Perioperative Methadone for Spine Surgery: A Scoping Review.

Complex spine surgery is associated with significant acute postoperative pain. Methadone possesses pharmacological properties that make it an attractive analgesic modality for major surgeries. This scoping review aimed to summarize the evidence for the perioperative use of methadone in adults undergoing complex spine surgery. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A search was performed using MEDLINE, CINAHL, Cochrane Library, Scopus, Embase, and Joanna Briggs between January 1946 and April 2023. The initial search identified 317 citations, of which 12 met the criteria for inclusion in the review. There was significant heterogeneity in the doses, routes of administration, and timing of perioperative methadone administration in the included studies. On the basis of the available literature, methadone has been associated with reduced postoperative pain scores and reduced postoperative opioid consumption. Though safety concerns have been raised by observational studies, these have not been confirmed by prospective randomized studies. Further research is required to explore optimal methadone dosing regimens, the potential synergistic relationships between methadone and other pharmacological adjuncts, as well as the potential long-term antinociceptive benefits of perioperative methadone administration.

Regional Anesthesia Techniques in Modern Neuroanesthesia Practice: A Narrative Review of the Clinical Evidence.

Neurosurgical procedures are often associated with significant postoperative pain that is both underrecognized and undertreated. Given the potentially undesirable side effects associated with general anesthesia and with various pharmacological analgesic regimens, regional anesthetic techniques have gained in popularity as alternatives for providing both anesthesia and analgesia for the neurosurgical patient. The aim of this narrative review is to present an overview of the regional techniques that have been incorporated and continue to be incorporated into modern neuroanesthesia practice, presenting in a comprehensive way the evidence, where available, in support of such practice for the neurosurgical patient.

Anemia and Optimal Transfusion Thresholds in Brain-Injured Patients: A Narrative Review of the Literature.

Anemia is a highly prevalent condition that may compromise oxygen delivery to vital organs, especially among the critically ill. Although current evidence supports the adoption of a restrictive transfusion strategy and threshold among the nonbleeding critically ill patient, it remains unclear whether this practice should apply to the brain-injured patient, given the predisposition to cerebral ischemia in this patient population, in which even nonprofound anemia may exert a detrimental effect on clinical outcomes. The purpose of this review is to provide an overview of the pathophysiological changes related to impaired cerebral oxygenation in the brain-injured patient and to present the available evidence on the effect of anemia and varying transfusion thresholds on the clinical outcomes of patients with acute brain injury.

Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial.

BACKGROUND: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma. METHODS: We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m2, 80 mg/m2, 135 mg/m2, 175 mg/m2, 215 mg/m2, and 260 mg/m2) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood-brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual. FINDINGS: 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12-12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40-215 mg/m2), and 12 patients were treated at dose level 6 (260 mg/m2). A total of 68 cycles of LIPU-MB-based blood-brain barrier opening were done (median 3 cycles per patient [range 2-6]). At a dose of 260 mg/m2, encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m2 in the case of the grade 3 encephalopathy, and to 215 mg/m2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood-brain barrier opening was most commonly associated with immediate yet transient grade 1-2 headache (12 [71%] of 17 patients). The most common grade 3-4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood-brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 µM [95% CI 0·022-0·063] in non-sonicated brain to 0·139 µM [0·083-0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 µM [0·562-1·747] in non-sonicated brain to 5·878 µM [3·462-9·980] µM in sonicated brain [5·9-times increase], p=0·0001). INTERPRETATION: LIPU-MB using a skull-implantable ultrasound device transiently opens the blood-brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing. FUNDING: National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family.

Multimodal Analgesia and Intraoperative Neuromonitoring.

Intraoperative neuromonitoring has been a valuable tool for ensuring the functional integrity of vital neural structures by providing real-time feedback to the operative team during procedures where neurological structures are at risk. Commonly used intravenous and inhaled anesthetic drugs are known to affect waveform parameters measured with various intraoperative neuromonitoring modalities. While the concept of opioid-sparing multimodal analgesia has gained popularity in recent years, the impact of such a strategy on intraoperative neuromonitoring remains poorly characterized, in contrast to the more well-established concepts and literature regarding the effects of other hypnotic agents on neuromonitoring quality. The purpose of this focused review is to provide an overview of the clinical evidence pertaining to the pharmacological interaction of certain multimodal analgesics with routine intraoperative neuromonitoring modalities.

