Robin Cremer
email: robin.cremer@chru-lille.fr

Philippe Hubert

Bruno Grandbastien

Grégoire Moutel

Francis Leclerc

Prevalence of questioning regarding life-sustaining treatment and time utilisation by forgoing treatment in Francophone PICUs

Keywords: withdrawing treatments, guideline adherence, intensive care unit, ethics, child, uncompensated care, patient care management, hospital costs

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

In developed countries, most children die in paediatric intensive care units (PICU) [START_REF] Mccallum | How children die in hospital[END_REF][START_REF] Van Der Wal | Circumstances of dying in hospitalized children[END_REF], where forgoing lifesustaining treatment (LST) is the most common mode of death with variable international practice [START_REF] Kipper | Evolution of the medical practices and modes of death on pediatric intensive care units in southern brazil[END_REF][START_REF] Althabe | Dying in the intensive care unit: Collaborative multicenter study about forgoing life-sustaining treatment in argentine pediatric intensive care units[END_REF][START_REF] Lago | Life support limitation at three pediatric intensive care units in southern brazil[END_REF][START_REF] Vernon | Modes of death in the pediatric intensive care unit: Withdrawal and limitation of supportive care[END_REF][START_REF] Burns | End-of-life care in the pediatric intensive care unit after the forgoing of life-sustaining treatment[END_REF][START_REF] Garros | Circumstances surrounding end of life in a pediatric intensive care unit[END_REF][START_REF] Adams | Evidence of self-report bias in assessing adherence to guidelines[END_REF][START_REF] Sprung | End-of-life practices in european intensive care units: The ethicus study[END_REF][START_REF] Devictor | Forgoing life-sustaining treatments in children: A comparison between northern and southern european pediatric intensive care units[END_REF][START_REF] Sprung | Reasons, considerations, difficulties and documentation of end-of-life decisions in european intensive care units: The ethicus study[END_REF]. Previous studies predominantly focused on patients who died, excluding children for whom the possibility to forgo LST was discussed but not implemented, and those who survived after a decision to forgo. Only a few described both decision-making processes (DMP) and end-of-life care [START_REF] Burns | End-of-life care in the pediatric intensive care unit: Attitudes and practices of pediatric critical care physicians and nurses[END_REF][START_REF] Zawistowski | A descriptive study of children dying in the pediatric intensive care unit after withdrawal of life-sustaining treatment[END_REF]. Though published guidelines contain recommendations to ensure collaborative decisions [START_REF] Academy | American academy of pediatrics. Committee on child abuse and neglect and committee on bioethics. Foregoing life-sustaining medical treatment in abused children[END_REF][START_REF] Truog | Recommendations for end-of-life care in the intensive care unit: The ethics committee of the society of critical care medicine[END_REF][START_REF]Withholding or withdrawing life sustaining treatment in children: A framework for practice[END_REF][START_REF] Hubert | Limitations et arrêts des traitements actifs en réanimation pédiatrique : Recommandations du gfrup[END_REF][START_REF] Truog | Recommendations for end-of-life care in the intensive care unit: A consensus statement by the american college [corrected] of critical care medicine[END_REF], time consumed by DMP remains undocumented. This multicenter, prospective study describes the forgoing of LST in francophone PICUs and units caring for both neonates and children (Neonatal and Paediatric Intensive Care Units: NPICU). W e assessed prevalence of questioning about appropriateness of LST and evaluated time utilisation related to DMP.

PATIENTS AND METHODS

The 35 NPICUs/PICUs affiliated to the francophone paediatric intensive care network (GFRUP) were invited to participate: 17 agreed and 15 provided the information requested. From June 15, 2006 to November 1, 2007, all consecutively admitted children were included. Preterm newborns (birth before 37 weeks of pregnancy) were excluded.

Definitions

Life sustaining treatment (LST) was defined as techniques to sustain respiratory, cardiovascular or renal function. Mode of death was classified as: [START_REF] Mccallum | How children die in hospital[END_REF] withdrawing LST, defined as active discontinuation of LST; [START_REF] Van Der Wal | Circumstances of dying in hospitalized children[END_REF] withholding LST, defined as refraining from any new LST; (3) death after a do-not resuscitate (DNR) order, defined as only refraining from attempting resuscitation in case of cardiac arrest; (4); death after full medical intervention and (5) brain death [START_REF] Shemie | Diagnosis of brain death in children[END_REF].

DMP began as soon as an individual (caregiver, parent, or the child himself) wondered about LST and ended when the child died or was discharged. Decision regarding LST was defined as the record, prior to the terminal event, of the medical decision (full medical intervention, DNR, withholding LST, withdrawing LST).

DMP were classified as (1) complete DMP (record of a decision and at least one decision-making meeting),

(2) abbreviated DMP (record of a decision but no data concerning decision-making meeting), (3) interrupted DMP (record of the date of the beginning of DMP, but no data concerning meeting and decision). We defined undocumented DMP when the recorded mode of death indicated that LST had been forgone with no record of a DMP. Parents' wishes were classified into: maximum treatment, forgoing treatment, "doctors should decide", and not expressed. Decision justifications were classified according to the Royal College of Paediatrics and Child Health [START_REF]Withholding or withdrawing life sustaining treatment in children: A framework for practice[END_REF]: (1) permanent vegetative state (the child will not react or relate with the outside world), (2) no chance situation (LST simply delays death without significant alleviation of suffering), (3) no purpose situation (the degree of impairment will be so great that it is unreasonable to expect the child to bear it), (4) unbearable situation (child and/or family feel that further treatment is more than can be borne), and (5) unclassifiable. Parents' reactions after the decision were classified into: (1) opposition, (2) resignation, (3) approval, or (4) not expressed. Sedation after a decision to forgo was classified into: (1) unchanged, (2) doubled/tripled, (3) quadrupled/quintupled, and (4) more than quintupled dose. Potassium chloride or neuromuscular blocking agent administration before withdrawing mechanical ventilation was defined as euthanasia. Because of potential litigation, , a 12.5% proportion of positive answers was forced in the database at random, to make the true positive answers unidentifiable. Final results were corrected, taking the 12.5% into account.

Data Collection and management

Demographics, dates of admission and discharge, mode of discharge or death, and main organ failure were recorded for all children. Severity was assessed by the PIM2 score [START_REF] Slater | Pim2: A revised version of the paediatric index of mortality[END_REF] and the day 1 PELOD score (D1PELOD) [START_REF] Leteurtre | Paediatric logistic organ dysfunction (pelod) score[END_REF]. Performance at admission and discharge was assessed by the POPC score [START_REF] Fiser | Assessing the outcome of pediatric intensive care[END_REF].

As soon as a DMP was initiated, a form was completed by the attending senior intensivist. Dates, durations, participants, and decisions at each step of the DMP were recorded.

Previously trained physicians (one per centre) entered data into a web-based database that respects confidentiality requirements (Epiconcept™, Paris, France). A research assistant screened the database weekly as quality control, and sent an error report to investigators. One quality control visit was done in each centre during the study. Patient data were collected anonymously, but a nominative list was held by investigators for quality control.

Statistical methods:

Results were expressed as percentages, median values, and interquartile ranges. The Chi-square test and the Kruskal-Wallis test were used for comparisons. A p value < 0.05 was considered as significant. For statistical analysis, decisions to withhold, to withdraw LST and DNR order were pooled into a single "decision to forgo" category.

Ethical considerations:

Study design was approved by the ethical committee of the Société de Réanimation de Langue Française on

Results

Fifteen centres participated in the study, representing two thirds of the PICU beds of the collective. Number of beds per PICU/NICU was 12 (11 -18), number of physicians 5 (3 -7), and number of non-medical caregivers 30 (24 -50).

Population

During the study, 5602 children were admitted (37192 days of stay), 410 died (7.3%). Median age was 12 months (1 -66) and sex ratio 1.31. Probability of death predicted by PIM2 was 1.7% (.8 -5.4), D1PELOD was 10

(1 -11), POPC 1 (1 -3) at admission, and 2 (1 -3) at discharge, length of stay 2 days (1 -6). Main organ failure at admission was: respiratory (44.4%), cardiovascular (19.6%), neurological (18.8%), and gastro-intestinal (5.0%).

Mode of death was: brain death in 66 (16.1%), death after full medical intervention in 169 (41.2%), after withholding LST in 37 (9.1%), after withdrawing LST in 87 (21.2%), and after DNR order in 51 (12.4%). Thus, 175 deaths (42.7%) followed a decision to forgo treatment.

Initiation of DMP

LST were questioned in 308 children (5.5%), by the attending physician in 281, by the child himself in 15, by nurses in 8, and by parents in 1. Delay for questioning was one day after admission (0 -4). The prevalence of questioning was 13.3 per 100 patient-days. Of these 308 children, 189 (61%) died, representing 46% of all deaths. Comparison of these 308 children with the others appears in table 1.

Decision-making processes

Of the 308 DMP initiated, 220 (71.4%) led to at least one decision (total 269 decisions). Of these 220 children, 150 died after a decision to forgo (36.6% of deaths) and 7 despite a maximal treatment decision, 18 children survived after a maximal treatment decision and 45 survived despite a decision to forgo. Among these 220 DMP, 193 were complete and 27 were abbreviated. When comparing recorded modes of death and data regarding DMP, we observed that 25 children died after forgoing LST, while the anticipated decision had not been recorded

(figure 1): 11 were interrupted DMP and 14 were undocumented DMP. The justifications of the 269 decisions are presented in table 2 and the corresponding last decisions in figure 1.

Preparing decisions

405 parent conferences were organised to discuss the possibility to forgo LST. Among the 220 children with at least one decision, 297 conferences were organised (2 per child (1 -3)), duration 30 minutes (25 -40) for each).

The attending nurse was present during 219 conferences (73.7%) and the referring resident during 104 (35%). An external expert estimated prognosis for 154 of these 220 children (70.0%).

Parents' opinions were recorded for 129 of the 193 children with complete DMP. Fathers' and mothers' opinions were similar for 82 (45 wishes to forgo, 18 "doctor should decide", 12 not expressed, 7 maximal treatment wishes). Among the 47 remaining cases with discrepancies between parents' opinions, wishes to forgo treatment versus maximal treatment were never recorded. Delay for obtaining parents' opinion was 5 (2 -10) days after admission.

Decision-making

Two hundred and forty decision-making meetings were organized for 193 children ( Parents were informed that there would be a meeting in 127 cases (52.9%); they knew the date in 100 (41.7%).

Among the 193 complete DMP, 20 decisions to forgo were made where neither parent had expressed any wishes, and 5 where one parent previously requested maximal treatment.

Presenting and implementing the decisions

Among the 269 decisions, 233 were presented to parents (87.6%) by the intensivist in charge of the patient during a 30-minute (25 -45) conversation. The referring resident and a nurse were present at 33.5% and 75.1% of these conferences, respectively.

Of the 193 children with complete DMP, 175 parents' reactions were recorded. Fathers' and mothers' reactions were similar for 122 (77 approvals, 42 resignations, 2 absence of reaction, 1 opposition). In one case, the father voiced opposition to maximal treatment while the mother did not express any preference. In all other cases, the reactions were approval or resignation when the second parent did not expressed anything or was absent.

The 269 decisions were implemented after 9 days after admission (3.5 -17). Considering only the final decision for each child (220 decisions), 134 (61%) led to major changes in treatment. These changes were implemented 1 day (0 -3) after the decision. Among these 134, LST was withdrawn in 93 children (table 3). The intensivist in charge of the patient was present at the bedside during the implementation of the decision in 132 cases (98.5%), the referring nurse in 131 (97.8%) and the referring resident in 51 (38.1%). The option of being present was offered to parents for 121 children (90.3%) and 108 were present (80.6%). The two children whose parents were opposed to maximal treatment survived.

Outcome

In the 193 children with complete DMP, the interval between final decision and death or discharge was 2 days

(1 -3) and 6 days (2 -9) respectively. The POPC at discharge was 4 (3 -4) for the 52 children who survived after complete processes, 3.5 (2.5 -4) for the 6 with abbreviated processes and 4 (4 -6) for the 54 with interrupted processes. Clinical outcome appears in figure 1.

Time utilisation

For the 193 children with a complete DMP, the cumulative time for a whole decision-making process was 660 min per child (450 -975), including 60 min per child (45 -90) for preparing the decisions with parents, 400 min per child (240 -65) for decision-making and 60 min (45 -90) for presenting the decisions to parents.

DISCUSSION

In this study, the incidence of questioning about the appropriateness of LST was 5.5% of admissions and the prevalence 13.3 per cent patient-days. More than 42% of deaths followed a decision to forgo LST. More than 30% of children survived despite the appropriateness of LST being questioned (23% despite a decision to forgo).

Median caregiver's time used for making and presenting the decisions was 11 hours per child.

Our recording of all the DMP as soon as the appropriateness of LST was questioned provides original data such as incidence and prevalence of questioning, time consumption, and outcome of children who survived, unavailable from previous studies that recorded only modes of death [START_REF] Devictor | Forgoing life-sustaining treatments in children: A comparison between northern and southern european pediatric intensive care units[END_REF][START_REF] Martinot | No resuscitation orders and withdrawal of therapy in french paediatric intensive care units. Groupe francophone de réanimation et d'urgences pédiatriques[END_REF][START_REF] Devictor | Forgoing life-sustaining treatments: How the decision is made in french pediatric intensive care units[END_REF]. The 13.3 per cent patient-day prevalence reflects a high level of routine questioning, as encouraged by the GFRUP's guidelines [START_REF] Hubert | Limitations et arrêts des traitements actifs en réanimation pédiatrique : Recommandations du gfrup[END_REF]. Even though most guidelines published since 1994 recommended collaborative decisions [START_REF] Academy | American academy of pediatrics. Committee on child abuse and neglect and committee on bioethics. Foregoing life-sustaining medical treatment in abused children[END_REF][START_REF] Truog | Recommendations for end-of-life care in the intensive care unit: The ethics committee of the society of critical care medicine[END_REF][START_REF]Withholding or withdrawing life sustaining treatment in children: A framework for practice[END_REF][START_REF] Hubert | Limitations et arrêts des traitements actifs en réanimation pédiatrique : Recommandations du gfrup[END_REF][START_REF] Truog | Recommendations for end-of-life care in the intensive care unit: A consensus statement by the american college [corrected] of critical care medicine[END_REF][START_REF] Medical | Withholding and withdrawing life-prolonging medical treatment : Guidance for decision making Editor 27. Ethics Committee of the Society of Critical Care Medicine[END_REF][27][START_REF] Gfrup | Limitations et arrêts des traitements en réanimation pédiatrique[END_REF], caregivers' time consumption has never been studied. In a one-day cross sectional study in 90 French ICUs (6 PICUs), end of life conferences lasted 31.5 minutes, similar to our data [START_REF] Fassier | One-day quantitative cross-sectional study of family information time in 90 intensive care units in france[END_REF]. In our study, time for making and presenting each decision represented an important investment for PICU teams, especially as it did not account for time to implement decisions. The physician-nurse partnership remains central to multidisciplinary care and the PICU team-family partnership permits the child's best interest to be determined together. Organising these partnerships needs time, which should be better valued by health system compensation policies to promote palliative practices in PICU.

The fact that modes of discharge or death and data regarding DMP were separately recorded is another original feature of our study. We observed that 14.3% of deaths following a decision to forgo LST occurred with no record of a decision-meeting or bedside discussion. French law pertaining to patients' rights at the end of life [30] requests exhaustive recording of all DMP, thus these deaths may be considered as potential malpractice. In our study, the decision was recorded prior to the terminal event in two thirds of DMP. The main treatments withdrawn were mechanical ventilation and vasoactive drugs. Sedatives that were administered when LST were withdrawn were benzodiazepines and opiates, in accordance with published end of life practices in PICUs [START_REF] Althabe | Dying in the intensive care unit: Collaborative multicenter study about forgoing life-sustaining treatment in argentine pediatric intensive care units[END_REF][START_REF] Burns | End-of-life care in the pediatric intensive care unit after the forgoing of life-sustaining treatment[END_REF][START_REF] Sprung | End-of-life practices in european intensive care units: The ethicus study[END_REF][START_REF] Zawistowski | A descriptive study of children dying in the pediatric intensive care unit after withdrawal of life-sustaining treatment[END_REF][START_REF] Sykes | The use of opioids and sedatives at the end of life[END_REF].

Most children received usual to triple doses of sedatives, as reported in retrospective studies in US PICUs [START_REF] Burns | End-of-life care in the pediatric intensive care unit after the forgoing of life-sustaining treatment[END_REF][START_REF] Zawistowski | A descriptive study of children dying in the pediatric intensive care unit after withdrawal of life-sustaining treatment[END_REF].

Neuromuscular blocking agents and potassium chloride were used below the 12.5% detection threshold induced by our anonymisation methodology. Finally, most children who died after a decision to forgo were accompanied by their parents (>80%), referring nurse (>97%) and referring physician (>98%). Thus, incorporation of palliative practices into PICU, the main goal of the GFRUP's guidelines, has been successfully achieved. The main difficulties in implementing the guidelines were anticipating the correct date for the decision-making meeting (mostly scheduled for the following day). This partly explains why 12% of decision-making meetings were organized without a nurse and 11% with a nurse in charge of the patient for the first time. We do not know why DMP was interrupted before a decision had been made for 56 children who survived. Was the process fair for these children who had developed severe neurological sequelae? Future guidelines should indicate that all initiated processes must be continued until a decision to forgo or continue LST.

Another important result is that 23% of children survived despite a decision to forgo. This outcome has only previously been reported in adults (9.5% of ICU patient survived despite a decision to forgo was made in ICU) [START_REF] Ferrand | Withholding and withdrawal of life support in intensive-care units in france: A prospective survey. French latarea group[END_REF]. This high proportion indicates the need for a care plan for these children and raises the problem of acceptability of PICU decisions by subsequent teams [START_REF] Cremer | Que deviennent les décisions de limitation ou d'arrêt des traitements actifs quand les enfants sortent vivants de réanimation pédiatrique ?[END_REF][START_REF] Cremer | Pourquoi les décisions de limitation des traitements en réanimation ne sont elles pas partagées avec les professionnels assurant les soins de l'enfant avant et après la réanimation[END_REF]. Further guidelines should address this to improve continuity of care for these children [START_REF] Cremer | Que deviennent les décisions de limitation ou d'arrêt des traitements actifs quand les enfants sortent vivants de réanimation pédiatrique ?[END_REF][START_REF] Fraser | Place of death and palliative care following discharge from paediatric intensive care units[END_REF].

