Skeletal Muscle Relaxants and Their Impact on Intracranial Pressure in Neurosurgery

Introduction

Neuromuscular blocking agents, also known as muscle relaxants, are used to paralyze skeletal muscle, blocking the transmission of nerve impulses at the myoneural junction. They are frequently used in anesthesia to facilitate endotracheal intubation, optimize surgical conditions, and assist with mechanical ventilation in patients who have reduced lung compliance. Neuromuscular blocking agents come in 2 forms: depolarizing neuromuscular blocking agents, such as succinylcholine, and non-depolarizing neuromuscular blocking agents, such as rocuronium, vecuronium, atracurium, cisatracurium, and mivacurium [1,2].

The main depolarizing neuromuscular blocker is succinylcholine, which is widely used due to its rapid onset and short duration of action, making it ideal for rapid sequence inductions [3]. Non-depolarizing neuromuscular blockers can be subdivided into 2 classes based on their chemical structure: steroidal, including rocuronium, vecuronium, and pancuronium, and benzylisoquinoline, including mivacurium, atracurium, and cisatracurium [2].

Various muscle relaxants have specific effects on intracranial pressure. Muscle relaxants in patients with intracranial pathology do not cross the blood-brain barrier, or do so only to a small extent. They can also affect brain function secondarily by histamine release, systemic hemodynamic changes, metabolic effects, and altered afferent stimulation from muscle. Thus, in this article, we aim to discuss the different uses of different muscle relaxant drugs and their effect on brain function and intracranial pressure [4].

Using muscle relaxants as part of general anesthesia and neurosurgery anesthesia protocols is a widely accepted practice. Two benefits are expected from neuromuscular blockade in neurosurgery: (1) reduction of intracranial pressure, by lowering intrathoracic and central venous pressures, and (2) prevention of coughing or movements and their potentially disastrous consequences. It is believed that since muscle relaxants do not cross the blood-brain barrier, they generally exert only indirect effects on the central nervous system, meaning they do not have any deleterious effects on cognitive function [4].

Over time, neuroanesthesia has evolved and benefited from new volatile, short-acting agents and novel administration techniques. Although neurosurgery has considerably changed throughout the years, it is still associated with severe risks, and using the wrong agent can lead to major repercussions [4].

When choosing the appropriate muscle relaxant for a procedure, it is important to remember that factors such as acid-base imbalances and kidney or liver dysfunction will affect its action [5,6]. It is also extremely important to remember the proper selection of skeletal muscle relaxants in situations requiring increased vigilance, such as in pregnant women or oncology patients after chemotherapy or radiotherapy [2,7,8]. Due to the many factors that can influence the duration of drug effects and the risk of residual block, monitoring of neuromuscular blockade using train-of-four monitoring should be performed [9].

In this article, we compared major neuromuscular blocking agents used in neurosurgery. We focused on reviewing the muscle relaxants that are the closest to being ideal neuromuscular blockers and that have the least detrimental effect on the cardiovascular or cerebrovascular systems. This article aims to review the role of muscle relaxants and reversal agents in neurosurgical procedures.

Symptoms of Increased Intracranial Pressure

Increased intracranial pressure presents clinically through a range of symptoms. It is suspected in patients with symptoms such as worsening headache, disturbances in consciousness (primarily quantitative), and the presence of pathological focal signs, nausea, vomiting, and papilledema, which is usually a late sign, with limited value in cases of rapidly progressing conditions [10]. A late sign of increased intracranial pressure is the Cushing reflex. This refers to 3 conditions that occur together: high blood pressure, bradycardia, and irregular breathing [10]. Proper and rapid recognition of the clinical symptoms of increased intracranial pressure is important for implementing appropriate treatment and preventing brain tissue hypoperfusion [11].

Assessment of High Intracranial Pressure

The assessment of intracranial pressure can be a useful tool for evaluating a patient’s condition. There are various methods of intracranial pressure monitoring, which can be divided into invasive and noninvasive methods. Invasive methods include the intraventricular catheter (the most accurate device), subdural screw (bolt), and epidural sensor. These are typically used in life-threatening neurological emergencies, and their use can be associated with numerous complications [11]. Noninvasive methods include transcranial Doppler ultrasound, otic methods, acoustic methods, venous ophthalmodynamometry, anterior fontanelle pressure monitoring (in newborns), physical examination, and neuroimaging, which can detect typical changes such as compression of the convexity, subarachnoid space, and ventricle adjacent to the mass; enlargement of the perimesencephalic cistern on the side of the mass, accompanied by obliteration of the cistern on the other side; obliteration of both cisterns; and enlargement of the ventricle opposite the mass [12–14].

It is recommended to monitor intracranial pressure and intracranial perfusion pressure through imaging studies and clinical symptoms as part of protocol-driven care in patients at risk for intracranial hypertension. This can serve as a guide for further management – whether conservative or invasive – although there is still no exact cutoff value that would recommend a specific course of action [11].

It is important to remember that invasive and noninvasive methods encounter numerous challenges in terms of measurement and proper interpretation of results. Despite significant technological advances and improvements in management, there is still ongoing debate about the best method for measuring intracranial pressure and translating the results into clinical management [15].

It is believed that intracranial pressure should be measured invasively. Typically, an intracranial pressure probe or an external ventricular catheter is used, allowing for cerebrospinal fluid drainage and intracranial pressure measurement. The use of invasive methods enables the monitoring of pressure and its changes [11].

Treatment Methods for Increased Intracranial Pressure

To reduce intracranial pressure, conservative and surgical treatments can be used, with the choice of approach depending on the cause and the patient’s clinical condition. Conservative treatments include hyperosmolar therapy, bedside maneuvers, such as adjusting head and neck position and elevating the head of the bed, transient hyperventilation, use of medications (eg, barbiturates), and hypothermia. If these methods are resistant, sedation, the use of muscle relaxants to create a neuromuscular block, intubation, and mechanical ventilation are used. Glucocorticosteroids are occasionally effective in cases of vasogenic edema in primary or metastatic brain tumors. Surgical methods include cerebrospinal fluid drainage in cases of hydrocephalus, while for intracranial hematoma, large infarct, or tumor, decompression is performed [11]. Hyperosmotic therapy in the form of mannitol or hyperosmotic saline can be helpful in reducing intracranial pressure in cases of subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, and hepatic encephalopathy. In patients with progressive neurological deficits due to cerebral edema accompanying cerebral infarction, hyperosmotic therapy can be used and does not cause midline shift. High-dose mannitol (at least 1.2 to 1.4 g/kg) can be used in comatose trauma patients with preoperative acute subdural hematoma or intraparenchymal temporal lobe hemorrhage [16].

Succinylcholine’s Characteristics and Use in Patients Undergoing Neurosurgery

Succinylcholine is a depolarizing neuromuscular blocking agent. It adheres to the postsynaptic cholinergic receptors of the end motor endplate, inducing a continuous disruption that results in transient fasciculations or involuntary muscle contractions and subsequent skeletal muscle paralysis [17].

In one of the studies, it was shown that succinylcholine increases intracranial pressure in cats, and it was suggested that succinylcholine can be contraindicated in patients undergoing neurosurgery [17].

Another study reported that, previously, for rapid sequence intubation, succinylcholine was a preferred drug of choice due to its fast onset and duration of action but was shown to increase intracranial pressure and hyperkalemia [18].

Overall, we do not have a clear understanding of how succinylcholine acts on intracranial pressure. Numerous studies have shown that it does increase it, but some other studies had other outcomes [19,20]. Therefore, succinylcholine should be carefully used in patients undergoing neurosurgery.

In another study, we could see that succinylcholine used together with metocurine prevented the increase of intracranial pressure [21].

Characteristics of Benzylisoquinoline

Benzylisoquinolines are a diverse group of compounds derived from plant metabolites. These agents are widely used as muscle relaxants in anesthetic practice. They are non-depolarizing relaxants that cause neither blockage of the vagus nerve nor of the sympathetic ganglia [22,23].

To use muscle relaxants in neurosurgical patients with reduced intracranial compliance, these agents should have a minimal impact on hemodynamics and intracranial pressure. Benzylisoquinolinium-based neuromuscular blocking agents have many advantages, such as rapid metabolism and elimination, which allow for the fast and complete recovery of patients after surgical procedures [22,23]. Currently, this group of medications includes intermediate-acting atracurium, cisatracurium, and short-acting mivacurium [22,23]. These drugs are metabolized via Hoffmann elimination, making them a good alternative in cases of renal dysfunction. However, available publications show that in patients with impaired kidney function, the effect of cisatracurium can be prolonged, and in patients with end-stage renal disease, the use of mivacurium can result in a prolonged neuromuscular block [6]. In the guidelines published by the French Society of Anaesthesia and Intensive Care Medicine, the impact of renal and liver dysfunction on the use of skeletal muscle relaxants is considered [9,24]. In cases of renal failure, the use of cisatracurium and atracurium is likely recommended [6].

Characteristics of Atracurium

A mild to moderate reduction in intracranial pressure can be expected after using muscle relaxants. This is related to the relaxation of the skeletal muscles during the surgical procedure. However, many such agents exhibit undesirable cardiovascular effects that can lead to a secondary increase in intracranial pressure. This occurs because of the effects of such drugs on the sympathetic and parasympathetic nervous systems [25]. Acid-base balance disturbances will affect the duration and strength of atracurium’s action. Acidosis, metabolic and respiratory, will enhance the drug’s effect. Conversely, respiratory alkalosis and metabolic alkalosis will diminish the drug’s effect [5].

Atracurium’s Effect on Intracranial Pressure and Use in Neurosurgery

Atracurium is a new neuromuscular blocking agent that is believed to not have undesirable effects on the cardiovascular system. In the study by Minton et al, it was discovered that there was a rise of 4 mm Hg in intracranial pressure after the administration of atracurium. However, the increase has been attributed to cerebral vasodilation and increased intracranial blood volume [25].

Atracurium effects on intracranial pressure were also evaluated by Rosa et al and Unni et al, in 1986. It was found that at clinically used doses, atracurium does not affect sympathetic or parasympathetic nervous conduction. Nonetheless, it might cause histamine release into the bloodstream. Certain researchers argue that these quantities are enough to generate unwanted hemodynamic consequences in certain patients, including low arterial pressure and increased heart rate [26,27].

Furthermore, it has been theorized that hypotension can be caused by histamine release, particularly when atracurium is administered as a bolus. A study from 2017 researched the incidence of hypotension in critically ill patients receiving continuous infusion of atracurium or cisatracurium [28]. Both medications caused similar decreases in blood pressure. However, it was uncertain whether these results were driven by histamine release.

In a comparative study from 1995, continuous infusions of atracurium were administered to patients with severe traumatic brain injury to determine its ability to control increased intracranial pressure. Both used agents (atracurium and midazolam) turned out to be effective in controlling otherwise unstable intracranial pressure [29].

In summary, despite its recognized potential for histamine release and central nervous system stimulation, we can conclude that atracurium is safe for use in anesthesia and neurologic intensive care [25,29].

Characteristics of Cisatracurium

Cisatracurium is a novel, intermediate-acting, non-depolarizing muscle relaxant. It is an isomer of atracurium. Atracurium and cisatracurium are inactivated by plasma hydrolysis and Hofmann elimination; therefore, they do not accumulate in patients with renal or hepatic failure [1,28].

Use of Cisatracurium in Neurosurgery

The effectiveness of cisatracurium in cerebral and cardiac circulation was compared to that of atracurium in neurosurgical patients in a comparative study by Schramm et al [30]. Histamine release is the principal mechanism by which newer benzylisoquinoline muscle relaxants produce hemodynamic effects in humans. It directly causes vasodilation of cerebral effects, therefore increasing intracranial pressure and cerebral blood volume. Since cisatracurium releases less histamine than does atracurium, it was shown that cisatracurium had no impact on intracranial pressure, cerebral perfusion pressure, cerebral regulation of blood volume, or mean arterial pressure values. Moreover, cisatracurium produces less plasma laudanosine, the primary metabolite of atracurium, which is responsible for stimulating the central nervous system and can cause seizures [26,30,31]. Furthermore, another study by Schram et al showed that cisatracurium would also be a beneficial muscle relaxant used in patients with severe brain injury [31].

The results from these studies suggest that cisatracurium might be a more appropriate neuromuscular blocking agent than atracurium, administered as continuous sedation or in bolus [30]. It can be especially useful in adult patients with severe brain injury and increased intracranial pressure, due to its greater cardiovascular stability, without causing cerebral or cardiovascular hemodynamic effects [30,31].

Mivacurium’s Characteristics and Impact on Intracranial Pressure in Patients Undergoing Neurosurgery

Mivacurium is a non-depolarizing muscle relaxant that is short-acting, as opposed to atracurium and cisatracurium [1].

In a study on monitoring neuromuscular blockade induced by mivacurium, it was shown that for individuals for whom train-of-four monitoring on the upper limb is impossible or contraindicated, a potential alternative method appears to be accelerometry on the eye muscles, despite the observed faster onset and recovery times, compared with measurements taken on the corrugator supercilii muscle [32]. Some devices allow for the assessment of train-of-four by evaluating stimulation of the tibial nerve in the lower limb. In one study, it was shown that the measurement of time-to-onset in the tibial nerve assessment is comparable to that measured on the corrugator supercilia [33].

In a study conducted by Loan et al, mivacurium had significant cardiovascular effects that, in contrast to those of atracurium and cisatracurium, were related to the speed of injection. The observed effects included a combination of decreased arterial pressure and systemic resistance, with an increased cardiac index. These findings are indicative of the histamine release that neuromuscular blockers in this group are well known for [26,30,34].

Previous studies have suggested that atracurium has a higher potential than mivacurium to produce hemodynamic effects related to histamine release. However, one study showcased the opposite tendency, whereby mivacurium had a higher capability to release histamine and temporarily cause unwanted hemodynamic adverse effects, which can be significant in patients with cardiovascular or cerebral disease [34].

A newer study, performed in 1999 by Cafiero et al, demonstrated a different outcome. They evaluated the effects of mivacurium on intracranial pressure in patients undergoing neurosurgery. All patients received mivacurium as a single bolus dose, and multiple measurements of intracranial pressure and cerebrospinal fluid pressure were performed before and during the operation. Intracranial pressure was measured via intraventricular catheter, and cerebrospinal fluid pressure was measured via a catheter in the lumbar subarachnoid space. The researchers concluded that mivacurium does not influence or increase intracranial pressure and cerebrospinal fluid pressure. Moreover, no abnormal cardiocirculatory parameters were recorded in any of the patients [35].

Based on the above studies, it can be presumed that mivacurium is a suitable neuromuscular blocking drug in the treatment of patients with intracranial pathology.

In summary, cisatracurium has the least effect on cardiovascular and cerebrovascular systems, from benzylisoquinoline-derived muscle relaxants [30]. Atracurium and mivacurium both affect these systems, however, only in doses bigger than clinically used [25,34]. Therefore, research has shown that all of the neuro-blockers mentioned above are safe to use on neurosurgical patients during surgeries, and cisatracurium is the closest agent to being an ideal muscle relaxant from this group.

Aminosteroid Neuromuscular Blocking Agents

Aminosteroids are the group of steroids with amino-substituted steroid nuclei. Aminosteroids have neuromuscular blocking function. They appear as antagonists of the nicotinic acetylcholine receptor and produce outcomes by blocking acetylcholine signaling in the general nervous system. Here, we will be describing the influence of some aminosteroids used in neurosurgery on intracranial pressure. These drugs are pipecuronium bromide, pancuronium bromide, and vecuronium bromide [1,36].

Of interest, when doctors administer aminosteroids with steroids simultaneously by infusion, and this process is prolonged, it can lead to critical illness polyneuropathy, which is intense muscle weakness. This process relates mainly to vecuronium and rocuronium [36].

The aminosteriod drugs include pipecuronium, pancuronium, vecuronium, and rocuronium. Renal function disorders affect the action of these drugs, causing their effects to be prolonged [6]. Disorders of acid-base balance will also affect the duration of action of these drugs, which should be considered when planning surgery. In the case of rocuronium, vecuronium, and pancuronium, acidosis enhances their effects, while alkalosis diminishes them [6].

Characteristics of Pipecuronium

First, principally, pipecuronium bromide, known by the brand names Arduan and Pycuron, is a small molecule and non-depolarizing aminosteroid muscle relaxant used during anesthesia and surgical procedures. Its general mechanism of action is responsible for blocking nicotinic acetylcholine receptors in the neuromuscular junction, meaning that it provokes paralysis of skeletal muscles by blockage of neural transmission in the myoneural junction. The action of this drug can be antagonized by anticholinesterase agents, for example, neostigmine [37,38].

Pipecuronium bromide is the strongest neuromuscular agent managing blockage in the aminosteroid class of drugs, which also plays a role as an antagonist of M2 and M3 muscarinic receptors; however, it does not have any effect on consciousness or pain control [37,38].

Muscles that are paralyzed by pipecuronium bromide include levator muscles of the eyelids, muscles of mastication, limb muscles, abdominal muscles, muscles of the glottis, intercostal muscles of the thorax, and the diaphragm [37,38].

Characteristics of Pancuronium

Pancuronium, known by the brand name Pavulon, is the second aminosteroid muscle relaxant, most often used in neonates, which influences the paralysis of the respiratory system, resulting in easier tracheal intubation or mechanical intubation; however, it also possesses many other medical uses [39].

Pancuronium is a long-acting neuromuscular blocking agent with non-depolarizing characteristics. The general process of pancuronium action is similar to that of pipecuronium, of inhibiting the nicotinic acetylcholine receptor in the place of neuromuscular junction, resulting in blockage of acetylcholine binding. In other words, this drug is a competitive nicotinic antagonist. Another characteristic of this drug is modest vagolytic activity, but no ganglioplegic action, meaning that it inhibits the action of the vagus nerve on the heart, gastrointestinal tract, and other internal organs causing. This, for example, increases heart rate, but does not block ganglion activity. Normally it has a lower effect on the circulatory system and on histamine release. The onset of action of pancuronium is very low, comparing it with that of other drugs from the same group [39].

The reversed effect of pipecuronium can be done by anticholinesterase agents, for example, neostigmine, but also pyridostigmine and edrophonium.

The conditions of patients for which pancuronium is administered include bronchospasm; epilepsy; hypoxia, in patients who have resistance to mechanical ventilation and an unstable cardiovascular system, and in whom the use of sedatives is prohibited; severe tetanus or poisoning, where the spasm of muscles prevent proper ventilation; and shivering, with reduced oxygen needs and tracheal intubation, where succinylcholine is contraindicated [40].

In patients with renal failure, pancuronium decreases plasma clearance, prolongs neuromuscular blockade, and increases heart rate, mean arterial pressure, and cardiac output [6,16]. Patients can also have intraoperative recall, which leads to morbidity and psychological trauma [39].

Because pancuronium has a long duration of action, it can be associated with greater residual blockage after reversal, when we compare it to intermediate and short-acting neuromuscular blocking drugs [40].

Comparison of Use of Pipecuronium and Pancuronium in Neurosurgery

Thiel et al compared 2 groups of 10 patients arranged for intracranial surgery in a supine position, without any symptoms of increased intracranial pressure. Pancuronium 0.1 mg/kg and pipecuronium 0.1 mg/kg were administered as a bolus into cerebrospinal fluid pressure. Cerebrospinal fluid pressure was monitored through a lumbar subarachnoid catheter in 5 steps: before, and 3, 5, 10, and 30 min after pipecuronium and pancuronium were administered. The whole process was observed following anesthesia. Cerebrospinal fluid pressure decreased minimally after injection of both drugs, without any important differences between the study groups. Heart rate and arterial pressure were elevated mostly in patients given pancuronium but persisted as stable after pipecuronium was given [41].

