Intraoperative monitoring of the central and peripheral nervous systems: a narrative review.

The central and peripheral nervous systems are the primary target organs during anaesthesia. At the time of the inception of the British Journal of Anaesthesia, monitoring of the central nervous system comprised clinical observation, which provided only limited information. During the 100 yr since then, and particularly in the past few decades, significant progress has been made, providing anaesthetists with tools to obtain real-time assessments of cerebral neurophysiology during surgical procedures. In this narrative review article, we discuss the rationale and uses of electroencephalography, evoked potentials, near-infrared spectroscopy, and transcranial Doppler ultrasonography for intraoperative monitoring of the central and peripheral nervous systems.

The Association of Physiological and Pharmacological Anesthetic Parameters With Motor-Evoked Potentials: A Multivariable Longitudinal Mixed Model Analysis.

BACKGROUND: During spinal surgery, the motor tracts can be monitored using muscle-recorded transcranial electrical stimulation motor-evoked potentials (mTc-MEPs). We aimed to investigate the association of anesthetic and physiological parameters with mTc-MEPs. METHODS: Intraoperative mTc-MEP amplitudes, mTc-MEP area under the curves (AUC), and anesthetic and physiological measurements were collected retrospectively from the records of 108 consecutive patients undergoing elective spinal surgery. Pharmacological parameters of interest included propofol and opioid concentration, ketamine and noradrenaline infusion rates. Physiological parameters recorded included mean arterial pressure (MAP), bispectral index (BIS), heart rate, hemoglobin O2 saturation, temperature, and Etco2. A forward selection procedure was performed using multivariable mixed model analysis. RESULTS: Data from 75 (69.4%) patients were included. MAP and BIS were significantly associated with mTc-MEP amplitude (P < .001). mTc-MEP amplitudes increased by 6.6% (95% confidence interval [CI], 2.7%-10.4%) per 10 mm Hg increase in MAP and by 2.79% (CI, 2.26%-3.32%) for every unit increase in BIS. MAP (P < .001), BIS (P < .001), heart rate (P = .01), and temperature (P = .02) were significantly associated with mTc-MEP AUC. The AUC increased by 7.5% (CI, 3.3%-11.7%) per 10 mm Hg increase of MAP, by 2.98% (CI, 2.41%-3.54%) per unit increase in BIS, and by 0.68% (CI, 0.13%-1.23%) per beat per minute increase in heart rate. mTc-MEP AUC decreased by 21.4% (CI, -38.11% to -3.98%) per degree increase in temperature. CONCLUSIONS: MAP, BIS, heart rate, and temperature were significantly associated with mTc-MEP amplitude and/or AUC. Maintenance of BIS and MAP at the high normal values may attenuate anesthetic effects on mTc-MEPs.

Anesthesia and intraoperative neurophysiological spinal cord monitoring.

PURPOSE OF REVIEW: We will explain the basic principles of intraoperative neurophysiological monitoring (IONM) during spinal surgery. Thereafter we highlight the significant impact that general anesthesia can have on the efficacy of the IONM and provide an overview of the essential pharmacological and physiological factors that need to be optimized to enable IONM. Lastly, we stress the importance of teamwork between the anesthesiologist, the neurophysiologist, and the surgeon to improve clinical outcome after spinal surgery. RECENT FINDINGS: In recent years, the use of IONM has increased significantly. It has developed into a mature discipline, enabling neurosurgical procedures of ever-increasing complexity. It is thus of growing importance for the anesthesiologist to appreciate the interplay between IONM and anesthesia and to build up experience working in a team with the neurosurgeon and the neurophysiologist. SUMMARY: Safety measures, cooperation, careful choice of drugs, titration of drugs, and maintenance of physiological homeostasis are essential for effective IONM.

Influence of an "Electroencephalogram-Based" Monitor Choice on the Delay Between the Predicted Propofol Effect-Site Concentration and the Measured Drug Effect.

BACKGROUND: Clinicians can optimize propofol titration by using 2 sources of pharmacodynamic (PD) information: the predicted effect-site concentration for propofol (Ceprop) and the electroencephalographically (EEG) measured drug effect. Relation between these sources should be time independent, that is, perfectly synchronized. In reality, various issues corrupt time independency, leading to asynchrony or, in other words, hysteresis. This asynchrony can lead to conflicting information, making effective drug dosing challenging. In this study, we tried to quantify and minimize the hysteresis between the Ceprop (calculated using the Schnider model for propofol) and EEG measured drug effect, using nonlinear mixed-effects modeling (NONMEM). Further, we measured the influence of EEG-based monitor choice, namely Bispectral index (BIS) versus qCON index (qCON) monitor, on propofol PD hysteresis. METHODS: We analyzed the PD data from 165 patients undergoing propofol-remifentanil anesthesia for outpatient surgery. Drugs were administered using target-controlled infusion (TCI) pumps. Pumps were programmed with Schnider model for propofol and Minto model for remifentanil. We constructed 2 PD models (direct models) relating the Schnider Ceprop to the measured BIS and qCON monitor values. We quantified the models' misspecification due to hysteresis, on an individual level, using the root mean squared errors (RMSEs). Subsequently, we optimized the PD models' predictions by adding a lag term to both models (lag-time PD models) and quantified the optimization using the RMSE. RESULTS: There is a counterclockwise hysteresis between Ceprop and BIS/qCON values. Not accounting for this hysteresis results in a direct PD model with an effect-site concentration which produces 50% of the maximal drug effect (Ce50) of 6.24 and 8.62 µg/mL and RMSE (median and interquartile range [IQR]) of 9.38 (7.92-11.23) and 8.41(7.04-10.2) for BIS and qCON, respectively. Adding a modeled lag factor of 49 seconds to the BIS model and 53 seconds to the qCON model improved both models' prediction, resulting in similar Ce50 (3.66 and 3.62 µg/mL for BIS and qCON) and lower RMSE (median (IQR) of 7.87 (6.49-9.90) and 6.56 (5.28-8.57) for BIS and qCON. CONCLUSIONS: There is a significant "Ceprop versus EEG measured drug effect" hysteresis. Not accounting for it leads to conflicting PD information and false high Ce50 for propofol in both monitors. Adding a lag term improved the PD model performance, improved the "pump-monitor" synchrony, and made the estimates of Ce50 for propofol more realistic and less monitor dependent.

Comparisons of Electroencephalographically Derived Measures of Hypnosis and Antinociception in Response to Standardized Stimuli During Target-Controlled Propofol-Remifentanil Anesthesia.

BACKGROUND: Current electroencephalogram (EEG)-derived measures provide information on cortical activity and hypnosis but are less accurate regarding subcortical activity, which is expected to vary with the degree of antinociception. Recently, the neurophysiologically based EEG measures of cortical input (CI) and cortical state (CS) have been shown to be prospective indicators of analgesia/antinociception and hypnosis, respectively. In this study, we compared CI and an alternate measure of CS, the composite cortical state (CCS), with the Bispectral Index (BIS) and another recently developed measure of antinociception, the composite variability index (CVI). CVI is an EEG-derived measure based on a weighted combination of BIS and estimated electromyographic activity. By assessing the relationship between these indices for equivalent levels of hypnosis (as quantified using the BIS) and the nociceptive-antinociceptive balance (as determined by the predicted effect-site concentration of remifentanil), we sought to evaluate whether combining hypnotic and analgesic measures could better predict movement in response to a noxious stimulus than when used alone. METHODS: Time series of BIS and CVI indices and the raw EEG from a previously published study were reanalyzed. In our current study, the data from 80 patients, each randomly allocated to a target hypnotic level (BIS 50 or BIS 70) and a target remifentanil level (Remi-0, -2, -4 or -6 ng/mL), were included in the analysis. CCS, CI, BIS, and CVI were calculated or quantified at baseline and at a number of intervals after the application of the Observer's Assessment of Alertness/Sedation scale and a subsequent tetanic stimulus. The dependency of the putative measures of antinociception CI and CVI on effect-site concentration of remifentanil was then quantified, together with their relationship to the hypnotic measures CCS and BIS. Finally, statistical clustering methods were used to evaluate the extent to which simple combinations of antinociceptive and hypnotic measures could better detect and predict response to stimulation. RESULTS: Before stimulation, both CI and CVI differentiated patients who received remifentanil from those who were randomly allocated to the Remi-0 group (CI: Cohen's d = 0.65, 95% confidence interval, 0.48-0.83; CVI: Cohen's d = 0.72, 95% confidence interval, 0.56-0.88). Strong correlations between BIS and CCS were found (at different periods: 0.55 < R2 < 0.68, P < 0.001). Application of the Observer's Assessment of Alertness/Sedation stimulus was associated with changes in CI and CCS, whereas, subsequent to the application of both stimuli, changes in all measures were seen. Pairwise combinations of CI and CCS showed higher sensitivity in detecting response to stimulation than CVI and BIS combined (sensitivity [99% confidence interval], 75.8% [52.7%-98.8%] vs 42% [15.4%-68.5%], P = 0.006), with specificity for CI and CCS approaching significance (52% [34.7%-69.3%] vs 24% [9.1%-38.9%], P = 0.0159). CONCLUSIONS: Combining electroencephalographically derived hypnotic and analgesic quantifiers may enable better prediction of patients who are likely to respond to tetanic stimulation.

Comparing Motor-Evoked Potential Characteristics of NEedle versus suRFACE Recording Electrodes during Spinal Cord Monitoring-The NERFACE Study Part I.

Muscle-recorded transcranial electrical stimulation motor-evoked potentials (mTc-MEPs) are used to assess the spinal cord integrity. They are commonly recorded with subcutaneous needle or surface electrodes, but the different characteristics of mTc-MEP signals recorded with the two types of electrodes have not been formally compared yet. In this study, mTc-MEPs were simultaneously recorded from the tibialis anterior (TA) muscles using surface and subcutaneous needle electrodes in 242 consecutive patients. Elicitability, motor thresholds, amplitude, area under the curve (AUC), signal-to-noise ratio (SNR), and the variability between mTc-MEP amplitudes were compared. Whereas amplitude and AUC were significantly higher in subcutaneous needle recordings (p < 0.01), motor thresholds and elicitability were similar for surface and subcutaneous needle recordings. Moreover, the SNRs were >2 in more than 99.5% of the surface and subcutaneous needle recordings, and the variability between consecutive amplitudes was not significantly different between the two recording electrode types (p = 0.34). Surface electrodes appear to be a good alternative to needle electrodes for spinal cord monitoring. They are non-invasive, can record signals at similar threshold intensities, have adequately high SNRs, and record signals with equivalent variability. Whether surface electrodes are non-inferior to subcutaneous needle electrodes in detecting motor warnings is investigated in part II of the NERFACE study.

Use of NEedle Versus suRFACE Recording Electrodes for Detection of Intraoperative Motor Warnings: A Non-Inferiority Trial. The NERFACE Study Part II.

In the NERFACE study part I, the characteristics of muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs) recorded from the tibialis anterior (TA) muscles with surface and subcutaneous needle electrodes were compared. The aim of this study (NERFACE part II) was to investigate whether the use of surface electrodes was non-inferior to the use of subcutaneous needle electrodes in detecting mTc-MEP warnings during spinal cord monitoring. mTc-MEPs were simultaneously recorded from TA muscles with surface and subcutaneous needle electrodes. Monitoring outcomes (no warning, reversible warning, irreversible warning, complete loss of mTc-MEP amplitude) and neurological outcomes (no, transient, or permanent new motor deficits) were collected. The non-inferiority margin was 5%. In total, 210 (86.8%) out of 242 consecutive patients were included. There was a perfect agreement between both recording electrode types for the detection of mTc-MEP warnings. For both electrode types, the proportion of patients with a warning was 0.12 (25/210) (difference, 0.0% (one-sided 95% CI, 0.014)), indicating non-inferiority of the surface electrode. Moreover, reversible warnings for both electrode types were never followed by permanent new motor deficits, whereas among the 10 patients with irreversible warnings or complete loss of amplitude, more than half developed transient or permanent new motor deficits. In conclusion, the use of surface electrodes was non-inferior to the use of subcutaneous needle electrodes for the detection of mTc-MEP warnings recorded over the TA muscles.

Near-infrared spectroscopy monitoring during endovascular treatment for acute ischaemic stroke.

Introduction: The aim of endovascular treatment (EVT) for acute ischaemic stroke is to relieve the cerebral tissue hypoxia in the area supplied by the occluded artery. Near-infrared spectroscopy (NIRS) monitoring is developed to assess regional cerebral tissue oxygen haemoglobin saturation (rSO2). We aimed to investigate whether NIRS can detect inter- and intra-hemispheric rSO2 differences during EVT. Patients and methods: In this prospective, observational study, patients undergoing EVT for a proximal intracranial occlusion of the anterior circulation between May 2019 and November 2020, were included. A four-wavelength NIRS monitor (O3® Regional Oximeter (Masimo, Irvine, CA)) was used to measure rSO2 during EVT with sensors placed over the temporal lobes in 20 patients and over the frontal lobes in 13 patients. The Wilcoxon signed-rank test was used to test for inter-hemispheric rSO2 differences after groin puncture and after recanalisation, and intra-hemispheric rSO2 changes before and after recanalisation. Results: In the temporal cohort, no inter-hemispheric rSO2 differences were observed after groin puncture (median [IQR] rSO2 affected hemisphere, 70% [67-73] and unaffected hemisphere, 70% [66-72]; p = 0.79) and after recanalisation. There were no intra-hemispheric rSO2 changes over time. In the frontal cohort, no inter- and intra-hemispheric rSO2 differences or changes were found. Discussion and conclusion: A NIRS monitor could not detect inter- and intra-hemispheric rSO2 differences or changes during EVT, irrespective of the sensor position. It is likely that even with temporal sensor application, a significant proportion of the received NIRS signal was influenced by oxygenation of surrounding tissues.

Performance of Basic Life Support by Lifeboat Crewmembers While Wearing a Survival Suit and Life Vest: A Randomized Controlled Trial.

Introduction: Crewmembers of the "Royal Netherlands Sea Rescue Institution" (KNRM) lifeboats must wear heavy survival suits with integrated lifejackets. This and the challenging environment onboard (boat movements, limited space) might influence Basic Life Support (BLS) performance. The primary objective of this study was to assess the impact of the protective gear on single-rescuer BLS-quality. Material and Methods: Sixty-five active KNRM crewmembers who had recently undergone a BLS-refresher course were randomized to wear either their protective gear (n = 32) or their civilian clothes (n = 33; control group) and performed five 2-min sessions of single rescuer BLS on a mannequin on dry land. BLS-quality was assessed according to Dutch and European Resuscitation guidelines. A between group analysis (Mann-Whitney U) and a repeated within group analysis of both groups (Friedman test) were performed. Results: There were no major demographic differences between the groups. The protective gear did not significant impair BLS-quality. It was also not associated with a significant increase in the perceived exertion of BLS (Borg's Rating scale). Compression depth, compression frequency, the percentage of correct compression depth and of not leaning on the thorax, and ventilation volumes in both groups were suboptimal when evaluated according to the BLS-guidelines. Conclusions: The protective gear worn by KNRM lifeboat-crewmembers does not have a significant influence on BLS-quality under controlled study conditions. The impact and significance on outcome in real life situations needs to be studied further. This study provides valuable input for optimizing the BLS-skills of lifeboat crewmembers.

Hypotension during endovascular treatment under general anesthesia for acute ischemic stroke.

OBJECTIVE: The effect of anesthetic management (general anesthesia [GA], conscious sedation, or local anesthesia) on functional outcome and the role of blood pressure management during endovascular treatment (EVT) for acute ischemic stroke is under debate. We aimed to determine whether hypotension during EVT under GA is associated with functional outcome at 90 days. METHODS: We retrospectively collected data from patients with a proximal intracranial occlusion of the anterior circulation treated with EVT under GA. The primary outcome was the distribution on the modified Rankin Scale at 90 days. Hypotension was defined using two thresholds: a mean arterial pressure (MAP) of 70 mm Hg and a MAP 30% below baseline MAP. To quantify the extent and duration of hypotension, the area under the threshold (AUT) was calculated using both thresholds. RESULTS: Of the 366 patients included, procedural hypotension was observed in approximately half of them. The occurrence of hypotension was associated with poor functional outcome (MAP <70 mm Hg: adjusted common odds ratio [acOR], 0.57; 95% confidence interval [CI], 0.35-0.94; MAP decrease ≥30%: acOR, 0.76; 95% CI, 0.48-1.21). In addition, an association was found between the number of hypotensive periods and poor functional outcome (MAP <70 mm Hg: acOR, 0.85 per period increase; 95% CI, 0.73-0.99; MAP decrease ≥30%: acOR, 0.90 per period; 95% CI, 0.78-1.04). No association existed between AUT and functional outcome (MAP <70 mm Hg: acOR, 1.000 per 10 mm Hg*min increase; 95% CI, 0.998-1.001; MAP decrease ≥30%: acOR, 1.000 per 10 mm Hg*min; 95% CI, 0.999-1.000). CONCLUSIONS: Occurrence of procedural hypotension and an increase in number of procedural hypotensive periods were associated with poor functional outcome, whereas the extent and duration of hypotension were not. Randomized clinical trials are needed to confirm our hypothesis that hypotension during EVT under GA has detrimental effects.

Administration and monitoring of intravenous anesthetics.

PURPOSE OF REVIEW: The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all steps of the pharmacokinetic and dynamic cascade influencing this dose-effect relationship. RECENT FINDINGS: The ultimate goal when administering a particular dose of a drug is to obtain the desired clinical effect, taking into account interindividual pharmacokinetic and dynamic variability. Recent findings suggest that effect compartment-controlled target-controlled infusion systems and measurement of (surrogate) clinical drug effects might be helpful in an attempt to optimize the administration intravenous anesthetics and opioids. Additionally, recent findings suggest that the pharmacokinetic and dynamic interaction between anesthetics and opioids is important and such be taking into account when optimizing drug administration. Hereby, feedback control technology and advisory displays depicting these interactions have been studied. SUMMARY: Anesthetic drug administration might be optimized by applying knowledge from clinical pharmacokinetics and dynamics.

Clinical Pharmacokinetics and Pharmacodynamics of Propofol.

Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at the GABAA receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers' knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.