When compared to the results of the previous French multicentre study undertaken in 1999 [START_REF] Devictor | Forgoing life-sustaining treatments: How the decision is made in french pediatric intensive care units[END_REF], our study demonstrates interesting trends regarding the evolution of practice since guidelines were written [START_REF] Hubert | Limitations et arrêts des traitements actifs en réanimation pédiatrique : Recommandations du gfrup[END_REF] and French law acknowledged the right for physicians to forgo treatments [30]. In the previous study, deaths following a decision to forgo represented 43% of total deaths. This indicates that the legalisation of forgoing treatments has not increased this proportion, even though it reduced the risk of litigation. Since 1999, the main improvement in practice relates to the involvement of nurses (nurse participation at decision-making meetings increased from 46% to 88%) and information given to parents (parents aware of the decision-making meetings increased from 11% to 53% and presentation of the decisions from 19% to 87%). Surprisingly, parents' opinion was formally recorded prior to only 46.3% of decisions. This contrasts with the quasi-exhaustive information given to parents after the decisions. However, data about parents' wishes and reactions showed that physicians did not seek informed consent, but absence of opposition. Even though the shared decision model is gaining ground, the GFRUP's guidelines recommend giving parents choice regarding their level of involvement in the DMP. A recent qualitative study, reported that French parents agreed that LST decisions should be made by physicians [START_REF] Carnevale | The moral experience of parents regarding life-support decisions for their critically-ill children: A preliminary study in france[END_REF], and French law has ratified that the physician who is in charge of the patient must be the bearer of the decision, after listening parents' wishes and obtaining the advice of an external consulting colleague [30,37].

The main limitation of our study is its self-monitoring design. Because of the absence of an independent investigator, discrepancies between perceived and true parent satisfaction could not be studied. Nevertheless, the exhaustive inclusion of more than 5000 PICU children provides new insights such as the incidence of questioning and time consumed by DMP. Moreover, this study gives updated data concerning forgoing treatment in PICUs, useful in improving the guidelines and end of life care in PICU.

CONCLUSIONS

The prevalence of questioning about the appropriateness of LST was 13.3 per 100 patient-days, so on any given day in each 10 bed PICU, there was more than one child for whom a DMP was underway. Twenty-three per cent of children survived despite a decision to forgo LST, which underlines the need to elaborate a care plan for these children. Also DMP represented a large amount of staff time that is undervalued but necessary to ensure optimal palliative practice in PICU.

  June 29 th 2006. The database was declared to the French authorities (CNIL) on May 3 th 2006.

  the patient for at least two days(1 -5). At least one other nursing team member attended 40.1% of meetings [median 1 (0 -2)], and an outside expert 70.5% [median 1 (0 -2)].The first meeting was planned 1 day (1 -5.5) and was held 2 days (1 -6) after initiating the DMP. During the 193 first meetings, there were 54 withdrawing decisions, 57 withholding decisions, 48 DNR orders, 22 consensual decisions to continue treatments and 7 decisions to continue treatment in the absence of consensus. In five cases no decision was made because some medical data were missing. Thirty previous decisions were modified during the 38 second meetings and 4 during the 7 third meetings. All but one change resulted in further limitation of treatment.

  1 in 155 children, 2 in 31, 3 in 5, and 4 in 2) including 16 discussions during a routine staff meeting, 23 discussions at the bedside, and 201 dedicated meetings. The latter lasted 45 minutes (30 -60) with 10 (8 -12) participants. The PICU director attended 59.4% of these meetings, the head nurse 69%, a psychologist 24.4% and a chaplain 1.4%. At least one resident attended 90.3% [2 residents (1 -3)], and a nurse 88% [1 nurse (1 -2)]; 88.9% of nurses had cared for

Table 2 : Motivations of the 269 anticipated decisions regarding LST, according to the classification of the Royal College of Paediatrics and Child Health

 2 [START_REF]Withholding or withdrawing life sustaining treatment in children: A framework for practice[END_REF]

		All decisions n (%)	Withholding decisions and DNRO n (%)	Withdrawing decisions n (%)	Maximal treatment decisions n (%)
	Missing data for decision making	6 (2.2)	NA	NA	6 (13.6)
	No consensus	8 (3)	NA	NA	8 (18.2)
	Predictable permanent vegetative state	59 (21.9)	29 (21.8)	30 (32.6)	NA
	No chance situation	44 (16.4)	19 (14.3)	25 (27.2)	NA
	No purpose situation	77 (28.6)	48 (36.1)	29 (31.5)	NA
	Unbearable situation	9 (3.3)	4 (3)	5 (5.4)	NA
	Unclassifiable or not applicable	66 (24.5)	33 (24.8)	3 (3.3)	30 (68.2)
	Total	269 (100)	133 (100)	92 (100)	44 (100)
	DNRO: do-not-resuscitate order -NA: not applicable

Table 3 : sedative treatment in the 104 children for whom it was modified after the last decision

 3

			New sedative treatment			Maintained sedative treatment
		Normal dose	Double to triple dose	Quadruple to quintuple dose	More than quintuple dose	No change in dose	Double to triple dose	Quadruple to quintuple dose	More than quintuple dose
	Benzodiazepines	15	14	4	1	16	20	7	4
	Opiates	23	12	4	2	15	22	5	8
	Barbiturates	8	6	1	5	0	1	0	9

ACKNOWLEDGMENTS

This work was supported by grants from the Réseau Mère-Enfant de la Francophonie and the French ministry of health (PHRC AOM08179-NI07014). We thank the investigators for their record keeping and Dr Susanne Rogers for correcting the manuscript.

Appendix: GFRUP's study group on forgoing treatments Data were collected in the NPICU/PICUs of the following centers: American Memorial Hospital, CHU de Reims, France; Hôpital Charles Nicolle, CHU de Rouen, France; Hôpital Arnaud de Villeneuve, CHU de

Competing interests

The authors declare that they have no competing interests. [START_REF] Slater | Pim2: A revised version of the paediatric index of mortality[END_REF] -PELOD score: Pediatric Logistic Organ Dysfunction score [START_REF] Leteurtre | Paediatric logistic organ dysfunction (pelod) score[END_REF], POPC; Pediatric Overall Performance Category [START_REF] Fiser | Assessing the outcome of pediatric intensive care[END_REF].-LST: life sustaining treatment.

