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LIDOCRIT : Effect of Continuous Intravenous LIDOcaine on Discomfort in Postoperative CRITical Care Inpatients

Not Applicable
Not yet recruiting
Conditions
Post-surgery Critical Incare
Interventions
Registration Number
NCT07043023
Lead Sponsor
Rennes University Hospital
Brief Summary

Although pain management in intensive care units and intensive care units has improved since the DOLOREA study, research into therapies and techniques to optimise analgesia is still needed. The many adverse effects of morphine are well known, and it has been observed that excessive sedation during the first 48 hours is associated with an increase in mortality and length of stay. Multimodal analgesia protocols, preferably including non-morphine analgesics, could improve the comfort of critical care patients.

Comfort is a central element of critical care and perioperative management, as demonstrated by Patients-Reported Outcomes (PRO), new assessment tools that take into account the patient as a whole. The (Inconfort of REAnimation Patients) IPREA questionnaire, a specific scale for assessing the comfort of critical care patients, is an example of a PRO.

Lidocaine is a voltage-dependent sodium channel blocker, used as a local anaesthetic and antiarrhythmic agent, whose intravenous administration produces analgesic effects, particularly on hyperalgesia. The widely demonstrated clinical benefits in scheduled and major surgery (reduced post-operative pain, reduced doses of anaesthetic agents and opiates, reduced post-operative nausea and vomiting) have led to recommendations for its use. Furthermore, adverse events associated with lidocaine in continuous infusion are minimal.

Based on the early Comfort using Analgesia (eCASH), minimal Sedative and maximal Human care) concepts, the recent PADIS (Pain, Agitation, Delirium, Immobility, Sleep deprivation) recommendations, which determine levels of evidence and research avenues for improving the quality of care, conclude that intravenous lidocaine may be beneficial, but there is a lack of data.

The investigators are therefore proposing a randomised placebo-controlled clinical trial to assess the effectiveness of lidocaine infused continuously for 48 hours on the perceived comfort of post-operative critical care patients, as assessed by the IPREA score.

IPREA, an 18-item score exploring PADIS, is a direct, relevant, objective and reproducible assessment criterion for evaluating algorithms for improving the quality of care. The data on sources of discomfort reveal the importance of pain, dyspnoea, thirst and sleep deprivation, which are all influenced by the analgesia-sedation protocol. Incorporating lidocaine with anti-hyperalgesic properties into the protocol should reduce discomfort in critical care patients.

Detailed Description

The choice of analgesia protocol will be left to the discretion of the clinician between MORPHINE CHLORHYDRATE, SUFENTANIL and REMIFENTANIL for objectives of Behavioral Pain Scale (BPS) (3 to 5) or pain visual analogue scale (VAS) \< 4.

The use of co-analgesics intraoperatively (Paracetamol, Nefopam, NSAIDs (nonsteroidal anti-inflammatory drugs) such as Ketoprofen or Ibuprofen, Ketamine) is authorised (data not collected).

If a hypnotic is required intraoperatively, the choice of agent is left to the discretion of the clinician.

Once the sedation-analgesia protocol has been discontinued, pain relief is left to the clinician's discretion.

Patients are monitored from randomisation until discharge from the critical care unit or until a maximum of 30 days post-operatively.

In the event of an adverse reaction linked to lidocaine (see list in § 8.2.), the doctor stops administration of the product.

The blind is lifted (see § 9.2 'Insu (or blinding)'). If the patient is in the lidocaine group, the lidocaine plasma concentration is measured to check for a toxic plasma concentration (see § 5.6 'Management of biological samples').

It should be noted that the completion of an assay or discontinuation of treatment does not result in the patient's withdrawal from the clinical trial. Patient follow-up continues until the end of the trial.

If the patient is discharged from critical care before the 30th post-operative day, the patient's vital status on the 30th post-operative day will be collected.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
246
Inclusion Criteria
  1. Patient over 18
  2. Patient admitted immediately post-operatively in critical care (scheduled or emergency admission, e.g. post-operative exploratory laparotomy, cardiac surgery, major orthopaedic surgery such as polytrauma patients, vascular surgery at risk of complications such as open aortic surgery)
  3. Anticipated length of stay in critical care ≥ 48h
  4. Membership of a social security scheme
  5. Informed consent signed by the patient or by a close relative or legal representative or, failing this, the emergency procedure

Non-inclusion Criteria:

