When we think about anaesthesia, some words come to mind, as hypnosis, sleep and unconsciousness, and all of this is achieved with general anaesthesia, whether they are inhalation or intravenous agents. They promote generalized depression of the central nervous system. However, there's a type of anaesthesia in which this generalized depression of the CNS doesn't occur, some parts are even stimulated instead.
This is what we will see shortly, after the clip. Bring it on! Dissociative Anaesthesia What's up NAVE crew!
In this video lesson from Anaesthesia Unravelled we'll be talking about dissociative anaesthesia. Dissociative anaesthesia is one of the most versatile anaesthetic modalities, for three reasons: the first is because it can be administered intramuscularly. The second is that it promotes analgesia and the third is that the therapeutic window is very wide.
The first dissociative anaesthetic agent used was phencyclidine. This happened in the 50's, however, just after ten years, it was mostly left aside, because of some undesirable effects, such as anxiety, delirium and psychosis. Since then, ketamine has been the main representative of this group and, in veterinary medicine, it's frequently used, mainly, as I said, because it can be done intramuscularly.
In patients that we have difficulty obtaining a venous access, like wild or aggressive animals, dissociative anaesthesia becomes an appealing option. Ketamine is a racemic mixture. It is composed of two enantiomers.
The S+ molecule is the one responsible for analgesia, whether the R- molecule is linked to the undesirable effects of ketamine. Tiletamine is another dissociative agent, the most potent of this group. Commercially, we are only able to buy tiletamine combined to zolazepam, which is a benzodiazepine.
We'll understand the reason for this combination soon, OK? For us to understand the clinical effects of this anaesthesia, we have to know the mechanism of action of dissociative anaesthetics. Mechanism of action The main excitatory neurotransmitter in the CNS is glutamate and it acts mainly on NMDA receptors, that are present in more than 80% of neurons.
The activation of these receptors promotes neuronal excitation. We went over this in the pain and analgesia video lessons, so go check it out, OK? The dissociative anaesthetics are blockers of NMDA receptors, non-competitive to glutamate, that is, they act in a different site.
In this case, there's a depression of the cerebral cortex, inhibiting the nervous system, decreasing the stimuli of touch, pain, temperature and vision, with the exception of smell. The dissociative anaesthetics, however, also block catecholamine reuptake. So, the blockade of NMDA receptors and of serotonin reuptake stimulates the limbic system, that is related to emotions, like learning, memory, dreams, sensations of pleasure, and others.
So we have, at the same time, an inhibited area of the brain, that is the cerebral cortex, and an stimulated area of the brain, which is the limbic system. This is all quite curious, because the animal is anesthetized at that moment, but it is not in hypnosis, which means that we can't say this animal is under general anaesthesia. Another important thing is that, besides blocking the reuptake of catecholamines, they also block the muscarinic receptors, so we have the activation of the sympathetic system and inhibition of the parasympathetic system.
Adriano, come on, just say it. I don't know. .
. Just get on with it! I don't know.
. . Come on!
Just say it. Oh, alright. .
. Well, I gave some serious thought as to whether I would be talking about this or not, but, considering my position as a teacher and influencer, I really need to mention it. Well guys, unfortunately, ketamine is one of the drugs most widely used illegally.
It is known as 'Special K', 'K', 'Cat Valium', 'Jet' and many others names. People use it due to its hallucinogen effects, described as a feeling of leaving the body, seeing things, unicorns, gnomes. .
. in short, if you are stupid enough to use it illicitly, know that ketamine is related to early Parkinson's disease, schizophrenia, psychosis episodes, urinary incontinence, depression and a great load of others effects. So, think hard before you go killing yourself just to see unicorns or gnomes.
You see any gnomes? Didn't see no gnome. .
. Sure thing? This place is full of them.
. . Let's return to our previous line of thought, that's more important.
Something important about ketamine, that we mentioned in the adjuvant's lesson, is about its analgesic effects. So, this blocking of NMDA receptors results in analgesia. It also acts on opioid receptors, as part of the analgesic effects can be reversed with naloxone.
This means that the dissociative agents promote analgesia, especially somatic, and this is a huge difference if we compare it to general anaesthetics. Next, we’ll be looking into the pharmacological effects that dissociative agents promote, however, they should not be used by themselves, but as a part of an anaesthetic protocol. With that, we may reduce the undesirable effects of these drugs.
Clinical effects Regarding the central nervous system, we have an increase in cerebral blood flow and vessel dilation, resulting in an increased intracranial pressure. Some people spread the information that dissociative anaesthetics are convulsants, as some animals receiving dissociative anaesthesia develop seizures, but this is not correct, OK? The seizure is secondary to the increased intracranial pressure, but only happens in patients which have some history of seizure, and not in those without this problem, so it is not recommended to use dissociative anaesthesia in those animals.
Something else of importance is the permanency of protective reflexes, as on the eyelids and laryngotracheal. Also, there's eyeball centralization and the presence of nystagmus. The effects of dissociative agents on the cardiovascular system can be good or bad, depending on our patient.
As there's adrenergic stimulation, there's going to be tachycardia, hypertension, and increase in cardiac output. But, as the heart will beat faster, the systolic volume will decrease. This can be good, for instance, in hypotensive or dehydrated patients.
The problem is that, while in tachycardia, the myocardium demands more oxygen, so if we have a cardiac patient, this type of anaesthesia is not the best. The breathing pattern changes little in dissociative anesthesia. The animal shows a longer inspiratory time and a shorter expiratory time, which is known as apneustic breathing.
