Nociception level response to calibrated stimulations in children: First assessment of the nociception level index in pediatric anesthesia.

INTRODUCTION: Intraoperative monitoring of nociception has made great progress in adult anesthesia. However, pediatric data are scarce. The Nociception Level (NOL) is one of the most recent indexes of nociception. Its originality is that it provides a multiparametric assessment of nociception. In adults, NOL monitoring allowed lower perioperative opioid requirements, hemodynamic stability, and qualitative postoperative analgesia. So far, the NOL has never been used in children. Our objective was to validate the ability of NOL to provide a quantitative assessment of nociception in anesthetized children. METHODS: In 5-12 years old children anesthetized with sevoflurane and alfentanil (10 µg kg-1), before surgical incision, we performed three standardized tetanic stimulations (5 s, 100 Hz) of different intensities (10-30-60 mA) in a randomized order. NOL, heart rate, blood pressure and Analgesia-Nociception Index variations were assessed after each stimulation. RESULTS: Thirty children were included. Data were analyzed with a covariance pattern linear mixed regression model. NOL increased after the stimulations (p < 0.05 at each intensity). NOL response was influenced by stimulation intensity (p < 0.001). Heart rate and blood pressure were barely modified by the stimulations. Analgesia-Nociception Index decreased after the stimulations (p < 0.001 at each intensity). Analgesia-Nociception index response was not influenced by stimulation intensity (p = 0.064). NOL and Analgesia-Nociception Index responses were significantly correlated (Pearson r = 0.47; p < 0.001). CONCLUSIONS: NOL allows a quantitative assessment of nociception under anesthesia in 5-12 years-old children. This study provides a solid basis for all future investigations on NOL monitoring in pediatric anesthesia. REGISTRATION: NCT05233449.

Teleconsultation in pediatric anesthesia: First assessment of feasibility, quality, and satisfaction in France.

INTRODUCTION: The COVID-19 pandemic has prompted the development of anesthesia teleconsultation in many countries. In pediatric anesthesia, data about anesthesia teleconsultation are scarce. The main objective of this prospective descriptive study was to provide an evaluation of the feasibility of pediatric anesthesia teleconsultation. Perception of the safety and quality, parental and medical satisfaction were also assessed. METHODS: From September to December 2020, patients undergoing a pediatric anesthesia teleconsultation in Toulouse University Hospital, using the TeleO™ dedicated teleconsultation platform were prospectively included. Feasibility was defined as the rate of anesthesia teleconsultations successfully performed using the TeleO™ platform alone. Questionnaires regarding the quality, safety, and satisfaction were filled in by physicians and families. RESULTS: A total of 114 children (3 months-17 years) were included in the study. Feasibility was 82%, failure was mainly caused by technical issues. Physicians estimated that the safety and quality of anesthetic preparation were optimal in 100% of cases. Anesthetists were satisfied (VAS ≥70/100) with the medical, technical, and relational (child/parents) aspects of anesthesia teleconsultation in 91%, 64%, and 84%/90% of cases respectively. Almost all parents (97%) stated that they would agree to anesthesia teleconsultation for a future procedure. CONCLUSION: In this first assessment, pediatric anesthesia teleconsultation appears to be feasible, with high rates of medical and parental satisfaction. Physicians' perception of the safety and quality of this process were positive. Improving the technical process might be a key determinant to promote further development of pediatric anesthesia teleconsultation.

Quantitative assessment of a pediatric nociception monitor in children under sevoflurane anesthesia.