  1. Weight over 100 kg
  2. Hypersensitivity to one of the active substances used for anaesthesia or to one of the excipients.
  3. Known acute porphyria,
  4. Pregnant or breast-feeding women
  5. Patients who have received or are about to receive peri-medullary analgesia intra-operatively or post-operatively.
  6. Patient who has received or will receive loco-regional analgesia intra-operatively or post-operatively.
  7. Severe head injury, open cephalic neurosurgery, interventional neuroradiology
  8. Recovered cardiorespiratory arrest
  9. Noradrenaline doses > 0.5 μg/kg/min
  10. Stage IV/V chronic renal failure, not on dialysis
  11. Severe hepatocellular insufficiency at inclusion (Child-Pugh C)
  12. Bradycardia < 50 bpm on antiarrhythmic drugs
  13. Clinical convulsive seizure at inclusion
  14. Predictable inability to answer the questionnaire (cognitive impairment, non-Francophone)
  15. Known participation in another interventional research study (RIPH1 or RIPH2)
  16. Known situation of deprivation of liberty or legal protection (safeguard of justice, guardianship or curatorship)
Exclusion Criteria

Patients under court protection will be excluded as soon as the investigator is aware of their status.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LidocaineLidocaine (drug)Lidocaine 2%, bolus of 0.075 ml/kg real weight (i.e. 1.5 mg/kg) then continuous intravenous administration by electric syringe at 0.05 ml/kg/h (i.e. 1 mg/kg/h) for 48 hours
PlaceboPlaceboPlacebo (sodium chloride 0.9%), bolus of 0.075 ml/kg of real weight then continuous intravenous administration by electric syringe at 0.05 ml/kg/h for 48h
Primary Outcome Measures
NameTimeMethod
IPREAWithin 24 hours of discharge from critical care or, failing that, within 24 hours of the 15th day of hospitalisation in critical care.

Overall score on the Inconforts of Patients in Intensive Care (IPREA) questionnaire.

Comfort is assessed by the patient him/herself, using a self-assessment scale IPREA, which is explained and conducted with the medical or paramedical staff in the intensive care unit or intensive care unit.

The IPREA questionnaire was developed specifically for critical incare patients.

The patient rates his discomfort on a 100 mm graduated visual scale presented horizontally (0: no discomfort, 100: maximum discomfort) for 18 items including (noise, excess light, discomfort of sleeping in intensive care bed, lack of sleep, thirst, hunger, cold, heat, pain, presence of pipes, lack of privacy, anxiety, isolation, limitation of visits, absence of telephone, lack of information, difficulty breathing, depression).

The overall score is calculated from the average of each item, giving a score from 0 (minimum discomfort) to 100 (maximum discomfort).

Secondary Outcome Measures
NameTimeMethod
Occurrence of pneumoniaDuring the stay in critical care, including, in the event of transfer, the stay in critical care in the transfer hospital, up to day 30

Occurrence of pneumonia according to the Recommandations Formalisées d'Experts (RFE) Société française d'anesthésie et de réanimation (SFAR)/Société de Réanimation de Langue Française (SRLF) 2017 'Healthcare-associated pneumonia' criteria in the appendix.

In the event of death or premature exit, the criterion will be assessed for the period preceding death or exit.

IPREA - Sensitivity analysis of the main criterionWithin 24 hours of discharge from critical care or, failing that, within 24 hours of the 15th day of hospitalisation in critical care.

Sensitivity analysis of the main criterion

Data from patients who died will be imputed according to the following strategy:

* the values of patients who died before D7 at the worst value of the IPREA score (100),

* values for patients who died after D7 by multiple imputation.

The IPREA questionnaire was developed specifically for critical incare patients. The patient rates his discomfort on a 100 mm graduated visual scale presented horizontally (0: no discomfort, 100: maximum discomfort) for 18 items including (noise, excess light, discomfort of sleeping in intensive care bed, lack of sleep, thirst, hunger, cold, heat, pain, presence of pipes, lack of privacy, anxiety, isolation, limitation of visits, absence of telephone, lack of information, difficulty breathing, depression). The overall score is calculated from the average of each item, giving a score from 0 (minimum discomfort) to 100 (maximum discomfort).

IPREAWithin 24 hours of discharge from critical care or, failing that, within 24 hours of the 7th day of hospitalisation in critical care

Patients who have died will be considered as not evaluable.

Overall score on the IPREA questionnaire. Comfort is assessed by the patient him/herself, using a self-assessment scale IPREA, which is explained and conducted with the medical or paramedical staff in the intensive care unit or intensive care unit. The IPREA questionnaire was developed specifically for critical incare patients. The patient rates his discomfort on a 100 mm graduated visual scale presented horizontally (0: no discomfort, 100: maximum discomfort) for 18 items including (noise, excess light, discomfort of sleeping in intensive care bed, lack of sleep, thirst, hunger, cold, heat, pain, presence of pipes, lack of privacy, anxiety, isolation, limitation of visits, absence of telephone, lack of information, difficulty breathing, depression). The overall score is calculated from the average of each item, giving a score from 0 (minimum discomfort) to 100 (maximum discomfort).