Based on the results, it was concluded that pipecuronium is a safe alternative to pancuronium during neurosurgical procedures in patients without abnormally high intracranial pressure [41].

Vecuronium’s Characteristics and Use in Neurosurgery

A third non-depolarizing neuromuscular blocking agent from a group of muscle relaxant-aminosteroids used during general anesthesia in surgical procedures is called vecuronium, known with the brand name Norcuron. This drug is classified as a monoquaternary homolog of pancuronium and has a short onset of action [42].

The advantages of vecuronium are its shorter duration of action than pancuronium, lack of remarkable cardiovascular effects, lack of dependence on kidney function for elimination, and easy reversibility. It competitively binds to cholinergic receptors located at motor end plates, resulting in muscle relaxation that typically works as an adjunct to general anesthesia. Thus, it is a bisquaternary nitrogen compound that prevents depolarization and inhibition of calcium ion release, which leads to no muscle contraction [42].

Vecuronium has a similar structure to pancuronium; the only difference is the lack of a quaternizing methyl group in the 2-piperidine substitution. Interestingly, vecuronium has high lipid solubility, resulting in a high amount of biliary elimination [42].

According to a study by Rosa et al, in patients with intracranial tumors undergoing anesthesia in neurosurgery, after administration of vecuronium 0.1 mg/kg, the intracranial pressure slightly decreased, but there was no effect on cerebral and systemic hemodynamics, such as heart rate and arterial pressure [43].

Characteristics of Rocuronium

Rocuronium is a rapid-acting and reversible drug that belongs to aminosteroid non-depolarizing neuromuscular blockers used in modern anesthesia to facilitate endotracheal intubation and provide skeletal muscle relaxation during surgery or mechanical ventilation [1,44].

Rocuronium’s Use in Neurosurgery

During any neurosurgery, it is important for anesthesiologists to remember that, from the induction till the beginning of the surgery, the time is much longer than in any other kind of operation [45]. This is due to the fact that during this time there are no surgical stimuli, and attenuation of anesthesia is unavoidable, to achieve proper hemodynamic parameters. Moreover, a very important aspect, especially during spinal surgery, is intraoperative neurophysiological monitoring. Studies by Doğruel et al and Zhang et al showed the effects between different doses of rocuronium bromide that act on the intraoperative monitoring of motor evoked potentials [44,45].

Regarding doses of administrated rocuronium, Doğruel et al showed that patients who underwent neurosurgery, including craniotomy, and received rocuronium at doses 1.2 mg kg−1 in rapid-sequence induction had a significantly shorter time to achieve complete block than did patients who underwent the same surgery but received rocuronium in doses of 0.6 mg/kg. The patients who were treated with rapid-sequence induction were also observed to have better intubation quality scores. In addition to this advantage, after administration of 1.2 mg kg−1 of rocuronium, in some cases, there was no need to give additional doses of neuromuscular blocking agents during preparation of the patient for surgery [44].

For spinal surgeries, the main goal is to achieve adequate muscle relaxation and not inhibit intraoperative neurophysiological monitoring. Zhang et al showed that, to achieve this goal, the best dosage of rocuronium among 6.0, 9.0, and 12.0 μg/kg/min was 9.0 μg/kg/min [45].

The influence of anti-epileptic drugs on non-depolarizing neuromuscular blocking agents can cause their resistance. A study by Kim et al showed that the exception is valproic acid, which increases the rocuronium requirement, and the reversal effect of this action is achieved with magnesium sulphate [46].

In patients with brain trauma, succinylcholine was commonly used, and rocuronium was avoided due to its prolonged duration of action, which did not allow the neurological examination of the patient. Today, when sugammadex is widely available, rocuronium is used more often due to the fact that it can be reversed with sugammadex at any time after its administration [18]. Rocuronium does not show any effect on intracranial pressure and cerebral perfusion pressure [47].

Table 1 summarizes the results of previous studies on the effects of neuromuscular blocking agents on cerebrovascular outcomes [19–21,25–27,29–31,35,41,43,47–50].

Reversal Agents

The reversal agents acetylcholinesterase inhibitors are a group of drugs that prevent the breakdown of acetylcholine in the neuromuscular space. They reverse the action of non-depolarizing neuromuscular blockers [51,52].

Characteristics of Neostigmine

Today, the most commonly used drug for neuromuscular block recovery is neostigmine. It inhibits acetylcholinesterase, leading to more acetylcholine being available in the synapse, and therefore, triggers better muscular contraction [53].

Due to its quaternary nitrogen and non-lipophilic structure, it cannot pass the blood-brain barrier, which is why it has no effect on the central nervous system [53]. However, any damage to the blood-brain barrier during surgery or due to brain trauma can lead to increased permeability of the blood-brain barrier. If neostigmine enters the central nervous system, it reduces the incidence of postoperative cognitive decline in patients. This is due to the fact that by inhibiting cholinesterase activity, neostigmine reduces acetylcholine hydrolysis and leads to increases in the use of acetylcholine [51,52,54].

The most common anticholinergic adverse effects of neostigmine are bradyarrhythmia, hypotension, and bronchoconstriction, which can be life-threatening for patients. To prevent these conditions, patients should get atropine or glycopyrrolate [51,53].

Characteristics of Sugammadex

Sugammadex is a new and promising agent used in anesthesia practice. It works by irreversibly binding to vecuronium or rocuronium. The free rocuronium found in plasma binds to sugammadex and promotes the diffusion of the remaining rocuronium molecules out of the neuromuscular junctions. Sugammadex has an extremely rapid onset of action, which is a very important aspect in case of recovery after general anesthesia as well as in emergency situations, for instance, when tracheal intubation fails after administration of muscle relaxant [51,55].

Use of Sugammadex and Neostigmine in Neurosurgery Patients

Studies about the effects of sugammadex and neostigmine on patients undergoing neurosurgery have considered the following evaluation criteria: return of spontaneous breathing, extubation, train-of-four, bispectral index, Glasgow Coma Scale score, Modified Aldrete score, Ramsay Sedation score, vital signs, and existing complications [51,55].

The studies showed no significant changes between those 2 drugs. The full conductivity of the vecuronium-induced block restored by 2 mg kg−1 sugammadex is significantly faster, being less than 3 min, than the recovery by neostigmine, which requires almost 18 min. Moreover, studies showed that sugammadex was associated with an increase in the Glasgow Coma Scale score of 1 to 8 points [55,56].

Sugammadex also showed no adverse effects associated with acetylcholinesterase inhibitors. This is due to the fact that this drug binds only to neuromuscular block agents and does not act on any receptors [53,55].

Conclusions

Skeletal muscle relaxants are used in preparing patients for neurosurgical procedures. Current research suggests that these drugs can affect intracranial pressure. However, studies have been conducted on small patient groups, and their results are not entirely consistent. Based on current knowledge, when planning a neurosurgical operation or suspecting or identifying elevated intracranial pressure in a patient, it is important to consider the potential impact of these muscle relaxants on intracranial pressure when choosing the most appropriate drug.

Due to the aforementioned lack of sufficient evidence, it is currently not possible to identify a specific muscle relaxant that would be universally applicable for neurosurgical procedures or for treatment or care of patients in the intensive care unit with elevated intracranial pressure. Promising drugs appear to be atracurium and cisatracurium, which have either reduced intracranial pressure or helped control it [25–27,29–31,35]. Succinylcholine, on the other hand, has been shown in available studies to either increase intracranial pressure or have no effect on it; therefore, its use should be carefully considered in advance [19–21]. The final choice of drug depends on the anesthesiologist, their clinical experience and preferences, the patient’s clinical condition, and any coexisting diseases, such as kidney or liver failure (Table 2) [19–21,25–27,29–31,35,41,43,47–50].

Future Directions

Due to the limited number of studies and reports, further research involving a larger number of patients should be conducted to verify and objectify the current knowledge. This is crucial for conducting neurosurgical operations more safely. Despite significant progress in the field of intracranial pressure measurement, further studies are still needed regarding intracranial pressure measurement methods and the correlation of different methods with clinical outcomes to enable the selection of the best approach.