Elevated preoptic brain activity in zebrafish glial glycine transporter mutants is linked to lethargy-like behaviors and delayed emergence from anesthesia.

Delayed emergence from anesthesia was previously reported in a case study of a child with Glycine Encephalopathy. To investigate the neural basis of this delayed emergence, we developed a zebrafish glial glycine transporter (glyt1 - / -) mutant model. We compared locomotor behaviors; dose-response curves for tricaine, ketamine, and 2,6-diisopropylphenol (propofol); time to emergence from these anesthetics; and time to emergence from propofol after craniotomy in glyt1-/- mutants and their siblings. To identify differentially active brain regions in glyt1-/- mutants, we used pERK immunohistochemistry as a proxy for brain-wide neuronal activity. We show that glyt1-/- mutants initiated normal bouts of movement less frequently indicating lethargy-like behaviors. Despite similar anesthesia dose-response curves, glyt1-/- mutants took over twice as long as their siblings to emerge from ketamine or propofol, mimicking findings from the human case study. Reducing glycine levels rescued timely emergence in glyt1-/- mutants, pointing to a causal role for elevated glycine. Brain-wide pERK staining showed elevated activity in hypnotic brain regions in glyt1-/- mutants under baseline conditions and a delay in sensorimotor integration during emergence from anesthesia. Our study links elevated activity in preoptic brain regions and reduced sensorimotor integration to lethargy-like behaviors and delayed emergence from propofol in glyt1-/- mutants.

REsidual Neuromuscular Block Prediction Score Versus Train-of-Four Ratio and Respiratory Outcomes: A Retrospective Cohort Study.

BACKGROUND: Residual neuromuscular blockade is associated with an increased incidence of postoperative respiratory complications. The REsidual neuromuscular block Prediction Score (REPS) identifies patients at high risk for residual neuromuscular blockade after surgery. METHODS: A total of 101,510 adults undergoing noncardiac surgery under general anesthesia from October 2005 to December 2018 at a tertiary care center in Massachusetts were analyzed for the primary outcome of postoperative respiratory complications (invasive mechanical ventilation requirement within 7 postoperative days or immediate postextubation desaturation [oxygen saturation {Spo2} <90%] within 10 minutes). The primary objective was to assess the association between the REPS and respiratory complications. The secondary objective was to compare REPS and train-of-four (TOF) ratio <0.90 on the strength of their association with respiratory complications. RESULTS: A high REPS (≥4) was associated with an increase in odds of respiratory complications (adjusted odds ratio [OR], 1.13 [95% confidence interval {CI}, 1.06-1.21]; P < .001). In 6224 cases with available TOF ratio measurements, a low TOF ratio (<0.9) was associated with respiratory complications (adjusted OR, 1.43 [95% CI, 1.11-1.85]; P = .006), whereas a high REPS was not (adjusted OR, 0.96 [95% CI, 0.74-1.23]; P = .73) (P = .018 for comparison between ORs). CONCLUSIONS: The REPS may be implemented as a screening tool to encourage clinicians to use quantitative neuromuscular monitoring in patients at risk of residual neuromuscular blockade. A positive REPS should be followed by a quantitative assessment of the TOF ratio.

Ease of Application of Various Neuromuscular Devices for Routine Monitoring.

BACKGROUND: Subjective evaluations to confirm recovery from neuromuscular blockade with a peripheral nerve stimulator (PNS) is inadequate. Quantitative monitors are the only reliable method to confirm adequate recovery of neuromuscular function. Unfortunately, many clinicians are unfamiliar with such devices and there is concern that the introduction of objective monitoring would be exceedingly laborious and could cause workflow delays. This study investigates how long it takes experienced nurse anesthetists to apply various neuromuscular devices as well as their perception regarding the ease of application. METHODS: Twenty nurse anesthetists were consented and participated in an educational session that familiarized them with 3 devices: SunStim Plus PNS (SunMed, Grand Rapids, MI), the acceleromyography-based IntelliVue NMT device (Philips, Amsterdam, the Netherlands), and electromyography-based TetraGraph device (Senzime B.V., Uppsala, Sweden). Participants were timed while placing each monitor on patients in a real-world setting. For the quantitative devices (IntelliVue NMT and TetraGraph), participants were also timed when obtaining calibrated baseline train-of-four (TOF) ratios. Friedman test and pairwise Wilcoxon signed-rank tests were used to evaluate the difference in time to connect different devices. Participants were surveyed about how easy they found it to utilize these devices. RESULTS: After adjusting for multiple comparison, time to connect was significantly less for PNS (median, 29; range, 16-58 seconds) compared to either the TetraGraph device (median, 62.8; range, 32-101 seconds; P < .001) or the IntelliVue NMT device (median, 46; range: 28-90 seconds; P < .001). The difference in time to connect between the TetraGraph device and the IntelliVue NMT device was not statistically significant (P = .053), but it took significantly less time to calibrate the TetraGraph device than the IntelliVue NMT device (median difference, -16; range, -88 to 49 seconds; P = .002). The participants found applying either the IntelliVue NMT device (P = .042) or the TetraGraph device (P = .048) more difficult than applying a PNS while finding it easier to calibrate the TetraGraph device versus the IntelliVue NMT device (P < .001). CONCLUSIONS: It takes 19 seconds longer to apply a quantitative neuromuscular monitor (the IntelliVue NMT device) than a PNS. While this difference reached significance, this relatively minimal additional time represents an inappropriate barrier to the application of quantitative monitors. Regardless of which quantitative monitor was utilized, these nurse anesthetists found the application and utilization of such devices relatively straightforward.

Electroencephalogram (EEG) in COVID-19: A systematic retrospective study.

OBJECTIVES: Although rare, neurological manifestations in SARS-CoV-2 infection are increasingly being reported. We conducted a retrospective systematic study to describe the electroencephalography (EEG) characteristics in this disease, looking for specific patterns. METHODS: EEGs performed in patients with positive PCR for SARS-CoV-2 between 25/03/2020 and 06/05/2020 in the University Hospital of Bicêtre were independently reviewed by two experienced neurologists. We used the American Clinical Neurophysiology Society's terminology for the description of abnormal patterns. EEGs were classified into five categories, from normal to critically altered. Interobserver reliability was calculated using Cohen's kappa coefficient. Medical records were reviewed to extract demographics, clinical, imaging and biological data. RESULTS: Forty EEGs were reviewed in 36 COVID-19 patients, 18 in intensive care units (ICU) and 22 in medicine units. The main indications were confusion or fluctuating alertness for 23 (57.5%) and delayed awakening after stopping sedation in ICU in six (15%). EEGs were normal to mildly altered in 23 (57.5%) contrary to the 42.5% where EEG alterations were moderate in four (10%), severe in eight (20%) and critical in five (12.5%). Generalized periodic discharges (GPDs), multifocal periodic discharges (MPDs) or rhythmic delta activity (RDA) were found in 13 recordings (32.5%). EEG alterations were not stereotyped or specific. They could be related to an underlying morbid status, except for three ICU patients with unexplained encephalopathic features. CONCLUSION: In this first systematic analysis of COVID-19 patients who underwent EEG, over half of them presented a normal recording pattern. EEG alterations were not different from those encountered in other pathological conditions.

Individualized Quality Data Feedback Improves Anesthesiology Residents' Documentation of Depth of Neuromuscular Blockade Before Extubation.

Reversal of neuromuscular blockade is an important anesthesia quality measure, and anesthesiologists should strive to improve both documentation and practice of this measure. We hypothesized that the use of an electronic quality database to give individualized resident anesthesiologist feedback would increase the percentage of cases that residents successfully documented quantitative depth of neuromuscular blockade before extubation. The mean baseline success rate among anesthesiology residents was 80% (95% confidence interval [CI], 78-81) and increased by 14% (95% CI, 11-17; P < .001) after the residents were given their individualized quality data. Practice patterns improved quickly but were not sustained over 6 months.

