Withholding or withdrawal of treatment under French rules: a study performed in 43 intensive care units

Abstract

Background

In France, decisions to limit treatment fall under the Leonetti law adopted in 2005. Leading figures from the French world of politics, science, and justice recently claimed for amendments to the law, considering it incomplete. This study, conducted before any legislative change, aimed to investigate the procedural aspects of withholding/withdrawing treatment in French ICUs and their adequacy with the existing law.

Methods

The characteristics of patients qualified for a withholding/withdrawal procedure were prospectively collected in 43 French ICUs. The study period (60 or 90 days under normal operating conditions) took place in the first half of 2013.

Results

During the study period, 777 (14 %) of 5589 admitted patients and 584 (52 %) of 1132 patients dying in the ICU had their treatment withheld or withdrawn. Whereas 344 patients had treatment(s) withheld (i.e., not started or not increased if already engaged), 433 had one or more treatment(s) withdrawn. Withdrawal of treatment was applied in 156 of 223 (70 %) brain-injured patients, compared to 277 of 554 (50 %) patients with other reasons for admission (p < 0.01). At the time of the decision-making, the patient's wishes were known in 181 (23 %) of the 777 cases in one or more different way(s): 73 (9.4 %) from the patient, 10 (1.3 %) by advance directives, 10 (1.3 %) through a designated trusted person, and 108 (13.9 %) reported by the family or close relatives. An external consultant was involved in less than half of all decisions (356 of 777, 46 %). Of the 777 patients qualified for a withholding/withdrawal procedure, 133 (17 %) were discharged alive from the hospital (126 after withholding, 7 after withdrawal).

Conclusions

More than half of deaths in the study population occurred after a decision to withhold or withdraw treatment. Among patients under withholding/withdrawal procedures, brain-injured subjects were more likely to undergo a withdrawal procedure. The prevalence of advance directives and designated trusted persons was low. Because patients' preferences were unknown in more than three quarters of cases, decisions remained primarily based on medical judgment. Limitations, especially withholding of treatment, did not preclude survival and hospital discharge.

Lesieur et al. Annals of Intensive Care (2015) 5:15

DOI 10.1186/s13613-015-0056-x

http://crossmark.crossref.org/dialog/?doi=10.1186/s13613-015-0056-x&domain=pdf

Web End = Olivier Lesieur1,2*, Maxime Leloup1, Frdric Gonzalez2,3, Marie-France Mamzer2 and EPILAT study group

Abstract

Background: In France, decisions to limit treatment fall under the Leonetti law adopted in 2005. Leading figures from the French world of politics, science, and justice recently claimed for amendments to the law, considering it incomplete. This study, conducted before any legislative change, aimed to investigate the procedural aspects of withholding/withdrawing treatment in French ICUs and their adequacy with the existing law.

Methods: The characteristics of patients qualified for a withholding/withdrawal procedure were prospectively collected in 43 French ICUs. The study period (60 or 90 days under normal operating conditions) took place in the first half of 2013.

Results: During the study period, 777 (14 %) of 5589 admitted patients and 584 (52 %) of 1132 patients dying in the ICU had their treatment withheld or withdrawn. Whereas 344 patients had treatment(s) withheld (i.e., not started or not increased if already engaged), 433 had one or more treatment(s) withdrawn. Withdrawal of treatment was applied in 156 of 223 (70 %) brain-injured patients, compared to 277 of 554 (50 %) patients with other reasons for admission (p < 0.01). At the time of the decision-making, the patients wishes were known in 181 (23 %) of the 777 cases in one or more different way(s): 73 (9.4 %) from the patient, 10 (1.3 %) by advance directives, 10 (1.3 %) through a designated trusted person, and 108 (13.9 %) reported by the family or close relatives. An external consultant was involved in less than half of all decisions (356 of 777, 46 %). Of the 777 patients qualified for a withholding/ withdrawal procedure, 133 (17 %) were discharged alive from the hospital (126 after withholding, 7 after withdrawal).

Conclusions: More than half of deaths in the study population occurred after a decision to withhold or withdraw treatment. Among patients under withholding/withdrawal procedures, brain-injured subjects were more likely to undergo a withdrawal procedure. The prevalence of advance directives and designated trusted persons was low. Because patients preferences were unknown in more than three quarters of cases, decisions remained primarily based on medical judgment. Limitations, especially withholding of treatment, did not preclude survival and hospital discharge.

Keywords: Withholding treatment; Life support care; Medical futility; Prognosis; Brain injury; Advance directives

* Correspondence: mailto:[email protected]

Web End [email protected]

1Ranimation, CH Saint-Louis, 17019 La Rochelle, France

2EA 4569, Universit Paris Descartes, 75006 Paris, FranceFull list of author information is available at the end of the article

2015 Lesieur et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0

Web End =http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

RESEARCH Open Access

Withholding or withdrawal of treatment under French rules: a study performed in 43 intensive care units

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 2 of 12

Background

Several decades ago, most patients who suddenly died in the hospital underwent cardiopulmonary resuscitation before death. From the 1950s onward, the development of artificial life-sustaining and/or organ-substituting techniques delivered in intensive care units (ICUs) has shifted the definition of death from a sudden and unexpected event to a partially controlled process. Far from searching to avoid death at any cost irrespective of the ensuing living conditions, the primary goal of intensive care is to return the highest number of critically ill patients to a quality of life they would find acceptable [1]. Because interfering in the dying process is not always in the patients best interest, life-prolonging therapies may be withheld or withdrawn when they are deemed futile.

