Impact of Arterial CO2 Tension on Management and Outcome in Patients With Acute Hypoxemic Respirator Failure and ARDS (CO2 LUNG SAFE)

Incidence of Hypercapnia and Impact of Arterial CO2 Tension on Management and Outcome in Patients With Acute Respiratory Distress Syndrome (ARDS)

There appears to be considerable variability in the approach physicians use to manage arterial carbon dioxide tensions, in patients in the early phases [first 48 hours] of ARDS (Acute hypoxemic respiratory failure and). A number of specific concerns exist, particularly the use of greater than needed inspired oxygen concentrations (potentially in 40% patients), and the proportion of hypocapnic patients in our cohort.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome; Acute Severe Respiratory Failure

Detailed Description

This study will address a number of specific concerns, including:

1. the incidence of hypocapnia and hypercapnia;
2. the factors (e.g. ventilatory mode) contributing to hypocapnia and hypercapnia;
3. the impact of hypocapnia and hypercapnia on progression of ARDS, duration of ventilation, ICU stay, hospital stay and patient outcome;
4. the impact of pH (respiratory versus metabolic cause) on outcome variables.

LUNG SAFE was a prospective observational study. There was not patient intervention. The current analysis is a secondary analysis of this existing database.

Data will be abstracted form the database on all patients meeting the inclusion criteria for ARDS (during the first 2 days from AHRF onset) for the following variables: Patient's demographic characteristics (age, sex) and chronic comorbidities, Arterial PCO2, pH in first 48 hours, Data on P/F ratio over course of illness, Duration of ventilation, ICU stay, hospital survival in patients identified as being exposed to hypocapnia (pCO2 < or = to 30mmHg) and hypercapnia (PCO2 > or = to 45mmHg); Main ventilatory variables: mode of ventilation, tidal volume, respiratory.

Descriptive statistics will include proportions for categorical and mean (standard deviation) or median (interquartile range) for continuous variables, according the data distribution. The amount of missing data in the LUNG SAFE database is low so no assumptions will be made for missing data.

In order to investigate the relationship between PaCO2 and management factors, the investigators will stratify study population according the presence or absence of hypercapnia and will evaluate differences in management factors, using appropriate statistical tests. In detail, proportions will be compared using chi-squared or Fisher exact tests and mean values were compared using T-test or Wilcoxon rank sum test, as appropriate. Shapiro-Wilks test will be used to assess normality in data distribution. Moreover, they will perform univariate and multivariable logistic regression models using hypercapnia as dependent variable. Stepwise regression approach with significance alpha levels of 0.05 (both for entry and retention) will be used to establish a set of independent predictors. Odds ratios (ORs) and 95% confidence intervals (CIs) will be reported as measure of association.

They will assess the association of hypercapnia with different outcomes (ARDS progression, duration of mechanical ventilation, ICU and hospital stay and mortality) using generalized linear regression models (Poisson or Logistic regression models, according outcome distribution) and adjusting the relationship with all possible confounders identified with stepwise approach. Results will be reported as ORs, incidence rate ratios and corresponding 95% CI.

Particular attention will be given to the relationship and interaction between pH and PaCO2.

Survival analysis (Kaplan-Meier approach) will be used to estimate the time of liberation from invasive mechanical ventilation, of ICU and hospital discharge, and of hospital mortality within 28 days of AHRF onset in patients with and without hypercapnia. Differences in survival time will be assess by Log-Rank test.

• Study Type: Observational
• Enrollment (Actual): 4500

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Guy Marie FRANCOIS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients over 18 years of age who fulfilled clinical criteria for ARDS and Acute Hypoxaemic respiratory failure were recruited into the LUNG SAFE trial (NCT02010073) that was published in JAMA, 2016 Jul 19;316(3):347).

Description

Inclusion Criteria:

• All patients meeting criteria for ARDS. Fulfillment of criteria for Acute Hypoxaemic respiratory failure (AHRF) and fulfillment of Berlin criteria for ARDS during the first two days after AHRF onset.

Exclusion Criteria:

• Age < 18

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
4500 patients with ARDS; This is a secondary analysis of data from the LUNG SAFE database to determine the impact of alterations in arterial carbon dioxide tensions in patients with ARDS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence	The incidence of hypercapnia [i.e. PaCO2 > 45 mmHg] when ARDS arises	LUNG SAFE was a prospective observational study. Patients were followed until hospital discharge or day 90, whichever came first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity	The severity of hypercapnia [i.e. PaCO2 > 45 mmHg] when ARDS arises ARDS	LUNG SAFE was a prospective observational study. Patients were followed until hospital discharge or day 90, whichever came first
Hypercapnia	Factors (e.g. ventilatory mode) contributing to hypercapnia in patients with ARDS	LUNG SAFE was a prospective observational study. Patients were followed until hospital discharge or day 90, whichever came first
Hypercapnia	The impact of hypercapnia on outcome on the progression of ARDS	LUNG SAFE was a prospective observational study. Patients were followed until hospital discharge or day 90, whichever came first
pH ((potential of hydrogen)	The impact of pH (respiratory versus metabolic cause) on outcome variables	LUNG SAFE was a prospective observational study. Patients were followed until hospital discharge or day 90, whichever came first

Collaborators and Investigators

• Sponsor: European Society of Intensive Care Medicine
• Investigators: Principal Investigator: John LAFFEY, National University of Ireland, Galway; Principal Investigator: Giacomo BELLANI, University of Milano-Bicocca (Monza, Italy)

Publications and helpful links

General Publications

• Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. Erratum In: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350.
• Laffey JG, Bellani G, Pham T, Fan E, Madotto F, Bajwa EK, Brochard L, Clarkson K, Esteban A, Gattinoni L, van Haren F, Heunks LM, Kurahashi K, Laake JH, Larsson A, McAuley DF, McNamee L, Nin N, Qiu H, Ranieri M, Rubenfeld GD, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Correction to: Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study. Intensive Care Med. 2018 Jan;44(1):157-165. doi: 10.1007/s00134-017-4981-z.
• de Prost N, Pham T, Carteaux G, Mekontso Dessap A, Brun-Buisson C, Fan E, Bellani G, Laffey J, Mercat A, Brochard L, Maitre B; LUNG SAFE investigators; ESICM trials group; REVA network. Etiologies, diagnostic work-up and outcomes of acute respiratory distress syndrome with no common risk factor: a prospective multicenter study. Ann Intensive Care. 2017 Dec;7(1):69. doi: 10.1186/s13613-017-0281-6. Epub 2017 Jun 19.
• Laffey JG, Madotto F, Bellani G, Pham T, Fan E, Brochard L, Amin P, Arabi Y, Bajwa EK, Bruhn A, Cerny V, Clarkson K, Heunks L, Kurahashi K, Laake JH, Lorente JA, McNamee L, Nin N, Palo JE, Piquilloud L, Qiu H, Jimenez JIS, Esteban A, McAuley DF, van Haren F, Ranieri M, Rubenfeld G, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: insights from the LUNG SAFE prospective cohort study. Lancet Respir Med. 2017 Aug;5(8):627-638. doi: 10.1016/S2213-2600(17)30213-8. Epub 2017 Jun 15.
• Dreyfuss D, Gaudry S, Madotto F, Laffey JG. Some remaining important questions after LUNG SAFE : Discussion of "Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study". Intensive Care Med. 2017 Apr;43(4):598-599. doi: 10.1007/s00134-017-4706-3. Epub 2017 Feb 17. No abstract available.
• Laffey JG, Bellani G, Pham T, Fan E, Madotto F, Bajwa EK, Brochard L, Clarkson K, Esteban A, Gattinoni L, van Haren F, Heunks LM, Kurahashi K, Laake JH, Larsson A, McAuley DF, McNamee L, Nin N, Qiu H, Ranieri M, Rubenfeld GD, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators and the ESICM Trials Group. Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study. Intensive Care Med. 2016 Dec;42(12):1865-1876. doi: 10.1007/s00134-016-4571-5. Epub 2016 Oct 18. Erratum In: Intensive Care Med. 2017 Nov 14;:
• Bellani G, Laffey JG, Pham T, Madotto F, Fan E, Brochard L, Esteban A, Gattinoni L, Bumbasirevic V, Piquilloud L, van Haren F, Larsson A, McAuley DF, Bauer PR, Arabi YM, Ranieri M, Antonelli M, Rubenfeld GD, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study. Am J Respir Crit Care Med. 2017 Jan 1;195(1):67-77. doi: 10.1164/rccm.201606-1306OC.
• Bellani G, Laffey JG, Pham T, Fan E; LUNG SAFE Investigators and the ESICM Trials Group. The LUNG SAFE study: a presentation of the prevalence of ARDS according to the Berlin Definition! Crit Care. 2016 Sep 9;20(1):268. doi: 10.1186/s13054-016-1443-x. No abstract available.
• Bellani G, Pham T, Laffey J; LUNG-SAFE Investigators; ESICM Trials Group. Incidence of Acute Respiratory Distress Syndrome--Reply. JAMA. 2016 Jul 19;316(3):347. doi: 10.1001/jama.2016.6471. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): September 30, 2018
• Study Completion (Actual): December 30, 2018

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (Actual): January 30, 2018

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Prognosis; ARDS; Lung; Sepsis; Hypercapnia; Respiratory infection; Organ failure; Outcome Research; Acute Respiratory Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: CO2LUNGSAFE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No