Risk factors of inadequate emergence following general anesthesia with an emphasis on patients with substance dependence history.

BACKGROUND: This study aims to define the incidence and risk factors of both emergence agitation and hypoactive emergence in adult patients and substance-dependent patients following general anesthesia to elaborate on the risk factors and precise management of them. METHODS: The study recruited 1,136 adult patients who received elective surgeries under general anesthesia for this prospective observational study. Inadequate emergence was determined according to the Richmond Agitation-Sedation Scale (RASS). Emergence agitation was defined as a RASS ≥ +1 point, and hypoactive emergence was defined as a RASS ≤ -2 points. Subgroup analyses were then conducted on patients with substance dependence. RESULTS: Inadequate emergence in the post-anesthesia care unit (PACU) occurred in 20.3% of patients, including 13.9% with emergence agitation and 6.4% with hypoactive emergence. Ninety-five patients had a history of substance dependence. Compared to divorced patients, never-married and presently married patients, who underwent gynecological and thoracic surgeries, had a lower risk of agitation. Neurologic disorders, intraoperative blood loss, intraoperative morphine, and PACU analgesic drug administration were associated with increased agitation risk. Hypertension and psychological disorders, intraoperative opioids, and PACU Foley catheter fixation were associated with increased hypoactive emergence risk. Substance-dependent patients had higher risk for agitation (21.1%, P = 0.019) and hypoactive emergence (10.5%, P = 0.044). CONCLUSIONS: Inadequate emergence in PACU following general anesthesia is a significant problem correlated with several perioperative factors. Patients with a history of substance dependence appear to be more at risk of inadequate emergence than the general population.

Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice.

Electroencephalogram monitoring during propofol (PRO) anesthesia typically features low-frequency oscillations, which may be involved with thalamic reticular nucleus (TRN) modulation. TRN receives noradrenergic inputs from the locus coeruleus (LC). We hypothesized that specific noradrenergic connections in the TRN may contribute to the emergence from PRO anesthesia. Intranuclei norepinephrine (NE) injections (n = 10) and designer receptors exclusively activated by designer drugs (DREADDs) (n = 10) were used to investigate the role of noradrenergic inputs from the LC to the TRN during PRO anesthesia. Whole-cell recording in acute brain slice preparations was used to identify the type of adrenoceptor that regulates noradrenergic innervation in the TRN. An intracerebral injection of NE into the TRN delays arousal in mice recovering from PRO anesthesia (means ± sd; 486.6 ± 57.32 s for the NE injection group vs. 422.4 ± 48.19 s for the control group; P = 0.0143) and increases the cortical-δ (0.1-4 Hz, 25.4 ± 2.9 for the NE injection group vs. 21.0 ± 1.7 for the control group; P = 0.0094) oscillation. An intra-TRN injection of NE also decreased the EC50 of PRO-induced unconsciousness (57.05 ± 1.78 mg/kg for the NE injection group vs. 72.44 ± 3.23 mg/kg for the control group; P = 0.0096). Moreover, the activation of LC-noradrenergic nerve terminals in the TRN using DREADDs increased the recovery time [466.1 ± 44.57 s for the clozapine N-oxide (CNO) injection group vs. 426.1 ± 38.75 s for the control group; P = 0.0033], decreased the EC50 of PRO-induced unconsciousness (64.77 ± 3.40 mg/kg for the CNO injection group vs. 74.00 ± 2.08 mg/kg for the control group; P = 0.0081), and increased the cortical-δ oscillation during PRO anesthesia (23.29 ± 2.58 for the CNO injection group vs. 19.56 ± 1.9 for the control group; P = 0.0213). In addition, whole-cell recording revealed that NE augmented the inhibitory postsynaptic currents in the TRN neurons via the α1-adrenoceptor. Our data indicated that enhanced NE signaling at the noradrenergic terminals of the LC-TRN projection delays arousal from general anesthesia, which is likely mediated by the α1-adrenoceptor activation. Our findings open a door for further understanding of the functions of various LC targets in both anesthesia and arousal.-Zhang, Y., Fu, B., Liu, C., Yu, S., Luo, T., Zhang, L., Zhou, W., Yu, T. Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice.

