Dexmed/Buspirone Synergism on Shivering

Do Dexmedetomidine and Buspirone Synergistically Reduce the Threshold, Gain, and Maximum Intensity of Shivering?

The purpose of this research is to determine if the combination of buspirone and dexmedetomidine are effective as a treatment to induce therapeutic hypothermia. The design of the study includes four study days done in random order. The days are as follows: 1) Control (no drug); 2) Buspirone 60 mg orally; 3) Dexmedetomidine (delivered by a computer-controlled IV infusion to a target plasma concentration of 0.6 ng/ml); and, 3) the combination of buspirone 60 mg and dexmedetomidine (target plasma concentration of 0.6 ng/ml). a 20 cm-long catheter will be inserted into a cubital vein using standard aseptic technique In addition to the PIC line catheter, a simple peripheral catheter will be inserted into the other arm for drug administration. Throughout the study period, mean-skin temperature will be maintained at 31°C by adjusting the temperature of circulating water (Cincinnati Sub-Zero, Cincinnati, OH) and forced-air warmers (Augustine Medical, Inc., Eden Prairie, MN). Furthermore, the back, upper-body, and lower-body will individually be maintained at the designated skin temperature. Lactated Ringer's solution cooled to ≈3°C will be infused via the PIC-line at rates sufficient to decrease tympanic membrane temperature ≈1.5°C/h. Fluid will be administered as long as oxygen consumption or electromyographic intensity (see below) continues to increase or a total of 5 liters of fluid is given. Heart rate will be measured continuously using an electrocardiogram; blood pressure will be determined oscillometrically at 5 min intervals at the ankle. In case heart rate and/or blood pressure changes unexpectedly (by more than 30% of the baseline), the study will stop and the volunteer will be re-warmed immediately.

Dexmedetomidine (delivered by a computer-controlled IV infusion to target a plasma concentration of 0.6 ng/mL) will be given during controlled hypothermia

the combination of 60 mg buspirone and dexmedetomidine (target plasma concentration of 0.6 ng/mL) will be given during controlled hypothermia

Inclusion Criteria: 18-40 years normal weight (BMI <35) healthy Exclusion Criteria: obese (BMI >35) taking any drugs thyroid disease, dysautonomia, or Raynaud's syndrome severe claustrophobia