Opioid-free Analgesia in Intensive Care Unit (OFICU)

Centre Hospitalier Universitaire de Nīmes

Status and phase: Enrolling; Phase 4

Conditions: Intubation

Treatments: Drug: OFA multimodal analgesia; Drug: Standard multimodal analgesia

Study type: Interventional

Funder types: Other

Identifiers

NCT05825560

LOCAL/2022/RW-01

2022-003273-37 (EudraCT Number)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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50 participants in 2 patient groups

Control group

Active Comparator group

Description:

Analgesia combines paracetamol (1g every 6 to 8 hours according to age and weight recommendations) and remifentanil, adapted according to a tiered administration system depending on the Behavior Pain Scale (BPS) and the theoretical ideal weight. Remifentanil doses are adjusted so that the patient has a BPS score of 4 or less. Reassessment of analgesia will be carried out every 30 minutes until analgesic adaptation is complete, then every 2 hours as is usually done in our department. If the BPS is less than or equal to 4, the therapeutic de-escalation will be done with a reverse algorithm until the analgesic drugs are stopped. After the sedation balance phase, the patient's BPS will be assessed every 2 hours.

Treatment:

Drug: Standard multimodal analgesia

OFA Group

Experimental group

Description:

A fixed combination of nefopam and tramadol will be initiated at daily doses. An initial dose of 50mg tramadol and 20mg nefopam IV over 30 min. will be administered. Reassessment of analgesia will be performed every 30 min. for two hour and then every 2 hours. * If BPS is \> 4, administration of ketamine with an initial bolus of 0.15mg/kg followed by continuous administration at a dose of 0.15mg/kg/hour. * If the BPS is \< 4, remifentanil is introduced at the minimum effective dose, in a stepwise fashion according to the theoretical ideal weight * In the event of maximum pain requiring the full range of therapies in the algorithm the total dose of tramadol will be 450mg/day and nefopam 120mg/day, in accordance with summaries of product characteristics. * If the BPS \< or = 4, the therapeutic de-escalation will be done with a reverse algorithm until the analgesic drugs are stopped, according to the following scheme: remifentanil, ketamine, tramadol and then nefopam.

Treatment:

Drug: OFA multimodal analgesia