Lidocaine for Opioid Sparing in Vaso-occlusive Crisis of Sickle Cell Disease

• Lidocain (Drug): Lidocaine hydrochloride 20 mg/mL, solution, 20 mL ampoule for IV administration (25 ampoules) Administration : parenteral route on peripheral or central venous catheter. - Bolus of 1.5 mg/kg bolus dur
• Placebo (Drug): Placebo is 20 mL ampoules of sodium chloride (NaCl 0.9%) for injection Administration : parenteral route on peripheral or central venous catheter. * Bolus of 1.5 mg/kg bolus during 30 minutes, with a maxium dose of 180 mg (18mL) * Immediately followed by a continuous infusion of 1 mg/kg/h (max 120mg/h = 12mL/h) during 72 hours.
• Standard of care (Drug): Standard of care

Primary outcomes

• Cumulative parenteral opioid dose between randomization and discharge from the intensive care unit expressed in morphine milligram equivalent. [up to 28 days]: To determine whether adding lidocaine to the standard of care in pain during severe vaso-occlusive crisis has an effect on the cumulative opioid consumption expressed as morphine milligram equivalent (MME)

Secondary outcomes

• Intensive Care Unit length of stay [up to 28 days]
• hospital length of stay [up to 28 days]
• Visual analogue pain Scale score during Intensive Care Unit stay [up to 28 days]: Compare between groups the pain intensity as evaluated using a Visual Analogue pain Scale from 0 (no pain) to 10 (very intense pain).
• Categorical Pain Score during Intensive Care Unit stay [up to 28 days]: Compare between groups the pain intensity as evaluated using Categorical Pain Score (CPS)
• Time of resolution of severe vaso-occlusive crisis [up to 28 days]: presence of at least three of the following four criteria: * continuous apyrexia for the last 8 hours, * no need for intravenous opioid infusion for the last 8 hours, * ability to walk or move without pain, * absence of spontaneous pain with a CPS ≤1
• time to last parenteral opioid dose [up to 28 days]: Time from randomisation to the last parenteral opioid dose
• vaso-occlusive crisis complications during Intensive Care Unit stay [up to 28 days]: secondary acute chest syndrome
• vaso-occlusive crisis complications during Intensive Care Unit stay [up to 28 days]: need for blood transfusion
• vaso-occlusive crisis complications during Intensive Care Unit stay [up to 28 days]: need for red blood cell exchange
• vaso-occlusive crisis complications during Intensive Care Unit stay [up to 28 days]: need for life-supporting therapies defined as invasive mechanical ventilation or dialysis or vasopressor support
• quality of life with reduced impact of Sickle Cell Disease on health [At Day 28]: Score of French version of Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). It is a patient-reported outcome measurement system with a 39 items questionnaire, assessing several aspects of SCD impact on general health state. For the present study, the questionnaires regarding emotional impact, pain episodes, pain impact, Social Functionning will be used.
• safety profile of lidocaine infusion [at 28 days]: Compare between groups safety profile of lidocaine infusion at D28
• Rate of readmission for vaso-occlusive crisis after Intensive Care Unit discharge [At day 28]: Frequency of any adverse events and frequency of serious adverse events
• Assess the economic efficiency of lidocaine added to standard of care compared to standard of care alone [At day 28]: Incremental cost-effectiveness ratio (cost per Quality-Adjusted Life-Year, QALY) comparing lidocaine + standard of care (SOC) to SOC alone

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age >= 18 years
* Known sickle cell disease with an SS, SC, Sβ, or Sβ+ genotype
* Patient admitted to the Intensive Care Unit for Vaso-Occlusive Crisis and/or ACS as the main reason for admission:

  * Vaso-Occlusive Crisis defined by acute pain or tenderness, affecting at least one part of the body, including limbs, ribs, sternum, head (skull), spine, and/or pelvis, not attributable to other causes
  * Acute Chest Syndrome defined by the association of clinical respiratory sign(s): dyspnea and/or chest pain and/or auscultatory abnormality (crepitants and/or bronchial breathing) with a new pulmonary infiltrate on chest X-ray, thoracic CT-scan, or lung ultrasound.
* Treatment with parenteral morphine or oxycodone started less than 72 hours prior to inclusion
* Patient or next of kin informed about the study and having consented to the participation of the patient in the study. If patient is no competent and no next of kin can be contacted during screening for the study, trial inclusion will be completed as an emergency procedure by the Intensive Care Unit physician, in compliance with French law.
* French speaking
* Patient with health care insurance

Exclusion Criteria:

* Pregnant women or nursing mothers; Women of child bearing potential will be tested for pregnancy before inclusion
* Patients under guardianship, curatorship or under legal protection
* Prisoners or subjects who are involuntarily incarcerated
* Sickle Cell Disease acute complication other than Vaso-Occlusive Crisis or Acute Chest Syndrome as the main reason for admission:

priapism, stroke, acute splenic sequestration, acute hepatic sequestration, bone marrow necrosis…

* Patients wearing a lidocaine-medicated plaster at the time of screening for inclusion
* Known or assumed hypersensitivity to lidocaine hydrochloride, other local anaesthetics (e.g., bupivacaine or ropivacaine) or an excipient
* Patients treated with anti-arhythmic drugs known to induce torsade de pointe.
* Patients on chronic or occasional treatment with drugs that interact with the 3A cytochrome isoenzymes (CYP3A) and/or 1A2 cytochrome isoenzymes (CYP1A2)
* Patients with recurrent porphyria, porphyria in remission, or known asymptomatic carriage of gene mutations responsible for porphyria
* Epileptic patients
* Hypovolemic shock or shock of other cause at screening for inclusion
* Known atrioventricular block, QT prolongation or other heart conduction disorder or heart failure
* Chronic respiratory failure with long term non invasive ventilation (excluding Continuous Positive Air way pressure), or long term oxygen therapy at home
* Acute Respiratory Distress Syndrome according to The 2012 Berlin definition
* Acute or Chronic liver failure with MELD > 19
* Acute or Chronic kidney failure with clearance <30mL/min/m2 according to CKD-EPI
* Body weight <40kg and >120kg
* Prior inclusion in the study in the last 3 months
* Patient under invasive mechanical ventilation
* Altered consciousness with Glasgow coma scale <13
* Patient already included in a clinical drug