Abstract
Drugs used in neuroanesthesia should be able to provide optimal brain conditions for surgery and also help maintain adequate brain tissue perfusion to meet increased regional metabolic demands. The ability to not only rapidly achieve deeper intraoperative anesthesia levels but also allow quick postoperative recovery of consciousness, good analgesic effects, no epileptogenic effects, minimal interference with neuromonitoring modalities, no adverse effects on other body organs, and capability of preserving systemic and cerebral hemodynamic stability are some of the desirable attributes of a neuroanesthetic drug. The beneficial cerebral effects of these drugs would be maintenance of cerebral autoregulation, vasoreactivity to carbon dioxide (CO 2 ) and coupling of cerebral blood flow and cerebral metabolic rate, and prevention of increases in intracranial pressures and cerebral blood volume.
Keywords
Anesthetics, Inhalational, Intravenous, Neuropharmacology, Neuroprotection, Opioids
Outline
Anesthetic Drugs and Sedatives 104
Intravenous Anesthetic Agents 104
Barbiturates 105
Cerebral Effects of Barbiturates 105
Other Effects of Barbiturates 105
Current Status 107
Recent Research 107
Propofol 107
Cerebral Effects of Propofol 107
Other Effects of Propofol 107
Current Status 107
Recent Research 107
Etomidate 108
Cerebral Effects of Etomidate 108
Other Effects of Etomidate 108
Current Status 108
Recent Research 108
Ketamine 108
Cerebral Effects of Ketamine 109
Other Effects of Ketamine 109
Current Status 109
Recent Research 109
Benzodiazepines 109
Cerebral Effects of Benzodiazepines 110
Other Effects of Benzodiazepines 110
Current Status 110
Recent Research 110
Opioids 110
Dexmedetomidine 111
Recent Research 111
Inhalational Anesthetic Agents 111
Desflurane 111
Cerebral Effects of Desflurane 112
Other Effects of Desflurane 112
Current Status 112
Recent Research 113
Sevoflurane 113
Cerebral Effects of Sevoflurane 113
Other Effects of Sevoflurane 113
Current Status 113
Recent Research 113
Isoflurane 113
Cerebral Effects of Isoflurane 114
Other Effects of Isoflurane 114
Current Status 114
Recent Research 114
Nitrous Oxide 114
Xenon 115
Neuromuscular Blocking Agents 115
Local Anesthetic Agents 116
Miscellaneous Drugs 116
Future Directions in Neuropharmacology 116
Conclusion 116
References 118
With the advent of newer neurosurgeries like minimally invasive procedures, endovascular neurosurgeries and complex revascularization operations, increased use of sophisticated intraoperative neurological monitors, and significant advances in neurocritical care, the scope of neuroanesthesia has also expanded tremendously. This has necessitated a quest for more capable, more rapidly titratable, and safer drugs for anesthesia and sedation. Drugs used in neuroanesthesia should be able to provide optimal brain conditions for surgery and also help maintain adequate brain tissue perfusion to meet increased regional metabolic demands. The ability to not only rapidly achieve deeper intraoperative anesthesia levels but also allow quick postoperative recovery of consciousness, good analgesic effects, no epileptogenic effects, minimal interference with neuromonitoring modalities, no adverse effects on other body organs, and capability of preserving systemic and cerebral hemodynamic stability are some of the desirable attributes in a neuroanesthetic drug. The beneficial cerebral effects of these drugs would be maintenance of cerebral autoregulation, vasoreactivity to carbon dioxide (CO 2 ) and coupling of cerebral blood flow (CBF) and cerebral metabolic rate (CMR), and prevention of increases in intracranial pressures (ICPs) and cerebral blood volume (CBV).
The correct choice of drugs and their doses for anesthesia and sedation is thus vital in preventing further worsening of the intracranial pathology or introduction of a new cerebral insult. This necessitates a better understanding of the cerebral effects and other important issues related to the commonly used anesthetics and sedatives, and is the main scope of this chapter. Discussion on other drugs and adjuvants used in neurosurgical practice can be found elsewhere in this book.
Anesthetic Drugs and Sedatives
Anesthetic drugs cause their cerebral effects by producing metabolic and functional changes in the central nervous system (CNS). Broadly, intravenous agents tend to reduce both CBF and CMR in a parallel manner and maintain their coupling, while inhalational agents decrease the CMR and increase the CBF and appear not to maintain coupling. However, anesthesia-related CBF–CMR coupling may vary under different brain conditions as the effects of anesthetics on CBF is influenced by both a direct effect on the cerebral vascular tone (vasoconstriction or vasodilatation) and indirect changes in the CMR. Furthermore, this dual mechanism of action makes it difficult to predict whether anesthetics can cause an “intracerebral steal” or the beneficial “reverse intracerebral steal” phenomenon in the pathological brain in which CO 2 reactivity and autoregulation may be lost. Anesthetics also produce changes in the ICP by changing the CBF and thereby the CBV, and by their influence on cerebrospinal fluid (CSF) dynamics, i.e., the rate of production and reabsorption of CSF. The cerebral effects of anesthetics are also governed by their systemic effects, primarily on the blood pressure, arterial CO 2 , and body temperature.
A promising attribute of anesthetic drugs that has been identified lately is that some of them have the potential for neuroprotective effects and may even be able to reduce neuronal damage from ischemic insults. These effects are attributed to their ability to reduce neuronal activity and metabolic rates. Lidocaine, thiopental, and sevoflurane have shown to be protective against ischemia in animal studies, particularly when given at the beginning of an ischemic insult due to their proposed “preconditioning effect.” However, the clinical utility of anesthetics in preventing and ameliorating ischemic damage needs further investigation. The neuroprotective effects of various anesthetic drugs are discussed in a separate chapter.
Recent suggestions that anesthetic drugs can cause neurotoxicity and postoperative cognitive dysfunction (POCD) is an area of great concern for the anesthetists. Detailed discussion on this important subject can be found elsewhere in this book.
Intravenous Anesthetic Agents
Intravenous anesthetic agents are small hydrophobic compounds that when injected, enter the highly perfused and lipophilic tissues in the brain and spinal cord where they produce anesthesia in a single circulation time. Termination of anesthesia with these drugs does not reflect metabolism but their redistribution out of the CNS into the blood and then into the lesser perfused tissues like muscles and viscera. Drug redistribution can cause accumulation and slower recovery from its effects.
Barbiturates
Barbiturates are CNS depressant drugs commonly used in neurological practice for providing mild sedation to total anesthesia, and also as anticonvulsants, hypnotics, anxiolytics and analgesics. While sodium thiopental (thiobarbiturates), thiamylal (thiobarbiturates), and methohexital (oxybarbiturates) are used for induction of anesthesia, amobarbital is mainly used for performing “the Wada test,” also known as the “intracarotidsodium amobarbital procedure” used for testing cerebral language and memory representation of the cerebral hemispheres. Barbiturates are derivatives of barbituric acid (2,4,6-trioxohexahydropyrimidine) ( Fig. 6.1 ) and act primarily as γ-aminobutyric acid (GABA) receptor agonists ( http://en.wikipedia.org/wiki/Barbiturate ). They also act on the glutamate, adenosine, and nicotinic acetylcholine receptors. The clinically recommended dosages and pharmacokinetics of barbiturates are summarized in Table 6.1 .
| Anesthetic Agents | Thiopentone Sodium | Propofol | Etomidate | Ketamine |
|---|---|---|---|---|
| Induction dose (mg/kg) | 3–5 | 2.0–2.5 | 0.2–0.4 | 0.5–1.5 |
| Induction duration (mins) | 5–8 | 4–8 | 4–8 | 10–15 |
| t 1/2 (h) | 12.1 | 1.8 | 2.9–5.3 | 3 |
| Clearance (mL/kg/min) | 3.4 | 23–50 | 18–25 | 19.1 |
| Protein binding(%) | 85 | 95–99 | 76 | 12 |
Cerebral Effects of Barbiturates ( Table 6.2 )
Barbiturates produce cerebral function depression and cause a dose-dependent decrease in cerebral metabolic rate for oxygen consumption (CMRO 2 ) and CBF till the electroencephalograph (EEG) becomes isoelectric. The induction dose of thiopental causes a 25–30% decrease in CMRO 2 with a maximum 55% decrease occurring at 2–5 times that dose. They cause a reduction in ICP due to decreases in CBF and CBV, and also maintain cerebral autoregulation and CO 2 reactivity. In low doses, thiopental sodium causes no change in the rate of CSF formation, and either no change or an increase in the resistance to reabsorption of CSF, but in higher doses, it causes decrease in CSF formation rate with either no change or a decrease in the resistance to resorption resulting in a raised ICP. As autoregulation is similar in both brain and spinal cord, high-dose barbiturate therapy causes a significant decrease in spinal cord blood flow (SCBF) suggestive of a protective effect of barbiturates on spinal cord injury, although spinal cord metabolism seems to be less sensitive to depression by barbiturates.
| Anesthetic Agents/Muscle Relaxants | ICP | CPP | CBF | CMRO 2 | CSF Dynamics | BBB | Epileptogenic | |
|---|---|---|---|---|---|---|---|---|
| Resistance to Resorption | CSF Formation | |||||||
| Xenon | ↓ | ↓/− | ↓ | ↓↓ | ? | ? | + | No |
| Isoflurane | ↑/− | ↓/− | ↑ | ↓↓ | ↓/−/↑ | − | + | No |
| Sevoflurane | ↑/− | ↓/− | ↑ | ↓↓ | ↑ | ↓ | + | Yes |
| Desflurane | ↑/−− | ↓/− | ↑ | ↓↓ | − | −/↑ | + | No |
| Nitrous oxide | ↑↑ | ↓↓ | ↑ | ↑ | − | − | + | Yes |
| Thiopentone sodium | ↓↓ | ↑↑ | ↓↓↓ | ↓↓↓ | −/↓ | ↑/−/↓ | + | No |
| Propofol | ↓↓ | ↑↑ | ↓↓ | ↓↓ | − | − | + | No |
| Etomidate | ↓↓ | ↑↑ | ↓↓ | ↓↓ | −/↓ | −/↓ | + | Yes |
| Ketamine | ↑↑ | ↓↓ | ↑↑ | ↑ | − | ↑ | + | Yes |
| Midazolam | ↓/− | ↑/− | ↓ | ↓ | −/↓ | −/↑ | + | No |
| Fentanyl | ↑/−/↓ | ↓/− | ↓/−/↑ | ↓/− | −/↓ | ↑/−/↓ | + | Yes |
| Sufentanil | ↑/−/↓ | ↓/− | ↓/−/↑ | ↓/− | − | ↑/−/↓ | + | Yes |
| Remifentanil | ↑/−/↓ | − | ↓/−/↑ | ↓/− | − | − | + | Yes |
| Vecuronium | − | − | − | − | − | − | / | No |
| Rocuronium | − | − | − | − | − | − | / | No |
| Succinylcholine | ↑/− | ↓/− | ↑/− | ↑/− | − | − | / | No |
| Dexmedetomidine | ↓ | ↑ | ↓↓ | ↓↓ | − | − | + | Yes |
Other Effects of Barbiturates
Barbiturates cross the blood–brain barrier (BBB) very rapidly. Methohexital has been shown to reduce the seizure threshold, and hence seizure activity may be a concern on emergence from barbiturate anesthesia. Cognitive impairment on chronic use of barbiturates is well known; both propofol and barbiturates were shown to cause severe cognitive side effects, but the result was confounded by the differences in age distribution in the two study groups. Curcumin, a substance in turmeric, is being considered as a safe and effective adjuvant to barbiturates in preventing cognitive impairment due to its antioxidant, antiinflammatory, and neuroprotective properties. Recent literature has demonstrated that drugs that antagonize N -methyl- d -aspartate (NMDA) receptors and agonize GABA receptors produce widespread neurodegeneration in the developing brain. Fredriksson et al. observed a reduction in cognitive function in rodents, after a combination of thiopental or propofol and ketamine at postnatal day 10 and at 8–10 weeks of age. Significant systemic effects of barbiturates include hypotension and respiratory depression.
Current Status
Due to its ICP-reducing and possibly neuroprotective effects, barbiturates continue to be used widely in neurosurgical anesthesia, especially in patients with raised ICP. However, barbiturates may require vasopressor support to maintain cerebral perfusion pressure (CPP) and may cause delayed recovery due to accumulated effects.
Recent Research
At present, there is no evidence to prove that the administration of barbiturates in patients with acute severe head injury improves the overall outcome. A systematic review in 2012 has also found inefficient evidence in favor of its effectiveness as an anxiolytic drug.
Propofol
The chemical formulation of propofol is 2,6-diisopropylphenol ( Fig. 6.2 ). It is used for induction and maintenance of general anesthesia as well as for sedation. Propofol is also known as “milk of amnesia,” because of its milklike appearance. The presently available preparation of propofol is 1% (10 mg/mL), which contains 2.25% of glycerol as a tonicity-stabilizing agent, 10% soybean oil, and 1.2% purified egg phospholipid as an emulsifier, with sodium hydroxide to adjust the pH. The mechanism of action of propofol is either though activation of GABA receptors or blocking action on sodium channels. A 2004 research also suggests that the endocannabinoid system may also contribute significantly to the anesthetic action of propofol. The recommended clinical dosage and pharmacokinetics of propofol is summarized in Table 6.1 .
Cerebral Effects of Propofol ( Table 6.2 )
Propofol causes decreases in CMRO 2 and CBF similar to barbiturates, the reduction in CMRO 2 being less than decreases in CBF. It also causes decreases in ICP by decreasing the CBF; the ICP is lowered while maintaining the CPP, unlike with barbiturates and inhalational anesthetic agents like sevoflurane and isoflurane. In clinical dosages, it does not affect cerebral autoregulation. The CO 2 vasoreactivity is preserved, and hence, hyperventilation will decrease the ICP under propofol anesthesia. Propofol has no effect on the production and resorption of CSF. The SCBF autoregulation is maintained with low- and high-dose propofol infusion. It induces depression of metabolic activity in spinal cord gray matter also. Propofol may also have direct cerebral vasoconstrictive activity.
Other Effects of Propofol
Propofol as a highly lipophilic drug crosses BBB and placenta and distributes into the breast milk too. The anticonvulsant effect of propofol is not clear as some data suggest a proconvulsant effect when used with other drugs. A measurable postoperative memory impairment has been observed in patients who have received 1–2 h of anesthesia with propofol and remifentanil. No differences in the incidence of POCD has been demonstrated in patients anesthetized with xenon, propofol, desflurane, or sevoflurane. Propofol anesthesia for prolonged period (5 h) can cause death of neurons and oligodendrocytes in both the fetal and neonatal brain. Hence prolonged infusion in small children is best avoided as it can cause acidosis, heart failure, and even death.
Current Status
It is useful anesthetic for neurosurgery due to favorable cerebral effects, rapid onset and recovery, and minimal interference with neurophysiological monitoring. Cerebral vasoconstriction makes it a suitable drug for vascular neurosurgeries. It is useful in patients with intracranial hypertension, but caution is required as it can decrease CPP due to associated hypotension.
Recent Research
Propofol is widely used in pediatric and adult populations its safety in neonates has not been defined and at present, there is no evidence supporting its use in neonates. Both thiopental sodium and propofol are used for the treatment of refractory status epilepticus, but there is no clear evidence supporting the efficacy of either of the two drugs in terms of clinical outcome.
Etomidate
Etomidate is a short-acting anesthetic agent used for induction of general anesthesia and for sedation. The chemical formulation of etomidate is ethyl 3-[(1R)-1-phenylethyl] imidazo 5-carboxylate ( Fig. 6.3 ). Etomidate has limited suppression of ventilation and lack of histamine release and protects from myocardial and cerebral ischemia. The “etomidate speech and memory test” is used to determine speech lateralization in patients prior to performing lobectomies to remove epileptogenic centers in the brain. The drug acts primarily on GABA receptors and is highly protein bound. It is metabolized by hepatic and plasma esterases to inactive products. The pharmacological characteristics of etomidate are described in Table 6.1 .
Cerebral Effects of Etomidate ( Table 6.2 )
Etomidate reduces CMRO 2 and CBF in a parallel manner to produce an isoelectric EEG. The maximal fall in CMRO 2 is achieved after a fall in CBF, and this effect is possibly due to a direct effect causing cerebral vasoconstriction. It also causes a dose-dependent fall in ICP following reduction in CBF. In pediatric patients with severe traumatic brain injury, single-dose etomidate administration results in significant reductions in ICP and improvement in CPP. The reactivity to CO 2 is maintained well under etomidate anesthesia. Its effect on cerebral autoregulation has not been evaluated. Etomidate in low dose causes no change in the rate of CSF formation and resistance to CSF resorption. However, in higher doses etomidate causes reduction in rate of CSF formation with either decrease or no change in resistance to CSF resorption.
Other Effects of Etomidate
It is a hydrophobic drug and crosses BBB very rapidly like barbiturates; the CNS effect lasts only for few minutes. Etomidate has been used to protect against cerebral ischemia in high risk patients, however no human trials are available to support the evidence. Also its role in seizure control has not been proven. Etomidate can cause POCD in elderly patients. Prolonged infusion of etomidate can cause propylene glycol toxicity that can clinically present as hyperosmolality with an increased osmolal gap, hemolysis, hemoglobinuria, and metabolic acidosis. It can cause adrenocortical suppression and involuntary muscle activity.
Current Status
Lack of cardiovascular side effects makes etomidate a useful neuroanesthetic. It can also be used safely for neurophysiological monitoring as it maintains both somatosensory evoked potential (EP) and motor EP threshold. It should be avoided or used cautiously in patients with seizure history.
Recent Research
Etomidate provides more stable hemodynamic parameters as compared to propofol. It can be used safely without serious cortisol suppression lasting more than 24 h. In comparison with ketamine for rapid sequence induction, etomidate does not provide superior intubating conditions and more favorable hemodynamic response to laryngoscopy and tracheal intubation.
Ketamine
Ketamine is a phencyclidine derivative, and its chemical formulation is arylcyclohexylamine ( Fig. 6.4 ). It produces a state called “dissociated anesthesia,” which is characterized by the presence of dissociation between thalamocortical and limbic system. It also provides intense analgesia as well as amnesia. Because of the possibility of increased airway secretions and emergence delirium, it is advised to give an antisialagogue (glycopyrrolate) and midazolam as premedication in patients receiving ketamine. Ketamine mainly binds to NMDA receptors. It acts on other receptors like opioid receptors, GABA receptors, muscarinic receptors, voltage-sensitive sodium channels, and calcium channels. The pharmacological characteristics of ketamine are described in Table 6.1 .
Cerebral Effects of Ketamine ( Table 6.2 )
Unlike other intravenous anesthetic agents, ketamine increases the CBF and CMRO 2 . At subanesthetic doses, ketamine acts as a potent cerebral vasodilator and increases the CBF by 60% in normal situations. In patients with brain tumor and aneurysmal resection, 1 mg/kg ketamine administration does not cause increase in middle cerebral artery velocity. It was believed earlier that an induction dose of ketamine significantly increases the ICP and hence was considered contraindicated in patients with a raised ICP. However, some studies have found its use safe when accompanied with hyperventilation. Cerebral autoregulation and CO 2 reactivity are well maintained with ketamine. It increases the rate of CSF formation but either decreases or causes no change in resistance to CSF resorption. Ketamine has protective effects on the spinal cord. It prevents loss of antioxidant activity in spinal cord tissue in cord injury cases.
