Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.

Left ventricular global longitudinal strain and acute myocardial injury in patients with sickle cell disease admitted to the intensive care unit for vaso-occlusive crisis.

In patients with sickle cell disease (SCD), SCD-related cardiomyopathy may be partly due to repeated ischaemic events related to sickling during vaso-occlusive crises, but few clinical studies support this hypothesis. We evaluated the incidence of acute myocardial ischaemia during vaso-occlusive crises as assessed by the left ventricular global longitudinal strain (LVGLS) and high-sensitive cardiac troponin T (hs-cTnT). We included adult patients with SCD admitted to the intensive care unit (ICU) for vaso-occlusive crisis. We collected hs-cTnT and measured LVGLS with echocardiography at admission (day 1), day 2, day 3 and ICU discharge. Among 55 patients included, considering only the first hospitalization of patients admitted several times, 3 (5%) had elevated hs-cTnT at ≥1 time point of the ICU stay. It was ≤2 times the upper limit of normal in two of these patients. LVGLS was altered at ≥1 time point of the ICU stay in 13 (24%) patients. Both hs-cTnT and LVGLS were abnormal at ≥1 time point of the hospital stay in 2 (4%) patients. Acute myocardial injury as assessed by troponin elevation and LVGLS impairment was a rare event during vaso-occlusive crises.

A predictive mortality score in ANCA-associated renal vasculitis.

BACKGROUND: Several scores have been developed to predict mortality at ANCA-Associated Vasculitis (AAV) diagnosis. Their prognostic value in Caucasian patients with kidney involvement (AAV-GN) remains uncertain as none have been developed in this specific population. We aimed to propose a novel and more accurate score specific for them. METHODS: This multicentric study included patients diagnosed with AAV-GN since January 2000 in 4 nephrology Centers (recorded in the Maine-Anjou AAV-GN Registry). Existing scores and baseline characteristics were assessed at diagnosis before any therapeutic intervention. A multivariable analysis was performed to build a new predictive score for death. Its prognosis performance (AUROC and C-index) and accuracy (Brier score) was compared to existing scores. 185 patients with AAV-GN from the RENVAS registry were used as a validation cohort. RESULTS: 228 patients with AAV-GN from the Maine-Anjou registry were included to build the new score. It included the 4 components most associated with death: age, history of hypertension or cardiac disease, creatinine, and hemoglobin levels at diagnosis. 194 patients had all the data available to determine the performance of the new score and existing scores. The new score performed better than the previous ones in the development and in the validation cohort. Among the scores tested, only FFS (Five-Factor Score) and JVAS (Japanese Vasculitis Activity Score) had good performance in predicting death in AAV-GN. CONCLUSIONS: This original score, named DANGER (Death in ANCA Glomerulonephritis -Estimating the Risk), may be useful to predict the risk of death in AAV-GN patients. Validation in different populations is needed to clarify its role in assisting clinical decisions.

Bedside personalized methods based on electrical impedance tomography or respiratory mechanics to set PEEP in ARDS and recruitment-to-inflation ratio: a physiologic study.

BACKGROUND: Various Positive End-Expiratory Pressure (PEEP) titration strategies have been proposed to optimize ventilation in patients with acute respiratory distress syndrome (ARDS). We aimed to compare PEEP titration strategies based on electrical impedance tomography (EIT) to methods derived from respiratory system mechanics with or without esophageal pressure measurements, in terms of PEEP levels and association with recruitability. METHODS: Nineteen patients with ARDS were enrolled. Recruitability was assessed by the estimated Recruitment-to-Inflation ratio (R/Iest) between PEEP 15 and 5 cmH2O. Then, a decremental PEEP trial from PEEP 20 to 5 cmH2O was performed. PEEP levels determined by the following strategies were studied: (1) plateau pressure 28-30 cmH2O (Express), (2) minimal positive expiratory transpulmonary pressure (Positive PLe), (3) center of ventilation closest to 0.5 (CoV) and (4) intersection of the EIT-based overdistension and lung collapse curves (Crossing Point). In addition, the PEEP levels determined by the Crossing Point strategy were assessed using different PEEP ranges during the decremental PEEP trial. RESULTS: Express and CoV strategies led to higher PEEP levels than the Positive PLe and Crossing Point ones (17 [14-17], 20 [17-20], 8 [5-11], 10 [8-11] respectively, p < 0.001). For each strategy, there was no significant association between the optimal PEEP level and R/Iest (Crossing Point: r2 = 0.073, p = 0.263; CoV: r2 < 0.001, p = 0.941; Express: r2 < 0.001, p = 0.920; Positive PLe: r2 = 0.037, p = 0.461). The PEEP level obtained with the Crossing Point strategy was impacted by the PEEP range used during the decremental PEEP trial. CONCLUSIONS: CoV and Express strategies led to higher PEEP levels than the Crossing Point and Positive PLe strategies. Optimal PEEP levels proposed by these four methods were not associated with recruitability. Recruitability should be specifically assessed in ARDS patients to optimize PEEP titration.

Adding 6-month parameters for the prediction of kidney prognosis in ANCA-associated glomerulonephritis.

Background: Antineutrophil-cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with kidney involvement (AAV-GN) frequently evolves to end-stage kidney disease (ESKD) despite aggressive immunosuppressive treatment. Several risk scores have been used to assess renal prognosis. We aimed to determine whether kidney function and markers of AAV-GN activity after 6 months could improve the prediction of ESKD. Methods: This retrospective and observational study included adult patients with AAV-GN recruited from six French nephrology centers (including from the Maine-Anjou AAV registry). The primary outcome was kidney survival. Analyses were conducted in the whole population and in a sub-population that did not develop ESKD early in the course of the disease. Results: When considering the 102 patients with all data available at diagnosis, Berden classification and Renal Risk Score (RRS) were not found to be better than kidney function [estimated glomerular filtration rate (eGFR)] alone at predicting ESKD (C-index = 0.70, 0.79, 0.82, respectively). Multivariables models did not indicate an improved prognostic value when compared with eGFR alone.When considering the 93 patients with all data available at 6 months, eGFR outperformed Berden classification and RRS (C-index = 0.88, 0.62, 0.69, respectively) to predict ESKD. RRS performed better when it was updated with the eGFR at 6 months instead of the baseline eGFR. While 6-month proteinuria was associated with ESKD and improved ESKD prediction, hematuria and serological remission did not. Conclusion: This work suggests the benefit of the reassessment of the kidney prognosis 6 months after AAV-GN diagnosis. Kidney function at this time remains the most reliable for predicting kidney outcome. Of the markers tested, persistent proteinuria at 6 months was the only one to slightly improve the prediction of ESKD.

Effect on capillary refill time of volume expansion and increase of the norepinephrine dose in patients with septic shock.

BACKGROUND: Capillary refill time (CRT) has been suggested as a variable to follow during the course of septic shock. We systematically investigated the effects on CRT of volume expansion and norepinephrine. METHODS: In 69 septic shock patients, we recorded mean arterial pressure (MAP), cardiac index (CI), and 5 consecutive CRT measurements (video method, standardized pressure applied on the fingertip) before and after a 500-mL saline infusion in 33 patients and before and after an increase of the norepinephrine dose in 36 different patients. Fluid responders were defined by an increase in CI ≥ 15%, and norepinephrine responders by an increase in MAP ≥ 15%. RESULTS: The least significant change of CRT was 23%, so that changes in CRT were considered significant if larger than 23%. With volume expansion, CRT remained unchanged on average in patients with baseline CRT < 3 s (n = 7) and in all but one patient with baseline CRT ≥ 3 s in whom fluid increased CI < 15% (n = 13 "fluid non-responders"). In fluid responders with baseline CRT ≥ 3 s (n = 13), CRT decreased in 8 patients and remained unchanged in the others, exhibiting a dissociation between CI and CRT responses. The proportion of patients included > 24 h after starting norepinephrine was higher in patients with such a dissociation than in the other ones (60% vs. 0%, respectively). Norepinephrine did not change CRT significantly (except in one patient) if baseline CRT was ≥ 3 s and the increase in MAP < 15% (n = 6). In norepinephrine responders with prolonged baseline CRT (n = 11), it increased in 4 patients and remained unchanged in the other ones, which exhibited a dissociation between MAP and CRT responses. CONCLUSIONS: In septic shock patients with prolonged CRT, CRT very rarely improves with treatment when volume expansion increases cardiac output < 15% and increasing norepinephrine increases MAP < 15%. When the effects of fluid infusion on cardiac output and of norepinephrine on MAP are significant, the response of CRT is variable, as it decreases in some patients and remains stable in others which exhibit a dissociation between changes in macrohemodynamic variables and in CRT. In this regard, CRT behaves as a marker of microcirculation. TRIAL REGISTRATION: ClinicalTrial.gov (NCT04870892). Registered January15, 2021. Ethics committee approval CE SRLF 21-25.

