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Resume La fragilite est un syndrome multidimensionnel caracterise par une diminution des reserves fonctionnelles physiques, physiologiques et psychosociales qui augmente la vulnerabilite et diminue la resistance au stress. Dans la population generale, la prevalence de la fragilite augmente exponentiellement avec l’âge. A 65 ans, elle est

ICU patients with SARS-CoV-2-related pneumonia are at risk to develop a central dysautonomia which can contribute to mortality and respiratory failure. The pupillary size and its reactivity to light are controlled by the autonomic nervous system. Pupillometry parameters (PP) allow to predict outcomes in various acute brain injuries. We aim at assessing the most predictive PP of in-hospital mortality and the need for invasive mechanical ventilation (IV).We led a prospective, two centers, observational study. We recruited adult patients admitted to ICU for a severe SARS-CoV-2 related pneumonia between April and August 2020. The pupillometry was performed at admission including the measurement of baseline pupillary diameter (PD), PD variations (PDV), pupillary constriction velocity (PCV) and latency (PDL).Fifty patients, 90 % males, aged 66 (60-70) years were included. Seven (14 %) patients died in hospital. The baseline PD (4.1 mm [3.5; 4.8] vs 2.6 mm [2.4; 4.0], P = 0.009), PDV (33 % [27; 39] vs 25 % [15; 36], P = 0.03) and PCV (3.5 mm.sA reduced baseline PD is associated with bad outcomes in COVID-19 patients admitted in ICU. It is likely to reflect a brainstem autonomic dysfunction.

Purpose: To depict the specific brain networks that are modulated by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD), using diffusion tensor imaging-based ...

Introduction Mechanisms of postoperative sleep architecture disturbances and sleep-disordered breathing are uncertain. The authors hypothesised that patients undergoing surgery under regional anaesthesia without opioids used for postoperative analgesia would experience lesser changes in these parameters than patients operated under general anaesthesia with per- and postoperative opioids. Patients and methods After ethical approval and informed consent, patients undergoing total hip replacement were included in a prospective, randomised trial comparing 3 groups of patients: (1) S-LPB group receiving spinal anaesthesia and postoperative analgesia by lumbar plexus block; (2) GA-PCA group receiving general anaesthesia and postoperative analgesia by morphine patient-controlled analgesia; (3) GA-LPB group receiving general anaesthesia and postoperative analgesia by lumbar plexus block. Outcome measurements were polysomnographic parameters of sleep architecture and sleep-disordered breathing. Results Eighteen patients completed the 5-night study protocol (preoperative night: N-1, postoperative nights: N1 to N4). The percentage of rapid eye movement (REM) sleep decreased by 49% and 47% during N1 in the GA-PCA and GA-LPB groups respectively. A rebound phenomenon of more than 40% in the GA-PCA group and 25% in the GA-LPB group was observed during N2 and N3. Apnoea hypopnoea index (AHI) and the number of arousals per hour were significantly increased during N2 and N3 when compared with N-1 in the GA-groups. No sleep architecture disturbances and no sleep-disordered breathing were measured in the S-LPB group. Conclusion Postoperative sleep architecture and breathing pattern were disturbed in GA groups. Both were preserved under spinal anaesthesia associated with a free opioid postoperative analgesia.

BACKGROUND General anesthesia dramatically decreases the activity of the autonomic nervous system. Most of the hypnotic agents used to induce anesthesia inhibit sympathetic cardiovascular regulation and baroreflex control in a dose-dependent manner, lowering cardiac adaptability during the operation. The consequence of this effect in children during and after surgery has never been studied to date. AIM The aim of this study was to follow the variations in autonomic cardiac indices in children younger than 8 years old after general anesthesia (6-24 hours) in programmed surgery. METHOD A prospective descriptive monocentric study of 44 children under 8 years old who underwent scheduled surgery at our hospital center (Saint-Etienne University Hospital, France) was performed between June 1, 2016 and November 1, 2016. Heart rate variability was monitored for 24 hours using Holter-ECG devices and the resulting data were interpreted using linear and nonlinear analyses. RESULTS Compared to baseline thresholds before surgery, all heart rate variability indices decreased dramatically during general anesthesia. After awakening, a slight reduction in sympathetic activity persisted 6 hours after surgery, but all measurements of sympathetic and parasympathetic activity had returned to baseline thresholds 12 hours after the operation. Twenty-four hours after surgery, some parameters had increased above the corresponding baseline levels. CONCLUSION Autonomic nervous function normalizes rapidly (within 12 hours) in prepubertal children. This study indicates that general anesthesia does not seem to increase the long-term risk of autonomic dysfunction in these patients.

