Discussion
In this reanalysis of a prospective database of 419 critically ill stroke patients requiring invasive mechanical ventilation, we show that survival 1 year after ICU admission is poor (23%) with no improvement over the 21 years of the study period. After adjustment for stroke subtype, neurological presentation and the extent of non-neurological organ failure, the reason for intubation remained independently associated with survival. Intubation for acute respiratory failure or coma was associated with comparable survival hazard ratios, whereas intubation for seizure was not associated with a worse prognosis than for elective procedure. By contrast, receiving an acute-phase therapy was associated with improved survival. Although 1-year survival did not improve over the study period, stroke patients included in the most recent period had more comorbidities and presented higher ICU admission SOFA scores.
The 1-year survival rate of 23% we found is consistent with previously published rates of 8-40% in studies focusing on MV stroke patients [
11‐
15]. However, these studies have included patients admitted before the year 2000 and do not embrace the improvement in stroke care of the past 2 decades. To the best of our knowledge, there has been no study reporting long-term survival (i.e., at 1 year) in the specific population of MV stroke patients in the last 15 years. In our study, we show that from 1997 to 2016, with a stable stroke case mix over time, 1-year survival did not improve. This finding is surprising as the use of acute-phase stroke therapies increased over the study period (from 2.9% in 1996–2002 to 21% in 2010–2016). However, patients admitted to the ICU in the third period appeared to have more comorbidities and had more organ failures than in the previous 2, suggesting a modification of ICU admission policy over time. Thus, we hypothesize that the expected gain in survival brought by acute stroke therapies has been mitigated by increased severity of admitted stroke patients. Despite this increase in patient severity, ICU and hospital length of stay decreased both in the whole population and in survivors. More recently, in a United States population-based study of 99,700 stroke patients with MV included from 2005 to 2011 [
8], hospital survival was 44%, compared to 31% in our study. Those figures are difficult to compare, as the case-mix of stroke subtype and the distribution of reason for intubation may be different. Among the 14 centers of our study, 5 centers (representing 188 (45%) patients) had on-site 24/7 interventional radiology, and it is likely that the admission policy of other participating centers was not oriented on procedural patients. Thus, we can hypothesize that the proportion of patients deemed neurologically too severe to be eligible for acute-phase stroke therapy or out of the window of therapeutic opportunity was higher in our cohort than in the most recently studied cohorts [
8‐
10].
Among the factors associated with 1-year survival identified in our study, the reason for intubation appears to be a strong predictor. We found that intubation for a cardiac arrest or an altered mental status is associated with worse 1-year survival compared to intubation for an elective procedure. In particular, it is striking to note that in our cohort, there were no survivors in patients admitted for cardiac arrest following stroke. By comparison, in 352 AIS patients with in-hospital cardiac arrests, 1-year mortality was 96% [
29], and in 92 patients with out-of-hospital cardiac arrest caused by ICH or SAH, there were no patients with a favorable neurologic outcome [
30]. By contrast, intubation for a seizure was not associated with impaired outcome. Only four studies have previously assessed the impact of the reason for intubation and have shown that acute respiratory failure and coma were associated with worse outcomes [
12,
15,
19,
31]. The reason for intubation appears to be a simple bedside clinical element that can assist the decision of admission of an acutely ill stroke patient.
The strengths of our study include a multicenter population from a high-quality prospective database with a focus on a well-defined population of acute stroke patients requiring invasive mechanical ventilation. However, our study has also limitations. First, the OUTCOMEREA database has not been built specifically for stroke studies, and all data regarding stroke are retrospective, collected from hospitalization records. Hence, data on potentially useful scores for prognostication in this setting, such as the NIHSS scores, are lacking [
6]. Furthermore, only long-term vital status was available, and evaluation of long-term functional outcomes with an appropriate tool (i.e., the modified Rankin scale) would have added valuable information. Second, the results of the study may lack generalizability as this is an exclusively French cohort including only medical and polyvalent ICUs and no specialized neuro-ICU. Furthermore, only 45% of the cohort was treated with on-site neurosurgery and interventional radiology, and it is possible that we selected a population with a high proportion of patients not eligible for acute-phase stroke therapy. Although moderate-quality evidence suggests that admission to a specialized NICU compared to a general ICU improves outcome of all stroke patients [
32‐
34], organization of acute stroke care in France allows admission to NICU mainly for comatose ICH patients deemed to benefit from early surgery, or severe SAH patients requiring endovascular treatment for treatment of ruptured aneurysm and/or invasive intracranial pressure monitoring. Third, our cohort comprised 3 distinct stroke etiologies (AIS, ICH, and SAH) that have different admission characteristics, risk factors, brain damage pathophysiology, complications, treatments, and prognosis. However, the results of the multivariate model are adjusted on the type of stroke, and Fig.
