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Peer-reviewedCC BY 4.0PLOS One

Dexmedetomidine effects on metabolic rate over 5 days in humans

  • Clifton W. Callaway1
  • Alexandra J. Weissman1
  • Katharyn L. Flickinger1
  • Victor Wu1
  • Jenna Monteleone1
  • Ryann DeMaio1
  • Mara Hierro1
  • Daniel Neofes2
  • Omarf Ortega-Reyes1
  • Tao Sheng1
  • Marianna Salinas1
  • Paul Lerro2
6 more authors
  • Francis X. Guyette1
  • Benjamin D. H. Gordon2
  • Marie Mortreux3
  • Kathleen Melanson3
  • Daniel J. Buysee4
  • Philip E. Empey5
5 affiliations
  1. 1Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
  2. 2Department of Health and Human Development, University of Pittsburgh School of Education, Pittsburgh, Pennsylvania, United States of America
  3. 3Department of Nutrition, University of Rhode Island College of Health Sciences, Kingston, Rhode Island, United States of America
  4. 4Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
  5. 5Center for Clinical Pharmaceutical Sciences, Department of Pharmacy, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, United States of America and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, United States of America
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Abstract

The alpha-2-adrenergic agonist drug dexmedetomidine induces sleep-like sedation and reduces global metabolic rate. Drug-induced metabolic suppression sustained over days in humans could be a strategy for reducing energy expenditure (EE), oxygen consumption (VO2), and carbon dioxide production (VCO2) during prolonged rescue or austere conditions with limited life-support. We tested the feasibility of reducing EE, VO2 and VCO2 measured with intermittent indirect calorimetry using subcutaneous infusion of dexmedetomidine 1 µg/kg/hour for 18 hours per day over five days in healthy adults. Five participants received multiple days of dexmedetomidine in a laboratory setting, and five separate participants received placebo for one or five days. Relative to resting metabolic rate, dexmedetomidine infusion reduced VO2 (effects, 95%CI, at 6-hour time epoch: −0.084 L/min, −0.145 to −0.023), VCO2 (−0.067 L/min, −0.130 to −0.005) and EE (−577 kcal/day, −1016 to −137). Relative to placebo, dexmedetomidine produced light sedation (Richmond Agitation Sedation Score: −1.25; 95%CI −1.70 to −0.80 relative to placebo), with lower heart rate (−15 beats/minute; 95%CI −23 to −7) and core body temperature (−1.3ºC; 95%CI −1.7 to −0.8). Dexmedetomidine effects on all physiological variables decreased over time and were absent after day 2. Maximum and minimum plasma drug levels did not change over days. Participants reported rebound anxiety and insomnia after the study. Administering a sedating level of dexmedetomidine that reduces VO2, VCO2, and EE for 2 days was feasible in healthy adults. However, tolerance to drug effects develops by 3 days, which is a critical limitation for long-term use of this drug regimen.

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Cite

BibTeXRIS
BibTeX
@article{callaway2026dexmedetomidine,
  title = {{Dexmedetomidine effects on metabolic rate over 5 days in humans}},
  author = {Clifton W. Callaway and Alexandra J. Weissman and Katharyn L. Flickinger and Victor Wu and Jenna Monteleone and Ryann DeMaio and Mara Hierro and Daniel Neofes and Omarf Ortega-Reyes and Tao Sheng and Marianna Salinas and Paul Lerro and Francis X. Guyette and Benjamin D. H. Gordon and Marie Mortreux and Kathleen Melanson and Daniel J. Buysee and Philip E. Empey},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0359711},
  url = {https://doi.org/10.1371/journal.pone.0359711},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Dexmedetomidine effects on metabolic rate over 5 days in humans
AU  - Clifton W. Callaway
AU  - Alexandra J. Weissman
AU  - Katharyn L. Flickinger
AU  - Victor Wu
AU  - Jenna Monteleone
AU  - Ryann DeMaio
AU  - Mara Hierro
AU  - Daniel Neofes
AU  - Omarf Ortega-Reyes
AU  - Tao Sheng
AU  - Marianna Salinas
AU  - Paul Lerro
AU  - Francis X. Guyette
AU  - Benjamin D. H. Gordon
AU  - Marie Mortreux
AU  - Kathleen Melanson
AU  - Daniel J. Buysee
AU  - Philip E. Empey
PY  - 2026
DA  - 2026/10/27
JO  - PLOS One
DO  - 10.1371/journal.pone.0359711
UR  - https://doi.org/10.1371/journal.pone.0359711
AB  - The alpha-2-adrenergic agonist drug dexmedetomidine induces sleep-like sedation and reduces global metabolic rate. Drug-induced metabolic suppression sustained over days in humans could be a strategy for reducing energy expenditure (EE), oxygen consumption (VO2), and carbon dioxide production (VCO2) during prolonged rescue or austere conditions with limited life-support. We tested the feasibility of reducing EE, VO2 and VCO2 measured with intermittent indirect calorimetry using subcutaneous infusion of dexmedetomidine 1 µg/kg/hour for 18 hours per day over five days in healthy adults. Five participants received multiple days of dexmedetomidine in a laboratory setting, and five separate participants received placebo for one or five days. Relative to resting metabolic rate, dexmedetomidine infusion reduced VO2 (effects, 95%CI, at 6-hour time epoch: −0.084 L/min, −0.145 to −0.023), VCO2 (−0.067 L/min, −0.130 to −0.005) and EE (−577 kcal/day, −1016 to −137). Relative to placebo, dexmedetomidine produced light sedation (Richmond Agitation Sedation Score: −1.25; 95%CI −1.70 to −0.80 relative to placebo), with lower heart rate (−15 beats/minute; 95%CI −23 to −7) and core body temperature (−1.3ºC; 95%CI −1.7 to −0.8). Dexmedetomidine effects on all physiological variables decreased over time and were absent after day 2. Maximum and minimum plasma drug levels did not change over days. Participants reported rebound anxiety and insomnia after the study. Administering a sedating level of dexmedetomidine that reduces VO2, VCO2, and EE for 2 days was feasible in healthy adults. However, tolerance to drug effects develops by 3 days, which is a critical limitation for long-term use of this drug regimen.
SN  - 1932-6203
ER  -