Are Elevated CO2 Levels Impeding Care in COPD Exacerbations?
Extracorporeal CO₂ Removal in Clinical Practice. An Interactive Case Study.
This interactive case study was organised and funded by Vantive Health LLC.
Medical writing support was provided by Jessica Jinks, EMJ, London, UK. Technical and editorial support was provided by EMJ.
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These interactive case studies were developed with support from Jörg Kurz, Vantive Global Medical Director of Organ Support Therapies, Vantive Health LLC, Munich, Germany.
These are hypothetical patient cases and outcomes may not be reflective of clinical studies or real-life circumstances. This includes reference to agents that may be used off-label or for unlicensed indications. The mention of these agents and their uses is intended solely for educational purposes and should not be considered an endorsement or recommendation for their use outside approved indications. Please always consult guidelines and local prescribing information in your country of practice, as information may vary.
2/18
Case Presentation
A 57‑year‑old male presents with progressive shortness of breath and cough. Initial assessment shows: pH: 7.25 PaCO₂: 58 mmHg He is receiving oxygen therapy: 6 L/min O₂ via nasal cannula The patient reports worsening dyspnoea over the past 24 hours despite increasing oxygen use.
Severe COPD (GOLD Stage III)1
Chronic hypercapnia
Two hospitalisations for ARF in the past year.
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2026. Available at: https://goldcopd.org/wp-content/uploads/2026/01/GOLD-REPORT-2026-v1.3-8Dec2025_WMV2.pdf. Last accessed: 9 March 2026.
ARF: acute respiratory failure; GOLD: Global Initiative for Chronic Obstructive Lung Disease; PaCO2: partial pressure of CO2 in arterial blood.
3/18
GOLD Guidelines for COPD
Clinicians have thus far adhered to the established GOLD Guidelines, which recommend COPD management strategies intended for global use, to be adapted based on local healthcare systems, resources, and regulations.1 The GOLD strategy provides globally accepted guidance for COPD management, including:1
Assessment of airflow limitation using spirometry (FEV1) Classification of disease severity (GOLD Stages I–IV) Evidence-based recommendations for pharmacologic therapy, oxygen therapy, and ventilatory support Guidance on management of aeCOPD
For acute exacerbations with hypercapnic respiratory failure, GOLD recommends:1
Controlled oxygen therapy (target SpO2 88–92%) Bronchodilators and systemic corticosteroids Consideration of NIV when respiratory acidosis develops Antibiotics when bacterial infection is suspected or clinically indicated
aeCOPD: acute exacerbation of COPD; FEV1: forced expiratory volume in 1 second; GOLD: Global Initiative for Chronic Obstructive Lung Disease; NIV: non-invasive ventilation.
4/18
Despite receiving high-flow oxygen, the patient continues to deteriorate. Current concerns include:
Persistent hypercapnia Respiratory acidosis Increasing work of breathing
This raises concern for acute hypercapnic respiratory failure secondary to COPD exacerbation. The clinical team must determine the next diagnostic and management step.
5/18
Question 1: What is your immediate next management step?
A
Order arterial blood gas and chest X-ray
B
Escalate to mechanical NIV (bilevel positive airway pressure/continuous positive airway pressure)
C
Escalate to intubation for invasive mechanical ventilation
D
Options A and B
Note that more information from blood gas is needed to understand patient progression. Additionally, high-flow oxygen alone is not preventing further issues. Invasive mechanical ventilation is generally deferred at this stage unless there are contraindications to NIV or signs of life‑threatening deterioration.1 NIV plus conventional therapy reduces mortality and intubation rates in patients with aeCOPD with respiratory acidosis.2-4 NIV failure remains possible, particularly in patients with severe acidosis or inadequate response after initiation.1
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2026. Available at: https://goldcopd.org/wp-content/uploads/2026/01/GOLD-REPORT-2026-v1.3-8Dec2025_WMV2.pdf. Last accessed: 9 March 2026. Plant PK et al. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet. 2000;355(9219):1931-5. Brochard L et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333(13):817-22. Kramer N et al. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med. 1995;151(6):1799-806.
aeCOPD: acute exacerbation of COPD; NIV: non-invasive ventilation.
