Opioid-free Analgesia in Intensive Care Unit

Phase 4RecruitingNCT05825560

Centre Hospitalier Universitaire de Nīmes50 enrolled

Overview

ICU patients experience moderate to severe pain. Studies and guidelines point out the benefits of multimodal analgesia on pain control, opioid spare and on lowering its adverse effects. However, no recommendation about drugs or protocol has been formulated. In our study, investigators studied the feasibility and the impact on Remifentanil spare of a standardized protocol using multimodal analgesia (Paracetamol, Nefopam, Tramadol, Ketamine, Remifentanil) compared to the standard-of-care strategy using Paracetamol and Remifentanil. The investigators conducted a prospective, ''proof of concept'', randomized, double-blind, parallel group, placebo-controlled trial. The investigators studied multimodal analgesia versus standard-of-care in ICU patients requiring sedation-analgesia for invasive mechanical ventilation.The investigators hypothesized that Remifentanil consumption decrease by 15% with the use of a standardized multimodal analgesia strategy

ICU patients requiring sedation-analgesia for mechanical ventilation for at least 48 hours are randomized in 2 parallel groups : control arm using ''standard of care'' analgesia (Paracetamol and Remifentanil), and interventional arm using multimodal analgesia at different level according to pain accessed by BPS (Step 1 : Paracetamol, Nefopam, Tramadol, Step 2 : Ketamine, Step 3 : Remifentanil). Sedation drugs are standard of care (Propofol and Midazolam if Propofol isn't enough) to obtain prescribed sedation accessed by RASS. Double-bling is kept for 72 hours until the primary outcome is obtained. The investigators hypothesize a 15% reduction of Remifentanil consumption in the interventional group.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient hospitalized in ICU and requiring sedation-analgesia for mechanical ventilation. * Patient undergoing mechanical ventilation for more than 2 hours and less than 24 hours. * Informed consent signed by the patient or his trusted person, legal representative, family member, curator or tutor, or emergency consent procedure. * Patient affiliated to the French Government Public Health Insurance. * Patient over 18 years old. Exclusion Criteria: * Patient already involved in a trial that might influence our primary endpoint. * Patient in exclusion-period determined by another trial or study. * Patient who is likely to be requiring less than 48 hours of mechanical ventilation. * Patient with contraindication or allergies to at least one of the following medication : paracetamol, nefopam, tramadol, ketamine, remifentanil. * Patient with hepatic insufficiency (defined as PT \< 50%). * Parturient or breast-feeding patient. * Patient suffering from moderate to severe Acute Respiratory Distress Syndrome (ARDS), with decreased PaO2/FiO2 ratio under 150mmHg after respiratory optimization (courant volume 6mL/kg and PEEP \> 5mbar). * Patient requiring curare treatment. * Patients with an indication for locoregional analgesia prior to extubation (perineural sealing, epidural analgesia).

Outcomes

Primary Outcomes

Daily remifentanil consumption (after randomisation)

daily consumption of remifentanil between the 24th hour and the 48th hour after randomisation of patients admitted to the ICU and requiring at least 48 hours of mechanical ventilation

Time frame: 48th hour after randomisation

Secondary Outcomes

Impact of a non-opioid analgesia strategy on morphine savings at D7

Cumulative dose of remifentanil

Time frame: Day 28

Impact of an opioid-free analgesia strategy on sedative consumption

Number of lived days free of remifentanil

Time frame: Day 28

Impact of an opioid-free analgesia strategy on sedative consumption

Daily consumption of sedative drugs from inclusion to D28

Time frame: Day 28

Impact of a non-opioid analgesia strategy on the duration of mechanical ventilation

Number of live days free of mechanical ventilation

Time frame: Day 28

Impact of an opioid-free analgesia strategy on norepinephrine

Number of lived days free of norepinephrine

Time frame: Day 28

Impact of a non-opioid analgesia strategy on organ failure at D28

SOFA Score (Sepsis-related Organ Failure Assessment)

Time frame: Day 28

Impact of a non-opioid analgesia strategy on fluid intake

Daily fuid intake in milliliter

Time frame: Day 28

Impact of a non-opioid analgesia strategy on mental confusion

CAM ICU test

Time frame: Day 28

Impact of a non-opioid analgesia strategy on the occurrence of morphine-related adverse events

Presence of one or more events of special interest or expected adverse events: constipation, bradycardia, bladder globe, nausea, vomiting, liver disturbance, serotonin syndrome

Time frame: Day 28

Impact of a non-opioid analgesia strategy on the incidence of ventilator-associated pneumonia

Presence of pneumonia associated with mechanical ventilation

Time frame: Day 28

Impact of a non-opioid analgesia strategy on extubation failure rates

extubation failure and cause (reintubation within 48 hours of first extubation)

Time frame: 48 hours after extubation

Impact of a non-opioid analgesia strategy onICU and hospital length of stay

Length of stay in the intensive care unit and in the hospital

Time frame: Day 90

Impact of the non-opioid analgesia strategy on vital prognosis at D28 and D90.

Vital status at day 28 and day 90

Time frame: Day 90

Impact of a non-opioid analgesia strategy on morphine dependence at D90

Opioid use at D90

Time frame: Day 90

Opioid-free Analgesia in Intensive Care Unit

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts