Hello everyone, thanks for joining us today in this brief presentation. I want to thank the American Academy of Neurological Surgery for inviting me this year to make a couple of presentations. The first one basically pertains to common infusions used in the neurosurgical ICU. As you guys know, there are several intravenous agencies, especially DRIPS, that we employ in the neurosurgical critical care setting in order to care for our patients. One of the most important ones, of course, are vasopressors, vasopressor support for the hemodynamic unstable patient. Several instances in the world of neurosurgery can present with the hemodynamic instability in the intra-op, in the OR, when the patient arrives post-surgery and during the stay in the ICU, in which they require additional support in order to keep a normal blood pressure, or also when we augment the patient's blood pressure in order to optimize the cerebroperficient pressure, or when we do it to treat cerebrovasospasm. Some of the agents include inotropes, such as dopamine, dobutamine, myelinone. Catecholaminergic agents, such as norepinephrine, phenylephrine, epinephrine, and also other agents with systemic and splenic vasoconstriction, such as vasopressin, which can also be used in cases of diabetes insipidus. Norepinephrine, very commonly used, preferred to be used over a central line, like any other vasopressor. However, at the beginning of the patient care, if you don't have central access, you can use a certain amount of dosages and length of time through a large-bore peripheral IV or through an intra-osseous IL line. The goal is usually to keep the patient's map above 65 millimeters of mercury, unless higher goals are needed, like I mentioned at the beginning, when you are trying to increase the cerebroperficient pressure or when you're treating vasospasm. The mechanism of action, beta-1 adrenergic and alpha-adrenergic as well, it increases the contractility of the heart rate and reduces vasoconstriction, of course, through the alpha action. The initial dose is 0.025 to 1 micrograms per kick per minute, with a maximum dose up to 3.3. However, it's very important to identify that when you're approaching doses of 0.3 to 0.5 micrograms per kick per minute, it's very prudent and recommended to start thinking about adding other vasopressor agents to avoid other side effects that will come from high doses of norepinephrine. Phenylephrine is one that has a pure alpha-adrenergic activity, produces vasoconstriction, hence increasing the systemic vascular resistance. Initial dosing, as I'm showing in there, 0.5 to 2 micrograms per kick per minute, and the max dose up to 5 micrograms per kick per minute. It's not uncommon that we sometimes go up to 5 in some cases. Side effects is that it may decrease the stroke volume and also cause bradycardia. A couple of special situations, one of them in which phenylephrine should be avoided is in acute right ventricular failure due to pulmonary embolism, due to the effect on pulmonary vasculature of this agent, which will cause vasoconstriction. Another one is aortic insufficiency, that even though you may think that increasing the peripheral vascular resistance will not be the best idea in somebody who has a failing aortic valve, it is actually the pressure of choice because it actually does increase the coronary field, hence increasing the cardiac performance. In situations in which, you know, you are already maxed out in two or three pressures, rule of thumb, if you're already in three pressures, go ahead and, you know, start epinephrine if the patient is able to tolerate it. It hits all the receptors, beta-1s, alpha-1s, anatropic and coronatropic effects as a consequence of that, and can help you sustain the blood pressure, especially in patients that are extremely severely hemodynamically unstable. Doses from 0.01 to 0.5 micrograms per kg per minute. Wean it off as soon as you can, you know, or you can use it at the same time with other pressures, like I mentioned, and continue with them after you've been able to decrease the dose or wean off the doses of epinephrine. Bisupressing is a drug that sometimes is overlooked in our population, but it's very useful in particular circumstances, especially in severe acidotic shock. It's one of the few medicines that actually works well in an acidic environment. The other agents that we've been talking about do not perform well when there is an acidemia. This drug produces peripheral and splenic vasoconstriction, so you need to watch out for signs of peripheral hyperperfusion and also bowel ischemia following up, you know, lactic acids and mixed venous gases are very important when you use bisupressing to assure that there is still some good systemic perfusion. It can also be used, you know, in lieu of DDAVP in cases of diabetes insipidus or populations with severe neurological injury, for example, in severe TBI, they tend to develop diabetes insipidus and bisupressing as a good agent for both hemodynamic support and also for the treatment of this condition. That also just I'm showing there, so the lower end up to 0.04 as used for shock and others higher up to 0.8 in cases of GI hemorrhage when we're trying to achieve good stomach vasoconstriction. One of the things with bisupressing, though, we've got to be mindful in our patients with intracranial hypertension that due to the fact that bisupressing is going to retain free water and it could lead to hyponatremia as well. So being mindful of these values and trending the sodiums when using bisupressing is very important when somebody, when it's being used in somebody with increased intracranial pressure. Endotropic agents, like I mentioned before, dopamine, dopamine, dopamine amylurinone, different mechanisms of action, of course, support of, you know, low ejection fractions. One of the conditions that we deal with in the neurosurgical ICU following especially subarachnoid hemorrhage, but it can be also triggered by the TBI, it can be triggered by ICH, by large ischemic stroke as well, is a stress cardiomyopathy, also known as Takotsubo's cardiomyopathy. One of the things we've got to take into account is that it has high risk for arrhythmia and agents like amylurinone can cause vasodilation and then hypotension because of their peripheral effects. And I just wanted to mention amylurinone is also used as a management of cerebrovasospasm through the Montreal Protocol. The Montreal Protocol that I'm showing here basically shows the use of doses of amylurinone starting with the bolus and followed by an infusion of 0.75 micrograms per kg per minute and adjusting the infusion up to 1.25 micrograms per kg per minute. And when you reach this dosage, usually you need to add an agent such as norepinephrine or you can use, if possible, as well phenylephrine in order to provide some peripheral vasoconstriction to control the hypotensive effects of this medication. That was a brief, very brief, basic review of the drips that were used for vasopressors. Then we're going to talk about sedation. Sedation is very important in an aerosurgical ICU, not only to keep our patients away from desynchrony with a mechanical ventilator, for example, but it's also used as one of the tiers for the treatment of increased intracranial hypertension. Why? Because sedation decreases the cerebral consumption of oxygen, hence decreases the intracranial pressure. Different agents with different mechanisms of action, midazolam, propofol, ketamine, presidex, opioids, etomidate is used sometimes, especially for rapid sequence intubation. In terms of deep medicines that we use to control intracranial hypertension, we count propofol and ketamine as well. We learned a lot about ketamine during the COVID pandemic when the propofol was consumed and not widely available, so we started using ketamine as well to sedate our patients. Ketamine also has a very, very good utility in status epilepticus and in intracranial hypertension as well. As far as propofol, it's an anesthetic agent. When we talk about the RAS, you guys are familiar with the RAS sedation skill. We use them to produce deep pharmacological induced coma. And the goal when we use propofol in the surgery is basically to, besides, of course, to have a synchronic with a mechanical ventilator, being a short-acting agent, is to decrease the amount of cerebral consumption of oxygen, which also leads to a decrease in intracranial hypertension. We've got to be mindful that we need to follow triglycerides and also lipase to make sure we're not inducing pancreatitis due to the amount of lipids that the emulsion of propofol contains. And it usually is titrated, you know, according to an electron cephalogram or a beast monitor, if you're familiar with it. Another thing that we have to be careful about, it's the risk of developing propofol infusion syndrome, which is more often than not irreversible acidosis. You're going to see a high increase in triglycerides, sometimes increase of lactic acid, sometimes increase of CPK. But what you develop for sure is a very severe acidotic disturbance in your acid-base status, which sometimes can be actually fatal. It's more common, of course, you know, in the pediatric population. Preferred overabundance of the acetamines, you know, where you're anticipating a short term of intubation. And the doses, you know, you can see 5 mg per kg per minute and increases by, you know, 5 to 10 to the maximum doses of 50 to 100 mcg per kg per minute. Midazolam used for sedation, for decrease of oxygen consumption by the brain and also for the treatment of seizures, as you guys well know. It is preferred to the use of in patients who are going to have a prolonged duration of sedation and intubation, for example, in severe TBIs and high-grade supraaginal hemorrhages. You use it, of course, as a drip whenever you're able to wean it. You know, the use of intermediate pushes is also advised. And the initial doses there, infusion doses from 1 to 8 mg per hour. Now, the midazolam can be used as well in higher doses. We have patients sometimes in refractory status epilepticus that we have them on doses all the way up to 30, 35 mg of midazolam, which is an elevated dose especially. Other patients that require a lot of not only of midazolam but other drugs are patients that have a history of chronic substance abuse. They have a higher threshold and they have a lot of tolerance to these medications as well. So, both of them are useful depending on the dosages and, you know, for control of seizures as well as ICP control. For ICP control, you want to require, of course, a lower RAS score of minus 5. Another drug that is being used more and more is Presidex. One important thing is that it doesn't depress your respiratory drive. It's a selective alpha-2 adenoreceptor agonist. It can cause, though, bradycardia hypotension, which can be quite severe, and they're going to require pressure support sometimes. It doesn't produce, you know, any benefit in ICP control per se, and it's ideally used as a temporary agent as well. Another potential complication of Presidex or side effects, so to speak, will be a fever. Every time that you have a patient in a neurosurgical ICU that has developed a fever, in addition to ruling out the common offenders, such as telectasis, infections, DVTs, also keep an eye on the amount of Presidex that you're giving that can actually be causing a fever in our patients. Like I mentioned at the beginning, etomidate is mostly used for rapid sequence intubations, but it can also be used for procedural sedation at the dose of 0.2 to 0.3 milligrams per kilogram. Other agents that we use in the neurosurgical ICU with two particularly utilities is, number one, for control of intracranial hypertension, and number two in cases of severe ARDS hypoxemia and severe dyssynchrony with a mechanical ventilator. During the COVID pandemic, like I said, you know, we use a lot of these agents. You know, we actually led to shortages of some of them. In the neurosurgical ICU, we particularly like cis-ultracurin because they have Hofmann's kinetics. That basically means that there is no participation of the liver or the kidney in the metabolism of the drug. So, the effect of cis-ultracurin in the bloodstream degrades on its own in the bloodstream, unlike rocuronium or vicuronium, for example, that has a longer half-life. The effect of cis-ultracurin tends to, you