Baseline Level and Reduction in PaCO2 are Associated with the Treatment Effect of Long-Term Home Noninvasive Positive Pressure Ventilation in Stable Hypercapnic Patients with COPD: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Purpose The evidence of long-term home noninvasive positive pressure ventilation (LTHNIPPV) in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD) is controversial. In this meta-analysis study, we sought to establish whether a baseline level and reduction in partial pressure of arterial carbon dioxide (PaCO2) were associated with the treatment effect of LTHNIPPV in these patients. Patients and Methods Six electronic databases were comprehensively searched from January 1980 until June 2020. Randomized clinical trials (RCTs) comparing LTHNIPPV with control treatment were included. Two authors independently extracted data, assessed the study quality, and used the GRADE approach to evaluate evidence quality. The main outcome was mortality. Results Nineteen studies involving 1482 patients (LTHNIPPV, n = 730; control, n = 752) were included. LTHNIPPV significantly reduced mortality (relative risk [RR] = 0.76; 95% confidence interval [CI]: 0.61–0.95; p = 0.02; I 2 = 14%), the frequency of hospital admissions, PaCO2, and improved partial pressure of oxygen (PaO2) compared to control treatment. LTHNIPPV also relieved dyspnea and improved exercise capacity and health-related quality of life (HRQL) but showed no significant benefit for improving the forced expiratory volume in one second in predicted (FEV1% pred). Subgroup analysis revealed that the baseline level and reduction in PaCO2 were associated with decreased mortality (baseline PaCO2 ≥ 55 mmHg RR = 0.69, P = 0.02; vs baseline PaCO2 < 55 mmHg RR = 0.87, P = 0.32; and higher dPaCO2 RR = 0.42, P < 0.0001; vs lower dPaCO2 RR = 0.91, P = 0.38). Conclusion LTHNIPPV significantly reduced mortality. The baseline level and reduction in PaCO2 were associated with the treatment effect of LTHNIPPV in patients with stable hypercapnic COPD. Large-scale, multicenter RCTs are needed to confirm our results.

Practical Guide to Management of Long-Term Noninvasive Ventilation for Adults With Chronic Neuromuscular Disease

“…However, information is accumulating on the protean adverse biological effects of elevated or reduced partial pressures of arterial carbon dioxide (PaCO2) in animal models and humans. 16,[29][30][31][32][33][34][35][36] In agreement with several current guidelines and statements, 21,37,38 we recommend titration of home assisted ventilation to normalize PaCO2 as well as PaO2 to the extent possible without necessitating excessive peak inspiratory pressures, breathing discomfort, or other problematic tradeoffs. All 3 goals are achievable for many people with neuromuscular respiratory failure: however, tradeoffs are sometimes necessary for those with a concomitant severe thoracic skeletal abnormality or lung disease that requires high positive inspiratory pressures to overcome high airway resistance or low respiratory system compliance.…”

Chronic obstructive pulmonary disease (COPD) and COPD-like phenotypes

“…Early studies of home nocturnal NIV in those patients showed no benefit ( 49 , 50 ) but recent randomized controlled trials (RCTs) showed improvement in clinical outcomes, including reduction in hospitalizations and mortality benefit ( Figure 1 ) ( 51 , 52 ). Recent meta-analyses found an improvement in mortality, hospitalizations, dyspnea, exercise capacity, and health-related quality of life relative to standard treatment ( 53 , 54 ). It seems that the benefit is related to a particular ventilator strategy, known as high intensity, that includes large inspiratory to expiratory airway pressure difference, high minute ventilation, and reducing baseline CO 2 levels by 25%, as well as with selection of patients with severe disease, those with FEV 1 % predicted < 50% and PaCO 2 > 52 mmHg ( 51 , 52 , 55 ).…”

“…RCTs with favorable outcomes recruited patients with severe lung function impairment and hypercapnia who had a recent COPD-related hospitalization or chronic hypoxemic respiratory failure ( 51 , 52 , 56 ). A recent metanalysis showed that both higher baseline arterial CO 2 levels and greater magnitude of the CO 2 reduction from NIV are associated with greater improvement in clinical outcomes ( 53 ). Nevertheless, this may merely reflect that these patients are sicker and benefit more from treatment.…”