Driving pressure in ARDS patients

Article

Author: Clinical Experts Group, Hamilton Medical

Date of first publication: 02.04.2020

Last change: 02.04.2020

First published: 02.06.2017 Reference 6 changed from abstract to publication, additional data added

ARDS is characterized by lung collapse and consolidation leaving just a small portion of aerated lung remaining, which is at risk of ventilator-induced lung injuries (baby-lung concept).

Take-away messages

Driving pressure (ΔP) represents the ratio between tidal volume and respiratory system compliance, and is calculated as the difference between plateau pressure and total PEEP
A multilevel mediation analysis of data from 2,365 ARDS patients showed that ΔP was the ventilator variable associated most strongly with hospital survival
Results from 2,377 patients enrolled in the LUNG SAFE study showed that ΔP less than 14 cmH2O was associated with lower hospital mortality in both moderate and severe ARDS patients
In the absence of strong recommendations based on data from prospective randomized controlled trials, it seems reasonable to aim at keeping ΔP below 14 cmH2O
Recent evidence has shown that driving pressure was automatically limited to less than 14 cmH2O in 95% of patients ventilated in Adaptive Support Ventilation (ASV) mode

Driving pressure a substitue for lung strain

As the aerated lung has normal compliance, the reduction in respiratory system compliance is mainly due to the non-aerated part of the lung, and can serve as an estimation of the end-expiratory lung volume. In turn, the ratio between tidal volume and end-expiratory lung volume represents the strain applied to the lung. Therefore, the ratio between tidal volume and respiratory system compliance – also called driving pressure (ΔP) – can be considered a substitute for lung strain. Driving pressure is calculated as the difference between plateau pressure and total PEEP, and can be measured quite easily using end-inspiratory and end-expiratory occlusions respectively.

Association between ΔP and mortality

A multilevel mediation analysis of individual pooled data from 2,365 ARDS patients included in four randomized controlled trials showed that ΔP was the ventilator variable associated most strongly with hospital survival. Any change in tidal volume or PEEP affected the outcome only when associated with a decrease in ΔP (Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755. doi:10.1056/NEJMsa14106391).

A large observational study aimed at better understanding the global impact of acute respiratory failure (the LUNG SAFE study) was conducted in 459 intensive care units in 50 countries around the world. Results showed that ARDS occurs in 10% of all patients admitted to the ICU, with a hospital mortality of 40% (Bellani G, Laffey JG, Pham T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries [published correction appears in JAMA. 2016 Jul 19;316(3):350] [published correction appears in JAMA. 2016 Jul 19;316(3):350]. JAMA. 2016;315(8):788-800. doi:10.1001/jama.2016.02912). The 2,377 ARDS patients enrolled in the study who received mechanical ventilation and fulfilled the ARDS criteria on day 1 or 2 were included in a subsequent analysis to determine the risk factors for mortality, with the focus placed on ventilator settings (Laffey JG, Bellani G, Pham T, et al. Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study [published correction appears in Intensive Care Med. 2017 Nov 14;:]. Intensive Care Med. 2016;42(12):1865-1876. doi:10.1007/s00134-016-4571-53). The mean tidal volume used was found to have no effect on hospital mortality for any patient group, whereas PEEP of less than 12 cmH2O was associated with higher hospital mortality in the subgroup of moderate ARDS patients. Driving pressure below 14 cmH2O was associated with lower hospital mortality in both moderate and severe ARDS patients, while plateau pressure below 25 cmH2O was also associated with lower hospital mortality in severe ARDS patients. In a multivariate analysis including only passively ventilated patients, both a higher ΔP and higher plateau pressure were independently associated with higher hospital mortality. The slope of the curve for risk of mortality was relatively flat up to a ΔP of 10 cmH2O, and increased linearly above this value. This study corroborates the relevance and external validity of using ΔP in a clinical setting.

These results, however, should not be seen as implying that tidal volume is of no importance for lung protection. Most of the patients included in this study did indeed receive low tidal volumes. What the study does show is that when a low tidal volume is used, ΔP is an important variable to monitor for assessing the risk of hospital mortality. Although there is no data from prospective randomized controlled studies available to provide strong recommendations as to what the ΔP should be, it would seem reasonable to advocate keeping ΔP below 14 cmH2O.

How to lower driving pressure

There are several methods available for limiting ΔP, such as muscle relaxants, use of the prone position, decreasing instrumental dead space, veno-venous extracorporeal CO2 removal, and ECMO (Grieco DL, Chen L, Dres M, Brochard L. Should we use driving pressure to set tidal volume?. Curr Opin Crit Care. 2017;23(1):38-44. doi:10.1097/MCC.00000000000003774). Efficient lung recruitment and adequate PEEP titration are also associated with a decrease in ΔP (Borges JB, Hedenstierna G, Larsson A, Suarez-Sipmann F. Altering the mechanical scenario to decrease the driving pressure. Crit Care. 2015;19(1):342. Published 2015 Sep 21. doi:10.1186/s13054-015-1063-x5).

