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The aim of this study was to describe the prevalence, characteristics and outcome of critically burn patients with pulmonary HSV reactivation.Retrospective, single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients with bronchoalveolar lavage performed for pneumoniae suspicion and screened for HSV from January 2013 and April 2017. We used logistic regression to identify factors associated with HSV reactivation and outcomes.94 patients were included, mean age was 51 (39-64) years; median total body surface area burned was 36 (25-54)% and ICU mortality 38%. Fifty-five patients (59%) had pulmonary HSV reactivation and 30 (55%) were treated with acyclovir. Patients with HSV reactivation were more severely ill with higher SOFA score at admission compared to patient without HSV reactivation (6 [3-8] vs. 2 [1-4], p0.0001 respectively). In multivariate analysis, sex, SOFA score at admission and smoke inhalation were significantly associated with HSV reactivation. Only septic shock was associated with 90-day mortality when HSV reactivation was not.Pulmonary HSV reactivation is frequent among severely ill burn patients. Initial severity and smoke inhalation are risk factors. Antiviral treatment was not associated with outcome.

Background Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. Methods We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. Results Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75–24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47–84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27–18.6)] as being independently associated with in-ICU mortality. Conclusions SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

International audience; 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

Hypoalbuminemia is a frequent condition in the first 24 h after a severe burn injury and is associated with worse outcomes.We investigated the relation between very early hypoalbuminemia (6 h after admission) and clinical outcome in a retrospective cohort admitted to our unit for severe burn injuries between 2012 and 2017.73 severely burned patients were included, with a delay of admission of 3 (2-4) h. In a context of early exogenous supply of albumin, admission and 4H Albuminemia (Alb4 h) were significantly lower in deceased patients (respectively, 34 (29-37) vs 27 (23-30) g/l; p = 0.009 and 27 (24-32) vs 21 (17-27) g/l; p = 0.022) whereas albuminemia ≥6 h were not. The best threshold value of Alb4 h to discriminate 28-day mortality was 23 g/l. Patients with an Alb4 h 23 g/l had a higher 28-day mortality than patients with an Alb4 h ≥ 23 g/l (42% vs 11%; p = 0.003); adjusted OR = 4.47 (95% CI 1.15-17.36); p = 0.03.In severely burned patients receiving early albumin supply, early hypoalbuminemia is associated with higher mortality whereas later albuminemia (≥6 h) is not. Exploration of whether early albumin infusion (8-12 h post injury) may alter clinical outcome is warranted.

Hypotension during general anesthesia is associated with poor outcome. Continuous monitoring of mean blood pressure (MAP) during anesthesia is useful and needs to be reliable and minimally invasive. Conventional cuff measurements can lead to delays due to its discontinuous nature. It has been shown that there is a relationship between MAP and photoplethysmography (PPG) parameters like the dicrotic notch and perfusion index (PI). The objective of the study was to continuously estimate MAP from PPG. Pulse wave analysis based on PPG was implemented using either notch relative amplitude (MAPNRA), notch absolute amplitude (MAPNAA) or PI (MAPPI) to estimate MAP from PPG waveform features during general anesthesia. Estimated MAP values were compared to brachial cuff MAP (MAPcuff) and to radial invasive MAP (MAPinv). Forty-six patients were analyzed for a total of 235 h. Compared to MAPcuff, mean bias and limits of agreement were 1 mmHg (− 26 to +29), − 1 mmHg (− 10 to +8) and − 3 mmHg (− 21 to +13) for MAPNRA, MAPNAA and MAPPI respectively. Compared to MAPinv, mean absolute error (MAE) was 20 mmHg [10 to 39], 11 mmHg [5 to 18] and 16 mmHg [9 to 24] for MAP derived from MAPNRA, MAPNAA and MAPPI respectively. When calibrated every 5 min, MAPNAA showed a MAE of 6 mmHg [5 to 9]. MAPNAA provides the best estimates with respect to brachial cuff MAP and invasive MAP. Regular calibration allows to reduce drift over time. Beat to beat estimation of MAP during general anesthesia from the PPG appears possible with an acceptable average error.

International audience; Background: Dyspnea is a traumatic experience. Only limited information is available on dyspnea in intubated critically ill patients. Our objectives were 1) To quantify the prevalence and severity of dyspnea, 2) To evaluate the impact of dyspnea on intensive care unit (ICU) length of stay and post-traumatic stress disorder (PTSD) 90 days after ICU discharge.Methods: Prospective cohort study in 10 ICUs in France. In patients intubated for more than 24 hours, dyspnea was quantified with a visual analog scale (from zero to 10) as soon as they were able to communicate, the following day and prior spontaneous breathing trials. PTSD was defined by an Impact of Event Scale-Revised score ≥ 22.Results: Among the 612 patients assessed, 34% reported dyspnea, with a median dyspnea rating of 5 (interquartile range, 4-7). ICU length of stay was not significantly different between dyspneic and non-dyspneic patients (6 [3-12] and 6 [3-13] days, respectively; P=0.781). Mortality was not different between groups. Of the 153 patients interviewed on day 90, a higher proportion of individuals with probable PTSD was observed among patients who were dyspneic on enrolment (29% vs. 13%, P=0.017). The density of dyspnea (number of dyspneic episodes divided by time from enrolment to extubation) were independently associated with post-traumatic stress disorder (odds ratio: 1.07, 95% confidence interval: 1.01-1.13, P=0.031).Conclusion: Dyspnea was frequent and intense in intubated critically ill patients. ICU length of stay was not significantly different among patients reporting dyspnea, but PTSD was more frequent at day 90.

Lactate albumin ratio (LAR) has been used as a prognostic marker associated with organ failure in critically ill septic patients. LAR and its association with outcomes has never been studied in burned patients. The aim of this study was to evaluate the ability of LAR to predict 28-day mortality.A retrospective cohort study including all burn patients hospitalized in intensive care unit. The primary endpoint was the 28-day mortality.One thousand three hundred thirty four patients were screened, and 471 were included between June 2012 and December 2018. Briefly, the population study was mainly composed by men (249, 59.1%), the median age, TBSA burned, full thickness, ABSI and IGS2 were 52 [34-68], 20 [10-40], 8 [1-23], 7 [5-9] and 25 [15-40] respectively. Fifty-two patients (12.4%) died at day 28 after admission. At admission, the LAR level was lower in 28-day survivors compared non-survivors (0.05 [0.04, 0.08] vs 0.12 [0.07, 0.26], p 0.001 respectively). In multivariate analysis accounting for ABSI, LAR levels at admission 0.13 was independently associated with 28-day mortality (adjusted OR = 3.98 (IC95 1.88-8.35)). The ability of LAR at admission to discriminate 28-day mortality showed an AUC identical when compared to SOFA and ABSI scores (0.81 (IC95 0.74-0.88), 0.80 (IC95 0.72-0.85) and (0.85 (IC95 0.80-0.90), p 0.05, respectively). Patients with LAR levels ≥ 0.13 at admission had higher 28-day mortality (40.6% vs 6.8%, p 0.001, HR 7.39 (IC95 4.28-12.76)).At admission, LAR is an easy and reliable marker independently associated to 28-day mortality in patients with severe burn injury, but prediction by LAR does not perform better than lactate level alone.

Short title: Clinical Usefulness of Perfusion Index; International audience; Photoplethysmography (PPG) has been extensively used for pulse oximetry monitoring in anaesthesia, perioperative and intensive care. However, some components of PPG signal have been employed for other purposes, such as non-invasive haemodynamic monitoring. Perfusion index (PI) is derived from PPG signal and represents the ratio of pulsatile on non-pulsatile light absorbance or reflectance of the PPG signal. PI determinants are complex and interlinked, involving and reflecting the interaction between peripheral and central haemodynamic characteristics, such as vascular tone and stroke volume. Recently, several studies have shed light on the interesting performances of this variable, especially assessing regional or neuraxial block success, and haemodynamic monitoring in anaesthesia, perioperative and intensive care. Nevertheless, no review has yet been published concerning the interest of PI in these fields. In this narrative review will be exposed first the physiological and pathophysiological determinants of PI, and then the mean to measure this value as well as its potential limitations. In the second part, the existing data concerning usefulness of PI in different clinical settings such as operating theatres, intensive care units and emergency departments will be presented and discussed. Finally, the perspectives concerning the use of PI and mentioned aspects that should be explored regarding this tool will be underlined.

Proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of renal function. This study evaluated the association of concentrations of plasma penKid with death and risk of acute kidney injury (AKI) in severely ill burn patients.A prospective observational study in two centers with severely ill adult burn patients was conducted. The inclusion criteria were total body surface area (TBSA) burns15%, with burn injury occurring72 h before intensive care unit (ICU) admission and plasma sample taken at admission. The primary endpoint was 90-day mortality. The secondary endpoints were AKI and a combined endpoint of 90-day mortality and/or AKI. Mortality was also evaluated in the sub-group of patients with sub-clinical AKI, defined as a patient without AKI but with elevated penKid.A total of 113 consecutive patients were enrolled. The median age was 48 years (Interquartile range [IQR] 33-64), the median burn TBSA was 35% (IQR 25-53), and 90-day mortality was 31.9%. Thirty-one percent of the patients had AKI, and 41.6% of patients had the combined endpoint. There was a stepwise decrease in survival from patients without AKI, sub-AKI, and with AKI (survival rate 90.0% [95% CI 82.7-97.9], 66.7% [95% CI 48.1-92.4], and 31.4% [95% CI 19.3-51.3], respectively, p0.001). Plasma penKid concentration was significantly higher in non-survivors compared to survivors (86.9 pmol/L [IQR 53.3-166.1] versus 52.9 pmol/L [IQR 37.1-70.7]; p = 0.0001) and in patients with AKI compared to patients without AKI (86.4 pmol/L [IQR 56.5-153.4] versus 52.5 pmol/L [IQR 35.5-71.2]; p0.001). Penkid provided added value on top of serum creatinine (Screat) and Sepsis Related Organ Failure Assessment (SOFA) scores to predict 90-day mortality (combined c-index of 0.738 versus 0.707; p = 0.024 and 0.787 versus 0.752; p0.001).Plasma penKid concentration at admission was associated with an increased risk of death in burn patients. PenKid has additional prognostic value on top of Screat and SOFA to predict 90-day mortality.

Background Dipeptidyl peptidase-3 (DPP3) is a metallopeptidase which cleaves bioactive peptides, notably angiotensin II, and is involved in inflammation regulation. DPP3 has been proposed to be a myocardial depressant factor and to be involved in circulatory failure in acute illnesses, possibly due to angiotensin II cleavage. In this study, we evaluated the association between plasmatic DPP3 level and outcome (mortality and hemodynamic failure) in severely ill burn patients. Methods In this biomarker analysis of a prospective cohort study, we included severely ill adult burn patients in two tertiary burn intensive care units. DPP3 was measured at admission (DPP3admin) and 3 days after. The primary endpoint was 90-day mortality. Secondary endpoints were hemodynamic failure and acute kidney injury (AKI). Results One hundred and eleven consecutive patients were enrolled. The median age was 48 (32.5–63) years, with a median total body surface area burned of 35% (25–53.5) and Abbreviated Burn Severity Index (ABSI) of 8 (7–11). Ninety-day mortality was 32%. The median DPP3admin was significantly higher in non-survivors versus survivors (53.3 ng/mL [IQR 28.8–103.5] versus 27.1 ng/mL [IQR 19.4–38.9]; p admin but decreased levels on day 3. Patients with circulatory failure had higher DPP3admin (39.2 ng/mL [IQR 25.9–76.1] versus 28.4 ng/mL [IQR 19.8–39.6]; p = 0.001) as well as patients with AKI (49.7 ng/mL [IQR 30.3–87.3] versus 27.6 ng/mL [IQR 19.4–41.4]; p = 0.001). DPP3admin added prognostic value on top of ABSI (added chi2 12.2, p = 0.0005), Sequential Organ Failure Assessment (SOFA) score at admission (added chi2 4.9, p = 0.0268), and plasma lactate at admission (added chi2 6.9, p = 0.0086) to predict circulatory failure within the first 48 h. Conclusions Plasma DPP3 concentration at admission was associated with an increased risk of death, circulatory failure, and AKI in severely burned patients. Whether DPP3 plasma levels could identify patients who would respond to alternative hemodynamic support strategies, such as intravenous angiotensin II, should be explored.

Objectives Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission. Design Retrospective, multicenter, national study over an 18-year period (2000-2017). Setting Thirty-one French ICUs. Patients The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. Measurements and main results Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality. Conclusions Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.

Rationale: Because encouraging rates for hospital and long-term survival of immunocompromised patients in ICUs have been described, these patients are more likely to receive invasive therapies, like extracorporeal membrane oxygenation (ECMO). Objectives: To report outcomes of immunocompromised patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and to identify their pre-ECMO predictors of 6-month mortality and main ECMO-related complications. Methods: Retrospective multicenter study in 10 international ICUs with high volumes of ECMO cases. Immunocompromised patients, defined as having hematological malignancies, active solid tumor, solid-organ transplant, acquired immunodeficiency syndrome, or long-term or high-dose corticosteroid or immunosuppressant use, and severe ECMO-treated ARDS, from 2008 to 2015 were included. Measurements and Main Results: We collected demographics, clinical data, ECMO-related complications, and ICU- and 6 month–outcome data for 203 patients (median Acute Physiology and Chronic Health Evaluation II score, 28 [25th–75th percentile, 20–33]; age, 51 [38–59] yr; Pa(O(2))/Fi(O(2)), 60 [50–82] mm Hg before ECMO) who fulfilled our inclusion criteria. Six-month survival was only 30%, with a respective median ECMO duration and ICU stay of 8 (5–14) and 25 (16–50) days. Patients with hematological malignancies had significantly poorer outcomes than others (log-rank P = 0.02). ECMO-related major bleeding, cannula infection, and ventilator-associated pneumonia were frequent (36%, 10%, and 50%, respectively). Multivariate analyses retained fewer than 30 days between immunodeficiency diagnosis and ECMO cannulation as being associated with lower 6-month mortality (odds ratio, 0.32 [95% confidence interval, 0.16–0.66]; P = 0.002), and lower platelet count, higher Pco(2), age, and driving pressure as independent pre-ECMO predictors of 6-month mortality. Conclusions: Recently diagnosed immunodeficiency is associated with a much better prognosis in ECMO-treated severe ARDS. However, low 6-month survival of our large cohort of immunocompromised patients supports restricting ECMO to patients with realistic oncological/therapeutic prognoses, acceptable functional status, and few pre-ECMO mortality-risk factors.

We aimed at assessing the predictive value of plasmatic Neutrophil Gelatinase Associated Lipocalin (pNGAL) at admission and severity scores to predict major adverse kidney events (MAKE, defined as death and/or need for renal replacement therapy (RRT) and/or non-renal recovery at day 90) in critically ill burn patients.Single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients (total burned body surface20%) from January 2012 until January 2015 with a pNGAL dosage at admission. Reclassification of patients was assessed by Integrated Discrimination Improvement (IDI).87 patients were included. Mean age was 47.7 (IQ 25-75: 33.4-65.2) years; total burn body surface area was 40 (IQ 25-75: 30-55) % and ICU mortality 36%. 39 (44.8%) patients presented a MAKE, 32 (88.9%) patients died at day 90. pNGAL was higher in the MAKE group (423 [IQ 25-75: 327-518]pg/mL vs 184 [IQ 25-75: 147-220]pg/mL, p0.001). In multivariate analysis, pNGAL and abbreviated burn severity index (ABSI) remained associated with MAKE (OR 1.005 [CI 95% 1.0005-1.009], p=0.03 and OR 1.682 [CI95%1.038-2.726], p=0.035 respectively). Adding pNGAL to abbreviated burn severity index, simplified organ failure assessment and the simplified acute physiology score 2 did outperform clinical scores for the prediction of MAKE and AKI and for most severe forms of AKI and allowed a statistically significant reclassification of patients compared to ABSI for MAKE, RRT, AKI at Day 7 and AKI during hospitalization with a number of patients needed to screen to detect one extra episode of MAKE was 44, 13 for severe AKI and 15 for AKI.pNGAL at admission is associated with the risk of MAKE in this population, and outperform severity scores when associated. Interventional studies are now needed to assess if impact of biomarkers-guided strategies would improve outcome.