Optimal Hemodynamic Parameters for Brain-injured Patients in the Clinical Setting: A Narrative Review of the Evidence.

Defining optimal hemodynamic targets for brain-injured patients is a challenging undertaking. The physiological interference observed in various intracranial pathologies can have varying effects on cerebral physiology at different time points. This narrative review provides an overview of cerebral autoregulatory physiology and common misconceptions, and examines the physiological considerations and clinical evidence for determining optimal hemodynamic parameters in acutely brain-injured patients with relevance to modern neuroanesthesia and neurocritical care practice.

Electroencephalographic Burst-Suppression, Perioperative Neuroprotection, Postoperative Cognitive Function, and Mortality: A Focused Narrative Review of the Literature.

Burst-suppression is an electroencephalographic pattern that results from a diverse array of pathophysiological causes and/or metabolic neuronal suppression secondary to the administration of anesthetic medications. The purpose of this review is to provide an overview of the physiological mechanisms that underlie the burst-suppression pattern and to present in a comprehensive way the available evidence both supporting and in opposition to the clinical use of this electroencephalographic pattern as a therapeutic measure in various perioperative settings.

Albumin Use in Brain-injured and Neurosurgical Patients: Concepts, Indications, and Controversies.

Human albumin has been used extensively for decades as a nonwhole blood plasma replacement fluid in the perioperative and critical care setting. Its potential advantages as a highly effective volume expander must be weighed, however, against its potential harm for patients in the context of various neurological states and for various neurosurgical interventions. This narrative review explores the physiological considerations of intravenous human albumin as a replacement fluid and examines the extant clinical evidence for and against its use within the various facets of modern neuroanesthesia and neurocritical care practice.

The Impact of the Global SARS-CoV-2 (COVID-19) Pandemic on Neuroanesthesiology Fellowship Programs Worldwide and the Potential Future Role for ICPNT Accreditation.

BACKGROUND: The COVID-19 pandemic is an international crisis placing tremendous strain on medical systems around the world. Like other specialties, neuroanesthesiology has been adversely affected and training programs have had to quickly adapt to the constantly changing environment. METHODS: An email-based survey was used to evaluate the effects of the pandemic on clinical workflow, clinical training, education, and trainee well-being. The impact of the International Council on Perioperative Neuroscience Training (ICPNT) accreditation was also assessed. RESULTS: Responses were received from 14 program directors (88% response rate) in 10 countries and from 36 fellows in these programs. Clinical training was adversely affected because of the cancellation of elective neurosurgery and other changes in case workflow, the introduction of modified airway and other protocols, and redeployment of trainees to other sites. To address educational demands, most programs utilized online platforms to organize clinical discussions, journal clubs, and provide safety training modules. Several initiatives were introduced to support trainee well-being during the pandemic. Feelings of isolation and despair among trainees varied from 2 to 8 (on a scale of 1 to 10). Fellows all reported concerns that their clinical training had been adversely affected by the coronavirus disease 2019 (COVID-19) pandemic because of decreased exposure to elective subspecialty cases and limited opportunities to complete workplace-based assessments and training portfolio requirements. Cancellation of examination preparation courses and delayed examinations were cited as common sources of stress. Programs accredited by the ICPNT reported that international networking and collaboration was beneficial to reduce feelings of isolation during the pandemic. CONCLUSION: Neuroanesthesia fellowship training program directors introduced innovative ways to maintain clinical training, educational activity and trainee well-being during the COVID-19 pandemic.

Cautionary findings for motor evoked potential monitoring in intracranial aneurysm surgery after a single administration of rocuronium to facilitate tracheal intubation.

Administration of rocuronium to facilitate intubation has traditionally been regarded as acceptable for intraoperative motor evoked potential (MEP) monitoring because of sufficiently rapid spontaneous neuromuscular blockade recovery. We hypothesized that residual neuromuscular blockade, in an amount that could hinder optimal neuromonitoring in patients undergoing intracranial aneurysm clipping, was still present at dural opening. We sought to identify how often this was occurring and to identify factors which may contribute to prolonged blockade. Records of 97 patients were retrospectively analyzed. Rocuronium was administered to facilitate intubation with no additional neuromuscular blockade given. Prolonged spontaneous recovery time to a train-of-four (TOF) ratio of 0.75 after rocuronium administration was defined as 120 min, which was approximately when dural opening and the setting of baseline MEPs were occurring. Logistic regression analysis was used to identify factors related to prolonged spontaneous recovery time. Prolonged spontaneous recovery time to a TOF ratio of 0.75 was observed in 44.3% of patients. Multivariable analysis showed that only the dosage of rocuronium based on ideal body weight had a positive correlation with prolonged spontaneous recovery time (P = 0.01). There was no significant association between dosage of rocuronium based on total body weight, age, sex, or body temperature and prolonged recovery time. This study demonstrates that the duration of relaxation for MEP monitoring purposes is well-beyond the routinely recognized clinical duration of rocuronium. Residual neuromuscular blockade could result in lower amplitude MEP signals and/or lead to higher required MEP stimulus intensities which can both compromise monitoring sensitivity.