Adaptive Support Ventilation (ASV®) and INTELLiVENT®-ASV (Not available in all marketsa) select the tidal volume according to respiratory mechanics. If respiratory system compliance is decreased, the automatically selected tidal volume will be lower. Results of a prospective observational study focusing on the ΔP selected by ASV in 255 patients with different lung conditions showed the median ΔP to be 8 (7 - 10), 9 (8 - 11), and 10 (8 - 12) cmH2O for normal lungs, ARDS, and COPD patients, respectively (p < 0.001). Within the group of ARDS patients, the median ΔP was 9 (9-11), 9 (8-12), and 10 (9-12) cmH2O, respectively for mild, moderate, and severe conditions (p = 0.54). For moderate and severe ARDS patients, an open-lung strategy combining a recruitment maneuver (sustained inflation at 40 cmH2O for 10 s) followed by a decremental PEEP trial focusing on oxygenation (SpO2) was implemented (Arnal JM, Saoli M, Garnero A. Airway and transpulmonary driving pressures and mechanical powers selected by INTELLiVENT-ASV in passive, mechanically ventilated ICU patients. Heart Lung. 2020;49(4):427-434. doi:10.1016/j.hrtlng.2019.11.0016).

Footnotes

a. Not available in all markets

References

1. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755. doi:10.1056/NEJMsa1410639
2. Bellani G, Laffey JG, Pham T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries [published correction appears in JAMA. 2016 Jul 19;316(3):350] [published correction appears in JAMA. 2016 Jul 19;316(3):350]. JAMA. 2016;315(8):788-800. doi:10.1001/jama.2016.0291
3. Laffey JG, Bellani G, Pham T, et al. Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study [published correction appears in Intensive Care Med. 2017 Nov 14;:]. Intensive Care Med. 2016;42(12):1865-1876. doi:10.1007/s00134-016-4571-5
4. Grieco DL, Chen L, Dres M, Brochard L. Should we use driving pressure to set tidal volume?. Curr Opin Crit Care. 2017;23(1):38-44. doi:10.1097/MCC.0000000000000377
5. Borges JB, Hedenstierna G, Larsson A, Suarez-Sipmann F. Altering the mechanical scenario to decrease the driving pressure. Crit Care. 2015;19(1):342. Published 2015 Sep 21. doi:10.1186/s13054-015-1063-x
6. Arnal JM, Saoli M, Garnero A. Airway and transpulmonary driving pressures and mechanical powers selected by INTELLiVENT-ASV in passive, mechanically ventilated ICU patients. Heart Lung. 2020;49(4):427-434. doi:10.1016/j.hrtlng.2019.11.001

Driving pressure and survival in the acute respiratory distress syndrome.

Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755. doi:10.1056/NEJMsa1410639

Link to article

BACKGROUND

Mechanical-ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (VT), and higher positive end-expiratory pressures (PEEPs) can improve survival in patients with the acute respiratory distress syndrome (ARDS), but the relative importance of each of these components is uncertain. Because respiratory-system compliance (CRS) is strongly related to the volume of aerated remaining functional lung during disease (termed functional lung size), we hypothesized that driving pressure (ΔP=VT/CRS), in which VT is intrinsically normalized to functional lung size (instead of predicted lung size in healthy persons), would be an index more strongly associated with survival than VT or PEEP in patients who are not actively breathing.

METHODS

Using a statistical tool known as multilevel mediation analysis to analyze individual data from 3562 patients with ARDS enrolled in nine previously reported randomized trials, we examined ΔP as an independent variable associated with survival. In the mediation analysis, we estimated the isolated effects of changes in ΔP resulting from randomized ventilator settings while minimizing confounding due to the baseline severity of lung disease.

RESULTS

Among ventilation variables, ΔP was most strongly associated with survival. A 1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], 1.31 to 1.51; P<0.001), even in patients receiving "protective" plateau pressures and VT (relative risk, 1.36; 95% CI, 1.17 to 1.58; P<0.001). Individual changes in VT or PEEP after randomization were not independently associated with survival; they were associated only if they were among the changes that led to reductions in ΔP (mediation effects of ΔP, P=0.004 and P=0.001, respectively).

CONCLUSIONS

We found that ΔP was the ventilation variable that best stratified risk. Decreases in ΔP owing to changes in ventilator settings were strongly associated with increased survival. (Funded by Fundação de Amparo e Pesquisa do Estado de São Paulo and others.).

Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries.

Bellani G, Laffey JG, Pham T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries [published correction appears in JAMA. 2016 Jul 19;316(3):350] [published correction appears in JAMA. 2016 Jul 19;316(3):350]. JAMA. 2016;315(8):788-800. doi:10.1001/jama.2016.0291

Link to article

IMPORTANCE

Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS).

OBJECTIVES

To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition.

DESIGN, SETTING, AND PARTICIPANTS

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 undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents.

EXPOSURES

Acute respiratory distress syndrome.

MAIN OUTCOMES AND MEASURES

The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS.

RESULTS

Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS.

CONCLUSIONS AND RELEVANCE

Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT02010073.

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

Laffey JG, Bellani G, Pham T, et al. Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study [published correction appears in Intensive Care Med. 2017 Nov 14;:]. Intensive Care Med. 2016;42(12):1865-1876. doi:10.1007/s00134-016-4571-5

Link to article

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.

