Effect of combined intraoperative use of the Nociception Level (NOL) and bispectral (BIS) indexes on desflurane administration.

BACKGROUND: Currently, nociception monitors are not part of standard anaesthesia care. We investigated whether combined intraoperative nociception (NOL index) and anaesthesia (BIS index) monitoring during general anaesthesia would reduce anaesthetics consumption and enhance intraoperative safety and postoperative recovery when compared to standard of care monitoring (SOC). METHODS: In this randomised study, we included 60 patients undergoing colonic surgery under desflurane/remifentanil anaesthesia and epidural analgesia. Patients received either standard monitoring or combined BIS + NOL index monitoring. In the monitored group, remifentanil infusion was titrated to achieve a NOL index below 20. Desflurane was adjusted to BIS values (45-55). In the SOC group, remifentanil and desflurane were titrated on vital signs and MAC. The primary outcome was intraoperative desflurane consumption. RESULTS: Fifty-five patients were analysed. Desflurane administration was reduced in the monitored group from 0.25 ± 0.05 to 0.20 ± 0.06 mL kg-1 h-1 (p < 0.001). The cumulative time with a BIS under 40 was significantly higher in the SOC group with a median time of 12.6 min (95% CI: 0.6-80.0) versus 2.0 min (95% CI: 0.3-5.83) (p = 0.023). Time for extubation was significantly shorter in the monitored group: 4.4 min (95% CI: 2.4-4.9) versus 6.28 min (95% IC: 5.0-8.2) (p = 0.003). We observed no differences in remifentanil or phenylephrine requirements during anaesthesia or in postoperative outcome measures, such as postoperative pain, opioid consumption, neurocognitive recovery. CONCLUSION: Combined intraoperative monitoring of anaesthesia and nociception during colonic surgery resulted in less desflurane consumption and quicker extubation time compared to standard clinical care monitoring.

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.

"Impact of Nociception Level (NOL) index intraoperative guidance of fentanyl administration on opioid consumption, postoperative pain scores and recovery in patients undergoing gynecological laparoscopic surgery. A randomized controlled trial".

STUDY OBJECTIVE: The Nociception Level (NOL) index uses a multiparametric approach to measure the balance between sympathetic and parasympathetic systems activity. Recently, a strong correlation between the NOL index response to nociceptive stimuli and the level of opioid analgesia during surgery was reported. Others observed that intraoperative doses of remifentanil and sufentanil were reduced when the NOL index was used. So far, no study has evaluated the impact of NOL-guided fentanyl antinociception in laparoscopic gynecological surgery. The primary hypothesis of this present study was to evaluate whether intraoperative NOL-guided fentanyl administration would reduce intra-operative opioid consumption. Secondary hypotheses were to assess whether this would lead to lower postoperative opioid consumption and pain scores, as well as improved postoperative outcomes. SETTING: University hospital, operating room. PATIENTS: 70 adult patients, ASA 1-3, scheduled for total laparoscopic hysterectomy. INTERVENTIONS: Patients were randomized into 2 groups: SOC (standardization of care) and NOL (using the NOL index to guide the administration of fentanyl). The depth of anesthesia was monitored with BIS™. Intraoperative fentanyl boluses were administered based on heart rate and mean arterial pressure variations in the SOC group, and NOL index for the NOL group. MEASUREMENTS: Fentanyl total intraoperative dose administered was collected and also averaged per hour. Pain scores and hydromorphone consumption were assessed in the post-anesthesia care unit and up to 24 h. MAIN RESULTS: Sixty-six patients completed the study, 33 in each group. Total intraoperative fentanyl administration was not different between the two groups (217 (70) in the NOL group vs 280 (210) in the SOC group (P = 0.11)). Nevertheless, intraoperative fentanyl administration per hour was reduced by 25% in the NOL-guided group compared to the SOC group: 81 (24) vs 108 (66) µg.h-1, respectively (P = 0.03). Hydromorphone consumption and pain scores in the post-anesthesia care unit and at 24 h were not significantly different between the two groups. CONCLUSION: NOL-guided analgesia allowed for a 22% reduction of the total amount of intraoperative fentanyl which was not significant. Nevertheless, results reported a significant reduction by 25% in the doses of fentanyl averaged per hour of surgery and administered in the NOL-guided group compared with the standardized practice in laparoscopic gynecological surgery. The pain measured postoperatively was similar in the two groups while the average postoperative consumption of opioids to achieve the same level of pain scores in post-anesthesia care unit and at 24 h was not significantly reduced. Further larger multicenter studies centered towards postoperative outcomes are needed.