INTRODUCTION: Intraoperative monitoring of nociception has recently made substantial progress in adult anesthesia. In contrast, pediatric data are scarce. Newborn-Infant Parasympathetic Evaluation (NIPE index, Mdoloris Medical Systems, Loos, France) is the first nociception index specifically designed for young children. It is a dimensionless index comprised between 0 and 100. Two previous studies suggested that NIPE could indeed 'detect' nociception in anesthetized children. The objective of our study was to investigate if NIPE allowed to detect and to provide a quantitative assessment of nociception in children. METHODS: Children were anesthetized with sevoflurane, and received a bolus of alfentanil (10 µg/kg before intubation). Before surgical incision, each participant received three tetanic stimulations (5 s, 100 Hertz) with a 5 min interval, in a randomized order: 10, 30 and 60 milliamps. NIPE and heart rate variations were assessed after each stimulation. RESULTS: Thirty children (2.4±1.6 years) were included. Mean delay between alfentanil and the first stimulation was 19±4 min. Mean baseline NIPE was 75±10. NIPE variation after the stimulations was significant at 10, 30 and 60 mA (linear mixed regression model, p<0.001). The intensity of stimulation significantly influenced the amplitude of NIPE variation (linear mixed regression model p<0.001), but had no statistically significant effect on heart rate variation (p=0.52). DISCUSSION: NIPE might allow a quantitative assessment of nociception in young children in these anesthetic conditions. This study provides a basis for future research investigating the potential benefits of NIPE-guided intraoperative analgesia in pediatric anesthesia. TRIAL REGISTRATION NUMBER: NCT04381637.

Monitoring of analgesia level during general anesthesia in children.

PURPOSE OF REVIEW: Monitoring of intraoperative nociception has made substantial progress in adult anesthesia during the last 10 years. Several monitors have been validated and their use has been associated with intraoperative or postoperative benefits in the adult population. In pediatric anesthesia, less data are available. However, several recent publications have assessed the performance of nociception monitors in children, and investigated their potential benefits in this context. This review will describe the main validated intraoperative nociception monitors, summarize adult findings and describe the available pediatric data. RECENT FINDINGS: Six intraoperative nociception indices were included in this review. Among them, four have shown promising results in children: Surgical Pleth Index (GE-Healthcare, Helsinki, Finland), Analgesia-Nociception Index (Mdoloris Medical Systems, Loos, France), Newborn-Infant Parasympathetic Evaluation (Mdoloris Medical Systems), and Pupillometry (IDMED, Marseille, France). The relevance of Skin Conductance (MedStorm innovations, AS, Oslo, Norway) under general anesthesia could not be established. Finally, the Nociception Level (Medasense, Ramat Gan, Israel) still requires to be investigated in children. SUMMARY: To date, four monitors may provide a relevant assessment of intraoperative nociception in children. However, the potential clinical benefits associated with their use to guide analgesia remain to be demonstrated.

Epidemiology and complications of anaesthesia in the French centres that participated to NECTARINE: A secondary analysis.

INTRODUCTION: Neonatal and infant anaesthesia are associated with a high risk of perioperative complications. The aim of the current study was to describe those risks in France using the French data from the NECTARINE study. MATERIAL AND METHODS: Data from the French centres that participated to the NECTARINE study were analysed. The primary goal of the study was the description of patients' characteristics, procedures and perioperative management and their comparison with the results of the European NECTARINE study. Secondary outcomes were the description of major perioperative complications and death. RESULTS: Overall, 926 procedures collected in 15 centres (all teaching hospitals) were analysed. Comparison between the French and European NECTARINE cohorts found few differences related to patients' characteristics and procedures. The rate of interventions for critical events (respiratory, haemodynamic, and metabolic) was similar between the two cohorts. Near-infrared spectroscopy monitoring was used in 12% of procedures. Nearly none of the thresholds for these interventions met the published standards. By day 30, complications (respiratory, haemodynamic, metabolic, renal, and liver failure) and death were observed in 14.4% [95% CI 11.6-16.4]% and 1.8% [95% CI 1.1-2.9] of cases, respectively. DISCUSSION: Although the health status of the patients in the French cohort was less severe, procedures, management and postoperative complications and mortality rates were similar to the European cohort. However, thresholds for interventions were often inadequate in both cohorts. Efforts should be undertaken to improve the knowledge and use of new monitoring devices in this population.

Analgesia Nociception Index-Guided Remifentanil versus Standard Care during Propofol Anesthesia: A Randomized Controlled Trial.

The clinical benefits to be expected from intraoperative nociception monitors are currently under investigation. Among these devices, the Analgesia Nociception-Index (ANI) has shown promising results under sevoflurane anesthesia. Our study investigated ANI-guided remifentanil administration under propofol anesthesia. We hypothesized that ANI guidance would result in reduced remifentanil consumption compared with standard management. This prospective, randomized, controlled, single-blinded, bi-centric study included women undergoing elective gynecologic surgery under target-controlled infusion of propofol and remifentanil. Patients were randomly assigned to an ANI or Standard group. In the ANI group, remifentanil target concentration was adjusted by 0.5 ng mL-1 steps every 5 min according to the ANI value. In the Standard group, remifentanil was managed according to standard practice. Our primary objective was to compare remifentanil consumption between the groups. Our secondary objectives were to compare the quality of anesthesia, postoperative analgesia and the incidence of chronic pain. Eighty patients were included. Remifentanil consumption was lower in the ANI group: 4.4 (3.3; 5.7) vs. 5.8 (4.9; 7.1) µg kg-1 h-1 (difference = -1.4 (95% CI, -2.6 to -0.2), p = 0.0026). Propofol consumption was not different between the groups. Postoperative pain scores were low in both groups. There was no difference in morphine consumption 24 h after surgery. The proportion of patients reporting pain 3 months after surgery was 18.8% in the ANI group and 30.8% in the Standard group (difference = -12.0 (95% CI, -32.2 to 9.2)). ANI guidance resulted in lower remifentanil consumption compared with standard practice under propofol anesthesia. There was no difference in short- or long-term postoperative analgesia.

Prediction of reactivity during tracheal intubation by pre-laryngoscopy tetanus-induced ANI variation.

The ANI is a nociception monitor based on the high frequency parts of heart rate variability. Tracheal intubation may induce potentially deleterious hemodynamic disturbances or motor reactions if analgesia is inadequate. We investigated whether ANI modification generated by a standardized moderate short tetanic stimulation performed before laryngoscopy could predict hemodynamic or somatic reactions to subsequent intubation. We designed a prospective, interventional, monocentric, pilot study. Regional ethics board approved the study, written informed consent was obtained from each participant. Before laryngoscopy, under steady-state total intravenous anaesthesia with propofol and remifentanil, the ulnar nerve was stimulated with a 5 s tetanus (70 mA, 50 Hz). After another steady-state period, orotracheal intubation was performed. ANI variation, hemodynamic parameters and somatic reactions associated with tetanus and intubation were collected. To assess the predictability of hemodynamic or somatic reaction during laryngoscopy by tetanus-induced ANI variation, we calculated the area under the corresponding Receiver Operating Characteristic curve (AUCROC) and the 95% confidence intervals. Thirty-five patients were analyzed. ANI decreased by 21 ± 17 after tetanus. Regarding the ability of tetanus-induced ANI variation to predict hemodynamic or somatic reactions during subsequent intubation, the AUCROCs [95% CI] were 0.61 [0.41-0.81] and 0.52 [0.31-0.72] respectively. ANI varied after a short moderate tetanic stimulation performed before laryngoscopy but this variation was not predictive of a hemodynamic or somatic reaction during intubation.Trial registration NCT04354311, April 20th 2020, retrospectively registered.

Relationship between pre-incision Pupillary Pain Index and post-incision heart rate and pupillary diameter variation in children.

BACKGROUND: The Pupillary Pain Index is a recent pupillometric index designed to assess the level of analgesia under general anesthesia in children and adults. If analgesia is inadequate, acute nociceptive stimuli such as skin incision may induce significant hemodynamic disturbances. AIMS: Our aim was to investigate the potential relationship between pre-incision Pupillary Pain Index and heart rate increase following skin incision in children. METHODS: This was a prospective, non-randomized, registered pilot study. We included children undergoing surgery under general anesthesia. Pupillary Pain Index was assessed 2 min before skin incision. Then, heart rate maximal variation (ΔHR ) and pupillary diameter maximal variation (ΔPD ) in the minute following incision were recorded. Spearman coefficient was calculated to characterize the relationship between Pupillary Pain Index and ΔHR or ΔPD . Using receiver operating characteristic curve analysis, we also studied the predictive value of pre-incision Pupillary Pain Index for heart rate and pupillary diameter reactivity. RESULTS: 53 patients were included (10 ± 4 years, 40 ± 19 kg). There was a modest correlation between pre-incision Pupillary Pain Index and ΔHR (Spearman rs = 0.35 [0.05-0.57], p = .011), and between pre-incision Pupillary Pain Index and ΔPD (Spearman rs = 0.54 [0.33-0.71], p < .001). Regarding the predictive value of Pupillary Pain Index for heart rate or pupillary diameter reactivity, the corresponding areas under the receiver operating characteristic curves were 0.90 [0.82-0.99] and 0.78 [0.65-0.93], respectively. A threshold of Pupillary Pain Index <3 predicted the absence of heart rate reactivity at incision with a good performance (negative predictive value = 1). CONCLUSIONS: In children, pre-incision Pupillary Pain Index was moderately correlated with post-incision nociception. Pre-incision Pupillary Pain Index had good predictive performances for heart rate or pupillary diameter reactivity to skin incision. Pre-incision Pupillary Pain Index <3 might predict the absence of heart rate reaction to incision.

The newborn infant parasympathetic evaluation in pediatric and neonatology: a literature review.

PURPOSE: The Newborn Infant Parasympathetic Evaluation (NIPE) is a heart rate variability-based technology for assessing pain and comfort in neonates and infants under 2-years-old. This review aims to investigate the clinical utility of the NIPE. METHODS: Two investigators screened Pubmed/Medline and Google Scholar for relevant studies, independently. One investigator extracted data, which were reviewed by a second investigator. RESULTS: The NIPE was used during/after painful stimuli (6 studies), in the context of general anaesthesia (2 studies), and for comfort assessment (6 studies). A) Evaluation of procedural pain/distress: 2 studies reported that the mean-NIPE could be used for reliable monitoring of prolonged pain, and one study reported the association between instant-NIPE and pain after a stimulus but the instant-NIPE represents the NIPE average over 3 min. Two studies found no correlation between the NIPE and comfort behavior/pain scales, but they mainly differed in patients' gestational age and evaluation methodology. B) There are only 2 studies for the evaluation of nociception during surgery under general anaesthesia with contradictory results. C) Studies assessing neonates' comfort reported increased NIPE scores during skin-to-skin contact and during facilitated tucking associated with a human voice. No effect on NIPE scores of facilitated tucking during echocardiography was reported in preterm infants. One study reported significantly different NIPE scores with 2 surfactant therapy protocols. Overall, study populations were small and heterogeneous. CONCLUSION: The results regarding NIPE's performances differ between studies. Given the limited number of studies and the heterogeneous outcomes, more studies are required to confirm the NIPE usefulness in the different clinical settings.

Effect of Different Concentrations of Propofol Used as a Sole Anesthetic on Pupillary Diameter: A Randomized Trial.

BACKGROUND: Pupillometry monitoring under general anesthesia is based on the assumption that pupillary diameter variations reflect the adequacy of the provided analgesia to the intensity of the nociceptive surgical stimulus. The accurate interpretation of pupillometric data requires establishing clearly what the expected baseline unstimulated pupillary diameter at each specific level of hypnosis is. Opioids decrease pupillary diameter in a dose-dependent fashion. In contrast, the effects of hypnotic drugs on pupillary diameter are not well known. Our aim was to describe the potential relationship between propofol predicted effect-site concentrations (Cets) ranging from 1 to 3 µg/mL and pupillary diameter. METHODS: Patients were randomized to receive propofol by target-controlled infusion at a predicted Cet of 1, 2, or 3 µg/mL (groups P1, P2, and P3, respectively). Pupillary diameter measurements were performed after 10 minutes of steady-state propofol infusion at the randomized Cet. No stimulation was performed during the study. Heart rate and bispectral index (BIS) were continuously recorded. RESULTS: Forty patients were included: (13, 14, and 13 in groups P1, P2, and P3, respectively). Mean pupillary diameter was 5.7 mm (1 mm) in group P1, 4.8 mm (1.3 mm) in group P2, and 3.3 mm (0.8 mm) in group P3. Propofol had a dose-dependent effect on pupillary diameter (linear regression R = 0.45, P < .001). Pupillary diameter was positively correlated with the BIS (Spearman r = 0.75 [95% confidence interval (CI), 0.54 to -0.87] P < .001). CONCLUSIONS: From 1 to 3 µg/mL of predicted Cet, propofol has a dose-dependent effect on pupillary diameter. Within this concentrations range, there is a positive correlation between BIS and pupillary diameter. The subcortical effect of propofol on pupillary diameter is correlated to its effect on the cortex. Studies assessing pupillary diameter as a marker of the nociception-antinociception balance should be performed in patients with a standardized depth of hypnosis.

Assessment of Coagulation by Thromboelastography During Ongoing Postpartum Hemorrhage: A Retrospective Cohort Analysis.

BACKGROUND: Rapid assessment of hemostasis during postpartum hemorrhage (PPH) is essential to allow characterization of coagulopathy, to estimate bleeding severity, and to improve outcome. Point of care (POC) coagulation monitors could be of great interest for early diagnosis and treatment of coagulation disorders in PPH. METHODS: Women with ongoing PPH >500 mL who clinically required an assessment of coagulation with thromboelastography (TEG) were included. The primary aim of this retrospective observational cohort study was to assess the predictive accuracy of TEG parameters for the diagnosis of coagulation disorders (hypofibrinogenemia ≤2 g/L, thrombocytopenia ≤80,000/mm, prothrombin ratio ≤50%, or activated partial thromboplastin time ratio ≥1.5) during PPH. The analyzed TEG parameters were Kaolin-maximum amplitude (K-MA), Kaolin-maximum rate of thrombus generation using G (K-MRTGG), functional fibrinogen-maximum amplitude (FF-MA), and functional fibrinogen-maximum rate of thrombus generation using G (FF-MRTGG). Secondary aims of this study were (1) comparison of the time delay between classical parameters and velocity curve-derived parameters (K-MA versus K-MRTGG and FF-MA versus FF-MRTGG) and (2) evaluation of the accuracy of TEG parameters to predict severe hemorrhage estimated by calculated blood losses. RESULTS: Ninety-eight patients were included with 98 simultaneous TEG analyses and laboratory assays. All parameters had an excellent predictive performance. For the Kaolin assay, no significant difference was evidenced between K-MA and K-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm (respective area under the curve [AUC], 0.970 vs 0.981). For the functional fibrinogen assay, no significant difference was evidenced between FF-MA and FF-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L (respective AUC, 0.988 vs 0.974). For both assays, the time to obtain results was shorter for the velocity parameters (K-MRTGG: 7.7 minutes [2.4 minutes] versus K-MA: 24.7 minutes [4.2 minutes], P < .001; FF-MRTGG: 2.7 minutes [2.7 minutes] versus FF-MA: 14.0 minutes [4.3 minutes], P < .001). All TEG parameters derived from the Kaolin and functional fibrinogen assays and Clauss fibrinogen were significantly predictive of severe PPH >2500 mL. CONCLUSIONS: During PPH, when coagulation assessment is indicated, TEG provides a rapid and reliable detection of hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm. No difference in performance was evidenced between the velocity-derived parameters (K-MRTGG and FF-MRTGG) and the classical parameters (K-MA and FF-MA). However, velocity-derived parameters offer the advantage of a shorter time to obtain results: FF-MRTGG parameter is available within ≤5 minutes. POC assessment of hemostasis during PPH management may help physicians to diagnose clotting disorders and to provide appropriate hemostatic support.

Revision of expert panel's guidelines on postoperative pain management.

The French Society of Anaesthesia and Intensive Care Medicine (SFAR) published experts' guidelines on the care of postoperative pain. This was an update of the 2008 guidelines. Fourteen experts analysed the literature (PubMed™, Cochrane™) on questions that had not been treated in the previous guidelines, or to modify the guidelines following new data in the published literature. The used method is invariably the GRADE© method, which guarantees a rigorous work. Seventeen recommendations were formalised on the assessment of perioperative pain, and most particularly in non-communicating patients, on opioid and non-opioid analgesics and on anti-hyperalgesic drugs, such as ketamine and gabapentinoids, as well as on local and regional anaesthesia. The concept of vulnerability and therefore the identification of the most fragile patients in terms of analgesics requirements were specified. Because of the absence of sufficient data or new information, no recommendation was made about analgesia monitoring, the procedures for the surveillance of patients in conventional care structures, or perinervous or epidural catheterism.

Management of the child's airway under anaesthesia: The French guidelines.

OBJECTIVE: To provide French guidelines about "Airway management during paediatric anaesthesia". DESIGN: A consensus committee of 17 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie-Réanimation, SFAR) and the Association of French speaking paediatric anaesthesiologists and intensivists (Association Des Anesthésistes Réanimateurs Pédiatriques d'Expression Francophone, ADARPEF) was convened. The entire process was conducted independently of any industry funding. The authors followed the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to assess the quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Few recommendations were not graded. METHODS: The panel focused on 7 questions: 1) Supraglottic Airway devices 2) Cuffed endotracheal tubes 3) Videolaryngoscopes 4) Neuromuscular blocking agents 5) Rapid sequence induction 6) Airway device removal 7) Airway management in the child with recent or ongoing upper respiratory tract infection. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. The analysis of the literature and the redaction of the recommendations were then conducted according to the GRADE® methodology. RESULTS: The SFAR Guideline panel provides 17 statements on "airway management during paediatric anaesthesia". After two rounds of discussion and various amendments, a strong agreement was reached for 100% of the recommendations. Of these recommendations, 6 have a high level of evidence (Grade 1 ± ), 6 have a low level of evidence (Grade 2 ± ) and 5 are experts' opinions. No recommendation could be provided for 3 questions. CONCLUSIONS: Substantial agreement exists among experts regarding many strong recommendations for paediatric airway management.

Epidemiology and incidence of severe respiratory critical events in ear, nose and throat surgery in children in Europe: A prospective multicentre observational study.

BACKGROUND: Ear, nose and throat (ENT) surgery, the most frequently performed surgical procedure in children, is a strong predictor for peri-operative respiratory complications. However, there is no clear information about peri-operative respiratory severe critical events (SCEs) associated with anaesthesia management of ENT children in Europe. OBJECTIVE: To characterise the epidemiology and incidence of respiratory SCEs during and following ENT surgery in Europe and to identify the risk factors for their occurrence. DESIGN: A secondary analysis of the Anaesthesia PRactice In Children Observational Trial, a prospective observational multicentre cohort trial. SETTING: The study included 261 centres across 33 European countries and took place over a consecutive 2-week recruitment period between April 2014 and January 2015. PATIENTS: We extracted data from 5592 ENT surgical procedures that were performed on 5572 children aged 6.0 (3.6) years (mean (SD)) from the surgical database and compared these with data from 15 952 non-ENT surgical children aged 6.7 (4.8) years. MAIN OUTCOME MEASURES: The primary outcome was the incidence of respiratory SCEs (laryngospasm, bronchospasm and new onset of postoperative stridor). Secondary outcomes were the differences in epidemiology between ENT children and non-ENT surgical children and the risk factors for the occurrence of respiratory SCEs. RESULTS: The incidence (95% confidence interval) of any respiratory SCE (laryngospasm, bronchospasm and postoperative stridor) was 3.93% (3.46 to 4.48) and was significantly higher than that observed in non-ENT surgical children [2.61% (2.37 to 2.87)], with a relative risk of 1.51 (1.28 to 1.77), P less than 0.0001. Younger age (14% decrease in critical events by increasing year, P < 0.0001), history of snoring, recent upper respiratory tract infection and recent wheezing increased the risk of suffering a SCE by over two-fold (P < 0.0001). There was also some evidence for a positive association with age below 4.6 years and lower surgical volume thresholds (<20 cases/2 weeks). CONCLUSION: The results of this study provide additional evidence for strong associations between risk factors and respiratory SCEs in children having ENT surgery. These observations may facilitate the implementation of good clinical practice recommendations for ENT patients in Europe. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01878760.

EEG profiles during general anesthesia in children: A comparative study between sevoflurane and propofol.

BACKGROUND: In this prospective study, we describe the electroencephalographic (EEG) profiles in children anesthetized with sevoflurane or propofol. METHODS: Seventy-three subjects (11 years, range 5-18) were included and randomly assigned to two groups according to the anesthetic agent. Anesthesia was performed by target-controlled infusion of propofol (group P) or by sevoflurane inhalation (group S). Steady-state periods were performed at a fixed randomized concentration between 2, 3, 4, 5, and 6 µg.ml-1 of propofol in group P and between 1, 2, 3, 4, and 5% of sevoflurane in group S. Remifentanil was continuously administered throughout the study. Clinical data, Bispectral Index (BIS), and raw EEG were continuously recorded. The relationship between BIS and anesthetic concentrations was studied using nonlinear regression. For all steady-state periods, EEG traces were reviewed to assess the presence of epileptoid signs, and spectral analysis of raw EEG was performed. RESULTS: Under propofol, BIS decreased monotonically and EEG slowed down as concentrations increased from 2 to 6 µg.ml-1 . Under sevoflurane, BIS decreased from 0% to 4% and paradoxically rose from 4% to 5% of expired concentration: this increase in BIS was associated with the occurrence of fast oscillations and epileptoid signs on the EEG trace. Propofol was associated with more delta waves and burst suppression periods compared to sevoflurane. CONCLUSION: Under deep anesthesia, the BIS and electroencephalographic profiles differ between propofol and sevoflurane. For high concentrations of sevoflurane, an elevated BIS value may be interpreted as a sign of epileptoid patterns or EEG fast oscillations rather than an insufficient depth of hypnosis.

Pupillary Pain Index Changes After a Standardized Bolus of Alfentanil Under Sevoflurane Anesthesia: First Evaluation of a New Pupillometric Index to Assess the Level of Analgesia During General Anesthesia.

BACKGROUND: The pupillary pain index (PPI) is a novel pupillometric index, designed to assess intraoperative analgesia. It is based on the evaluation of the pupillary response to electrical stimuli of increasing intensity. It ranges from 1 (low level of pupillary reactivity, high level of analgesia) to 10 (high level of pupillary reactivity, low level of analgesia). In this first evaluation of the PPI, our objective was to investigate the PPI changes after a bolus of 10 µg·kg(-1) of alfentanil in children under sevoflurane general anesthesia. METHODS: After ethics committee approval and informed consent, 20 healthy children (9 ± 5 years) undergoing elective surgery under general anesthesia were included in this prospective, open, registered pilot study (NCT02646592). Anesthetic induction was standardized with sevoflurane 6% and propofol 1 mg·kg(-1). After tracheal intubation, sevoflurane concentration was maintained at 2% for 10 minutes. A first PPI measurement was performed (PPI-1), and a bolus of 10 µg·kg(-1) was administered. Two minutes after this bolus, a second PPI measurement was performed (PPI-2). Heart rate, blood pressure, and bispectral index were recorded before and after each PPI measurement. Resting pupillary diameter was recorded before each PPI measurement. PPI scores before and after the bolus of alfentanil were compared using a Wilcoxon signed rank test. RESULTS: PPI scores decreased after administration of a bolus of alfentanil (median difference: -3 [95% confidence interval, -4 to -2]). The median (quartiles) of PPI-1 (baseline, before alfentanil) was 6 (4, 7), and the median (quartiles) of PPI-2 (after alfentanil) was 2 (2, 3) (P < .001). No difference was found in resting pupillary diameter before PPI-1 and PPI-2 (2.2 ± 0.2 and 2.2 ± 0.3 mm, respectively; P = .86). There were no significant changes in heart rate or blood pressure after PPI measurements (P = .46 and .49, respectively). Bispectral index was slightly increased after PPI measurements (P = .01; mean bispectral index increase <5%). No withdrawal movements occurred during PPI measurements. CONCLUSIONS: There was a significant decrease in PPI after alfentanil administration. The results of this pilot study suggest that PPI score decreases when the level of analgesia increases. PPI measurement was not associated with a clinical or hemodynamic nociceptive response. This new index might provide useful information to individually adapt opioid administration before nociceptive stimuli under general anesthesia.

Peri-operative respiratory adverse events in children with upper respiratory tract infections allowed to proceed with anaesthesia: A French national cohort study.

BACKGROUND: Peri-operative respiratory adverse events (PRAEs) in paediatric patients with upper respiratory tract infections (URTIs) remain inadequately explored in patients allowed to proceed to anaesthesia and surgery. OBJECTIVE: To determine the incidence and risk factors of PRAE in children with URTI allowed to proceed to anaesthesia. DESIGN: Multicentre cohort study performed over 6 months in France. SETTING: Sixteen centres with dedicated paediatric anaesthetists. PATIENTS: Eligible patients were aged from 0 to 18 years with URTI symptoms on admission or a history of such over the preceding 4 weeks. MAIN OUTCOMES: The primary outcome of the study was to determine predictors of PRAE. Secondary outcomes were: predictors of peri-operative arterial desaturation and of the decision to proceed with anaesthesia and surgery in children with URTI. RESULTS: Overall, 621 children were included and 489 (78.7%) anaesthetised. Of those anaesthetised, 165 (33.5%) and 97 (19.8%) experienced PRAE and arterial desaturation, respectively. Factors predictive of PRAE included patient age, tracheal intubation and the absence of midazolam premedication. Factors predictive of peri-operative arterial desaturation included patient age, anaesthetist experience, endoscopic procedures and the presence of other PRAE. Factors predicting proceeding to anaesthesia in the context of URTI included anaesthetist experience, emergency procedures and the absence of severe URTI symptoms. CONCLUSION: The risk of PRAE in patients anaesthetised in the presence of URTI was similar to previous publications - close to 30%. In the light of our findings, first, current rescheduling indications should be questioned, and second, further medical and organisational strategies should be investigated to reduce PRAE in children with URTI. TRIAL REGISTRATION: The study was registered in the European Networks of Centers for Pharmacoepidemiology and Pharmacovigilance (EUPAS16436).

Influence of Depth of Hypnosis on Pupillary Reactivity to a Standardized Tetanic Stimulus in Patients Under Propofol-Remifentanil Target-Controlled Infusion: A Crossover Randomized Pilot Study.

BACKGROUND: Pupillometry allows the measurement of pupillary diameter variations in response to nociceptive stimuli. This technique has been used to monitor the balance between analgesia and nociception. Under general anesthesia, the amplitude of pupillary dilation is related to the amount of administered opioids. The objective of this study was to determine whether at a constant infusion rate of opioids, the pupillary response was influenced by depth of hypnosis assessed by the bispectral index (BIS). METHODS: Twelve patients (14-20 years) anesthetized for orthopedic surgery were included. Under propofol-remifentanil target-controlled infusion, remifentanil effect site target concentration was fixed at 1 ng/mL. Two measures of pupillary reflex dilation were performed on each patient in a randomized order: one at BIS 55 and one at BIS 25. These levels of BIS were obtained by adjusting propofol target concentration and maintained for 10 minutes before each measure. For each measure, we applied a standardized tetanic stimulation on the patient's forearm (60 mA, 100 Hz, 5 seconds). All measures were performed before the beginning of surgery. RESULTS: Pupillary dilation was significantly greater at BIS 55 than at BIS 25: 32.1% ± 5.3% vs 10.4% ± 2.5% (mean difference estimate [95% confidence interval]: 21.8% [12.9-30.6], P < .001), without carryover effect (P = .30) nor period effect (P = .52). Hemodynamic parameters and BIS were not modified by the stimulation. CONCLUSIONS: In patients receiving a constant infusion of remifentanil at a target concentration of 1 ng/mL, pupillary dilation after a standardized tetanic stimulation was influenced by depth of hypnosis assessed by the BIS.