Figure 1: Study flow chart

308 children for whom a process was initiated (1) 88 children for whom the process was interrupted (3) 220 children for whom at least one decision (2) 1 Defined as the record of a date of initiation of a decision-making process.

2 Defined as the record, prior to the terminal event, of at least one choice by PICU staff among four possible options: full medical intervention, DNR, withholding LST, withdrawing LST, associated with the record of the corresponding date.

3 Defined as the record of a date of initiation of a decision-making process but the absence of data concerning decision-making process. 4 Defined as the record of at least a decision with the corresponding date but the absence of data concerning decision-making meeting or bedside discussion 5 Defined as the record of an anticipated decision regarding LST and the record of a decision-making meeting.


Lucie Laurent

Jean-Louis Millot

Patrice Andrieu

Valérie Camos

Caroline Floccia

Fabien Mathy
email: fabien.mathy@unice.fr.

Inner Speech sustains Predictable Task Switching: Direct Evidence in Adults

Keywords: task switching, cognitive control, inner speech, language, electromyography

It has been proposed that inner speech supports task selection in task switching studies, especially when the need for endogenous control is increased. This has been established through the suppression of inner speech in cognitive-flexibility tasks that leads to poorer performance. The aim of this study is to quantify the role of inner speech in a flexibility task by using surface laryngeal electromyography, which, contrary to previous studies, enables participants to freely verbalize the tasks. We manipulated endogenous and exogenous flexibility in a mathematical switching task paradigm. Experiment 1 shows that inner speech acts as a support for switching and is recruited more often when the tasks are of an endogenous type. The main result of Experiment 2 that language is recruited more for the mixing cost than for the switch cost (regardless of the endogenous factor) extends past findings obtained through articulatory suppression.

Inner Speech sustains Predictable Task Switching: Direct Evidence in Adults

Although several models have been developed to account for switching processes (e.g., [START_REF] Altmann | An integrated model of cognitive control in task switching[END_REF][START_REF] Gilbert | Task switching: A PDP model[END_REF][START_REF] Meiran | Modeling cognitive control in task-switching[END_REF], the specific role of speech in switching and more specifically, inner speech, remains to be clarified. Inner speech has long been hypothesized to be a vehicle of thought and voluntary control (e.g., [START_REF] Luria | Speech development and the formation of mental processes[END_REF][START_REF] Reed | The existence and function of inner speech in thought processes[END_REF], and one of the most common techniques used to explore the role of inner speech in flexibility tasks is to disrupt speech through the use of articulatory suppression (Baddeley, Chincotta, & Adlam, 2001;[START_REF] Bryck | Task selection cost asymmetry without task switching[END_REF]Cinan & Tanor, 2002;[START_REF] Dunbar | Toward a cognitive account of frontal lobe function: Simulating frontal lobe deficits in normal subjects[END_REF][START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF][START_REF] Goschke | Intentional reconfiguration and involuntary persistence in task set switching[END_REF]Kray, Eber, & Lindenberger, 2004;[START_REF] Miyake | Inner speech as a retrieval aid for task goals: The effects of cue type and articulatory suppression in the random task cuing paradigm[END_REF][START_REF] Saeki | Effect of articulatory suppression on task-switching performance: Implications for models of working memory[END_REF]. From these studies inner speech appears to be an important determinant of task switching. For example, the switch cost (i.e., the difference in RT between task-switch trials and consecutive same-task trials) was found to increase when subjects were unable to use inner speech (e.g. [START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF]. One interpretation is that inner speech contributes to effectively recode tasks and facilitates executive processes, a language function sometimes referred to as extracommunicative [START_REF] Lupyan | Extracommunicative functions of language: Verbal interference causes selective categorization impairments[END_REF].

Previous studies have shown that verbal self-instructions can be used to support task switching [START_REF] Kirkham | The impact of verbal instructions on goal-directed behaviour[END_REF][START_REF] Kray | Verbal self-instructions in task switching: A compensatory tool for action-control deficits in childhood and old age?[END_REF], suggesting that encouraging the use of speech rather than denying it can have beneficial effects.

Following up on these findings we decided to promote its use and directly quantify its involvement by adding laryngeal surface electromyography measurements (EMG) to behavioral parameters such as response time and switch cost. One advantage of this method is to avoid using articulatory suppression, which can be viewed by participants as a non-natural process that disrupts task performance. The EMG device, which measures the electrical impulses of muscles using electrodes applied to the surface of the skin, makes it possible to observe speech signals even when speech is internalized [START_REF] Garrity | Electromyography: A review of the current status of subvocal speech research[END_REF][START_REF] Sokolov | Inner Speech and Thought[END_REF]. The electrical activity of laryngeal muscles can be detected whether or not the face or mouth is moving, and whether or not sound is emitted [START_REF] Betts | Small-vocabulary speech recognition using surface electromyography[END_REF][START_REF] Jou | Towards continuous speech recognition using surface electromyography[END_REF]. The current view on the relationship between inner speech and motor activation is that the recruitment of the motor system will depend on the level of inner speech in the task at hand (e.g. [START_REF] Geva | The neural correlates of inner speech defined by voxel-based lesion-symptom mapping[END_REF][START_REF] Perrone-Bertolotti | What is that little voice inside my head? Inner speech phenomenology, its role in cognitive performance, and its relation to self-monitoring[END_REF], with time-constrained and/or attention-demanding tasks more likely to recruit the motor system. Since the switching tasks used in the current study are both rapid and attention-demanding, we expect participants to fully engage in the motor production system underlying inner speech, allowing us to detect inner speech production with the EMG technique.

