Depth of Anesthesia and Nociception Monitoring: Current State and Vision For 2050.

Anesthesia objectives have evolved into combining hypnosis, amnesia, analgesia, paralysis, and suppression of the sympathetic autonomic nervous system. Technological improvements have led to new monitoring strategies, aimed at translating a qualitative physiological state into quantitative metrics, but the optimal strategies for depth of anesthesia (DoA) and analgesia monitoring continue to stimulate debate. Historically, DoA monitoring used patient's movement as a surrogate of awareness. Pharmacokinetic models and metrics, including minimum alveolar concentration for inhaled anesthetics and target-controlled infusion models for intravenous anesthesia, provided further insights to clinicians, but electroencephalography and its derivatives (processed EEG; pEEG) offer the potential for personalization of anesthesia care. Current studies appear to affirm that pEEG monitoring decreases the quantity of anesthetics administered, diminishes postanesthesia care unit duration, and may reduce the occurrence of postoperative delirium (notwithstanding the difficulties of defining this condition). Major trials are underway to further elucidate the impact on postoperative cognitive dysfunction. In this manuscript, we discuss the Bispectral (BIS) index, Narcotrend monitor, Patient State Index, entropy-based monitoring, and Neurosense monitor, as well as middle latency evoked auditory potential, before exploring how these technologies could evolve in the upcoming years. In contrast to developments in pEEG monitors, nociception monitors remain by comparison underdeveloped and underutilized. Just as with anesthetic agents, excessive analgesia can lead to harmful side effects, whereas inadequate analgesia is associated with increased stress response, poorer hemodynamic conditions and coagulation, metabolic, and immune system dysregulation. Broadly, 3 distinct monitoring strategies have emerged: motor reflex, central nervous system, and autonomic nervous system monitoring. Generally, nociceptive monitors outperform basic clinical vital sign monitoring in reducing perioperative opioid use. This manuscript describes pupillometry, surgical pleth index, analgesia nociception index, and nociception level index, and suggest how future developments could impact their use. The final section of this review explores the profound implications of future monitoring technologies on anesthesiology practice and envisages 3 transformative scenarios: helping in creation of an optimal analgesic drug, the advent of bidirectional neuron-microelectronic interfaces, and the synergistic combination of hypnosis and virtual reality.

Prevalence and Risk Factors for Chronic Postsurgical Pain after Cardiac Surgery: A Single-center Prospective Cohort Study.

BACKGROUND: Chronic postsurgical pain is a common complication of surgery. The role of psychologic risk factors like depression and anxiety is substantially understudied in cardiac surgery. This study sought to identify perioperative factors associated with chronic pain at 3, 6, and 12 months after cardiac surgery. The authors hypothesize that baseline psychologic vulnerabilities have a negative influence on chronic postsurgical pain. METHODS: The authors prospectively collected demographic, psychologic, and perioperative factors in a cohort of 1,059 patients undergoing cardiac surgery at the Toronto General Hospital between 2012 and 2020. Patients were followed and completed chronic pain questionnaires at 3, 6, and 12 months after surgery. RESULTS: The study included 767 patients who completed at least one follow-up questionnaire. The incidence of postsurgical pain (more than 0 out of 10) at 3, 6, and 12 months after surgery was 191 of 663 (29%), 118 of 625 (19%), and 89 of 605 (15%), respectively. Notably, among patients reporting any pain, the incidence of pain compatible with a neuropathic phenotype increased from 56 of 166 (34%) at 3 months to 38 of 97 (39%) at 6 months and 43 of 67 (64%) at 12 months. Factors associated with postsurgical pain scores at 3 months include female sex, pre-existing chronic pain, previous cardiac surgery, preoperative depression, baseline pain catastrophizing scores, and moderate-to-severe acute pain (4 or more out of 10) within 5 postoperative days. CONCLUSIONS: Nearly one in three patients undergoing cardiac surgery reported pain at 3 months of follow-up, with approximately 15% reporting persistent pain at 1 yr. Female sex, pre-existing chronic pain, and baseline depression were associated with postsurgical pain scores across all three time periods.

Generalizability of nociception level as a measure of intraoperative nociceptive stimulation: A retrospective analysis.

BACKGROUND: Nociception-guided intraoperative opioid administration might help reduce postoperative pain. A commonly used and validated nociception monitor system is nociception level (NOL), which provides the nociception index, ranging from 0 to 100, with 0 representing no nociception and 100 representing extreme nociception. We tested the hypothesis that NOL responses are similar in men and women given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies. METHODS: We conducted a retrospective cohort analysis of trial data from eight prospective NOL validation studies. Among 522 noncardiac surgical patients enrolled in these studies, 447 were included in our analysis. We assessed NOL responses to various noxious and non-noxious stimuli. RESULTS: The average NOL in response to 315 noxious stimuli was 47 ± 15 (95% CI = 45-49). The average NOL in response to 361 non-noxious stimuli was 10 ± 12 (95% CI = 9-11). NOL responses were similar in men and women, in patients given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies. CONCLUSION: Nociception level appears to provide accurate estimates of intraoperative nociception over a broad range of patients and anesthetic conditions.

Prediction of acute postoperative pain based on intraoperative nociception level (NOL) index values: the impact of machine learning-based analysis.

The relationship between intraoperative nociception and acute postoperative pain is still not well established. The nociception level (NOL) Index (Medasense, Ramat Gan, Israel) uses a multiparametric approach to provide a 0-100 nociception score. The objective of the ancillary analysis of the NOLGYN study was to evaluate the ability of a machine-learning aglorithm to predict moderate to severe acute postoperative pain based on intraoperative NOL values. Our study uses the data from the NOLGYN study, a randomized controlled trial that evaluated the impact of NOL-guided intraoperative administration of fentanyl on overall fentanyl consumption compared to standard of care. Seventy patients (ASA class I-III, aged 18-75 years) scheduled for gynecological laparoscopic surgery were enrolled. Variables included baseline demographics, NOL reaction to incision or intubation, median NOL during surgery, NOL time-weighted average (TWA) above or under manufacturers' recommended thresholds (10-25), and percentage of surgical time spent with NOL > 25 or < 10. We evaluated different machine learning algorithms to predict postoperative pain. Performance was assessed using cross-validated area under the ROC curve (CV-AUC). Of the 66 patients analyzed, 42 (63.6%) experienced moderate to severe pain. NOL post-intubation (42.8 (31.8-50.6) vs. 34.8 (25.6-41.3), p = 0.05), median NOL during surgery (13 (11-15) vs. 11 (8-13), p = 0.027), percentage of surgical time spent with NOL > 25 (23% (18-18) vs. 20% (15-24), p = 0.036), NOL TWA < 10 (2.54 (2.1-3.0) vs. 2.86 (2.48-3.62), p = 0.044) and percentage of surgical time spent with NOL < 10 (41% (36-47) vs. 47% (40-55), p = 0.022) were associated with moderate to severe PACU pain. Corresponding ROC AUC for the prediction of moderate to severe PACU pain were 0.65 [0.51-0.79], 0.66 [0.52-0.81], 0.66 [0.52-0.79], 0.65 [0.51-0.79] and 0.67 [0.53-0.81]. Penalized logistic regression achieved the best performance with a 0.753 (0.718-0.788) CV-AUC. Our results, even if limited by the small number of patients, suggest that acute postoperative pain is better predicted by a multivariate machine-learning algorithm rather than individual intraoperative nociception variables. Further larger multicentric trials are highly recommended to better understand the relationship between intraoperative nociception and acute postoperative pain.Trial registration Registered on ClinicalTrials.gov in October 2018 (NCT03776838).

University of Montreal's Clinician-Investigator Program: A 10-Year Descriptive Evaluation.

PURPOSE: Clinician-investigators have an important role in the development and implantation of new therapies and treatment modalities; however, there have been several reports highlighting a pending shortage in the clinician-investigators' workforce. In Canada, the Royal College has promoted the development of clinician-investigators programs (CIP) to facilitate the training of these individuals. There is currently a paucity of data regarding the outcomes of such programs. This study aims to identify the strengths and areas of improvement of the Montreal University CIP.  Methods: An internet-based 51-question survey was distributed to all the alumni from the University of Montreal CIP. Participation was voluntary and no incentives were provided. The response rate was 64%.  Results: Among respondents, 50% (n=16) had completed their clinical residency and all CIP requirements. The majority of these individuals (63%) had become independent investigators and had secured provincial and national funding. Satisfaction of the respondents was high regarding the overall program (85%), the research skills developed during the CIP (84%) and the financial support obtained during the program (72%). The satisfaction rate regarding career planning was lower (63%).  Conclusion: This survey demonstrates that, while indicators are favorable, some areas still require improvement. Several steps to improve the CIP have been identified; notably, the transition from the CIP to early independent career has been identified as critical in the development of clinician-investigators and steps have been taken to improve this progression.

Comparison of carbetocin as a bolus or an infusion with prophylactic phenylephrine on maternal heart rate during Cesarean delivery under spinal anesthesia: a double-blinded randomized controlled trial.

PURPOSE: Carbetocin, an oxytocin analog, given as a postpartum hemorrhage prophylaxis in elective Cesarean deliveries, frequently causes tachycardia and hypotension. Phenylephrine infusion has been shown to prevent spinal anesthesia-induced hypotension. The goal of this study was to evaluate if a slow infusion of carbetocin would reduce maternal heart rate variation and hemodynamic disturbances compared with a rapid bolus in parturients receiving a prophylactic phenylephrine infusion during elective Cesarean delivery. METHODS: In this double-blinded randomized controlled trial, 70 healthy parturients were allocated to either a bolus group or an infusion group. At cord clamping, participants in the bolus group received carbetocin 100 µg as a rapid intravenous bolus, while participants in the infusion group received carbetocin 100 µg over 10 min. The primary outcome was the variation in maternal heart rate from baseline during the 20 min following cord clamping. Secondary outcomes included blood pressure, cardiac output, and stroke volume variations during the study period, measured with the ClearSight™ hemodynamic monitor. RESULTS: Maximum heart rate variation was not different between the groups: bolus group, mean (standard deviation) 29.8 (25.2)% vs infusion group, 27.2 (23.3)%; P = 0.67. The increase in heart rate occurred significantly earlier in the bolus group than in the infusion group (median [interquartile range] time, 105 [69-570] sec vs 485 [255-762] sec; P = 0.02; group × time interaction: two-way repeated measures ANOVA, P = 0.04). There was no significant difference in maximum variations for the other hemodynamic parameters between the groups. CONCLUSION: Carbetocin infused over ten minutes did not reduce the magnitude of maternal heart rate variation but delayed its occurrence. This finding could be relevant to the anesthesiologist caring for parturients in whom a slight increase in maternal heart rate is clinically undesirable. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03404544); registered 19 January 2018.

RéSUMé: OBJECTIF: Lorsque la carbétocine, un analogue de l'ocytocine, est administrée à titre de prophylaxie pour les hémorragies du post-partum dans les accouchements par césarienne programmée, cet agent provoque fréquemment une tachycardie et une hypotension. Il a été démontré qu'une perfusion de phényléphrine prévenait l'hypotension induite par la rachianesthésie. L'objectif de cette étude était d'évaluer si une perfusion lente de carbétocine réduirait la variation de fréquence cardiaque maternelle et les perturbations hémodynamiques par rapport à un bolus rapide chez les parturientes recevant une perfusion prophylactique de phényléphrine pendant un accouchement par césarienne programmée. MéTHODE: Dans cette étude randomisée contrôlée à double insu, 70 parturientes en bonne santé ont été allouées à un groupe bolus ou à un groupe perfusion. Lors du clampage du cordon, les participantes du groupe bolus ont reçu 100 µg de carbétocine sous forme de bolus intraveineux rapide, tandis que les participantes du groupe perfusion ont reçu 100 µg de carbétocine sur dix minutes. Le critère d'évaluation principal était la variation de la fréquence cardiaque maternelle par rapport aux valeurs de base au cours des 20 minutes suivant le clampage du cordon. Les critères secondaires comprenaient la tension artérielle, le débit cardiaque et les variations du volume d'éjection au cours de la période d'étude, tels que mesurés avec le moniteur hémodynamique ClearSight™. RéSULTATS: La variation maximale de fréquence cardiaque n'était pas différente entre les groupes : groupe bolus, moyenne (écart type) 29,8 (25,2) % vs groupe perfusion, 27,2 (23,3) %; P = 0,67. L'augmentation de la fréquence cardiaque s'est produite significativement plus tôt dans le groupe bolus que dans le groupe perfusion (temps médian [écart interquartile], 105 [69-570] sec vs 485 [255-762] sec; P = 0,02;× interaction groupe x temps : ANOVA bidirectionnelle à mesures répétées, P = 0,04). Il n'y avait pas de différence significative dans les variations maximales pour les autres paramètres hémodynamiques entre les groupes. CONCLUSION: La carbétocine perfusée pendant dix minutes n'a pas réduit l'ampleur de la variation de la fréquence cardiaque maternelle, mais a retardé son apparition. Cette découverte pourrait être pertinente pour l'anesthésiologiste qui prend soin de parturientes chez qui une légère augmentation de la fréquence cardiaque maternelle serait cliniquement indésirable. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03404544); enregistrée le 19 janvier 2018.

Intrapandemic regional anesthesia as practice: a historical cohort study in patients undergoing breast cancer surgery.

BACKGROUND: The COVID-19 pandemic has markedly increased delays in oncologic surgeries because of the virus's impact on traditional anesthetic management. Novel protocols, developed to protect patients and medical professionals, have altered the ways and instances in which general anesthesia (GA) can be safely performed. To reduce virus exposure related to aerosol-generating procedures, it is now recommended to avoid GA when feasible and promote regional anesthesia instead. At our institution, we observed faster postoperative recovery in patients who received paravertebral blocks for breast cancer surgery instead of GA. This led us to formally evaluate whether regional anesthesia instead of GA helped improve time to hospital discharge. METHODS: We conducted a historical cohort study to retrospectively analyze two cohorts of patients: prepandemic vs intrapandemic. We obtained approval from our institutional ethics committee to review files of consecutive patients who underwent breast cancer surgery between 30 March 2020 and 30 June 2020 (intrapandemic group; N = 106) and consecutive patients-moving backwards-from 28 February 2020 to 6 December 2019 (prepandemic group; N = 104). The primary outcome was the length of time between the end of surgery to readiness for hospital discharge. Secondary outcomes included the incidence of postoperative nausea and vomiting (PONV), the need for postoperative analgesia, and the duration of stay in the postanesthesia care unit (PACU). RESULTS: The median [interquartile range (IQR)] time to readiness for hospital discharge was significantly lower in patients who received paravertebral blocks for breast cancer surgery compared with GA (intrapandemic group, 119 [99-170] min vs prepandemic group, 191 [164-234] min; P < 0.001) as was the incidence of PONV (3% vs 11%; P = 0.03) and median [IQR] PACU durations of stay (29 [21-39] min vs 46 [37-63] min; P < 0.001). CONCLUSIONS: Patients who received paravertebral blocks for breast cancer surgery in the intrapandemic group were ready for hospital discharge earlier, spent less time in the PACU, and experienced less PONV than those who received GA in the prepandemic group. With growing surgical wait times, concerns related to aerosol-generating procedures, and recommendations to avoid GA when feasible, paravertebral blocks as the principal anesthetic modality for breast cancer surgery offered benefits for patients and medical teams.

RéSUMé: CONTEXTE: La pandémie de COVID-19 a considérablement augmenté les retards dans les chirurgies oncologiques en raison de l'impact du virus sur la prise en charge anesthésique traditionnelle. De nouveaux protocoles, mis au point pour protéger les patients et les professionnels de la santé, ont modifié les façons et les cas dans lesquels une anesthésie générale (AG) peut être réalisée en toute sécurité. Afin de réduire l'exposition au virus liée aux interventions génératrices d'aérosols, il est maintenant recommandé d'éviter l'AG lorsque possible et de privilégier l'anesthésie régionale. Dans notre établissement, nous avons observé une récupération postopératoire plus rapide chez les patientes ayant reçu des blocs paravertébraux pour une chirurgie de cancer du sein au lieu d'une AG. Cela nous a menés à évaluer de façon formelle si l'anesthésie régionale au lieu de l'AG avait contribué à réduire les délais jusqu'au congé de l'hôpital. MéTHODE: Nous avons réalisé une étude de cohorte historique afin d'analyser rétrospectivement deux cohortes de patientes : prépandémie vs intrapandémie. Nous avons obtenu l'approbation de notre comité d'éthique institutionnel pour examiner les dossiers de patientes consécutives ayant bénéficié d'une chirurgie de cancer du sein entre le 30 mars 2020 et le 30 juin 2020 (groupe intrapandémie; n = 106) et des patientes consécutives ­ en reculant ­ du 28 février 2020 au 6 décembre 2019 (groupe prépandémie; n = 104). Le critère d'évaluation principal était le délai entre la fin de la chirurgie et le moment où les patientes étaient prêtes à recevoir leur congé de l'hôpital. Les critères d'évaluation secondaires comprenaient l'incidence de nausées et vomissements postopératoires (NVPO), la nécessité d'une analgésie postopératoire et la durée de séjour en salle de réveil (SDR). RéSULTATS: Le délai médian [écart interquartile (ÉIQ)] jusqu'à la disposition au congé de l'hôpital était significativement plus court chez les patientes ayant reçu des blocs paravertébraux pour une chirurgie de cancer du sein plutôt qu'une AG (groupe intrapandémie, 119 [99-170] min vs groupe prépandémie, 191 [164­234] min; P < 0,001), tout comme l'incidence de NVPO (3 % vs 11 %; P = 0,03) et les durées médianes [ÉIQ] de séjour en salle de réveil (29 [21­39] min vs 46 [37­63] min; P < 0,001). CONCLUSION: Les patientes qui ont reçu des blocs paravertébraux pour une chirurgie de cancer du sein dans le groupe intrapandémie étaient prêtes à quitter l'hôpital plus tôt, ont passé moins de temps en salle de réveil et ont ressenti moins de NVPO que celles qui ont reçu une AG dans le groupe prépandémie. Avec des temps d'attente pour accès à la chirurgie de plus en plus longs, des préoccupations liées aux interventions génératrices d'aérosols et les recommandations d'éviter l'AG lorsque possible, les blocs paravertébraux ont offert des avantages aux patientes et aux équipes médicales en tant que principale modalité anesthésique pour la chirurgie de cancer du sein.

Impact of Processed Electroencephalography in Cardiac Surgery: A Retrospective Analysis.

OBJECTIVE: The use of brain function monitoring with processed electroencephalography (pEEG) during cardiac surgery is gaining interest for the optimization of hypnotic agent delivery during the maintenance of anesthesia. The authors sought to determine whether the routine use of pEEG-guided anesthesia is associated with a reduction of hemodynamic instability during cardiopulmonary bypass (CPB) separation and subsequently reduces vasoactive and inotropic requirements in the intensive care unit. DESIGN: This is a retrospective cohort study based on an existing database. SETTING: A single cardiac surgical center. PARTICIPANTS: Three hundred patients undergoing cardiac surgery, under CPB, between December 2013 and March 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred and fifty patients had pEEG-guided anesthesia, and 150 patients did not have a pEEG-guided anesthesia. Multiple logistic regression demonstrated that pEEG-guided anesthesia was not associated with a successful CPB separation (p = 0.12). However, the use of pEEG-guided anesthesia reduced by 57% the odds of being in a higher category for vasoactive inotropic score compared to patients without pEEG (odds ratio = 0.43; 95% confidence interval: 0.26-0.73; p = 0.002). Duration of mechanical ventilation, fluid balance, and blood losses were also reduced in the pEEG anesthesia-guided group (p < 0.003), but there were no differences in organ dysfunction duration and mortality. CONCLUSION: During cardiac surgery, pEEG-guided anesthesia allowed a reduction in the use of inotropic or vasoactive agents at arrival in the intensive care unit. However, it did not facilitate weaning from CPB compared to a group where pEEG was unavailable. A pEEG-guided anesthetic management could promote early vasopressor weaning after cardiac surgery.

Nociception level index variations in patients with complex regional pain syndrome: a pilot study.

The nociception level index (NOL) is a multi-parameter index that incorporates changes in autonomic parameters to evaluate nociception, with more painful stimuli causing more pronounced index variations. How this nociception monitor relates to the pain experience is uncertain, and patients with chronic pain may respond differently to acute pain due to alterations in pain processing. The goal of this pilot study was to evaluate NOL index variations after a painful physiotherapy exercise in patients with upper limb complex regional pain syndrome. Baseline NOL indexes were recorded using a finger probe (PMD-200™ Monitor, Medasense, Israel) and patient reported baseline pain scores using an 11-point numeric rating scale (NRS). Patients then performed a painful physiotherapy exercise and NOL index and pain scores were again recorded. The same procedure and recordings were repeated after a stellate ganglion block. Data were analyzed using a paired Student T test and a P value < 0.05 was considered statistically significant. Twenty patients (12/20 female, 10/20 right-sided) were included in this study. Patients reported moderate baseline pain (4.0 ± 2.7) despite having a low baseline NOL index (7.66 ± 5.76 out of 100). NRS and NOL index scores increased significantly during exercise, both before and after the block. The NOL index increased significantly when patients reported increased pain, indicating that it could eventually be useful in the objective assessment of acute pain in the chronic pain patients. However, NOL index was not able to reflect pain levels at rest, before the painful stimulation, in this chronic pain population. Further studies are needed to better assess NOL index utility at rest and to confirm these findings in this specific chronic pain population.

VACuum INtubation (VACcIN) box restricts the exhaled air dispersion generated by simulated cough: description and simulation-based tests of an innovative aerosolization protective prototype.

The COVID-19 pandemic has caused personal protective equipment shortages worldwide and required healthcare workers to develop novel ways of protecting themselves. Anesthesiologists in particular are exposed to increased risks of contamination when performing interventions such as airway manipulations. We developed and tested an aerosolization protective device which contains aerosols around the patient's airway and helps eliminate particles using negative pressure. This intubation box is a polymethyl methacrylate prism with openings for gloves, integrated suction and ventilation connectors. We conducted a randomised controlled series of tests to detect 0.5 µm particles after a simulated cough inside the intubation box, using a high-fidelity simulation mannequin. Setting and main outcome: We measured particle concentrations inside the box with and without suction turned on, in both negative and positive pressure operating rooms. We also obtained particle concentrations outside our box and compared them to non-airtight barrier devices. One minute following simulated cough, the mean number of particles per cubic foot in our box with suction on is around 45% that with the suction off (1,462,373 vs 3,272,080, P < 0.0001) in the negative pressure room, and four times lower than with the suction off (760,380 vs 3,088,700, P < 0.0001) in the positive pressure room. After a simulated cough inside the box, particles can be detected in front of the anesthesiologist's face with a non-airtight device, while none are detected when our box is sealed and its suction turned on. The use of our negative pressure intubation box prevents contamination of surroundings and increases particle elimination, regardless of room pressure.

Description of the validity of the Analgesia Nociception Index (ANI) and Nociception Level Index (NOL) for nociception assessment in anesthetized patients undergoing surgery: a systematized review.