Substantial variability exists between countries, institutions, and physicians in the decision to withhold or withdraw (WhWd) life-sustaining treatment in critically ill patients [210]. At an individual level, available prognostic indexes are not accurate enough to make definite end-of-life decisions without foretelling a destiny that would become self-fulfilling (self-fulfilling prophecy) [5, 11, 12]. Moreover, withholding/withdrawal decision-making may be considered by stakeholders (patients, relatives, and caregivers) with different hopes and preferences influenced by age, gender, religion, culture, education, training, and geography [5, 10, 1320]. Legislation, case mix, availability of ICU resources, and organization of care in the institution/region may also influence physicians attitude towards end-of-life care [4, 21]. Furthermore, the lack of a consensus-based model for decision-making may favor variability in withholding/ withdrawal decisions, published guidelines mainly focusing on general principles rather than practical details [22, 23].

In France, the decision to withhold or withdraw treatment falls under the law n 2005370 of April 22, 2005 related to patients rights and to the end-of-life (so-called Leonetti law), which authorizes the withholding or withdrawal of curative therapies when deemed useless, disproportionate or to have no other effect than solely the artificial preservation of life [24]. Continuing such treatment with no hope of benefit or cure would equate to an undue therapeutic obstinacy, especially for patients who are no longer able to express their wishes. In this setting, when current or further life-sustaining treatments appear to be of no overall benefit for a patient, the law stipulates that any WhWd decision should only be made after a formal procedure of collegial deliberation [23, 24]. Obtaining an external opinion from an independent consultant is a compulsory part of the procedure. In addition to medical factors, the Leonetti law specifies that the discussion must integrate the patients wishes spontaneously expressed or written in advance directives, the

opinion of the trusted person (if appointed), and the family and/or close relatives.

Leading figures from the French world of politics, science, and law recently claimed for amendments to the law reinforcing patients rights. The aims of this prospective observational study, conducted before any legislative changes, were to investigate the incidence of withholding/withdrawal decisions in French ICUs and to evaluate how these procedures were implemented with regard to the legislation in force.

Methods

This report is a secondary analysis of a previous study designed to assess the theoretical eligibility as organ donors of patients deceased after end-of-life decisions [25]. The study was performed in 43 French ICUs (15 units in university-affiliated centers, 28 in general hospitals). The institutional review board (CPP Paris Ile de France II, IRB registration: 00001072) approved the protocol. The study period (60 or 90 consecutive days in normal operating conditions) took place during the first half of 2013. All patients admitted to the ICU who underwent a WhWd procedure according to the terms of the French Leonetti law were enrolled in the survey.

The epidemiological data recorded during the ICU stay included age, gender, medical history, reasons for admission, Simplified Acute Physiology Score (SAPS) II index [26], Knaus [27], McCabe [28], and Charlson [29] scores on admission, relevant clinical and biological characteristics, Sequential Organ Failure Assessment (SOFA) score [30] at the time of the WhWd decision, reasons for the decision, implemented measures, and outcome of the patient (deceased or discharged alive). By convention, a SOFA organ sub-score of 3 or more was considered as an organ failure. WhWd patients discharged from the ICU were followed until discharge from the hospital or death in the ward.

For WhWd patients, we analyzed how the limitations were carried out with regard to the contribution of care-givers in end-of-life decisions (including consultant physicians), patient or surrogate decision-maker involvement, and advance directives. Reasons for limiting treatment (based on items proposed by the French intensive care society [23]), participants in the decision-making process, and type of treatment withheld or withdrawn were registered by the local investigator using a form developed for this purpose.

Limitations differentially included withholding or/and withdrawing therapies like cardiopulmonary resuscitation, endotracheal intubation, ventilatory support, renal replacement therapy, inotrope use, urgent surgery, antimicrobial therapy, blood product transfusion, nutrition, and hydration. A three-level hierarchy for classifying decisions used the more active mode of limitation (stop > do not

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 3 of 12

increase > do not start) if more than one was performed. Withdrawing was defined as the decision to stop a treatment already undertaken. Withholding was defined as the decision not to start or increase a treatment beyond a critical threshold. Patients were classified as withheld (Wh) patient if withholding was the single limitation made and as withdrawn (Wd) patient if treatments were both withheld and withdrawn. Within the Wh sub-group, the patients who had one or more do not increase order(s) were compared to those exclusively qualified for do not start instruction(s).

Statistical analysis

Results are expressed as mean standard deviation (SD) or median and interquartile (IQR) for continuous variables and percentage with 95 % confidence interval (CI) for categorical variables. Simple regression analysis was used to establish the relationship between continuous variables (SAPS II, mortality rate) and the WhWd decision rates among the 43 participating ICUs. Comparisons of patients were based on t test or the MannWhitney U test for continuous variables and on chi-square (2) test or Fishers exact test for categorical variables, as appropriate. A two-tailed p value < 0.05 was considered statistically significant. We used univariate and multivariate logistic regression analyses with Wh/Wd as a binary procedural variable to assess associations with categorical variables. All relevant univariate indexes with p value less than 0.2 were included in the multivariate logistic regression model (age > 70 years, comorbidities, reasons for admission, organ failures). Descriptive statistics, univariate, and multivariate regressions were performed using Epi InfoTM

(Centers for Disease Control and Prevention, Atlanta, GA) and the R statistical package (R Core Team, R Foundation for Statistical Computing, Vienna, Austria).

