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.

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.

Feasibility of open abdomen surgery treatment for near fatal necrotizing enterocolitis in preterm infants.

INTRODUCTION: Necrotizing Enterocolitis (NEC) remained a dramatic complication leading to death or neonatal morbidities in preterms. For some, Intra-Abdominal Hypertension (IAH) and Abdominal Compartment Syndrome worsened the multi-organ failure. An open abdomen surgery could be an alternative to conventional surgical treatment to move beyond this stage. OBJECTIVES: To retrospectively describe the clinical course, pre- and post-operative features of preterms suffering from severe NEC with IAH treated by open abdomen surgery and referred to our center from October 2007 to September 2019. Our secondary objective is to identify various risk factors for mortality in this population. METHODS: Data on neonatal, clinical, biological, pre and post-operative features and outcome were collected. Univariate analyses were performed to compare their pre and post-operative features stratifying on outcome. RESULTS: Among 29 included patients, 14 (48%) survived to discharge without short bowel syndrome. Death was associated with an earlier postnatal age at NEC (16.3 ± 9.1 versus 31.3 ± 25.9 days; p = 0.004) and followed a withdrawal of treatment in 60% of cases. Surgery was associated with a significant improvement of respiratory and hemodynamic features (decrease of mean ventilator pressure from 13.1 ± 5.4 to 11.3 ± 4.0 cmH2O, p < 0.001), oxygen requirement (mean FiO2 decreased from 65.0% ± 31.2 to 49.0% ± 24.6, p < 0.001) and inotropic score (from 38.6 ± 70.1 to 29.9 ± 64.3, p < 0.001). In the survival group, pre and post-operative findings exhibited a significant increase of serum lactate concentrations from 2.7 ± 1.6 to 11.0 ± 20.3 mmol/L (p = 0.02) but a similar pH. CONCLUSION: Open abdomen surgery could be considered to rescue preterms with near fatal NEC. IAH and Abdominal Compartment Syndrome in these preterms should be investigated through further studies. LEVEL OF EVIDENCE: Level III.

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.

Sevoflurane Sedation with AnaConDa-S Device for a Child Undergoing Extracorporeal Membrane Oxygenation.

BACKGROUND: Deep sedation in critically ill children undergoing extracorporeal membrane oxygenation (ECMO) can be challenging. Volatile anesthetics like sevoflurane can be a good alternative for patients hospitalized in pediatric intensive care units, in whom adequate sedation is difficult to obtain. CASE DESCRIPTION: We report here the first pediatric case of a patient under extracorporeal membrane oxygenation receiving sedation by sevoflurane using the AnaConDa-S device. This 2-year-old girl, suffering from congenital diaphragmatic hernia, was put on extracorporeal membrane oxygenation due to a persistent pulmonary hypertension following metapneumovirus infection. Despite high doses of drugs, neither satisfactory sedation nor analgesia could be reached. Sevoflurane allowed her to be released and we were able to wean her from certain drugs. Her physiological parameters and the indicators of pain and sedation improved. CONCLUSION: Anesthesia using sevoflurane with the AnaConDa-S device is efficient for children under ECMO. CLINICAL SIGNIFICANCE: This is the first pediatric report on anesthesia with sevoflurane under ECMO. HOW TO CITE THIS ARTICLE: Soreze Y, Piloquet J-E, Amblard A, Constan I, Rambaud J, Leger P-L. Sevoflurane Sedation with AnaConDa-S Device for a Child Undergoing Extracorporeal Membrane Oxygenation. Indian J Crit Care Med 2020;24(7):596-598.

Management of severe thermal burns in the acute phase in adults and children.

