The effect of hypothermia on the protein binding of lidocaine in plasma from six healthy volunteers was studied in vitro. A significant increase (p <0.001) in the unbound fraction of lidocaine was found at 24°C (38.3 [SD 7.0] %) compared to 37°C (30.7 [SD 6.0] %). A further reduction in temperature to 10°C resulted in a slight but not statistically significant increase in the free fraction of the drug (39.9 [SD 10.2] %). As a conclusion, hypothermia enhances the transfer of lidocaine over the blood-brain barrier. In order to avoid unwanted side effects or frank toxicity, caution is recommended when administering highly protein-bound drugs during hypothermic conditions.
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