Background Potential methods for objective assessment of postoperative pain include the Analgesia Nociception Index™ (ANI), a real-time index of the parasympathetic tone, the pupillary light reflex (PLR), and the variation coefficient of pupillary diameter (VCPD), a measure of pupillary diameter (PD) fluctuations. Until now, the literature is divided as to their respective accuracy magnitudes for assessing a patient's pain. The VCPD has been demonstrated to strongly correlate with pain in an obstetrical population. However, the pain induced by obstetrical labour is different, given its intermittent nature, than the pain observed during the postoperative period. The aim of the current study was to compare the respective values of these variables at VAS scores ≥4. Methods After approval by the Ethics Committee, 345 patients aged on average 50 (SD 17) yr (range: 18–91 yr) of age were included. The protocols of general anaesthesia and postoperative analgesia were left to the anaesthetist's discretion. Some 40 min after tracheal intubation, VAS, ANI, PD, PLR, and VCPD values were recorded. Results VCPD correlates more strongly (r=0.78) with pain as assessed with the VAS than ANI (r=−0.15). PD and PLR are not statistically correlated with VAS. The ability of VCPD to assess the pain of patients (VAS≥4) is strong [area under the curve (AUC): 0.92, confidence interval (CI): 0.89–0.95], and better than for ANI (AUC: 0.39, CI: 0.33–0.45). Conclusions Our study suggests that VCPD could be a useful tool for monitoring pain in conscious patients during the postoperative period. Clinical trial registration NCT 03267979.

BACKGROUND: Potential methods for objective assessment of postoperative pain include the Analgesia Nociception Index™ (ANI), a real-time index of the parasympathetic tone, the pupillary light reflex (PLR), and the variation coefficient of pupillary diameter (VCPD), a measure of pupillary diameter (PD) fluctuations. Until now, the literature is divided as to their respective accuracy magnitudes for assessing a patient's pain. The VCPD has been demonstrated to strongly correlate with pain in an obstetrical population. However, the pain induced by obstetrical labour is different, given its intermittent nature, than the pain observed during the postoperative period. The aim of the current study was to compare the respective values of these variables at VAS scores ≥4. METHODS: After approval by the Ethics Committee, 345 patients aged on average 50 (SD 17) yr (range: 18–91 yr) of age were included. The protocols of general anaesthesia and postoperative analgesia were left to the anaesthetist's discretion. Some 40 min after tracheal intubation, VAS, ANI, PD, PLR, and VCPD values were recorded. RESULTS: VCPD correlates more strongly (r=0.78) with pain as assessed with the VAS than ANI (r=−0.15). PD and PLR are not statistically correlated with VAS. The ability of VCPD to assess the pain of patients (VAS≥4) is strong [area under the curve (AUC): 0.92, confidence interval (CI): 0.89–0.95], and better than for ANI (AUC: 0.39, CI: 0.33–0.45). CONCLUSIONS: Our study suggests that VCPD could be a useful tool for monitoring pain in conscious patients during the postoperative period. CLINICAL TRIAL REGISTRATION: NCT 03267979.

Pupillary diameter (PD) varies under the influence of the sympathetic as well as parasympathetic systems, increasing proportionally with pain intensity. Such variations however, should not be confused with pupillary fluctuations, which refer to the fast and permanent PD fluctuations induced by the ongoing interplay between the sympathetic and parasympathetic systems, which we propose to measure using the variation coefficient of PD (VCPD). This study aimed first at correlating PD, PD increase during a contraction, and VCPD, with pain rated using a numeric rating scale (NRS) during obstetrical labor, and then at comparing such correlations with each other. Forty patients were included in the study, and 160 simultaneous ratings (NRS, PD, and VCPD) were taken: 40 in the presence of uterine contractions and 40 in the absence of such contractions, before and 20 minutes after epidural analgesia. VCPD correlates more strongly (r = .77) than PD increase (r = .42) with pain rated using a NRS. The ability of VCPD to predict the occurrence of NRS scores ≥4 during obstetrical labor is .97 (confidence interval, .93–1.0). When measured over 10 seconds during contraction, VCPD correlates more strongly than PD increase with pain rated using the NRS. Such stronger correlation allows for an easy assessment of antinociception-nociception balance. Perspective The VCPD allows for an objective assessment of pain in laboring women. It could allow for an easy assessment of pain in noncommunicating patients: newborns or very old patients, patients with serious psychological conditions, assessment during the immediate postoperative period, or in intensive care units.

Background Postoperative analgesia after oropharyngeal carcinoma surgery remains poorly studied. This study investigates the effects of mandibular nerve block (MNB) with ropivacaine 10 mg ml−1 in conjunction with general anaesthesia (GA) on postoperative analgesia after partial glossectomy or transmandibular lateral pharyngectomy. Methods In a randomized double-blind study, 42 patients (21 in each group) received an MNB by the lateral extra-oral approach (MNB group) or a deep s.c. injection of normal saline (control group). Both groups received a standardized general anaesthetic. Postoperative analgesia included fixed dose of i.v. acetaminophen and morphine via a patient-controlled analgesia device. Consumption of morphine and supplemental analgesics and pain scores at rest were measured. Results The mean cumulative morphine consumption was reduced by 56 and 45% at 12 and 24 h after operation in the MNB group. The administration of analgesic rescue medications was delayed in the MNB group. The visual analogue scale (VAS) pain scores were comparable in the two groups during the first 24 h. Adequate analgesia (mean VAS ≤ 3) was observed throughout the study period in the MNB group, but only from 4 h after operation onwards in the control group. The number of patients who experienced severe pain (VAS > 7) during the first postoperative day was lower in the MNB group than in the control group (3 vs 10. respectively, P Conclusions In this study, MNB performed before GA for oropharyngeal carcinoma surgery improved postoperative analgesia, resulting in reduced morphine consumption at 24 h and severe pain in fewer patients.

International audience; Intracranial hemorrhage, whether due to traumatic brain injury or ruptured cerebral aneurysm, is characterized by major neurological damage and a high mortality rate. Apart from cerebral vasospasm and mass effect, brain injury results from the release of unclotted blood that contacts neurons causing calcic stress. The combination of memantine with vitamin D, a neurosteroid hormone, may prevent blood neurotoxicity. Our purpose was to examine the potential protective effects of memantine + vitamin D against lysed or clotted blood in cortical neuronal cultures. We provide the first evidence that cortical axons in contact with lysed blood degenerate less after exposure to lysed blood in microfluidic neuronal cultures enriched with both memantine and vitamin D compared to control medium and cultures enriched with only memantine or only vitamin D. The reported synergistic neuroprotective effect of memantine + vitamin D, the combination originating an effect stronger than the sum, strongly encourages using both drugs following intracranial hemorrhage.

