vs. 96 (92–99) %, p = 0.029]. After exclusion of two patients from analysis for protocol violation, no (0 %) patients in the intervention group and five (21 %) patients in the reference group had SpO₂ below 80 % (p = 0.050). We recorded no significant difference between the groups in intubation-related complications or ICU mortality.

Conclusions

A novel strategy for preoxygenation in hypoxaemic patients, adding HFNC for apnoeic oxygenation to NIV prior to orotracheal intubation, may be more effective in reducing the severity of oxygen desaturation than the reference method using NIV alone.

     

Ventilator-related causes of lung injury: the mechanical power

Purpose

We hypothesized that the ventilator-related causes of lung injury may be unified in a single variable: the mechanical power. We assessed whether the mechanical power measured by the pressure–volume loops can be computed from its components: tidal volume (TV)/driving pressure (?P _aw), flow, positive end-expiratory pressure (PEEP), and respiratory rate (RR). If so, the relative contributions of each variable to the mechanical power can be estimated.

Methods

We computed the mechanical power by multiplying each component of the equation of motion by the variation of volume and RR:

$${\text{Power}}_{\text{rs}} = {\text{RR}} \cdot \left\{ {\Delta V^{2} \cdot \left[ {\frac{1}{2} \cdot {\text{EL}}_{\text{rs}} + {\text{RR}} \cdot \frac{{\left( {1 + I:E} \right)}}{60 \cdot I:E} \cdot R_{\text{aw}} } \right] + \Delta V \cdot {\text{PEEP}}} \right\},$$

where ?V is the tidal volume, EL_rs is the elastance of the respiratory system, I:E is the inspiratory-to-expiratory time ratio, and R _aw is the airway resistance. In 30 patients with normal lungs and in 50 ARDS patients, mechanical power was computed via the power equation and measured from the dynamic pressure–volume curve at 5 and 15 cmH₂O PEEP and 6, 8, 10, and 12 ml/kg TV. We then computed the effects of the individual component variables on the mechanical power.

Results

Computed and measured mechanical powers were similar at 5 and 15 cmH₂O PEEP both in normal subjects and in ARDS patients (slopes = 0.96, 1.06, 1.01, 1.12 respectively, R ² > 0.96 and p < 0.0001 for all). The mechanical power increases exponentially with TV, ?P _aw, and flow (exponent = 2) as well as with RR (exponent = 1.4) and linearly with PEEP.

Conclusions

The mechanical power equation may help estimate the contribution of the different ventilator-related causes of lung injury and of their variations. The equation can be easily implemented in every ventilator’s software.

     

Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography

Purpose

Higher positive end-expiratory pressure might induce lung inflation and recruitment, yielding enhanced regional lung protection. We measured positive end-expiratory pressure-related lung volume changes by electrical impedance tomography and by the helium dilution technique. We also used electrical impedance tomography to assess the effects of positive end-expiratory pressure on regional determinants of ventilator-induced lung injury.

Methods

A prospective randomized crossover study was performed on 20 intubated adult patients: 12 with acute hypoxemic respiratory failure and 8 with acute respiratory distress syndrome. Each patient underwent protective controlled ventilation at lower (7 [7, 8] cmH₂O) and higher (12 [12, 13] cmH₂O) positive end-expiratory pressures. At the end of each phase, we collected ventilation, helium dilution, and electrical impedance tomography data.

Results

Positive end-expiratory pressure-induced changes in lung inflation and recruitment measured by electrical impedance tomography and helium dilution showed close correlations (R ² = 0.78, p < 0.001 and R ² = 0.68, p < 0.001, respectively) but with relatively variable limits of agreement. At higher positive end-expiratory pressure, recruitment was evident in all lung regions (p < 0.01) and heterogeneity of tidal ventilation distribution was reduced by increased tidal volume distending the dependent lung (p < 0.001); in the non-dependent lung, on the other hand, compliance decreased (p < 0.001) and tidal hyperinflation significantly increased (p < 0.001). In the subgroup of ARDS patients (but not in the whole study population) tidal hyperinflation in the dependent lung regions decreased at higher positive end-expiratory pressure (p = 0.05), probably indicating higher potential for recruitment.

Conclusions

Close correlations exist between bedside assessment of positive end-expiratory pressure-induced changes in lung inflation and recruitment by the helium dilution and electrical impedance tomography techniques. Higher positive end-expiratory pressure exerts mixed effects on the regional determinants of ventilator-induced lung injury; these merit close monitoring.

     

Type III procollagen is a reliable marker of ARDS-associated lung fibroproliferation

Purpose

A specific biomarker of post-ARDS fibroproliferation could be useful in the identification of patients who could benefit from therapies aiming to modulate fibroproliferation such as corticosteroids.The aim of this prospective study was to determine the best threshold of the N-terminal-peptidetype III procollagen (NT-PCP-III) in non-resolving ARDS to validate this threshold according to the outcome.

