Sustained metabolic reduction and hypothermia in humans

Area of Science:

• Physiology
• Pharmacology
• Space Medicine

Background:

• Metabolic reduction is a key adaptation for survival in resource-scarce environments.
• Lowering human metabolism can conserve oxygen and reduce waste, crucial for long-duration spaceflight and extreme terrestrial conditions.
• Previous studies showed dexmedetomidine's potential for short-term metabolic reduction.

Purpose of the Study:

• To investigate a longer-acting dexmedetomidine dosing strategy for sustained metabolic reduction.
• To evaluate the efficacy of a sublingual loading dose followed by a subcutaneous infusion (SQI) of dexmedetomidine.
• To assess the impact of SQI dexmedetomidine, with and without surface cooling, on metabolic rate over six hours.

Main Methods:

• Eleven healthy volunteers received an oral loading dose of dexmedetomidine followed by a six-hour SQI.
• Seven participants also underwent surface cooling to enhance heat loss.
• Metabolic rate was measured using indirect calorimetry, and core body temperature was monitored via telemetry.

Main Results:

• Energy expenditure decreased from baseline in all participants, irrespective of surface cooling.
• Core body temperature significantly dropped in the group receiving surface cooling, reaching a median of 35.4°C.
• The administration of dexmedetomidine via SQI was found to be safe and effective in reducing metabolic rate.

Conclusions:

• A regimen of sublingual loading dose followed by a six-hour SQI of dexmedetomidine effectively reduces metabolic rate in humans.
• This extended-duration administration method holds potential for applications requiring metabolic suppression.
• Further research is warranted to explore alternative administration methods, efficacy without a loading dose, and long-term tolerance.