Extracorporeal Lung Support for Hypercapnic Ventilatory Failure

Severe Asthma

Near-fatal asthma is a life-threatening subset of asthma, sometimes requiring mechanical ventilation.¹² Because of air-flow obstruction with hyperinflation and the development of intrapulmonary shunt, often caused by atelectasis and mucous plugging, patients with severe asthma frequently show a rapid onset with severe hypoxemia as well as a persistent hypercapnia.¹² Other relevant pathophysiologic events include lactic acidosis with signs of exhaustion, worsening of mental status, and hemodynamic instability.¹² Despite the fact that NIV, together with conventional medical treatment, decreases respiratory muscle work and improves alveolar ventilation, it is not recommended for patients with acute severe asthma due to the lack of evidence.¹³ In addition, intubation in this scenario could be challenging and not without risks. Therefore, extracorporeal lung support has been considered a valid option in the management of patients with severe asthma to avoid sedation and intubation and their negative effects. In the case of a hypercapnic pediatric patient, the use of ECMO has been described as a viable therapeutic option to treat hypercapnic respiratory failure accompanied by a left-lung atelectasis.¹⁴ Recently, Schneider et al¹⁵ demonstrated that extracorporeal CO₂ removal was an effective tool for management of severe respiratory acidosis in a patient with a near-fatal asthma attack who was failing NIV. Following resolution of the acute attack, after 34 h of extracorporeal CO₂ removal treatment, the patient was completely weaned without any complication.

Acute Interstitial Lung Disease

Idiopathic interstitial pneumonias are a group of heterogeneous lung diseases with unknown etiology. The case reported by Petzoldt et al¹⁶ was affected by nonspecific interstitial pneumonia, the first line treatment for which is high-dose corticosteroids. The authors described the successful management of a patient with severe refractory hypercapnia and signs of encephalopathy using the arteriovenous pumpless extracorporeal lung assist device (Novalung, Talheim, Germany) as rescue therapy.¹⁶ Because of the poor prognosis of other forms of idiopathic interstitial pneumonias, such as the idiopathic pulmonary fibrosis, the use of extracorporeal CO₂ removal should be limited to potentially reversible conditions or to use as a transplantation bridge.

COPD

Respiratory support is often needed in patients with severe COPD exacerbation, and NIV is currently considered the preferred choice for these patients when acute hypercapnic respiratory failure occurs.¹³ Although NIV reduces mortality, the need for endotracheal intubation, and the length of hospital stay in these patients,¹³ it can fail. In addition, COPD patients who require intubation after NIV failure usually have a poor outcome with high mortality rates.¹⁷ Moreover, NIV is not indicated in patients with cardiac and respiratory arrest, and it could be difficult to apply when patients are agitated, unable to protect the airway, and unable to manage excessive secretions.¹⁸ Thus, extracorporeal CO₂ removal has been proposed for the treatment of patients suffering a COPD exacerbation to avoid invasive mechanical ventilation. The rationale is to combine the improvement of alveolar ventilation by using NIV with muscle unloading provided by removing CO₂ directly from the blood, using an extracorporeal device. Similarly, a physiologic basis for the application of extracorporeal CO₂ removal to accelerate the weaning process from the endotracheal intubation has been demonstrated.^19,20 In fact, extracorporeal CO₂ removal was able to reduce inspiratory effort, avoiding the shallow-breathing pattern and maintaining stable P_aCO2 levels when applied during T-piece weaning trial in severely hypercapnic COPD subjects previously intubated for an episode of respiratory acidosis.¹⁹

Although extracorporeal low-blood flow devices are extremely efficient from a physiologic standpoint, scientific evidence is still limited. The majority of data are from case reports and observational studies, one of them quite large but performed in different groups of subjects (ie, those receiving NIV with a high likelihood of requiring invasive ventilation, those who could not be weaned from NIV, and finally those receiving invasive ventilation who had failed attempts to wean).²¹ Randomized controlled studies have never been done. There have been 3 case-control studies published to date. In a retrospective study using a pumpless extracorporeal lung assist, 21 cases were matched with contemporaneous controls (only one fourth of the sites) based on diagnosis, age, Simplified Acute Physiology Score II, and pH ± 0.05 before extracorporeal CO₂ removal or intubation. Nineteen (90%) of the 21 subjects treated with pumpless extracorporeal lung assist did not require intubation.²² Median P_aCO2 levels and pH in arterial blood before treatment were 84 mm Hg and 7.28, respectively; within 24 h, median P_aCO2 levels and pH had significantly improved to 52.1 mm Hg and 7.44.

Twenty-five subjects considered at risk of NIV failure were treated with NIV plus extracorporeal CO₂ removal by Del Sorbo et al.²³ NIV criteria for failure were identified as the presence of 2 or more of the following conditions for a duration of at least 2 h: (1) frequency > 30 breaths/min, (2) arterial pH ≤ 7.30, (3) P_aCO2 > 20% of the baseline value, and (4) use of accessory muscles or paradoxical abdominal movements. Compared with 21 matched NIV historical control subjects, the adjunction of extracorporeal CO₂ removal to NIV was able to reduce acutely CO₂ levels, decreasing the relative risk of intubation by 73% (hazard ratio 0.27, 95% CI 0.07–0.98, P = .047). However, relevant extracorporeal CO₂ removal-associated adverse events were observed in 13 subjects (52%).²³ A systematic review assessed the efficacy and safety of extracorporeal CO₂ removal in 87 subjects with hypercapnic respiratory failure across 10 different studies, showing heterogeneous data.³ Sources of heterogeneity included the subjects' characteristics, the types of extracorporeal CO₂ removal devices, the anticoagulation protocols, and the sizes of the vascular access. Despite these limitations, the majority of subjects in this review successfully were sustained on NIV and avoided intubation (93%); furthermore, more than half of the subjects were weaned from mechanical ventilation (53%). These high success rates in the primary outcomes, however, must be interpreted very cautiously, given the clear selection bias associated with case series data. Besides, all of the studies were associated with a high rate of complications; a total of 11 major and 30 minor complications were found.

Only 3 studies presented data on ICU and hospital stay and mortality, and they proved to be contrasting.³ The available physiologic data, comparing primarily pre- with post-extracorporeal CO₂ removal changes in the same patients, suggest rapid and sustained improvements in ventilatory parameters, including pH, P_aCO2, and breathing frequency, but not in oxygenation as measured using P_aO2/F_IO2. Another multi-center case-control study²⁴ showed that intubation was avoided in 14 of 25 extracorporeal CO₂ removal subjects (56%). Once again, relevant extracorporeal CO₂ removal-associated adverse events were observed in over one third of cases. Last, despite the shorter period of invasive mechanical ventilation in the extracorporeal CO₂ removal group, there were no significant differences in stay or in 28-d mortality (16% vs 12%) and 90-d mortality (28% vs 28%) rates between the 2 groups. In conclusion, the topic appears to be clinically relevant and innovative. These data provide the basis for randomized clinical trials needed to assess the risk–benefit balance of extracorporeal CO₂ removal in COPD exacerbations. In addition, further investigations are needed to elucidate more clearly the cost-effectiveness as well as ethical implications of this treatment.