Maintaining optimum analgesia in anesthetized patients is challenging due to the inability to self-report pain or exhibit pain-related behaviours. The Analgesia Nociception Index (ANI) (based on heart rate variability [HRV]) and the Nociception Level Index (NOL) (based on HRV, photoplethysmography, skin conductance, and temperature) both include HRV and provide continuous index monitoring for nociception assessment. The research question was: "What are the validation strategies of the NOL and ANI for nociception assessment in anesthetized patients?". The objectives were to describe and analyze the validation strategies and results. A systematized review was conducted using a comprehensive search with keywords under three concepts (nociception/pain, ANI/NOL, and validity) in four databases. A quality assessment using an adapted GRADE approach for measurement tools, and a risk of bias assessment using QUADAS-2 tool were performed by two reviewers. Out of 525 results, 15 validation studies were included. Strategies included hypothesis testing, discriminative, and criterion validation. Significant changes in ANI/NOL values were found in response to nociceptive stimuli at different opioid concentrations (hypothesis testing). Higher ANI/NOL values were observed during nociceptive stimuli (discriminative). AUCs ranging from 0.83 to 0.99 were obtained to detect nociceptive stimuli (criterion). Both technologies performed superiorly in detecting nociceptive stimuli compared to individual monitoring of HR and blood pressure. Although the aforementioned validation strategies are deemed appropriate, in the absence of a gold standard, criterion validation findings should be interpreted with caution. Moreover, reliability could be examined using test-retest with consistent ANI/NOL values during a stable time-interval.

Current trends in anesthetic depth and antinociception monitoring: an international survey.

Current trends in anesthetic depth (i.e., hypnosis) and antinociception monitoring are unclear. We thus aimed to determine contemporary perspectives on monitoring these components of anesthesia during general anesthesia. Participants received and responded anonymously to an internet-based international survey supported by the European Society of Anaesthesiology and Intensive Care. Comparisons, when applicable, were carried out using Chi2 analysis or Fischer's exact test. A total of 564 respondents, predominantly from Europe (80.1%), participated. There was a strong participation from Belgium (11.5%). A majority (70.9%) of anesthetists considered hypnotic monitoring important on most occasions to always. In contrast, a majority (62.6%) never or only occasionally considered antinociception monitoring important. This difference in the perceived importance of anesthetic depth versus antinociception monitoring was significant (p < 0.0001). A majority of respondents (70.1%) believed that guiding hypnosis and antinociception using these monitors would improve patient care on most occasions to always. Nonetheless, a substantial number of participants were unsure if hypnotic (23%) or antinociception (32%) monitoring were recommended and there was a lack of knowledge (58%) of any published algorithms to titrate hypnotic and/or antinociceptive drugs based on the information provided by the monitors. In conclusion, current trends in European academic centers prioritize anesthesia depth over antinociception monitoring. Despite an agreement among respondents that applying strategies that optimize anesthetic depth and antinociception could improve outcome, there remains a lack of knowledge of appropriate algorithms. Future studies and recommendations should focus on clarifying goal-directed anesthetic strategies and determine their impact on perioperative patient outcome.

Impact of chronic treatment by ß1-adrenergic antagonists on Nociceptive-Level (NOL) index variation after a standardized noxious stimulus under general anesthesia: a cohort study.

During the perioperative period, nociception control is certainly one of the anesthesiologist's main objectives when assuming care of a patient. There exists some literature demonstrating that the nociceptive stimuli experienced during surgery are responsible for peripheral and central sensitization phenomena, which can in turn lead to persistent postsurgical pain. An individualized approach to the evaluation and treatment of perioperative nociception is beneficial in order to avoid the sensitization phenomena that leads to prolonged postoperative pain and to minimize the consumption of opiates and their adverse effects. In terms of sensitivity, specificity, and positive/negative predictive values when compared to heart rate (HR) and mean arterial pressure (MAP), recent literature has shown that the NOL variation (ΔNOL) is the best index to distinguish noxious from non-noxious stimuli. Chronic treatment with ß1-adrenergic antagonists may constitute a limitation to the use of the NOL index. ß1-adrenergic antagonists induce a depressive action on the heart rate, which results in a limitation of its variability after a noxious stimulus. Since heart rate and heart rate variability are two parameters integrated into the NOL index, the validity of the NOL index in a population of patients receiving ß1-adrenergic antagonists has not yet been determined. Our study sought to explore the NOL index, the BIS, and the heart rate variation in a group of patients under chronic treatment with ß1-adrenergic antagonists submitted to standardized noxious stimulus under general anesthesia. We then compared those results to a control group of patients from our previous study (CJA group) that received no ß1-adrenergic antagonist chronic treatment. The patients in this study were subjected to a standardized anesthetic protocol from induction up to 3 min after a standardized tetanic stimulus to the ulnar nerve at a frequency of 100 Hz and an amperage of 70 mA, for a duration of 30 s. Data were electronically recorded to obtain NOL, BIS, and heart rate values every 5 s for the duration of the protocol. The NOL maximal mean value reached after noxious stimulation was not different between our two cohorts (CJA: 30(14) versus BETANOL: 36(14) (p = 0.12)). There was no statistically significant difference between our cohorts in regards of the NOL AUC representing the variation of the NOL over a 180 s period (CJA: 595(356) versus BETANOL: 634(301) (p = 0.30)). However, a repeated measurement ANCOVA identified slight statistically significant differences between our cohorts in the peak of variation of the NOL index between 20 and 65 s after noxious stimulation, the NOL index of the cohort of beta-blocked patients being higher than the CJA patients. Moreover, the time to reach the maximum value was not different (CJA: 73(37) versus BETANOL: 63(41) (p = 0.35)). NOL sensitivity and specificity to detect a noxious stimulus under general anesthesia were similar in patients taking beta-blockers or not, and were better than those of heart rate and Bispectral index (AUC NOL 0.97, CI(0.92-1), versus AUC BIS 0.78, CI(0.64-0.89) and AUC HR 0.66, CI(0.5-0.8)). In conclusion, the NOL index is a reliable monitor to assess nociception in a population of patients under chronic beta-blocker therapy. Patients under such therapy achieve similar maximal NOL values over a 180 s period after a standardized noxious stimulus and the NOL variation over time, represented by the AUC is not significantly different from a cohort of non-beta-blocked patients. Whether the patient takes beta-blockers or not, sensitivity of the NOL index is greater than that seen for BIS index or heart rate to detect an experimental noxious stimulus under general anesthesia.

Ultrasound evaluation of inferior vena cava compression in tilted and supine term parturients.

PURPOSE: Hypotension is common following spinal anesthesia (SA) during elective Cesarean delivery (CD). Although common practice is to alleviate inferior vena cava (IVC) compression, limited evidence supports a 15° tilt for CD. We measured collapsibility of the IVC in supine and 15° left lateral tilt positions with ultrasound before and after SA and phenylephrine infusion in term parturients. METHODS: Twenty term parturients scheduled for CD were recruited for this prospective study. Ultrasound measurements of the IVC were taken 1) supine before SA, 2) tilted 15° before SA, 3) supine after SA, and 4) tilted 15° after SA. A phenylephrine infusion was begun after injection of SA. The primary outcome was to evaluate the impact of position on the IVC collapsibility index (IVCCI): a measure of the difference between the maximum and minimum IVC diameter with respiration. RESULTS: The mean (standard deviation) IVCCI (%) before SA was higher in the supine 19.5 (8.0) than in the tilted 15.0 (6.4) position (mean difference, 4.5; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). After SA, there was no significant difference between IVCCI (%) in the supine 17.8 (8.3) and tilted 14.2 (6.9) position (mean difference, 3.5; 95% CI, -0.9 to 7.9; P = 0.13). There was no correlation between the pre-spinal IVVCI measurements and the quantity of phenylephrine used during the surgery. CONCLUSION: The IVCCI was lower in the 15° tilt position than in the supine position, but not after SA with a phenylephrine infusion. Ultrasound imaging can help identify IVC compression. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03410199); registered 18 January 2018.

RéSUMé: OBJECTIF: L'hypotension est fréquente après une rachianesthésie pendant un accouchement par césarienne programmée (CP). Bien que la pratique courante consiste à atténuer la compression de la veine cave inférieure (VCI), des données probantes limitées encouragent une latéralisation de 15 ° durant la CP. Avec l'échographie, nous avons mesuré la collapsibilité de la VCI en décubitus dorsal et en position d'inclinaison latérale gauche de 15° avant et après la rachianesthésie et la perfusion de phényléphrine chez des parturientes à terme. MéTHODE: Vingt parturientes à terme devant subir une CP ont été recrutées dans le cadre de cette étude prospective. Les mesures échographiques de la VCI ont été prises 1) en décubitus dorsal avant la rachianesthésie, 2) avec une latéralisation de 15° avant la rachianesthésie, 3) en décubitus dorsal après la rachianesthésie, et 4) avec une latéralisation de 15° après la rachianesthésie. Une perfusion de phényléphrine a été amorcée après l'injection de la rachianesthésie. Le critère d'évaluation principal était l'impact de la position sur l'indice de collapsibilité de la VCI (ICVCI), soit une mesure de la différence entre les diamètres maximal et minimal de la VCI avec respiration. RéSULTATS: Le ICVCI moyen (écart type) (%) avant la rachianesthésie était plus élevé en décubitus dorsal, à 19,5 (8,0), qu'en position latéralisée, à 15,0 (6,4) (différence moyenne, 4,5; intervalle de confiance [IC] 95 %, 0,1 à 8,9; P = 0,04). Après la rachianesthésie, aucune différence significative n'a été observée entre l'ICVCI (%) en décubitus dorsal, à 17,8 (8,3), et en position latéralisée, à 14,2 (6,9) (différence moyenne, 3,5; IC 95 %, -0,9 à 7,9; P = 0,13). Il n'y avait aucune corrélation entre les mesures de l'ICVCI pré-rachianesthésie et la quantité de phényléphrine utilisée pendant la chirurgie. CONCLUSION: L'ICVCI était plus bas en position latéralisée à 15 ° qu'en décubitus dorsal, mais pas après une rachianesthésie avec une perfusion de phényléphrine. L'échographie peut aider à identifier la compression de la VCI. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03410199); enregistrée le 18 janvier 2018.

Face transplantation: anesthesia and other organizational considerations.

In 2005, the first facial vascularized composite allotransplant was performed in France. In May 2018, our team at Maisonneuve-Rosemont Hospital, Montreal, Quebec, had the privilege to participate in the first facial transplant in Canada. Interdisciplinary collaboration, coordination, and communication formed the cornerstone of this medical undertaking and, ultimately, its success. This report details the anesthetic and organizational considerations of our experience.

RéSUMé: En 2005, la première allogreffe de tissu composite vascularisée faciale était réalisée en France. En mai 2018, notre équipe à l'Hôpital Maisonneuve-Rosemont, à Montréal, au Québec, a eu le privilège de participer à la première greffe faciale au Canada. La collaboration, la coordination et la communication interdisciplinaires ont constitué les pierres angulaires de ce projet médical et, ultimement, de son succès. Ce compte-rendu détaille les considérations anesthésiques et organisationnelles de notre expérience.

A randomized controlled trial comparing nociception level (NOL) index, blood pressure, and heart rate responses to direct laryngoscopy versus videolaryngoscopy for intubation: the NOLint project.

