Best injectable anesthetic with minimal cardiovascular effects is named Etomidate. However it is not commonly used for veterinary anesthesia. Following etomidate is thiopentone (some hypotension and reflex tachycardia) then propofol (hypotension) and ketamine (tachycardia and hypertension)

Yes, similar to Dr Sultan’s point, Ketamine is widely used in situations where cardiovascular depression needs to be avoided. It tends to cause mild cardiovascular stimulation. It may exacerbate confusion and causes hallucinations, but breathing and cardiac output are generally maintained.

Etomidate is used internationally, but I have no personal experience of its use.

Pure volatile agent (gas) approaches - eg sevoflurane induction and maintenance - also have much to commend them, as the vapour is exhaled and so the drug can be removed from the body if the dose seems excessive. I’ve used this to anesthetize the most frail patents, some over 100 years old, with hip fractures and dislocations. It’s very well tolerated.

I've never heard of using "urethane." Do you mean "Ultane" (Desflurane)? I never use Desflurane and believe it should be banned from use because of its dangerous pulmonary toxicity. Neither do I use etomidate because it notoriously undermines postoperative survival. Propofol is inherently dangerous and I never use it, either. I avoid paralysis whenever possible, for reasons that should be obvious. For anesthetic induction for short cases I use as little as 100mcg fentanyl administered IV at least three minutes before mask induction to allow it to reach peak effect, because it obtunds the sense of smell. Then I use mask induction with Sevoflurane, and increase the Sevo to maximum concentration (8%) until systolic blood pressure falls below 100 torr, which confirms adequate control of sympathetic nervous activity, and I am able to ventilate the patient by mask. This produces excellent vocal cord relaxation that is equivalent to paralysis but without the hazards associated with paralysis. Once the airway is secured, I switch to isoforane 1% (1/2 MAC) and maintain the end-tidal CO2 at a minimum of 50 torr to enable "permissive hypercarbia." I use "front-loading" with fentanyl or sufentanil to assure adequate analgesia, and/or spinal or epidural analgesia so as to minimize the toxic effects of the inhalation agents and optimize surgical outcome.

BTY I nearly attended Vancouver for my anesthesia residency 40 years ago and have regretted not doing so ever since. Is there any chance that you might perform a controlled clinical study that could test and confirm the superior surgical outcomes afforded by supplementing anesthesia with generous analgesia and hypercarbia? It's time to end the horrible hoax imposed by the "founder" of MD anesthesiology, Dr. Ralph Waters. Seldom has so much harm been caused to so many people by anyone other than a politician or general. If there is any possibility that such a study could be performed in Canada, then I would be more than happy to help. www.stressmechanism.com [email protected]

Thank you everyone for your answers so far.

The one thing I forgot to mention is that I am asking for potential use in preclinical experiments and that system of interest is cardiovascular.

We cannot use inhalant anesthetic as the intervention we are using need to be off iso/or any other gaseous anesthetic. I like the idea of using etomidate but according to my information it is not long-lasting and it does not have any analgesic effects like urethane.

I would appreciate any other suggestions

There is a fundamental difference between anesthesia, which is a form of hypnosis that inhibits consciousness, and analgesia, which inhibits nociception. Hypnotic agents, including isoforane and Etomidate, exert their benefits by preventing consciousness from perceiving nociception as pain, which catastrophically exaggerates harmful sympathetic nervous activity induced by surgery. This generally enables animals and people to survive surgery, but hypnotic agents do not prevent nociception from harmfully activating sympathetic ganglia in the chest and abdomen. Worse yet, the elimination of consciousness abolishes the inhibitory "corticofugal" pathways from the brain to the spinal cord that normally inhibit spinal cord nociception pathway activity. Therefore analgesia must be added to anesthesia to optimize protection against surgical stress, and optimize surgical outcome. Can you describe the experiment you are planning to perform? If I understand your experimental protocol I might be able to help you perfect it, or find medications that will be helpful for your purposes.

Dear Mehdi Ahmadian, KETOFOL (Propofol-50%+Ketamine-50%) is a useful alternative. This combination has an almost stable cardiovascular profile.

Ketamine and Propofol are both hypnotics; both lack analgesic properties; neither of them will prevent nociception that harmfully activates sympathetic nervous activity, exaggerates blood pressure, and causes tissue hypoxia. Combining these agents will only complicate and confuse your experimental results. Blood pressure is a false God. When surgical nociception is effectively controlled, blood pressure is low. In other words, blood pressure is NOT the "driving force" of blood flow, as commonly presumed.

“Each time a change can be observed in the height of a manometer applied to an artery, the experimenter must ask himself which of the two factors of the arterial pressure has varied, or whether the two factors, power and resistance, have been modified at the same time.  In the absence of a criterion which would allow one to decide with complete certainty this litigious question, often enough physiologists have chosen the hypothesis which best accorded with their preconceived ideas.”---Etienne Jules Marey 1881 

"The development of our knowledge of the circulation has been bedeviled by the fact that the measurement of blood flow is so complicated, whereas that of blood pressure is so easy: hence the blood pressure manometer has exerted an almost hypnotic influence, though bodily organs don't need pressure but flow."-----Adolf Jarisch 1928

Dear Lewis S Coleman, Ketamine has a quite strong analgesic property.

Dear Dr. Alam,

With due respect, I beg to differ. Granted, there is near-universal confusion on this subject. True analgesics such as opioids and local analgesics (lidocaine, marcaine, prilocaine and so forth) inhibit nociception pathways and prevent harmful sympathetic nervous activity that releases von Willebrand Factor from the vascular endothelium and activates factor VIII. Factor VIII activity closes the capillary gate and reduces microvascular perfusion of organs and tissues, and thereby harmfully undermines tissue oxygenation.

Inhalation anesthetic agents and hypnotic agents including ketamine, benzodiazepines, barbiturates and so forth inhibit consciousness, and thereby prevent consciousness from perceiving nociception as pain. This reduces the body's reaction to surgical stimulation, and enables most individuals to survive surgery, but it doesn't inhibit harmful nociception, because spinal cord nociception pathways are little affected by hypnotic agents.

For example, a paraplegic patient may be unable to perceive painful procedures in his lower body, but his spinal cord nociception pathways nevertheless remain intact in the distal spinal cord segment below his neck injury. These spinal cord nociception pathways are freed from descending inhibition from the brain, so that stimulation of nociceptors in the lower body can cause exaggerated nociception pathway activity that grossly exaggerates SNS activity. This manifests as hypertension, and can even cause death in some cases.

If you are performing research on animals, this may perturb your experimental results. The attached paper will hopefully explain all this in greater detail.