2 shows that the prognostic impact of the reason for intubation appears consistent among stroke subtypes. Fourth, as endovascular thrombectomy has mainly been developed after 2015, only a small fraction of our cohort is concerned and the survival trends we show may not take into account the recent survival benefits related to this procedure [
4]. Fifth, as for all studies focusing on populations with a high rate of WLST, our study bears an inherent bias by self-fulfilling prophecy [
35]. Sixth, as all centers did not participate throughout the 21 years of the study period, we cannot analyze any variation of incidence of admission of stroke patients with mechanical ventilation.
Acknowledgements
Members of the OUTCOMEREA Study Group—Scientific Committee: Jean‐François Timsit (Medical and Infectious Diseases ICU, Bichat‐Claude Bernard Hospital, Paris, France; UMR 1137 Inserm‐Paris Diderot university IAME, F75018, Paris); Elie Azoulay (Medical ICU, Saint Louis Hospital, Paris, France); Maïté Garrouste‐Orgeas (ICU, Saint‐Joseph Hospital, Paris, France); Jean‐Ralph Zahar (Infection Control Unit, Angers Hospital, Angers, France); Christophe Adrie (Physiology, Cochin Hospital, Paris, France); Michael Darmon (Medical ICU, Saint Etienne University Hospital, St Etienne, France); and Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, and UMR 1137 Inserm, Paris Diderot university IAME, F75018, Paris, France).
Biostatistical and information system expertise: Jean‐Francois Timsit (Medical and Infectious Diseases ICU, Bichat‐Claude Bernard Hospital, Paris, France; UMR 1137 Inserm—Paris Diderot university IAME, F75018, Paris); Corinne Alberti (Medical Computer Sciences and Biostatistics Department, Robert Debré Hospital, Paris, France); Adrien Français (Integrated Research Center U823, Grenoble, France); Aurélien Vesin (OUTCOMEREA organization and Integrated Research Center U823, Grenoble, France); Stephane Ruckly (OUTCOMEREA organization and Inserm UMR 1137 IAME, F75018, Paris); Sébastien Bailly (Grenoble university hospital Inserm UMR 1137 IAME, F75018, Paris) and Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, and Inserm UMR 1137 IAME, F75018, Paris, France); Frederik Lecorre (Supelec, France); Didier Nakache (Conservatoire National des Arts et Métiers, Paris, France); and Aurélien Van‐nieuwenhuyze (Tourcoing, France).
Investigators of the OUTCOMEREA database: Dr Romain HERNU, Christophe Adrie (ICU, CH Melun, and Physiology, Cochin Hospital, Paris, France); Carole Agasse (medical ICU, university hospital Nantes, France); Bernard Allaouchiche (ICU, Pierre benite Hospital, Lyon, France); Olivier Andremont (ICU, Bichat Hospital, Paris, France); Pascal Andreu (CHU Dijon, Dijon, France); Laurent Argaud (Medical ICU, Hospices Civils de Lyon, Lyon, France); Claire Ara‐Somohano (Medical ICU, University Hospital, Grenoble, France); Elie Azoulay (Medical ICU, Saint Louis Hospital, Paris, France); François Barbier (medical‐surgical ICU, Orleans, France), Déborah Boyer (ICU, CHU Rouen, France), Jean‐Pierre Bedos (ICU, Versailles Hospital, Versailles, France); Thomas Baudry (Medial ICU, Edouard Heriot hospital, Lyon France), Jérome Bedel (ICU, Versailles Hospital, Versailles, France), Julien Bohé (ICU, Hôpital Pierre Benite, Lyon France), Lila Bouadma (ICU, Bichat Hospital, Paris, France); Jeremy Bourenne (Réanimation des urgencies, Timone‐2; APHM, Marseille, France); Noel Brule (medical ICU, university hospital Nantes, France); Cédric Brétonnière (medical ICU, university hospital Nantes, France); Christine Cheval (ICU, Hyeres Hospital, Hyeres, France); Julien Carvelli (Réanimation des urgencies, Timone‐2; APHM, Marseille, France);Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, France); Elisabeth Coupez (ICU, G Montpied