OFICU: OPIOID-FREE ANALGESIA IN ICU IN INTENSIVE CARE UNIT
Study Details
Study Description
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, we 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. We conducted a prospective, ''proof of concept'', randomized, double-blind, parallel group, placebo-controlled trial. We studied multimodal analgesia versus standard-of-care in ICU patients requiring sedation-analgesia for invasive mechanical ventilation.We hypothesized that Remifentanil consumption decrease by 15% with the use of a standardized multimodal analgesia strategy
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
ICU patients requiring sedation-analgesia for mechanical ventilation for at least 72 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.
We hypothesize a 15% reduction of Remifentanil consumption in the interventional group.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Control group 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. |
Drug: Standard multimodal analgesia
Standard remifentanil analgesia
|
| Experimental: OFA Group 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. |
Drug: OFA multimodal analgesia
Multimodal opioid free analgesia
|
Outcome Measures
Primary Outcome Measures
- Daily remifentanil consumption (after randomisation) [48th hour 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 72 hours of mechanical ventilation
Secondary Outcome Measures
- Impact of a non-opioid analgesia strategy on morphine savings at D7 [Day 28]
Cumulative dose of remifentanil
- Impact of an opioid-free analgesia strategy on sedative consumption [Day 28]
Number of lived days free of remifentanil
- Impact of an opioid-free analgesia strategy on sedative consumption [Day 28]
Daily consumption of sedative drugs from inclusion to D28
- Impact of a non-opioid analgesia strategy on the duration of mechanical ventilation [Day 28]
Number of live days free of mechanical ventilation
- Impact of an opioid-free analgesia strategy on norepinephrine [Day 28]
Number of lived days free of norepinephrine
- Impact of a non-opioid analgesia strategy on organ failure at D28 [Day 28]
SOFA Score (Sepsis-related Organ Failure Assessment)
- Impact of a non-opioid analgesia strategy on fluid intake [Day 28]
Daily fuid intake in milliliter
- Impact of a non-opioid analgesia strategy on mental confusion [Day 28]
CAM ICU test
- Impact of a non-opioid analgesia strategy on the occurrence of morphine-related adverse events [Day 28]
Presence of one or more events of special interest or expected adverse events: constipation, bradycardia, bladder globe, nausea, vomiting, liver disturbance, serotonin syndrome
- Impact of a non-opioid analgesia strategy on the incidence of ventilator-associated pneumonia [Day 28]
Presence of pneumonia associated with mechanical ventilation
- Impact of a non-opioid analgesia strategy on extubation failure rates [48 hours after extubation]
extubation failure and cause (reintubation within 48 hours of first extubation)
- Impact of a non-opioid analgesia strategy onICU and hospital length of stay [Day 90]
Length of stay in the intensive care unit and in the hospital
- Impact of the non-opioid analgesia strategy on vital prognosis at D28 and D90. [Day 90]
Vital status at day 28 and day 90
- Impact of a non-opioid analgesia strategy on morphine dependence at D90 [Day 90]
Opioid use at D90
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient hospitalized in ICU and requiring sedation-analgesia for mechanical ventilation.
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Patient undergoing mechanical ventilation for more than 2 hours and less than 24 hours.
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Informed consent signed by the patient or his trusted person, legal representative, family member, curator or tutor, or emergency consent procedure.
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Patient affiliated to the French Government Public Health Insurance.
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Patient over 18 years old.
Exclusion Criteria:
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Patient already involved in a trial that might influence our primary endpoint.
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Patient in exclusion-period determined by another trial or study.
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Patient who is likely to be requiring less than 72 hours of mechanical ventilation.
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Patient with contraindication or allergies to at least one of the following medication : paracetamol, nefopam, tramadol, ketamine, remifentanil.
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Patient with hepatic insufficiency (defined as PT < 50%).
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Parturient or breast-feeding patient.
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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).
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Patient requiring curare treatment.
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Patient requiring ICU after undergoing major surgery (laparotomy or thoracotomy).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Remy WIDEHEM | Nîmes | Gard | France | 30029 |
Sponsors and Collaborators
- Centre Hospitalier Universitaire de Nīmes
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- LOCAL/2022/RW-01
- 2022-003273-37