Dr. James Marx discusses improving the care and use of mice in biomedical research, with a focus on the pharmacology behind the effects of anesthetics on respiration.
- Effects of anesthesia on respiration in mice
- Overview of methods to monitor anesthetized mice
- Observations and future research on monitoring beyond respiration
Dr. Marx begins this webinar with an introduction to anesthetic monitoring in mammalian species. Although such monitoring provides valuable information on the animal’s condition, in mice this tends to be limited and requires specialized equipment.
“Everything we described for the large animal anesthesia can be measured in the mouse, just it’s much more difficult because of the small size of the mouse.”
Dr. Marx emphasizes that monitoring the respiratory system is extremely important, noting that 50% of anesthetic deaths in humans are associated with hypoxia; all anesthetics depress respiration, resulting in a decreased ability to respond to hypoxia or hypercapnia.
Respiratory monitoring can be achieved using pulse oximetry or measuring respiratory rate. Dr. Marx explains that the relationship between partial pressure of oxygen and hemoglobin saturation is not linear, which is why pulse oximetry is helpful in monitoring oxygen status in the mouse. Mechanisms of respiratory depression include: sensor depression, muscular activity inhibition, and atelectasis.
“. . . there’s been a couple studies showing that atelectasis is definitely occurring in our anesthetized mice, and it isn’t just . . . during surgery . . . but atelectasis has been shown to be associated with an increase in inflammation after surgery.”
Dr. Marx then discusses a study that revealed both inhaled isoflurane and injectable ketamine-xylazine dramatically decrease the response to carbon dioxide in mice. Further studies showed that when using a carrier gas of 21% oxygen, resulting pulse oximetry values averaged 79%. These extremely low hemoglobin saturation levels affect brain function, and even though the mice recover normally, this may have long-term effects on behavior.
Monitoring respiratory rate gives a good indication of when an animal is in distress. Therefore, understanding the anesthetic protocol, knowing the normal respiratory rate for your mice, and more frequent monitoring will result in lower mortality rates.
“If you’re just looking at the mouse and monitoring continuously, but not taking the respiratory rate, you will not get this information.”
Dr. Marx then provides an overview of the various anesthetic depths and how to confirm the animal is in an ideal plane of anesthesia by testing whether they respond to a noxious stimulus. Preferably, no voluntary movement is observed but an autonomic response is still present. He concludes the webinar highlighting other vital signs in addition to respiration to monitor and areas requiring further study, including whether providing 100% oxygen to the animal may result in oxygen toxicity.
- Would you suggest doing a pilot experiment with new animal models or knockout mice where you don’t know their “arrest threshold” to determine that threshold?
- While adequate ventilation is critical, respiratory patterning and cardiorespiratory coupling are also impaired when using inhaled anesthetics – do you have any guidance for minimizing these confounders?
- Do you have resources for the “normal values” for heart rate and respiration rate for rats under both inhalant and injectable anesthesia?
- Should all of the recommendations mentioned in the presentation for monitoring mice be used for rats as well or should people using rats/larger rodents consider using another monitoring method?
- At what point do you extubate your mice and stop providing supplemental oxygen?
- For supplemental oxygen, would you recommend 100% or 21% oxygen? And for delivery of isoflurane, there are some anesthesia machines that use room air for delivery versus an oxygen tank or concentrator at differing percentages – what is your recommendation?
- What is the best route for administering atipamezole? Atipamezole IV is contraindicated in larger animal species due to profound hypotension and is labelled for intramuscular, but since intramuscular is not so commonly used in mice, does IP administration cause the same type of hypotension and is subcutaneous administration too low?
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Pathobiology, School of Veterinary Medicine
University of Pennsylvania