Nouvelles approches dans la prévention et le traitement du sepsis

Lipopolysaccharide’s (LPS) metabolism is complex, and it is still not used as a consistent biomarker or therapeutic target during sepsis. We used a novel LPS quantification method, able to detect lipoprotein-associated LPS in plasma, using 3-hydroxy myristate (3HM), a specific compound. We measured the 3HM levels in a cohort of patients admitted to intensive care and healthy volunteers. Septic patients had higher levels of 3HM, as did non-survivors of sepsis. Substantial levels of 3HM were also found in healthy subjects, suggesting that LPS is tightly integrated with human metabolism. Then, we demonstrated that the adsorption of LDL (low density lipoproteins) lipoproteins by LDL apheresis reduces the circulating levels of LPS, in vitro in the plasma of septic subjects, but also in vivo in hypercholesterolemic patients. Overall, these results provide important information for the understanding of endotoxemia, and open therapeutic perspectives for extracorporeal treatment during sepsis.Le lipopolysaccharide (LPS) a un métabolisme complexe, et n’a pas encore pu être utilisé efficacement comme biomarqueur ou cible thérapeutique au cours du sepsis. Nous avons utilisé une méthode de quantification du LPS par le 3-hydroxy myristate (3HM), un composé spécifique, qui permet de détecter le LPS associé aux lipoprotéines dans le plasma. Nous avons dosé les taux de 3HM dans une cohorte de patients admis en réanimation et chez des sujets volontaires sains. Les patients septiques avaient des taux plus élevés de 3HM, de même que les patients non-survivants au sepsis. Des taux substantiels de 3HM étaient aussi retrouvés chez les sujets sains, suggérant que le LPS est étroitement intégré au métabolisme humain. Ensuite, nous avons démontré que l’adsorption des lipoprotéines LDL (low density lipoproteins) par LDL aphérèse réduit les taux circulants de LPS, in vitro sur du plasma de sujets septiques, mais aussi in vivo chez des patients hypercholestérolémiques. Globalement, ces résultats apportent de informations importantes pour la compréhension de l’endotoxémie, et ouvrent des perspectives thérapeutiques d’épuration extracorporelle au cours du sepsis

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

LPS role during sepsis : description of circulating LPS levels using mass spectrometry in a cohort of critically ill patients, and investigation of LDL apheresis as an alternative for extracorporeal removal .

Le lipopolysaccharide (LPS) a un métabolisme complexe, et n’a pas encore pu être utilisé efficacement comme biomarqueur ou cible thérapeutique au cours du sepsis. Nous avons utilisé une méthode de quantification du LPS par le 3-hydroxy myristate (3HM), un composé spécifique, qui permet de détecter le LPS associé aux lipoprotéines dans le plasma. Nous avons dosé les taux de 3HM dans une cohorte de patients admis en réanimation et chez des sujets volontaires sains. Les patients septiques avaient des taux plus élevés de 3HM, de même que les patients non-survivants au sepsis. Des taux substantiels de 3HM étaient aussi retrouvés chez les sujets sains, suggérant que le LPS est étroitement intégré au métabolisme humain. Ensuite, nous avons démontré que l’adsorption des lipoprotéines LDL (low density lipoproteins) par LDL aphérèse réduit les taux circulants de LPS, in vitro sur du plasma de sujets septiques, mais aussi in vivo chez des patients hypercholestérolémiques. Globalement, ces résultats apportent de informations importantes pour la compréhension de l’endotoxémie, et ouvrent des perspectives thérapeutiques d’épuration extracorporelle au cours du sepsis.Lipopolysaccharide’s (LPS) metabolism is complex, and it is still not used as a consistent biomarker or therapeutic target during sepsis. We used a novel LPS quantification method, able to detect lipoprotein-associated LPS in plasma, using 3-hydroxy myristate (3HM), a specific compound. We measured the 3HM levels in a cohort of patients admitted to intensive care and healthy volunteers. Septic patients had higher levels of 3HM, as did non-survivors of sepsis. Substantial levels of 3HM were also found in healthy subjects, suggesting that LPS is tightly integrated with human metabolism. Then, we demonstrated that the adsorption of LDL (low density lipoproteins) lipoproteins by LDL apheresis reduces the circulating levels of LPS, in vitro in the plasma of septic subjects, but also in vivo in hypercholesterolemic patients. Overall, these results provide important information for the understanding of endotoxemia, and open therapeutic perspectives for extracorporeal treatment during sepsis

Rôle du PLPS au cours du sepsis : description des atux circulants de LPS par spectrométrie de masse au sein d'une cohorte de patients de réanimation, et perspectives d'épuration extracorporelle par LDL aphérèse