The increase in cardiac output induced by a decrease in positive end-expiratory pressure reliably detects volume responsiveness: the PEEP-test study.

BACKGROUND: In patients on mechanical ventilation, positive end-expiratory pressure (PEEP) can decrease cardiac output through a decrease in cardiac preload and/or an increase in right ventricular afterload. Increase in central blood volume by fluid administration or passive leg raising (PLR) may reverse these phenomena through an increase in cardiac preload and/or a reopening of closed lung microvessels. We hypothesized that a transient decrease in PEEP (PEEP-test) may be used as a test to detect volume responsiveness. METHODS: Mechanically ventilated patients with PEEP ≥ 10 cmH2O ("high level") and without spontaneous breathing were prospectively included. Volume responsiveness was assessed by a positive PLR-test, defined as an increase in pulse-contour-derived cardiac index (CI) during PLR ≥ 10%. The PEEP-test consisted in reducing PEEP from the high level to 5 cmH2O for one minute. Pulse-contour-derived CI (PiCCO2) was monitored during PLR and the PEEP-test. RESULTS: We enrolled 64 patients among whom 31 were volume responsive. The median increase in CI during PLR was 14% (11-16%). The median PEEP at baseline was 12 (10-15) cmH2O and the PEEP-test resulted in a median decrease in PEEP of 7 (5-10) cmH2O, without difference between volume responsive and unresponsive patients. Among volume responsive patients, the PEEP-test induced a significant increase in CI of 16% (12-20%) (from 2.4 ± 0.7 to 2.9 ± 0.9 L/min/m2, p < 0.0001) in comparison with volume unresponsive patients. In volume unresponsive patients, PLR and the PEEP-test increased CI by 2% (1-5%) and 6% (3-8%), respectively. Volume responsiveness was predicted by an increase in CI > 8.6% during the PEEP-test with a sensitivity of 96.8% (95% confidence interval (95%CI): 83.3-99.9%) and a specificity of 84.9% (95%CI 68.1-94.9%). The area under the receiver operating characteristic curve of the PEEP-test for detecting volume responsiveness was 0.94 (95%CI 0.85-0.98) (p < 0.0001 vs. 0.5). Spearman's correlation coefficient between the changes in CI induced by PLR and the PEEP-test was 0.76 (95%CI 0.63-0.85, p < 0.0001). CONCLUSIONS: A CI increase > 8.6% during a PEEP-test, which consists in reducing PEEP to 5 cmH2O, reliably detects volume responsiveness in mechanically ventilated patients with a PEEP ≥ 10 cmH2O. Trial registration ClinicalTrial.gov (NCT 04,023,786). Registered July 18, 2019. Ethics Committee approval CPP Est III (N° 2018-A01599-46).

Norepinephrine and Vasopressin in Hemorrhagic Shock: A Focus on Renal Hemodynamics.