Introduction Un travail recent a propose d’utiliser la stimulation de la conque auriculaire, innervee par la branche auriculaire du nerf vague, pour stimuler le noyau du tractus solitaire au niveau du tronc cerebral (centre parasympathique : pΣ), avec un effet comparable a celui de la stimulation directe du nerf vague au niveau cervical utilisee dans l’epilepsie refractaire [1] . Le but de notre etude est d’observer l’effet de la stimulation transcutanee du nerf vague au niveau de la conque auriculaire sur la douleur, evaluee par 3 parametres : – l’Echelle Visuelle Analogique (EVA) ; – la variabilite de la frequence cardiaque (VFC) par le biais de l’ANI ® (Metrodoloris, Lille), dont la valeur represente la fraction du pΣ, exprimee en pourcentage ; – la diminution du diametre pupillaire lors d’un flash lumineux de 320 Lux, appele reflexe photomoteur (RPM), medie par le pΣ. Nous avons utilise le videopupillometre AlgiScan ® (iDMed, Marseille). La Fig. 1 montre l’endroit de la stimulation. Materiel et methodes Apres accord du CPP et consentement, 21 patients ASA 1–2, âgees de 18 a 45 ans, ont ete inclus dans l’etude. La stimulation du nerf vague a ete realisee en salle de reveil, 1 heure apres l’extubation, au niveau de la conque de l’oreille gauche par 2 electrodes au contact de la peau, chez des patients douloureux en post-operatoire, avant administration d’antalgiques de recours. L’intensite a ete montee par pallier de 0,25 mA jusqu’a obtenir un picotement, sans atteindre le seuil douloureux, a la frequence de 25 Hz, puis diminuee de 0,25 mA pour se situer juste en dessous du seuil de sensibilite. Pour chaque sujet, un enregistrement de 10 minutes a ete realise en condition de stimulation, et un enregistrement de 10 minutes hors stimulation (placebo), de facon randomisee, a 10 minutes d’intervalle. 42 mesures simultanees de l’EVA, de l’ANI ® et du RPM ont ainsi ete realisees dans des conditions standardisees d’eclairage, œil controlateral ouvert : 21 avec et 21 sans stimulation. Resultats Le Tableau 1 presente les valeurs de l’EVA, de la FC, de l’ANI ® et du RPM, avec et sans stimulation de la conque auriculaire gauche. La stimulation transcutanee de la conque auriculaire diminue significativement l’EVA et la FC. Elle augmente l’ANI ® et l’amplitude du RPM, temoignant de l’activation du pΣ. Discussion La stimulation transcutanee de la conque auriculaire gauche pendant 10 minutes diminue la douleur post-operatoire en salle de reveil, evaluee par l’EVA, par la VFC et par le RPM. Ce resultat ouvre des perspectives de traitement de la douleur par stimulation transcutanee, qui devront etre confirmees par des travaux ulterieurs.

Introduction Le diametre pupillaire (DP) varie sous la double influence des systemes sympathique (Σ), dilatateur de la pupille, et parasympathique (pΣ), irido-constricteur. Il diminue en reponse a un flash lumineux de maniere reflexe, appele reflexe photomoteur (RPM), medie par le pΣ. Si l’on exerce un stimulus douloureux, la diminution reflexe du DP induite par la lumiere est inhibee pendant la stimulation nociceptive, et cet effet est bloque par les morphiniques [1] . L’abolition du RPM pourrait ainsi constituer une mesure objective de l’efficacite de l’analgesie chez les patients non communicants. Il existe d’autre part des fluctuations permanentes du DP, dues aux interactions constantes entre les systemes Σ et pΣ. Nous avons automatise la mesure de cette variabilite du DP (VDP) en integrant un algorithme de calcul dans le videopupillometre AlgiScan ® (iDMed, Marseille). Nous proposons d’etudier l’interet de cette mesure pour evaluer la douleur chez des patients conscients, et en particulier pour discriminer les patients les plus douloureux (EVA ≥ 5). Materiel et methodes Apres accord du Comite d’ethique et information, 166 patients âges de 18 a 90 ans ont ete enregistres en salle de reveil, en postoperatoire de chirurgies cardiovasculaire, maxillo-faciale, gynecologique, ORL, ortho-traumatologique, urologique ou de neurochirurgie. Le protocole anesthesique etait laisse libre, de meme que l’analgesie postoperatoire. Nous avons etudie la VDP sur 10 secondes, puis la diminution du DP lors d’un flash lumineux de 320 Lux (RPM). Nous avons recherche ensuite la correlation entre ces deux parametres et la douleur evaluee a l’aide de l’Echelle Visuelle Analogique (EVA). La Fig. 1 presente le synoptique de l’etude. Resultats Le Fig. 2 presente l’EVA, la frequence cardiaque (FV), le DP de base, le RPM lors d’un flash lumineux de 320 Lux, et la VDP de base (en dehors de toute stimulation lumineuse) chez les patients presentant une EVA r = 0,18 ; p = 0,018). La VDP de base presente par contre une relativement bonne correlation avec l’EVA ( r = 0,45 ; p p 6,4 % (cut-off de Youden) est correlee a une EVA ≥ 5 (valeur predictive (VP) positive = 0,90 ; VP negative = 0,60 ; sensibilite = 0,82 ; specificite = 0,75) : Fig. 3 . Discussion Le calcul automatise sur 10 secondes de la VDP en dehors de toute stimulation est plus fortement correlee a la douleur evaluee a l’aide de l’echelle EVA que le RPM. La VDP est en outre independante des conditions de realisation de la mesure (conditions d’eclairage, occlusion ou non de l’œil controlateral). Ce parametre, utilisable au lit du patient, pourrait permettre une evaluation simple de la douleur chez des patients conscients.

