[Osmotic demyelination syndrome and overly rapid correction of hyponatremia]. / Syndrome de démyélinisation osmotique : quelle vitesse de correction de la natrémie ?

Hyponatremia is a frequent condition in hospitalized patients and is associated with significant morbidity and mortality. An association between rapid correction of hyponatremia and the occurrence of osmotic demyelination syndrome has been reported. Osmotic demyelination syndrome may present with severe neurologic symptoms, including in rare cases locked-in. Therefore, rapid correction of hyponatremia is recommended only in the presence of severe symptoms. In those cases, hypertonic saline (NaCl 3% 2 ml/Kg over 20 minutes) is recommended with close plasma sodium monitoring. After symptoms improvement, increases in sodium concentration should not exceed 8 mmol/l/24h. In cases without severe neurologic symptoms, the use of 3% NaCl solution should be avoided, and management should target the underlying causes of hyponatremia.

L'hyponatrémie est fréquente à l'hôpital avec une morbimortalité significative. Une association entre la vitesse de correction d'une hyponatrémie et la survenue d'un syndrome de démyélinisation osmotique (SDO) a été mise en évidence dans des études observationnelles. Dès lors, une correction rapide d'une hyponatrémie doit être réservée aux patients avec des symptômes sévères d'hyponatrémie. Dans ces situations, l'utilisation de NaCl 3 % (2 ml/kg) en bolus est recommandée avec des contrôles rapprochés de la natrémie. Après l'amélioration des symptômes, une vitesse de correction inférieure à 8 mmol/24 heures est indiquée. En l'absence de symptômes sévères, il est préférable d'éviter l'utilisation du NaCl 3 % et de traiter selon le mécanisme sous-jacent.

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study.

BACKGROUND: The use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored. METHODS: We conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models. RESULTS: Among 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively. CONCLUSION: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03558646.

Tryptophan catabolism in Pseudomonas aeruginosa and potential for inter-kingdom relationship.

BACKGROUND: Pseudomonas aeruginosa (Pa) is a Gram-negative bacteria frequently involved in healthcare-associated pneumonia with poor clinical outcome. To face the announced post-antibiotic era due to increasing resistance and lack of new antibiotics, new treatment strategies have to be developed. Immunomodulation of the host response involved in outcome could be an alternative therapeutic target in Pa-induced lung infection. Kynurenines are metabolites resulting from tryptophan catabolism and are known for their immunomodulatory properties. Pa catabolizes tryptophan through the kynurenine pathway. Interestingly, many host cells also possess the kynurenine pathway, whose metabolites are known to control immune system homeostasis. Thus, bacterial metabolites may interfere with the host's immune response. However, the kynurenine pathway in Pa, including functional enzymes, types and amounts of secreted metabolites remains poorly known. Using liquid chromatography coupled to mass spectrometry and different strains of Pa, we determined types and levels of metabolites produced by Pa ex vivo in growth medium, and the relevance of this production in vivo in a murine model of acute lung injury. RESULTS: Ex vivo, Pa secretes clinically relevant kynurenine levels (µM to mM). Pa also secretes kynurenic acid and 3-OH-kynurenine, suggesting that the bacteria possess both a functional kynurenine aminotransferase and kynurenine monooxygenase. The bacterial kynurenine pathway is the major pathway leading to anthranilate production both ex vivo and in vivo. In the absence of the anthranilate pathway, the kynurenine pathway leads to kynurenic acid production. CONCLUSION: Pa produces and secretes several metabolites of the kynurenine pathway. Here, we demonstrate the existence of new metabolic pathways leading to synthesis of bioactive molecules, kynurenic acid and 3-OH-kynurenine in Pa. The kynurenine pathway in Pa is critical to produce anthranilate, a crucial precursor of some Pa virulence factors. Metabolites (anthranilate, kynurenine, kynurenic acid) are produced at sustained levels both ex vivo and in vivo leading to a possible immunomodulatory interplay between bacteria and host. These data may imply that pulmonary infection with bacteria highly expressing the kynurenine pathway enzymes could influence the equilibrium of the host's tryptophan metabolic pathway, known to be involved in the immune response to infection. Further studies are needed to explore the effects of these metabolic changes on the pathophysiology of Pa infection.

Decreased CRRT Filter Lifespan in COVID-19 ICU Patients.

(1) Background: Increased thromboembolic events and an increased need for continuous renal replacement therapy (CRRT) have been frequently reported in COVID-19 patients. Our aim was to investigate CRRT filter lifespan in intensive care unit (ICU) COVID-19 patients. (2) Methods: We compared CRRT adjusted circuit lifespan in COVID-19 patients admitted for SARS-CoV-2 infection to a control group of patients admitted for septic shock of pulmonary origin other than COVID-19. Both groups underwent at least one session of CRRT for AKI. (3) Results: Twenty-six patients (13 in each group) were included. We analysed 117 CRRT circuits (80 in the COVID-19 group and 37 in the control group). The adjusted filter lifespan was shorter in the COVID-19 group (17 vs. 39 h, p < 0.001). This trend persisted after adjustment for confounding factors (-14 h, p = 0.037). Before CRRT circuit clotting, the COVID-19 group had a more procoagulant profile despite higher heparin infusion rates. Furthermore, we reported a decreased relation between activated partial thromboplastin time (aPTT) and cumulative heparin dose in COVID-19 patients when compared to historical data of 23,058 patients, suggesting a heparin resistance. (4) Conclusion: COVID-19 patients displayed a shorter CRRT filter lifespan that could be related to a procoagulant profile and heparin resistance.

COVID-19 is Associated with an Unusual Pattern of Brain Microbleeds in Critically Ill Patients.

BACKGROUND AND PURPOSE: Covid-19, initially described as a respiratory system's infection, is currently more and more recognized as a multiorganic disease, including neurological manifestations. There is growing evidence about a potential neuroinvasive role of SARS-CoV-2. The purpose of this study is to describe new findings, in the form of cerebral microbleeds affecting different brain structures, observed in MRIs of critically ill patients. METHODS: For this purpose, the MR images of 9 patients with a common pattern of abnormal findings (2 women/7 men; 55-79 years of age; mean age: 67.7 years) were depicted. All patients were tested positive for SARS-CoV-2 and presented with delayed recovery of consciousness or important agitation, requiring brain MRI. RESULTS: All patients had suffered from severe (5/9) or moderate (4/9) acute respiratory distress syndrome, requiring prolonged stay in the intensive care unit. Their common MRI finding was the presence of microbleeds in unusual distribution with a specific predilection for the corpus callosum. Other uncommon locations of microbleeds were the internal capsule (5/9), as well as middle cerebellar peduncles (5/9). Subcortical regions were also affected in the majority of patients. CONCLUSIONS: Brain MRI raised evidence that Covid-19 or its related treatment may involve the brain with an unusual pattern of microbleeds, predominantly affecting the corpus callosum. The mechanism of this finding is still unclear but the differential diagnosis should include thrombotic microangiopathy related to direct or indirect-through the cytokine cascade-damage by the SARS-CoV-2 on the endothelium of brain's vessels, as well as mechanisms similar to the hypoxemia brain-blood-barrier injury.