Pharmacokinetic Profile of Lidocaine Given as a Weight-based Infusion for Postoperative Surgical Pain Control

1. Background Information

1.1 Investigational Product Lidocaine HCl 2%, perioperative intravenous weight-based infusion over 48 h

1.2 Summary of Literature Given the ongoing opiate epidemic there is a need for alternative multimodal analgesia approaches to post-surgical pain. Intravenous lidocaine infusions are known to be effective for the management of acute perioperative pain,(1-5) and may help prevent the development of chronic pain(6). Guidelines have been developed to guide clinical practice (6) and lidocaine infusions are used routinely in many centres throughout Canada for post-surgical pain management.

The currently accepted plasma lidocaine levels required for acute analgesia are 1.1 - 4.2 μg/mL (7-9) with a tighter goal of 2.5 - 3.5 μg/mL recommended in other papers (6). Minor adverse CNS effects have been described at a plasma level of 5-10 μg/mL, with more serious CNS and CVS effects reported at levels greater than 10 μg/mL(6,7,9). Minor CNS effects therefore occur at levels outside but close to the upper limits of the described therapeutic ranges.

Current pharmacokinetic data used to guide lidocaine infusions have been derived largely from studies using healthy volunteers. Factors such as age, BMI and the stress response to surgery can alter pharmacokinetics via mechanisms including altered hepatic blood flow and changes in serum proteins(6-8,12). Accurate pharmacokinetic modelling of weight-based lidocaine infusions in elderly patients and in those with higher BMI following major surgery is incomplete however and detailed pharmacokinetic data for these patient groups is required to optimize safe and effective analgesia.