Results

Study population

During the study period, 5589 patients (age: 62 17 years; gender ratio M/F: 1.6; SAPS II: 44 22) were admitted to 43 ICUs (616 beds). A total of 4457 patients (80 %) were discharged alive from the ICU. One thousand one hundred thirty-two patients (20 %) died in the ICU. The median (IQR) mortality rate across the 43 participating ICUs was 20.8 (1725) %. Over half of the deceased patients (584/1132, 52 %) underwent a formalized WhWd procedure before death.

Of the 5589 patients admitted, 777 (14 %; age: 68 14 years; gender ratio M/F: 1.8; SAPS II: 60 20; SOFA: 7 [411]) underwent Wh (344 patients, 6 %) and/or Wd (433 patients, 8 %) measures (Figs. 1 and 2). Table 1 shows the study population for each participating ICU with regard to end-of-life decisions and outcome (deceased or discharged alive). The median (IQR), minimum, and

maximum proportions of WhWd patients across the 43 ICUs were 13.2 (1019), 4, and 30 %, respectively. The proportion of WhWd patients across the 43 ICUs correlated with SAPS II (p < 0.02, Fig. 3a) and mortality rates (p < 0.001, Fig. 3b). Baseline data, reasons for admission, and outcome of the 777 WhWd patients are shown in Tables 2 (all) and 3 (separating Wh and Wd).

WhWd decision-making

Whatever the procedure (Wh or Wd), the median (IQR) time from the ICU admission to the WhWd decision was 4 (113) days. At the time of the decision-making, the patients wishes were known in 181 cases (23 %), on the basis of one or more different source(s) of information: spontaneously voiced (73 cases, 9.4 %), written in advance directives (10 cases, 1.3 %), expressed by a designated trusted person (10 cases, 1.3 %), and/or reported by the family or close relatives (108 cases, 13.9 %). An external consultant physician was involved in the decision-making process in less than half of the 777 cases (356 patients, 46 %): 142/344 (41.3 %) and 214/433 (49.4 %) cases for Wh and Wd, respectively (p < 0.05).

The rationales most often claimed to justify the WhWd decision were the following:

1) No additional information needed for decision-making: 602 patients (77 %)

2) Limited subsequent functional autonomy: 581 patients (75 %)

3) Absence of curative strategy: 559 patients (72 %)4) Non-responsive to medical therapy: 516 patients (66 %)5) Advanced or terminal stage of a severe and incurable disease: 474 patients (61 %)

6) Limited subsequent relational quality of life: 442 patients (57 %)

7) Limited functional autonomy before hospital admission: 317 patients (41 %)

8) Very advanced age: 210 patients (27 %)9) Perception of disproportionate and non-beneficial treatment voiced by patients relatives: 172 patients (22 %)

10)Wish to limit treatment voiced by patient: 110 patients (14 %)

Table 4 shows organ failures, treatment engaged, and rationales for WhWd at the time of the decision-making, separating Wh and Wd.

Implemented measures

The WhWd measures implemented are detailed in Fig. 4 separating do not start, do not increase (Fig. 4a), and stop orders (Fig. 4b). After a first WhWd order, 89 patients (11.5 %) received additional measures for limitation of therapy. Endotracheal ventilation was the life-sustaining

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 4 of 12

Fig. 1 Flow chart. WhWd withhold or withdraw treatment, ICU intensive care unit

treatment most often engaged at the time of the decision-making (375 patients) and subsequently withdrawn (227), with (147) or without (80) removal of the endotracheal tube.

Withdrawal of treatment was applied in 156 of 223 (70 %) brain-injured patients, compared to 277 of 554 (50 %) patients with other reasons for admission pooled, who had

treatment equally withheld or withdrawn (p < 0.01). WhWd patients with chronic respiratory diseases and/ or respiratory failure as reason for admission had treatment preferentially withheld than withdrawn (Table 3). For the WhWd patients classified C or D on the Knaus scale, those with cognitive impairment (Table 3), and/or those for whom limited autonomy before admission was

Fig. 2 Characteristics of patients admitted over the study period. WhWd withhold or withdraw treatment, Alive discharged alive from the ICU,

CDD circulatory determination of death, BDD brain determination of death, deceased in the ICU, M/F sex ratio, SAPS Simplified Acute Physiology

Score, LOS length of stay

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 5 of 12

Table 1 Study population in the 43 participating ICUs ICU Hospital ICU

beds,

N

1 General 12 48 58 35 10 4 (8) 1/3 1 (25)2 General 10 48 68 49 21 4 (8) 2/2 2 (50)3 General 8 49 64 45 24 2 (4) 0/2 1 (50)4 General 12 63 67 48 22 12 (19) 1/11 0 (0)5 University 9 71 52 39 17 7 (10) 0/7 0 (0)6 General 8 78 62 39 19 17 (22) 14/3 6 (35)7 General 12 83 70 47 31 25 (30) 11/14 5 (20)8 General 10 86 64 44 19 15 (17) 11/4 4 (27)9 General 8 87 66 44 20 16 (18) 14/2 4 (25)10 General 8 89 63 44 21 18 (20) 9/9 5 (28)11 University 15 96 61 44 23 12 (13) 5/7 2 (17)12 General 10 96 64 47 20 12 (13) 5/7 4 (33)13 General 12 99 61 48 21 7 (7) 1/6 1 (14)14 General 12 102 64 52 26 26 (25) 17/9 12 (46)15 University 15 106 65 48 19 21 (20) 2/19 1 (5)16 General 12 109 68 46 20 10 (9) 2/8 1 (10)17 General 17 111 61 50 30 26 (23) 15/11 10 (38)18 University 15 112 57 55 35 18 (16) 7/11 4 (22)19 University 15 118 59 46 25 20 (17) 5/15 3 (15)20 General 12 119 58 38 15 23 (19) 11/12 8 (35)21 General 10 121 60 40 17 21 (17) 14/7 3 (14)22 University 14 123 66 54 33 23 (19) 8/15 4 (17)23 University 12 125 50 26 21 17 (14) 2/15 0 (0)24 General 14 126 61 51 29 18 (14) 1/17 0 (0)25 General 12 129 63 39 21 16 (12) 3/13 2 (13)26 University 26 132 56 39 18 16 (12) 7/9 8 (50)27 General 15 132 61 49 22 10 (8) 4/6 1 (10)28 General 10 135 69 48 15 6 (4) 3/3 2 (33)29 General 18 135 63 51 23 27 (20) 9/18 9 (33)30 General 16 141 66 55 31 27 (19) 23/4 7 (26)31 General 12 152 65 51 31 38 (25) 23/15 14 (37)32 General 23 154 58 46 21 16 (10) 7/9 7 (44)33 University 12 156 59 40 12 20 (13) 9/11 6 (30)34 General 22 156 64 51 20 36 (23) 20/16 16 (44)35 University 15 159 58 38 14 12 (8) 9/3 2 (17)36 University 22 171 59 45 25 19 (11) 6/13 0 (0)37 University 11 181 69 28 8 9 (5) 3/6 4 (44)38 University 20 182 57 44 16 24 (13) 7/17 8 (33)39 General 18 183 65 46 23 19 (10) 8/11 2 (11)40 General 25 224 62 42 20 34 (15) 5/29 2 (6)

ICU

admissions,

N

Mean

age, years

Mean

SAPS II

In-ICU death

rate, %

Wh/Wd

patients N/N

WhWd patients, N

(% admissions)

Discharged alive from the ICU after

WhWd, N (% WhWd)

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 6 of 12

Table 1 Study population in the 43 participating ICUs (Continued)

41 General 18 240 60 41 18 28 (12) 13/15 7 (25)42 University 15 266 59 35 11 15 (6) 13/2 6 (40)43 University 24 296 61 45 13 31 (10) 14/17 9 (29) All 616 5589 777 (14) 344/433 193(25)

SAPS Simplified Acute Physiology Score, WhWd withhold or withdraw treatment, ICU intensive care unit

a rationale to justify WhWd (Table 4), treatment was more likely to be withheld than withdrawn. In a multivariate analysis, neurological (OR 4.5; 95 % CI 3.36.2), hematological(2.4; 1.34.6), renal (1.8; 1.22.6), and circulatory (1.5; 1.12.1) failures at the time of the decision were significantly associated with Wd vs Wh.

Among the 344 Wh patients, 105 only had do not start instructions prohibiting cardiopulmonary resuscitation (91), renal replacement therapy (72), inotrope use(64), endotracheal (58) or non-invasive (20) ventilation, surgery (51), blood product transfusion (35), antibiotics(17), and oxygenation (1). Compared to the 239 Wh patients who had do not start and/or do not increase instructions, these 105 patients had lower median SAPS II (49 vs 57), total SOFA score (4 vs 6), rate of respiratory (22 vs 40 %) and circulatory (17 vs 35 %) failures, and death rate (33 vs 57 %) in the ICU (p < 0.01). Conversely, chronic respiratory diseases were more frequent in this group (48 vs 33 %).

Patients outcome

Of the 4812 patients without WhWd measures, 4264 (89 %) left the ICU alive, while 548 (11 %) died in the ICU.

Of the 777 WhWd patients, 193 (25 %) survived and were discharged from the ICU, whereas 584 (75 %) died in the ICU. The median (IQR) time from withholding/ withdrawal completion to death in the ICU was 2 days (16) after withholding (172/344 deaths after Wh, 50 %), and 1 day (03) after withdrawal (412/433 deaths after

Wd, 95 %). Sixty more WhWd patients died on the ward after discharge from the ICU, which means that 133 patients (17 % of all WhWd patients) were discharged alive from the hospital (Fig. 1).

Discussion

Contrary to ethicists [21, 22, 31], many intensivists clearly distinguish between withholding and withdrawal decisions, with the former being perceived as more passive [3, 4, 10, 32, 33]. Physicians unwillingness to withdraw life-sustaining therapy has been previously associated with religion, culture, experience, and gender [14, 3337]. Rather than focusing on differences between centers, our study aimed to identify the conditions that specifically led to withdraw and/or withhold therapy. By establishing a three-level hierarchy of decisions (stop > do not increase > do not start), we demonstrated that more active limitations involved patients with acute organ failures, high severity indexes, and great dependence on life-sustaining therapy. Brain-injured patients were also more likely to undergo a withdrawal procedure, whereas patients with chronic respiratory disease, pre-existing disability affecting autonomy or cognition, and/or respiratory failure on admission had treatment preferentially withheld than withdrawn. Whatever the level of limitation applied, the patients wishes were unknown in more than three quarters of cases at the time of the decision-making. Thus, decisions to limit treatment were predominantly based on medical judgment. Amazingly, while withdrawals of life-sustaining

A B

R2 = 0.15

R2 = 0.29

Rate of WhWd patients

Mean SAPS II ICU mortality rate

Fig. 3 Relationship between SAPS II (a), mortality rate (b), and WhWd decision rate among the 43 participating ICUs. SAPS Simplified Acute Physiology

Score, WhWd withhold or withdraw treatment, ICU intensive care unit

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 7 of 12

Table 2 Baseline data of the 777 WhWd patients

Number Percent 95 % CI Knaus A 185 24 21.027.2

B 224 29 25.932.4 C 276 35.8 32.439.3 D 87 11.3 9.213.8 MD 5Mc Cabe 0 315 40.9 37.444.4

1 299 38.8 35.342.3 2 157 20.4 17.623.4 MD 6Risk factors

Hypertension 385 49.6 46.053.2 Tobacco 238 30.7 27.534.1 Diabetes 183 23.6 20.726.8 Dyslipidemia 175 22.6 19.725.7 Alcohol 159 20.5 17.723.5 Chronic diseases

Cardiac 282 36.3 32.939.8 Pulmonary 235 30.2 27.133.6 Neurological 130 16.7 14.219.6 Renal 109 14.0 11.716.7 Vascular 101 13.0 10.815.6 Hepatic 77 9.9 7.912.3 Intestinal 54 6.9 5.39.0 Neurological deficit

Cognition 94 12.1 9.914.6 Swallowing 46 5.9 4.47.9 Hemiplegia 22 2.8 1.84.3 Tetraplegia 11 1.4 0.72.6 Malignancies 221 28.4 25.331.8 Rare diseases 44 5.7 4.27.6 Reason for ICU admission

Respiratory failure 259 33.3 30.036.8 Shock and MOF 215 27.7 24.631.0 Post-cardiac arrest coma 150 19.3 16.622.3 Stroke 49 6.3 4.78.3 Head trauma 24 3.1 2.04.6 Other 80 10.3 8.312.7

WhWd withhold or withdraw treatment, ICU intensive care unit, MOF multiple organ failure, CI confidence interval, MD missing data

treatment (with hastening of death as a possible risk) were thoroughly argued, a consultant physician was involved at the level of the decision-making in less than half cases.

There is an extensive literature based on questionnaire and epidemiological surveys exploring attitudes of intensive care physicians on forgoing treatments. Influenced

by multiple factors, practices vary considerably between and within countries [3, 4, 10, 32, 3840]. Although most Western physicians consider withholding/withdrawing treatment usual, respondents to a recent multinational survey in Asia reported that they commonly withheld (70.2 %) but rarely withdrew (20.7 %) treatments [10]. In a hypothetical scenario of post-anoxic coma with septic shock, Asian physicians are less likely to withhold or withdraw life-sustaining treatments, and more likely to do everything (53.8 %) than those in Western countries (USA < 40 %, Southern Europe < 30 %, Canada < 20 %, Australia < 10 %, Northern and Central Europe < 10 %) [10, 32, 38]. In 37 ICUs from 17 European countries (20002001), Sprung found that 76 % of deaths were preceded by some kind of limitation, with a clear downward North/South tendency between regions. Amazingly, the French centers who volunteered to take part in the survey could not obtain approval from their ethics committee [3]. However, despite inter-unit variability, our data are close to those collected in 1997 by the French LATAREA group in terms of proportion of ICU patients undergoing WhWd measures (14 vs 11 %) or dying after a decision to limit life-supporting therapies (52 vs 53 %) and proportion of withholding/withdrawal decisions (41/59 vs 44/56 %) [2]. These two French surveys were completed 16 years apart, the former (LATAREA) before and the latter (EPILAT) after enactment of the Leonetti law. Considering such apparently limited impact on WhWd rates (despite the higher median age and SAPS II in our study population), one could argue that the law provided a legal framework for practices that already existed informally.

Because most patients in the ICU lack decision-making capacity, WhWd discussions are often shared between physicians, nurses, and family members or relatives acting as surrogates and representing the patients values and preferences [21]. One important finding from this study is that decisions regarding WhWd are primarily founded on medical judgment. The low level of patients being directly or indirectly involved in the decision-making (23 %) may reflect that many were unable to express their preferences once hospitalized, and/ or that they did not anticipate such conditions of being before admission. While French Parliament unanimously passed the Leonetti law in 2005 after a long and highly publicized debate, the prevalence of advance directives or designated trusted person remains low. The availability and legal value of advance directives widely differ by country and show the balance between the culture of patient autonomy and that of paternalism in medical care[41]. In a survey of US citizens aged 60 years or older who have died of any cause between 2000 and 2010, the proportion of decedents with advance directives increased from 47 % in 2000 to 72 % in 2010 [42].

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 8 of 12

A

Withheld treatment: do not start or do not increase

Do not start

Do not increase

0 300 600

Cardiopulmonary resuscitation Renal replacement therapy

Urgent surgery if needed Blood product transfusion

Inotrope use

Antibiotics Endotracheal ventilation Non-invasive ventilation

Urgent surgery needed Oxygenation

ECMO

726 590589472401

22

122

191 143

227 1729147227

326

29

64 2

Do not start and do not increase orders are expressed as numbers of patients involved (of 777 WhWd)

B

0 100 200

Endotracheal ventilation

With extubation

Inotrope use

Antibiotics Nutrition et hydratation Renal replacement therapy

Blood product transfusion

Non-invasive ventilation

Oxygenation

Withdrawn treatment

227

147

161

152

132

Stop

90

48

21

7

Stop orders are expressed as numbers of patients involved (of 433 Wd)

Fig. 4 WhWd measures implemented separating do not start, do not increase, (a) and stop (b) orders. WhWd withhold or withdraw treatment,

Wd withdraw treatment

According to the French law, the procedure should also involve an independent corroboration of the diagnosis and prognosis by an external physician who is missing in more than half the cases in our study. The rate of external corroboration is only slightly higher in case of treatment withdrawal (vs withholding). Whereas hospital specialists know best in their particular domains about the prognosis for diseases, it could be hypothesized that only skilled intensivists could assess the benefitrisk/ burden balance of life-sustaining therapies such as ventilatory support, inotrope use, renal replacement therapy, or extracorporeal oxygenator. Because many hospitals only have one ICU, referring to an independent and relevant arbitration may be challenging.

Treatment limitations in brain-injured patients differ from those applied to patients with end-stage irreversible diseases. In the former category (post-anoxic coma, stroke, head trauma), patients are rarely or never conscious at the time of the decision-making and cannot be involved in the discussion. Moreover, continuation of treatment may prolong life for months or years at the cost of being in a severely disabled state that such patients would not have accepted [41]. In our study, brain-injured patients qualified for a WhWd procedure, who empirically had the poorest ability to participate directly in decision-making, were more likely to undergo withdrawal rather than withholding of treatment compared to patients with non-neurologic diseases. By comparison,

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 9 of 12

Table 3 Baseline data and outcome of the 777 WhWd patients, separating withholding and withdrawal of treatment

Withholding, Withdrawal, pN = 344 N = 433Age (years) median (IQR) 71 (6281) 69 (6078) 0.03

Male 222 (64.5) 282 (65.1) 0.9 SAPS II median (IQR) 55 (4470.5) 62 (5075) <0.01 Knaus C and D 188 (54.7) 175 (40.4) <0.01 McCabe = 0 129 (37.5) 186 (43.0) 0.12 Charlson score 5 (36) 5 (36) 0.5 Chronic diseases:Cardiac 135 (39.2) 147 (33.9) 0.13 Pulmonary 128 (37.2) 107 (24.7) <0.01 Neurological 63 (18.3) 67 (15.5) 0.29 Renal 50 (14.5) 59 (13.6) 0.71 Vascular 43 (12.5) 58 (13.4) 0.71 Hepatic 30 (8.7) 47 (10.9) 0.32 Intestinal 26 (7.6) 28 (6.5) 0.32 Neurological deficit:Cognition 51 (14.5) 43 (9.9) 0.02 Swallowing 24 (7.0) 22 (5.1) 0.17 Hemiplegia 9 (2.6) 13 (3.0) 0.46 Tetraplegia 7 (2.0) 4 (0.9) 0.16 Malignancies 90 (26.2) 131 (30.3) 0.20 Rare diseases 17 (4.9) 27 (6.2) 0.27 Reasons for admission:Respiratory failure 139 (40.4) 120 (27.7) <0.01 Shock and MOF 90 (26.2) 125 (28.9) 0.4 Brain injury 67 (19.5) 156 (36.0) <0.01 Post-cardiac arrest 48 (14.0) 102 (23.6) <0.01 Stroke 13 (3.8) 36 (8.3) <0.01 Head trauma 6 (1.7) 18 (4.2) 0.04 Other 48 (14.0) 32 (7.4) <0.01 LOS (days) in the ICU median (IQR) 9.5 (424) 7 (317.5) <0.01 Discharge alive from the ICU 172 (50.0) 21 (4.8) <0.01 Delay WhWd to the last day in the ICU median (IQR) 3 (19) 1 (03) <0.01

Values are represented as number (%), unless stated otherwise.

WhWd withhold or withdraw treatment, SAPS Simplified Acute Physiology Score, ICU intensive care unit, MOF multiple organ failure, LOS length of stay

patients with chronic respiratory diseases, pre-existing limited autonomy, and/or respiratory failure as reason for admission had treatment preferentially withheld than withdrawn in this study. One potential explanation is that prognostic indexes based on several factors in combination may predict outcome with better accuracy in neuro-critical care than in other areas in medicine [41, 4346]. In case of brain injury, the predicted outcome measure is either death or poor functional fate. For patients with congestive cardiac failure, obstructive bronchitis, cirrhosis, kidney disease, or cancer, it is rarely

possible to prognosticate with certainty that a chronically ill subject would not survive an acute episode [47]. These patients need to undergo a time-limited trial of intensive care prior to any prognostication or WhWd decision [13, 31, 48]. However, most prediction models were not developed with the specific aim of informing end-of-life decisions [12, 41].