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.

Effect of electroencephalography-guided anesthesia on neurocognitive disorders in elderly patients undergoing major non-cardiac surgery: A trial protocol The POEGEA trial (POncd Elderly GEneral Anesthesia).

INTRODUCTION: The number of elderly patients undergoing major surgery is rapidly increasing. They are particularly at risk of developing postoperative neurocognitive disorders (NCD). Earlier studies suggested that processed electroencephalographic (EEG) monitors may reduce the incidence of postoperative NCD. However, none of these studies controlled for intraoperative nociception levels or personalized blood pressure targets. Their results remain unclear if the reduction in the incidence of postoperative NCD relates to avoidance of any electroencephalographic pattern suggesting excessive anesthesia depth. OBJECTIVE: The objective of this trial is to investigate-in patients ≥ 70 years old undergoing major non-cardiac surgery-the effect of EEG-guided anesthesia on postoperative NCD while controlling for intraoperative nociception, personalized blood pressure targets, and using detailed information provided by the EEG monitor (including burst suppression ratio, density spectral array, and raw EEG waveform). MATERIAL AND METHODS: This prospective, randomized, controlled trial will be conducted in a single Canadian university hospital. Patients ≥ 70 years old undergoing elective major non-cardiac surgery will be included in the trial. The administration of sevoflurane will be adjusted to maintain a BIS index value between 40 and 60, to keep a Suppression Ratio (SR) at 0%, to keep a direct EEG display without any suppression time and a spectrogram with most of the EEG wave frequency within the alpha, theta, and delta frequencies in the EEG-guided group. In the control group, sevoflurane will be administered to achieve an age-adjusted minimum alveolar concentration of [0.8-1.2]. In both groups, a nociception monitor will guide intraoperative opioid administration, individual blood pressure targets will be used, and cerebral oximetry used to tailor intraoperative hemodynamic management. The primary endpoint will be the incidence of NCD at postoperative day 1, as evaluated by the Montreal Cognitive Assessment (MoCA). Secondary endpoints will include the incidence of postoperative NCD at different time points and the evaluation of cognitive trajectories up to 90 days after surgery among EEG-guided and control groups. STUDY REGISTRATION: NCT04825847 on ClinicalTrials.gov.

A narrative review on the potential benefits and limitations of deep neuromuscular blockade.

BACKGROUND: Neuromuscular blockade was shown to improve surgical conditions. However, the risk of residual neuromuscular blockade upon extubation prevents anaesthesiologists from maintaining complete paralysis. For this reason, deep NMB is still underused in anaesthesia. This review focused on answering six questions revolving around the use of deep NMB versus moderate NMB. METHODS: This was a non-exhaustive narrative review based on 6 selected relevant questions: does deep NMB 1) improve surgical conditions? 2) reduce surgical complications? 3) facilitate a reduction in intraoperative pneumoperitoneum pressure (PnP)? 4) does a reduction in intraoperative PnP impact clinical outcomes? 5) does the combination of deep NMB and lower PnP improve respiratory parameters? 6) improve OR efficiency or readmission rates? RESULTS: This review highlights some of the key studies that have demonstrated potential benefits of deep NMB, but it also included reports showing no benefit, highlighting that the evidence is not unequivocal. Deep NMB does in fact improve surgical conditions, but whether this improvement translates into improved clinical outcomes is far from concluded. Indeed, there is an increased risk or residual curarisation, especially if patients are not monitored and reversed appropriately. The most important benefit of deep NMB may be the prevention of unacceptable surgical working conditions. The other potential major benefits are the reduction in PnP and reduction in pain. Deep NMB must be used with appropriate monitoring. CONCLUSION: Deep NMB was associated with an improvement in surgical conditions, reduction in PnP, pain, and complications; but further research is needed to definitively prove this relationship.

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.

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.

Impact of intravenous phenylephrine bolus administration on the nociceptive level index (NOL).

Recently, the nociceptive level index (NOL) was shown to more specifically and sensitively detect noxious stimuli during anesthesia, in comparison to previous methods that relied on such parameters as heart rate (HR) and mean blood pressure (MAP). An ongoing study (NCT#03410485) evaluates the intraoperative combination of both NOL and bispectral (BIS) indices to improve quality of recovery after colorectal surgery. Our ethical committee (REB approval #CER15083) initially agreed on an interim analysis of the data from the first 30 patients. More specifically, this present report analyzed all the intravenous phenylephrine (PE) boluses administered during anesthesia as part of our study protocol to see whether they had a significant impact on NOL values as well as other parameters: HR, MAP, BIS index. For this trial, remifentanil and phenylephrine were given in both groups based on a specific algorithm. All study parameters were recorded electronically. Our analysis for the present specific outcome evaluated NOL index for 30 s before the intravenous PE bolus (1 µg kg-1) was given and until 5 min afterwards. The average NOL values after PE bolus, as well as MAP, HR and BIS indices, were recorded and analyzed. A total of 178 events of PE boluses were identified for 28 patients (two were excluded). Median baseline NOL was 3 (1.8-8.3) CI 95% 5.7-8.7; post-PE bolus: 5.3 (2.7-9.9) (95% CI 6.6-8.9; Wilcoxon matched-pairs signed rank test (WMPSRT), P = 0.0003). When analyzing delta NOL (difference between pre- and post-PE bolus in NOL values) for each patient, the median delta NOL was 2.9 (1.2-6.1) (95% CI 3.6-5.5) with 95% of the subjects keeping a delta NOL under 10. MAP and HR values showed expected significant variations after PE bolus: a slight increase and slight decrease, respectively. BIS index values did not change after PE bolus. Our present results demonstrate that intravenous phenylephrine boluses of 1 µg kg-1 had the expected impact on hemodynamic parameters: a significant but very slight increase in MAP and decrease in HR, which might lack clinical relevance. Our report also demonstrates that these same phenylephrine boluses induce a statistically significant increase of the NOL index which does not seem to have much of a clinical relevance for the novel NOL index used to monitor intraoperative nociception as well as for the more classical BIS index for depth of anesthesia. Nevertheless, doses of intravenous PE bolus used in the present study (1 µg kg-1) might be regarded as smaller than more conventional ones (100-200 µg per bolus). Further studies need to be done with the latter doses.

Efficacy and safety of remifentanil in a rapid sequence induction in elderly patients: A three-arm parallel, double blind, randomised controlled trial.

BACKGROUND: Rapid sequence induction (RSI) is recommended in patients at risk of aspiration, but induced haemodynamic adverse events, including tachycardia. In elderly patients, this trial aimed to assess the impact of the addition of remifentanil during RSI on the occurrence of: tachycardia (primary outcome), hypertension (due to intubation) nor hypotension (remifentanil). METHODS: In this three-arm parallel, double blind, multicentre controlled study, elderly patients (65 to 90 years old) hospitalised in three centres and requiring RSI were randomly allocated to three groups, where anaesthesia was induced with etomidate (0.3mg/kg) followed within 15seconds by either placebo, or low (0.5µg/kg), or high (1.0µg/kg) doses of remifentanil, followed by succinylcholine 1.0mg/kg. Heart rate (HR) and mean arterial pressure (MAP) were recorded before induction and after intubation. RESULTS: In total, eighty patients were randomised and analysed. Baseline HR and MAP were similar between groups. For primary endpoint, the absolute change in HR between induction and intubation was greater in the control group (15 bpm; 95% CI [8-21]) than that in the remifentanil 0.5µg/kg group (4 bpm; 95% CI [-1-+8]; P=0.005) and the remifentanil 1.0µg/kg group (-3 bpm; 95% CI [-9-+3]; P<0.0001). The increase in MAP was greater in the placebo group than in both remifentanil groups (P<0.0001). Twice as many hypertension episodes were recorded in the placebo group compared to the remifentanil 0.5µg/kg and 1.0µg/kg groups (60%, 30%, and 28% patients respectively; P=0.032), but no placebo patients experienced hypotension episodes versus 11% and 24% in the remifentanil 0.5µg/kg and 1.0µg/kg groups respectively (P=0.016). CONCLUSION: Remifentanil (0.5-1.0µg/kg) prevents the occurrence of tachycardia and hypertension in elderly patients requiring RSI.

Enhanced recovery short-stay hip and knee joint replacement program improves patients outcomes while reducing hospital costs.

INTRODUCTION: An attractive option to reduce hospital length of stay (LOS) after hip or knee joint replacement (THA, TKA) is to follow the Enhanced Recovery After Surgery principles (ERAS) to improve patient experience to a level where they will feel confident to leave for home earlier. The objective of this study was to evaluate the implementation of short-stay protocol following the ERAS principles. HYPOTHESIS: We hypothesized that our ERAS THA and TKA short-stay protocol would result in a lower complication rate, shorter hospital LOS and reduced direct health care costs compared to our standard procedure. MATERIAL AND METHODS: We compared the complications rated according to Clavien-Dindo scale, hospital LOS and costs of the episode of care between a prospective cohort of 120 ERAS short-stay THA or TKA and a matched historical control group of 150 THA or TKA. RESULTS: Significantly lower rate of Grade 1 and 2 complications in the ERAS short-stay group compared with the standard group (mean 0.8 vs 3.0, p<0.001). No difference was found between the 2 groups for Grade 3, 4, or 5 complications. The mean hospital LOS for the ERAS short-stay group decreased by 2.8 days for the THAs (0.1 vs 2.9 days, p<0.001) and 3.9 days for the TKAs (1.0 vs 4.9 days, p<0.001). The mean estimated direct health care costs reduction with the ERAS short-stay protocol was 1489 CAD per THA and 4158 CAD per TKA. DISCUSSION: In many short-stay protocols, focus has shifted from ERAS goals of a reduction in complications and improved recuperation to use length of stay as the main factor of success. Implementation of an ERAS short-stay protocol for patients undergoing THA or TKA at our institution resulted not only in reduced hospital LOS, but also in improved patient care and reduced direct health care costs. LEVEL OF EVIDENCE: Level II.

Impact of anesthesia management during cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for the treatment of colorectal peritoneal carcinomatosis on intra- and postoperative outcomes: A systematic review protocol.

BACKGROUND: The impact of the anesthesia management during cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal carcinomatosis (CRPC) on postoperative outcomes might be of major importance in the process of postoperative recovery. It might have a significant impact on intra- and postoperative outcomes, but the evaluation of this impact seems to be under-reported. To investigate the question whether the anesthesia management was reported in previous studies done in this population and if it had any impact on postoperative outcomes, we propose to conduct a systematic review of the published literature. METHODS: For this review, we will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Medline/PubMed, Embase, EBM Reviews and the Cochrane Database of Systematic Reviews (CDSR) will be systematically consulted for eligible studies without age, gender, ethnic, and language restriction. The goal of this review will be to assess whether anesthesia monitoring, dosing, and analgesia protocols were reported in this literature on this specific procedure and whether the impact of the anesthesia management on intraoperative safety and postoperative recovery was evaluated. RESULTS: The results of this systematic review will allow to answer the initial question: has the impact of anesthesia management on intraoperative safety and patients' postoperative recovery already been studied and reported in the past for this type of major surgery? And does anesthesia have any impact on postoperative outcomes? DISCUSSION: In the hypothesis that the impact of anesthesia management on patients' postoperative recovery has never been studied, or very little reported in previous studies in this type of major surgery, it would be justified to conduct a randomized controlled trial on this specific objective. REGISTRATION: This systematic review protocol was registered in PROSPERO, under the registration number CRD42019124162.

Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli.

BACKGROUND: The Pain Monitoring Device (PMD) monitor (Medasense Biometrics Ltd., Ramat Gan, Israel) uses the Nociception Level (NOL) index, a multiple parameter-derived index that has recently shown a good sensitivity and specificity to detect noxious stimuli. The aim of this study was to assess the latest version of the device (PMD200TM) on variations of the NOL response after standardized tetanic stimuli to study the correlation between remifentanil doses and NOL. METHODS: Data from 26 patients undergoing midline laparotomy and receiving a desflurane-remifentanil-based anesthetic coupled with low thoracic epidural analgesia were analyzed. A standardized tetanic stimulus was applied to the forearm of the patients at different remifentanil infusion rates. The primary aim was to evaluate the correlation between post-tetanic stimulation NOL values from the PMD200 and remifentanil doses. The NOL index variations after experimental and clinical stimuli were also compared with heart rate (HR), mean arterial pressure (MAP), and Bispectral Index™ (BIS). RESULTS: A correlation between post-tetanic stimulation NOL values and remifentanil doses was found (r = -0.56; 95% confidence interval [CI], -0.70 to -0.44; P < 0.001). The NOL discriminated noxious from non-noxious states with the maximal Youden's index value of the NOL receiver operating characteristic (ROC) curve showing a specificity of 88% (95% CI, 69.0 to 100) and sensitivity of 79.1% (95% CI, 56.2 to 95.5). The area under the NOL ROC curve (AUC, 0.9; 95% CI, 0.84 to 0.95) was significantly different from the other variables (P < 0.001 vs HR; P < 0.001 vs MAP; P < 0.001 vs BIS). CONCLUSIONS: The NOL value after noxious stimulus decreased with incremental remifentanil doses, showing a significant inverse correlation between the NOL index and opioid doses. The sensitivity and specificity of NOL to discriminate between noxious and non-noxious stimuli suggests its interesting potential as a monitor of nociception intensity during anesthesia. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02884778); 27 July, 2016.

Dexmedetomidine Versus Remifentanil for Monitored Anesthesia Care During Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Randomized Controlled Trial.

BACKGROUND: We hypothesized that, compared to remifentanil, dexmedetomidine used for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) performed under monitored anesthesia care (MAC) in nonintubated patients would result in fewer episodes of major respiratory adverse events (number of episodes of bradypnea, apnea or desaturation) but no difference in satisfaction with perioperative conditions. METHODS: Sixty (American Society of Anesthesiologists physical status I-III) patients scheduled to undergo EBUS-TBNA under MAC were randomized to receive either remifentanil (0.5 µg/kg IV bolus) in 10 minutes, followed by 0.05-0.25 µg/kg/min, or dexmedetomidine (0.4 µg/kg IV bolus) in 10 minutes, followed by 0.5-1.0 µg/kg/h. The primary outcome was the number of major respiratory adverse events (bradypnea, apnea, or hypoxia). The secondary outcomes included hemodynamic variables, discharge time from the postanesthesia care unit, endotracheal lidocaine use, patient's sedation using the Observer Assessment of Alertness/Sedation Scale, operative conditions, operator and patient satisfaction, pain, coughing, vocal cord mobility, recall, and nausea/vomiting. RESULTS: Dexmedetomidine produced significantly fewer episodes of major respiratory events (bradypnea, apnea, or desaturation), with 0 [0-0.5] episodes versus 2 [0-5] (median [interquartile range]) (P = .001), than did remifentanil. Fewer episodes of bradypnea or apnea (dexmedetomidine: 0 [0-0] versus remifentanil: 0 [0-0.5]; P = .031), and fewer episodes of desaturation (dexmedetomidine: 0 [0-0.5] versus remifentanil: 1 [0-4]; P = .039) were recorded in the dexmedetomidine group. The time needed for patients to meet postanesthesia care unit discharge criteria (Aldrete score: 9) after EBUS-TBNA was longer in the dexmedetomidine group (10 [3-37.5] minutes) versus the remifentanil group (3 [3-5] minutes) (P < .001). No differences were observed in the 2 groups for sedation depth (Observer Assessment of Alertness/Sedation Scale), endotracheal lidocaine use, operative conditions, operator and patient satisfaction, pain, coughing, vocal cord mobility, recall, and nausea/vomiting episodes. CONCLUSIONS: Dexmedetomidine resulted in fewer respiratory adverse events during EBUS-TBNA under MAC, when compared to remifentanil, with no difference in overall operative conditions. However, dexmedetomidine use was associated with delayed postoperative discharge.

Validation of the PMD100 and its NOL Index to detect nociception at different infusion regimen of remifentanil in patients under general anesthesia.

