==== Front Crit Care Critical Care 1364-8535 1466-609X BioMed Central London 3402 10.1186/s13054-020-03402-7 Research Impact of advance directives on the variability between intensivists in the decisions to forgo life-sustaining treatment Smirdec Margot 1 Jourdain Mercé 2 Guastella Virginie 3 Lambert Céline 4 Richard Jean-Christophe 5 Argaud Laurent 6 Jaber Samir 7 Klouche Kada 8 Medard Anne 9 Reignier Jean 10 Rigaud Jean-Philippe 11 Doise Jean-Marc 12 Chabanne Russell 13 Souweine Bertrand 14 Bourenne Jeremy 15 Delmas Julie 16 Bertrand Pierre-Marie 17 Verdier Philippe 18 Quenot Jean-Pierre 19 Aubron Cecile 20 Eisenmann Nathanael 21 Asfar Pierre 22 Fratani Alexandre 23 Dellamonica Jean 24 Terzi Nicolas 25 Constantin Jean-Michel 26 Van Lander Axelle 2728 Guerin Renaud 29 Pereira Bruno 4 http://orcid.org/0000-0003-4545-7461Lautrette Alexandre alautrette@chu-clermontferrand.fr 213031 1 grid.411163.00000 0004 0639 4151Department of Anaesthesiology and Critical Care Medicine, Estaing Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France 2 grid.503422.20000 0001 2242 6780INSERM U1190, CHU Lille, Department of Critical Care Medicine, Roger Salengro Hospital, Univ. Lille, 59000 Lille, France 3 grid.411163.00000 0004 0639 4151Palliative Care Unit, Louise Michel Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France 4 grid.411163.00000 0004 0639 4151Biostatistics Unit (DRCI), University Hospital of Clermont-Ferrand, Clermont-Ferrand, France 5 grid.413852.90000 0001 2163 3825Medical Intensive Care Unit, La Croix Rousse Hospital, University Hospital of Lyon, Lyon, France 6 grid.413852.90000 0001 2163 3825Medical Intensive Care Unit, Edouard Herriot Hospital, University Hospital of Lyon, Lyon, France 7 grid.157868.50000 0000 9961 060XDepartment of Anaesthesiology and Critical Care Medicine, Saint Eloi Hospital, University Hospital of Montpellier, Montpellier, France 8 grid.157868.50000 0000 9961 060XMedical Intensive Care Unit, Lapeyronnie Hospital, University Hospital of Montpellier, Montpellier, France 9 grid.411163.00000 0004 0639 4151Cardiac Surgery Intensive Care Unit, Department of Anaesthesiology and Critical Care Medicine, Montpied Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France 10 grid.277151.70000 0004 0472 0371Medical Intensive Care Unit, Hotel-Dieu Hospital, University Hospital of Nantes, Nantes, France 11 Intensive Care Unit, Pasteur Hospital, Hospital of Dieppe, Dieppe, France 12 Intensive Care Unit, Morey Hospital, Hospital of Chalon-Sur-Saône, Chalon-sur-Saône, France 13 grid.411163.00000 0004 0639 4151Neurocritical Care Unit, Department of Anaesthesiology and Critical Care Medicine, Montpied Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France 14 grid.411163.00000 0004 0639 4151Medical Intensive Care Unit, Montpied Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France 15 grid.414336.70000 0001 0407 1584Emergency Intensive Care Unit, La Timone Hospital, University Hospital of Marseille, Marseille, France 16 Intensive Care Unit, Puel Hospital, Hospital of Rodez, Rodez, France 17 Intensive Care Unit, Veil Hospital, Hospital of Cannes, Cannes, France 18 Intensive Care Unit, Hospital of Montluçon, Montluçon, France 19 grid.31151.37Medical Intensive Care Unit, Mitterrand Hospital, University Hospital of Dijon, Dijon, France 20 grid.6289.50000 0001 2188 0893Medical Intensive Care Unit, Centre Hospitalier Universitaire de Brest, Université de Bretagne Occidentale, Brest, France 21 grid.418113.e0000 0004 1795 1689Intensive Care Unit, Centre Jean Perrin, 54 Rue Montalembert, BP69, 63003 Clermont-Ferrand, Cedex 1, France 22 grid.411147.60000 0004 0472 0283Medical Intensive Care Unit, Larrey Hospital, University Hospital of Angers, Angers, France 23 grid.50550.350000 0001 2175 4109Intensive Care Unit, Department of Anaesthesiology and Critical Care Medicine, Saint-Louis Hospital, Assistance Publique Hopitaux de Paris, Paris, France 24 grid.410528.a0000 0001 2322 4179Medical Intensive Care Unit, l’Archet Hospital, University Hospital of Nice, Nice, France 25 grid.410529.b0000 0001 0792 4829Medical Intensive Care Unit, Michallon Hospital, University Hospital of Grenoble, Grenoble, France 26 grid.462844.80000 0001 2308 1657GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France 27 grid.494717.80000000115480420UPU ACCePPt, Université Clermont Auvergne, Clermont-Ferrand, France 28 grid.493090.70000 0004 4910 6615EA-481, Laboratoire de Neurosciences, UBFC, Besançon, France 29 grid.411163.00000 0004 0639 4151Intensive Care Unit, Department of Anaesthesiology and Critical Care Medicine, Estaing Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France 30 grid.494717.80000000115480420LMGE «Laboratoire Micro-Organismes: Génome Et Environnement», UMR CNRS 6023, Clermont-Auvergne University, Clermont-Ferrand, France 31 Intensive Care Medicine, Montpied Teaching Hospital, 54 Rue Montalembert, BP69, 63003 Clermont-Ferrand, Cedex 1, France 2 12 2020 2 12 2020 2020 24 67227 8 2020 20 11 2020 © The Author(s) 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. Methods We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients’ characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). Results A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain. Conclusions ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist’s decision took priority. Further research is needed to improve the matching of the physicians’ decision with the patient’s wishes. Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530. Keywords Advance directivesDecisions to forgo life-sustaining treatmentICUissue-copyright-statement© The Author(s) 2020 ==== Body Background A decision to forgo life-sustaining treatment (DFLST) is made by 3–30% of intensive care unit (ICU) patients and is recorded in 90% of decedent patients [1]. The DFLST includes decisions about no-escalation or withholding or withdrawal of treatment that lead to differences in mortality [2]. These decisions are made by the patient, the physician or close relatives, or result from a shared decision-making process. However, there are numerous limitations to this process. A DFLST made by the family can be influenced by their preferences [3] or by the psychological symptoms associated with ICU admission such as anxiety/depression and post-traumatic stress disorder, which prevent the patient’s wishes being clearly reported [4]. In addition, misperceptions about the patient’s prognosis by the surrogate can lead to differing expectations by physicians and family and delay decision-making [5, 6]. When making a DFLST, physicians are greatly influenced by their personal characteristics including religion and culture [7, 8], which results in considerable variability in their decisions [7, 9]. This variability is constant within the same specialty or structure [10–14]. Patients want physicians to follow their wishes [15], but most ICU patients are not able to properly communicate these wishes because they lack decision-making capacity. Advance directives (ADs) give incapacitated patients the opportunity to indicate what treatment they wish to have [16]. There is a worldwide consensus that physicians should respect the patient’s ADs [17]. In a given setting, when the respect of the patient’s wishes has priority over the personal opinion of the physician, ADs could lead to a decrease in variability in DFLSTs among physicians. However, there is no discussion between the patient and the physician to explain the wishes expressed in ADs. As a result, the physician may interpret the patient’s wishes differently from what was intended. Our study assessed whether ADs, drawn up by patient after receiving information about DFLSTs and viewing a related video with an intensivist-investigator, would reduce variability in DFLST between intensivists compared to decision-making without ADs. The other aim of the study was to identify the factors associated with DFLSTs or with change in DFLSTs when ADs were available. Methods We conducted a multicenter, prospective, simulation study, in France from September 2017 to March 2018. The study was approved by the local French ethics committee (Comité de Protection des Personnes Sud-Est VI de Clermont-Ferrand (IRB00008526; No. 2016/CE87). A consent form was collected from all participants (patients and intensivists) after they had been informed orally and received a written information form. The study was registered on the ClinicalTrials.gov website under number: NCT03013530 in January 2017 and complied with the guidelines of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) [18]. Patients and advance directives The patients participating in the study were selected from the cohort of consecutive outpatients seen during January–March 2017 for follow-up of chronic disease in the cardiology, pulmonology or nephrology departments of the University Hospital of Clermont-Ferrand. The patient selection criteria were severe stage of chronic cardiac or kidney or respiratory failure associated with comorbid conditions, and life expectancy of less than 5 years according to McCabe score [19], but without acute episode or cognitive impairment on the basis of criteria described by Appelbaum [20]. Of the 23 patients selected, 1 died before the meeting with the intensivist-investigator, 1 was transferred to the palliative care unit, 13 declined and 8 accepted to participate in the study. The characteristics of the 8 patients are shown in Additional file 1. One intensivist-investigator (MS) met each of the eight patients at their home or at a hospital office to provide personalized, clear and full information about DFLSTs and ADs using a video and to suggest that they draw up ADs. The intensivist-investigator had 5 years of ICU practice experience and a master’s diploma in ethics. She was trained in communication skills and in face-to-face conversation about ADs. The video, which lasted 10 min, explained ICU life-sustaining treatment, DFLSTs, and the objectives of ADs as laid out in the guidelines of the French Health Authority. During the meeting, the AD forms of the French Health Authority were given to the patient, who had the opportunity to ask questions about DFLSTs, ADs or end-of-life. The patients were then asked questions to check they had understood the information given. The AD forms comprise 11 pages in which patients can designate a surrogate, express their wishes about life-sustaining treatments in the free-text boxes and 15 pages of guidelines about the writing of wishes, and the use of ADs by physicians in accordance with the French law of 2016 [21], which requires physicians to comply with the patients’ wishes except if the ADs are obviously inappropriate [22]. At the end of the meeting, the patients were invited to draw up their ADs or to take time to discuss with relatives. One patient made a second meeting with the intensivist-investigator to ask further questions. The median time of the meetings was 85.6 [60; 120] min. The ADs were returned within 1 month of the meeting. Study procedure Two clinical scenarios were created by a multidisciplinary team made up of two physicians in palliative care and three intensivists who did not participate in the study. Scenario 1 was followed by six questions and Scenario 2 by four, and both investigated the use of life-sustaining treatment (ICU admission, intubation, renal replacement therapy, vasoactive drugs, tracheotomy) for community-acquired pneumonia with septic shock and for septic shock after gastrointestinal surgery, respectively (see Additional file 2). The possible replies were “yes” or “no” for six questions and “yes” or “partially” or “no” for four questions. The replies were rated 1, 0.5 or 0 if they corresponded to a DFLST, a partial DFLST or no DFLST, respectively. The sum of these ten replies made up a DFLST score ranging from 0 if there was no DFLST to 10 if there was DFLST for all questions. The two scenarios were submitted online to intensivists from 27 French ICUs in 14 university hospitals and in 9 general hospitals. Each intensivist independently and anonymously completed the questionnaires of the two scenarios for each of eight patients with only the patient’s characteristics available (round 1) and then with the same characteristics and the patient’s ADs available (round 2). Round 2 was submitted to intensivists 2 weeks after completion of round 1 (see Additional file 3). Statistical analysis The primary endpoint was variability in DFLSTs between intensivists when ADs were available (round 2) and when they were not (round 1) expressed as the relative standard deviation (RSD; range 0–1; a high rate indicates high inter-intensivist variability). The second endpoint was the identification of factors associated with the DFLSTs or with changes in DFLSTs when ADs were provided. The patient characteristics given to intensivists for the two rounds were age, sex, housing, relatives, medical history, comorbid conditions defined as all diseases or trauma current or previous with the stage or complications reported by the patient or retrieved from medical chart, treatments and dependence in activities of daily living [23]. The recorded characteristics of the intensivists were age, sex, status of intensivist, length of practical experience, speciality of anesthesiology and critical care, religion, interest in ethics, traumatic experience of an end-of-life situation, type of hospital, type of ICU, number of beds and number of intensivists in the ICU, DFLST protocol available in ICU and number of DFLSTs per week. The number of patients participating in the study was fixed according to the feasibility of answering 20 questions per patient for each round and the case-mix. The sample size of intensivists was fixed to assess how ADs affected the change in variability between intensivists in the DFLSTs. We calculated that at least 120 intensivists evaluating eight patients were necessary to show a 20% relative difference of variability (sample size for a two-sample standard deviations F test), for a two-sided type I error at 5%, a statistical power of 90% and an intra-class correlation coefficient at 0.5, i.e., 960 DFLST scores per round. All statistical analyses were performed with Stata software (version 15, StataCorp, College Station USA, TX). Continuous data were expressed, according to statistical distribution, as mean and standard-deviation or median and interquartile range. The assumption of normality was studied using the Shapiro–Wilk test. Changes in DFLSTs were compared between rounds 1 and 2 with random-effects models taking into account between and within intensivist variability (intensivists as random-effect). Pitman’s test was used to compare RSD. The agreement on DFLSTs between intensivists (inter-agreement) and the within intensivists agreement (intra-agreement) on DFLSTs between the two rounds for each patient were studied using intra-class correlation coefficient (ICC) estimated by the mixed models mentioned above. ICC was interpreted according to standard recommendations: < 0.2 (negligible agreement), 0.20–0.39 (weak agreement), 0.40–0.59 (moderate agreement), 0.60–0.79 (good agreement) and ≥ 0.8 (excellent agreement). To determine the characteristics of the ICU physicians associated with DFLSTs in round 1 or with the change in DFLSTs when ADs were provided, random-effects models (i.e., linear mixed models) were carried out with the following parameters as fixed covariates: age, sex, status of intensivist, type of hospital, type of ICU, length of practice and religion. The session effect associated with the two measurement times was studied in the same way. The results are expressed in terms of standardized mean differences and 95% confidence intervals. All analyses were performed with a two-sided type I error of 5%. No missing data were observed. To evaluate the representativeness of the participating intensivists, a sensitivity analysis was performed to compare their characteristics with those of the non-participating intensivists. Non-participating intensivists were intensivists contacted but who did not reply to all the questions of the two rounds. A qualitative analysis of ADs was made by a multidisciplinary team composed of two intensivists, one psychologist, one physician in palliative care and two biostatisticians using Alceste software (IMAGE, CNRS, France). Results Of the 170 intensivists contacted, 123 from 27 ICUs completed the two rounds and made up the study population. Their demographic characteristics are given in Table 1. There was no difference between the study population and non-participating intensivists. A total of 19,680 intensivists’ decisions from the two rounds were analyzed.Table 1 Characteristics of intensivists Variable Intensivists contacted n = 170 Participating intensivists n = 123 Non-participating intensivists n = 47 p value Male gender, n (%) 113 (63.8) 84 (68.3) 26 (55.3) 0.11 Age (years), mean ± sd 39.9 ± 8.5 40.0 ± 8.5 39.8 ± 8.6 0.88 Status of intensivist, n (%)  Assistant 37 (21.8) 24 (19.5) 13 (27.7)  Senior 105 (61.8) 78 (63.4) 27 (57.5) 0.51  Professor 28 (16.4) 21 (17.1) 7 (14.8) Length of overall professional experience (years), median [IQR] 6 [3; 15] 7 [3; 15] 6 [3; 15] 0.61  < 5 years, n (%) 60 (35.3) 43 (35.0) 17 (36.2)  5–15 years, n (%) 73 (42.9) 50 (40.6) 23 (48.9) 0.37  > 15 years, n (%) 37 (21.8) 30 (24.4) 7 (14.9) Specialty of anesthesiology and critical care 101 (59.4) 73 (59.3) 28 (59.6) 0.98 Religion, n (%)  Catholic 66 (38.8) 47 (38.2) 19 (40.4)  Protestant 5 (2.9) 4 (3.3) 1 (2.1)  Islam 5 (2.9) 3 (2.4) 2 (4.3) 0.74  Other 10 (5.9) 9 (7.3) 1 (2.1)  None 84 (49.5) 60 (48.8) 24 (51.1) Intensivists with an interest in ethics, n (%) 127 (74.7) 90 (73.2) 37 (78.7) 0.56 Intensivists with a traumatic experience of an EOL situation, n (%) 79 (46.5) 57 (46.3) 22 (46.8) 0.96 ICU in university hospital, n (%) 128 (75.3) 94 (76.4) 34 (72.3) 0.58 Type of ICU, n (%)  Medical 72 (43.1) 52 (43.0) 20 (43.5)  Surgery 20 (12.0) 14 (11.6) 6 (13.0) 0.96  Mixed 75 (44.9) 55 (44.4) 20 (43.5) Number of beds in ICU, median [IQR] 15 [10;18] 15 [10;18] 13 [10; 18] 0.19 Number of intensivists in ICU, median [IQR] 7 [5;10] 7 [5;10] 7 [5;8] 0.09 DFLST Protocol available in ICU, n (%) 112 (65.9) 77 (62.6) 35 (74.5) 0.14 Number of DFLST performed in ICU, n (%)  < 1/week 75/158 (47.5) 53/119 (44.5) 22/39 (56.4) 0.20 DFLST decision to forgo life-sustaining treatment, EOL end-of life, ICU intensive care unit, IQR interquartile range Impact of ADs on the DFLSTs and on the variability in DFLSTs The proportions of DFLSTs for rounds 1 and 2 are shown in Fig. 1a, b.Fig. 1 Proportions of DFLSTs in round 1 (a) and round 2 (b). Legend: Black bars correspond to DFLSTs; Gray bars correspond to partial DFLSTs; White bars correspond to no-DFLSTs. S1: Scenario 1; S2: scenario 2; Q: Question The DFLST score was higher with ADs (round 2) than without ADs (round 1) (6.02 95%CI [5.85; 6.19] vs 4.92 95%CI [4.75; 5.10], p < 0.001) (Table 2). There was no significant change in inter-intensivists variability when ADs were provided (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84) (Table 2). In three patients, the RSD decreased but remained high (Table 2). Inter-intensivists agreement on DFLSTs was moderate (ICC = 0.42) without ADs (round 1) and weak (ICC = 0.28) with ADs (round 2). Intra-intensivists agreements on DFLSTs between the two rounds ranged from weak (ICC = 0.22) to moderate (ICC = 0.56) (Table 2).Table 2 Variability in the DFLST scores (RSD) and the within intensivist agreements (ICC) DFLST score ICC for intensivists Median [95% CI] RSD Round 1 Round 2 p value Round 1 Round 2 p value Patient #1 5.63 [5.20; 6.06] 7.04 [6.62; 7.47] < 0.001 0.43 0.34 0.82 0.48 Patient #2 4.18 [3.84; 4.52] 6.31 [5.86; 6.75] < 0.001 0.46 0.4 0.003 0.22 Patient #3 4.69 [4.29; 5.08] 5.97 [5.53; 6.42] < 0.001 0.47 0.42 0.18 0.47 Patient #4 2.86 [2.54; 3.18] 3.84 [3.45; 4.22] < 0.001 0.61 0.56 0.035 0.25 Patient #5 4.70 [4.25; 5.14] 5.81 [5.43; 6.19] < 0.001 0.53 0.36 0.08 0.38 Patient #6 8.37 [8.02; 8.71] 8.16 [7.76; 8.55] 0.237 0.23 0.27 0.13 0.56 Patient #7 2.42 [2.12; 2.73] 3.72 [3.30; 4.14] < 0.001 0.71 0.63 < 0.001 0.24 Patient #8 6.54 [6.14; 6.95] 7.32 [6.88; 7.76] 0.001 0.35 0.34 0.44 0.37 All patients 4.92 [4.75; 5.10] 6.02 [5.85; 6.19] < 0.001 0.56 0.46 0.84 0.56 CI confidence interval, DFLST decision to forgo life-sustaining treatment, RSD relative standard deviation, ICC: intra-class correlation coefficient Identification of factors associated with the DFLSTs and with the change in DFLSTs when ADs were available In the univariate analyses of the overall data of the eight patients, no factor associated with the DFLST score in round 1 or with the change in the DFLST score when ADs were available was identified (Table 3).Table 3 Univariate analysis for the identification of factors associated with the DFLSTs and with the change in DFLSTs when advance directives were available Variable DFLST score in round 1 Mean ± SD Correlation coefficient p value Change in DFLST score between round 1 and round 2 Mean ± SD Correlation coefficient p value Gender  Female 5.06 ± 2.72 0.42 1.09 ± 2.48 0.96  Male 4.86 ± 2.80 1.10 ± 2.43 Age (years) 0.035 0.46 0.027 0.57 Status of intensivist  Assistant 4.91 ± 2.91 0.74 0.98 ± 2.48 0.79  Senior 4.98 ± 2.74 1.15 ± 2.42  Professor 4.74 ± 2.73 1.06 ± 2.53 Length of overall professional experience  < 5 years 4.86 ± 2.81 0.23 1.18 ± 2.45 0.42  5–15 years 4.77 ± 2.72 0.94 ± 2.33  > 15 years 5.27 ± 2.79 1.23 ± 2.63 Specialty of anesthesiology and critical care  Yes 4.98 ± 2.76 0.62 1.09 ± 2.46 0.75  No 4.86 ± 2.81 1.15 ± 2.42 Religion  Catholic 4.94 ± 2.74 0.74 1.18 ± 2.37 0.78  Protestant 4.75 ± 2.61 0.78 ± 1.90  Islam 4.06 ± 2.58 0.73 ± 2.97  Other 4.68 ± 3.06 0.79 ± 2.75  None 5.00 ± 2.77 1.12 ± 2.46 Intensivists with an interest in ethics  Yes 5.01 ± 2.80 0.22 1.14 ± 2.49 0.52  No 4.69 ± 2.70 0.99 ± 2.34 Intensivists with a traumatic experience of an EOL situation  Yes 4.79 ± 2.73 0.27 1.27 ± 2.44 0.09  No 5.04 ± 2.80 0.95 ± 2.45 Hospital type  General 4.74 ± 2.93 0.37 1.33 ± 2.43 0.18  University 4.98 ± 2.72 1.03 ± 2.45 Type of ICU  Medical 4.99 ± 2.81 1.12 ± 2.37  Surgery 4.81 ± 2.82 0.89 0.56 ± 2.67 0.14  Mixed 4.90 ± 2.73 1.19 ± 2.45 Number of beds in ICU 0.062 0.61 − 0.10 0.12 Number of intensivists in ICU 0.018 0.87 − 0.05 0.28 DFLST Protocol available in ICU  Yes 5.05 ± 2.80 0.16 1.10 ± 2.37 0.92  No 4.71 ± 2.72 1.11 ± 2.57 Number of DFLST performed in ICU  < 1/week 4.70 ± 2.84 0.12 1.15 ± 2.62 0.75  ≥ 1/week 5.07 ± 2.69 1.08 ± 2.26 DFLST decision to forgo life-sustaining treatment, EOL end-of life, ICU intensive care unit, SD standard deviation Qualitative analysis of ADs A qualitative analysis of ADs was performed on the verbatim texts amounting to 4091 words. Three themes, accounting for 59% of the words, emerged from the ADs: (1) wills of end-of-life and relatives, (2) unwanted things including therapeutic obstinacy and (3) fear of pain and loss of autonomy (Fig. 2). The most frequently occurring words were “life,” “I” and “my.” The word “death” was never stated. The patients expressed themselves in articulate well-structured sentences.Fig. 2 Main themes emerging from the advance directives Discussion Our results show that when provided with ADs, intensivists made more DFLSTs but this did not alter the great variability between them in their decisions. No factor associated with this variability was identified, suggesting multiple causes that were non-specific to the characteristics of the intensivists. In addition, the qualitative analysis of ADs highlighted the concerns expressed by the patient after they had received full and clear information about DFLST from an intensivist. These results are noteworthy because they show the limitations of the use of ADs. This study highlights the issue of variability between intensivists in the taking of DFLSTs even when ADs are provided. Great variability has been previously reported in several studies [12, 13, 24–27] and attributed to individual physician characteristics such as religion, culture and geographic regions [7, 8]. The goal of ADs is to enable physicians to comply with the patient’s wishes or request, irrespective of their own personal characteristics [15, 16]. In theory, therefore, ADs should eliminate variability but our findings showed that physicians disagreed about DFLSTs even when ADs were available. There are several possible explanations of this finding. First, the intensivists did not use the ADs to make DFLSTs. However, DFLSTs increased when ADs were available. Second, ADs expressed in free-text boxes led to more possible interpretations of patients’ wishes than ADs drawn up in tick-box form, which includes the use of medical terms for instructions that are easily understood by intensivists and provide clear answers to DFLSTs [28]. In studies assessing the interrater reliability for each section of the POLST form using a binary “yes/no” approach, the Κappa coefficients varied from 0.70 to 1.00 [29]. It is possible that the variability among intensivists is low in the binary “yes/no” approach of DFLSTs wishes. However, the possible replies in our study were “yes,” “no” and sometimes “partial.” Our study differs from these previous reports by the number of questions and the size of the study population, which ensure the robustness of the findings. A DFLST is a complex but singular process in which the context, the chances of success, the discomfort of treatment, uncertainty regarding prognosis, potential disability and the wishes of the patient are important considerations [30]. ADs with free-text boxes do not allow an exhaustive approach that encompasses in all situations, but give patients the opportunity to express their convictions about the physical or mental impairment [31] that could guide intensivists in their choice of DFLSTs. However, the wording used by the patient can be ambiguous or inappropriate to initiate or to withdraw treatment. The applicability of wishes expressed in ADs results from a match between a hypothetical situation and the medical situation affecting the patient [32]. In our study, the ADs rarely indicated specific wishes about life-sustaining treatments despite information about ICU treatments. This finding could explain the lack of impact of ADs on the high variability between intensivists in the DFLSTs. In this qualitative approach, the influence of relatives or physicians was not assessed. Study of these other areas could improve understanding of the drawing-up, acceptability and usefulness of ADs. The two forms of ADs are complementary and can be associated. After receiving full information during discussion with a healthcare agent, the patient could complete tick-boxes indicating clear DFLSTs that can be implemented whatever the situation and use free-text boxes to express values that could help guide the physician in making DFLSTs in situations not previously considered. The decision about resuscitation status is easily made by the patient and can be registered in a tick-box. In contrast, the initiation of renal replacement therapy is an abstract concept that is discussed according to clinical condition and for which the expression of value is more relevant. The surrogate can add nuances and clarifications to the values relayed in ADs so that the best decisions are made according to the specific condition and prognosis of the patient [33]. A surrogate involved in the drafting of values could limit the influence of the intensivist in the decision-making process using ADs [34]. Alternatively, the physician’s interpretation of values could be assessed in clinical scenarios. Feedback on DFLSTs made by a sample of intensivists in clinical scenarios would allow the patient to modify ADs so that the intensivists’ decisions comply with her or his own and thereby reduce inter-intensivist variability. Our study has a number of limitations. First, our analyses were performed on the ADs of eight patients. This sample, in agreement with the study feasibility assessment, is not an exhaustive representation of the French population. Nevertheless, the ADs in the study were real documents, which could be used in the decision-making process in clinical practice [35]. Second, to standardize the process, only one intensivist-investigator briefed the patients about DFLSTs and ADs. However, this approach entails the risk of personal influence by the clinician, which can lead to cognitive bias. Third, we do not rule out that the DFLSTs made by intensivists in the scenarios could differ from those taken in everyday practice. However, only a simulation study provides the standardization of situations, which allows assessment of variability between physicians. Our simulation study was time-consuming and unpaid, which could have restricted the participation of some intensivists. The intensivists taking part may have had an interest in ethics and hence were perhaps not representative of the profession as a whole. Fourth, our study design gave no information about family and ICU team discussions or staff opinion. Many DFLSTs are made with non-intensivist physicians, relatives or nurses. Their influence on DFLSTs was not assessed in our study, which focused on the intensivists because they are the main decision-makers for DFLST in the ICU. Fifth, most ADs were collected within 1 month of a single meeting which for some patients could have been too short time to formulate their wishes in full. However, the information about ADs, given by an intensivist-investigator with a video, was of a quality as high as that provided in clinical practice [36] and similar to that used in reference publications [33, 37]. Conclusions Our study shows that when ADs were available, intensivists were more likely to make DFLSTs. However, ADs did not reduce high inter-intensivist variability in the decision-making process. The great variability observed show that the intensivist’s preferences had priority. Further research is needed to establish a process that achieves a better matching of the physicians’ decisions with the patient’s wishes. Supplementary Information Additional file 1. Characteristics of the 8 patients who wrote advance directives (table). Additional file 2. The two clinical scenarios (text). Additional file 3. Flow chart and timing of the study (Figure). Abbreviations ADsAdvance directives DFLSTDecision to forgo life-sustaining treatment CIConfidence intervals ICCIntra-class correlation coefficient ICUIntensive care unit POLSTPhysician orders for life-sustaining treatment RSDRelative standard deviation Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information The online version contains supplementary material available at 10.1186/s13054-020-03402-7. Acknowledgements We are indebted to Mr. Jeffrey Watts for assistance in the preparation of the manuscript. Members of the Facing group: Geoffrey Ledoux (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation Lille); Lea Satrebuisson (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Sophie Six (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Céline Dupre (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Patrick Girardie (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Anahita