6/18
Examination Information/Laboratory Results
The patient is rapidly escalated to NIV due to worsening respiratory acidosis. Despite initiation of NIV, the patient continues to demonstrate persistent hypercapnia.
Current arterial blood gas
PaCO₂: >60 mmHg pH: <7.30
Although NIV has been initiated promptly, the patient remains tachypnoeic and hypercapnic, raising concern about treatment response.
NIV: non-invasive ventilation; PaCO2: partial pressure of CO2 in arterial blood; SpO2: peripheral O2 saturation.
Respiratory rate: 28 breaths/min Heart rate: 110 bpm Blood pressure: 140/85 mmHg SpO₂: 91%
NIV settings
Inspiratory positive airway pressure: 18 cmH₂O Expiratory positive airway pressure: 6 cmH₂O
7/18
Guideline Perspective
International guidelines consistently recommend NIV as first-line ventilatory support in patients with acute hypercapnic respiratory failure due to COPD exacerbation.¹
According to recent GOLD guidance:1
High-flow oxygen systems and mechanical NIV are indicated in patients with COPD and acute respiratory failure NIV improves gas exchange NIV reduces the work of breathing NIV lowers the need for intubation
Reduce hospitalisation duration Improve survival Decrease complications associated with invasive ventilation
For these reasons, guidelines emphasise that NIV should be attempted whenever clinically appropriate before escalation to invasive ventilation.1
GOLD: Global Initiative for Chronic Obstructive Lung Disease; NIV: non-invasive ventilation.
8/18
Risks of Invasive Mechanical Ventilation in aeCOPD
Why Intubation Is Considered a Last Resort
Ventilator-associated pneumonia Barotrauma and dynamic hyperinflation Difficulty with ventilator weaning Increased ICU length of stay
Because of these risks, guidelines recommend exhausting non-invasive strategies before intubation whenever possible.1
Invasive mechanical ventilation is a life-saving intervention when clinically indicated, though associated with known risks for patients with aeCOPD.1
Complications can include:1
Although NIV is preferred, invasive mechanical ventilation may be required if a patient fails to improve or develops life-threatening complications.2 According to GOLD recommendations, escalation to intubation may be considered when patients develop:2
Persistent life-threatening hypoxaemia despite HFNT or NIV Unable to tolerate HFNT and/or NIV Status post-respiratory or cardiac arrest Diminished consciousness, psychomotor agitation inadequately controlled by sedation Massive aspiration or persistent vomiting Persistent inability to remove respiratory secretions Severe haemodynamic instability without response to fluids and vasoactive drugs Severe ventricular or supraventricular arrhythmias
In clinical practice, the decision to intubate requires careful reassessment of the patient's trajectory and response to NIV.
A frequently cited study examining outcomes in patients with COPD with acute hypercapnic respiratory failure demonstrated a substantial difference in mortality depending on the need for invasive ventilation.* In an observational study by Ucgun et al.:1
Patients not requiring invasive mechanical ventilation had a mortality rate of 8% Patients requiring invasive ventilation had a mortality rate of 52.9%
These findings support optimising NIV therapy while maintaining close monitoring and proceeding promptly to invasive ventilation when NIV fails or clinical deterioration warrants intubation. *This association may reflect baseline severity and patient selection. Historical observational findings should not be used in isolation. Interpret alongside contemporary data and guideline-based escalation criteria.
Ucgun I et al. Predictors of hospital outcome and intubation in COPD patients admitted to the respiratory ICU for acute hypercapnic respiratory failure. Respir Med. 2006;100(1):66-74. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2026. Available at: https://goldcopd.org/wp-content/uploads/2026/01/GOLD-REPORT-2026-v1.3-8Dec2025_WMV2.pdf. Last accessed: 9 March 2026.
aeCOPD: acute exacerbation of COPD; GOLD: Global Initiative for Chronic Obstructive Lung Disease; HFNT: high-flow nasal cannula; NIV: non-invasive ventilation.
