This post turned out a bit longer than I expected, so I broke it up into two parts. Excuse my science-y jargon and please do leave comments if anything is unclear!
Rodent anesthesia falls into two main types: Chemical or Inhalant.
Chemical anesthesia involves the administration of a drug or several drugs via subcutaneous injection. The most common drug of choice is a combination of ketamine and xylazine.
Xylazine is an alpha-2-adrenergic agonist sedative with short lived analgesia. As a sedative, the drug depresses, or slows down, the respiratory and cardiovascular system and relaxes the muscles. Too much “slowing down” can be dangerous, especially in mice, where surgeries are generally conducted be a single technician and changes in respiration and cardiovascular function are usually monitored only by visual inspection. If a person is occupied with the technical aspects of the surgery, slight changes may be easy to miss. When the respiratory or cardiovascular systems become over-depressed, this is an overdose and death can result.
Ketamine is a “dissociative anesthetic” which renders animals unable to move. Lubrication of the eyes is absolutely required because the eyes remain open while the animal is in this dissociative state. Failing to lubricate the eyes during surgery can result in blindness due to drying of the cornea. Recovery from ketamine can take up to several hours and during this time, the animal must be monitored closely.
By combining the two drugs, you are able to produce a sedate animal which is unable to move. This is suitable for short surgeries. However, the recovery period is often rough. Animals often appear “groggy” and may not resume normal activities for some time after.
Ketamine-xylazine is favoured because it is relatively cheap and non-technical, requiring only the drugs and needles with which to administer the injection. As well, there are no wastes produced from these chemicals which may be dangerous to the animal or the handler.
However, it is not suitable for long or invasive surgeries and comes with a few complications:
Ketamine-xylazine injection also does not produce lasting analgesia, or pain relief. Additional painkillers are generally recommended before and after the surgery.
Many animals react differently to ketamine-xylazine injection. A dosage which works well in one strain of mice may not work well in another. As well, individual mice may metabolize the drug at slightly different rates, such that a dose that results in 1 hour of anesthesia in one mouse may only give 45 minutes in its cagemate. This can be disastrous if a surgery is predicated to take 50 minutes to complete. As such, the appropriate dosage must always be tested for each new strain of mice and for each new experiment, and allowing plenty of time for unexpected results. The technician should also always have extra drug ready, should the animal show signs of waking up.
The amount of cardiovascular and respiratory depression is also dangerous, as I mentioned, and this danger increases during longer or more complicated surgeries. Every time you have to administer a bit of extra drug to keep the animal unconscious, you risk administrating an overdose.
Luckily, there are other methods for producing a surgical level of anesthesia, which I will discuss in the next post.
[Photo by Dale Tidy]