Monitored Anesthesia Care Under a Combination of Low-Dose Remimazolam Infusion and Flumazenil Antagonism: A Case Report.

Remimazolam is a novel benzodiazepine known for its short-acting properties. The safe use of flumazenil antagonism following remimazolam infusion remains a subject of debate. We present a case of monitored anesthesia care managed to be safe through low-dose remimazolam infusion and flumazenil antagonism. Pharmacokinetic simulations revealed that low-dose remimazolam was practically useful as one of the components of multimodal sedation/analgesia. Subsequent sedation with the readministration of remimazolam after a dose of flumazenil could also be attained.

Successful recording of direct cortical motor-evoked potential from a pediatric patient under remimazolam anesthesia: a case report.

BACKGROUND: Intraoperative motor-evoked potential (MEP) monitoring reduces postoperative motor deficits. Propofol-based total intravenous anesthesia is the gold standard for intraoperative myogenic MEPs. Although there is no contraindication to administering propofol in adults with peanut, soy, or egg allergies, its safety in children with these allergies remains unclear. CASE PRESENTATION: A 12-year-old girl required general anesthesia under intraoperative direct cortical MEP (dc-MEP) monitoring due to supratentorial glioma. Remimazolam-based anesthesia was selected, instead of propofol, due to the patient's egg hypersensitivity. Stable myogenic MEPs were recorded throughout the surgery with remimazolam at 0.9 mg/kg/h and remifentanil at 0.35 µg/kg/min, following adjustments of stimulation intensity and titration of remimazolam infusion. Neither intraoperative memory nor motor deficits were present after surgery. CONCLUSIONS: We present a pediatric case whose dc-MEP was recorded under remimazolam anesthesia. The cardiovascular stability and avoidance of propofol infusion syndrome with remimazolam were superior to propofol.

Intraoperative panic attack in patients undergoing awake craniotomy: a retrospective analysis of risk factors.

PURPOSE: Intraoperative anxiety is the most common psychological response of the patient during awake craniotomy. Psychological stress can trigger patient decline, resulting in failed awake craniotomy and significantly poor outcomes. This study aimed to identify the risk factors for panic attack (PA) during awake craniotomies. METHODS: With the local ethics committee approval, we conducted a manual chart review of the medical record of patients who underwent consecutive awake craniotomies between November 1999 and October 2016 at Tokyo Women's Medical University. A total of 405 patients were identified and assigned to 2 groups based on the Diagnostic and Statistical Manual of Mental Disorders-V criteria: those that met the PA criteria (Group PA) and those that did not (Group non-PA). Patient characteristics and the incidence of the PA specifier were collected. The features of the two groups were statistically compared, and risk factors for PA occurrence were determined by regression analysis. RESULTS: Sixteen of 405 patients met the diagnostic criteria of PA. Patients' characteristics were not statistically different between the groups. Multivariate logistic regression showed that intraoperative anxiety (p = 0.0002) and age younger than 39 years (as opposed to age > = 39 years; p = 0.0328) were significantly associated with the occurrence of PA during awake craniotomy. CONCLUSIONS: For patients undergoing awake craniotomy, intraoperative anxiety and age younger than 39 years were considered risk factors of PA. As PA often necessitates conversion to general anesthesia, intensive perioperative psychological support and pain management are required to achieve patient satisfaction and the surgical goal of awake craniotomy.

Respiratory Monitoring During Gamma Knife Radiosurgery: Anesthesiological Aspects.

Gamma Knife surgery (GKS) is a minimally invasive neurosurgical procedure, generally performed under moderate sedation along with local analgesia for fixation of a stereotactic frame to the patient's head, and is managed mostly by nonanesthesiologists. There are some risks for respiratory function during GKS and definite specifics for its management, since the presence of the stereotactic frame may impede access to the patient's airway and interfere with direct visual observation of him or her by medical personnel. Continuous monitoring for early detection of respiratory depression and timely intervention in the event of an emergency seem essential during radiosurgical procedures, but no relevant standards have been established to date. Since hypoventilation appears in advance of desaturation, sole monitoring of peripheral oxygen saturation (SpO2) by pulse oximetry is insufficient for detection of an early respiratory decline. According to the American Society of Anesthesiologists (ASA) practice guidelines for sedation and analgesia by nonanesthesiologists, the adequacy of ventilation during moderate and deep sedation should be evaluated by continuous observation of qualitative clinical signs and monitoring of end-tidal carbon dioxide (EtCO2). Overall, combined use of pulse oximetry and capnography may be recommended during GKS and may enhance its safety, especially in cases of medically fragile, uncooperative, or pediatric patients.

