Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Non-invasive monitoring of nociception under general anesthesia by pupillometry

Le monitorage de la nociception est l'un des défis actuels en anesthésie. L'objectif final du développement de ce monitorage est d'administrer pour chaque patient, à chaque étape de la chirurgie, la juste dose d'analgésiques. En pratique clinique habituelle, les anesthésistes diagnostiquent la nociception par la survenue de mouvements, l'augmentation de la fréquence cardiaque ou de la pression artérielle. Mais ces paramètres ne sont ni précoces, ni sensibles, ni spécifiques. Plusieurs moniteurs ont été développés ces dernières années dans l'optique d'améliorer l'évaluation de la nociception. La stimulation nociceptive induit une augmentation du diamètre pupillaire : ce phénomène est appelé Réflexe de Dilatation Pupillaire (RDP) à la douleur chez le sujet éveillé, RDP à la nociception chez le sujet inconscient. La pupillométrie est basée sur la mesure des variations du diamètre pupillaire. Le pupillomètre est constitué d'une caméra infra-rouge qui reconnaît l'orifice pupillaire, suit ses mouvements, et mesure son diamètre instantané. Ce dispositif est non-invasif : aucun élément du pupillomètre n'est en contact avec l'oeil du patient. Notre démarche de recherche s'inscrit dans le processus d'étude de la pupillométrie comme outil de monitorage de la nociception per-opératoire. Dans une première partie, nous détaillons les circuits physiologiques qui construisent le rationnel de l'utilisation de la pupillométrie dans cette indication. Nous évoquons successivement l'innervation autonome pupillaire, les circuits ascendants de la nociception, les circuits descendants anti-nociceptifs, les sites et mécanismes d'action des morphiniques, ainsi que le retentissement de l'anesthésie sur l'ensemble de ces réseaux. Nous présentons enfin les données relatives à la pupillométrie sous anesthésie déjà connues au début de ce travail. Puis nous proposons une série de trois publications originales : Tout d'abord, nous avons complété la validation de la pupillométrie en tant que monitorage quantitatif de la nociception sous anesthésie. Il était déjà démontré que la dilatation pupillaire était inversement corrélée à la quantité d'opioïdes administrés avant une stimulation standardisée. Pour compléter ces résultats, nous avons démontré que cette dilatation pupillaire était également positivement corrélée à l'intensité de la stimulation nociceptive pour une même dose d'opioïdes administrés. Ainsi, la dilatation pupillaire est un paramètre dont l'importance est liée à l'intensité de l'activation des circuits nociceptifs. Dans une deuxième étude, nous avons mis en évidence les bénéfices cliniques associés au monitorage pupillométrique per-opératoire pour le patient. Nous avons montré que le guidage pupillométrique peropératoire du rémifentanil était associé à une moindre consommation de morphiniques per et post-opératoires, pour une efficacité analgésique équivalente. Nos résultats suggèrent également une possible diminution associée de l'incidence des douleurs chroniques post-opératoires. Enfin, nous avons réalisé la première étape de validation d'un nouvel outil pupillométrique, le Pupillary Pain Index, qui propose une approche innovante basée sur l'anticipation de la réaction nociceptive, et non sur son diagnostic a-posteriori. Nous avons montré qu'en diminuant la réactivité du patient à la nociception au moyen de morphiniques, l'index PPI, supposé représenter la réactivité du patient, diminuait également. En adaptant l'analgésie sur la réaction « prévisible », il deviendrait possible d'éviter plutôt que de corriger l'inadéquation entre l'analgésie et la stimulation nociceptive. Pour conclure, nous discutons l'ensemble de ces résultats, les perspectives de recherche à venir, la place de la pupillométrie au sein de l'ensemble des moniteurs de nociception, son implémentation pratique dans les blocs opératoires, et les questions d'ordre général soulevées par le développement de ce type de technologies dans notre spécialité.The monitoring of nociception is one of the current challenges in anesthesiology. The final goal of these techniques is to provide for each patient, at each stage of the surgical procedure, the adequate dosage of analgesics. Anesthesiologists traditionally assess nociception based on heart rate or blood pressure variations. But these parameters are neither specific nor sensitive. Several monitors have been developed in the last decade to improve the assessment of nociception. Nociceptive stimulation results in an increase in pupillary diameter: this phenomenon is called 'Pupillary Reflex Dilation' (PRD). Pupillometry is based on the measurement of pupillary diameter variations. The device is equipped with an infrared camera that recognizes, tracks and measures the pupil. This technique is non-invasive: no part of the device ever touches the eye of the patient. Our research process is centered on the use of pupillometry as a monitor of intraoperative nociception. As an introduction, we describe the physiological pathways involved in pupillary diameter regulation, nociception, anti-nociception; we detail the mechanisms of action of opioids and explain how anesthesia influences these processes. We also present the data about PRD under general anesthesia that were already available at the beginning of our project. Then, we present three original publications: The first study contributes to the validation of pupillometry as a quantitative tool to assess nociception under anesthesia. We have demonstrated that pupillary dilation was positively correlated with the intensity of a nociceptive stimulation for a standardized analgesia. Thus, the amplitude of pupillary dilation depends on the degree of activation of the nociceptive pathways. In the second study, we have evidenced clinical benefits for the patients, associated with the intraoperative monitoring of nociception by pupillometry. In this randomized controlled trial, intra- and postoperative opioid consumption were decreased when pupillometry was used to adjust intraoperative remifentanil, compared to standard care. Postoperative analgesia was similar in both groups. In addition, our results suggested that pupillometry might also decrease the incidence of chronic pain. Finally, we achieved the first step of the validation process of a new pupillometric tool, the Pupillary Pain Index (PPI). The PPI is an innovative approach to nociception monitoring, based on the anticipation of the nociceptive reaction, and not on its a-posteriori correction. The PPI is supposed to assess the probability of a clinical reaction to nociception. We have demonstrated that when we decreased the patient's expected reactivity to nociception by a bolus of opioid, the PPI decreased as well. If we could adjust analgesia on the 'predicted' reactivity of the patient, we would be able to avoid rather than correct a possible inadequacy between analgesia and nociceptive stimuli. To conclude, we discuss all these results, future research perspectives, the status of pupillometry among the other nociception monitors, its practical implementation in operating theatres, and the general issues raised by the development of these technologies in our specialty

