Noninvasive Ventilation in Patients With Do-Not-Intubate and Comfort-Measures-Only Orders

A Systematic Review and Meta-analysis

Michael E. Wilson, MD; Abdul M. Majzoub, MD; Claudia C. Dobler, MD, PhD; J. Randall Curtis, MD, MPH; Tarek Nayfeh, MD; Bjorg Thorsteinsdottir, MD; Amelia K. Barwise, MB, BCh, BAO; Jon C. Tilburt, MD, MPH; Ognjen Gajic, MD, MSc; Victor M. Montori, MD, MSc; M. Hassan Murad, MD, MPH


Crit Care Med. 2018;46(8):1209-1216. 

In This Article

Abstract and Introduction


Objectives: To assess the effectiveness of noninvasive ventilation in patients with acute respiratory failure and do-not-intubate or comfort-measures-only orders.

Data Sources: MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to January 1, 2017.

Study Selection: Studies of all design types that enrolled patients in the ICU or hospital ward who received noninvasive ventilation and had preset do-not-intubate or comfort-measures-only orders.

Data Extraction: Data abstraction followed Meta-analysis of Observational Studies in Epidemiology guidelines. Data quality was assessed using a modified Newcastle-Ottawa Scale.

Data Synthesis: Twenty-seven studies evaluating 2,020 patients with do-not-intubate orders and three studies evaluating 200 patients with comfort-measures-only orders were included. In patients with do-not-intubate orders, the pooled survival was 56% (95% CI, 49–64%) at hospital discharge and 32% (95% CI, 21–45%) at 1 year. Hospital survival was 68% for chronic obstructive pulmonary disease, 68% for pulmonary edema, 41% for pneumonia, and 37% for patients with malignancy. Survival was comparable for patients treated in a hospital ward versus an ICU. Quality of life of survivors was not reduced compared with baseline, although few studies evaluated this. No studies evaluated quality of dying in nonsurvivors. In patients with comfort-measures-only orders, a single study showed that noninvasive ventilation was associated with mild reductions in dyspnea and opioid requirements.

Conclusions: A large proportion of patients with do-not-intubate orders who received noninvasive ventilation survived to hospital discharge and at 1 year, with limited data showing no decrease in quality of life in survivors. Provision of noninvasive ventilation in a well-equipped hospital ward may be a viable alternative to the ICU for selected patients. Crucial questions regarding quality of life in survivors, quality of death in nonsurvivors, and the impact of noninvasive ventilation in patients with comfort-measures-only orders remain largely unanswered.


Noninvasive ventilation (NIV), including continuous positive airway pressure and bilevel positive airway pressure, has been shown to be effective in treating acute respiratory failure in different conditions, often preventing the need for invasive mechanical ventilation.[1–5] Most studies in acute respiratory failure have focused exclusively on patients without preset limits on life support. The goals of treatment and expected outcomes of NIV vary significantly depending on whether patients want to receive all possible life-sustaining treatments (full code), have elected to have preset limits to life support, such as a do-not-intubate (DNI) approach, or prefer to pursue a comfort-measures-only (CMO) approach.[6,7] Some experts have called into question the utility of considering NIV for patients with preset limits on life support, arguing that the burdens of NIV may outweigh potential benefits and could merely extend the dying process without providing an acceptable quality of life in survivors or an acceptable quality of death in nonsurvivors.[8–10]

To develop a treatment plan that honors patient preferences and achieves patient-centered goals, clinicians need accurate and applicable prognostic information regarding different treatment pathways. Although NIV is commonly used in patients with DNI and CMO orders and various studies have evaluated patient outcomes, individual studies have often faced limitations such as small sample size, generalizability limited to a single center or country, and lack of information about outcomes for patients with different types of respiratory failure. Several narrative reviews have reported findings from a limited number of studies regarding outcomes of NIV in patients with DNI and CMO orders.[6,8,11] However, a systematic review and meta-analysis has not been performed to date.

The objective of our study was to evaluate two key questions (Figure 1). Key question 1: Among patients with an existing DNI status who received NIV for acute respiratory failure, what were the survival, quality of life, and tolerance of treatment? Key question 2: Among patients with an existing CMO status who received NIV for acute respiratory failure, what were the dyspnea control, opioid requirement, tolerance of treatment, and survival? For key question 1, we also sought to compare outcomes of patients according to the primary cause of acute respiratory failure, as well as the location of NIV treatment (i.e., hospital ward vs ICU).

Figure 1.

Analytic framework. NIV = noninvasive ventilation.