9/18
Question 2: What could be considered as the next step in managing this patient?
Trial of higher NIV settings
Start invasive mechanical ventilation
Evaluate for ECCO2R
A further trial of higher NIV settings was not selected at this point because optimised NIV had already failed to produce meaningful improvement in respiratory acidosis, hypercapnia, and clinical signs of respiratory distress. Try another option
Invasive mechanical ventilation was not selected at this point because the patient had not yet been described as meeting emergency intubation criteria, and the team judged that an intubation-avoidance strategy could still be considered.1 Try another option
The team decided to evaluate the patient for ECCO2R because persistent hypercapnia and respiratory acidosis despite optimised NIV suggested a high risk of NIV failure, while an intubation-avoidance strategy was still considered feasible in this selected patient.1 ECCO2R may be considered in selected patients in experienced centers to support CO2 removal and potentially avoid invasive mechanical ventilation, provided that close monitoring and clear rescue-intubation criteria remain in place.1 Continue to learn more about ECCO2R
ECCO2R: extracorporeal CO2 removal; GOLD: Global Initiative for Chronic Obstructive Lung Disease; NIV: non-invasive ventilation.
10/18
How Does ECCO₂R Work?
O2 and CO2 exchange are governed by distinct physiological principles. Oxygen delivery is largely limited by haemoglobin saturation, so achieving adequate oxygenation with extracorporeal support requires relatively high blood flow rates, often in the range of several litres per minute.1 As ECCO2R operates at substantially lower blood flow rates than ECMO, it cannot deliver sufficient oxygen to the circulation and therefore is not suitable for providing clinically meaningful oxygenation support.2,3
Figure 1: Interaction between artificial and native lung.
CO2 transport differs in that most CO2 circulates as dissolved gas or bicarbonate and diffuses readily across the alveolar capillary membrane. This rapid equilibration enables effective CO2 removal to occur at much lower extracorporeal blood flow rates, typically in the range of a few hundred millilitres per minute (for low-flow ECCO2R).1,4 The physiological basis for employing ECCO2R is as follows: by partially removing CO2 from the blood, thereby reducing the burden of CO2 elimination via the lungs.1-4
Merola R et al. Extracorporeal carbon dioxide removal in acute respiratory distress syndrome: physiologic rationale and phenotype-based perspectives. Medicina (Kaunas). 2026;62(2):236. Azzi M et al. Extracorporeal CO2 removal in acute exacerbation of COPD unresponsive to non-invasive ventilation. BMJ Open Respir Res. 2021;8(1):e001089. Hanks J et al. On the horizon: extracorporeal carbon dioxide removal. Cleve Clin J Med. 2022;89(12):712-8. Combes A et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. Ann Intensive Care 2024;14:132.
ECCO2R: extracorporeal CO2 removal; PaO2: partial pressure of arterial O2; rCO2: rate of CO2 production; RQ: respiratory quotient; VILI: ventilator-induced lung injury.
11/18
ECCO2R in NIV Settings
ECCO2R may be considered in selected patients with COPD exacerbation receiving NIV* who develop persistent hypercapnic respiratory failure and are at risk of requiring invasive mechanical ventilation.1
Failure of NIV to correct hypercapnia Persistent severe respiratory acidosis pH ≤7.25 PaCO2 >70 mmHg
Clinical triggers
Aim: support gas exchange and potentially reduce the need for endotracheal intubation in selected patients.
*Use subject to local guidelines/institutional protocols.
Elmasry D et al. Protocol-based implementation of combined extracorporeal carbon dioxide removal and continuous renal replacement therapy using the PrismaLung platform: a critical care innovation. J Anesth Crit Care Open Access. 2025;17(5):140-4. Parrilla-Gómez FJ et al. The role of extracorporeal CO2 removal from pathophysiology to clinical applications with focus on potential combination with RRT: an expert opinion document. Front Med (Lausanne). 2025;12:1651213.
CIRF: clinical indicators of respiratory failure; ECCO2R: extracorporeal CO2 removal; NIV: non-invasive ventilation; PAB: paradoxical abdominal breathing; PaCO2: partial pressure of CO2 in arterial blood; RR: respiratory rate; SAD: severe accessory muscle use.
12/18
Question 3: Which findings support consideration of ECCO₂R?
pH remains ≤7.25
PaCO₂ >70 mmHg
Failure of NIV to correct hypercapnia
All of the above
For patients with aeCOPD, hypercapnia and respiratory acidosis may increase the odds of a prolonged hospital stay.1
Crisafulli E et al. Clinical variables predicting the risk of a hospital stay for longer than 7 days in patients with severe acute exacerbations of chronic obstructive pulmonary disease: a prospective study. Respir Res. 2018;19(1):261.
aeCOPD: acute exacerbations of COPD; ECCO2R: etxracorporeal CO2 removal; NIV: non-invasive ventilation; PaCO2: partial pressure of CO2 in arterial blood.
13/18
Treatment Decision Point
The patient’s labs are now showing:
pH 7.24; PaCO₂ 62 mmHg PaO₂/FiO₂=150 on current NIV
The patient has no contraindications for ECCO₂R (bleeding diathesis, anticoagulation issues).
Severe hypercapnia and respiratory acidosis can cause NIV to fail, leaving patients with no recourse but intubation.1,2 In selected studies, predictive models have estimated a high risk of NIV failure in patients meeting specific criteria:
Patients with low blood pH (<7.25), APACHE II ≥29, and GCS <11 have been shown to face >70% predicted risk of NIV failing.3 Among patients with blood pH 7.25–7.29, APACHE II ≥29, and GCS ≥11 after 2 h of NIV, the risk of NIV failure was shown to increase to approximately 90%, with pH being a main influencing factor for NIV failure.3
Ozyilmaz E et al. Timing of noninvasive ventilation failure: causes, risk factors, and potential remedies. BMC Pulm Med. 2014;14:19. British Thoracic Society Standards of Care Committee. Non-invasive ventilation in acute respiratory failure. Thorax. 2002;57(3):192-211. Confalonieri M et al. A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J. 2005;25(2):348-55.
APACHE: Acute Physiology and Chronic Health Evaluation; ECCO2R: extracorporeal CO2 removal; FiO2: fraction of inspired O2; GCS: Glasgow Coma Score; NIV: non-invasive ventilation; PaCO2: partial pressure of CO2 in arterial blood; PaO2: partial pressure of O2.
14/18
ECCO2R Therapy in Patients with aeCOPD
ECCO2R has been investigated as an adjunct to NIV in selected patients with aeCOPD to improve hypercapnia and potentially reduce the need for intubation.1-3 In patients at risk of NIV failure due to hypercapnia or respiratory acidosis, ECCO2R may help manage PaCO2 and avoid intubation.1,2,4 Use of ECCO2R during NIV has reduced intubation risk by 73% versus historical controls,2 and in patients who are NIV-refractory, 85–90% have avoided intubation.1,3 COPD exacerbation outcomes desired from implementing ECCO2R:5
Work of breathing: Significant reduction in respiratory effort NIV failure prevention: Success rate >50% in selected studies Weaning facilitation: Earlier extubation in mechanically ventilated patients
What ECCO₂R set up looks like at the bedside.5
Once a decision to start ECCO₂R is made, teams follow device-specific initiation settings to establish safe and effective extracorporeal CO₂ removal.
Below is an example of initial settings reported for a specific ECCO2R system (PrismaLung+), as described in the published literature.5
Actual ECCO2R settings vary depending on patient characteristics, clinical goals, and device configuration.
