Thanks for joining us. I want to thank the AANS APP program for inviting me to give this quick talk. We are going to talk about a rapid review of ICU infusions, basically medicines that are commonly used in our neurosurgical ICUs in order to achieve misuppression support, sedation, pharmacological paralysis, and also board suppression, you know, for management of intracranial hypertension and also for the management of refractory status epilepticus. As I said, we'll start with suppressors first, and we're going to see that we have several agents that you guys are probably really familiar with, norepinephrine, phenylephrine, vasopressin, and other drops such as dopamine, dopamine, amilrinone, and also epinephrine, which are more common, more often than not, it is our last resource when the patient is severely hemodynamically unstable. When we talk about norepinephrine, it is widely used, you know, to sustain good vasopressure support, especially in cases of cardiogenic shock and in cases of sepsis as well. Another use of norepinephrine and phenylephrine as well are in the treatment of cerebral vasospasm in order to prevent the patient to go into delayed cerebral ischemia. We set blood pressure goals, you know, and then we titrate the drips to those in order to improve the cerebral perfusion pressure and avoid ischemic strokes. Other than that, norepinephrine is used to keep a goal, a MAP goal, more than 65 unless, you know, a higher goal is needed in case of vasospasm or intracranial hypertension in which you need a higher MAP to optimize the CPP. It is a stimulator of beta-1 adrenergic and alpha-adrenergic receptors. It also increases contractility, heart rate, and vasoconstriction peripherally. The initial doses are shown in there, and the ones that we mostly, you know, use is from 0.025 to 1 microgram per kg per minute. Maximum dosage is, you know, 1, 2, 3, 3.3 micrograms per kg per minute. Preferred to be infused through a central line. If you don't have a central line, sometimes it's permissive to give low doses of vasopressors through a peripheral line, and the main risk of that being, you know, extravasation and causing necrosis of the surrounding tissue. Brain is another agent that is a pure alpha-adrenergic agonist. Basically, it produces a significant amount of peripheral vasoconstriction, which may decrease the stroke volume if your volume status is not, you know, what you want it to be due to the fact that the heart has to pump harder against peripheral resistance. It can also induce bradycardia, so it's a good agent that can be potentially used in patients with atrial fibrillation with RVR when they are not unstable. I'm sorry, when they are not stable. Initial doses are shown in there, and the maximum dose that we usually use is up to 5 micrograms per kg per hour. Like I mentioned initially, epinephrine is something that we're going to use, you know, as a last resort, or in cases in which the patient's hemodynamic status is severely compromised, it's a potent B1-adrenergic, moderate alpha-1-adrenergic, and it also has a risk of producing dysrhythmias. The dosage is 0.01 to 0.5 micrograms per kg per minute. One thing to be really mindful of is that in case of neurological injury, sometimes you're going to develop a condition that's called a stress cardiomyopathy, which is caused by adrenergic, I think called aminergic surge due to neurological injury, and it can be exacerbated certainly for the use of exogenous adrenergic drugs. However, they are the ones that allow us to keep the blood pressure up, so it's kind of, it goes a little bit into the vicious cycle until the AX1 fraction of the contractility of the heart actually starts to improve. Another thing about catecholamines, they do not work well in an acidic environment, so it's very important to, you know, make sure that our acid-base status is optimized. Unlike vasopressin, vasopressin works really well in an acidic environment, so we sometimes add it, you know, as a coadjuvant, along with norepinephrine especially, in order to have a good, you know, blood pressure response to the vasopressin support. We've got to be careful because it doesn't only produce peripheral, but also sputum, vasoconstriction that can lead to bowel ischemia. It can cause, you know, fluid retention and lead to hyponatremia. It is also used in cases of diabetes and C, because you guys probably have had that experience when somebody has progressed to death by neurologic criteria, and then they develop GI. Vasopressin is good for hemodynamic management and also for, you know, treating the hyponatremia that the patients develop when they progress to death by neurologic criteria. Dosages are shown, and higher doses are used for isogenic shock, and in the case of, you know, GI hemorrhage, upper GI hemorrhage, more often than not. Now, we're going to the inotropics, you know, dopamine, dobutamine, and milrinone support the case of low EF, useful in Takatsubo's cardiomyopathy for neurologic injury. We've got to be careful, though, about high risk for ischemia, especially dobutamine, and that vasodilation that can lead to hypotension that milrinone causes. Another use of