During hemorrhagic shock, blood loss causes a fall in blood pressure, decreases cardiac output, and, consequently, O2 transport. The current guidelines recommend the administration of vasopressors in addition to fluids to maintain arterial pressure when life-threatening hypotension occurs in order to prevent the risk of organ failure, especially acute kidney injury. However, different vasopressors exert variable effects on the kidney, depending on the nature and dose of the substance chosen as follows: Norepinephrine increases mean arterial pressure both via its α-1-mediated vasoconstriction leading to increased systemic vascular resistance and its ß1-related increase in cardiac output. Vasopressin, through activation of V1-a receptors, induces vasoconstriction, thus increasing mean arterial pressure. In addition, these vasopressors have the following different effects on renal hemodynamics: Norepinephrine constricts both the afferent and efferent arterioles, whereas vasopressin exerts its vasoconstrictor properties mainly on the efferent arteriole. Therefore, this narrative review discusses the current knowledge of the renal hemodynamic effects of norepinephrine and vasopressin during hemorrhagic shock.

Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study.

BACKGROUND: Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs. RESULTS: We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, ß and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70-100) vs. 90% (60-100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04-1.08], p < 0.001), SOFA score (aOR = 1.18 [1.12-1.23], p < 0.001) and immunosuppression (aOR = 1.82 [1.1-3.0], p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38-1.26], p = 0.23). CONCLUSIONS: In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.

Effects of mean arterial pressure target on mottling and arterial lactate normalization in patients with septic shock: a post hoc analysis of the SEPSISPAM randomized trial.

BACKGROUND: In patients with septic shock, the impact of the mean arterial pressure (MAP) target on the course of mottling remains uncertain. In this post hoc analysis of the SEPSISPAM trial, we investigated whether a low-MAP (65 to 70 mmHg) or a high-MAP target (80 to 85 mmHg) would affect the course of mottling and arterial lactate in patients with septic shock. METHODS: The presence of mottling was assessed every 2 h from 2 h after inclusion to catecholamine weaning. We compared mottling and lactate time course between the two MAP target groups. We evaluated the patient's outcome according to the presence or absence of mottling. RESULTS: We included 747 patients, 374 were assigned to the low-MAP group and 373 to the high-MAP group. There was no difference in mottling and lactate evolution during the first 24 h between the two MAP groups. After adjustment for MAP and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was associated with a significantly higher risk of death at day 28 and 90. Patients without mottling or with mottling < 6 h and lactate ≥ 2 mmol/L have a higher probability of survival than those with mottling ≥ 6 h and lactate < 2 mmol/L. CONCLUSION: Compared with low MAP target, higher MAP target did not alter mottling and lactate course. Mottling lasting for more than 6 h was associated with higher mortality. Compared to arterial lactate, mottling duration appears to be a better marker of mortality.

Proteinuria Increases the PLASMIC and French Scores Performance to Predict Thrombotic Thrombocytopenic Purpura in Patients With Thrombotic Microangiopathy Syndrome.

INTRODUCTION: PLASMIC and French scores have been developed to help clinicians in the early identification of patients with thrombotic thrombocytopenic purpura (TTP). Nevertheless, the validity of these scores in thrombotic microangiopathy (TMA) cohorts with low TTP prevalence remains uncertain. We aimed to evaluate their diagnostic value in routine clinical practice using an unselected cohort of patients with TMA. We also analyzed the value of adding proteinuria level to the scores. METHODS: We retrospectively included all patients presenting with a biological TMA syndrome between January 1, 2008, and December 31, 2019, in a tertiary hospital. TMA etiology was ascertained, and scores were evaluated. Modified scores, built by adding 1 point for low proteinuria (<1.2 g/g), were compared with original scores for TTP prediction. RESULTS: Among 273 patients presenting with a full biological TMA syndrome, 238 were classified with a TMA diagnosis. Complete scores and proteinuria level were available in 134 patients with a TTP prevalence of 7.5%. Area under the receiver operating characteristic curve (AUC) of PLASMIC and French scores for TTP diagnosis was 0.65 (0.46-0.84) and 0.72 (0.51-0.93), respectively. AUC of modified PLASMIC and French scores was 0.76 (0.59-0.92) (P = 0.003 vs. standard score) and 0.81 (0.67-0.95) (P = 0.069 vs. standard score), respectively. Specificity, positive predictive value (PPV), and positive likelihood ratio of high-risk scores were significantly improved by adding proteinuria level. CONCLUSION: PLASMIC and French scores have low predictive values when applied to an unselected TMA cohort. Including proteinuria level in the original scores improves their performance for TTP prediction.

Longitudinal changes in compliance, oxygenation and ventilatory ratio in COVID-19 versus non-COVID-19 pulmonary acute respiratory distress syndrome.

BACKGROUND: Differences in physiology of ARDS have been described between COVID-19 and non-COVID-19 patients. This study aimed to compare initial values and longitudinal changes in respiratory system compliance (CRS), oxygenation parameters and ventilatory ratio (VR) in patients with COVID-19 and non-COVID-19 pulmonary ARDS matched on oxygenation. METHODS: 135 patients with COVID-19 ARDS from two centers were included in a physiological study; 767 non-COVID-19 ARDS from a clinical trial were used for the purpose of at least 1:2 matching. A propensity-matching was based on age, severity score, oxygenation, positive end-expiratory pressure (PEEP) and pulmonary cause of ARDS and allowed to include 112 COVID-19 and 198 non-COVID pulmonary ARDS. RESULTS: The two groups were similar on initial oxygenation. COVID-19 patients had a higher body mass index, higher CRS at day 1 (median [IQR], 35 [28-44] vs 32 [26-38] ml cmH2O-1, p = 0.037). At day 1, CRS was correlated with oxygenation only in non-COVID-19 patients; 61.6% and 68.2% of COVID-19 and non-COVID-19 pulmonary ARDS were still ventilated at day 7 (p = 0.241). Oxygenation became lower in COVID-19 than in non-COVID-19 patients at days 3 and 7, while CRS became similar. VR was lower at day 1 in COVID-19 than in non-COVID-19 patients but increased from day 1 to 7 only in COVID-19 patients. VR was higher at days 1, 3 and 7 in the COVID-19 patients ventilated using heat and moisture exchangers compared to heated humidifiers. After adjustment on PaO2/FiO2, PEEP and humidification device, CRS and VR were found not different between COVID-19 and non-COVID-19 patients at day 7. Day-28 mortality did not differ between COVID-19 and non-COVID-19 patients (25.9% and 23.7%, respectively, p = 0.666). CONCLUSIONS: For a similar initial oxygenation, COVID-19 ARDS initially differs from classical ARDS by a higher CRS, dissociated from oxygenation. CRS become similar for patients remaining on mechanical ventilation during the first week of evolution, but oxygenation becomes lower in COVID-19 patients. TRIAL REGISTRATION: clinicaltrials.gov NCT04385004.

Retrospective and Systematic Analysis of Causes and Outcomes of Thrombotic Microangiopathies in Routine Clinical Practice: An 11-Year Study.

Background: Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined. The objectives of the present study were, therefore, to describe the etiologies, management, and the outcomes of patients presenting with TMA in real-life clinical practice. Methods: We conducted a retrospective study between 01/01/2008 and 31/12/2018 that included all consecutive patients presenting with biological TMA syndrome at admission or developing during hospitalization. Patients were identified from the laboratory databases, and their medical files were reviewed to confirm TMA diagnosis, to determine etiology, and to analyze their therapeutic management and outcomes. Results: During this period, 239 patients with a full TMA biological syndrome were identified, and the TMA diagnosis was finally confirmed in 216 (90.4%) after the cases were reviewed. Primary TMAs (thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome) were diagnosed in 20 of 216 patients (9.3%). Typical HUS was diagnosed in eight patients (3.7%), and the most frequent secondary TMAs were HELLP syndrome (79/216, 36.6%) and active malignancies (30/219, 13.9%). ADAMTS13 measurements and alternative complement pathway analyses were performed in a minority of patients. Multiple factors identified as TMA triggers were present in most patients, in 55% of patients with primary TMA, vs. 44.7% of patients with secondary TMA (p = 0.377). Death occurred in 57 patients (23.4%) during follow-up, and dialysis was required in 51 patients (23.6%). Active malignancies [odds ratio (OR) 13.7], transplantation (OR 4.43), male sex (OR 2.89), and older age (OR 1.07) were significantly associated with death. Conclusion: Secondary TMAs represent many TMA causes in patients presenting a full TMA biological syndrome during routine clinical practice. Multiple factors favoring TMA are present in about half of primary or secondary TMA. ADAMTS13 and complement pathway were poorly explored in our cohort. The risk of death is particularly high in patients with malignancies as compared with patients with other TMA.