Introduction Le stress en situation d’urgence peut generer des conduites inappropriees, voire dangereuses. Son evaluation pourrait aboutir a limiter la prise de decision par la personne qui y est soumise. Le Bilan Flash Psychologique (BFP) est un dispositif d’auto-evaluation qui permet a l’aide de 3 reglettes type « Echelle visuelle analogique » d’evaluer le niveau de stress, d’epuisement moral et d’epuisement physique, cotes a l’aide d’un curseur, entre 0 et 10. Le score BFP est obtenu en faisant la somme des 3 composantes, un BFP entre 11 et 18 necessitant une prise en charge psychologique differee, un BFP entre 19 et 30 une prise en charge immediate [1] . Le diametre pupillaire (DP) varie sous la double influence des systemes sympathique (Σ), dilatateur de la pupille, et parasympathique (pΣ), irido-constricteur. Il diminue en reponse a un flash lumineux de maniere reflexe, appele reflexe photomoteur (RPM), medie par le pΣ. Si l’on soumet l’organisme a un stress, l’amplitude du RPM est diminuee [2] . Cette diminution du RPM pourrait constituer une mesure objective du stress. Nous avons utilise dans ce travail le video pupillometre AlgiScan® (iDMed, Marseille) pour evaluer l’interet de la mesure pupillaire pour evaluer le stress physique et psychique de sapeurs-pompiers en intervention, par comparaison avec le score BFP. Materiel et methodes Vingt-sept sapeurs-pompiers professionnels du SDIS 42 participant a une manœuvre sauvetage-deblaiement de 6 heures se sont portes volontaires pour cette etude. Une evaluation du BFP et un enregistrement de la variation du DP lors d’un flash lumineux de 320 Lux ont eu lieu avant (« avant ») et a la fin de la manœuvre (« apres »). La Fig. 1 presente le synoptique de l’etude. Resultats Le Tableau 1 presente les 3 composantes du score BFP et leur somme, ainsi que l’amplitude du RPM, avant et a la fin de la manœuvre. Le score BFP global augmente entre le debut et la fin de la manœuvre (p 11 ou 19 (cut-off de Youden). Discussion Une mesure ponctuelle sur 10 secondes du RPM realisee a l’aide d’un video pupillometre sur le terrain est correlee au niveau de stress physique et psychique de sapeurs-pompiers lors d’un exercice sauvetage-deblaiement de 6 heures. Ce travail ouvre la voie au monitorage en continu de la pupille qui pourrait permettre un suivi en temps reel sur le terrain du niveau de stress physique et psychique de sapeurs-pompiers en intervention ou de medecins de garde exposes a des situations anxiogenes ou d’epuisement.

International audience

There is mounting evidence showing the value of low-dose corticosteroids in patients with septic shock requiring vasopressor therapy. It remains unclear whether adrenal function tests should be carried out systematically to guide the decision on glucocorticoid therapy.The retrospective study was conducted in 52 patients in three university hospital ICUs. We included consecutive patients with catecholamine-dependent septic shock who had not received ketoconazole, glucocorticoids, or etomidate in the 24 h before the ACTH test, and who had survived to day 3 after the shock onset. All patients had a 250-microg ACTH test before systematic glucocorticoid therapy was started. Various definitions of relative adrenal insufficiency were used (based on cortisol basal level and/or change in cortisol level after ACTH stimulation). We defined hemodynamic improvement as a 50% reduction in the vasoactive agent dose in the 3 days following the initiation of glucocorticoid treatment. The relationship between the hemodynamic improvement and the results of the adrenal function tests was analyzed.Hemodynamic improvement occurred in 29 patients (55.8%). Baseline characteristics, sites of infection, types of micro-organisms and antibiotic management did not differ between patients with and those without hemodynamic improvement. Relative adrenal insufficiency whatever the definition was not associated with hemodynamic improvement.In catecholamine-dependent septic shock patients managed with systematic glucocorticoid therapy the results of ACTH stimulation do not predict hemodynamic improvement.