Effect of Perioperative Intravenous Lidocaine on Postoperative Opioid Related-side Effects After Open HEPatectomy: a Multicentre Prospective Randomized Controlled Study
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 312
- 试验地点
- 9
研究概览
简要总结
Liver resection is increasingly performed for hepatic tumors, mainly primary liver cancers and resectable metastases, but also for some benign lesions. Postoperative pain is often significant, regardless of the surgical technique, making effective pain control essential to promote early mobilization and reduce complications.
Current standard care relies on multimodal analgesia, combining several drugs administered during surgery, with morphine administered as rescue therapy when required. Morphine is associated with side effects such as nausea, vomiting, ileus, hypoxemia, opioid-induced hyperalgesia, and transient cognitive impairment. Therefore, there is a need to optimize pain management while reducing opioid consumption and related adverse effects.
Intravenous (IV) lidocaine has well-documented anti-inflammatory effects and is effective against neuropathic pain. Several studies have shown that intravenous lidocaine may be associated with improved analgesia, reduced opioid consumption, shorter hospital stay, and decreased postoperative ileus, nausea, and vomiting-particularly in abdominal and genitourinary surgeries. Therefore, Intravenous (IV) lidocaine may be a valuable alternative for postoperative pain management after liver surgery.
National guidelines now recommend perioperative Intravenous (IV) lidocaine for abdominal surgeries but its efficacy in liver surgery has not yet been established due to a lack of specific evidence (more specific data are needed). Findings from other types of abdominal surgery suggest a potential benefit, which should be confirmed by dedicated clinical trials and robust multicenter evaluation such as the ILHEP protocol.
The goal of this clinical trial is to assess the effect of intravenous perioperative lidocaine on postoperative opioid related-side effects and to formally confirm the safety of lidocaine during hepatic surgical procedures. The hypothesis is that Intravenous (IV) lidocaine compared with placebo (a look-alike substance that contains no drug e.g. a saline solution) would improve postoperative outcome by reducing opioid related side-effects in patients undergoing liver surgery and benefitting of the same baseline analgesia.
In the context of this trial, patients will receive either intravenous lidocaine or placebo according to their assigned randomization group during standardized general anesthesia, and will then be followed throughout their hospital stay until discharge or up to a maximum of 28 days.
An ancillary study will be conducted in patients enrolled at the coordinating center in Rennes to assess exposure to lidocaine during intravenous administration and to evaluate the relationship between blood concentrations and adverse events.
详细描述
Patients scheduled for surgery under general anesthesia meeting the inclusion criteria will be eligible. During the preoperative anesthesia consultation (from Day-30 to Day-1), the investigator will present the study and the objectives of the research to the patient. When the patient arrives for admission, on the same day as the experimental visit or the day before (from Day-1 or Day 0), the investigator will verify the inclusion criteria and collect the written informed consent. Once inclusion has been validated, data will be collected : Socio-demographic data / Clinical data / List of chronic medications prior to surgery.
After signing the consent form and before the first dose of medication is taken, participants will be randomized into the control (placebo) or experimental group (lidocaine). In order to ensure group compatibility, a plan of randomization will be used : patients will be assigned to the treatment group in chronological order of randomization numbers, using a centralized randomization method via Ennov software (Ennov Clinical, Groupe Ennov, Paris, France). Randomization will be carried out online by investigators as close as possible to the surgery (Day-1 or Day 0). Participants and investigators will be blinded to the intervention.
Regarding the surgical procedure, general anesthesia will be standardized, and patients will receive either placebo or lidocaine according to the group to which they were assigned during randomization.
Physicians will be warned to reinject sufentanil or remifentanil during surgery in an opioid sparing spirit.
The postoperative protocol will be standardized. Extubation defines the Hour 0 for assessment of the primary criterion events. Aside from the placebo or lidocaine administered according to their randomization group, all patients will receive standard postoperative treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criterion 1 : Age ≥ 18 years
- •Inclusion criterion 2 : Undergoing a scheduled surgery for open hepatectomy
- •Inclusion criterion 3 : Effective contraception in accordance with CFTG recommendations
- •Inclusion criterion 4 : Having received oral and written information about the protocol and having signed a consent form to take part in this research
- •Inclusion criterion 5 : Affiliated to a social security scheme
排除标准
- •Exclusion criterion 1 : Weight > 100 kg
- •Exclusion criterion 2 : Allergy or contraindication to lidocaine or one of its excipients and, in particular:
- •Known hypersensitivity to lidocaine hydrochloride, to amide-type local anesthetics, or to any of the excipients (sodium chloride, sodium hydroxide solution or concentrated hydrochloric acid solution, water for injection)
- •Treatment with following antiarythmic medication : class I, class III or Sotalol
- •Heart failure NYHA grade 3-4, AV-block >1, without pacemaker
- •Acute porphyria
- •Recurrent porphyrias
- •Uncontrolled epilepsy / Seizure at enrollment
- •Exclusion criterion 3 : Allergy to one of the drugs used for anaesthesia or one of their excipients
- •Exclusion criterion 4 : Nefopam contraindication and, in particular:
- •Renal insufficiency (Creatinine clearance < 15 mL/min)
- •Untreated glaucoma
- •Uncontrolled epilepsy
- •Exclusion criterion 5 : Ketoprofen contraindication and, in particular:
- •Renal insufficiency (Creatinine clearance < 50 mL/min)
- •Inflammatory bowel disease
- •Exclusion criterion 6 : Urgent surgery
- •Exclusion criterion 7 : Transplant surgery or transplanted patients
- •Exclusion criterion 8 : Surgery with planned regional anaesthesia
- •Exclusion criterion 9 : Patient with a preoperative Sp02 < 95%
- •Exclusion criterion 10 : Obstructive sleep apnea syndrome
- •Exclusion criterion 11 : Severe hepatic insufficiency (Prothrombin Ratio < 15%)
- •Exclusion criterion 12 : Patient with an ongoing opioid medication that will blur the results
- •Exclusion criterion 13 : Adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of their liberty, pregnant or breast-feeding women, minors, persons unable to express their consent, persons hospitalized for a different reason
- •Exclusion criterion 14 : Known participation in other interventional research (RIPH1 or RIPH2)
研究组 & 干预措施
Lidocaine Group
Standard anaesthesia protocol with lidocaine
干预措施: Standardized General Anesthesia Induction and Maintenance Protocol incorporating Intravenous Lidocaine (Drug)
Control Group
Standard anaesthesia protocol with placebo (NaCl)
干预措施: Standardized General Anesthesia Induction and Maintenance Protocol incorporating Placebo (Drug)