Sevoflurane versus PRopofol combined with Remifentanil anesthesia Impact on postoperative Neurologic function in supratentorial Gliomas (SPRING): protocol for a randomized controlled trial.

BACKGROUND: Patients with intracranial tumors are more sensitive to anesthetics than the general population and are therefore more susceptible to postoperative neurologic and neurocognitive dysfunction. Sevoflurane or propofol combined with remifentanil are widely used general anesthetic regimens for craniotomy, with neither regimen shown to be superior to the other in terms of neuroprotective efficacy and anesthesia quality. There is no evidence regarding the variable effects on postoperative neurologic and neurocognitive functional outcome under these two general anesthetic regimens. This trial will compare inhalational sevoflurane or intravenous propofol combined with remifentanil anesthesia in patients with supratentorial gliomas and test the hypothesis that postoperative neurologic function is equally affected between the two regimens. METHODS: This is a prospective, single-center, randomized parallel arm equivalent clinical trial, which is approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20,160,051). Patients with supratentorial gliomas diagnosed by magnetic resonance imaging will be eligible for the trial. Written informed consent will be obtained before randomly assigning each subject to either the sevoflurane-remifentanil or propofol-remifentanil group for anesthesia maintenance to achieve an equal-desired depth of anesthesia. Intraoperative intervention and monitoring will follow a standard anesthetic management protocol. All of the physiological parameters and other medications administered during the intervention will be recorded. The primary outcome will be neurologic function change assessed by National Institute of Health Stroke Scale (NIHSS) within 4 h after general anesthesia when observer's assessment of alertness/sedation (OAA/S) reaches 4. Secondary outcomes will include NIHSS and modified NIHSS change 1 and 2 days after general anesthesia, hemodynamic stability, intraoperative brain relaxation, quality of anesthesia emergence, quality of anesthesia recovery, postoperative cognitive function, postoperative pain, postoperative neurologic complications, as well as perioperative medical expense. DISCUSSION: This randomized equivalency trial will primarily compare the impacts of sevoflurane-remifentanil and propofol-remifentanil anesthesia on short-term postoperative neurologic function in patients with supratentorial gliomas undergoing craniotomy. The exclusion criteria are strict to ensure that the groups are comparable in all aspects. Repeated and routine neurologic evaluations after operation are always important to evaluate neurosurgical patients' recovery and any newly presenting complications. The results of this trial would help specifically to interpret anesthetic residual effects on postoperative outcomes, and perhaps would help the anesthesiologist to select the optimal anesthetic regimen to minimize its impact on neurologic function in this specific patient population. TRIAL REGISTRATION: The study was registered and approved by the Chinese Clinical Trial Registry (Chinese Clinical Trial Registry, ChiCTR-IOR-16009177). Principle investigator: Nan Lin (email address: linnan127@gmail.com) and Ruquan Han (email address: hanrq666@aliyun.com) Date of Registration: September 8th, 2016. Country of recruitment: China.

Somatosensory evoked potential loss due to intraoperative pulse lavage during spine surgery: case report and review of signal change management.

Intraoperative neurophysiologic monitoring (IONM) includes various neurophysiologic tests which assess the functional integrity of the central and peripheral nervous systems during surgical procedures which place these structures at risk for iatrogenic injury. The rational for using IONM is to provide timely feedback of changes in neural function to enable the reversal of such insult before the development of irreversible neural injury. There are various causes of intraoperative loss of neuromonitoring signals and it is important to systematically rule out all possible causes quickly and thoroughly in order to target the cause of signal loss, correct it and take measures to prevent the same in the future. One such rare cause, is targeted and pressurized cold (room temperature) irrigation of the surgical site, which may induce irritation and vasospasm leading to ischemia of the affected portion of the spinal cord, hence leading to signal changes. We present this case to stress the importance of having knowledgeable members of the team who are well acquainted with all aspects of monitoring in close proximity to the operating room, so as to minimize troubleshooting time. Furthermore, we suggest the use of warm (body temperature) saline during irrigation to the surgical site, especially when using pressurized irrigation systems.