Hospital, Clermont‐Ferrand, France); Martin Cour Medial ICU, Edouard Heriot hospital, Lyon France), Michael Darmon (ICU, Saint Etienne Hospital, Saint Etienne, France); Etienne de Montmollin (Bichat hospital and UMR 1137 Inserm –Paris Diderot university IAME, F75018, Paris, France), Loa Dopeux (ICU, G Montpied Hospital, Clermont‐Ferrand, France); Anne‐Sylvie Dumenil (Antoine Béclère Hospital, Clamart, France); Claire Dupuis (Bichat hospital and UMR 1137 Inserm –Paris Diderot university IAME, F75018, Paris, France), Jean‐Marc Forel (AP HM, Medical ICU, Hôpital Nord Marseille), Marc Gainnier (Réanimation des urgencies, Timone‐2; APHM, Marseille, France), Charlotte Garret (medical ICU, university hospital Nantes, France); Steven Grangé (ICU, CHU Rouen, France), Antoine Gros (ICU, Versailles Hospital, Versailles, France), Akim Haouache (Surgical ICU, H Mondor Hospital, Creteil, France); Romain Hernu (Medical ICU, Hospices Civils de Lyon, Lyon, France); Tarik Hissem (ICU, Eaubonne, France), Vivien Hon Tua Ha (ICU, CH Meaux, France); Sébastien Jochmans (ICU, CH Melun); Jean‐Baptiste Joffredo (ICU, G Montpied Hospital, Clermont‐Ferrand, France); Hatem Kallel (ICU, Cayenne General Hospital, Cayenne, France); Guillaume Lacave (ICU, Versailles Hospital, Versailles, France), Alexandre Lautrette (ICU, G Montpied Hospital, Clermont‐Ferrand, France); Virgine Lemiale (Medical ICU, Saint Louis Hospital, Paris, France); Mathilde Lermuzeaux (ICU, Bichat Hospital, Paris, France), Guillaume Marcotte (Surgical ICU, Hospices Civils de Lyon, Lyon, France); Jordane Lebut (ICU, Bichat Hospital, Paris, France); Maxime Lugosi (Medical ICU, University Hospital Grenoble, Grenoble, France); Eric Magalhaes (ICU, Bichat Hospital, Paris, France), Sibylle Merceron (ICU, Versailles Hospital, Versailles, France), Bruno Mourvillier (ICU, Bichat Hospital, Paris, France); Benoît Misset (ICU, Saint‐Joseph Hospital, Paris, France and Medical ICU CHU Rouen, France); Bruno Mourvillier (ICU, Bichat Hospital, Paris, France); Mathilde Neuville (ICU, Bichat Hospital, Paris, France), Laurent Nicolet (medical ICU, university hospital Nantes, France); Johanna Oziel (Medico‐surgical ICU, hôpital Avicenne APHP, Bobigny, France), Laurent Papazian (Hopital Nord, Marseille, France), Benjamin Planquette (pulmonology ICU, George Pompidou hospital Hospital, Paris, France); Jean‐Pierre Quenot (CHU Dijon, Dijon, France); Aguila Radjou (ICU, Bichat Hospital, Paris, France), Marie Simon (Medial ICU, Edouard Heriot hospital, Lyon France), Romain Sonneville (ICU, Bichat Hospital, Paris, France), Jean Reignier (medical ICU, university hospital Nantes, France); Bertrand Souweine (ICU, G Montpied Hospital, Clermont‐Ferrand, France); Carole Schwebel (ICU, A Michallon Hospital, Grenoble, France); Shidasp Siami (ICU, Eaubonne, France); Roland Smonig (ICU, Bichat Hospital, Paris, France); Gilles Troché (ICU, Antoine Béclère Hospital, Clamart, France); Marie Thuong (ICU, Delafontaine Hospital, Saint Denis, France); Guillaume Thierry (ICU, Saint‐Louis Hospital, Paris, France); Dany Toledano (ICU, Gonesse Hospital, Gonesse, France); Guillaume Van Der Meersch, Medical Surgical ICU, university hospital Avicenne), Marion Venot (Medical ICU, Saint Louis Hospital, Paris, France); Olivier Zambon (medical ICU, university hospital Nantes, France).
Study Monitors: Julien Fournier, Caroline Tournegros, Stéphanie Bagur, Mireille Adda, Vanessa Vindrieux, Sylvie de la Salle, Pauline Enguerrand, Loic Ferrand, Vincent Gobert, Stéphane Guessens, Helene Merle, Nadira Kaddour, Boris Berthe, Samir Bekkhouche, Kaouttar Mellouk, Mélaine Lebrazic, Carole Ouisse, Diane Maugars, Christelle Aparicio, Igor Theodose, Manal Nouacer, Veronique Deiler, Myriam Moussa, Atika Mouaci, Nassima Viguier, Fariza Lamara and Sophie Letrou.