Hello dear researchers. I am a beginner researcher who faced the following problem. During the experiment on rats, the rats die within 40-60 minutes. This process is accompanied by a drop in blood pressure and an increase in heart rate. Urethane is used as an anesthetic at a dosage of 1.3 g/kg, and the rats are ventilated using a ventilator with oxygen. Ventilation volume 1 ml/100 g, frequency 60/min. We tried to change the anesthetic to thiopental, without a positive result. Perhaps someone has encountered a similar problem and can provide advice?
You may try Ketamine @ dose of 8-10mg/Kg through intramuscular route.
Actually all anaesthetic drug can be used but should be used in proper dosing for different route if administration . For example Inj Ketamine 1-2 mg/kg i v and i.m dose 3-5 mg/kg . inj Propofol 1-2 mg /kg
My area of expertise is not animal research anaesthesia. But I’ve been anaesthetising humans for almost 40 yrs. there are likely to be a variety of reasons not the least being control of your dose, and preparation of the patient or in your case the poor little rat. It’s probably worthwhile discussing with a veterinarian specialising in anaesthesia to give you a more nuanced approach to different species. Regards John
Like Dr. Akers, I have 40 years of experience anesthetizing humans, but none anesthetizing rats. I would suggest that you read the attached Sielenkamper study that employed isoflurane (commonly used for humans) to anesthetize the rats. Secondly, I would suggest that mechanical hyperventilation is a bad idea for for all types of animals as well as humans. There’s a wealth of clinical research in humans documenting how hyperventilation dangerously depletes CO2 and undermines all aspects of oxygen uptake, transport, and delivery to cells. Try reading my attached review article that details CO2 pathophysiology in humans, which share the mammalian stress mechanism with rats. Thirdly, depending on the additional stresses you plan to introduce on the rats, you will likely need to complement the anesthesia with some sort of analgesia, such as the epidural analgesia used in the Sielenkamper study or opioid supplementation that inhibits nociception pathways in the spinal cord. To appreciate this, I recommend that you read the attached study that originally described the mammalian stress mechanism. Better yet, check my website www.stressmechanism.com or my book “50 Years Lost in Medical Advance” that is available on Amazon. Most animal research is wasted because the researchers didn’t appreciate the role of anesthesia and analgesia.
As mentioned by Drs. Akers and Coleman.
My experience with pigs* was that, like humans, a balanced anesthetic, consisting of more than one drug, provides a much more stable hemodynamic profile. I would expect the same would be true with rats.
No single drug works to provide anesthesia (sleep) and analgesia (nocioception), with or without amnesia. Paralysis requires a different class of drugs.
We would need to see your current protocol for more detailed recommendations, including about how you're ventilating the rats, etc.
*it was the reason I ended up going into Anesthesiology as a specialty.
Dear Christine, May I ask where you performed your anesthesiology residency and whether you were taught, as I was at UCLA, to hyperventilate your patients and use narcotics with caution? Given your experience with animal research, I suspect you would appreciate my book “50 Years Lost in Medical Advance.” If you are willing to review the book, please contact me via my website www.stressmechanism.com.
Ketamine and dexomeditomedine will control only the Consciousness pathway. They won’t control the nociception or tissue disruption pathways. Furthermore, by eliminating consciousness, they will abolish the inhibitory influence of consciousness on spinal cord nociception pathways. Stress mechanism hyperactivity cannot be effectively controlled with a single agent. Check my publications listed earlier.
Ketamine and an alpha agonist (xylazine, medetomidine, clonidine dexmedetomidine, whatever) form the basis for much veterinary anaesthesia I gather. Certainly useful for taking down danger animals. And if combined with an opioid will have a significant impact on ascending nociceptive information. The ketamine will significantly impact the information, its registration and evaluation at several levels above and including thalamus, insula, cingulate cortex, prefrontal cortex, hippocampus and amygdaloid structures to name a few. When used in robust doses it enables significantly less of agents such as propofol or volatiles which are potentially the more concerning in larger doses on neurocognitive function, (esp in the vulnerable brain). In my practice I see a significant number of dangerous animals- patients in various degre of poly substance intoxication or withdrawal in a large tertiary referral trauma hospital. I’ve found the vetinary approach has its merits in these patients. Unfortunately we don’t have atipamazole the alpha 2 agonist reversal available for humans in Australia.
Obviously the cost of running a research lab will determine the drugs you want to spend money on. So if your used to using urethane on your rats (which I presume is pretty cheap in large volumes) then what we’ve been talking about may be overkill (pardon the pun). But if your technique of hyperventilating will impact on your results then you need a better approach.
Where I’m from the the technique of hyperventilation was usually in a curarized patient with N2O and little volatile, was called the Liverpool technique. As Dr Coleman indicates it was not an ideal approach.
Dear Dr. Akers, Your commentary suggests that you would be a good candidate to review my book, which was very recently published on Amazon. It’s called “50 Years Lost in Medical Advance: The Discovery of Hans Selye’s Stress Mechanism.” If you are willing to produce a review of the book that I can use to promote publication, then I will provide you with a free PDF copy. However, you’ll need a Skype address or other electronic vehicle because the book is 500 pages---too big to send as an email attachment. As an anesthesiologist you will be better equipped to appreciate the book than the average civilian, and your review would be valuable. You can learn more via my website www.stressmechanism.com, and you can communicate with me via that website.
Ketamine is an interesting drug. Most anesthesiologists in my experience believe that it is a perfect solution for all sorts of situations. I am skeptical. I suspect that it offers little better control of surgical stress than ordinary inhalation agents, and it needs to be supplemented with narcotics or block techniques to control nociception, and to optimize safety it should be accompanied by elective endotracheal intubation and “permissive” hypercarbia. My reasoning is provided in detail in the book.
Dear Dr Coleman, thank you very much for asking me to review your book. I’m very happy to have a look, though I must admit my expertise is more in pain medicine rather than stress response at a basic level. I might not give you the gravitas that you may require.
I agree that as a sole agent ketamine is limited and to provide a more complete anaesthetic it is best when combined with other agents. Certainly an Alpha 2 agonist and opioid helps and low dose bzd. there’s been a lot of interesting work over the last 10 yrs from the basic neuroscience realm. I can forward reviews. My own interest is in the realm of psychedelic and the potential for therapy in pain medicine. I expect it will be limited but there’s some very exciting advances in basic neuroscience and these drugs are useful tools for looking at neural correlates of consciousness. Regards John Akers
Dear Dr. Akers, many thanks for both your references and for considering the book review. Can you provide me with a Skype address so that I can send you a PDF copy? I’ll read your articles with interest to see how they fit with the operation of the stress mechanism that I propose in the book.
What I think calculated inj ketamine i.m can given without too much side effects
Choice would be inj ketamine bcz of less chance of Respiratory depression and provide good analgesia. But For short procedure , alternative to inj ketamine is , inj Dexmedetomidine at appropriate dose
Once you use ketamine in appropriate dose it will be sufficient. Use it
Urethane is used when there is no plan for recovery and the animal is going to be sedated for longer periods (e.g one session electrophysiology recording). Thus I think you cannot change to ketamine. According to my personal experience, you can do It without artificial ventilation. Maybe there is a problem with your ventilator try it without the ventilator so you can find out what is this a case