BACKGROUND: The NOL index is based on multiparametric analysis of heart rate (HR), skin conductance, wave plethysmography, and their time derivative. The aim of this study was to evaluate the NOL to detect standardized nociceptive stimuli with various remifentanil dosages under general anesthesia. METHODS: A prospective, observational study at a single center (NCT02602379) included 40 ASA I to III patients undergoing laparotomy under remifentanil-desflurane anesthesia with epidural analgesia. A tetanic stimulation was applied (forearm) at remifentanil intravenous (IV) infusion of 0.005, 0.05, 0.1, and 0.15 µg/kg/min. NOL and its variations were compared with other parameters namely heart rate, mean arterial pressure, Bispectral Index, and Analgesia Nociception Index (ANI). Receiver operating characteristic (ROC) curves were plotted to assess the response to both intubation and standardized stimulus under remifentanil infusion of 0.005 µg/kg/min. RESULTS: The post-stimulation NOL values at remifentanil doses of 0.005, 0.05, 0.1 and 0.15 µg/kg/min (39 [23-55], 15 [7-30], 8 [4-14] and 8.5 [4-15]) were significantly higher than pre-stimulation counterparts (P<0.0001). For all other parameters, there was also significant difference between pre- and post-stimulation values at all remifentanil dosages (P<0.0001). Area under the ROC curve (AUC) for the NOL during standardized stimulation was larger than for all other parameters at the exception of ANI (P=0.94). The AUC of NOL for nociception during tracheal intubation was greater (0.93 vs. 0.84 and 0.64 for ANI and HR, respectively). CONCLUSIONS: NOL monitoring is a promising index to assess the level of nociception in patients under general anesthesia.

Evaluation of the analgesia nociception index (ANI) in healthy awake volunteers.

BACKGROUND: Analgesia might be evaluated with simple changes in vital signs, a non-specific and non-sensitive method. Heart rate variability (HRV) correlates with autonomous nervous system activity and can be used to evaluate painful stimuli. Heart rate variability is then transformed into a numeric scale called the analgesia nociception index (ANI), where higher values represent predominant parasympathetic tone, thus low nociception. Under general anesthesia, the ANI decreases following painful stimuli and increases after administration of analgesia, but significant interindividual variability is present. The goal of the present study was to evaluate the ANI as a pain index in healthy awake volunteers. METHODS: Following research ethics board approval, participants were positioned supine in a calm operating room. The participants' vital signs and ANI were monitored. After evaluation of all parameters without any stimulation, 23 volunteers received a 2 Hz electrical stimulus at the wrist with increasing current intensity from 0-30 mA (5 mA increments). The current was kept constant for three minutes at each level, and the volunteers rated their pain on a numeric rating scale (NRS) every minute. The Pearson correlation coefficient and linear regression were used to analyze the relationship between the ANI and the NRS score. The ANI absolute values and the variations from baseline were both analyzed. RESULTS: There was a very weak negative correlation between the NRS score and ANImean (Pearson, -0.089; 95% confidence interval [CI], -0.192 to -0.014; P = 0.045) and between the NRS score and ∆ANImean (Pearson, -0.174; 95% CI, -0.272 to -0.072; P < 0.001; regression slope, -0.586; 95% CI, -0.930 to -0.243; P < 0.001). Heart rate, blood pressure, and respiratory rate did not vary significantly throughout the study. CONCLUSIONS: These findings provide little evidence to support use of the ANI in awake subjects or in awake patients such as those in the emergency room or in the intensive care unit. Nevertheless, based on an important difference between the expected correlation and the real correlation between the ANI and the NRS scores found in our results, the present study might be underpowered. Studies with a larger sample size would be required to enable firm conclusions about the clinical utility of the ANI in this population of awake volunteers as well as in awake patients. This study was registered with ClinicalTrials.gov (NCT02589093).

Interference between surgical magnetic drapes and pacemakers: an observational study comparing commercially available devices and a new magnetically isolated drape.

BACKGROUND: Magnetic fields may potentially interfere with the function of cardiovascular implantable electronic devices. Sterile magnetic drapes used to hold surgical instruments are often placed on the patient's thorax, and they are likely to interfere with the function of these devices. METHODS: Thirty patients were recruited to compare a new prototype surgical magnetic drape (LT10G™ by Menodys) made with bottom-isolated ferrite magnets to the Covidien magnetic drape we used in a previous study. Twenty additional patients were recruited to compare the prototype drape with four commercially available surgical magnetic drapes. RESULTS: Magnetic interference was found in 33 of the 50 total patients (70 %) when the Covidien drape was placed over the pacemaker. Of the 20 additional patients, 5 patients (25 %) displayed magnetic interference with a second type of surgical magnetic drape. A third magnetic drape caused interference in one patient (5 %), whereas a larger drape of the same model did not interfere in any patient. No patients demonstrated magnetic interference with the prototype drape. CONCLUSION: Bottom isolation of magnets in the prototype magnetic drape (LT10G™) used during surgery prevents magnetic interference in all patients when placed over the pacemaker. Three of the four commercially available magnetic drapes tested demonstrated magnetic interference. Flipping the prototype drape is not recommended as it may expose non-isolated magnets to the cardiovascular implantable electronic device.

