Background. Identification of patients who may become hypercapnic, or develop acidotic hypercapnic respiratory failure (AHRF), is important in chronic obstructive pulmonary disease (COPD) to avoid hospital admission and select patients for use of home NIV. This study aimed to identify factors associated with presence and development of hypercapnia. Methods. 1224 patients, 637 with COPD and 587 with alpha 1 antitrypsin deficiency (AATD), from 4 previously established patient cohorts, were included in cross-sectional analyses of hypercapnia (PaCO2 ≥ 6.5 kPa or 48.8 mmHg), focusing on phenotypic features of COPD and mortality. Longitudinal associations of rising PaCO2 were also assessed. A second cohort of 160 COPD patients underwent sleep studies and 1-year follow-up, analysing in a similar way, incorporating additional information from their sleep studies if appropriate. Results. Hypercapnia was 15 times more common in usual COPD than AATD ( p < 0.01 ) after adjustment for baseline differences by regression. Independent predictors of hypercapnia in COPD included FEV1 and current use of oxygen; these variables, together with lack of emphysema, explained 11% of variance in CO2. Increasing PaCO2 also associated with higher risk of death ( p = 0.03 ). 44/160 patients exhibited sleep disordered breathing. The sleep study cohort also showed an association of low FEV1 with hypercapnia. Prior hospital admission for AHRF was also clinically significant, being a feature of almost double the number of hypercapnic patients in both test and sleep study COPD cohorts. Conclusion. Lower FEV1 and prior AHRF are the main associations of hypercapnia in COPD, which carries a poor prognosis, particularly worsening over time.

The effectiveness of bi-level positive airway pressure (BiPAP) in patients with acute hypercapnic respiratory failure (AHRF) due to etiologies other than chronic obstructive pulmonary disease (COPD) is unclear. To systematically review the evidence regarding the effectiveness of BiPAP in non-COPD patients with AHRF. The Cochrane Library, MEDLINE, EMBASE, and CINAHL Plus were searched according to prespecified criteria (PROSPERO-CRD42018089875). Randomized controlled trials (RCTs) assessing the effectiveness of BiPAP versus continuous positive airway pressure (CPAP), invasive mechanical ventilation, or O 2 therapy in adults with non-COPD AHRF were included. The primary outcomes of interest were the rate of endotracheal intubation (ETI) and mortality. Risk-of-bias assessment was performed, and data were synthesized and meta-analyzed where appropriate. Two thousand four hundred and eighty-five records were identified after removing duplicates. Eighty-eight articles were identified for full-text assessment, of which 82 articles were excluded. Six studies, of generally low or uncertain risk-of-bias, were included involving 320 participants with acute cardiogenic pulmonary edema (ACPO) and solid tumors. No significant differences were seen between BiPAP ventilation and CPAP with regard to the rate of progression to ETI (risk ratio [RR] = 1.49, 95% confidence interval [CI], 0.63–3.62, P = 0.37) and in-hospital mortality rate (RR = 0.71, 95% CI, 0.25–1.99, P = 0.51) in patients with AHRF due to ACPO. The efficacy of BiPAP appears similar to CPAP in reducing the rates of ETI and mortality in patients with AHRF due to ACPO. Further research on other non-COPD conditions which commonly cause AHRF such as obesity hypoventilation syndrome is needed.

Background. The use of ward-based noninvasive ventilation (NIV) for acute hypercapnic respiratory failure (AHRF) unrelated to chronic obstructive pulmonary disease (COPD) remains controversial. This study evaluated the outcomes and failure rates associated with NIV application in the ward-based setting for patients with AHRF unrelated to COPD. Methods. A multicentre, retrospective cohort study of patients with AHRF unrelated to COPD was conducted. COPD was not the main reason for hospital admission, treated with ward-based NIV between February 2004 and December 2018. All AHRF patients were eligible; exclusion criteria comprised COPD patients, age < 18 years, pre-NIV pH < 7.35, or a lack of pre-NIV blood gas. In-hospital mortality was the primary outcome; univariable and multivariable models were constructed. The obesity-related AHRF group included patients with AHRF due to obesity hypoventilation syndrome (OHS), and the non-obesity-related AHRF group included patients with AHRF due to pneumonia, bronchiectasis, neuromuscular disease, or fluid overload. Results. In total, 479 patients were included in the analysis; 80.2% of patients survived to hospital discharge. Obesity-related AHRF was the indication for NIV in 39.2% of all episodes and was the aetiology with the highest rate of survival to hospital discharge (93.1%). In the multivariable analysis, factors associated with a higher risk of in-hospital mortality were increased age (odds ratio, 95% CI: 1.034, 1.017–1.051, P < 0.001 ) and pneumonia on admission (5.313, 2.326–12.131, P < 0.001 ). In the obesity-related AHRF group, pre-NIV pH < 7.15 was associated with significantly increased in-hospital mortality (7.800, 1.843–33.013, P = 0.005 ); however, a pre-NIV pH 7.15–7.25 was not associated with increased in-hospital mortality (2.035, 0.523–7.915, P = 0.305 ). Conclusion. Pre-NIV pH and age have been identified as important predictors of surviving ward-based NIV treatment. Moreover, these data support the use of NIV in ward-based settings for obesity-related AHRF patients with pre-NIV pH thresholds down to 7.15. However, future controlled trials are required to confirm the effectiveness of NIV use outside critical care settings for obesity-related AHRF.

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