IPREA - 8 itemsWithin 24 hours of discharge from critical care or, failing that, within 24 hours of the 15th day of hospitalisation in critical care.

Result per item of 8 items of the IPREA score, achieved :

* Noise

* Thirst

* Pain

* Medical devices (catheters, intubation tubes, etc.)

* Sleepiness

* Dyspnoea

* Anxiety

* Depression

Patients who have died will be considered as not evaluable.

Overall score on the IPREA (Inconforts of Patients in Intensive Care) questionnaire. Comfort is assessed by the patient him/herself, using a self-assessment scale IPREA, which is explained and conducted with the medical or paramedical staff in the intensive care unit or intensive care unit. The IPREA questionnaire was developed specifically for critical incare patients. The patient rates his discomfort on a 100 mm graduated visual scale presented horizontally (0: no discomfort, 100: maximum discomfort) for 18 items. The overall score is calculated from the average of each item, giving a score from 0 (minimum discomfort) to 100 (maximum discomfort).

Cumulative opioid consumptionOver the first 6 post-surgery days

Cumulative opioid consumption (in mg IV morphine equivalent, or µg Remifentanil or µg Sufentanil)

In the event of death or premature exit, the criterion will be assessed for the period preceding death or exit.

Duration of invasive mechanical ventilationUntil discharge from critical care, including, in the event of transfer, the stay in critical care in the transfer hospital, or, failing this, until day 30

Duration of invasive mechanical ventilation in critical care

In the event of death or premature exit, the criterion will be assessed for the period preceding death or exit.

Occurrence of re-intubationWithin 48 hours of extubation (until discharge from critical care, including, in the event of transfer, the stay in critical care in the transfer hospital, or, failing that, until day 30)

Occurrence of re-intubation

In the event of death or premature exit, the criterion will be assessed for the period preceding death or exit.

Duration of sedationUntil discharge from critical care, including, in the event of transfer, the stay in critical care in the transfer hospital, or, failing this, until day 30

Duration of sedation

In the event of death or premature exit, the criterion will be assessed for the period preceding death or exit.

Duration of stay in critical careUntil day 30

Duration of stay in critical care, including, in the event of transfer, the stay in critical care in the transfer hospital

In the event of death or premature exit, the criterion will be assessed for the period preceding death or exit.

Duration of stay in hospitalUntil day 30

Duration of stay in hospital including, in the event of transfer, the stay in the transfer hospital

In the event of death or premature exit, the criterion will be assessed for the period preceding death or exit.

Vital statusDay 30

Vital status In the event of premature discharge, the vital status will be censored on the date of discharge.

Incidence of serious adverse reactions attributable to lidocaineFor the duration of the treatment and 24 hours after the end of the treatment

Incidence of serious adverse reactions attributable to lidocaine :

* Conduction disorders on Electrocardiogram (ECG) not present before treatment,

* Cardiac arrest

* Respiratory arrest

* Anaphylactic shock of any grade

* Hypotension requiring the introduction of noradrenaline or a significant (\>20%) increase in the dose of noradrenaline (if treatment with noradrenaline was already underway when the experimental treatment was initiated).

* Bradycardia requiring the introduction of atropine

* Bradycardia requiring the introduction of dobutamine

* Bradycardia requiring the introduction of isoprenaline

* Convulsive seizures

* Presumed lidocaine intoxication defined by the presence of two of the following:

* Vertigo

* Dysgeusia

* Perioral and lingual paresthesias, dysarthria

* Blurred vision

* Tinnitus, hearing dysfunction

* Tremor

In the event of death or premature exit, the criterion will be assessed for the period preceding death or exit.

Trial Locations

Locations (15)

CHU d'Angers - RCA (Réanimation Chirurgicale A)

🇫🇷

Angers, France

CHU d'Angers - RCB (Réanimation Chirurgicale B)

🇫🇷

Angers, France

CHU de Brest - Réanimation Cardiaque

🇫🇷

Brest, France

CH Louis Pasteur (Chartres) - Réanimation

🇫🇷

Chartres, France

CHU de Nantes - Hôpital Guillaume et René Laennec - Réanimation Chirurgicale Polyvalente

🇫🇷

Nantes, France

CHU de Nantes - Hôpital Guillaume et René Laennec - Réanimation CTCV

🇫🇷

Nantes, France

CHU de Nantes - Hôtel-Dieu - Réanimation chirurgicale

🇫🇷

Nantes, France

CHU de Poitiers - Réanimation Chirurgicale

🇫🇷

Poitiers, France

CHU de Rennes - Réanimation chirurgicale

🇫🇷

Rennes, France

CHU de Rennes - Réanimation CTCV

🇫🇷

Rennes, France

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CHU d'Angers - RCA (Réanimation Chirurgicale A)
🇫🇷Angers, France
Sigismond LASOCKI, MD
Principal Investigator

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