High-Flow Nasal Cannula Oxygen in Patients with Acute Respiratory Failure and Do-Not-Intubate or Do-Not-Resuscitate Orders: A Systematic Review

In this systematic review of six studies, all with a high risk of bias, a significant proportion of patients with a DNI and/or DNR order who used HFNC oxygen survived to hospital discharge. Oxygen saturation and respiratory rate consistently improved in the three studies that reported these outcomes. Only one study (published as a conference abstract only to date),¹⁸ however, measured patient-important outcomes related to symptom management and found no significant difference in dyspnea or morphine dose requirements in patients on HFNC oxygen compared with patients on conventional oxygen. HFNC oxygen was generally well tolerated and only had to be stopped in <5% of patients due to intolerance. We found no studies that assessed the quality of life in survivors or the quality of death in nonsurvivors.

Based on the limited evidence in the included studies, HFNC may be a viable treatment option for patients with preset treatment limitations who have acute respiratory failure—with potential benefits of improved oxygenation, decreased respiratory rates, and hospital survival in a proportion of patients. Nevertheless, this systematic review highlights the vast paucity of data available to guide the use of HFNC oxygen in patients with treatment limitations and acute respiratory failure. Only a few studies, which were at high risk of bias, have been conducted on this topic to date. There is an inadequate evidence base to evaluate the comparative effectiveness of HFNC oxygen (versus NPPV versus conventional oxygen versus palliative opioids) in patients with DNI orders or comfort measures only orders.

Our review included two studies that evaluated the comparative effectiveness of HFNC oxygen in patients with DNI and/or DNR orders. The first retrospective observational study compared HFNC oxygen with conventional oxygen in patients with DNR and DNI orders and malignancy—and found no change in dyspnea—but did note an increase in mortality with HFNC oxygen (76% versus 51%).¹⁸ The second observational study compared HFNC oxygen with NPPV in patients with DNR orders with malignancy noted no difference in mortality.¹⁷ In patients with full-code orders, systematic reviews have shown that HFNC oxygen (compared with conventional oxygen) was associated with possible reductions in intubation rates, respiratory rates, and improvements in oxygenation—with no difference in mortality, dyspnea, patient comfort, or ICU/hospital length of stay. Compared with NPPV, HFNC oxygen was associated with similar rates of intubation and mortality.^4-6,21

Future studies in patients with acute respiratory failure and DNI and/or DNR orders should identify which treatment modality (HFNC oxygen compared with other modalities, such as NPPV, conventional oxygen, with or without palliative opioids) impacts outcomes, such as dyspnea reduction while maintaining an alert mental status, short- and long-term quality of life in survivors, and quality of death in nonsurvivors. Future studies should also identify the optimal treatment pathway to utilize when patients using HFNC oxygen fail this therapy (eg, transition to NPPV versus intensifying palliative opioids) as well as the optimal process to withdraw palliative HFNC oxygen.²² Identifying which patient populations may benefit from different treatment pathways should also be considered as different treatment strategies may be more beneficial in different patient populations (eg, based on cause and severity of acute respiratory failure). In addition, it should be noted that the primary goal of care might affect which outcomes are the most important to measure. While patients with comfort measures only, orders usually have a primary goal to prepare for a high-quality death, patients with DNI and/or DNR orders (but without comfort measures only orders) may have a primary goal to survive—but with the desire not to endure the high burden of intubation and mechanical ventilation if it became necessary. Finally, future studies should utilize high-quality study designs (eg, randomized controlled trials) that enable robust evaluation of comparative effectiveness of clinically relevant treatment strategies.

While several previous systematic reviews have evaluated the efficacy of HFNC in patients with acute respiratory failure without preset limitations on life support; to our knowledge, this is the first systematic review to assess outcomes in patients rigorously with preset treatment limitations. Our review is, however, limited by the high risk of bias of the studies that were included (single-center nature, retrospective observational study designs, small sample sizes, and lack of a description of how DNI and/or DNR statuses were determined) as well as the small number of studies available to be included.