Lipopolysaccharide’s (LPS) metabolism is complex, and it is still not used as a consistent biomarker or therapeutic target during sepsis. We used a novel LPS quantification method, able to detect lipoprotein-associated LPS in plasma, using 3-hydroxy myristate (3HM), a specific compound. We measured the 3HM levels in a cohort of patients admitted to intensive care and healthy volunteers. Septic patients had higher levels of 3HM, as did non-survivors of sepsis. Substantial levels of 3HM were also found in healthy subjects, suggesting that LPS is tightly integrated with human metabolism. Then, we demonstrated that the adsorption of LDL (low density lipoproteins) lipoproteins by LDL apheresis reduces the circulating levels of LPS, in vitro in the plasma of septic subjects, but also in vivo in hypercholesterolemic patients. Overall, these results provide important information for the understanding of endotoxemia, and open therapeutic perspectives for extracorporeal treatment during sepsis.Le lipopolysaccharide (LPS) a un métabolisme complexe, et n’a pas encore pu être utilisé efficacement comme biomarqueur ou cible thérapeutique au cours du sepsis. Nous avons utilisé une méthode de quantification du LPS par le 3-hydroxy myristate (3HM), un composé spécifique, qui permet de détecter le LPS associé aux lipoprotéines dans le plasma. Nous avons dosé les taux de 3HM dans une cohorte de patients admis en réanimation et chez des sujets volontaires sains. Les patients septiques avaient des taux plus élevés de 3HM, de même que les patients non-survivants au sepsis. Des taux substantiels de 3HM étaient aussi retrouvés chez les sujets sains, suggérant que le LPS est étroitement intégré au métabolisme humain. Ensuite, nous avons démontré que l’adsorption des lipoprotéines LDL (low density lipoproteins) par LDL aphérèse réduit les taux circulants de LPS, in vitro sur du plasma de sujets septiques, mais aussi in vivo chez des patients hypercholestérolémiques. Globalement, ces résultats apportent de informations importantes pour la compréhension de l’endotoxémie, et ouvrent des perspectives thérapeutiques d’épuration extracorporelle au cours du sepsis

New-onset atrial fibrillation in ICU: A FROG in the throat

Lettre à l'éditeur ("International Journal of Cardiology" vol. 270, p. 189).https://www.sciencedirect.com/science/article/pii/S016752731833883X?via%3Dihu

How can we best organise communication with patients’ families?

IF 1.542 (2016)International audienc

Vasopressor Cumulative Dose Requirement and Risk of Early Death During Septic Shock

International audienceSeptic shock is the primary cause of death in intensive care units, with about 20% of patients dying in the first 3 days. To design future trials focused on early mortality, we require knowledge of early indicators that can detect patients at high risk of early death from refractory septic shock.The aim of this study was to assess whether the cumulative dose of vasopressors (CDV), calculated as the cumulative dose of epinephrine + norepinephrine, is a predictor of early death (within 72 hours) attributable to refractory septic shock (EDASS). This substudy of the EPISS trial was based on 370 patients admitted to a French ICU for septic shock between 2009 and 2011. The area under the receiving operating characteristic (ROC) curve was calculated for the CDV at 6, 12, 24, 36, and 48 hours after vasopressor initiation, and a strategy to predict the risk of EDASS was built based on selected times and thresholds.Among the 370 patients included, 51 (14%) died within the first 72 hours with 40 (11%) EDASS. A strategy in two steps (CDV ≥ 800 μg/kg at 6 hours and/or CDV ≥ 2600 μg/kg at 24 hours) was able to predict EDASS with sensitivity of 45%, specificity 97%, positive predictive value 78% and negative predictive value 94%. Overall, our results confirm that early death directly attributable to septic shock could be effectively predicted by the CDV in the first hours of treatment. These results will help to select patients eligible for innovative therapies aimed at improving early mortality in septic shock

Intensive care unit strain should not rush physicians into making inappropriate decisions, but merely reduce the time to the right decisions being made

International audienc

Intersecting vulnerabilities in professionals and patients in intensive care

International audienceIn the context of healthcare delivery, the vulnerabilities of patients in the intensive care unit (ICU) are intricately linked with those experienced on a daily basis by caregivers in the ICU in a symbiotic relation, whereby patients who are suffering can in turn engender suffering in the caregivers. In the same way, caregivers who are suffering themselves may be a source of suffering for their patients. The vulnerabilities of both patients and caregivers in the ICU are simultaneously constituted through a process that is influenced on the one hand by the healthcare objectives of the ICU, and on the other hand, by the conformity of the patients who are managed in that ICU. The specific challenges of management in high-technology units such as an ICU may have consequences on the practices and work conditions of healthcare professionals. Constructing the patient, collectively redefining the patient's identity, and ascribing the patient to a specific healthcare trajectory enables professionals to circumscribe, contain and fight against the spectrum of extreme vulnerabilities of their patients. Imposing this normative framework is the sole means of guiding these professionals through their daily practices. In spite of this, situations of suffering remain a constitutive feature of the caregiving relation in the ICU

What are the ethical issues in relation to the role of the family in intensive care?

International audienceA large proportion of patients admitted to the intensive care unit (ICU) are unable to express themselves, often due to acute illness, shock or trauma, and this precludes any communication and/or consent for care that might reflect their wishes and opinions. In such cases, the only solution for the ICU physician is to include the patient's family in the healthcare decisions. This can represent a significant burden on the family, on top of the psychological distress of the ICU environment and hospitalisation of their relatives, and many family members may suffer from anxiety, depression or symptoms of post-traumatic stress disorder (PTSD) during or after the hospitalisation and/or death of a loved one in the ICU. Good communication remains the cornerstone of family satisfaction in the ICU. Information imparted to the patient and/or family should cover diagnosis, prognosis and treatment. Information should be given orally, in person, using accessible language. Several other measures that can lessen the burden on the families of patients in the ICU and help to reduce anxiety and stress are also detailed in this review. Overall, family-centred care in the ICU requires a systematic communication strategy within the healthcare team, combined with an environment that is as amenable as possible to the family's presence and involvement, in order to maximize family satisfaction with ICU care, and ensure that the patient's values and preferences are respected