Use of esophageal balloon pressure-volume curve analysis to determine esophageal wall elastance and calibrate raw esophageal pressure: a bench experiment and clinical study.

BACKGROUND: Accurate measurement of esophageal pressure (Pes) depends on proper filling of the balloon. Esophageal wall elastance (Ees) may also influence the measurement. We examined the estimation of balloon-surrounding elastance in a bench model and investigated a simplified calibrating procedure of Pes in a balloon with relatively small volume. METHODS: The Cooper balloon catheter (geometric volume of 2.8 ml) was used in the present study. The balloon was progressively inflated in different gas-tight glass chambers with different inner volumes. Chamber elastance was measured by the fitting of chamber pressure and balloon volume. Balloon pressure-volume (P-V) curves were obtained, and the slope of the intermediate linear section was defined as the estimated chamber elastance. Balloon volume tests were also performed in 40 patients under controlled ventilation. The slope of the intermediate linear section on the end-expiratory esophageal P-V curve was calculated as the Ees. The balloon volume with the largest Pes tidal swing was defined as the best volume. Pressure generated by the esophageal wall during balloon inflation (Pew) was estimated as the product of Ees and best volume. Because the clinical intermediate linear section enclosed filling volume of 0.6 to 1.4 ml in each of the patient, we simplified the estimation of Ees by only using parameters at these two filling volumes. RESULTS: In the bench experiment, bias (lower and upper limits of agreement) was 0.5 (0.2 to 0.8) cmH2O/ml between the estimated and measured chamber elastance. The intermediate linear section on the clinical and bench P-V curves resembled each other. Median (interquartile range) Ees was 3.3 (2.5-4.1) cmH2O/ml. Clinical best volume was 1.0 (0.8-1.2) ml and ranged from 0.6 to 1.4 ml. Estimated Pew at the best volume was 2.8 (2.5-3.5) cmH2O with a maximum value of 5.2 cmH2O. Compared with the conventional method, bias (lower and upper limits of agreement) of Ees estimated by the simple method was - 0.1 (- 0.7 to 0.6) cmH2O/ml. CONCLUSIONS: The slope of the intermediate linear section on the balloon P-V curve correlated with the balloon-surrounding elastance. The estimation of Ees and calibration of Pes were feasible for a small-volume-balloon. TRIAL REGISTRATION: Identifier NCT02976844 . Retrospectively registered on 29 November 2016.

Recovery of muscle function after deep neuromuscular block by means of diaphragm ultrasonography and adductor of pollicis acceleromyography with comparison of neostigmine vs. sugammadex as reversal drugs: study protocol for a randomized controlled trial.

