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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | dexmedetomidine |
|
| 2 | Experimental | Buspirone |
|
| 3 | Experimental | Buspirone and dexmedetomidine |
|
| Control | Placebo Comparator | No drug |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dexmedetomidine | Drug | Dexmedetomidine (delivered by a computer-controlled IV infusion to target a plasma concentration of 0.6 ng/mL) will be given during controlled hypothermia |
|
| Measure | Description | Time Frame |
|---|---|---|
| Shivering threshold | 3 hours | |
| maximum intensity of shivering | 3 hours | |
| gain of shivering | 3 hours |
| Measure | Description | Time Frame |
|---|---|---|
| hemodynamic responses | 3 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rainer Lenhardt, MD, PhD | University of Louisville School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Outcomes Research Institute, University of Louisville | Louisville | Kentucky | 40202 | United States |
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| ID | Term |
|---|---|
| D007035 | Hypothermia |
| ID | Term |
|---|---|
| D001832 | Body Temperature Changes |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| D002065 | Buspirone |
| D002066 | Busulfan |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| buspirone | Drug | Buspirone, 60 mg orally, will be given during controlled hypothermia. |
|
| Bus and Dex | Drug | the combination of 60 mg buspirone and dexmedetomidine (target plasma concentration of 0.6 ng/mL) will be given during controlled hypothermia |
|
| Control | Drug | No drugs given during controlled hypothermia |
|
| D013141 |
| Spiro Compounds |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010879 | Piperazines |
| D011743 | Pyrimidines |
| D011083 | Polycyclic Compounds |
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |