PBLD – 1
Anesthetic Management for Intracranial Tumor Resection: Making Rationale Pharmacological Choices
CASE: A 68 year-old man is brought to the operating room for a craniotomy for a right fronto-parietal tumor. He has a 1-year history of headaches that has progressively worsened over the past 2 months but no other obvious focal neurological deficits.
Past Medical History: Hypertension for the last 15 years, well controlled.
Imaging: Brain MRI shows a right fronto-temporal 4.2 cm tumor with well-circumscribed borders, peritumoral edema and 3 mm midline shift.
Past Surgical/Anesthetic History: laparoscopic cholecystectomy 2006, no past anesthetic problems
Physical Examination: 80 kg, anxious-appearing man
Neurological Examination: Non-focal, CN II-XII intact.
Vitals: BP 172/101, HR 58, RR 16, RR 15, T 37°C
Labs: Hemoglobin 15 g/dl, Sodium 140 mEq/L, Potassium 3.3 mEq/L, Glucose 130 mg/Dl, ECG – normal
- What are the goals for induction and maintenance of anesthesia in this patient?
- Would you use premedication (i.e. midazolam) in this patient? Why or why not?
- What are the relative advantages / disadvantages of volatile and intravenous anesthetic agents for craniotomy? Does this patient require total intravenous anesthesia (TIVA)?
- Would a remifentanil infusion offer any advantages over other opioids in the anesthetic management of this patient?
- If you use remifentanil, are you concerned about rebound hypertension when it is discontinued?
- Would a dexmedetomidine infusion be a useful adjunct in the anesthetic maintenance?
- With a starting heart rate of 58, do you have any concerns infusing remifentanil, dexmedetomidine, or a combination of both?
- Will your choice of anesthetic agent in this patient have an impact on early postoperative outcomes (such as postoperative pain, nausea/vomiting, intracerebral hemorrhage)?
- Should muscle relaxation be used to maintain akinesis in this patient? When would you want to use an alternative to muscle relaxants and what would you use?
- The anesthetic management of the patient undergoing craniotomy for supratentorial mass requires an in-depth understanding of the pharmacology of anesthetic agents and the principles of neuro-pathophysiology.
- Anesthetic goals: to provide a smooth and hemodynamically stable induction and maintenance, to maintain adequate cerebral perfusion pressure (CPP) (>70 mm Hg) and oxygenation, employ techniques that will optimize surgical exposure, achieve a rapid wakeup and neurological examination upon emergence, and achieve adequate postoperative pain control (1).
- There are few randomized clinical trials that guide the decision-making process for these patients, the anesthetic management is primarily guided by a combination of applied theory and expert consensus (2).
- In this PBLD, we will focus on the considerations for induction and maintenance of general anesthesia for craniotomy.
- The decision of whether to use anxiolytic premedication should be considered on an individual basis, after full consideration of the patient’s expected risks and benefits.
- Patient anxiety may result in tachycardia and hypertension, which increases the myocardial and cerebral O2 The blood pressure and heart rate should be monitored immediately upon arrival to the operating room. In the event of tachycardia or hypertension, a premedication may be useful.
- However, mild sedation has been shown to exacerbate or unmask focal neurologic dysfunction in patients with intracranial space occupying lesions in a drug-specific manner. Midazolam appears to produce more sedative-induced focal neurologic deficits compared with fentanyl and dexmedetomidine (3).
- Moreover, in elderly patients, the use of benzodiazepines (even midazolam, which has a relatively short half-life) is associated with an increased risk of postoperative delirium, hence fentanyl (0.5-1.0 mcg/kg) may be preferable.
- Fentanyl premedication can be particularly useful in reducing the amount of propofol required for induction of anesthesia, thereby minimizing the drop in blood pressure associated with a propofol bolus. Furthermore, fentanyl is useful in blunting the hemodynamic response to laryngoscopy (4).
- Patients with increased ICP deserve special consideration and caution. Sedation may slow the respiratory rate, resulting in increased arterial pCO2, upper airway obstruction, and hypoxemia. These effects may cause a sudden and extreme increase in ICP, resulting in a rapid deterioration of the patient’s neurological status.
- Our patient is anxious-appearing, but he also has a relatively large tumor and evidence of midline shift on imaging. For this reason it may be best to avoid a premedication in this patient if possible. Taking the time to talk with the patient may be useful in alleviating some of his anxiety. Ultimately, however, the decision to use a premedication should be made based on considerations of the potential risks and benefits.
- The use of benzodiazepines in the perioperative period might compromise the patient’s postoperative neurological status, making it difficult to distinguish the effects of the medication from the occurrence of early postoperative intracranial hemorrhage or other complications. Our patient is 68 years old, and while it may be better to avoid administering a premedication if the patient doesn’t “need” it, the decision again should be made on an individual case-by-case basis.
- It should be noted that when sedating medications are administered, the patient should be under constant supervision, and equipment for emergency airway management should be immediately available.
II. INDUCTION OF GENERAL ANESTHESIA
- Goals: General anesthesia should be induced in a manner that results in minimal changes in heart rate and blood pressure. Hypercarbia and hypoxemia should be avoided during induction.
- Several agents may be used to safely induce anesthesia in these patients. A slow and controlled induction with propofol titrated to effect may have less hypotensive effects than a rapid propofol bolus. However, it is important to note that a slow titration of propofol may result in coughing or difficult mask ventilation, which can possibly increase the ICP. In elderly or frail patients, etomidate may be a suitable alternative to propofol or thiopental for induction.
- Laryngoscopy and tracheal intubation has a profoundly stimulating effect associated with increased arterial blood pressure, heart rate, and ICP. The sympathetic response to laryngoscopy should be anticipated and prevented, and there are several ways this can be accomplished. When a remifentanil infusion is started early, it can be especially effective in blunting the response to laryngoscopy, with an additional bolus (1-1.5 mcg/kg) administered just prior to intubation. Intravenous fentanyl 1-3 mcg/kg is another good option, but it should be administered about 5 minutes prior to laryngoscopy to allow for adequate time for onset. Other options to consider include short-acting beta-blockers such as esmolol, calcium channel blockers such as nicardipine, and tracheal lidocaine.
- In the event of severe hypertension on laryngoscopy, the patients’ pupils should be assessed to rule out a possible brainstem herniation.
III. MAINTENANCE OF GENERAL ANESTHESIA
- Goals: to maintain ideal intracerebral hemodynamics, facilitate surgical exposure, facilitate neurophysiological monitoring, provide neuroprotection, and allow for a quick wake-up and neurological recovery.
- The optimal anesthetic maintenance regimen for patients undergoing craniotomy has been heavily debated in the literature (5).
- The pharmacological properties of intravenous anesthetics such as propofol may offer some advantages over inhalational agents in neuroanesthesia.
- All intravenous agents (with the exception of ketamine) reduce the cerebral metabolic rate (CMR) and cerebral blood flow (CBF), preserve autoregulation, and maintain coupling of CBF and CMR (6). Propofol anesthesia results in a lower ICP than sevoflurane or isoflurane anesthesia, suggesting improved operating conditions with a total intravenous anesthetic (TIVA) approach (7).
- The reduction in CBF with intravenous anesthetics may result in decreased cerebral oxygen saturation in areas of cerebral vasoconstriction (i.e. during hyperventilation). This may, at least in theory, result brain areas of regional hypoxia (6). Sevoflurane alternatively does not reduce cerebral oxygen saturation with hyperventilation.
- Ketamine causes an increase in CMR and CBV, and has traditionally been avoided in neurosurgical patients due to concerns of increasing ICP. Recent studies however have demonstrated that ketamine does not increase ICP, even in severe TBI patients who are sedated and ventilated, and its use should therefore not be discouraged because of ICP-related concerns (8-10). Furthermore, ketamine’s stimulatory effects on the sympathetic nervous system result in a favorable hemodynamic profile, and may be a useful adjunct in neurosurgical patients.
- At equipotent doses, cerebral metabolism is reduced with inhalational agents to the same degree as intravenous agents. At low concentrations of inhalational agents, the reduced CMR results in cerebral vasoconstriction. As concentrations increase, however, volatile agents have dose-dependent vasodilatory effects, causing an increase in CBF and uncoupling of CBF and CMR. At higher concentrations, inhalational agents may increase ICP and reduce surgical exposure, and impair cerebral autoregulation in response to decreases in CPP.
- Nitrous oxide (N2O) increases CBF without causing significant changes in CBV. When combined with other inhalational agents, N2O results in increased CBF and ICP. However, when combined with intravenous anesthetics, the cerebral vasodilatory effects of N2O are attenuated. Although studies regarding the effects of N2O on cerebral autoregulation and CMR have yielded inconsistent data, cerebral autoregulation seems to be maintained while CMR seems to increase with N2O use (11).
- Sevoflurane has the least vasodilatory effects of the inhalational agents. At concentrations below 1.0 MAC, sevoflurane does not increase CBV or ICP, and cerebral autoregulation is maintained. For these reasons, sevoflurane may be the most appropriate inhalational agent for neuroanesthesia.
- Volatile agents increase the latency of somatosensory evoked potentials and depress motor evoked potentials in a dose-dependent manner, while the effects of brainstem evoked potential are minimal. For these reasons, TIVA may be advantageous when intraoperative electrophysiological monitoring is used because the intravenous agents interfere least with electrophysiological monitoring.
- Prospective, randomized clinical trials have failed to consistently demonstrate that one anesthetic technique is advantageous over another with regards to time to recovery, extubation, or postoperative cognitive function (12-14). Furthermore, inhalational, TIVA, and combined anesthetic techniques offered similar intraoperative and postoperative hemodynamic profiles, postoperative outcomes, and total hospital stay and costs (15, 16).
- Currently the most commonly employed techniques are a sevoflurane-opioid or propofol-opioid anesthetic. Some authors recommend that the predictability and controllability of volatile techniques are preferred in elective, uncomplicated neurosurgical procedures. Because propofol decreases both ICP and CBV, TIVA may be more appropriate in more complicated patients where maximal brain relaxation is required (17). Alternatively a combined technique with a volatile agent, intravenous anesthetic, and opioid can be used.
- In recent years, the alpha-2 adrenergic receptor agonist dexmedetomidine has gained increasingly popularity for use in neurosurgical procedures because of sympatholytic properties and possible neuroprotective properties (18, 19). A dexmedetomidine infusion has been shown to result in stable hemodynamics during craniotomy without an increased incidence of bradycardia or hypotension (20-22).
- Furthermore, dexmedetomidine use has been shown to reduce sevoflurane, fentanyl, and antiemetic requirements, decrease ICP, and improve outcomes (23). When the infusion is started early, dexmedetomidine can also be useful in blunting the hemodynamic response to tracheal intubation (22, 24) and cranial pinning (25).
- Dexmedetomidine may also reduce the anesthetic and analgesic requirements, which may facilitate a rapid wake-up (26).
- In overweight and obese patients undergoing craniotomy for supratentorial tumor, a prospective, randomized clinical trial demonstrated that maintenance with desflurane resulted in shorter extubation and recovery times (27), earlier postoperative cognitive recovery and correction of hypercarbia compared with sevoflurane and isoflurane (28, 29).
- An infusion of opioids such as fentanyl or remifentanil can dramatically reduce the amount of volatile agent or propofol needed during craniotomy (30, 31), and has been shown to be effective in reducing the emergence time (32, 33).
- The use of remifentanil has been associated with the most rapid emergence and earliest cognitive recovery compared with other opioids (33-35), however patients may require more antihypertensive medications to maintain the mean arterial blood pressure within 20% of baseline on emergence (33). This rebound hypertension should be anticipated and aggressively treated, as hypertension in the early postoperative period is associated with intracranial hemorrhage. Labetalol has a rapid onset and may be especially useful in this context.
- Because remifentanil has a short half-life, a transition analgesic should be used to prevent pain and hypertension on emergence from general anesthesia. Long-acting opioids such as morphine and hydromorphone can be useful, but should be used judiciously because they can cause delirium and interfere with the postoperative neurological exam. Dexmedetomidine can reduce the analgesic requirements, and a scalp nerve block can also be useful in providing transitional analgesia (36).
- The use of neurophysiological monitoring will impact the choice of anesthetic agents administered. Volatile anesthetic agents are known to decrease the amplitude and increase the latency of somatosensory evoked potentials (SSEPs) in a dose-dependent manner, especially when the inhaled dose exceeds 0.5 the minimum alveolar concentration (MAC). An alternative anesthetic such as propofol should be available in these patients if the SSEP waveform is adversely affected at doses under 0.5 MAC.
Anesthetic Effects on ICP:
- The anesthetic management of a patient with an intracranial mass requires knowledge of the effects of anesthetic agents on CMRO2 and CBF. To reduce ICP and optimize surgical exposure, anesthetic agents are typically chosen that reduce both CMRO2 and CBF.
- Volatile agents are known to decrease CMRO2, but increase CBF at doses that exceed 0.6 MAC. However, In patients undergoing supratentorial tumor resection without midline shift, general anesthesia with 1 MAC of isoflurane or desflurane did not result in a change in ICP compared with baseline values, whereas mean arterial pressure and CPP significantly decreased compared with baseline values (37).
- Most intravenous agents, with the exception of ketamine, decrease both CBF and CMRO2. Ketamine as the sole anesthetic may increase both CBF and CMRO2, and is typically avoided in craniotomy. Nitrous oxide decreases CMRO2, but its effects on CBF are unclear.
- Patient movement during craniotomy for intracranial mass can be extremely dangerous, particularly when the patient’s head is fixed in cranial pins. When there are no contraindications, the use of a non-depolarizing muscle relaxant may be useful to achieve immobility.
- Succinylcholine may cause a mild and transient increase in ICP, and should not be used indiscriminately. The clinical significance of this increased ICP is unclear, however, and is thought to be only of concern in patients with previously elevated ICP.
- While the non-depolarizing muscle relaxants have minimal effects on intracerebral hemodynamics, it is generally recommended that long-acting muscle relaxants should be avoided because of the susceptibility of neurosurgical patients to the effects of myorelaxant hangover (17).
- The older antiepileptic medications (phenytoin, carbamazepine, phenobarbital, and valproic acid) may induce hepatic enzymes and result in an increased metabolism of muscle relaxants (2). Therefore, if a patient is taking one of these medications, the duration of shorter-acting muscle relaxants may be significantly shorter than otherwise anticipated.
- If motor evoked potential monitoring is planned, muscle relaxants are avoided and an alternative method of preventing patient movement should be employed. In this context, an opioid infusion can useful for achieving akinesis without the use of muscle relaxants. Remifentanil is especially useful in this context because of its short half-life and predictable analgesic effects.
- Bilotta F, Guerra C, Rosa G. Update on anesthesia for craniotomy. Current opinion in anaesthesiology. 2013;26(5):517-22.
- Rampil IJ, Probst S. Intracranial tumors. In: Ruskin KJ, Rosenbaum SH, Rampil IJ, editors. Fundamentals of Neuroanesthesia: A Physiologic Approach to Clinical Practice. New York: Oxford University Press; 2014. p. 151-61.
- Lin N, Han R, Zhou J, Gelb AW. Mild Sedation Exacerbates or Unmasks Focal Neurologic Dysfunction in Neurosurgical Patients with Supratentorial Brain Mass Lesions in a Drug-specific Manner. Anesthesiology. 2016.
- Bansal S, Ramesh VJ, Umamaheswara Rao GS. Fentanyl co-administration decreases the induction dose requirement of propofol in patients with supratentorial tumors and not in patients with spinal lesions. Journal of neurosurgical anesthesiology. 2012;24(4):345-9.
- Gruenbaum SE, Bilotta F. Propofol versus thiopental use in patients undergoing craniotomy. Minerva anestesiologica. 2014;80(7):753-5.
- Engelhard K, Werner C. Inhalational or intravenous anesthetics for craniotomies? Pro inhalational. Current opinion in anaesthesiology. 2006;19(5):504-8.
- Petersen KD, Landsfeldt U, Cold GE, Petersen CB, Mau S, Hauerberg J, et al. Intracranial pressure and cerebral hemodynamic in patients with cerebral tumors: a randomized prospective study of patients subjected to craniotomy in propofol-fentanyl, isoflurane-fentanyl, or sevoflurane-fentanyl anesthesia. Anesthesiology. 2003;98(2):329-36.
- Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on intracranial pressure in nontraumatic neurological illness. Journal of critical care. 2014;29(6):1096-106.
- Wang X, Ding X, Tong Y, Zong J, Zhao X, Ren H, et al. Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials. Journal of anesthesia. 2014;28(6):821-7.
- Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on ICP in traumatic brain injury. Neurocritical care. 2014;21(1):163-73.
- Rossi A, Steiner LA. Inhaled anesthetics. In: Ruskin KJ, Rosenbaum SH, Rampil IJ, editors. Fundamentals of Neuroanesthesia: A Physiologic Approach to Clinical Practice. New York: Oxford University Press; 2014. p. 120-30.
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