Spurious electroencephalographic activity due to pulsation artifact in the depth of anesthesia monitor.

BACKGROUND: The depth of anesthesia (DOA) is estimated based on the anesthesia-induced electroencephalogram (EEG) changes. However, the surgical environment, as well as the patient him/herself, generates electrical interferences that cause EEG waveform distortion. CASE PRESENTATION: A 52-year-old patient required general anesthesia due to the right femur necrotizing fasciitis. He had no history of epilepsy or head injury. His cardiovascular status was stable without arrhythmia under propofol and remifentanil anesthesia. The DOA was evaluated with Root® with SedLine® Brain Function Monitoring (Masimo Inc, Irvine, CA). The EEG showed a rhythmic, heart rate time-locked pulsation artifact, which diminished after electrode repositioning. Offline analysis revealed that the pulse wave-like interference in EEG was observed at the heart rate frequency. CONCLUSIONS: We experienced an anesthesia case that involves a pulsation artifact generated by the superficial temporal artery contaminating the EEG signal. Numerous clinical conditions, including pulsation artifact, disturb anesthesia EEG.

Suspected propofol infusion syndrome during normal targeted propofol concentration.

To this day, the pathophysiology and risk factors of propofol infusion syndrome (PRIS) remain unknown. Moreover, there is no widely accepted definition of PRIS, even though it is a potentially fatal condition. While many suspected cases of PRIS have been reported in both pediatric and adult populations, the actual propofol plasma concentration (Cp) has never been clarified. In this clinical report, we described the first suspected PRIS case in which the propofol Cp was measured 25 min after 226 min of propofol infusion (7.2 µg/mL), which was 12 times higher than the predicted value (0.6 µg/mL). In the presented case, we observed gradually progressive uncontrollable hypercapnia and tachycardia, followed by severe lactic acidosis during surgical anesthesia based on the target-controlled infusion of propofol. Levels of liver enzymes were slightly elevated which suggests little or no liver damage though propofol is mainly metabolized by the liver. Meanwhile, renal impairment, a common secondary feature of PRIS, occurred concomitantly when hypercapnia and metabolic acidosis were manifested. In this case, low or delayed propofol clearance might have been a triggering factor causing severe lactic acidosis.

The Impact of Intraoperative Magnetic Resonance Imaging on Patient Safety Management During Awake Craniotomy.

BACKGROUND: Awake craniotomy paired with intraoperative magnetic resonance imaging (iMRI) is now the established technique for maximizing surgical resection, while preserving neurological function. However, leaving an unsecured airway patient in the iMRI gantry represents considerable risk. Our study aimed at identifying the incidence of critical adverse events in unsecured airway patients during iMRI as part of awake craniotomy. MATERIALS AND METHODS: We conducted a clinical chart review of consecutive awake craniotomies performed between November 1999 and December 2015. Sequences of iMRI performed without invasive airway management were selected for assessment and the incidence of critical adverse events, including general convulsive seizure, respiratory arrest, nausea/vomiting and agitation, was identified. RESULTS: Critical adverse events occurred in 21 of 356 unsecured airway patients within 24 of the 579 iMRI sequences. In cases using the low-field strength open MRI scanner, emergency termination of scans due to patient decline was recorded in only 4 cases: no cases of cardiac arrest, accidental death, or thermal injury were recorded. Compared with cardiovascular monitoring, patient respiratory status was poorly recorded. CONCLUSIONS: In terms of anesthesia, concurrent use of iMRI for awake craniotomy is clinically acceptable providing potential intraoperative complications can be controlled. Further, the configuration of the iMRI scanner as well as the reduced exposure from the lower magnetic field strength was found to impact patient safety management. Therefore when a conscious patient is left in the gantry without airway support, it is advisable that levels of oxygenation and ventilation should be monitored at all times.

Can pediatric Gamma Knife radiosurgery be managed under monitored anesthesia care? A case presentation and proposal from anesthesiologists.

Gamma Knife radiosurgery is generally performed under procedural sedation and analgesia. However, there are some risks regarding the patient's respiratory function and the specifics of its management, since the presence of a stereotactic frame may impede access to the patient's airway and interfere with direct visual observation by medical personnel. Monitored anesthesia care, which is a specific anesthesia service for diagnostic or therapeutic procedures that involve various levels of sedation, analgesia and anxiolysis, is recognized as producing less physiologic disturbance while allowing a more rapid recovery than general anesthesia. The selection of suitable candidates and medications, as well as the early detection of respiratory deterioration are considered to be essential for patient safety.

A case of chronic hepatitis B merged with acute fatty liver of pregnancy with severe coagulopathy.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) is a life-threatening disorder, and its relevance to viral hepatitis B (HB) remains unknown. This case presents an initial experience of treating a patient with HB progressing to AFLP throughout pregnancy; anesthesiologists should also recognize its clinical feature for perioperative management. CASE PRESENTATION: A 28-year-old parturient was diagnosed as chronic HB (CHB) at 21 weeks gestation. Liver and kidney dysfunction appeared rapidly at 34 weeks gestation, suspected as acute exacerbation of either CHB or AFLP. Emergency cesarean section was carried out, after which maternal disseminated intravascular coagulation and hypothermia persisted. With multidisciplinary management, the patient and infant were discharged on postpartum days 64 and 12, respectively. CONCLUSIONS: Active CHB develops into AFLP. Antiviral therapy should be considered for parturient patients with CHB, particularly for those with high viral load. The most favorable outcome is prompt and accurate diagnosis to establish suitable termination method.

Electroencephalographic signals during anesthesia recorded from surface and depth electrodes.

PURPOSE: Anesthesiologists have increasingly started to use EEG-based indexes to estimate the level and type of unconsciousness. However, the physiology and biophysics are poorly understood in anesthesiological literature. METHODS: EEG was recorded from electrodes on the surface of head, including scalp, as well as DBS (deep brain stimulation) electrodes implanted deep in the brain. Mathematical modeling with a realistic head model was performed to create illustrative images of the sensitivity of electrode montages. RESULTS: EEG pattern of anesthesia, burst-suppression, is recordable outside of scalp area as well in the depth of brain because the EEG current loops produce recordable voltage gradients in the whole head. The typical electrodes used in anesthesia monitoring are most sensitive to basal surface of frontal lobes as well as frontal and mesial parts of temporal lobes. CONCLUSIONS: EEG currents create closed-loops, which flow from the surface of the cortex and then return to the inside of the hemispheres. In the case of widespread synchronous activity like physiological sleep or anesthesia, the currents recorded with surface and depth electrodes return through the base of brain and skull.

A case of failed awake craniotomy due to progressive intraoperative hyponatremia.

BACKGROUND: Perioperative seizure control is correlated with a better surgical outcome for awake craniotomy, but some anticonvulsants can induce hyponatremia. Mannitol has also been reported to be hyponatremic. CASE PRESENTATION: A 51-year-old right-handed man had malignant glioma in the left parietal lobe. Since anticonvulsant polytherapy did not stop his seizure activity, the daily dose of carbamazepine was increased beginning 17 days before awake craniotomy. The last preoperative blood examination indicated that his plasma sodium level had gradually decreased from 140 to 130 mEq/L. Following skin incision, 200 mL of 20% mannitol was administered and his plasma sodium level subsequently dropped to 117 mEq/L. The surgical strategy was changed so that the entire procedure would be performed under general anesthesia because severe intraoperative complications were anticipated. CONCLUSIONS: This case suggests that a perioperative electrolyte imbalance caused by drug interactions could be clinically significant for awake craniotomy.

Postoperative management with dexmedetomidine in a pregnant patient who underwent AVM nidus removal: a case report.

BACKGROUND: Following cerebral arteriovenous malformation (AVM) surgery, severe brain edema and hemorrhage may be caused by postoperative normal perfusion pressure breakthrough (NPPB). Sedation is necessary for this population. It is a challenge for the anesthesiologist to maintain hemodynamic stability without interfering with the neurological assessment. In Japan, propofol is contraindicated for pregnant patients. Dexmedetomidine is a versatile drug in anesthesia practice and may be useful for this situation. There is no report using dexmedetomidine for the purpose of NPPB control in pregnant patients. We describe the postoperative management with dexmedetomidine for a pregnant patient who underwent cerebral AVM nidus removal. CASE PRESENTATION: A 32-year-old patient presented with headache at the 16th week of gestation. Neuroimaging revealed an intraventricular hemorrhage and an AVM at the right anterior horn of the lateral ventricle which caused bleeding. A multidisciplinary team discussion was done, and then a craniotomy for AVM nidus removal was performed under general anesthesia. Preanesthetic aspiration prophylaxis and rapid sequence induction were added to our conventional anesthetic management. Hypotension occurred after anesthetic induction but the patient recovered by volume resuscitation and vasopressors. Anesthesia was maintained with 50% O2 in air and sevoflurane. The AVM was completely removed, and no perioperative complications occurred. Postoperative sedation with dexmedetomidine was used to prevent breakthrough hyperperfusion and cerebral edema. CONCLUSIONS: Dexmedetomidine infusion was used for postoperative sedation without causing any side effects, and it can be an alternative for sedation, especially when propofol is contraindicated.

A case of left frontal high-grade glioma diagnosed during pregnancy.

BACKGROUND: As pregnancy accelerates glioma growth, therapeutic abortion has been recommended prior to tumor resection. Additionally, it has also been suggested that the extent of glioma resection is closely correlated with patient survival. CASE PRESENTATION: A 162-cm, 61.4-kg, 30-year-old, right-handed primigravida was referred to our institution at 21 weeks gestation to obtain a second opinion. At 18 weeks gestation, the patient developed new-onset generalized convulsive seizures (GCSs), which were poorly controlled by anticonvulsant polytherapy, early in the second trimester. A 6-cm lesion located in her left frontal supplementary motor area (SMA) was suspected as a grade III glioma, classified according to the World Health Organization (WHO) guidelines. Due to the limited evidence on the use of adjuvant therapy during pregnancy, tumors causing neurological symptoms and seizures must be treated, in order to stabilize the maternal condition and enable a safe birth. In the case of pregnant patients, awake craniotomy using intraoperative magnetic resonance imaging (iMRI) is considered advantageous, achieving gross total resection with a reduction of direct cortical stimulation, which may induce seizure, and so reducing fetal exposure to anesthetics. The "Asleep-Awake-Asleep" technique was performed at 27 weeks and 2 days gestation. As use of propofol in pregnant patients is prohibited, general anesthesia was maintained through administration of sevoflurane and remifentanil until the first scan of iMRI, and was subsequently re-induced with dexmedetomidine when tumor removal had been accomplished. A supraglottic airway (SGA) was used until the patient's cranium was opened. There were no complications during either the procedure or the post-operative period. At 35 weeks gestation, the patient delivered a healthy baby of 2317 g. Pathological examination of the patient, revealed an anaplastic astrocytoma, thus radiotherapy and chemotherapy began 2 months post-delivery. There is no evidence of tumor recurrence in the patient and the child did not show any medical or developmental concerns at the point of the 17-month follow-up. CONCLUSIONS: Since evidence on the use of adjuvant therapy during pregnancy is limited, extensive resection with functional monitoring is recommended if a brain tumor is presumed to be malignant. Awake craniotomy is considered advantageous to pregnant patients because subjective movement preserves the patient's motor function and reduces fetal exposure to anesthetics. Therefore, providing multidisciplinary discussion takes place within the decision-making process, as well as careful perioperative preparation, awake craniotomy should be considered, even in the case of pregnant patients.

Conscious sedation with dexmedetomidine for implantation of a phrenic nerve stimulator in a pediatric case of late-onset congenital central hypoventilation syndrome.

Patients with congenital central hypoventilation syndrome (CCHS) develop alveolar hypoventilation resulting from a failure of central ventilatory control. Late-onset CCHS (LO-CCHS), which may be precipitated by severe respiratory infection or exposure to sedatives or general anesthesia, presents after the neonatal period. Since CCHS patients require lifelong mechanical-assisted ventilation, in western countries, diaphragm pacing is used to provide adequate alveolar ventilation and oxygenation during rest and daily activities. The main anesthesia-related concern regarding CCHS is postoperative respiratory failure or apnea, and anesthetic agents should be minimized to avoid further respiratory depression after surgery. A 5-year-old girl with LO-CCHS was referred to our hospital for implantation of a phrenic nerve stimulator for diaphragm pacing. Respiratory infection triggered the need for permanent nocturnal ventilator support at age 3 years and tracheotomy was performed at age 4 years. Repeated self-dislodgement of the ventilator tube led to hypoxic ischemic encephalopathy. The patient was thought to require mechanical ventilation under minimum sedation and pain management during the early postoperative period. The co-administration of dexmedetomidine and morphine provided effective conscious sedation with protection of the surgical site and without adverse events. She was discharged from the intensive care unit with a home ventilator at 3 days post-operation.

The effect of single low-dose dexamethasone on vomiting during awake craniotomy.

PURPOSE: Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. METHODS: We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. RESULTS: Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P < 0.0001) and at the end of surgery (P < 0.0001) showed significantly higher glucose levels in the dexamethasone group. Impaired wound healing was not observed in either group. CONCLUSION: A single low-dose of dexamethasone prevents intraoperative vomiting for awake craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.

An Unrecognized Function of Cholesterol: Regulating the Mechanism Controlling Membrane Phospholipid Asymmetry.

An asymmetric distribution of phospholipids in the membrane bilayer is inseparable from physiological functions, including shape preservation and survival of erythrocytes, and by implication other cells. Aminophospholipids, notably phosphatidylserine (PS), are confined to the inner leaflet of the erythrocyte membrane lipid bilayer by the ATP-dependent flippase enzyme, ATP11C, counteracting the activity of an ATP-independent scramblase. Phospholipid scramblase 1 (PLSCR1), a single-transmembrane protein, was previously reported to possess scrambling activity in erythrocytes. However, its function was cast in doubt by the retention of scramblase activity in erythrocytes of knockout mice lacking this protein. We show that in the human erythrocyte PLSCR1 is the predominant scramblase and by reconstitution into liposomes that its activity resides in the transmembrane domain. At or below physiological intracellular calcium concentrations, total suppression of flippase activity nevertheless leaves the membrane asymmetry undisturbed. When liposomes or erythrocytes are depleted of cholesterol (a reversible process in the case of erythrocytes), PS quickly appears at the outer surface, implying that cholesterol acts in the cell as a powerful scramblase inhibitor. Thus, our results bring to light a previously unsuspected function of cholesterol in regulating phospholipid scrambling.

[A Case of Psychogenic Tremor during Awake Craniotomy].

A 31-year-old woman with a left frontal and parietal brain tumor underwent awake craniotomy. Propofol/remifentanil general anesthesia was induced. Following craniotomy, anesthetic administrations ceased. The level of consciousness was sufficient and she was not agitated. However, the patient complained of nausea 70 minutes into the awake phase. Considering the adverse effects of antiemetics and the upcoming surgical strategy, we did not give any medications. Nausea disappeared spontaneously while the operation was suspended. When surgical intervention extended to the left caudate nucleus, involuntary movement, classified as a tremor, with 5-6 Hz frequency, abruptly occurred on her left forearm. The patient showed emotional distress. Tremor appeared on her right forearm and subsequently spread to her lower extremities. Intravenous midazolam and fentanyl could not reduce her psychological stress. Since the tremor disturbed microscopic observation, general anesthesia was induced. Consequently, the tremor disappeared and did not recur. Based on the anatomical ground and the medication status, her involuntary movement was diagnosed as psychogenic tremor. Various factors can induce involuntary movements. In fact, intraoperative management of nausea and vomiting takes priority during awake craniotomy, but we should be reminded that some antiemetics potentially induce involuntary movement that could be caused by surgery around basal ganglia.

Difficulty in identification of the frontal language area in patients with dominant frontal gliomas that involve the pars triangularis.

OBJECTIVE Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping. METHODS Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women's Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined. RESULTS The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%. Conclusions Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.