Methods

Concerning the best threshold of NT-PCP-III, all consecutive patients with a non-resolving ARDS were included if all the following criteria were fulfilled: moderate to severe ARDS lasting for at least 5 days, lung biopsy performed, serum and alveolar NT-PCP-III obtained within 1 week prior to biopsy, and no documented infection contra-indicating the corticosteroids. In the validation cohort part of the study, patients were included at day 7 if they presented a persistent moderate to severe ARDS.

Results

Nineteen of 32 patients had fibroproliferatio nonbiopsy. Serum and alveolar NT-PCP-III were higher in patients with fibroproliferation. Using a threshold of 9 µg/L, alveolar NT-PCP-III had the highest accuracy for diagnosing fibroproliferation (sensitivity = 89.5 % and specificity = 92.3 %). Regarding the 51 patients included in the validation cohort, the mortality rate at day 60 was increased in patients presenting an alveolar NT-PCP-III level higher than 9 µg/L (69 vs. 17 %, p < 0.001). The mean alveolar level of NT-PCP-III on day 7 was 8.1-fold higher in nonsurvivors (p = 0.03).

Conclusions

The determination of NT-PCP-III on BAL done at day 7 in persistent ARDS is able to identify patients with fibroproliferation who could be included in a trial of corticosteroids or any other treatment that might help resolve lung fibroproliferation.

     

The influence of PEEP and positioning on central venous pressure and venous hepatic hemodynamics in patients undergoing liver resection

Purpose

In order to assess the occurrence of blood congestion in the liver during liver resection, we aimed to evaluate the influence of a positive-end-expiratory-pressure (PEEP) and positioning of patients on central venous pressure (CVP) and venous hepatic blood flow parameters. We further analyzed correlations between CVP and venous hepatic blood flow parameters.

Methods

In 20 patients scheduled for elective liver resection we measured CVP and quantified venous hepatic hemodynamics by ultrasound assessment of flow-velocity and diameter of the right hepatic vein and the portal vein after equilibration following these maneuvers: M1: 0° supine position, PEEP 0 cmH₂O; M2: 0° supine position, PEEP 10 cmH₂O; M3: 20° reverse-trendelenburg position; PEEP 10 cmH₂O; M4: 20° reverse-trendelenburg position, PEEP 0cmH₂O.

Results

Changing from supine to reverse-trendelenburg position led to a significant decrease in CVP (M3 5.95?±?2.06 vs. M1 7.35?±?2.18 mmHg and M2 8.55?±?1.79 mmHg). A PEEP of 10 cmH₂O and reverse-trendelenburg position led to significant reduction of systolic (Vs_HV) and diastolic (Vd_HV) flow-velocities of the right hepatic vein (Vs_HV M3 19.96?±?6.47 vs. M1 27.81?±?11.03 cm s^?1;Vd_HV M3 14.94?±?6.22 vs. M1 20.15?±?10.34 cm s^?1 and M2 20.19?±?13.19 cm s^?1) whereas no significant changes of flow-velocity occurred in the portal vein. No correlations between CVP and diameters or flow-velocities of the right hepatic and the portal vein were found.

Conclusions

Changes of central venous pressure due to changes of PEEP and positioning were not correlated with changes of venous hepatic blood flow parameters as measured after equilibration. Strategies aiming for low central venous pressure cannot be supported by these results. However, before ruling out low-CVP-strategies during liver resections these results should be confirmed by further studies.

     

Prevalence and prognosis of cor pulmonale during protective ventilation for acute respiratory distress syndrome

Purpose

Pulmonary vascular dysfunction is common during acute respiratory distress syndrome (ARDS), but there is controversy concerning prevalence and prognosis of cor pulmonale during protective ventilation for ARDS.

Methods

This was a prospective observational study in an academic medical intensive care unit in France. Two hundred and twenty-six consecutive patients with moderate to severe ARDS (Berlin definition) ventilated with plateau pressure limited at 30 cmH₂O (mean PEEP of 8.8 ± 3.6 cmH₂O) underwent transesophageal echocardiography (TEE) within the first 3 days after the diagnosis of ARDS. Cor pulmonale was defined as a dilated right ventricle associated with septal dyskinesia.

Results

Cor pulmonale was detected in 49 patients (prevalence of 22 %; 95 % confidence interval, 16–27 %). Multivariate logistic regression identified infectious causes of lung injury and higher driving pressures as independent factors associated with cor pulmonale. Patients with cor pulmonale exhibited a higher incidence of shock (need for vasoactive drug) at the time of TEE and were more often managed with prone positioning and/or nitric oxide as adjunctive therapy for severe hypoxemia during ARDS course. The 28-day mortality rate was significantly higher in the group with cor pulmonale (60 vs. 36 %, p < 0.01). Multivariate logistic regression identified McCabe and Jackson class, lung injury not related to pneumonia, aspiration, or sepsis, lactic acidosis, driving pressure, and cor pulmonale as independent risk factors for 28-day mortality.