know, take effect a little bit longer than you use rocuronium, for example. Others, such as succinylcholine, that can be used for rapid pharmacologic paralysis. We have to watch for cardiac arrhythmias, we have to watch for hyperkalemia, rapid paralysis, and for the development of malignant hypertemia. In theory, it can increase the intracranial pressure, but you have to balance the risk of the benefit of raising it transiently versus, you know, being able to get your patient intubated in a timely fashion. Another thing to take into account, agents, another reason why I also prefer cis-ultracurin is that rocuronium induces the release of histamine in the brain, which is going to produce neuroexcitation and increases the cellular consumption of oxygen. Some of these, or a combination of the agents that we are talking about, can also be used for birth suppression. In birth suppression, we basically mean very, very flat with just intermediate activity in the electroencephalogram, which basically means deeply, deeply, deeply, deep sedation and pharmacologically induced coma. This is an example, as you can see there, that is long runs of not a completely flat line, but very suppressed cellular activity, followed by a burst of some waveforms. That is what birth suppression means. Like I mentioned, I started epileptics and ICP control are the main aims of this therapy, and there are many drugs that can be used to induce it, pentobarbital, propofol, midazolam, inhaled anesthetics such as isoflurane and desflurane, and as well as ketamine. We talked already about midazolam, and I'm mentioning here, you know, that it can potentially be done in a drip, followed by frequent pushes. Dosage is as high as 20, but I can say there are several locations in which you have to go higher like that, 30, 35 milligrams per hour of midazolam in order to achieve birth suppression. Pentobarbital is a very good agent in terms of producing or leading to birth suppression with a couple of bad caveats. Number one is that the only formulation in the U.S. is 40% propylene glycol formulation, and that can actually lead to reversible acidosis as well if propylene glycol accumulates in a significant fashion in the bloodstream. And also, it can definitely cause hemodynamic compromise. You can use it starting with a bolus, followed by an infusion with these guidelines that I have here, starting, you know, 10 milligrams per kick, bolus over 60 minutes, followed by a 5 milligrams per kick per hour infusion for 3 hours, and then increase the infusion to 1 milligram per kick per hour after you complete the load, and then you can have a maintenance dosage from 1 to 5. And, I mean, depending on what the aim of that therapy is, you can keep it, you know, for as long as needed, taking into account that the effect of the accumulation of propylene glycol is going to put you at a higher risk for irreversible acidosis. And then, in order not to, you know, trigger the recurrence of the status epilepticus, for example, or intercurrent hypertension, you can reduce the dose of, you know, by 50% every 12 hours, and then, you know, go from there as far as finishing the infusion with the need, more often than not, of agents that will continue acting on the, essentially, either to control seizures or to control ICP, such as, you know, propofol or midazolam, that may need to be continued after the pentobarbital has been weaned off. In general, when we talk about, you know, dosages, you know, of pentobarbital for sedation and also for therapeutic coma, it's very important to follow up the levels of pentobarbital. It has a very long half-life. It's something to take into account. In case, especially if somebody needs a brain-dead determination, you're going to have to wait until the levels go down below a certain level. For sedation, the levels are recommended from 1 to 5 micrograms per milliliter. For intercurrent hypertension therapy, from 30 to 40. For therapeutic coma, for suppression of status epilepticus, 20 to 50 micrograms per milliliter. Propofol, as we have talked before, the most important thing is to watch for PRIS, propofol infusion syndrome, when using high dosages. Loading dose, in this particular situation, for blood suppression, 1 to 2 milligrams per kick. Start at 20 micrograms per kick per minute. You can go as high as 100, 200, certainly. Just watch for your PRIS, especially in somebody that has, somebody that's young and is developing, you know, elevated CPKs. Keep an eye on that because your acid-base status is the next one that's going to follow, you know, if the complications persist. Ketamine is a drug that we've been using more and more. Propofol, as I mentioned, has a very significant amount of side effects, and we learned more about ketamine during the COVID pandemic because we didn't have enough amounts of propofol, certainly. But it's very useful when somebody is, for example, you know, dynamically compromised. Propofol induces hypotension. Ketamine induces hypertension, so it's very suitable for somebody that's hemodynamically unstable. And titrate with an electrocephalogram doses from 0.5 to 3 micrograms per kick with a loading dose, and then a continuous infusion of 0.1 micrograms per kick per hour to 5 micrograms per kick per hour. A max dose of 15 milligrams per kick per hour is recommended. However, sometimes we have gone higher in our practice, you know, up to 20 sometimes in cases that it was needed. The mechanism of action, you know, is the act on the NMDA receptor. Hence, there is some theories that it can potentially be neuroprotective as well. Another thing that, you know, people used to say in the past is that ketamine increases ICP. That's not true. It actually, you know, produces birth suppression. Hence, it will decrease your ICP. One thing to take into account is that ketamine can also produce volume overload because it comes in a large amount of volume, something to keep into account as well in the management for critical care neurosurgical patients. I want to thank everybody for your attention, and I hope to see you next year as well. Thank you.

neurosurgical ICU

vasopressors

sedation agents

norepinephrine

intracranial pressure

propofol