Do-not-intubate orders in patients with acute respiratory failure: a systematic review and meta-analysis
To assess the rates and variability of do-not-intubate orders in patients with acute respiratory failure.
We conducted a systematic review of observational studies that enrolled adult patients with acute respiratory failure requiring noninvasive ventilation or high-flow nasal cannula oxygen from inception to 2019.
Twenty-six studies evaluating 10,755 patients were included. The overall pooled rate of do-not-intubate orders was 27%. The pooled rate of do-not-intubate orders in studies from North America was 14% (range 9–22%), from Europe was 28% (range 13–58%), and from Asia was 38% (range 9–83%), p = 0.001. Do-not-intubate rates were higher in studies with higher patient age and in studies where do-not-intubate decisions were made without reported patient/family input. There were no significant differences in do-not-intubate orders according to illness severity, observed mortality, malignancy comorbidity, or methodological quality. Rates of do-not-intubate orders increased over time from 9% in 2000–2004 to 32% in 2015–2019. Only 12 studies (46%) reported information about do-not-intubate decision-making processes. Only 4 studies (15%) also reported rates of do-not-resuscitate.
One in four patients with acute respiratory failure (who receive noninvasive ventilation or high-flow nasal cannula oxygen) has a do-not-intubate order. The rate of do-not-intubate orders has increased over time. There is high inter-study variability in do-not-intubate rates—even when accounting for age and illness severity. There is high variability in patient/family involvement in do-not-intubate decision making processes. Few studies reported differences in rates of do-not-resuscitate and do-not-intubate—even though recovery is very different for acute respiratory failure and cardiac arrest.
KeywordsIntensive care units Critical care Acute respiratory failure Do-not-intubate Noninvasive ventilation Palliative care
This project received no funding.
Compliance with ethical standards
Conflicts of interest
The authors have no conflicts of interest to disclose.
- 4.Wilson ME, Majzoub AM, Dobler CC, Curtis JR, Nayfeh T, Thorsteinsdottir B, Barwise AK, Tilburt JC, Gajic O, Montori VM, Murad MH (2018) Noninvasive ventilation in patients with do-not-intubate and comfort-measures-only orders: a systematic review and meta-analysis. Crit Care Med 46(8):1209–1216PubMedGoogle Scholar
- 6.Azoulay E, Kouatchet A, Jaber S, Lambert J, Meziani F, Schmidt M, Schnell D, Mortaza S, Conseil M, Tchenio X, Herbecq P, Andrivet P, Guerot E, Lafabrie A, Perbet S, Camous L, Janssen-Langenstein R, Collet F, Messika J, Legriel S, Fabre X, Guisset O, Touati S, Kilani S, Alves M, Mercat A, Similowski T, Papazian L, Meert AP, Chevret S, Schlemmer B, Brochard L, Demoule A (2013) Noninvasive mechanical ventilation in patients having declined tracheal intubation. Intensive Care Med 39(2):292–301PubMedGoogle Scholar
- 8.Hart JL, Harhay MO, Gabler NB, Ratcliffe SJ, Quill CM, Halpern SD (2015) Variability among us intensive care units in managing the care of patients admitted with preexisting limits on life-sustaining therapies. JAMA internal Med 175(6):1019–1026Google Scholar
- 10.Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ (Clin Res ed) 339:b2535Google Scholar
- 11.Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P (2009) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. The Ottawa Hospital Research Institute. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed 26 Aug 2019
- 12.Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T (2013) Meta-analysis of prevalence. J Epidemiolog Community Health 67(11):974–978Google Scholar
- 13.Riley RD, Higgins JP, Deeks JJ (2011) Interpretation of random effects meta-analyses. BMJ (Clin Res Ed) 342:d549Google Scholar
- 17.Bugov D, Voigt LP, Yohannes-Tomicich J, Abbas Q, Tayban Y, Weiner R, Kostelecky N, Ramaker JS, Kirnicinii G, Haynes A (2015) High-flow nasal cannula oxygenation in cancer patients: practice patterns and outcomes. Chest 148(4):301AGoogle Scholar
- 21.Ugurlu AO, Sidhom SS, Khodabandeh A, Ieong M, Mohr C, Lin DY, Buchwald I, Bahhady I, Wengryn J, Maheshwari V (2016) Use and outcomes of noninvasive ventilation for acute respiratory failure in different age groups. Respir Care 61(1):36–43Google Scholar