Conclusion

Cor pulmonale occurrence is not negligible in ARDS patients ventilated with airway pressure limitation. Cor pulmonale was associated with sepsis and higher values of driving pressure and was an independent risk factor for 28-day mortality in our series.     

Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS

Purpose

Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO₂/FiO₂ ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS.

Methods

We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed.

Results

Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO₂ change was found according to oxygenation response or lung morphology.

Conclusions

In ARDS patients with a PaO₂/FiO₂ ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP.

     

The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia

Purpose

Severe ARDS is often associated with refractory hypoxemia, and early identification and treatment of hypoxemia is mandatory. For the management of severe ARDS ventilator settings, positioning therapy, infection control, and supportive measures are essential to improve survival.

Methods and results

A precise definition of life-threating hypoxemia is not identified. Typical clinical determinations are: arterial partial pressure of oxygen < 60 mmHg and/or arterial oxygenation < 88 % and/or the ratio of PaO₂/FIO₂ < 100. For mechanical ventilation specific settings are recommended: limitation of tidal volume (6 ml/kg predicted body weight), adequate high PEEP (>12 cmH₂O), a recruitment manoeuvre in special situations, and a ‘balanced’ respiratory rate (20-30/min). Individual bedside methods to guide PEEP/recruitment (e.g., transpulmonary pressure) are not (yet) available. Prone positioning [early (≤ 48 hrs after onset of severe ARDS) and prolonged (repetition of 16-hr-sessions)] improves survival. An advanced infection management/control includes early diagnosis of bacterial, atypical, viral and fungal specimen (blood culture, bronchoalveolar lavage), and of infection sources by CT scan, followed by administration of broad-spectrum anti-infectives. Neuromuscular blockage (Cisatracurium ≤ 48 hrs after onset of ARDS), as well as an adequate sedation strategy (score guided) is an important supportive therapy. A negative fluid balance is associated with improved lung function and the use of hemofiltration might be indicated for specific indications.

Conclusions

A specific standard of care is required for the management of severe ARDS with refractory hypoxemia.

     

Pediatric extubation readiness tests should not use pressure support

Purpose

Pressure support is often used for extubation readiness testing, to overcome perceived imposed work of breathing from endotracheal tubes. We sought to determine whether effort of breathing on continuous positive airway pressure (CPAP) of 5 cmH₂O is higher than post-extubation effort, and if this is confounded by endotracheal tube size or post-extubation noninvasive respiratory support.

Methods

Prospective trial in intubated children. Using esophageal manometry we compared effort of breathing with pressure rate product under four conditions: pressure support 10/5 cmH₂O, CPAP 5 cmH₂O (CPAP), and spontaneous breathing 5 and 60 min post-extubation. Subgroup analysis excluded post-extubation upper airway obstruction (UAO) and stratified by endotracheal tube size and post-extubation noninvasive respiratory support.

Results

We included 409 children. Pressure rate product on pressure support [100 (IQR 60, 175)] was lower than CPAP [200 (120, 300)], which was lower than 5 min [300 (150, 500)] and 60 min [255 (175, 400)] post-extubation (all p < 0.01). Excluding 107 patients with post-extubation UAO (where pressure rate product after extubation is expected to be higher), pressure support still underestimated post-extubation effort by 126–147 %, and CPAP underestimated post-extubation effort by 17–25 %. For all endotracheal tube subgroups, ≤3.5 mmID (n = 152), 4–4.5 mmID (n = 102), and ≥5.0 mmID (n = 48), pressure rate product on pressure support was lower than CPAP and post-extubation (all p < 0.0001), while CPAP pressure rate product was not different from post-extubation (all p < 0.05). These findings were similar for patients extubated to noninvasive respiratory support, where pressure rate product on pressure support before extubation was significantly lower than pressure rate product post-extubation on noninvasive respiratory support (p < 0.0001, n = 81).

Conclusions

Regardless of endotracheal tube size, pressure support during extubation readiness tests significantly underestimates post-extubation effort of breathing.

     

Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study

Purpose

To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.

Methods

The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1–2 who received invasive mechanical ventilation.

Results

2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO₂/FiO₂ ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores.

Conclusions

Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS.Trial Registration: ClinicalTrials.gov NCT02010073.

     

Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

Purpose

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.

Methods

We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume.

Results

Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P?=?0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P?=?0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P?=?0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher V_T.

Conclusions

Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).