milrinone in the neurosurgical world is through the Montreal Protocol, in which we infuse milrinone at certain dosages for the management of cerebral vasospasm. So, that's basically that quick review about pressure, vasopressor agents, and now we're going to move on to sedation that we use very commonly in the ICU. Agents such as midazolam, propofol, ketamine, presidex, opioids, and etomidate. I will review a few of them just real quick. Propofol, you know, used to achieve very rasc goals and decrease the cerebral consumption of oxygen, and the effect of propofol can also be used in order to reduce episodes of the kind of hypertension. We've got to be careful and always monitor our acid-base status and also monitor lipase and triglycerides. And also, you know, if you are doing it for other purposes, like we will review later in the case of birth suppression, we're going to make sure that we're following an electrocephalogram closely. Due to its short action, it's preferred over benzodiazepines due to the less risk of prolonged sedation and improving the time of extubation. And the dosages are the ones that I'm showing you in there. Sometimes it can be actually quite high, but we need to keep an eye on the patient's hemodynamic monitoring. And also, like I mentioned before, lipase, triglycerides, and acid-base status. Watch for, you know, PRIS, propofol infusion syndrome, in which, you know, you're going to develop irreversible acidosis, elevated CPK, and so forth, and the patient can go into irreversible shock as well. Versed or midazolam, you know, it can definitely accumulate in the system with a longer effect than propofol. And intermediate administration is encouraged. Initial doses, you know, can be proceedable 5 to 5 milligrams per kick. It's not uncommon, especially for birth suppression, we use higher doses as well. I'll show you later. But in general, for sedation to achieve a low RAS, you know, an infusion of 1 to 8 milligrams per hour, it's recommended. For ICP control, you have to, you know, basically go into higher dosages. It has actually an equivalent effect of ICP reduction, but with a longer, you know, effect if you're trying to wake up the patient. I might be thinking about extubation. Our next agent is Presidex, which can be used for sedation, can also be used for agitation, or for alcohol or substance withdrawal syndromes quite effectively. It's a selective alpha-2 adrenoreceptor agonist. Be careful, because sometimes it can cause bradycardia hypotension, and infusion rates go from 0.2 to 1.5 micrograms per kick per hour. It does not produce respiratory depression when you use it as well for ICP control. And it's ideally a temporary agent, less than 24 hours of use, if possible. Another agent is Cetamidate, mostly used for rapid sequences to intubation, you know, patients that are not hypertensive. It can be also used for procedural sedation, and the dose is 0.2 to 0.3 milligrams per kick. You know, I use it quite often in rapid sequence intubations in neurologic patients, again, when they are not hypertensive or when they're more dynamically compromised, because it does not cause hypotension in agents like Propofol, for example. That's about it as far as a quick review of pharmacological sedation. Now, we can talk about pharmacological paralysis, which is a step up in the management of, for example, the kind of hypertension or synchrony with a mechanical ventilator. It can be used for ICP control, synchrony with a mechanical ventilator, and the management of ARDS. And if you guys remember, you know, during the bad days of the COVID pandemic, we used a lot of paralytics in order to keep the patients in synchrony with events, and that led to, you know, actual shortages of agents. We were worried about Cystic Tachyurium for a while, for example, you know, here at our institution in Colorado. Agents that are more common, Rocuronium, Cystic Tachyurium, Vecuronium. I like Cystic Tachyurium particularly because it doesn't need to be adjusted for a renal or hepatic metabolism. It basically follows a Hofmann's degradation metabolism. So, and then when we talk about, you know, the polarizing ones, such as Succinylcholine, it actually allows for a rapid induction or a rapid paralysis with an effect quite quickly in paralyzing the muscle, but we got to make sure that we watch for, you know, cardiac arrhythmias, subsequent hyperkalemia, rheumatoid myelosis, the development of malignant hyperthermia. It has been said, you know, that it can increase the ICPs. However, if that's the only agent that you have available and the intubation is to be caused, it needs to happen fast, don't see a problem with using it, because with a patient, the longer the patient remains, airway is not protected, then the more ICP problems you're going to have. Also, be careful with rocuronium, even though we use them quite a bit, it can induce the release of histamine in the brain, which can, you know, histamine is a stimulating neurotransmitter, so it can increase to, it can lead to increase of ICP. We don't see it very often, but it's something to keep in mind. For example, other agents like Cystatricurium, they do not cause the release of histamine. So, that's about it for pharmacological paralysis and with depolarizing and non-depolarizing agents. Now, they asked me to talk to you about burst suppression, and burst suppression can be used for several things. You know, this is an electroencephalogram in which you see severe slowing, you know, basic flattening of the electroencephalographic waveforms with short periods of burst. That's basically what we call burst suppression, and it can be used for ICP control in cases of refractory, you know, ICP or intracranial hypertension, and also for the status epilepticus. Amongst the agents that we use to achieve this, we have pentobarbital, propofol, versed in high doses, inhaled gases like isoflurane and dysphorine that can be used mostly in the OR, and also ketamine. In order to achieve burst suppression with midazolam, you're going to need a significant amount of medication for this purpose. You know, you can start with a load of 0.2 milligrams per gig and repeat it every three to five minutes, watching the patient's hemodynamics until you have burst suppression in the electroencephalogram, and a maintenance dose can be as high as 20 milligrams per hour. It's not uncommon sometimes that we use that for ICP control. Pentobarbital is a very controversial drug, I will say, because even though it allows you to achieve burst suppression and ICP control and seizure control, you know, quite fast, it also has some toxicities that are related to it, because in the U.S. our solutions are 40% propylene glycol, which is going to induce, you know, acidosis. So we're going to be careful, you know, we're going to keep an eye on the osmolar gap, we're going to make sure that the patient does not become hypertensive, and then also avoid dopamine in combination with it, as it increases the consumption of oxygen. These are general guidelines, you know, when you use a pentobarbital load, or if you decide to start using infusion and go up, you know, up to two to, I mean, one to five milligrams per kick per hour, until you achieve burst suppression, and keep the patient in burst suppression, if it is for the status epilepticus, for at least 72 hours. And now we have had to do that longer for a control of ICP, or a pentobarbital coma, so to speak. After the 72 hours, or until you have deemed that it's time to take the patient off pentobarbital, there is a little bit of a guideline in which you reduce by 50% every two hours, until the infusion, you know, falls down below 0.5 milligrams per kick per hour, at which point you basically take the drip off. And these are different values of infusion for sedation, one to five micrograms per milliliter, for intercurrent hypertension therapy, a level of 30 to 40, and for therapeutic coma, from 20 to 50. And these are labels of pentobarbital in the bloodstream, that will allow you to, you know, monitor the effect, and the amount of drug that is being titrated. Again, very common use for refractory intercurrent hypertension, and refractory status epilepticus. We talked a little bit about Propofol, like I said before, and we have to follow up, you know, lipase and triglycerides, and watch for PRIS, when using you know, high doses. You can give a loading dose of one to two milligrams per kick, provided that you're monitoring hemodynamics very quickly. You can start your drip, you know, at 30 or 20 micrograms per kick per minute, with blood suppression usually achieve a level of 30 to 60 micrograms per kick per minute. There is no, you know, max dose that is being described. However, when you approach 150 to 200 micrograms per kick per hour, you know, you have to be really careful hemodynamically speaking, and usually when you look at PRIS, you know, Propofol Infusion Syndrome, it happens in younger people, and the pediatric population is particularly susceptible to it, and with doses, you know, above 80 micrograms per kick per minute, you know, it should be mandatory for the, for acid-based status CPKs, you know, to be watched very closely. Finally, another agent, Keramine, that we started to use quite a bit also during the pandemic, due to the, you know, shortages of Propofol and Versed, and actually it's an, as an off-label use can induce blood suppression. We use it in the status epilepticus when the patient is hemodynamically compromised. It's also titrated to blood suppression from a loading dose of 0.5 to 3 milligrams per kick, and a continuous dose up to 5 milligrams per kick per hour, with a maximum dose of 15 milligrams per kick per hour, and it actually provides you with good hemodynamic support as well, blood pressure-wise. As we reviewed before, you know, it's an NMDA receptor antagonist, and very important that Keramine, contrary to some beliefs, does not increase the ICP, but actually, you know, helps control the ICP when used for intracranial hypertension. Thank you very much for the attention. This has been a really quick and, you know, cross-review about some of the infusions that we're using during neurosurgical ICUs, and I hope that you guys find this helpful. Thank you.

neurosurgical ICUs

sedation

paralysis

burst suppression

vasopressor support