PURPOSE: The effect of direct laryngoscopy using a Macintosh blade (MAC) vs GlideScope™ videolaryngoscopy using a Spectrum LoPro blade (GVL) on nociceptive stimulation has not been quantitatively studied. This study used the new nociception level (NOL) index to compare the nociceptive response induced by GVL or MAC during laryngoscopy with or without intubation. METHODS: Patients underwent two laryngoscopies at four-minute intervals (L1, L2), one with GVL and the other with MAC (first randomization). A third laryngoscopy (L3) followed by tracheal intubation was performed four minutes after L2 (GVL or MAC, second randomization). Nociception was quantitatively assessed by NOL and standard hemodynamic parameters (heart rate [HR] and mean arterial pressure). For the crossover design, blade comparisons accounted for sequence and blade type. A possible carryover effect between laryngoscopies was assessed. RESULTS: In the 50 patients randomized, there was no carryover effect from one laryngoscopy to the next for all analyzed parameters. Nociception level index peak values were higher with MAC than GVL. Analysis of ΔNOL showed a lower nociceptive response with GVL for L1+L2 combined. Mean peak NOL values were significantly higher after L3+intubation than after L1+L2, for both GVL and MAC groups. Analysis of ΔHR values did not show a significant difference between GVL and MAC for any laryngoscopy. CONCLUSION: Laryngoscopy alone with GVL induces less nociception than with MAC. The NOL was more sensitive than HR at detecting nociceptive responses to MAC vs GVL. Additionally, and irrespective of which technique/blade was used, the combination of laryngoscopy + tracheal intubation produced a much greater nociceptive response than the laryngoscopy alone. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03277872); registered 29 August 2017.

RéSUMé: OBJECTIF: L'effet de la laryngoscopie directe avec une lame Macintosh (MAC) par rapport à la vidéolaryngoscopie à l'aide d'un GlideScope™ avec lame Spectrum LoPro (GVL) sur la stimulation nociceptive n'a pas été quantitativement étudié. Cette étude a utilisé le nouvel indice de niveau de nociception (NOL) pour comparer la réponse nociceptive induite par une laryngoscopie avec GVL ou MAC avec ou sans intubation. MéTHODE: Les patients ont subi deux laryngoscopies à des intervalles de quatre minutes (L1, L2), l'une par GVL et l'autre par MAC (première randomisation). Une troisième laryngoscopie (L3) suivie d'une intubation trachéale a été effectuée quatre minutes après L2 (GVL ou MAC, deuxième randomisation). La nociception a été quantitativement évaluée à l'aide de l'indice NOL, et les paramètres hémodynamiques standard (fréquence cardiaque [FC] et pression artérielle moyenne) ont été mesurés. Dans le volet croisé de l'étude, les comparaisons de lames ont tenu compte de la séquence et du type de lame. La possibilité d'un effet de persistance entre les laryngoscopies a été évaluée. RéSULTATS: Chez les 50 patients randomisés, il n'y a eu aucun effet de persistance d'une laryngoscopie à la suivante pour tous les paramètres analysés. Les valeurs maximales de l'indice de nociception étaient plus élevées avec les lames MAC qu'avec la vidéolaryngoscopie GVL. L'analyse de ΔNOL a montré une réponse nociceptive inférieure avec la vidéolaryngoscopie GVL pour L1+L2 combinés. Les valeurs maximales moyennes de NOL étaient significativement plus élevées après L3+intubation qu'après L1+L2, tant pour les groupes GVL que MAC. L'analyse des valeurs ΔFC n'a pas montré de différence significative entre les techniques GVL et MAC pour quelque laryngoscopie que ce soit. CONCLUSION: La laryngoscopie seule avec le GlideScope induit moins de nociception qu'avec une lame MAC. L'indice NOL était plus sensible que les FC pour détecter les réponses nociceptives à la laryngoscopie MAC vs GVL. En outre, et indépendamment de la technique/lame utilisée, la combinaison de laryngoscopie + intubation trachéale a produit une réponse nociceptive beaucoup plus importante que la laryngoscopie seule. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03277872); enregistrée le 29 août 2017.

Postoperative outcomes in surgical COVID-19 patients: a multicenter cohort study.

BACKGROUND: Data on postoperative outcomes of the COVID-19 patient population is limited. We described COVID-19 patients who underwent a surgery and the pandemic impact on surgical activities. METHODS: We conducted a multicenter cohort study between March 13 and June 192,020. We included all COVID-19 patients who underwent surgery in nine centres of the Province of Québec, the Canadian province most afflicted by the pandemic. We also included concomitant suspected COVID-19 (subsequently confirmed not to have COVID-19) patients and patients who had recovered from it. We collected data on baseline characteristics, postoperative complications and postoperative mortality. Our primary outcome was 30-day mortality. We also collected data on overall surgical activities during this first wave and during the same period in 2019. RESULTS: We included 44 COVID-19 patients, 18 suspected patients, and 18 patients who had recovered from COVID-19 at time of surgery. Among the 44 COVID-19 patients, 31 surgeries (71%) were urgent and 16 (36%) were major. In these patients, pulmonary complications were frequent (25%) and 30-day mortality was high (15.9%). This mortality was higher in patients with symptoms (23.1%) compared to those without symptoms (5.6%), although not statistically significant (p = 0.118). Of the total 22,616 cases performed among participating centres during the study period, only 0.19% had COVID-19 at the time of surgery. Fewer procedures were performed during the study period compared to the same period in 2019 (44,486 cases). CONCLUSION: In this Canadian cohort study, postoperative 30-day mortality in COVID-19 patients undergoing surgery was high (15.9%). Although few surgeries were performed on COVID-19 patients, the pandemic impact on surgical activity volume was important. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04458337 .

Assessing the antinociceptive effect of nitrous oxide to tetanic stimulation in anaesthetised patients with new intra-operative nociception monitors: An observational study.

