Pharmacokinetics of lidocaine infusion during surgery for glioblastoma

Glioblastoma (GBM) is the most common primary malignant brain tumor and is universally fatal. Human and laboratory studies have suggested lidocaine has anti-GBM efficacy. The objective of this study was to assess direct cytotoxicity as a possible mechanism of anti-GBM efficacy of lidocaine by quantifying the concentration of lidocaine in tumor tissue during resection.

Twelve patients with pathology-confirmed IDHwt GBM were included in this study. The study group received an intravenous bolus dose of 1.5 mg/kg IBW of lidocaine at induction of anesthesia followed by 2 mg/kg IBW/hr infusion. Craniotomy was performed in the standard fashion. Up to 3 fresh tumor specimens were collected hourly from each patient after confirmation of diagnosis by frozen section. Plasma samples were simultaneously collected. Lidocaine concentration was measured using mass spectroscopy. The maximum concentration of lidocaine (C_max), time from bolus to maximum concentration (T_max), and area under curve from 0 to 3 h (AUC) were calculated for each patient. Patients were followed for survival and adverse events.

The median tumor specimen C_max, T_max, and AUC values were 333 ng/mL (range 226-555), 179 min (range 126-211), and 20,665 ng*min/mL (range 8003-55,426), respectively. Peak lidocaine concentration in tumor was reached in 6 of 11 cases (excluding one patient due to missing the 3rd sample). Median C_max and T_max for plasma samples were 1195 ng/mL (range 951-1475) and 191 min (range 156-211), respectively. Median overall survival was 308 days (95 % CI: 74-413). Two grade 3 adverse events occurred which were deemed to be unlikely related to the study intervention.

While lidocaine infiltrates tumor tissue when administered intravenously during GBM surgery, concentrations do not reach levels previously demonstrated to inhibit tumor growth in in vitro studies (roughly 2*10⁸ ng/mL lidocaine). Alternative mechanisms may explain previously observed improved outcomes with lidocaine administration in human studies.