Dying Process, Intensive Care Medicine, Palliative Care, Sedation, Withdrawal of Life Support
Conditions
Keywords
End of life, intensive care medicine, mechanical ventilation, organ support, withdrawal, life support, sedation, palliative care
Brief summary
The ARREVE-3 trial will evaluate whether a structured palliative care protocol can improve end-of-life management for mechanically ventilated ICU patients in whom a decision to withdraw life-sustaining therapies has been made. This cluster-randomized controlled trial compares protocol-based care with usual practice across participating centers. The intervention includes comprehensive guidance on symptom management, sedation, nursing care, withdrawal procedures, and family support, supported by standardized staff training. The primary endpoint is adherence to recommended end-of-life practices, while secondary outcomes assess patient comfort, communication with relatives, and the impact on families and healthcare professionals
Detailed description
Among ICU patients who die after a decision to withdraw life-sustaining therapies, most are receiving mechanical ventilation (MV). Withdrawal of MV may cause discomfort, and end-of-life practices can have a lasting impact on both families and healthcare professionals. Despite international guidelines and recent legislative changes in France, end-of-life practices in the ICU remain highly variable, indicating substantial opportunities for improvement in patient comfort-focused management. The ARREVE-3 trial aimes to determine whether a structured palliative care protocol for mechanically ventilated patients undergoing withdrawal of life-sustaining therapies improves the quality of the dying process. Developed in collaboration with palliative care specialists, a psychologist, and a sociologist, the protocol provides standardized guidance on pharmacological and non-pharmacological interventions, including symptom assessment tools, sedation strategies, nursing care, and procedures for withdrawal of life-sustaining treatment. Structured recommendations for support of relatives are also included. ARREVE-3 is a pragmatic, interventional, cluster-randomized controlled trial, with participating ICUs being unit of randomization to minimize contamination between study arms. ICUs randomized to the intervention arm will apply the palliative care protocol, whereas control ICUs will continue to follow usual care. Physicians and nurses in intervention ICUs will receive standardized training from the coordinating team, complemented by a video-based educational module. Designated local champions within each ICU will support implementation and adherence.to the protocol. The primary endpoint is adherence to the protocol for end-of-life care. Secondary outcomes include patient comfort, quality of communication with relatives, and the impact of the end-of-life process on relatives and healthcare professionals.
Interventions
OTHERProtocol for palliative care and life-support withdrawal
In the intervention group, end-of-life care will be provided in accordance with the study protocol, which specifies pharmacological management, nursing care, management of life-sustaining organ support, procedures for the assessment of comfort and pain, and support for relatives. Medical and nursing staff in intervention centers will receive on-site, face-to-face training on the care protocol within each ICU. An instructional video detailing the protocol will also be available.
Sponsors
Nantes University Hospital
University of Burgundy
Centre Hospitalier Universitaire de Saint Louis APHP
University Hospital, Tours
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Cluster randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient: * Age ≥ 18 years * ICU admission for more than 48 hours * Receiving invasive mechanical ventilation * A documented decision to withdraw life-sustaining therapies, made through a multidisciplinary collegial process and communicated to the designated surrogate decision-maker, family, or relatives * At least one visit from a relative prior to the decision to withdraw life-sustaining therapies * Provision of informed consent for study participation, or, if the patient lacks decision-making capacity, consent obtained from a relative or legally authorized representative * Relative: * Age ≥ 18 years * Has received at least one medical update regarding the patient's clinical status from an ICU physician prior to the decision to withdraw life-sustaining therapies * Has provided informed consent for study participation
Exclusion criteria
* Patient: * Presence of a tracheostomy * Brain death or involvement in an organ donation procedure * Absence of any visit from a relative * Subject to legal guardianship or other legal protection measures * Incarcerated patient * Participation in another interventional research study focused on end-of-life care * Pregnant or breastfeeding woman * Relative: * Inability to understand or speak French * Subject to legal guardianship or other legal protection measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess whether, compared with usual care, the implementation of a palliative care protocol for mechanically ventilated patients-combined with dedicated staff training-improves adherence to guidelines. | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients receiving adequate sedation (RASS-5 within one hour before withdrawal of life-sustaining therapies) and withdrawal of mechanical ventilation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Sedation | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Maximum rate of continuous infusion of each sedative agent administered (within 1 hour before the first withdrawal of life sustaining therapies and death) |
| Proportion of Patients Receiving Medications Other Than Sedatives | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients receiving neuromuscular blocking agents, scopolamine, paracetamol (acetaminophen), or antiemetic agents. |
| Administration of neuromuscular blocking agents | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients receiving neuromuscular blocking agents |
| Administration of scopolamine | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients receiving scopolamine |
| Administration of paracetamol (acetaminophen) | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients receiving paracetamol (acetaminophen) |
| Administration of Receiving antiemetic agents | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients receiving antiemetic agents |
| The Semi-Lateral (¾ Lateral) Position | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients positioned in the semi-lateral (¾ lateral) position 1 hour before treatment withdrawal and 1 hour before death |
| Life-Sustaining Organ Support Management | From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients receiving dialysis, vasoactive drug and/or ECMO at inclusion and at death |
| Time from Inclusion to Extubation | From inclusion to date of extubation, assessed up to 28 days | Time interval between inclusion and extubation |
| Assessment of Sedation | From inclusion to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients with a Richmond Agitation-Sedation Scale (RASS) score of -5 or \> -4 (≥ -3) 1 hour before withdrawal of the first life-sustaining therapy (mechanical ventilation, vasopressors, or ECMO) and 1 hour before extubation |
| Assessment of Pain Management | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Higher Behavioral Pain Scale (BPS) score 1 hour before withdrawal of the first life-sustaining therapy (mechanical ventilation, vasopressors, or ECMO); BPS min = 3, max = 12; Higher scores correlate with increased pain intensity. |
| Assessment of Comfort Management | From 1h before the date of life-support withdrawal to date of ICU discharge or death, whichever came first, assessed up to 28 days | Proportion of patients with airway secretion scores of 3 or 4 |
| Assessment of Communication with Relatives | From inclusion to date of ICU discharge, assessed up to 28 days | Proportion of relatives who had at least three meetings with ICU caregivers |
| Assessment of Conflicts | From inclusion to date of ICU discharge, assessed up to 28 days | Level of conflicts between ICU healthcare givers and relatives, as rated on a 0-10 Likert scale. A higher score indicates a more intense conflict. |
| Assessment of Quality of Dying by Relatives | From inclusion to 1 month after death of the patient | Quality of Dying and Death questionnaire (QODD-1) assessed 1 month after death, as rated on a 0-10 Likert scale. Higher scores correlate with a more satisfactory level of care. |
| Anxiety and Depression in Relatives | From inclusion to 1, 3, 6, and 12 months after the death of the patient | Hospital Anxiety and Depression Scale (HADS) assessed 1, 3, 6, and 12 months after death. HADS min = 0, max = 42; Higher scores correlate with increased risk of anxiety and depression. |
| Post-Traumatic Stress Disorders in Relatives | From inclusion to 1, 3, 6, and 12 months after the death of the patient | Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) assessed 1, 3, 6, and 12 months after death. PCL-5 min = 0, max = 80; Higher scores correlate with increased risk of posttraumatic stress. |
| Prolonged Grief in Relatives | From inclusion to 12 months after the death of the patient | Prolonged Grief Disorder scale (PG-13) assessed 12 months after death. PG-13 min = 4, max = 48; Higher scores correlate with increased risk of prolonged grief. |
| Assessment of Quality of Dying by Healthcare Professionals | After the death of the patient, assessed up to 28 days | Quality of Dying and Death questionnaire (QODD-1), as rated on a 0-10 Likert scale. Higher scores correlate with a more satisfactory level of care. |
| Psychological Impact on Healthcare Professionals | After the death of the patient, assessed up to 28 days | Measure of Moral Distress for Healthcare Professionals (MMD-HP). MMD-HP min = 0, max = 432; Higher scores correlate with increased risk of moral distress. |
| Impact on ICU Organization and Staff | Up to 2 years | Perceived Stressors in Intensive Care Units (PS-ICU) assessing burnout at the end of the inclusion period. PS-ICU min = 0, max = 104; Higher scores correlate with increased risk of stress at work. |
Countries
France
Contacts
CONTACTAmélie SEGUIN, MD
CONTACTJean REIGNIER, MD Professor
PRINCIPAL_INVESTIGATORAmélie SEGUIN, MD
Nantes University Hospital
Outcome results
None listed