Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK—a randomized controlled trial

Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate‐targeted resuscitation is the gold‐standard under current guidelines, although it has several pitfalls including that non‐hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion‐targeted resuscitation might provide a real‐time response to increases in ow that could lead to a more timely decision to stop resuscitation, thus avoiding uid overload and the risks of over‐resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA‐SHOCK Study. Methods: ANDROMEDA‐SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion‐ targeted resuscitation is associated with lower 28‐day mortality compared to a lactate‐targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8‐hour study period pursuing normalization of capillary re ll time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with uid responsiveness assessment and uid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28‐day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the rst 28 days after randomization; multiple organ dysfunction during the rst 72 h after randomization; intensive care unit and hospital lengths of stay; and all‐cause mortality at 90‐day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two‐tailed type I error of 5%. All analysis will follow the intention‐to‐treat principle. Conclusions: If peripheral perfusion‐targeted resuscitation improves 28‐day mortality, this could lead to simpli ed algorithms, assessing almost in real‐time the reperfusion process, and pursuing more physiologically sound objec‐ tives. At the end, it might prevent the risk of over‐resuscitation and lead to a better utilization of intensive care unit resources

Ann Intensive Care

Unlike for septic shock, there are no specific international recommendations regarding the management of cardiogenic shock (CS) in critically ill patients. We present herein recommendations for the management of cardiogenic shock in adults, developed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF)), with the participation the French Society of Anesthesia and Intensive Care (SFAR), the French Cardiology Society (SFC), the French Emergency Medicine Society (SFMU), and the French Society of Thoracic and Cardiovascular Surgery (SFCTCV). The recommendations cover 15 fields of application such as: epidemiology, myocardial infarction, monitoring, vasoactive drugs, prehospital care, cardiac arrest, mechanical assistance, general treatments, cardiac surgery, poisoning, cardiogenic shock complicating end-stage cardiac failure, post-shock treatment, various etiologies, and medical care pathway. The experts highlight the fact that CS is a rare disease, the management of which requires a multidisciplinary technical platform as well as specialized and experienced medical teams. In particular, each expert center must be able to provide, at the same site, skills in a variety of disciplines, including medical and interventional cardiology, anesthesia, thoracic and vascular surgery, intensive care, cardiac assistance, radiology including for interventional vascular procedures, and a circulatory support mobile unit

Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis

BACKGROUND: Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS: A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS: Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION: A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes

Daisy-like crystals: Not just the result of sampling artifact and not only in urine.

peer reviewe

Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock The ANDROMEDA-SHOCK Randomized Clinical Trial

Importance Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. Objective To determine if a peripheral perfusion–targeted resuscitation during early septic shock in adults is more effective than a lactate level–targeted resuscitation for reducing mortality. Design, Setting, and Participants Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. Interventions Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. Main Outcomes and Measures The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation–, renal replacement therapy–, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. Results Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, −8.5% [95% CI, −18.2% to 1.2%]). Peripheral perfusion–targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, −1.00 [95% CI, −1.97 to −0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. Conclusions and Relevance Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality

Detection of activities of daily living impairment in Alzheimer's disease and mild cognitive impairment using information and communication technology

International audienceBackground: One of the key clinical features of Alzheimer's disease (AD) is impairment in daily functioning. Patients with mild cognitive impairment (MCI) also commonly have mild problems performing complex tasks. Information and communication technology (ICT), particularly techniques involving imaging and video processing, is of interest in order to improve assessment. The overall aim of this study is to demonstrate that it is possible using a video monitoring system to obtain a quantifiable assessment of instrumental activities of daily living (IADLs) in AD and in MCI. Methods: The aim of the study is to propose a daily activity scenario (DAS) score that detects functional impairment using ICTs in AD and MCI compared with normal control group (NC). Sixty-four participants over 65 years old were included: 16 AD matched with 10 NC for protocol 1 (P1) and 19 MCI matched with 19 NC for protocol 2 (P2). Each participant was asked to undertake a set of daily tasks in the setting of a "smart home" equipped with two video cameras and everyday objects for use in activities of daily living (8 IADLs for P1 and 11 for P2, plus 4 temporal execution constraints). The DAS score was then computed from quantitative and qualitative parameters collected from video recordings. Results: In P1, the DAS score differentiated AD (DASAD,P1 = 0.47, 95% confidence interval [CI] 0.38-0.56) from NC (DASNC,P1 = 0.71, 95% CI 0.68-0.74). In P2, the DAS score differentiated MCI (DASMCI,P2 = 0.11, 95% CI 0.05-0.16) and NC (DASNC,P2 = 0.36, 95% CI 0.26-0.45). Conclusion: In conclusion, this study outlines the interest of a novel tool coming from the ICT world for the assessment of functional impairment in AD and MCI. The derived DAS scores provide a pragmatic, ecological, objective measurement which may improve the prediction of future dementia, be used as an outcome measurement in clinical trials and lead to earlier therapeutic intervention

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock : The ANDROMEDA-SHOCK Randomized Clinical Trial

IMPORTANCE: Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. OBJECTIVE: To determine if a peripheral perfusion–targeted resuscitation during early septic shock in adults is more effective than a lactate level–targeted resuscitation for reducing mortality. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. INTERVENTIONS: Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation–, renal replacement therapy–, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. RESULTS: Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, −8.5% [95% CI, −18.2% to 1.2%]). Peripheral perfusion–targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, −1.00 [95% CI, −1.97 to −0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. CONCLUSIONS AND RELEVANCE: Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality.Facultad de Ciencias Médica

Sédimentogénèse et diagénèse des carbonates continentaux du Crétacé inférieur (présel) de la marge ouest africaine : modélisation et analogies

Les découvertes d’hydrocarbures dans les séries carbonatées très enfouies présel du Crétacé inférieur des marges brésiliennes ont relancé l’exploration dans la marge conjuguée ouest-africaine. Ces carbonates continentaux contiennent des faciès atypiques (ex. : boundstone à shrubs, grainstone à sphérulites), diversement interprétés comme hydrothermaux et/ou lacustres. Comprendre leur diagenèse et leur distribution est un enjeu crucial pour l’exploration. En tant que contribution à cet objectif, ce travail établit des liens entre la géochimie des carbonates continentaux et leur substratum. L’association de différents critères géochimiques permet de tracer l’origine lithologique des éléments chimiques incorporés dans les travertins et tufs aragonitiques et calcitiques (CATT). Le δ18O et le δ13C sont discriminants pour des CATT issus de roches ultramafiques. Les teneurs en Ba, Sr, Cr et Be permettent d’identifier les contributions volcaniques à granitiques. Des modèles numériques démontrent l’influence de la T°C et pCO2 sur l’altération d’un exemple de substrat enfoui. Cette altération produit des fluides aux pH alcalins à neutres, riches en Fe, HCO3+CO3 et en alcalins. Les concentrations en Ca, Mg, et Si, varient en fonction de la température. De tels apports peuvent favoriser des cimentations carbonatées à siliceuses. L’étude de l’habitus de tels ciments précoces de microquartz fibreux suggère une précipitation à partir (1) de fluides alcalins très évaporés, sous probable influence mantellique ou (2) de fluide neutres à acides, non à peu évaporés, sous possible influence felsique. L’ensemble des résultats démontre l’hétérogénéité spatiotemporelle des fluides diagénétiques.The discoveries offshore Brazil of deeply buried oil-prone Early Cretaceous carbonate reservoirs revitalized the exploration of their coeval counterparts offshore West Africa. These continental carbonates exhibit atypical facies (e.g. shrubby boundstone, spherulitic grainstone), which are interpreted as lacustrine and/or hydrothermal. A predictive understanding of the distribution and diagenesis of these deposits is required for exploration. As part of this long-term project, the present thesis shows the link between the geochemical signature of continental carbonates and their substratum. The use of several geochemical tracers allows the characterization of the source of elements of calcitic and aragonitic travertine and tufa (CATT). δ18O and δ13C values are particularly discriminant when CATT originate from ultramafic rocks, whereas Ba, Sr, Cr and Be concentrations can be used to identify a contribution from volcanic rocks and granites. Numerical models show the influence of T°C and pCO2 on the alteration of an example of buried substrate. This alteration produces mid-alkaline to near-neutral pH, with high Fe, HCO3+CO3, and alkali concentrations. Ca, Mg, and Si concentrations are temperature dependant. Such input can lead to carbonate and silica cementations. The study of the habitus of such early silica cements, characterized as fibrous microquartz suggest a precipitation from (1) alkaline, highly evaporated fluids, under a mantellic influence and (2) neutral to acid, moderately to non-evaporated fluids, under the influence of felsic rocks. These conclusions highlight the heterogeneity in space and time of the diagenetic fluids influencing the presalt carbonates

EVALUATION DE LA REACTIVATION VIRALE CHEZ LES PATIENTS DE REANIMATION MEDICO-CHIRURGICALE

AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF