Using the nociception level index to compare the intraoperative antinociceptive effect of propofol and sevoflurane during clinical and experimental noxious stimulus in patients under general anesthesia.

STUDY: Propofol and sevoflurane are two anesthetic agents widely used to induce and maintain general anesthesia (GA). Their intrinsic antinociceptive properties remain unclear and are still debated. OBJECTIVE: To determine whether propofol presents stronger antinociceptive properties than sevoflurane using intraoperative clinical and experimental noxious stimulations and evaluating postoperative pain outcomes. DESIGN: A prospective randomized monocentric trial. SETTING: Perioperative care. PATIENTS: 60 adult patients with ASA status I to III who underwent elective abdominal laparoscopic surgery under GA were randomized either in propofol or sevoflurane group to induce and maintain GA. INTERVENTIONS: We used clinical and experimental noxious stimulations (intubation, tetanic stimulation) to assess the antinociceptive properties of propofol and sevoflurane in patients under GA and monitored using the NOL index, BIS index, heart rate, and mean arterial blood pressure. MEASUREMENTS: We measured the difference in the NOL index alterations after intubation and tetanic stimulation during either intravenous anesthesia (propofol) or inhaled anesthesia (sevoflurane). We also intraoperatively measured the NOL index and remifentanil consumption and recorded postoperative pain scores and opioid consumption in the post-anesthesia care unit. Intraoperative management was standardized by targeting similar values of depth of anesthesia (BIS index), hemodynamic (HR and MAP), NOL index values (below the threshold of 20), same multimodal analgesia and type of surgery. MAIN RESULTS: We found the antinociceptive properties of propofol and sevoflurane similar. The only minor difference was after tetanic stimulation: the delta NOL was higher in the sevoflurane group (39 ± 13 for the propofol group versus 47 ± 15 for sevoflurane; P = 0.04). Intraoperative and postoperative pain outcomes and opioid consumption were similar between groups. CONCLUSIONS: Despite a precise intraoperative experimental and clinical protocol using the NOL index, propofol does not provide a higher level of antinociception during anesthesia or analgesia after surgery when compared to sevoflurane. Anesthesiologists may prefer propofol over sevoflurane to reduce PONV or anesthesia-related pollution, but not for superior antinociceptive properties.

Make me more comfortable: effects of a hypnosis session on pain perception in chronic pain patients.

Introduction: Approximately one-quarter of Canadians experience chronic pain, a debilitating condition often necessitating opioid use, which raises concerns regarding dependency and overdose risks. As an alternative, we developed the HYlaDO program (Hypnose de la Douleur, hypnosis of Pain in French), a novel self-hypnosis approach for chronic pain management. The development of this program followed the ORBIT model, a comprehensive framework for designing interventions encompassing several phases ranging from design to efficacy assessment. Methods: In the present work, we conducted a preliminary evaluation of the HYlaDO program with 21 participants (18 of the 21 patients were included in the analysis). The primary objective was to determine one session of the program's effectiveness in altering pain, anxiety and relaxation via pre-post analysis. The secondary goal was to examine the long-term effects across the same measures, in addition to the overall quality of life. Results: The results highlight the benefits of our approach, while participants reported short-term significant pain reduction, decreased anxiety, and increased relaxation. Additionally, preliminary trends suggest improvements in physical activity and quality of life metrics. Discussion: These positive outcomes highlight HYlaDO's potential as an alternative to opioid therapy for chronic pain. Encouraged by these results, we aim to extend our research to a broader and more diverse cohort, paving the way for comprehensive randomized controlled trials. This expansion will further validate HYlaDO's efficacy and its role in transforming chronic pain management.

Practicing self-hypnosis to reduce chronic pain: A qualitative exploratory study of HYlaDO.

Background: Nearly a quarter of Canada's population suffers from chronic pain, a long-lasting medical condition marked by physical pain and psychological suffering. Opioids are the primary treatment for pain management in this condition; yet, this approach involves several undesirable side effects. In contrast to this established approach, non-pharmacological interventions, such as medical hypnosis, represent an efficient alternative for pain management in the context of chronic pain. HYlaDO is a self-hypnosis program designed to improve pain management for people with chronic pain. Purpose: This research aimed to evaluate the HYlaDO program based on the proof-of-concept level of the ORBIT model and investigated participants' subjective experience. Research design: Qualitative study. Study sample: Seventeen participants with chronic pain took part in this study. Data collection: We conducted individual semi-structured interviews with patients who had participated in HYlaDO to identify the three targets of desired change: pain, anxiety and autonomy in self-hypnosis practice. Results: Thematic analysis revealed that the practice of hetero-hypnosis and self-hypnosis decreased (i) pain and (ii) anxiety. Also, it (iii) indicated the development of an independent and beneficial self-hypnosis practice by having integrated the techniques taught. Conclusion: These results confirm that the established targets were reached and support further development, implementation and scaling up of this program. Consequently, we believe it is justified to move to the next step of program development.

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.

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.

"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.

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.

Uterine Exteriorization Compared With In Situ Repair of Hysterotomy After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of exteriorized with in situ uterine repair on intraoperative nausea and vomiting during elective cesarean delivery under spinal anesthesia using a phenylephrine infusion. METHODS: This study was a randomized double-blinded controlled trial of 180 women undergoing elective cesarean delivery using a standardized anesthetic protocol. Patients were randomized to exteriorization (n=90) or in situ uterine repair (n=90). The spinal anesthetic, phenylephrine infusion, and blood pressure management were all standardized. The primary outcome was postdelivery intraoperative nausea and vomiting using a 4-point scale (0-3). A sample size of 80 patients per group was needed to demonstrate a 50% reduction in intraoperative nausea and vomiting with in situ repair. RESULTS: From November 2015 through July 2018, 180 patients were enrolled. Incidence of postdelivery intraoperative nausea and vomiting was 39% in the exteriorization group compared with 22% in the in situ group (P=.01). Incidence of hypotension (80% vs 50%; P<.001) and tachycardia (33% vs 17%; P=.02) was significantly higher in the exteriorization group, and more phenylephrine boluses were administered to this group (median 4 boluses [first and third quartiles 1.25-7] vs 2 [0-4]; P<.001). The duration of surgery, blood loss, and postoperative hemoglobin decline were similar between groups. CONCLUSION: In situ uterine repair for elective cesarean delivery under spinal anesthesia with a phenylephrine infusion is associated with less postdelivery intraoperative nausea and vomiting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02587013.

Low dose intravenous dexamethasone (4 mg and 10 mg) significantly prolongs the analgesic duration of single-shot interscalene block after arthroscopic shoulder surgery: a prospective randomized placebo-controlled study.

BACKGROUND: Although intravenous dexamethasone prolongs the analgesic duration of interscalene brachial plexus block, it is uncertain whether this effect can be observed using lower doses of dexamethasone. This study evaluated the impact of intravenous dexamethasone (4 mg and 10 mg) on the analgesic duration of single-shot interscalene block after arthroscopic shoulder surgery. We hypothesized that both doses would prolong the analgesic duration compared with placebo. METHODS: This was a prospective double-blind randomized placebo-controlled study in patients undergoing elective arthroscopic shoulder surgery under regional anesthesia with a single-shot interscalene block (0.5% ropivacaine 20 mL). Patients received dexamethasone 4 mg (D4), dexamethasone 10 mg (D10), or a placebo (normal saline [NS]) intravenously at the time of block completion. The primary outcome was the duration of analgesia, defined as the time from the onset of sensory blockade to the first analgesic request. The primary outcome was first analyzed with a Kruskal-Wallis test and then with a Mann-Whitney test for pairwise between-group comparison. RESULTS: Sixty-nine patients completed the study. The median [interquartile range] duration of analgesia was significantly different between the three groups (D4, 19.7 [16.9-23.3] hr; D10, 19.1 [11.5-22.8] hr; and NS, 11.8 [9.3-14.0] hr; P = 0.001). This difference was statistically significant for D4 and D10 compared with placebo (median difference [MD], 7.8 hr; 95% confidence interval [CI], 4.6 to 11.1 hr; P < 0.001; and MD, 7.4 hr; 95% CI, 4.2 to 10.5 hr; P = 0.001, respectively) but not for D4 compared with D10 (MD, 0.5 hr; 95% CI, -2.8 to 3.7 hr; P = 0.38). CONCLUSIONS: Low doses of intravenous dexamethasone (4 mg and 10 mg) significantly prolong the analgesic duration of interscalene block. This trial was registered at ClinicalTrials.gov (NCT02412657).