To examine how the use of inner speech varies as a function of switching conditions, participants were administered a predictable mathematical switching task that included both cued and non cued trials to directly contrast the effects of exogenous and endogenous control on inner speech in a within-subject design. Endogenous control is required when there is no available external cue that signals the next task to be performed, for instance when one has to remember an alternation pattern to switch from one task to another (ABAB, etc), while exogenous control is made possible by cuing the upcoming task (for instance, using an arithmetic symbol to indicate which operation to be performed next). Having to memorize a sequence to carry out tasks (ABAB, etc.) as in endogenous tasks usually slows down the alternation of the tasks in comparison to exogenous tasks because the participant is required to update the alternation process on the fly. In contrast, the presence of external cues as in exogenous tasks is supposed to alleviate the need for internal-self cuing, which has been hypothesized to be associated with the presence of covert self-instructions [START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF][START_REF] Miyake | Inner speech as a retrieval aid for task goals: The effects of cue type and articulatory suppression in the random task cuing paradigm[END_REF]. If task-switching costs reflect in part the amount of inner speech produced to recall which task needs to be performed next, we predict a greater reliance on inner speech in endogenous tasks than in exogenous tasks.

Although it is recommended to use different task-switching paradigms to clearly determine the role of verbal strategies in task-switching designs [START_REF] Kirkham | The impact of verbal instructions on goal-directed behaviour[END_REF], in our first experiment we chose to rely on a previous study by [START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF] that evaluated the impact of articulatory suppression in task-switching using list design (AAAA..., BBBB..., and ABAB...). However, instead of disrupting speech, we quantified the quantity of inner speech produced during the response delays. A specific hypothesis was that more covert vocalizations measured by electrophysiological measures can be found when longer response times are expected, and particularly in the non-cued conditions of the mixed blocks in which switches are required. Because switch costs were confounded with mixed costs in the first experiment, a second experiment tested an AABB mixed list design to better examine the relative effects of mixed costs and switch costs when the participants alternated between the tasks without having to switch tasks systematically.

Experiment 1

The current experimental design is similar to that of [START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF] in which the participants had to alternate between additions and subtractions in a mathematical taskswitching paradigm, with cued (exogenous) and non-cued (endogenous) conditions. They showed that disrupting inner speech particularly increased switch costs, and specifically so in the absence of cues. However, instead of disrupting speech via articulatory suppression to show its disruptive effect on switch costs [START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF], laryngeal EMG recordings were used in the present experiment to detect motor activity related to the use of inner speech. Our first goal was to quantify the amount of inner speech generated during the response time period, and to examine how it would vary as a function of the difficulty of the task (exogenous vs. endogenous) and the degree of switching involved (repeated vs. alternated). Our second and central aim was to examine whether the amount of inner speech as measured by the EMG would match the pattern of response times (RTs). In other words, if inner speech scaffolds the cognitive processes engaged in this time-pressured and attentiondemanding tasks, we expected a direct correspondence between the amount of inner speech and response times.

Participants

Thirty-two psychology students at the University of Franche-Comté (M = 22.2 years; SD = 2.9; 10 males and 22 females) volunteered to participate in this study in exchange for course credits.

Procedure

The mathematical task-switching paradigm used two conditions: an endogenous flexibility condition (referred to as Non-Cued; no cue was provided, which required the participant to keep track of the alternation of the tasks) and an exogenous flexibility condition (referred to as Cued; the symbols + and -were used to indicate the next task). Instead of the paper-and-pencil version of the original authors, we used a computerized version of the task to allow synchronization with EMG recordings and precise RT measurements. Another main difference with the original study was the use of symbol cues only (instead of using both color cues and symbol cues as in [START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF], because the symbol cues more strongly reduced the effect of articulatory suppression. All participants were tested in the two conditions, Cued and Non-Cued and the total duration of the experiment was about 20 minutes, including instructions and breaks. Each of the conditions included three blocks (Figure 1), one block in which the participants had to subtract the number 3 from each number, one block in which they had to add 3, and a third block in which they had to alternate between addition and subtraction (type of alternation ABABAB). Each condition consisted of a series of 84 two-digit numbers (13-96) with 28 numbers randomly assigned without repetition to each of the three blocks Addition, Subtraction and Alternation, so that no number appeared twice within the same condition. In all, each participant did 2 conditions × 3 blocks = 6 blocks, which represented a total of 6 blocks × 28 trials = 168 trials. The order of the first two blocks (one block of subtractions followed by a block of additions) was counterbalanced between the participants, but the third block was systematically the Alternation block across participants. The order of the two conditions (Cued and Non-Cued ) was also counterbalanced across participants. In the Cued condition, the mathematical symbols + or -appeared to the right of each number, whereas no symbol were presented in the Non-cued condition. The general instructions to add or subtract 3 to the stimuli, or to alternate in a given order, were presented visually before each block. During the task, each number appeared in the center of the screen and a response box was located in the lower part of the screen. In order to answer, the participants had to use a numeric keyboard and had no possibility to correct their answer. Each answer consisted of two digits and the next number appeared immediately after the second digit was typed. The participants were given a two-minute break between the two tasks.

Behavioural and electrophysiological measures

The E-Prime software that controlled stimulus presentation and RTs collection was In parallel to electromyography we also recorded RTs in milliseconds (excluding incorrect responses from our analyses). Following the terminology used by Meiran (2000, p. 236), we computed alternation costs, which are based on the difference between single task RT (i.e., participants repeat the same task before the mixing block occurs; e.g., AAAA…) and switch task RT (i.e., participants switch between two tasks during the alternating block; e.g., AB). In addition to the analysis of RTs and alternation costs as in [START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF], we also report the quantity of inner speech produced during the response delays across the different blocks and conditions. ANOVAs were conducted for each dependent variable (RT, alternation cost, QL integrals and QL amplitudes), with Cues (Cued vs. Noncued) and Block (Repeated task versus Alternated task blocks) as within factors.

Results and Discussion

Trials with RTs diverting more than 3 standard deviations from the individual mean RT or below 200 ms were considered outliers and were excluded from the analysis (following Goschke, 2000, p. 337), which corresponded to 1.6 % of the data.

Following Emerson and Miyake's results, we expected longer RTs in the Non-cued condition as compared to the Cued condition, as well as longer RTs in Alternated task blocks than in Repeated task blocks. We also expected larger switch costs overall in the Non-cued condition than in the Cued condition. ANOVA on response times (Figure 2A) showed a significant effect of the factor Block, F(1,31) = 98, p < .001, η p ² = .76, due to longer response times in the Alternated task blocks than in the Repeated task blocks. There was no main effect of the factor Cues, F(1,31) = .8, p = .40. Although descriptively the non-cued condition led to longer RTs than the cued condition for the alternated task block and not in the repeated task block, the Cues  Block interaction was no significant 1 , F(1,31) = 1.6, p = .22. Note that significance was however reached when the extreme values were not removed prior to analyses (F(1,31) = 4.7, p = .04, η p ² = .13), as this was done in the study by Emerson and Miyake.

Interestingly, when similar analyses were performed on the mean integral of the EMG signal during the RT interval, this interaction effect was significant (Figure 2B). Indeed, an ANOVA on the mean integral of the EMG showed a significant effect of the factor Block, F(1,31) = 44.5, p < .001, η p ² = .59, due to larger integrals in the Alternated task condition than in the Repeated task condition. Again, there was no main effect of the factor Cues, F(1,31) = .6, p = .43, but this time we observed a significant interaction between the Cues and Blocks, F(1,31) = 4.5, p = .04, η p ² = .13, due to a larger difference between the Cued vs. Non-cued conditions in the Alternated task blocks only. This interaction represents the slopes of Figure 2B, with significant higher switching costs in the Non-cued condition (M = 2.20 mV.ms; SD = 2.16) than in the Cued condition (M = 1.07 mV.ms; SD = 1.90).

1 The RT measures cannot however be easily compared because completion times were recorded by the experimenter with a stopwatch in this previous study. One issue with the current experiment is that switch costs are confounded with mixed costs because the tasks alternated systematically [START_REF] Bryck | Does executive task management require verbalization?[END_REF][START_REF] Lien | Age-related differences in switching between cognitive tasks: Does internal control ability decline with age?[END_REF][START_REF] Monsell | Task switching[END_REF], meaning that the differences in EMG between the repeated and the alternated tasks cannot be attributed solely to the cost of switching. This is particularly the case when the next task is not cued. A solution adopted in the next experiment was to use a mixed-task in which a task was either repeated from the previous trial or changed.

Experiment 2

To better characterize the effect of alternating tasks on inner speech, Experiment 2 was carried out to divide the alternation cost into a mixed cost and a switch cost [START_REF] Meiran | Modeling cognitive control in task-switching[END_REF].

When participants alternate using an ABAB pattern, it is impossible to tell whether a longer RT reflects a difficulty to operate the new task (switch cost) or a difficulty to maintain the pattern of task rules (mixed cost), or both. When participants are subjected to an AABB pattern, a same-task transition (hereafter called the no-switch condition) only involves a mixed cost, while a different-task transition (hereafter called a switch condition) implies both a mixed cost and a switch cost .

Participants

Twenty-three psychology graduate students at the University Nice Sophia-Antipolis (M= 24.5 years; SD = 5.2; 9 males) volunteered to participate in this study. The experiment was run with a total of 30 participants, but due to technical issues, data for seven participants were corrupted and had to be dismissed.

Procedure

The experimental design was similar to Experiment 1, except that an AABB pattern of alternating runs of two tasks was used instead of the ABAB pattern when participants alternated.

Results and Discussion

As in Experiment 1, trials with RTs diverting more than 3 standard deviations from the individual mean RT or below 200 ms were considered outliers and were excluded from the analysis, which corresponded to 5.3 % of the data. For each participant, we computed the mean integral EMG and the mean RT, as a function of the three task conditions: Single task, No-switch during the alternation block (this refers to the AA or BB cases) and Switch during the alternation block (referring to either of the AB and BA cases), referring later to the Task factor. Then, Mixed costs were computed by subtracting No-switch to Single, and Switch costs were computed by subtracting Switch to No-switch.

We performed for the two dependent variables (RT, integral EMG) separate repeatedmeasures ANOVAs, which showed a systematic main effect of the three task conditions (Fs(2,44) > 19, ps < .001; η p ² (RT) = .53, η p ² (EMG) = .47), but no effect of the factor Cues and no interaction (see Fig. 2C,D). The respective average RTs for the three conditions (Single task, No-switch and Switch) were 2167 ms (SD = 130), 2498 (140), and 2662 (156), with pairwise Bonferroni comparisons showing a significant difference between the Single task condition and the two other conditions of the Task factor. The respective average integral for EMG for the three conditions were 10.0 mV.ms (SD = 1.00), 11.6 (.99), and 11.9 (1.00),

with pairwise significant differences similar to what was observed in RTs.

Another two separate repeated-measures ANOVAs were run using the factor Cues and the factor Cost (Mixed vs. Switch cost; effects are visible on the two slopes between the three conditions on the x axis of Fig. 2C,D). We did not reach any significant effect with RTs, but analysis of the EMG signal showed more power. The ANOVA was significant for the factor Cost (F(1,22) = 4.7, p = .04; η p ² = .18, due to a large difference between the integral for the No-Switch condition (M = 1.64, SE = .30) and the Switch condition (M = .30, SE = .39).

There was no other significant effect, including when testing simple effects. This result tends to indicate that language is recruited more for maintaining the task-set AABB or updating the next task (A or B) than for switching (AB or BA) per se (the General Discussion is more specific about whether this large mixed cost on verbalization can be related to a task preparation effect that is present for both repeat and switch trials or switch trials only).

General Discussion

The first aim of this study was to establish whether the use of inner speech could be detected online during the execution of switching tasks. Our results clearly demonstrate that participants generate inner speech in these situations, confirming the proposal that the recruitment of the motor system for the production of inner speech is likely to be observed with attention-demanding tasks as those used in the current study (e.g. [START_REF] Geva | The neural correlates of inner speech defined by voxel-based lesion-symptom mapping[END_REF].

Our second goal was to investigate alternation costs (comparing Repeated task blocks and Alternated task blocks) as a function of the availability of cues (endogenous versus exogenous conditions), and test whether typical RT effects as obtained for example by [START_REF] Emerson | The role of inner speech in task switching: A dual-task investigation[END_REF] would be similarly found in the inner speech measurement patterns. First, we showed that in the absence of an external cue, that is, in the endogenous condition, participants in Exp. 1 presented a slight increase in the production of inner speech as compared to the exogenous condition, showing that they resorted more to inner speech when alternating between the tasks. Figures 2A and2B and the statistical outcomes clearly illustrate the close correspondence between response delays in the different conditions and the amount of inner speech generated during these periods. Our result fits nicely to the ideas suggested by [START_REF] Mayr | Control of Task Sequences: What is the Role of Language?[END_REF] that speech onset latencies and response times are highly synchronized when performing task sequences, probably because aloud verbalization helped with sequence updating.