Braune S et al. The feasibility and safety of extracorporeal carbon dioxide removal to avoid intubation in patients with COPD unresponsive to noninvasive ventilation for acute hypercapnic respiratory failure (ECLAIR study): multicentre case-control study. Intensive Care Med. 2016;42(9):1437-44. Del Sorbo L et al. Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control. Crit Care Med. 2015;43(1):120-7. Azzi M et al. Extracorporeal CO2 removal in acute exacerbation of COPD unresponsive to non-invasive ventilation. BMJ Open Respir Res. 2021;8(1):e001089. Hanks J et al. On the horizon: extracorporeal carbon dioxide removal. Cleve Clin J Med. 2022;89(12):712-8. Elmasry D et al. Protocol-based implementation of combined extracorporeal carbon dioxide removal and continuous renal replacement therapy using the PrismaLung platform: a critical care innovation. J Anesth Crit Care Open Access. 2025;17(5):140-4.
aeCOPD: acute exacerbations of COPD; ECCO2R: extracorporeal CO2 removal; ECMO: extracorporeal membrane oxygenation; NIV: non-invasive ventilation; PaCO2: partial pressure of CO2 in arterial blood.
15/18
This technology might not actually be able to positively impact PaCO2 or pH
Safety-related concerns
This technology may not be helpful in preventing intubation
No concerns
All options represent recognised clinical concerns with ECCO₂R, including safety-related concerns and variable effectiveness in reducing PaCO2 and preventing the need for intubation. Contemporary systems and protocols, including published post-market clinical follow-up data1 and observational studies such as Cobeta et al.,2 aim to mitigate these risks, but they remain important considerations in clinical decision‑making.
Question 4: What are some of your concerns for this patient being on ECCO2R?
Considerations when interpreting clinical trial data on ECCO₂R
VENT-AVOID: Use of Older Centrifugal Pump Technology May Explain Lack of Benefit Over Standard Care A 2024 meta-analysis suggests that many historical complications of ECCO₂R were related to older pump technology rather than the concept itself. Earlier studies, such as REST and VENT-AVOID, predominantly used centrifugal pumps, whereas contemporary ECCO₂R systems use peristaltic pumps, which provide more stable flow, reduce shear stress, and are associated with fewer bleeding and clotting complications.3 Findings from the 2024 VENT-AVOID trial indicated that the addition of ECCO₂R to standard care did not reduce intubation rates in patients with aeCOPD receiving NIV. However, the trial may have been underpowered to detect clinically meaningful differences. In addition, the ECCO₂R system used employed a centrifugal pump, and evidence suggests that centrifugal pumps operating at low blood flow rates may be associated with increased red blood cell damage compared with peristaltic (roller) pump systems.3-5
Combes A et al. A prospective clinical evaluation of new ECCO2R technology in mild to moderate ARDS patients: assessing ultra-lung-protective ventilation with PRISMALUNG. Crit Care. 2026;30(1):15. Cobeta P et al. Extracorporeal CO2 removal in severe respiratory acidotic intubated patients: a seven year experience observational study. Respir Med. 2025;240:108011. Barbič B et al. The failure of extracorporeal carbon dioxide removal may be a failure of technology. Am J Respir Crit Care Med. 2024;209(7):884-7. Duggal A et al. Reply to Tiruvoipati et al.: VENT-AVOID trial: avoiding acute hypercapnic respiratory failure! Am J Respir Crit Care Med. 2024;209(12):1515. Duggal A et al. Extracorporeal carbon dioxide removal to avoid invasive ventilation during exacerbations of chronic obstructive pulmonary disease: VENT-AVOID trial - a randomized clinical trial. Am J Respir Crit Care Med. 2024;209(5):529-42.
aeCOPD: acute exacerbation of COPD; ECCO2R: extracorporeal CO2 removal; NIV: non-invasive ventilation; PaCO2: partial pressure of CO2 in arterial blood.
16/18
Question 5: What would enable you to feel comfortable weaning this patient off ECCO2R and NIV?
Improved pH levels
Reduction in NIV support requirements
PaCO2 stabilising
Combination of the above
These criteria, when assessed alongside overall clinical stability (e.g., respiratory pattern, oxygenation, and haemodynamics), may support consideration of weaning ECCO2R. Inadequate or premature weaning may result in recurrence of hypercapnia or need for escalation of support.