Other Effects of Ketamine
Ketamine is highly lipid soluble and rapidly crosses the BBB producing quick onset of action and rapid recovery from anesthesia. Ketamine would be unlikely to have proconvulsant action; however, myoclonic and seizure like activities may occur in normal patients. It is known to cause emergence delirium, which occurs more frequently within an hour and is less frequent in children. Ketamine increases the amplitude of somatosensory EPs but decreases the auditory and visual evoked response in humans.
Current Status
It is not the first choice in neuroanesthesia, and is avoided in patients with raised ICP or decreased intracranial compliance.
Recent Research
According to Schreiberova et al., sedation by dexmedetomidine–ketamine–midazolam combination is a safe and suitable method for endovascular neurointerventions. It provides hemodynamic stability without respiratory depression.
Benzodiazepines
The chemical formula of benzodiazepine is C 9 H 8 N 2 ( Fig. 6.5 ). Benzodiazepines exert their CNS effects by escalating the effect of GABA neurotransmitter leading to hypnosis, sedation, anxiolysis, anticonvulsant effect, and anterograde amnesia. Side effects of this central action includes dizziness, sedation, weakness, loss of orientation, headache, irritability, aggression, sleep disturbances, and confusions.
Cerebral Effects of Benzodiazepines ( Table 6.2 )
Benzodiazepines (midazolam, diazepam, lorazepam) cause decrease in CBF and CMRO 2 in all doses. Midazolam also produces dose-related changes in regional CBF. These agents may produce EEG slowing but cannot completely eliminate EEG activity. They cause little or no increase in ICP but do not blunt the reflex increase in ICP during direct laryngoscopy. The benzodiazepine antagonist (flumazenil) can increase the ICP when used in large doses to reverse midazolam action. CBF autoregulation and CO 2 reactivity are well preserved with benzodiazepines. At low doses, benzodiazepines cause no change in the rate of CSF formation, but at higher doses, they decrease CSF formation; the resistance to resorption is either increased or there is no change.
Other Effects of Benzodiazepines
Low doses of midazolam are shown to preserve SCBF but higher doses can cause a decrease. Benzodiazepines cross the BBB. They also have potent anticonvulsant effects. Prolonged benzodiazepine infusions can cause encephalopathy. Seizures can be precipitated by the administration of large doses of benzodiazapine antagonist flumazenil. POCD can also be induced by benzodiazapines. The metabolism of benzodiazepine in neonates is very slow, and its effect can persist up to 2 weeks after birth if consumed during pregnancy resulting in the “floppy infant syndrome” characterized by hypotonia, CNS depression, and failure to suck.
Current Status
They are used as supplemental drugs in neuroanaesthesia. Use of flumazenil to reverse benzodiazepine-induced sedation must be done cautiously in patients with impaired intracranial compliance.
Recent Research
Although benzodiazepines are used to treat muscle spasms due to their muscle relaxant effects, there is no current evidence to support their efficacy for treatment of muscle spasm, especially in patients suffering from rheumatoid arthritis. Midazolam is commonly used as infusion to sedate children or neonates in the intensive care unit (ICU), but again, at present there is insufficient data to promote this use of midazolam and further research is required to evaluate the effectiveness of midazolam in neonates.
Opioids
All opioids have variable effects on cerebral circulation and metabolism, which is attributed to the other anesthetics used in combination. With a vasodilating drug, opioids produce cerebral vasoconstriction, and with drug having vasoconstriction properties, it produces vasodilation in cerebral circulation. In animal studies it has been found that fentanyl and sufentanil along with a volatile anesthetic agent CBF and CMRO 2 . However, sufentanil with no volatile agent in background produces an increase in CBF. There are some reports that show that both fentanyl and sufentanil increase ICP in patients with severe head injury. According to Werner et al., under well-controlled mean arterial blood pressure (MABP), sufentanil had significant effects on ICP in patients with head-injury, whereas with a low MABP it produced only transient increases in ICP. In one study there was no difference in ICP-elevating effect of fentanyl in patients with impaired and preserved autoregulation. Alfentanil and remifentanil produce little effect on ICP and CBF and middle cerebral artery velocity. These two drugs are considered ideal for neuroanesthesia and have shown satisfactory results in neurosurgical patients.