Limiting treatments in critically ill patients does not mean forgoing chances of survival. In the ETHICUS study, the rate of patients discharged alive from the hospital after withholding and withdrawal was 11 % (of

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 10 of 12

Table 4 Organ failures, treatment already engaged, and rationales for WhWd at the time of the decision-making, separating withholding and withdrawal of treatment

Withholding, Withdrawal, pN = 344 N = 433Total SOFA score median (IQR) 5 (39) 9 (513) <0.01

Total SOFA score 8 122 (35.5) 260 (60.0) <0.01 Total SOFA score 5 198 (57.6) 367 (84.8) <0.01 Total SOFA score 3 282 (82.0) 418 (96.5) <0.01 Respiratory failure 119 (34.6) 182 (42.0) 0.03 Neurologic failure 104 (30.2) 281 (64.9) <0.01 Circulatory failure 103 (29.9) 192 (44.3) <0.01 Hepatic failure 10 (2.9) 37 (8.5) <0.01 Hematologic failure 14 (4.1) 54 (12.5) <0.01 Renal failure 56 (16.3) 118 (27.3) <0.01 Treatments already engaged:

Endotracheal ventilation 213 (61.9) 375 (86.6) <0.01 Non-invasive ventilation 50 (27.9) 35 (17.3) <0.01 Inotrope use 107 (31.1) 206 (47.6) <0.01 Renal replacement therapy 24 (7.2) 100 (23.6) <0.01 Antibiotics 158 (45.9) 256 (59.1) <0.01 Blood product transfusion 46 (14.9) 77 (18.6) 0.11 Surgery needed 22 (6.4) 47 (10.9) 0.02 Rationales to justify WhWd:No additional information needed 246 (78.1) 356 (90.8) <0.01 Limited subsequent autonomy 252 (80.3) 329 (81.4) 0.34 Absence of curative therapy 199 (61.4) 360 (86.5) <0.01 Non-responsive to treatment 180 (56.6) 336 (83.6) <0.01 End-stage incurable severe disease 185 (58.4) 289 (73.5) <0.01 Limited subsequent relational QOL 177 (57.7) 265 (68.3) <0.01 Limited autonomy before admission 184 (55.9) 133 (33.8) <0.01 Very advanced age 101 (31.9) 109 (27.9) 0.14 Excessive treatment felt by relatives 59 (18.9) 113 (28.2) <0.01 Patients wish to limit treatment 59 (19.1) 51 (13.1) 0.02 Awareness of patients preferences 86 (25.0) 95 (21.9) 0.31 External consultant physician 142 (41.3) 214 (49.4) 0.02

Values are represented as number (%), unless stated otherwise.

SOFA sequential organ failure assessment, WhWd withhold or withdraw treatment, QOL quality of life. By convention, a SOFA organ sub-score of 3 or more was considered as organ failure

1594) and 1 % (of 1398), respectively [3]. In the French LATAREA study, 43 % of the Wh patients and 8 % of the Wd patients left the ICU alive [2]. A recent study from Norway reported a survival rate on hospital discharge of 37 and 0 % after withholding and withdrawal, respectively [49]. Our own survival rates on hospital discharge were 37 % after withholding and 2 % after withdrawal. Limitations did not solely involve patients who might die according to the physicians judgment. Even

though withholding and withdrawing therapy have been considered ethically equivalent [21, 22, 31], our survey showed that in reality the more active limitations were associated with sudden and severe pathologies and the more passive with chronic diseases affecting respiration, autonomy, or cognition. Rather than ratifying a foretold death, the intention of the withholding decision was in some circumstances to let nature take its course toward death or life while avoiding non-beneficial and burdening therapies.

The current study has several strengths. Prospectively carried out in a large number of units throughout a single country, it identified conditions specifically associated with withholding or withdrawal of treatment. Limitations of treatment were described in details separating do not start, do not increase, and stop instructions. The study also showed that the rights to dispose of ones health conferred on citizens by law (advance directives, trusted person) were under-used, and as a result, that decisions remained under physicians authority.

It also has limitations. First, it is uncertain whether the units involved in the study were representative of French practices. Second, information about sedation and anal-gesia given during the WhWd procedure (particularly Wd) was not collected. Third, neither the temporal steps of the WhWd procedure (first discussion, consensus reached within the staff, agreement obtained from families and/or relatives, implementation of the measures agreed) nor the prognostic indexes used to select patients for limitations were recorded.

Conclusions

In our study involving 43 French ICUs, more than half deaths occurred after a formal decision to withhold or withdraw therapies deemed non-beneficial. Brain-injured patients were more likely to undergo a withdrawal procedure, whereas patients with chronic respiratory disease and pre-existing disability affecting autonomy or cognition had treatment preferentially withheld than withdrawn. While the law authorizing such practices was passed in 2005, the prevalence of advance directives and designated trusted persons remains low. An external consultant was involved in less than half of all decisions. Because patients wishes are rarely known at the time of the decision-making, limitations remained primarily based on medical judgment.

AbbreviationsBDD: brain determination of death; CDD: circulatory determination of death; CI: confidence interval; FiO2: fraction of inspired oxygen; ICU: intensive care unit; IQR: interquartile; MD: missing data; OR: odds ratio; SAPS: Simplified Acute Physiology Score; SD: standard deviation; SOFA: Sequential Organ Failure Assessment; WhWd: withholding or withdrawing treatments.

Competing interestsThe authors declare that they have no competing interests.

Lesieur et al. Annals of Intensive Care (2015) 5:15 Page 11 of 12

Authors contributionsOL, ML, and MFM designed the study. OL, ML, and ESG gathered the data. OL and ML performed the statistical analysis. OL, ML, and FG wrote the manuscript. OL had full access to all the data in the study and had final responsibility for the decision to submit for publication. All authors read and approved the manuscript.

AcknowledgmentsThis study was supported by the non-profit organizations AADAIRC (Association dAide Domicile aux Insuffisants Respiratoires Chroniques) and Ouest-Transplant. The authors thank Marie-Line Cras, Nicolas Girard, and all the contributors (cited in the next paragraph) for their help in the implementation of the survey.

The EPILAT study group is composed of the following: Olivier Lesieur, Ranimation, CH Saint-Louis, 17019 La Rochelle, France; Maxime Leloup, Ranimation, CH Saint-Louis, 17019 La Rochelle, France; Frdric Gonzalez, Ranimation Mdico-Chirurgicale, CHU Avicenne, 93000 Bobigny, France; Marie-France Mamzer, EA 4569, Universit Paris Descartes, 75006 Paris, France; Olivier Baudin, Ranimation, CH dAngoulme, 16470 Saint-Michel, France; Martine Nyunga, Ranimation, CH Victor Provo, 59100 Roubaix, France; Julien Charpentier, Ranimation Mdicale, CHU Cochin, 75014 Paris, France; Jean Louis Dubost, Ranimation, CH Ren Dubos, 95300 Pontoise, France; Laurent Martin Lefevre, Ranimation, CHD, 85000 La Roche-sur-Yon, France; Frdric Guillaume, Ranimation, CH Saint-Louis, 17019 La Rochelle, France; Marina Thirion, Ranimation, CH Victor Dupouy, 95100 Argenteuil, France; Patrice Tirot, Ranimation, CH du Mans, 72037 Le Mans, France; Pascal Beuret, Ranimation, CH de Roanne, 42300 Roanne, France; Maud Jonas, Ranimation Mdicale, CHU de Nantes, 44093 Nantes, France; Mickal Moriconi, Ranimation, CH Cornouaille, 29107 Quimper, France; Jean Philippe Rigaud, Ranimation, CH de Dieppe, Dieppe 76200, France; Jean Pierre Quenot, Ranimation Mdicale, CHU de Dijon, 21000 Dijon, France; Danielle Reuter, Ranimation Mdicale, CHU Saint-Louis, 75010 Paris, France; Ren Robert, Ranimation Mdicale, CHU de Poitiers, 86021 Poitiers, France; Nicolas Pichon, Ranimation Polyvalente, CHU Dupuytren, 86042 Limoges, France; Thierry Boulain, Ranimation Mdicale, CHR dOrlans, 45000 Orlans, France; Renaud Chouquer, Ranimation, CH dAnnecy, 74374 Pringy, France; Antoine Ausseur, Ranimation, CH de Cholet, 49300 Cholet, France; Fabrice Bruneel, Ranimation, CH de Versailles, 78150 Le Chesnay, France; Caroline Perreau, Ranimation, CHU de Fort de France, 97261 Fort de France, France; Benjamin Zuber, CHPOT, CH de Versailles, 78150 Le Chesnay, France; Alexandra Brionne, Ranimation, CH de Niort, 79000 Niort, France; Benoit Giraud, Ranimation neurochirurgicale, CHU de Poitiers, 86021 Poitiers, France; Xavier Tchenio, Ranimation, CH de Bourg-en-Bresse, 01012 Bourg-en-Bresse, France; Grald Viquesnel, Ranimation Chirurgicale, CHU de Caen, 14033 Caen, France; Ccile Lory, Ranimation, CH de Guret, 23011 Guret, France; Malika Benrezkallah, Ranimation, CH de Valenciennes, 59300 Valenciennes, France; Diane Friedman, Ranimation, CHU Raymond Poincar, 92380 Garches, France; Jean Paul Gouello, Ranimation, CH de Saint Malo, 35400 Saint Malo, France; Thierry Vanderlinden, Ranimation, GHICL, 59462 Lomme, France; Michel Pinsard, Ranimation Chirurgicale, CHU de Poitiers, 86021 Poitiers, France; Benoit Misset, Ranimation, CH Saint Joseph, 75014 Paris, France; Emmanuel Antok, Ranimation, CHU Sud Runion, 97448 Saint Pierre, France; Fabienne Plouvier, Ranimation, CH dAgen, 47000 Agen, France; Didier Thevenin, Ranimation, CH Dr Schaffner, 62300 Lens, France; Marc-Olivier Fischer, Ranimation Chirurgie Cardiaque, CHU Caen, 14033 Caen, France; Olivier Gontier, Ranimation, CH de Chartres, 28630 Le Coudray, France; Marc Vinclair, Ranimation Neurochirurgicale, CHU Michallon, 38043 Grenoble, France; Christian Mirolo, Ranimation, CH Sud Essonne, 91152 Etampes, France; Franois Nicolas, Ranimation, CH de Chteauroux, 36000 Chteauroux, France; Willy-Serge Mfam, Ranimation Chirurgicale, CHR dOrlans, 45000 Orlans, France; David Petitpas, Ranimation, CH de Chalons, 51000 Chalons en Champagne, France.

Author details

1Ranimation, CH Saint-Louis, 17019 La Rochelle, France. 2EA 4569, Universit Paris Descartes, 75006 Paris, France. 3Ranimation Mdico-Chirurgicale, CHU Avicenne, 93000 Bobigny, France.

Received: 14 January 2015 Accepted: 28 May 2015

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