OBJECTIVES: To provide recommendations to facilitate the management of severe thermal burns during the acute phase in adults and children. DESIGN: A committee of 20 experts was asked to produce recommendations in six fields of burn management, namely, (1) assessment, admission to specialised burns centres, and telemedicine; (2) haemodynamic management; (3) airway management and smoke inhalation; (4) anaesthesia and analgesia; (5) burn wound treatments; and (6) other treatments. At the start of the recommendation-formulation process, a formal conflict-of-interest policy was developed and enforced throughout the process. The entire process was conducted independently of any industry funding. The experts drew up a list of questions that were formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes). Two bibliography experts per field analysed the literature published from January 2000 onwards using predefined keywords according to PRISMA recommendations. The quality of data from the selected literature was assessed using GRADE® methodology. Due to the current paucity of sufficiently powered studies regarding hard outcomes (i.e. mortality), the recommendations are based on expert opinion. RESULTS: The SFAR guidelines panel generated 24 statements regarding the management of acute burn injuries in adults and children. After two scoring rounds and one amendment, strong agreement was reached for all recommendations. CONCLUSION: Substantial agreement was reached among a large cohort of experts regarding numerous strong recommendations to optimise the management of acute burn injuries in adults and children.

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.

Stepwise Management of Severe Thoracogenic Scoliosis in Burned Child.

BACKGROUND: Skin and soft tissue retraction secondary to burns of the trunk may induce severe and progressive thoracogenic spinal deformities in children. Its management is rarely described. CASE DESCRIPTION: Our study reports a case of severe thoracic scoliosis in a 13-year-old adolescent, secondary to soft tissue retraction due to trunk burn in early childhood. The Cobb angle of the scoliosis was 100 degrees. The 3-stage surgical strategy consisted of scar excision and skin graft in the first stage, halo gravity traction in the second stage, and posterior correction and fusion of the spine in the third and final stage. The postoperative course was satisfactory, and late follow-up at 1 year showed stable correction of the spine, with satisfactory coronal and sagittal balance and good healing of skin and soft tissues. DISCUSSION: While spinal deformities secondary to burns are rare, they require specific, sequential, and multidisciplinary medical and surgical management. Our surgical strategy was to treat skin and soft tissues retractions first and then address spinal deformity. We used halo-gravity traction between the 2 surgical stages to help improve the spine deformity correction while reducing the risk of neurologic complications.

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.

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.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

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.

Pupillary reflex dilation in response to incremental nociceptive stimuli in patients receiving intravenous ketamine.

Pupillometry is a non-invasive monitoring technique, which allows dynamic pupillary diameter measurement by an infrared camera. Pupillary diameter increases in response to nociceptive stimuli. In patients anesthetized with propofol or volatile agents, the magnitude of this pupillary dilation is related to the intensity of the stimulus. Pupillary response to nociceptive stimuli has never been studied under ketamine anesthesia. Our objective was to describe pupillary reflex dilation after calibrated tetanic stimulations in patients receiving intravenous ketamine. After written consent, 24 patients of our pediatric burn care unit were included. They received an oral morphine premedication (0.3 mg kg-1) 1 h before their scheduled daily dressing change. Just before the procedure, they received 1 mg kg-1 of intravenous ketamine. Two minutes after this bolus, tetanic stimulations of incremental intensities were performed on the arm of each patient (5-10-20-30-40-60 mA, 60 s interval between stimulations). Pupillary diameter, heart rate and movements were recorded before and after each stimulation. Tetanic stimulations were associated with changes in pupillary diameter and heart rate. The magnitude of these changes was significantly influenced by the intensity of stimulation (ANOVA for repeated measures, p < 0.001). Movement was associated with a 32% increase in diameter (ROC curves, AUC 0.758) with 65% sensitivity and 77% specificity. In children, pupillary reflex dilation to nociceptive stimuli persists under deep sedation obtained with 1 mg kg-1 of intravenous ketamine combined with a 0.3 mg kg-1 oral morphine premedication, and its magnitude depends on the intensity of the stimulation. Our results confirm that pupillometry could be a relevant way to monitor nociception in anaesthetised subjects, including those receiving ketamine. Trial registration clinicaltrials.gov, NCT 02648412.