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.

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).