BACKGROUND: The extensive use of neuromuscular blocking agents (NMBAs) during surgical procedures still leads to potential residual paralyzing effects in the postoperative period. Indeed, neuromuscular monitoring in an intra-operative setting is strongly advocated. Acetylcholinesterase inhibitors can reverse muscle block, but their short half-life may lead to residual curarization in the ward, especially when intermediate or long-acting NMBAs have been administered. Sugammadex is the first selective reversal drug for steroidal NMBAs; it has been shown to give full and rapid recovery of muscle strength, thus minimizing the occurrence of residual curarization. Acceleromyography of the adductor pollicis is the gold standard for detecting residual curarization, but it cannot be carried out on conscious patients. Ultrasonography of diaphragm thickness may reveal residual effects of NMBAs in conscious patients. METHODS/DESIGN: This prospective, double-blind, single-center randomized controlled study will enroll patients (of American Society of Anesthesiologists physical status I-II, aged 18-80 years) who will be scheduled to undergo deep neuromuscular block with rocuronium for ear, nose, or throat surgery. The study's primary objective will be to compare the effects of neostigmine and sugammadex on postoperative residual curarization using two different tools: diaphragm ultrasonography and acceleromyography of the adductor pollicis. Patients will be extubated when the train-of-four ratio is > 0.9. Diaphragm ultrasonography will be used to evaluate the thickening fraction, which is the difference between the end expiratory thickness and the end inspiratory thickness, normalized to the end expiratory thickness. Ultrasonography will be performed before the initiation of general anesthesia, before extubation, and 10 and 30 min after discharging patients from the operating room. The secondary objective will be to compare the incidence of postoperative complications due to residual neuromuscular block between patients who receive neostigmine and those who receive sugammadex. DISCUSSION: Postoperative residual curarization is a topic of paramount importance, because its occurrence can cause complications and increase the length of stay in hospital and the related costs. Diaphragm ultrasound assessment may become a bedside integrative tool in the neuromuscular monitoring field to detect concealed residual curarization in surgical patients who have received paralyzing agents. TRIAL REGISTRATION: EudraCT, 2013-004787-62. Registered on 18 June 2014, as "Evaluation of muscle function recovery after deep neuromuscular blockade by acceleromyography of the adductor pollicis or diaphragmatic echography: comparison between sugammadex and neostigmine." ClinicalTrials.gov, NCT02698969 . Registered on 15 February 2016, as "Recovery of Muscle Function After Deep Neuromuscular Block by Means of Diaphragm Ultrasonography and Adductor Pollicis Acceleromyography: Comparison of Neostigmine vs. Sugammadex as Reversal Drugs."

Monitoring intraoperative neuromuscular blockade and blood pressure with one device (TOF-Cuff): A comparative study with mechanomyography and invasive blood pressure. / Monitorización intraoperatoria del bloqueo neuromuscular y la presión arterial con un solo dispositivo (TOF-Cuff): estudio comparativo con la mecanomiografía y la presión arterial invasiva.

OBJECTIVE: The overall objective of the study is to determine the ability of TOF-Cuff device (blood-pressure modified cuff, including stimulation electrodes) to monitor with the same device the non-invasive blood pressure (NIBP) and the depth of a neuromuscular blockade (NMB) induced pharmacologically, by stimulation of the brachial plexus at the humeral level and recording evoked changes in arterial pressure. MATERIAL AND METHOD: Clinical, single-centre, open-controlled study with 32 adult patients ASA I-III for scheduled elective surgery under general anaesthesia in supine position, for the validation of neuromuscular monitoring, comparing the values obtained from neuromuscular relaxation TOF-Cuff with those obtained by mechanomyography (MMG) (control method) during the recovery phase of NMB, when a TOF ratio>0.7 and>0.9 (primary endpoint) were reached respectively. And an additional consecutive study of 17 patients for validation of NIBP monitoring with TOF-Cuff device vs invasive blood pressure measured by an intra-arterial catheter. All data were analyzed using the Bland-Altman method. RESULTS: Recovery from NMB measured with the TOF-Cuff was earlier compared to MMG. Comparing TOF-ratio>0.9 measured with TOF-Cuff vs TOF-ratio>0.7 with MMG, a specificity of 91% and a positive predictive value of 84% were obtained. In NIBP measurement, the mean error and standard deviation of both systolic blood pressure (1.6±7mmHg) and diastolic blood pressure (-3.4±6.3) were within the European accuracy requirements for medical devices. CONCLUSIONS: The TOF-Cuff device has been shown to be valid and safe in the monitoring of NMB and in the measurement of NIBP, with no patient presenting any adverse events, skin-level lesions or residual pain. It is not interchangeable with MMG, having a TOF-ratio>0.9 quantified by the TOF-Cuff device, a good correlation with a TOF-ratio>0.7 on MMG.

Idiopathic decreased bispectral index during anaesthesia emergence: Possible causes for the phenomenon of paradoxical arousal. / Disminución idiopática del índice biespectral durante la educción anestésica: posibles causas del fenómeno delta paradójico.