Combes A et al. ECCO2R therapy in the ICU: consensus of a European round table meeting. Crit Care. 2020;24(1):490 Parrilla-Gómez FJ et al. The role of extracorporeal CO2 removal from pathophysiology to clinical applications with focus on potential combination with RRT: an expert opinion document. Front Med (Lausanne). 2025;12:1651213.
ECCO2R: extracorporal CO2 removal; NIV: non-invasive ventilation; PaCO2: partial pressure of CO2 in arterial blood.
17/18
Patient Outcomes
Day 2: Patient stable on NIV with ECCO₂R Day 3: Sweep gas tapered; ECCO₂R discontinued Day 5: NIV stopped Day 14: Discharged from ICU, returned home on baseline O₂ Week 6 follow‑up: Back at baseline, no further hypercapnic episodes
This timeline reflects the clinical course of a single illustrative case and should not be interpreted as a typical or expected outcome. ECCO₂R is associated with risks, including bleeding, thrombosis, and device-related complications, which must be considered when interpreting clinical outcomes.
ECCO2R: extracorporal CO2 removal; NIV: non-invasive; PaCO2: partial pressure of CO2 in arterial bloodventilation.
18/18
Key Takeaways/Teaching Points
NIV is recommended in international guidelines for patients with aeCOPD to reduce mortality and the need for intubation compared with conventional therapy alone.1-4
Severe hypercapnia and respiratory acidosis are major causes of NIV failure, often leaving intubation as the only remaining treatment option.5,6
In patients with aeCOPD at high risk of NIV failure, ECCO2R has been shown to control PaCO₂ and help avoid intubation, with studies reporting a 73% reduction in intubation risk compared with historical controls8 and intubation avoidance in 85–90% of patients who are NIV-refractory.7-10
Current marketed ECCO2R systems use peristaltic pumps, differing from the centrifugal pump systems evaluated in the REST and VENT-AVOID trials, which may influence clinical outcomes and interpretation of past evidence.11-13
ECCO2R clinical benefit remains under investigation as an adjunctive therapy for patients with aeCOPD experiencing severe exacerbations, particularly where hypercapnia threatens NIV success.
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2026. Available at: https://goldcopd.org/wp-content/uploads/2026/01/GOLD-REPORT-2026-v1.3-8Dec2025_WMV2.pdf. Last accessed: 9 March 2026. Plant PK et al. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet. 2000;355(9219):1931-5. Brochard L et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333(13):817-22. Kramer N et al. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med. 1995;151(6):1799-806. Ozyilmaz E et al. Timing of noninvasive ventilation failure: causes, risk factors, and potential remedies. BMC Pulm Med. 2014;14:19. British Thoracic Society Standards of Care Committee. Non-invasive ventilation in acute respiratory failure. Thorax. 2002;57(3):192-211. Braune S et al. The feasibility and safety of extracorporeal carbon dioxide removal to avoid intubation in patients with COPD unresponsive to noninvasive ventilation for acute hypercapnic respiratory failure (ECLAIR study): multicentre case-control study. Intensive Care Med. 2016;42(9):1437-44. Del Sorbo L et al. Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control. Crit Care Med. 2015;43(1):120-7. Azzi M et al. Extracorporeal CO2 removal in acute exacerbation of COPD unresponsive to non-invasive ventilation. BMJ Open Respir Res. 2021;8(1):e001089. Hanks J et al. On the horizon: extracorporeal carbon dioxide removal. Cleve Clin J Med. 2022;89(12):712-8. Barbič B et al. The failure of extracorporeal carbon dioxide removal may be a failure of technology. Am J Respir Crit Care Med. 2024;209(7):884-7. Duggal A et al. Reply to Tiruvoipati et al.: VENT-AVOID trial: avoiding acute hypercapnic respiratory failure! Am J Respir Crit Care Med. 2024;209(12):1515. Duggal A et al. Extracorporeal carbon dioxide removal to avoid invasive ventilation during exacerbations of chronic obstructive pulmonary disease: VENT-AVOID trial - a randomized clinical trial. Am J Respir Crit Care Med. 2024;209(5):529-42.
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