BACKGROUND: Nitrous oxide (N2O) has been used since the 19th century for its analgesic, antinociceptive and anxiolytic effects during surgical procedures in awake and anaesthetised patients. However, quantification of noxious stimuli that occur under general anaesthesia is a constant challenge for anaesthesiologists, and recently two new indices have been developed to assess intra-operative nociception. OBJECTIVE: The aim of this study was to quantify with new indices as well as with more classical clinical parameters the antinociceptive effect of N2O during general anaesthesia. DESIGN: Prospective, open label, patient-blinded, observational and descriptive trial. SETTING: Single-centre academic hospital. PARTICIPANTS: Forty American Society of Anesthesiologists' physical status 1 to 3 patients undergoing general anaesthesia for elective abdominal surgery via laparotomy were recruited. MAIN OUTCOMES MEASURES: Intra-operative pain was assessed using a standardised electrical stimulation of the forearm (tetanic stimulation at 70 mA, 100 Hz for 30 s), at 0, 25 and 50% inhaled N2O/O2. Heart rate (HR), mean arterial blood pressure, bispectral index, the analgesia nociception index and the nociception level (NOL) index were used to evaluate intra-operative nociception before and after each standardised tetanic stimulation. RESULTS: There was a 16% reduction of the analgesia nociception index reaction, a 31% reduction of the NOL reaction and a 51% reduction of the HR reaction to a standardised electrical tetanic nociceptive stimulation during administration of 50% N2O. Administration of 50 or 25% inhaled N2O produced the same quality of antinociception based on HR and NOL index analyses. HR and the NOL index were the best parameters to identify the antinociceptive effect of intra-operatively administered N2O. CONCLUSION: In anaesthetised patients, our study demonstrated clinically significant antinociceptive properties of N2O. Our results showed that low concentrations of N2O (25%) are as effective as higher concentrations (50%) to achieve a significant antinociceptive effect. These findings may help decrease negative effects of using higher concentrations of N2O, including its side effects and its environmental pollution. TRIAL REGISTRATION: ClinicalTrials.gov registration identifier: NCT02701478.

The impact of bolus versus continuous infusion of intravenous ketamine on bispectral index variations and desflurane administration during major surgery: The KETABIS study.

BACKGROUND: Although ketamine, a NMDA-receptor antagonist, tends to increase the bispectral index (BIS), it remains a widely used analgesic whenever administered in low doses during major surgery. OBJECTIVE: The objective of this study was to compare the impact of intravenous ketamine (given either as a continuous infusion or as a bolus) on BIS and to compare desflurane administration and postoperative outcomes between the groups. DESIGN: Prospective, randomised, parallel-group, open-label study. SETTING: University hospital, operating room. PARTICIPANTS: Fifty patients, scheduled for major abdominal surgery. INTERVENTIONS AND MAIN OUTCOMES MEASURES: Patients were randomised into two groups: ketamine by intravenous continuous infusion - group (KI) and ketamine by i.v. bolus - group (KB). In the KI group, ketamine at a rate of 0.25 mg kg-1 h-1 was commenced at skin incision (T0) and maintained at this rate for the duration of surgery. In group KB, a ketamine bolus of 0.25 mg kg-1was administered at T0 and repeated every hour. The difference in BIS between the groups was compared from T0 onwards. The amount of desflurane administered to keep BIS within the usual recommended range (40-60) was compared, as were the doses of phenylephrine and remifentanil. Postoperative pain and recovery outcomes were also assessed. RESULTS: After T0, the BIS increased significantly from baseline in group KB compared with group KI: the rise in BIS was 20 ±â€Š8 vs. 11 ±â€Š6, respectively (P = 0.0001). The between-group mean difference (95% confidence interval (CI), was 9 (5 to 13). In group KB, desflurane administration significantly increased for the first 15 min after T0: 6.3 ±â€Š1.8 vs. 3.8 ±â€Š1.3 ml (P < 0.0001) with a mean intergroup group difference (95% CI) of 2.4 (1.5 to 3.4) ml. There was no difference in desflurane administration when considering the full hour from T0 to T60 min: 16 ±â€Š9 vs. 15 ±â€Š5 ml (P = 0.63) with a mean intergroup difference (95% CI) of 1 (-3 to 5) ml. After surgery, pain scores, opioid consumption, incidence of nausea and vomiting and recovery scores were similar between groups. CONCLUSION: Compared with a continuous ketamine infusion, a ketamine bolus significantly increased the BIS after T0. In order to keep the BIS below 60, significantly more desflurane was administered from T0 to T15 min in group KB. To prevent such higher desflurane administration and its related atmospheric pollution, our results suggest administering intra-operative intravenous ketamine as an infusion rather than a bolus. TRIAL REGISTRATION: Clinicaltrials.gov registration identifier: NCT03781635.

Exploration of the Nociception Level (NOL™) Index for Pain Assessment during Endotracheal Suctioning in Mechanically Ventilated Patients in the Intensive Care Unit: An Observational and Feasibility Study.

BACKGROUND: Many patients in the intensive care unit (ICU) suffer from pain and are non-communicative. Therefore, alternative pain measures are necessary. Although behavioral pain measures are available, physiological measures are lacking. The Nociception Level index (NOL™) provides a value from combination of multiple physiological parameters to measure pain and its use in the ICU is new. AIM: To explore the use of a multiple physiological parameter measure for pain assessment, the NOL™ index, in mechanically ventilated patients able to self-report pain in the ICU. METHODS: A prospective cohort study was performed. Data were collected before, during, and 15 minutes after a non-nociceptive procedure (noninvasive blood pressure using cuff inflation) and a nociceptive procedure (endotracheal suctioning). NOL index, 0 to 10 pain intensity, and Critical-Care Pain Observation Tool (CPOT) scores were also obtained. Data were analyzed using Friedman and Mann-Whitney tests. Feasibility of study procedures was described. RESULTS: Out of 28 patients who consented, 17 remained eligible and data were analyzed for 15. Technical issues prevented obtaining a NOL signal in 2 patients. NOL values were higher during endotracheal suctioning (median = 41.6) compared with before (median = 11.2) and after the procedure (median = 11.8) and compared with cuff inflation (median = 15.1; Friedman test, p < .001). NOL values were associated with pain intensity and CPOT scores (Mann-Whitney tests, p < .05). CONCLUSIONS: The study procedures with the NOL were found feasible; NOL values could discriminate between nociceptive and non-nociceptive procedures, and values were associated with reference pain measures. Further NOL testing is required in other ICU patient groups and procedures.