Cognitive Aids for the Diagnosis and Treatment of Neuroanesthetic Emergencies: Consensus Guidelines on Behalf of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Education Committee.

Cognitive aids and evidence-based checklists are frequently utilized in complex situations across many disciplines and sectors. The purpose of such aids is not simply to provide instruction so as to fulfill a task, but rather to ensure that all contingencies related to the emergency are considered and accounted for and that the task at hand is completed fully, despite possible distractions. Furthermore, utilization of a checklist enhances communication to all team members by allowing all stakeholders to know and understand exactly what is occurring, what has been accomplished, and what remains to be done. Here we present a set of evidence-based critical event cognitive aids for neuroanesthesia emergencies developed by the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Education Committee.

Perspectives on Dexmedetomidine Use for Neurosurgical Patients.

The α2-adrenergic receptor agonist dexmedetomidine has sedative, anxiolytic, analgesic, and sympatholytic effects. The potential advantages of neuroprotection, minimal impact on neuronal function, stable hemodynamics, opioid and anesthesia sparing effects, and minimal respiratory depression during awake procedures render it an effective anesthetic adjuvant in various neurosurgical settings. However, both the benefits and drawbacks of the use dexmedetomidine in neuroanesthesia should be considered. This narrative review will summarize the applications of dexmedetomidine in various neurosurgical settings, highlighting evidence regarding both its common and controversial uses.

Cerebral Neuromonitoring During Cardiac Surgery: A Critical Appraisal With an Emphasis on Near-Infrared Spectroscopy.

Neurological complications of cardiac surgery have a large effect on patient outcomes. In this review, the value of several modes of central nervous system monitoring for improving perioperative care is critiqued. The electroencephalogram (EEG) has been used as a means for detecting brain ischemia. Even though EEG changes are specific for ischemia, the reliability is tempered by many confounding factors. The effectiveness of the processed EEG for ensuring amnesia during surgery is controversial, but it may have value for optimizing anesthetic dose and thus reducing the risk for delirium. Transcranial Doppler may be beneficial in confirming flow to both cerebral hemispheres during antegrade cerebral perfusion such as during aortic arch surgery and in detecting cerebral emboli. Transcranial Doppler can be used for monitoring cerebral autoregulation, allowing for individualization of blood pressure targets during surgery. Measures of adequacy of cerebral oxygen balance include jugular bulb venous oxygen saturation and near-infrared spectroscopy monitoring. Both monitors have limitations that reduce the sensitivity for detecting brain ischemia. Because near-infrared spectroscopy-measured regional cerebral oxygen saturation does not distinguish arterial from venous blood, these measurements reflect the adequacy of oxygen delivery versus demand. Over short periods, filtered regional cerebral oxygen saturation data may provide a clinically feasible method of monitoring cerebral autoregulation that overcomes many limitations of transcranial Doppler. Ongoing studies have demonstrated that the latter methodology for determining perioperative blood pressure targets has large potential for reducing organ injury from cardiac surgery.

A Randomized Controlled Trial of Low-Dose Tranexamic Acid versus Placebo to Reduce Red Blood Cell Transfusion During Complex Multilevel Spine Fusion Surgery.

BACKGROUND: Multilevel spine fusion surgery for adult deformity correction is associated with significant blood loss and coagulopathy. Tranexamic acid reduces blood loss in high-risk surgery, but the efficacy of a low-dose regimen is unknown. METHODS: Sixty-one patients undergoing multilevel complex spinal fusion with and without osteotomies were randomly assigned to receive low-dose tranexamic acid (10 mg/kg loading dose, then 1 mg·kg-1·hr-1 throughout surgery) or placebo. The primary outcome was the total volume of red blood cells transfused intraoperatively. RESULTS: Thirty-one patients received tranexamic acid, and 30 patients received placebo. Patient demographics, risk of major transfusion, preoperative hemoglobin, and surgical risk of the 2 groups were similar. There was a significant decrease in total volume of red blood cells transfused (placebo group median 1460 mL vs. tranexamic acid group 1140 mL; median difference 463 mL, 95% confidence interval 15 to 914 mL, P = 0.034), with a decrease in cell saver transfusion (placebo group median 490 mL vs. tranexamic acid group 256 mL; median difference 166 mL, 95% confidence interval 0 to 368 mL, P = 0.042). The decrease in packed red blood cell transfusion did not reach statistical significance (placebo group median 1050 mL vs. tranexamic acid group 600 mL; median difference 300 mL, 95% confidence interval 0 to 600 mL, P = 0.097). CONCLUSIONS: Our results support the use of low-dose tranexamic acid during complex multilevel spine fusion surgery to decrease total red blood cell transfusion.

Factors associated with blood transfusion during intracranial aneurysm surgery.

STUDY OBJECTIVE: The purpose of this study was to identify risk factors associated with intraoperative blood transfusions in patients presenting for intracranial aneurysm surgery in the current era of more restrictive transfusion guidelines. DESIGN: Retrospective observational cohort study with stepwise, multivariate binary logistic regression analysis. SETTING: Tertiary care university teaching hospital. PATIENTS: Four hundred seventy-one consecutive patients undergoing intracranial aneurysm surgery at Northwestern Memorial Hospital (Chicago, IL) from 2006 to 2012. INTERVENTION: Red blood cell transfusion (retrospective observational). MEASUREMENTS: Demographic data, medical comorbidities, hemoglobin levels, Hunt-Hess grades, intracranial aneurysm characteristics, presenting intracranial bleeding states, estimated blood losses, transfused red blood cells, and blood products. MAIN RESULTS: Forty-six patients (9.5%) received intraoperative red blood cell transfusions. Preoperative risk factors associated with transfusions were highly related to aneurysm rupture, including such parameters as older age (P < .001), lower presenting hemoglobin level (P < .001), preoperative rupture (P < .001), and higher Hunt-Hess grade (P < .001). Intraoperative risk factors included larger aneurysm size (>10 mm; P = .03), intraventricular hemorrhage (P < .001), and intracerebral hematoma evacuation (P = .02). Binary logistic regression modeling identified age (P < .001), presenting hemoglobin level (P < .001), larger aneurysm size (>10 mm; P = .003), elevated Hunt-Hess grade (P = .021), and intraoperative rupture (P = .013) as independent predictors of intraoperative red blood cell transfusion. CONCLUSION: The incidence of intraoperative red blood cell transfusion in intracranial aneurysm surgery in our patient cohort was 9.5%, and the most significant factors associated with transfusion were presenting hemoglobin level less than 11.7 g/dL and age greater than 52 years. It would seem advisable that these patients undergo routine type and cross-matching of red blood cells before intracranial aneurysm surgery.

Residual neuromuscular blockade in the postanesthesia care unit: observational cross-sectional study of a multicenter cohort.

BACKGROUND: Residual neuromuscular blockade after general anesthesia using nondepolarizing neuromuscular blocking agents has pathophysiological, clinical, and economic consequences. A significant number of patients under muscle relaxation sustain residual curarization. METHODS: Observational, prospective, multicenter study of a cohort of patients (Residual Curarization in Spain Study, ReCuSS). Residual blockade was defined as TOFr<0.9. Patients >18 years-old under general anesthesia, including at least one dose of non-depolarizing neuromuscular blocking agents, and transferred extubated and spontaneously ventilating to the postanesthesia care unit were included. Pre- and intraoperative data were recorded, including, patient characteristics, ASA physical status, experience of the anesthesiologist, type of surgery, temperature monitoring, surgery duration, neuromuscular blockade-related parameters, type of anesthesia (halogenated-balanced, intravenous propofol-based, other), and use of neuromuscular monitoring. RESULTS: A total of 763 patients from 26 hospitals were included, 190 patients (26.7%) showing residual paralysis. Female patients were more prone to residual neuromuscular blockade. Length of surgery, type of relaxant used (benzylisoquinolines), halogenated anesthesia, absence of intraoperative specific monitoring, avoidance of drug reversal, and neostigmine reversal (vs. sugammadex), were significantly related to residual blockade. In the postanesthesia care unit, patients with residual neuromuscular blockade had an increased incidence of respiratory events and tracheal reintubation. CONCLUSIONS: The incidence of residual blockade in Spain is similar to that published in other settings and countries. Female gender, longer duration of surgery, and halogenated drugs for anesthesia maintenance were related to residual paralysis, as were NMBA specific items, such as the use of benzylisoquinoline drugs, and the absence of reversal or reversal with neostigmine.