In a small percentage of patients, sound, touch and even nociceptive stimulation in the presence of a light anaesthetic depth does not cause an electroencephalogram wave pattern of cortical activation (α, ß waves) as would be expected, but leads to a slowed electroencephalogram pattern instead. We report the case of a patient who on emerging from anaesthesia showed very slowed brain activity on the electroencephalogram and reduced algorithmic value, that lasted approximately 5min coinciding with sound and tactile stimulation. After keeping her under observation for 24h during the postoperative period she did not present any brain disorder that could justify that event.

Residual neuromuscular blockade: management and impact on postoperative pulmonary outcome.

PURPOSE OF REVIEW: To revise the current literature on concepts for neuromuscular block management. Moreover, consequences of incomplete neuromuscular recovery on patients' postoperative pulmonary outcome are evaluated as well. RECENT FINDINGS: The incidence of residual paralysis may be as high as 70% and even small degrees of residual paralysis may have clinical consequences. Neostigmine should not be given before return of the fourth response of the train-of-four-stimulation and no more than 40-50 µg/kg should be given. Sugammadex acts more rapidly and more predictably than neostigmine. Finally, there is convincing evidence in the literature that incomplete neuromuscular recovery may lead to a poor postoperative pulmonary outcome. SUMMARY: New evidence has emerged about the pathophysiological implications of incomplete neuromuscular recovery. Not only are the pulmonary muscles functionally impaired, but respiratory control is also affected. Residual paralysis endangers the coordination of the pharyngeal muscles and the integrity of the upper airway. However, neuromuscular monitoring and whenever needed pharmacological reversal prevent residual paralysis.

[NON-CONVULSIVE EPILEPTIC SEIZURE IN PATIENT WITH DELAYED AWAKENING AFTER SUPRATENTORIAL TUMOR REMOVAL].

In some cases after elective neurosurgical procedures we use technique of delayed awakening of patients. Prolonged sedation however can hide the development of epileptic seizures and lead to the status epilepticus formation. This article is a demonstration and discussion of a clinical case of nonconvulsive status epilepticus during delayed awakening of the patient due to prolonged sedation after elective neurosurgical interventionsforsupratentorial brain tumor Presented case suggests the presence of significant risk of nonconvulsive status epilepticus during prolonged sedation. For early detection we advise to use continuous EEG monitoring during the entire period of sedation.

Residual neuromuscular blockade and postoperative critical respiratory events: literature review.

AIMS AND OBJECTIVES: To investigate and synthesise published literature on the associations between residual neuromuscular blockade and critical respiratory events of postoperative adult patients in the postanaesthesia care unit. BACKGROUND: Residual neuromuscular blockade continues to be common among patients transferred to the postanaesthesia care unit after general anaesthesia, while negative effects of residual neuromuscular blockade on respiratory function have been demonstrated in laboratory volunteers. DESIGN: Literature review. METHODS: Using key terms, a search was conducted in Cumulative Index for Nursing and Allied Health Literature, PubMed, Web of Science, Cochrane Database and EMBASE (January 1990-May 2013) for clinical trials or observational studies on the associations between residual neuromuscular blockade and critical respiratory events, published in English-language journals. RESULTS: Nine articles met the inclusion criteria. Residual neuromuscular blockade definition threshold differed between studies. Among critical respiratory events, only hypoxaemia was investigated in all included studies. Residual neuromuscular blockade was significantly associated with increased incidence of hypoxaemia during postanaesthesia care unit stay in most studies, while associations with the rest of the critical respiratory events were inconclusive. CONCLUSIONS: Although limited, existing research has provided evidence that patients with residual neuromuscular blockade are at high risk of early postoperative hypoxaemia. Further studies are needed to investigate independent associations between residual neuromuscular blockade and critical respiratory events, along with causality of these associations. The clinical importance of residual neuromuscular blockade for groups at high risk of critical respiratory events should also be investigated. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals have to be aware of the increased risk of hypoxaemia in patients with residual neuromuscular blockade. Efforts to decrease residual neuromuscular blockade incidence, combined with identification and appropriate evaluation of patients with residual neuromuscular blockade during postanaesthesia care unit stay, are recommended.