Should we use driving pressure to set tidal volume?

Grieco DL, Chen L, Dres M, Brochard L. Should we use driving pressure to set tidal volume?. Curr Opin Crit Care. 2017;23(1):38-44. doi:10.1097/MCC.0000000000000377

Link to article

PURPOSE OF REVIEW

Ventilator-induced lung injury (VILI) can occur despite use of tidal volume (VT) limited to 6 ml/kg of predicted body weight, especially in patients with a smaller aerated compartment (i.e. the baby lung) in which, indeed, tidal ventilation takes place. Because respiratory system static compliance (CRS) is mostly affected by the volume of the baby lung, the ratio VT/CRS (i.e. the driving pressure, ΔP) may potentially help tailoring interventions on VT setting.

RECENT FINDINGS

Driving pressure is the ventilatory variable most strongly associated with changes in survival and has been shown to be the key mediator of the effects of mechanical ventilation on outcome in the acute respiratory distress syndrome. Observational data suggest an increased risk of death for patients with ΔP more than 14 cmH2O, but a well tolerated threshold for this parameter has yet to be identified. Prone position along with simple ventilatory adjustments to facilitate CO2 clearance may help reduce ΔP in isocapnic conditions. The safety and feasibility of low-flow extracorporeal CO2 removal in enhancing further reduction in VT and ΔP are currently being investigated.

SUMMARY

Driving pressure is a bedside available parameter that may help identify patients prone to develop VILI and at increased risk of death. No study had prospectively evaluated whether interventions on ΔP may provide a relevant clinical benefit, but it appears physiologically sound to try titrating VT to minimize ΔP, especially when it is higher than 14 cmH2O and when it has minimal costs in terms of CO2 clearance.

Altering the mechanical scenario to decrease the driving pressure.

Borges JB, Hedenstierna G, Larsson A, Suarez-Sipmann F. Altering the mechanical scenario to decrease the driving pressure. Crit Care. 2015;19(1):342. Published 2015 Sep 21. doi:10.1186/s13054-015-1063-x

Link to article

Ventilator settings resulting in decreased driving pressure (ΔP) are positively associated with survival. How to further foster the potential beneficial mediator effect of a reduced ΔP? One possibility is promoting the active modification of the lung's "mechanical scenario" by means of lung recruitment and positive end-expiratory pressure selection. By taking into account the individual distribution of the threshold-opening airway pressures to achieve maximal recruitment, a redistribution of the tidal volume from overdistended to newly recruited lung occurs. The resulting more homogeneous distribution of transpulmonary pressures may induce a relief of overdistension in the upper regions. The gain in lung compliance after a successful recruitment rescales the size of the functional lung, potentially allowing for a further reduction in ΔP.

Airway and transpulmonary driving pressures and mechanical powers selected by INTELLiVENT-ASV in passive, mechanically ventilated ICU patients.

Arnal JM, Saoli M, Garnero A. Airway and transpulmonary driving pressures and mechanical powers selected by INTELLiVENT-ASV in passive, mechanically ventilated ICU patients. Heart Lung. 2020;49(4):427-434. doi:10.1016/j.hrtlng.2019.11.001

Link to article

BACKGROUND

Driving pressure (ΔP) and mechanical power (MP) are predictors of the risk of ventilation- induced lung injuries (VILI) in mechanically ventilated patients. INTELLiVENT-ASV® is a closed-loop ventilation mode that automatically adjusts respiratory rate and tidal volume, according to the patient's respiratory mechanics.

OBJECTIVES

This prospective observational study investigated ΔP and MP (and also transpulmonary ΔP (ΔPL) and MP (MPL) for a subgroup of patients) delivered by INTELLiVENT-ASV.

METHODS

Adult patients admitted to the ICU were included if they were sedated and met the criteria for a single lung condition (normal lungs, COPD, or ARDS). INTELLiVENT-ASV was used with default target settings. If PEEP was above 16 cmH2O, the recruitment strategy used transpulmonary pressure as a reference, and ΔPL and MPL were computed. Measurements were made once for each patient.

RESULTS

Of the 255 patients included, 98 patients were classified as normal-lungs, 28 as COPD, and 129 as ARDS patients. The median ΔP was 8 (7 - 10), 10 (8 - 12), and 9 (8 - 11) cmH2O for normal-lungs, COPD, and ARDS patients, respectively. The median MP was 9.1 (4.9 - 13.5), 11.8 (8.6 - 16.5), and 8.8 (5.6 - 13.8) J/min for normal-lungs, COPD, and ARDS patients, respectively. For the 19 patients managed with transpulmonary pressure ΔPL was 6 (4 - 7) cmH2O and MPL was 3.6 (3.1 - 4.4) J/min.

CONCLUSIONS

In this short term observation study, INTELLiVENT-ASV selected ΔP and MP considered in safe ranges for lung protection. In a subgroup of ARDS patients, the combination of a recruitment strategy and INTELLiVENT-ASV resulted in an apparently safe ΔPL and MPL.