Rouze (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Erika Decrucq-Parmentier (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Daniel Mathieu (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Julien Poissy (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Sébastien Préau (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Emmanuelle Jaillette (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Raphaël Favory (Centre Hospitalier Universitaire de Lille, Médecine Intensive Réanimation, Lille); Honade Yonis (Centre Hospitalier Universitaire de Lyon, Médecine Intensive Réanimation, Lyon); Romain Hernu (Centre Hospitalier Universitaire de Lyon, Médecine Intensive Réanimation, Lyon); Marie Simon (Centre Hospitalier Universitaire de Lyon, Médecine Intensive Réanimation, Lyon); Thomas Baudry (Centre Hospitalier Universitaire de Lyon, Médecine Intensive Réanimation, Lyon); Thomas Madelaine (Centre Hospitalier Universitaire de Lyon, Médecine Intensive Réanimation, Lyon); Adeline Grateau (Centre Hospitalier Universitaire de Lyon, Médecine Intensive Réanimation, Lyon); Martin Cour (Centre Hospitalier Universitaire de Lyon, Médecine Intensive Réanimation, Lyon); Gérald Chanques (Centre Hospitalier Universitaire de Montpellier, Anesthésie et Réanimation Chirurgicale, Montpellier); Julie Carr (Centre Hospitalier Universitaire de Montpellier, Anesthésie et Réanimation Chirurgicale, Montpellier); Matthieu Conseil (Centre Hospitalier Universitaire de Montpellier, Anesthésie et Réanimation Chirurgicale, Montpellier); Audrey De Jong (Centre Hospitalier Universitaire de Montpellier, Anesthésie et Réanimation Chirurgicale, Montpellier); Jean-Marc Delay (Centre Hospitalier Universitaire de Montpellier, Anesthésie et Réanimation Chirurgicale, Montpellier); Etienne Imhoff (Centre Hospitalier Universitaire de Montpellier, Anesthésie et Réanimation Chirurgicale, Montpellier); Bruno Souche (Centre Hospitalier Universitaire de Montpellier, Anesthésie et Réanimation Chirurgicale, Montpellier); Marina Thirion (Centre Hospitalier Universitaire de Montpellier, Anesthésie et Réanimation Chirurgicale, Montpellier); Aulère Buzançais (Centre Hospitalier Universitaire de Montpellier, Médecine Intensive Réanimation, Montpellier); Boris Jung (Centre Hospitalier Universitaire de Montpellier, Médecine Intensive Réanimation, Montpellier); Vincent Bruno (Centre Hospitalier Universitaire de Montpellier, Médecine Intensive Réanimation, Montpellier); Delphine Daubin (Centre Hospitalier Universitaire de Montpellier, Médecine Intensive Réanimation, Montpellier); Laura Platon (Centre Hospitalier Universitaire de Montpellier, Médecine Intensive Réanimation, Montpellier); Jean-Jacques Tudesq (Centre Hospitalier Universitaire de Montpellier, Médecine Intensive Réanimation, Montpellier); Liliane Landreau (Centre Hospitalier Universitaire de Montpellier, Médecine Intensive Réanimation, Montpellier); Henri Boby (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Nicolas Rascol (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Lucia Uta (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Vedat Eljezi (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Mélanie Chasteloux (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Nicolas Coullier (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Laurent Nicolet (Centre Hospitalier Universitaire de Nantes, Médecine Intensive Réanimation, Nantes); Charlotte Garret (Centre Hospitalier Universitaire de Nantes, Médecine Intensive Réanimation, Nantes); Noëlle Brule (Centre Hospitalier Universitaire de Nantes, Médecine Intensive Réanimation, Nantes); Agathe Delbove (Centre Hospitalier Universitaire de Nantes, Médecine Intensive Réanimation, Nantes); Maelle Martin (Centre Hospitalier Universitaire de Nantes, Médecine Intensive Réanimation, Nantes); Jean-Batptiste Lascarrou (Centre Hospitalier Universitaire de Nantes, Médecine Intensive Réanimation, Nantes); François Bougerol (Centre Hospitalier de Dieppe, Réanimation, Dieppe); Pierre-Louis Declercq (Centre Hospitalier de Dieppe, Réanimation, Dieppe); Marion Beuzelin (Centre Hospitalier de Dieppe, Réanimation, Dieppe); Jean-Pierre Eraldi (Centre Hospitalier de Dieppe, Réanimation, Dieppe); Antoine Marchalot (Centre Hospitalier de Dieppe, Réanimation, Dieppe); Thomas Poussant (Centre Hospitalier de Chalon-sur-Saône, Réanimation, Chalon-sur-Saône); Maël Hamet (Centre Hospitalier de Chalon-sur-Saône, Réanimation, Chalon-sur-Saône); Martial Delorme (Centre Hospitalier de Chalon-sur-Saône, Réanimation, Chalon-sur-Saône); Adrien Lhoumeau (Centre Hospitalier de Chalon-sur-Saône, Réanimation, Chalon-sur-Saône); Jen Darphin (Centre Hospitalier de Chalon-sur-Saône, Réanimation, Chalon-sur-Saône); Julien Pascal (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Charlotte Fernandez-Canal (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Aurélien Momon (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Julien Marin (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Laure Calvet (Centre Hospitalier Universitaire de Clermont-Ferrand, Médecine Intensive Réanimation, Clermont-Ferrand); Edouard Soum (Centre Hospitalier Universitaire de Clermont-Ferrand, Médecine Intensive Réanimation, Clermont-Ferrand); Claire Bachelier (Centre Hospitalier Universitaire de Clermont-Ferrand, Médecine Intensive Réanimation, Clermont-Ferrand); Kostas Bachoumas (Centre Hospitalier Universitaire de Clermont-Ferrand, Médecine Intensive Réanimation, Clermont-Ferrand); Thomas Godet (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Danièle Saurel (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Marie Vignaud (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Marc Gainnier (Centre Hospitalier Universitaire de Marseille, Médecine Intensive Réanimation, Marseille); Dominique Lambert (Centre Hospitalier Universitaire de Marseille, Médecine Intensive Réanimation, Marseille); Lucas Benarous (Centre Hospitalier Universitaire de Marseille, Médecine Intensive Réanimation, Marseille); Julien Carvelli (Centre Hospitalier Universitaire de Marseille, Médecine Intensive Réanimation, Marseille); Philippe Letocart (Centre Hospitalier de Rodez, Médecine Intensive Réanimation, Rodez); Arnaud Delahaye (Centre Hospitalier de