Discussion
In this single-centre retrospective study, comparing two cohorts, treated for AHRF with NIV in 2012–2013 and 2017–2018, before and after introduction of a new treatment guideline in 2016 recommending a more rapid rise in pressure and use of higher IPAP, we found a significantly better short-time and long-time survival in the later cohort. To our knowledge, this is the first study to show a lower mortality when providing NIV with higher IPAP i for treatment of AHRF secondary to AECOPD. Additionally, data from the present study suggest that the risk of mortality following hospitalisation is highest immediately after discharge. For patients who survived the first 30 days post hospital discharge, the 1-year survival remained high (figure 2, Kaplan-Meier plot). This is in accordance with studies on survival after hospitalisation with AECOPD.12
Our data show that the new treatment guidelines were well implemented, with a median IPAP of 20 cm H2O in 2017–2018 compared with 12 cm H2O in 2012–2013. Apart from updated recommendations regarding the algorithm for pressure settings for NIV, standard treatment of AECOPD and the indication for NIV treatment were unchanged from 2012 to 2018.
Over the recent years, attention to improve suboptimal NIV treatment has risen. Insufficient pressure settings, especially inadequate IPAP, will not increase alveolar ventilation significantly. Focus on a more rapid improvement of pH within the first 4 hours after initiation of NIV is essential to reduce relative risk of NIV failure.13 The improved survival in patients treated with higher IPAP in the present study, with otherwise comparable cohorts, suggests that using higher IPAP is more efficient to resolve AHRF and thus acute respiratory acidaemia. A rapid improvement of ventilation and patient’s recovery may also increase patient acceptance of NIV treatment and reduce the risk of NIV failure. Furthermore, shortening length of treatment reduces risks of complications associated with hospitalisation and immobilisation; pulmonary embolism, hospital acquired pneumonia, and loss of physical mobility.
Other aspects in general COPD care changed from 2012 to 2018 and may have contributed to preventing admissions with AHRF and improving patient survival. Treatment with LT NIV has been shown to prevent hospitalisation in the subgroup of most severely ill patients with COPD.5 LT NIV was introduced at the current department in the year 2000 and has become more frequent for the small subgroup of patients with COPD with chronic stable hypercapnia as well as for selected patients with recurrent exacerbations with AHRF.14 Pharmaceutical treatment with long-term prophylactic azithromycin, as anti-inflammatory therapy, to reduce risk of exacerbations in patients with a history of recurrent exacerbations has also become more widespread.15
In research regarding treatment survival, mortality rates in observational studies are commonly higher compared with RCTs. Risk of in-hospital mortality was 99 per 1000 (95% CI 70 to 139) in the 2017 Cochrane meta-analysis analysing the results of 12 RCTs.2 Published cohort studies on survival of AHRF show great variation in mortality. In a Danish nationwide register-based study of 12 847 patients admitted for AECOPD and treated with NIV in 2004 to 2011, median age 73.7 (IQR 66–80) years, in-hospital mortality was 24.4% (95% CI 24.3 to 24.5).16 Among patients alive at discharge, 26.4% (95% CI 26.3 to 26.5) died within 1 year. In a smaller Dutch retrospective single-centre study of 78 patients admitted with AHRF requiring NIV in 2009 to 2011, in-hospital mortality was 14.1%, with 1-year mortality of 43.6%.17 Mean age of the cohort was 71.0 (SD ±10.7) years, median FEV1 39.0% (IQR 28.6–52.9) and median PaCO2 before NIV 10.0 (IQR 8.5–11.2) kPa. Data from the national COPD audit in the UK in 2008 and 2014 showed a significantly improved in-hospital mortality of 24.9% and 16.8%, respectively.18 Findings were explained due to better adherence to guideline recommendations of ventilatory settings, although data on pressure settings were not recorded, as well as improvements of general care such as controlled oxygen and early antibiotic treatment. Further retrospective data from the UK compared two cohorts, 2004–2010 and 2013–2017, of patients with COPD and first episode of ward‐based NIV.19 In-hospital mortality rates were 17.6% and 20.5% (p=0.378). Characteristics of the two cohorts were as follows, respectively: median age of 72.1 (IQR 64.2–78.8) and 69.9 (IQR 63.7–76.9) years, FEV1 of 32 (IQR 24–39) and 35 (IQR 27–47)%, PaCO2 before NIV of 9.36 (IQR 27–47) and 10.34 (IQR 8.89–11.8) kPa and maximum IPAP of 15 cm H2O (IQR 12–18) and 18 (IQR 15–21).
Limitations of the present study are the limitations associated with a retrospective cohort study, the risk of selection and information bias with imprecise outcome registration and uneven collection of data. A potential selection bias is different selection of patients to whom physicians offered NIV treatment to in the two cohorts. As NIV was a newer, advanced technology in 2012–2013, physicians could have been more prone to select the most severely ill patients for NIV as rescue treatment, whereas in the later cohort, NIV could have been offered more broadly to patients with AHRF, despite the severity of acidaemia, comorbidities and performance status. However, baseline characteristics and blood gas levels of pH and PaCO2 at initiation of NIV were comparable in the cohorts, which contradicts a selection bias. As a single-centre study with a small size cohort, there is the potential risk of overstating positive results and the lack of external validity required to support a more widespread generalisation of the results. The in-hospital mortality was notably high in both cohorts compared with the previously mentioned studies, reflecting the demographic composition of patients treated at the hospital, with median age of 78 in both cohorts. Other factors associated with death such as FEV1 and pH and PaCO2 before NIV are in accordance with data from previous studies. NIV was ceiling therapy for 60% of patients in the 2012–2013 cohort and 42% of patients in the 2017–2018 cohort. This is also reflected in the small percentage of patients transferred to the ICU due to NIV failure. Furthermore, about one out of four DNI/DNR orders were placed later than 2 hours of admission in both cohorts.