Recruitability and effect of PEEP in SARS-Cov-2-associated acute respiratory distress syndrome.

BACKGROUND: A large proportion of patients with a SARS-Cov-2-associated respiratory failure develop an acute respiratory distress syndrome (ARDS). It has been recently suggested that SARS-Cov-2-associated ARDS may differ from usual non-SARS-Cov-2-associated ARDS by higher respiratory system compliance (CRS), lower potential for recruitment with positive end-expiratory pressure (PEEP) contrasting with severe shunt fraction. The purpose of the study was to systematically assess respiratory mechanics and recruitability in SARS-Cov-2-associated ARDS. METHODS: Gas exchanges, CRS and hemodynamics were assessed at 2 levels of PEEP (15 cmH2O and 5 cmH2O) within 36 h (day1) and from 4 to 6 days (day 5) after intubation. The recruited volume was computed as the difference between the volume expired from PEEP 15 to 5 cmH2O and the volume predicted by compliance at PEEP 5 cmH2O (or above airway opening pressure). The recruitment-to-inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and CRS at PEEP 5 cmH2O) was used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruitable patients. RESULTS: The R/I ratio was calculated in 25 of the 26 enrolled patients at day 1 and in 15 patients at day 5. At day 1, 16 (64%) were considered as highly recruitable (R/I ratio median [interquartile range] 0.7 [0.55-0.94]) and 9 (36%) were considered as poorly recruitable (R/I ratio 0.41 [0.31-0.48]). The PaO2/FiO2 ratio at PEEP 15 cmH2O was higher compared to PEEP 5 cmH2O only in highly recruitable patients (173 [139-236] vs 135 [89-167] mmHg; p < 0.01). Neither PaO2/FiO2 or CRS measured at PEEP 15 cmH2O or at PEEP 5 cmH2O nor changes in PaO2/FiO2 or CRS in response to PEEP changes allowed to identify highly or poorly recruitable patients. CONCLUSION: In this series of 25 patients with SARS-Cov-2 associated ARDS, 64% were considered as highly recruitable and only 36% as poorly recruitable based on the R/I ratio performed on the day of intubation. This observation suggests that a systematic R/I ratio assessment may help to guide initial PEEP titration to limit harmful effect of unnecessary high PEEP in the context of Covid-19 crisis.

Vasopressin and its analogues in shock states: a review.

Activation of arginine-vasopressin is one of the hormonal responses to face vasodilation-related hypotension. Released from the post-pituitary gland, vasopressin induces vasoconstriction through the activation of V1a receptors located on vascular smooth muscle cells. Due to its non-selective receptor affinity arginine-vasopressin also activates V2 (located on renal tubular cells of collecting ducts) and V1b (located in the anterior pituitary and in the pancreas) receptors, thereby potentially promoting undesired side effects such as anti-diuresis, procoagulant properties due to release of the von Willebrand's factor and platelet activation. Finally, it also cross-activates oxytocin receptors. During septic shock, vasopressin plasma levels were reported to be lower than expected, and a hypersensitivity to its vasopressor effect is reported in such situation. Terlipressin and selepressin are synthetic vasopressin analogues with a higher affinity for the V1 receptor, and, hence, potentially less side effects. In this narrative review, we present the current knowledge of the rationale, benefits and risks of vasopressin use in the setting of septic shock and vasoplegic shock following cardiac surgery. Clearly, vasopressin administration allows reducing norepinephrine requirements, but so far, no improvement of survival was reported and side effects are frequent, particularly ischaemic events. Finally, we will discuss the current indications for vasopressin and its agonists in the setting of septic shock, and the remaining unresolved questions.