Cerebral Effects of Opioids ( Table 6.2 )
Opioids have minimal effects on CBF and CMRO 2 in low doses, while in higher doses, there is a progressive reduction in both CBF and CMRO 2 . Like benzodiazepines, opioids also cause slowing of EEG activity but cannot eliminate it. Opioids directly produce either minimal reduction or no change in the ICP but can markedly raise the ICP secondary to respiratory depression causing hypercapnia. Large doses of opioids can cause hypotension and decrease the CPP and hence, should be used cautiously in neurosurgical patients. The opioid antagonist (naloxone) has minimal effects on CBF and ICP if given in titrated doses, but large doses of naloxone can cause intracranial hemorrhage and arrhythmias. Cerebral autoregulation and CO 2 reactivity are well preserved with all opioids. In low doses, they cause no change in rate of CSF formation and decrease the resistance to resorption of CSF. Fentanyl, at higher doses, decreases CSF formation with either an increase or no change in resistance to resorption, while alfentanil at higher doses causes no change in CSF formation and resistance to resorption. High doses of sufentanil cause no change in CSF formation and either no change or increase in resistance to resorption.
Other Effects of Opioids
All opioids cross the BBB. High doses of narcotics have been shown to produce seizures in laboratory animals but rarely in humans. Normeperidine, a metabolite of meperidine, is a known convulsant. Opioids and associated disturbances of calcium, sodium, and glucose homeostasis can cause POCD. Severe neonatal CNS depression is reported after maternal consumption of opioids. They have minimal effects on the somatosensory EPs.
Current Status
As clinical doses of most opioids produce minimal effects on cerebral circulation and metabolism, these are used widely in neurosurgical patients in combination with other anesthetics. However, caution is required when using them in patients with raised or unstable ICP.
Recent Research
No significant difference in extubation time was observed between patients receiving remifentanil and sufentanil by target control infusion during elective intracranial surgery. In comparison to continuous remifentanil infusion, a single dose of dexmedetomidine (0.5 μg/kg) provided smooth emergence with hemodynamic stability in patients undergoing cerebral aneurysm clipping.
Dexmedetomidine
Dexmedetomidine is an agonist of α 2 -adrenergic receptors in certain parts of the brain and acts as an anxiolytic, sedative, and analgesic. It provides sedation without causing risk of respiratory depression and is often used in the ICU for providing light to moderate sedation to critically ill patients. Its use is associated with less delirium. Data on the cerebral effects of dexmedetomidine are limited. It decreases the CBF, CMRO 2 , and ICP and can impair cerebral autoregulation, but it does not abolish CO 2 reactivity. Dexmedetomidine has an important role during awake craniotomy surgeries. Along with scalp block, dexmedetomidine provides an effective and safe anesthetic approach in these surgeries. Dexmedetomidine during general anesthesia may effectively inhibit or reduce perioperative stress responses in children with brain tumors. Both in vitro and in vivo studies have shown neuroprotective effects of dexmedetomidine ; however, the mechanism of neuroprotection is not yet clear. It does not cause any significant alteration in sensory or motor EPs.
Recent Research
A 2015 randomized controlled trial reports better controlled postoperative arterial pressures and superior analgesia with the use of dexmedetomidine during craniotomy. When used as an adjunct to total intravenous anesthesia, dexmedetomidine does not seem to alter EPs and therefore can be safely used during surgeries requiring neurophysiological monitoring. Infusion of low-dose ketamine and dexmedetomidine both provide good postoperative analgesia with minimal side effects. Both of the tested analgesic regimes can be used safely and effectively for postoperative pain relief in patients after spine surgery.
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