Clinical trial NCT05825560: Opioid-free Analgesia in Intensive Care Unit
Official title: Opioid-free Analgesia in Intensive Care Unit: a Prospective, Monocentric, Randomized, Double Blind, Feasability Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Intubation
Keywords: orotracheal intubation
mechanical ventilation
sedation analgesia
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2023-04-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Daily remifentanil consumption (after randomisation)
timeFrame: 48th hour after randomisation
Secondary outcomes:
measure: Impact of a non-opioid analgesia strategy on morphine savings at D7
timeFrame: Day 28
measure: Impact of an opioid-free analgesia strategy on sedative consumption
timeFrame: Day 28
measure: Impact of an opioid-free analgesia strategy on sedative consumption
timeFrame: Day 28
measure: Impact of a non-opioid analgesia strategy on the duration of mechanical ventilation
timeFrame: Day 28
measure: Impact of an opioid-free analgesia strategy on norepinephrine
timeFrame: Day 28
measure: Impact of a non-opioid analgesia strategy on organ failure at D28
timeFrame: Day 28
measure: Impact of a non-opioid analgesia strategy on fluid intake
timeFrame: Day 28
measure: Impact of a non-opioid analgesia strategy on mental confusion
timeFrame: Day 28
measure: Impact of a non-opioid analgesia strategy on the occurrence of morphine-related adverse events
timeFrame: Day 28
measure: Impact of a non-opioid analgesia strategy on the incidence of ventilator-associated pneumonia
timeFrame: Day 28
measure: Impact of a non-opioid analgesia strategy on extubation failure rates
timeFrame: 48 hours after extubation
measure: Impact of a non-opioid analgesia strategy onICU and hospital length of stay
timeFrame: Day 90
measure: Impact of the non-opioid analgesia strategy on vital prognosis at D28 and D90.
timeFrame: Day 90
measure: Impact of a non-opioid analgesia strategy on morphine dependence at D90
timeFrame: Day 90
Other outcomes:
Locations:
city: Nîmes
country: France
facility: Remy WIDEHEM
state: Gard
Study officials:
References:
citation: Wheeler KE, Grilli R, Centofanti JE, Martin J, Gelinas C, Szumita PM, Devlin JW, Chanques G, Alhazzani W, Skrobik Y, Kho ME, Nunnally ME, Gagarine A, Ergan BA, Fernando S, Price C, Lewin J, Rochwerg B. Adjuvant Analgesic Use in the Critically Ill: A Systematic Review and Meta-Analysis. Crit Care Explor. 2020 Jul 6;2(7):e0157. doi: 10.1097/CCE.0000000000000157. eCollection 2020 Jul.
citation: Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.