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Euthanasia by CO₂ inhalation affects potassium levels in mice
Ryan P Traslavina1, Edward J King, Andrew S Loar
1College of Veterinary Medicine, Cornell University, Ithaca, New York, USA. rpt25@cornell.edu
Summary
Elevated serum potassium in mice may be artifactual. Carbon dioxide (CO₂) euthanasia causes respiratory acidosis, leading to falsely high potassium levels. Ketamine-xylazine (KX) anesthesia with exsanguination provides more accurate mouse potassium measurements.
Area of Science:
- Laboratory Animal Science
- Clinical Pathology
- Physiology
Background:
- Reported high serum potassium levels in mice (≥8.0 mEq/L) are physiologically incompatible with life.
- Previous studies have published these high values as normal reference ranges.
- The discrepancy suggests potential artifactual causes in research settings.
Purpose of the Study:
- To investigate common research variables that may cause artifactual hyperkalemia in mice.
- To differentiate between true and artifactual serum potassium elevations.
- To establish optimal methods for accurate potassium measurement in mice.
Main Methods:
- Evaluated variables: collection site, clotting time, sample handling time, anesthesia type, and euthanasia method.
- Measured serum potassium in 75 C57BL/6NTac female mice (10-week-old).
- Compared euthanasia by CO₂ inhalation versus ketamine-xylazine (KX) anesthesia followed by exsanguination.
Main Results:
- Mice euthanized with CO₂ exhibited higher mean (7.0 ± 0.5 mEq/L) and range (6.0–8.1 mEq/L) serum potassium than KX-treated mice.
- CO₂ inhalation induced significant respiratory acidosis (lower pH, higher pCO₂, higher lactate).
- KX anesthesia followed by exsanguination yielded lower, more physiologically plausible potassium values.
Conclusions:
- Antemortem respiratory acidosis from CO₂ administration is a likely cause of artifactual hyperkalemia in mice.
- Ketamine-xylazine anesthesia with exsanguination is the preferred method for accurate mouse serum potassium determination.
- Research protocols should adopt KX anesthesia to avoid falsely elevated potassium readings.