Clinical sedation and bispectral index in burn children receiving gamma-hydroxybutyrate.

Background:  Gamma-hydroxybutyrate (GHB) may be an interesting hypnotic agent in burn patients because of its good respiratory or hemodynamic tolerance. However, its clinical and electroencephalographic (EEG) sedative effects are not yet described in children. The aim of this prospective and randomized study was to assess clinical and EEG effects of increasing intravenous (IV) doses of GHB in burn children requiring sedation for burn wound cares. Methods:  Thirty six children hospitalized in a burn care unit were included and randomly assigned into three groups (G) according to the single IV dose of GHB they received before burn wound care: 10 mg·kg(-1) in G10, 25 mg·kg(-1) in G25, or 50 mg·kg(-1) in G50. All patients received oral premedication (morphine and hydroxyzine) 30 min before GHB injection. Respiratory rate, heart rate, pulse oximetry, and bispectral index (BIS) were continuously monitored. Depth of sedation was clinically assessed using Observer's Assessment of Alertness and Sedation (OAAS) Score, every 2 min until recovery (i.e., OAAS = 4). Results:  Median age was 17.5 [12-34] months. Whatever the dose, BIS decreased after IV GHB. Nadir value of BIS was significantly lower in G25 and G50 than in G10, as was for OAAS score. Nadir values were reached after same delays in G25 and G50. Duration of sedation was dose-dependant. Conclusion:  Bispectral index decreased after GHB injection and was correlated with OAAS score. Deep sedation can be safely achieved with IV doses of 25 or 50 mg·kg(-1) , but the last dose was associated with prolonged duration of clinical sedation

Unexpected benefits of the COVID challenge: When critically ill adult patients are managed in a pediatric PACU

International audienc

Epidemiology and incidence of severe respiratory critical events in ear, nose and throat surgery in children in Europe

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

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

International audienceBACKGROUND : 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

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

International audienceThe 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