It's also possible to notice increased airway secretions, which can impair breathing. Generally, when animals undergo dissociative anaesthesia, they are not intubated and do not receive oxygen supplementation. This is done because the animal keeps the laryngotracheal reflexes and, theoretically, becomes more difficult to intubate.
I even slightly agree, however, on the larger species, it is fully possible to intubate, without trouble, and even if you can't, the oxygen can be supplied with a mask, to improve the fraction of inspired oxygen. Adriano, for God's sake. .
. you're being fussy. Well, my friend, I may be strict, but let me show you something.
In this research with horses, we induced the animals using dissociative anaesthesia, in which they stayed for about 15 minutes, and we can observe that, after 10 minutes, these animals were already showing hypoxemia, stressing that oxygen supplementation is necessary, even in short procedures. There are a lot of similar studies out there, with small animals, wild animals, you just have to look for it and you will certainly find them. Dissociative agents promote muscle stiffness.
This may, sometimes, result in some involuntary movements, That's why we always need to combine myorelaxant drugs with the dissociative agents, which is usually an alpha-2 adrenergic agonist or a benzodiazepine. Here it's worth highlighting: all the effects I'm telling you about are secondary to the dissociative agents, but as you associate a myorelaxant, these effects can change, depending on the association. We won't be able to focus on the details of each association, because there are several possibilities, but consider carefully the association and the effects that the combination will bring, OK?
The associative agents increase intraocular pressure, so it is not interesting to use them in patients which need stability of this pressure. They also produce some anti-inflammatory effect, modulating cytokine production, so it’s interesting to make ketamine a part of an anaesthetic protocol in patients with endotoxemia. Clinical applications Besides its analgesic effect, as we have already covered in other video lessons, ketamine can also be the basis of the anaesthesia.
In this case, our patient will be maintained in dissociative anaesthesia. This modality allows some superficial and outpatient procedures, like orchiectomy, as long as it is associated with a local block, is possible. Wound closures, too.
Now, an ovariohysterectomy shoudn't be done, as this anaesthesia does not enable access to cavities, much less orthopedics. Although it is possible to carry through the procedure, this animal will be feeling all the pain of the surgery. Ketamine may also be used as an anaesthetic induction agent, preceeding general anaesthesia.
In this case, we can't forget that it should also be associated with an alpha-2 adrenergic agonist or a benzodiazepine. Currently, this association is the basis for the induction of horses and cattle. Another clinical use of ketamine is to promote sedation, but here we may have a problem.
The low dose of ketamine, like half the anaesthetic dose, may already immobilize the patient, and sometimes people refer to that as sedation, but for me it is not. As I mentioned on the premedication lesson, sedation involves the generalized depression of the central nervous system, without hypnosis. When we use ketamine as premedication, be it with some other medication, we often have mydriasis, nystagmus and sometimes excitation.
So, obviously, this is not sedation, it's more of a lousy chemical restraint than anything else. Oh, but several textbooks say it's sedation. Yeah, cool, whatever.
Just don't go and use ketamine as premedication while I'm in the room, deal? Interesting facts There's a quite interesting fact regarding ketamine. For a long time we would hear and repeat - Yeah, including me - that ketamine wasn’t biotransformed in cats.
In fact, ketamine is biotransformed in canids and felids both, and it generates a metabolite called norketamine. Norketamine has a third of the anaesthetic power of ketamine. The difference is that canids can break down norketamine into inactive metabolites, while felids excrete norketamine in an active form, so, in patients with some kidney disorder, there's a prolongation of the dissociative anaesthesia.
Oh, so we can't use ketamine in cats. That's not what I'm saying, you can, but with some precautions. In this work, we anaesthetized 15 animals with urethral obstruction, with both propofol and ketamine.
Obviously, the animals that were dissociated took longer to return from anaesthesia, but the main factor was hydration. So, if we use a dissociative agent on a nephropath, we have to be extremely careful with hydration, so that this animal be capable of excreting the ketamine properly, OK? Tiletamine has two curious facts: the first is that its formulation is a powder associated with zolazepam, like I mentioned before, and this is interesting because, when we want to use it, for example, in wild and large animals, we can create a suspension of this powder, obtaining a solution with a lower volume of administration than, for instance, ketamine.
The problem is that it's awfully expensive, so I'm not convinced it's really worth it. The other interesting fact is that, as it's a combination of drugs, we need to understand the pharmacokinetics of zolazepam and that of tiletamine. In cats, zolazepam has a longer period of action than tiletamine, so they tend to be calmer during recovery.
In dogs, on the other hand, tiletamine's period of action is longer than zolazepam, so almost all dogs that receive this combination experience an awful, very turbulent recovery, with a lot of excitation. So, as we made clear, dissociative anaesthetics can be used in various ways. This table shows the doses, routes and period of action of each dissociative anaesthetic in domestic animals.
Remember that these doses can be quite variable and depend a lot on the combination that we are using, so this table brings the general idea only. We need to understand which drugs we are associating, in order to determine the correct dose for the species that we are working with. As conclusion to this video lesson, we have that dissociative anaesthesia has several advantages over general anaesthesia, such as routes of administration, analgesia and wide safety margin.
This modality of anaesthesia does not depress the brain entirely, so, there's no hypnosis. Dissociatives result in muscle stiffness, so they should always be associated to a myorelaxant. This modality of anaesthesia is not recommended for patients with neurological disorders, heart problems or surgeries resulting in moderate to severe pain.
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