Dexmed/Buspirone Synergism on Shivering

Study Overview
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Brief Summary
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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.

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

Conditions
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Hypothermia

Intervention / Treatment
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* Drug: dexmedetomidine
* Drug: buspirone
* Drug: Bus and Dex
* Drug: Control


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>dexmedetomidine | Drug: dexmedetomidine<br>* Dexmedetomidine (delivered by a computer-controlled IV infusion to target a plasma concentration of 0.6 ng/mL) will be given during controlled hypothermia<br>|
| Experimental: 2<br>Buspirone | Drug: buspirone<br>* Buspirone, 60 mg orally, will be given during controlled hypothermia.<br>|
| Experimental: 3<br>Buspirone and dexmedetomidine | Drug: Bus and Dex<br>* the combination of 60 mg buspirone and dexmedetomidine (target plasma concentration of 0.6 ng/mL) will be given during controlled hypothermia<br>|
| Placebo Comparator: Control<br>No drug | Drug: Control<br>* No drugs given during controlled hypothermia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shivering threshold |  | 3 hours | 
| maximum intensity of shivering |  | 3 hours | 
| gain of shivering |  | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hemodynamic responses |  | 3 hours |