Effects of Different Doses of Intravenous Lidocaine Infusion on Peri-operative Pain and Incidence of Postoperative Chronic Pain Within ERAS Protocols, a Dose Finding Study.

Enhanced recovery after surgery (ERAS) protocols or fast track surgery are a number of interventions which are carried out in the perioperative period. They are aimed to decrease the harmful effects of surgery on the body and help the patient recover better after surgery. ERAS has been shown to reduce the length of hospital stay, overall hospital costs, opioid consumption in the perioperative period and to reduce complication rates.

One of the most important components of ERAS is adequate perioperative pain control using a multi-modal analgesic approach to help decrease dependence on opioids and provide better recovery and less postoperative hospital stay. Also, the severity and duration of acute postoperative pain is one of the predictors of chronic postsurgical pain (CPSP). Neuroplasticity (spinal sensitization) following the trauma of surgery can transform an acute pain to chronic pain if not treated effectively by aggressive management of acute pain.

Lidocaine (or 2-(diethylamino)-N-(2.6-dimethylphenyl) acetamide) is the main prototype of amino-amide local anesthetics. It has analgesic, anti-hyperalgesic and anti-inflammatory properties, which enable its use as a general anesthetic adjuvant. It can reduce nociception, cardiovascular responses to surgical stress, postoperative pain, and analgesic requirements.

Accordingly, Lidocaine infusion can have a role in enhancing postoperative quality of recovery, decreasing incidence of chronic postoperative pain and even increasing overall survival in patients undergoing major surgeries like in pancreatectomy.

The Systemic effects of intravenous Lidocaine infusion depends on its plasma level which is affected by the rate and dose of administration, drug interactions and speed of metabolism and elimination. Around 90% of lidocaine undergoes hepatic metabolism (CYP3A4), with the production of active metabolites. During lidocaine continuous infusion, the accumulation of these metabolites may inhibit its biotransformation and might be involved in some cases of intoxication. The clearance rate of lidocaine is approximately 0.85 L/kg/h. Finally, lidocaine is eliminated by the kidney (10% of lidocaine is eliminated unchanged in the urine).

The target plasma concentrations for Lidocaine for providing effective analgesia is 2.4 ± 0.6 μg/mL, while side effects as - have been reported when the plasma concentration was higher than 5-8 μg/mL. The suggested dosing regimens mentioned in literature to achieve this effective plasma level while avoiding toxicity is a bolus of 1-2 mg/kg at surgery start followed by infusion of 1-2 mg/kg/h over the duration of the surgery which is a relatively wide range, specially, considering the wide variability in type and duration of surgeries, demographics, physical and medical status of patients and type of anesthetic agents and drugs used which all can affect Lidocaine activity, elimination \& toxicity.

To the best of our knowledge, no evidence exist in the literature that can point towards the ideal dosing regimen for intravenous Lidocaine infusion that can achieve the desired valuable clinical effects while decreasing the incidence of adverse side effects among the wide variety of surgeries and patients encountered within ERAS protocols.