- 22.Del Campo Molina E, Angel P, Garcia Delgado F, Artacho Ruiz R, Guzman Perez J, Fernandez Romero E, Caballero Gueeto F (2014) Is it ethical to use non-invasive mechanical ventilation (NIMV) in patients considered as to be under limitation of therapeutic efforts (LTE)? Intensive Care Med 40:S76–S77Google Scholar
- 23.Soler Barnes J, Carrillo Alcaraz A, Gonzalez Diaz G, Botias Arnau S, Lopez Martinez A, Alcazar Espin M, Llamas Fernandez N (2011) aaDo-not-intubated (DNI) order and non-invasive mechanical ventilation (NIMV). Crit Care Long Term Surviv Intensive Care Med 37:S69Google Scholar
- 26.Lemyze M, Mallat J, Nigeon O, Barrailler S, Pepy F, Gasan G, Vangrunderbeeck N, Grosset P, Tronchon L, Thevenin D (2013) Rescue therapy by switching to total face mask after failure of face mask-delivered noninvasive ventilation in do-not-intubate patients in acute respiratory failure. Crit Care Med 41(2):481–488PubMedGoogle Scholar
- 27.La Regina M, Marinaro A, Scuotri L, Corsini F, Orlandini F (2013) Non-invasive mechanical ventilation in internal medicine departments: a pilot study. Ital J Med 7(3):172–178Google Scholar
- 32.Liu JJ, Bell C, Campbell V, DeBacker J, Tamberg E, Lee C, Mehta S (2019) Noninvasive ventilation in patients with hematologic malignancy: a retrospective study. J Intensive Care Med 34(3):197–203Google Scholar
- 34.Hibi M, Shiraki A, Nagata K, Nei Y, Sato S, Nishimura N, Izumi S, Tachikawa R, Tomii K (2017) Comparison between high-flow nasal cannula oxygen therapy and non-invasive ventilation for respiratory care: a Japanese cross-sectional multicenter survey. Eur Respir J Conf Eur Respir Soc Int Congress ERS 50 (Supplement 61):PA1876Google Scholar
- 35.Brambilla AM, Prina E, Ferrari G, Bozzano V, Ferrari R, Groff P, Petrelli G, Scala R, Causin F, Noto P, Bresciani E, Voza A, Aliberti S, Cosentini R, Group PS (2019) Non-invasive positive pressure ventilation in pneumonia outside Intensive Care Unit: an Italian multicenter observational study. European Journal of Internal Medicine 59:21–26PubMedGoogle Scholar
- 38.Makino H, Nishikawa H, Taguchi Y, Kouda T, Kajiwara K, Kanematsu T (2018) Can high-flow nasal cannula improve comfort in elderly patients with acute respiratory failure? Am J Respir Crit Care Med Conf Am Thorac Soc Int Conf ATS 197 (MeetingAbstracts):A3249Google Scholar
- 39.Kang YS, Choi SM, Lee J, Park YS, Lee CH, Yoo CG, Kim YW, Han SK, Lee SM (2018) Improved oxygenation 48 hours after high-flow nasal cannula oxygen therapy is associated with good outcome in immunocompromised patients with acute respiratory failure. J Thorac Dis 10(12):6606–6615PubMedPubMedCentralGoogle Scholar
- 40.Long AC, Brumback LC, Curtis JR, Avidan A, Baras M, De Robertis E, Efferen L, Engelberg RA, Kross EK, Michalsen A, Mularski RA, Sprung CL (2019) Agreement with consensus statements on end-of-life care: a description of variability at the level of the provider, Hospital, and Country. Crit Care MedGoogle Scholar
- 48.Wennberg JE, Fisher ES, Stukel TA, Skinner JS, Sharp SM, Bronner KK (2004) Use of hospitals, physician visits, and hospice care during last six months of life among cohorts loyal to highly respected hospitals in the United States. BMJ (Clin Res Ed) 328(7440):607Google Scholar
- 57.Yadav KN, Gabler NB, Cooney E, Kent S, Kim J, Herbst N, Mante A, Halpern SD, Courtright KR (2017) Approximately one in three US adults completes any type of advance directive for end-of-life care. Health Aff (Project Hope) 36(7):1244–1251Google Scholar
- 58.Benoit DD, Jensen HI, Malmgren J, Metaxa V, Reyners AK, Darmon M, Rusinova K, Talmor D, Meert AP, Cancelliere L, Zubek L, Maia P, Michalsen A, Vanheule S, Kompanje EJO, Decruyenaere J, Vandenberghe S, Vansteelandt S, Gadeyne B, Van den Bulcke B, Azoulay E, Piers RD (2018) Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA. Intensive Care Med 44(7):1039–1049PubMedPubMedCentralGoogle Scholar
- 59.Sprung CL, Truog RD, Curtis JR, Joynt GM, Baras M, Michalsen A, Briegel J, Kesecioglu J, Efferen L, De Robertis E, Bulpa P, Metnitz P, Patil N, Hawryluck L, Manthous C, Moreno R, Leonard S, Hill NS, Wennberg E, McDermid RC, Mikstacki A, Mularski RA, Hartog CS, Avidan A (2014) Seeking worldwide professional consensus on the principles of end-of-life care for the critically ill. The Consensus for Worldwide End-of-Life Practice for Patients in Intensive Care Units (WELPICUS) study. Am J Respir Crit Care Med 190(8):855–866PubMedGoogle Scholar