Rodez, Médecine Intensive Réanimation, Rodez); Sophie Dufraisse (Centre Hospitalier de Rodez, Médecine Intensive Réanimation, Rodez); François Lenfant (Centre Hosptialier de Cannes, Médecine Intensive Réanimation, Cannes); Raphaël Chambon (Centre Hospitalier de Cannes, Médecine Intensive Réanimation, Cannes); Jerôme Bedel (Centre Hospitalier de Cannes, Médecine Intensive Réanimation, Cannes); Nicolas François (Centre Hospitalier de Montluçon, Réanimation, Montluçon); Thierry Comte (Centre Hospitalier de Montluçon, Réanimation, Montluçon); Pierre Couhault (Centre Hospitalier de Montluçon, Réanimation, Montluçon); Jean-Baptiste Roudaut (Centre Hospitalier Universitaire de Dijon, Médecine Intensive Réanimation, Dijon); Auguste Dargent (Centre Hospitalier Universitaire de Dijon, Médecine Intensive Réanimation, Dijon); Gwenaël Prat (Centre Hospitalier Universitaire de Brest, Médecine Intensive Réanimation, Brest); Vanessa Jean-Michel (Centre Hospitalier Universitaire de Brest, Médecine Intensive Réanimation, Brest); Beatrice Fourgeaud (Centre de Lutte Contre le Cancer Jean Perrin, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Charlotte Baud (Centre de Lutte Contre le Cancer Jean Perrin, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Cédric Darreau (Centre Hospitalier Universitaire de Angers, Médecine Intensive Réanimation, Angers); Pierre-Yves Olivier (Centre Hospitalier Universitaire de Angers, Médecine Intensive Réanimation, Angers); Mourad Benyamina (Centre Hosptitalier Universitaire Saint-Louis, Centre de traitement des Brûlés, Paris); François Depret (Centre Hosptitalier Universitaire Saint-Louis, Centre de traitement des Brûlés, Paris); Hervé Hyvernat (Centre Hospitalier Universitaire de Nice, Médecine Intensive Réanimation, Nice); Pierre-Eric Danin (Centre Hospitalier Universitaire de Nice, Médecine Intensive Réanimation, Nice); Nordine Ait Ben Said (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Raiko Blondonnet (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Clémence Deville (Centre Hospitalier Universitaire de Clermont-Ferrand, Nephrology, Clermont-Ferrand); Aurélien Mulliez (Centre Hospitalier Universitaire de Clermont-Ferrand, Service de Biostastistiques, Clermont-Ferrand); Pierre Cornillon (Clermont-Ferrand); David Brugnon (Centre Hospitalier Universitaire de Clermont-Ferrand, Soins palliatifs, Clermont-Ferrand); Lise Vernis (Centre Hospitalier Universitaire de Clermont-Ferrand, Anesthésie et Réanimation Chirurgicale, Clermont-Ferrand); Delphine Aguettaz (Centre Hospitalier Universitaire de Clermont-Ferrand, Cardiologie, Clermont-Ferrand); Lise Thibonnier (Centre Hospitalier Universitaire de Clermont-Ferrand, Pneumologie, Clermont-Ferrand); Hugues François (Centre Hospitalier Universitaire de Clermont-Ferrand, Pneumologie, Clermont-Ferrand); Frédérique Martins-Condé (Centre Hospitalier Universitaire de Clermont-Ferrand, Gériatrie, Clermont-Ferrand); Maeva Wongfat (Pole santé république, Néphrologie, Clermont-Ferrand); Ibrahim Moustapha (Centre Hospitalier Universitaire de Grenoble, Médecine Intensive Réanimation, Grenoble); Thibaud Pranal (Centre Hospitalier de Vichy, Réanimation, Vichy); François Brenat (Centre Hospitalier du Puy-en-Velay, Réanimation, Le Puy-en-Velay); Bertrand Combres (Centre Hospitalier d'Albi, Réanimation, Albi); Anne Veinstein (Centre Hospitalier Universitaire de Poitiers, Médecine Intensive Réanimation, Poitiers); Alexandre Boyer (Centre Hospitalier Universitaire de Bordeaux, Médecine Intensive Réanimation, Bordeaux). Authors’ contributions MS, AL and BP conceived and designed the study; MS, MJ, JCR, LA, SJ, KK, AM, JR, JPR, JMD, RC, BS, JB, JD, PMB, PV, JPQ, CA, NE, PA, AF, JD, NT, JMC and RG recruited the participants and collected the data; MS, AVL, VG, CL, RG, AL and BP analyzed and interpreted data; MS, AL and BP drafted the report and all authors contributed to review it. All authors approved the final version. All authors read and approved the final manuscript. Funding No Grant. Availability of data and materials The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethical approval and consent to participate Approved by the Institutional Review Board of the Comité Pour la Protection des Personnes Sud-Est 6 (IRB00008526; No.2016/CE87). Consent for publication Not applicable. Competing interests The others authors have no financial conflict of interest related to this study. ==== Refs References 1. Lobo SM De Simoni FHB Jakob SM Estella A Vadi S Bluethgen A Decision-making on withholding or withdrawing life support in the ICU: a worldwide perspective Chest 2017 152 321 329 10.1016/j.chest.2017.04.176 28483610 2. Lautrette A Garrouste-Orgeas M Bertrand P-M Goldgran-Toledano D Jamali S Laurent V Respective impact of no escalation of treatment, withholding and withdrawal of life-sustaining treatment on ICU patients’ prognosis: a multicenter study of the Outcomerea Research Group Intensive Care Med 2015 41 1763 1772 10.1007/s00134-015-3944-5 26149302 3. Ciroldi M Cariou A Adrie C Annane D Castelain V Cohen Y Ability of family members to predict patient’s consent to critical care research Intensive Care Med 2007 33 807 813 10.1007/s00134-007-0582-6 17361388 4. Lautrette A Peigne V Watts J Souweine B Azoulay E Surrogate decision makers for incompetent ICU patients: a European perspective Curr Opin Crit Care 2008 14 714 719 10.1097/MCC.0b013e3283196319 19005315 5. White DB Ernecoff N Buddadhumaruk P Hong S Weissfeld L Curtis JR Prevalence of and factors related to discordance about prognosis between physicians and surrogate decision makers of critically ill patients JAMA 2016 315 2086 2094 10.1001/jama.2016.5351 27187301 6. Luce JM A history of resolving conflicts over end-of-life care in intensive care units in the United States Crit Care Med 2010 38 1623 1629 10.1097/CCM.0b013e3181e71530 20512035 7. Sprung CL Cohen SL Sjokvist P Baras M Bulow H-H Hovilehto S End-of-life practices in European intensive care units: the Ethicus Study JAMA 2003 290 790 797 10.1001/jama.290.6.790 12915432 8. Sprung CL Woodcock T Sjokvist P Ricou B Bulow H-H Lippert A Reasons, considerations, difficulties and documentation of end-of-life decisions in European intensive care units: the ETHICUS Study Intensive Care Med 2008 34 271 277 10.1007/s00134-007-0927-1 17992508 9. Valley TS Admon AJ Zahuranec DB Garland A Fagerlin A Iwashyna TJ Estimating ICU benefit: a randomized study of physicians Crit Care Med 2019 47 62 68 10.1097/CCM.0000000000003473 30303839 10. Barnato AE Hsu HE Bryce CL Lave JR Emlet LL Angus DC Using simulation to isolate physician variation in intensive care unit admission decision making for critically ill elders with end-stage cancer: a pilot feasibility study Crit Care Med 2008 36 3156 3163 10.1097/CCM.0b013e31818f40d2 18936694 11. Kruser JM Aaby DA Stevenson DG Pun BT Balas MC Barnes-Daly MA Assessment of variability in end-of-life care delivery in intensive care units in the United States JAMA Netw Open 2019 2 e1917344 10.1001/jamanetworkopen.2019.17344 31825508 12. Hart JL Harhay MO Gabler NB Ratcliffe SJ Quill CM Halpern SD Variability among US intensive care units in managing the care of patients admitted with preexisting limits on life-sustaining therapies JAMA Intern Med 2015 175 1019 1026 10.1001/jamainternmed.2015.0372 25822402 13. Curtis JR Engelberg RA Teno JM Understanding variability of end-of-life care in the ICU for the elderly Intensive Care Med 2017 43 94 96 10.1007/s00134-016-4340-5 27033890 14. Wunsch H Harrison DA Harvey S Rowan K End-of-life decisions: a cohort study of the withdrawal of all active treatment in intensive care units in the United Kingdom Intensive Care Med 2005 31 823 831 10.1007/s00134-005-2644-y 15856168 15. Silveira MJ Kim SYH Langa KM Advance directives and outcomes of surrogate decision making before death N Engl J Med 2010 362 1211 1218 10.1056/NEJMsa0907901 20357283 16. Schenker Y White DB Arnold RM What should be the goal of advance care planning? JAMA Intern Med 2014 174 1093 1094 10.1001/jamainternmed.2014.1887 24861458 17. Sprung CL Truog RD Curtis JR Joynt GM Baras M Michalsen A 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 2014 190 855 866 10.1164/rccm.201403-0593CC 25162767 18. von Elm E Altman DG Egger M Pocock SJ Gøtzsche PC Vandenbroucke JP The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies Lancet Lond Engl 2007 370 1453 1457 10.1016/S0140-6736(07)61602-X 19. Jackson GG Arana-Sialer JA Andersen BR Grieble HG McCABE WR Profiles of pyelonephritis Arch Intern Med 1962 110 63 75 10.1001/archinte.1962.03620230109016 20. Appelbaum PS Clinical practice. Assessment of patients’ competence to consent to treatment N Engl J Med 2007 357 1834 1840 10.1056/NEJMcp074045 17978292 21. https://www.has-sante.fr/upload/docs/application/pdf/2016-11/da_formulaire_v2_maj.pdf 22. (2016) Ministère des Affaires Sociales et de la Santé: Arrêté du 3 août 2016 relatif au modèle de directives anticipées prévu à l’article L. 1111–11 du code de la santé publique. J Officiel 2016;0181 23. Katz S Assessing self-maintenance: activities of daily living, mobility, and instrumental activities of daily living J Am Geriatr Soc 1983 31 721 727 10.1111/j.1532-5415.1983.tb03391.x 6418786 24. Mark NM Rayner SG Lee NJ Curtis JR Global variability in withholding and withdrawal of life-sustaining treatment in the intensive care unit: a systematic review Intensive Care Med 2015 41 1572 1585 10.1007/s00134-015-3810-5 25904183 25. Alemayehu E Molloy DW Guyatt GH Singer J Penington G Basile J Variability in physicians’ decisions on caring for chronically ill elderly patients: an international study CMAJ Can Med Assoc J J Assoc Medicale Can 1991 144 1133 1138 26. Wunsch H Angus DC Harrison DA Collange O Fowler R Hoste EAJ Variation in critical care services across North America and Western Europe Crit Care Med 2008 36 2787–93 e1 9 27. Quill CM Ratcliffe SJ Harhay MO Halpern SD Variation in decisions to forgo life-sustaining therapies in US ICUs Chest 2014 146 573 582 10.1378/chest.13-2529 24522751 28. Halpern SD Small DS Troxel AB Cooney E Bayes B Chowdhury M Effect of default options in advance directives on hospital-free days and care choices among seriously ill patients: a randomized clinical trial JAMA Netw Open 2020 3 e201742 10.1001/jamanetworkopen.2020.1742 32227179 29. Lovadini GB Fukushima FB Schoueri JFL Dos Reis R Fonseca CGF Rodriguez JJC Evaluation of the interrater reliability of end-of-life medical orders in the physician orders for life-sustaining treatment form JAMA Netw Open 2019 2 e192036 10.1001/jamanetworkopen.2019.2036 30977852 30. Guidet B Hodgson E Feldman C Paruk F Lipman J Koh Y The Durban World Congress Ethics Round Table Conference Report: II. Withholding or withdrawing of treatment in elderly patients admitted to the intensive care unit J Crit Care 2014 29 896 901 10.1016/j.jcrc.2014.08.004 25216948 31. Gaster B Larson EB Curtis JR Advance directives for dementia: meeting a unique challenge JAMA 2017 318 2175 2176 10.1001/jama.2017.16473 29114779 32. Hartog CS Peschel I Schwarzkopf D Curtis JR Westermann I Kabisch B Are written advance directives helpful to guide end-of-life therapy in the intensive care unit? A retrospective matched-cohort study J Crit Care 2014 29 128 133 10.1016/j.jcrc.2013.08.024 24331948 33. Garrouste-Orgeas M Tabah A Vesin A Philippart F Kpodji A Bruel C The ETHICA study (part II): simulation study of determinants and variability of ICU physician decisions in patients aged 80 or over Intensive Care Med 2013 39 1574 1583 10.1007/s00134-013-2977-x 23765237 34. Chiarchiaro J Ernecoff NC Scheunemann LP Hough CL Carson SS Peterson MW Physicians rarely elicit critically ill patients’ previously expressed treatment preferences in intensive care units Am J Respir Crit Care Med 2017 196 242 245 10.1164/rccm.201611-2242LE 28707977 35. Council of Europe Recommendation CM/Rec(2009) 11 of the Committee of Ministers to member states on principles continuing powers of attorney and advance directives for incapacity Eur J Health Law 2010 17 205 210 10.1163/157180910X12665776638867 20443451 36. Miki R Becker CB Ide K Kawakami K Timing and facilitation of advanced directives in Japan Arch Gerontol Geriatr 2018 79 83 87 10.1016/j.archger.2018.08.003 30153604 37. Philippart F Vesin A Bruel C Kpodji A Durand-Gasselin B Garçon P The ETHICA study (part I): elderly’s thoughts about intensive care unit admission for life-sustaining treatments Intensive Care Med 2013 39 1565 1573 10.1007/s00134-013-2976-y 23765236