Leaky ryanodine receptors contribute to diaphragmatic weakness during mechanical ventilation

Ventilator-induced diaphragmatic dysfunction (VIDD) refers to the diaphragm muscle weakness that occurs following prolonged controlled mechanical ventilation (MV). The presence of VIDD impedes recovery from respiratory failure. However, the pathophysiological mechanisms accounting for VIDD are still not fully understood. Here, we show in human subjects and a mouse model of VIDD that MV is associated with rapid remodeling of the sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor (RyR1) in the diaphragm. The RyR1 macromolecular complex was oxidized, S-nitrosylated, Ser-2844 phosphorylated, and depleted of the stabilizing subunit calstabin1, following MV. These posttranslational modifications of RyR1 were mediated by both oxidative stress mediated by MV and stimulation of adrenergic signaling resulting from the anesthesia. We demonstrate in the murine model that such abnormal resting SR Ca2+ leak resulted in reduced contractile function and muscle fiber atrophy for longer duration of MV. Treatment with β-adrenergic antagonists or with S107, a small molecule drug that stabilizes the RyR1–calstabin1 interaction, prevented VIDD. Diaphragmatic dysfunction is common in MV patients and is a major cause of failure to wean patients from ventilator support. This study provides the first evidence to our knowledge of RyR1 alterations as a proximal mechanism underlying VIDD (i.e., loss of function, muscle atrophy) and identifies RyR1 as a potential target for therapeutic intervention

Impact des biomarqueurs de l'inflammation sur la définition du syndrome de détresse respiratoire aigu en réanimation

Le SDRA, répondant aux critères de la conférence américano-européenne de 1994, présente 2 morphologies pulmonaires bien distinctes : les formes focales et non-focales. La définition actuelle du SDRA semble regrouper une population hétérogène au sein d'un même syndrome. L'objectif de notre étude était de comparer ces 2 formes morphologiques avec les biomarqueurs plasmatiques spécifiques de l'agression pulmonaire du SDRA. Il s'agit d'une étude prospective, multicentrique observationnelle incluant les patients répondants aux critères actuels de SDRA. Un dosage plasmatique de sRAGE, PAI-1, sICMA-1 et SP-D ainsi qu'une imagerie pulmonaire étaient réalisés dans les 48h après le diagnostic de SDRA. Les SDRA étaient classés en forme focale (F) ou non-focale (NF). Le critère de jugement principal était la comparaison des concentrations plasmatiques des 4 biomarqueurs entre les 2 groupes : focale (F) et non-focale (NF). 112 patients ont pu être inclus de novembre 2010 à août 2011. 27% des patients présentaient une forme focale de SDRA et 73% une forme non-focale. Les concentrations plasmatiques de sRAGE et PAI-1 étaient plus basses dans le groupe F que dans le groupe NF. La courbe ROC de sRAGE permettait de prédire le caractère focal ou non-focal du SDRA pour un cutt-off de 1188pg/ml avec une Se de 94% et une Sp de 89%. Les concentrations plasmatiques de sICAM-1 et SP-D étaient comparables entre les 2 groupes. La mortalité à J28 et J90 était supérieure dans le groupe NF que dans le groupe F. Les formes focales présentent donc des lésions moins importantes des pneumocytes de type I et une perturbation moindre des voies de la fibrinolyse. Elles répondent probablement à une pathologie différente du SDRA tel qu'il est défini sur un plan physiopathologie. La réalisation de nouveaux essais cliniques sur une population plus homogène, focale ou non-focale, pourrait mettre en évidence des stratégies efficaces dans la prise en charge du SDRA, jusque là non-significatives.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

Brain Temperature: Physiology and Pathophysiology after Brain Injury

The regulation of brain temperature is largely dependent on the metabolic activity of brain tissue and remains complex. In intensive care clinical practice, the continuous monitoring of core temperature in patients with brain injury is currently highly recommended. After major brain injury, brain temperature is often higher than and can vary independently of systemic temperature. It has been shown that in cases of brain injury, the brain is extremely sensitive and vulnerable to small variations in temperature. The prevention of fever has been proposed as a therapeutic tool to limit neuronal injury. However, temperature control after traumatic brain injury, subarachnoid hemorrhage, or stroke can be challenging. Furthermore, fever may also have beneficial effects, especially in cases involving infections. While therapeutic hypothermia has shown beneficial effects in animal models, its use is still debated in clinical practice. This paper aims to describe the physiology and pathophysiology of changes in brain temperature after brain injury and to study the effects of controlling brain temperature after such injury

Letter: Hypnosis for Awake Surgery of Low-Grade Gliomas: Description of the Method and Psychological Assessment

International audienc

How to resume elective surgery in light of COVID-19 post-pandemic propofol shortage: The common concern of anaesthesists and surgeons

International audienc

Assessment of brain midline shift using sonography in neurosurgical ICU patients

Abstract Introduction Brain midline shift (MLS) is a life-threatening condition that requires urgent diagnosis and treatment. We aimed to validate bedside assessment of MLS with Transcranial Sonography (TCS) in neurosurgical ICU patients by comparing it to CT. Methods In this prospective single centre study, patients who underwent a head CT were included and a concomitant TCS performed. TCS MLS was determined by measuring the difference between the distance from skull to the third ventricle on both sides, using a 2 to 4 MHz probe through the temporal window. CT MLS was measured as the difference between the ideal midline and the septum pellucidum. A significant MLS was defined on head CT as >0.5 cm. Results A total of 52 neurosurgical ICU patients were included. The MLS (mean ± SD) was 0.32 ± 0.36 cm using TCS and 0.47 ± 0.67 cm using CT. The Pearson’s correlation coefficient (r2) between TCS and CT scan was 0.65 (P <0.001). The bias was 0.09 cm and the limits of agreements were 1.10 and -0.92 cm. The area under the ROC curve for detecting a significant MLS with TCS was 0.86 (95% CI =0.74 to 0.94), and, using 0.35 cm as a cut-off, the sensitivity was 84.2%, the specificity 84.8% and the positive likelihood ratio was 5.56. Conclusions This study suggests that TCS could detect MLS with reasonable accuracy in neurosurgical ICU patients and that it could serve as a bedside tool to facilitate early diagnosis and treatment for patients with a significant intracranial mass effect

Reversible Cerebral Vasoconstriction Syndrome with Intracranial Hypertension: Should Decompressive Craniectomy Be Considered

Background: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare cause of intracerebral hemorrhage (ICH) causing intracranial hypertension. Methods: Case report. Results: We report a case of RCVS-related ICH leading to refractory intracranial hypertension. A decompressive craniectomy was performed to control intracranial pressure. We discuss here the management of RCVS with intracranial hypertension. Decompressive craniectomy was preformed to avoid the risky option of high cerebral perfusion pressure management with the risk of bleeding, hemorrhagic complications, and high doses of norepinephrine. Neurological outcome was good. Conclusion: RCVS has a complex pathophysiology and can be very difficult to manage in cases of intracranial hypertension. Decompressive craniectomy should probably be considered