Naloxone reverses thrombin‐induced increase in TxB2 in patients treated with subtherapeutic dose of ketamine during wisdom teeth extraction

Abstract

In a prospective clinical study, we hypothesized that administration of a sub‐therapeutic dose of Ketamine (0.2 mg/kg) intraoperative would reduce the activity of TXB2 at 0 and 72 hours post surgery. Blood samples were obtained from Ketamine‐treated and untreated patients at three designated time points: before surgery, immediately (0 h) and 72 h after surgery. Purified platelets were obtained from the samples to assess TXB2 activity. The suspension of purified platelets (1e6 cells/mL) was equally divided into four treatment groups (n=3): vehicle (100 μL saline), Thrombin (2 unit/mL), Naloxone (0.1 mM), and Naloxone + Thrombin groups. Immediately following surgery both Ketamine‐treated and ‐untreated patient samples exhibited a decrease in TXB2 levels; however the Ketamine‐treated group TXB2 levels were significantly higher than the untreated group. At 72 h post‐surgery, a significant increase in concentration of TXB2 was observed. Thrombin treatment of purified platelets showed a significant increase in TXB2 levels before surgery, an effect which persisted only in the Ketamine‐treated group after surgery. The Thrombin induced increase in TXB2 levels following sub‐therapeutic dose of Ketamine was reversed by Naloxone treatment immediately after surgery, but not 72 h after surgery. The data suggests that intraoperative use of sub‐therapeutic dose of Ketamine modulates TXB2 levels in a Naloxone‐sensitive manner. (Funded by Oral Maxillofacial Surgery Foundation)