Performing post-tetanic count during rocuronium blockade has limited impact on subsequent twitch height or train-of-four responses.

BACKGROUND: Waiting five to six minutes before measuring a train-of-four (TOF) after a 50-Hz tetanic stimulation or post-tetanic count (PTC) in order to allow the facilitation of transmission to subside is commonly recommended but is based on limited evidence. The purpose of this study was to measure the TOF responses after PTC in one hand and to compare the responses with those in the contralateral (control) hand. METHODS: Twenty-two adult patients undergoing elective surgery under opioid-desflurane anesthesia were fitted with sensors to measure displacement of their thumbs in response to ulnar nerve stimulation. Rocuronium 0.6 mg·kg(-1) was administered and TOF stimulation was applied to both sides. One side was randomized to PTC (50-Hz tetanus followed by a three-second pause and 15 1-Hz stimuli) when the opposite (control) side recovered to 10% first twitch (T1) height. Train-of-four stimulation was continued bilaterally every 20 sec until 30 min after PTC. Comparisons of the T1 and TOF ratio (T4/T1) were made at two, five, ten, 20, and 30 min. RESULTS: The mean (standard deviation [SD]) T1 value in the PTC arm was 11.8 (7.1)% just before PTC. The T1 values were significantly greater in the PTC arm at two, five, and ten minutes, with mean (SD) differences of 6.3 (6.7)%, 9.4 (6.8)%, and 7.4 (3.9)%, respectively (P = 0.008). There were no significant differences in T1 values between groups at 20 and 30 min, and no statistically significant differences in T4/T1 values at any time. CONCLUSION: A small but clinically insignificant increase in T1 is seen for at least ten minutes after PTC without any detectable change in T4/T1 values. The TOF responses are reliable as early as one minute after PTC.

Replacing a double-lumen tube with a single-lumen tube or a laryngeal mask airway device to reduce coughing at emergence after thoracic surgery: a randomized controlled single-blind trial.

BACKGROUND: Coughing episodes occur frequently at extubation after thoracic surgery, and this may be due in part to the double-lumen tube (DLT). In this study, the DLT was replaced with either a single-lumen endotracheal tube (ETT) or a laryngeal mask airway (LMA) device or left in place, and the incidence of coughing at emergence was compared between the three groups. METHODS: Fifty-eight adults scheduled for thoracic surgery with a DLT were included. Exclusion criteria were an anticipated difficult airway, obesity, and contraindication to the use of an LMA ProSeal™ (LMA-P). After surgery but before emergence, patients were randomized to having the DLT (1) removed and replaced by an LMA-P (LMA-P Group), (2) removed and replaced by an ETT (ETT Group), or (3) left in place (DLT Group). The primary outcome was the number of coughing episodes at extubation. RESULTS: Among 184 patients screened, 124 did not meet inclusion criteria, and two patients, both in the ETT Group, were excluded after randomization, leaving 20, 18, and 20 patients in the LMA-P, ETT, and DLT Groups, respectively. There were fewer coughing episodes (median [quartiles]) in the LMA-P Group than in the DLT Group (0[0-1] vs 2[1-3], respectively; P = 0.01). In the DLT Group, 90% of patients coughed at least once. This incidence was not significantly different in the ETT Group (83%; P = 0.222) but was significantly reduced in the LMA-P Group (35%; P < 0.001). No patient had oxygen desaturation during airway exchange or at extubation. The incidence and severity of hoarseness and sore throat were similar in all groups. CONCLUSION: Coughing at extubation after thoracic surgery can be reduced if the DLT is replaced by an LMA-P before emergence. The number of patients in this trial was too small to evaluate the risks associated with exchanging the airway device. This trial was registered at ClinicalTrials.gov: NCT00925613.