Opioid-free Analgesia in Intensive Care Unit

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.

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).