Interestingly, the factor Cue did not have a strong effect in Exp. 1, particularly on RTs, regardless of our small sample size, and a similar result was obtained in Exp. 2. Participant debriefing suggest that they felt able to plan the tasks efficiently regardless of the presence of cues, and that because their planning was often taking place ahead of the cues, these cues turned out to be sometimes counter-productive. Therefore, cued or not cued, our tasks were predictable, and this makes it difficult to conclude exactly to what extent the recruitment of inner speech in the cued condition relative to the non-cued condition was genuinely due to the recall of the task needed to be performed next. Further experiments need to provide much stronger evidence that inner speech is recruited more often when the tasks are of an endogenous type, especially because we did not find an effect of the endogenous/exogenous factor for the second experiment in our EMG measures. However, one main result in Exp. 2 tends to show that verbalization was more critical for maintaining the task rules AABB or updating the next task A or B (rather than for the actual switching processes AB or BA), because inner speech was recruited more for mixed costs than for switch costs. Indeed, the slope in Fig. 2 D was steeper between the Repeated task and the Alternated task No-Switch conditions than between the No-switch and Switch conditions of the Alternated tasks. This result fits with the conclusion of [START_REF] Mayr | Control of Task Sequences: What is the Role of Language?[END_REF] that inner speech may be recruited as a tool for retrieving and activating the relevant task goal. However, preparing for the tasks at hand is a complex process that has generated some debate over whether the mixing cost is simply reflecting the ability to maintain instructions for all current tasks or the ability to both maintain instructions and to activate the appropriate task for the next trial (see Kieffaber, Kruschke, Cho, Walker, & Hetrick, 2013, p. 701). Some models assume that there is no need to activate the next task when the task is repeated.

The conclusion we favor, which is that verbalization is more critical for maintaining and updating the task rules, assumes that the preparation process is present for both no-switch conditions (when the trial n + 1 involves the same task as trial n) and switch conditions (when the trial n + 1 involves a different task) of the mixed tasks. Effectively, following Meiran (2000) -and we concur in our analysis -the mixed-cost is computed from substracting the No-switch conditions from the Single task conditions, and computation of the alternation cost subsequently assumes that the preceding mixed-cost (deducted in that case) combines with an extra switch cost when the task is being switched. Our analysis did not consider that the mixed-cost could be of a different nature when associated with a switch cost.

Also, the mixed-cost effect was larger on verbalization than on response times:

participants took longer to initiate a task switch, but they benefited only minimally from taskrepetition. In addition, this effect was stronger when measuring the inner speech signal than for the response times (the slope in Fig. 2 D was lower than in Fig. 2 C, between the Noswitch and Switch conditions; conversely, the slope was steeper between the Repeated task and the Alternated task No-Switch conditions). Whether related to the repeated trials only or to both repeated trials and switch trials [START_REF] Kieffaber | Dissociating stimulus-set and response-set in the context of task-set switching[END_REF], our results shows that proactive control seems to generate more verbalization to maintain and update tasks than when specifically switching to a different task. This dissociation between RT and EMG measures seems to indicate that EMG measures provide a better way of quantifying inner speech in cognitive processes compared to response times. However to stay on the safe side it would be more cautious to conclude that electromyography analysis seems more precise than RTs but that feature extraction methods need to be developed to decompose the signal into different components and reduce the noise to support such a strong conclusion.

At this point, these findings confirm that surface electromyography provides a means of quantifying inner speech in cognitive-flexibility processes, in conjunction with more traditional behavioral variables such as response time. Previous studies on the use of inner speech have only gone as far as showing that the suppression of inner speech leads to a decline in task-switching performance. Our study adds to these results by establishing a more direct relationship between decision times and inner speech without disrupting task performance, with results indicating that inner speech might play a predominant role when more endogenous control is required for the task at hand, but mostly when maintaining or updating is required.

Figure 1 .

 1 Figure1. Design of the two conditions in the switching task. Note that the => symbol indicates the expected answer (i.e., the green number on the right side), but this symbol was not displayed during the tasks.

  synchronized with an electromyograph (EMG 100 C, Biopac®) monitored by the AcqKnowledge 4.1 software. The electrodes used in this experiment (EL503, Biopac®) were silver chloride (Ag-AgCl) reference electrodes, measuring one centimeter in diameter (3.5 cm including the adhesive skin surface). Two pairs of electrodes were positioned one above the other with 4-cm vertical and horizontal gaps (2 cm on either side of the vertical medial line) and placed on the laryngeal muscles in order to record voice signals. The ground electrode was attached to the right wrist of each participant. Participants were instructed to refrain from coughing and to avoid the use of covert speech during the tasks.To analyze the EMG data (first sampled at 1000 Hz), we calculated the integral of the speech signals recorded during each stimulus-response interval. First, comb band stop filtering (frequency = 50 Hz) was used to process the EMG data in order to remove power line noise from the raw signal data recorded during the entire experiment for one participant, and a root mean square (RMS) function fully corrected the signal (using a time interval of 30 ms) after removing the baseline that was computed across the entire task. After integrating the two RMS-EMG signals using the trapezoidal rule, we averaged our data from the different electrodes to obtain a single integrated EMG value. We then used this signal to reflect the quantity of inner speech produced. In other words, we defined the quantity of speech (QL) as the amount of EMG signal during a given period, obtained by integrating the signal (expressed in mV.ms). QL was used to indicate both the intensity and the duration of inner speech. The mean amplitude (expressed in mV) during a given period was computed by dividing the integral by the time interval.

Figure 2 .

 2 Figure 2. Mean response times and mean EMG integral in Exp. 1 (A, B) and Exp. 2 (C, D) as a function of switch type (Cued vs Non-cued) in the Repeated vs. Alternated task blocks. Exp. 2 further distinguishes Switch trials and No Switch trials. Note. Error bars are +/-oneSE.

This research was supported in part by a grant from the Région de Franche-Comté AAP2010 awarded to Fabien Mathy and Lucie Laurent Inner Speech 2 with the support of the Maison des Sciences de l'Homme et de l'Environnement Ledoux USR 3124, and by funds from the MTC-NSC (Université Nice Sophia Antipolis) awarded to Fabien Mathy.