Risk factors and outcome associated with fungal infections in patients with severe burn injury: 10-year retrospective IFI-BURN study.

BACKGROUND: In burn patients, skin barrier disruption and immune dysfunctions increase susceptibility to invasive fungal diseases (IFDs) like invasive candidiasis (IC) and invasive mold infections (IMI). We provide an in-depth analysis of IFD-related factors and outcomes in a 10-year cohort of severe burn patients. METHOD: Retrospective cohort study including adult patients admitted to the Burn Intensive Care Unit (BICU) between April 2014 and May 2023 with Total Burn Surface Area (TBSA) ≥15%. Patients were classified as proven IFD according to EORTC/MSGERC criteria applicable for IC. Putative IMIs were defined with: ≥2 positive cultures from a skin biopsy/bronchoalveolar lavage OR ≥2 positive blood specific-qPCRs OR a combination of both. RESULTS: Among 1381 patients admitted, 276 consecutive patients with TBSA ≥15% were included. Eighty-seven (31.5%; IC n=30; IMI n=43; both n=14) patients fulfilled the criteria for probable/putative IFD. At Day 30 after the burn injury, the estimated cumulative incidence pr/pu IFD was 26.4% (95%CI 21.4-31.8%). Factors independently associated with IFDs were TBSA, severity scores and indoor burn injury (i.e., from confined space fire). Overall mortality was 15.3% and 36.8% in the no IFD, pr/pu IFD groups respectively (p<0.0001). IFD was independently associated with a risk of death (HR: 1.94 for pr/pu IFD; 95%CI, 1.12-3.36; p=0.019). DISCUSSION: This study describes 21st-century characteristics of IFDs in sever burn patients confirming known risk factors with thresholds and identifying the indoor injury as an independent factor associated to IFDs. This suggests a link to contamination caused by fire damage, which is highly susceptible to aerosolizing spores.

Early post-operative lactate increase following kidney transplant is associated with delayed graft function: A retrospective cohort study.

INTRODUCTION: Delayed graft function (DGF) is a frequent complication following kidney transplant. This study aimed to assess the association between early post-operative lactate variation and DGF. METHODS: This was a single center, retrospective cohort study between February 2021 and December 2022 in Saint-Louis Hospital (APHP, France). Venous lactate levels were measured immediately (H0) and 4 h (H4) after kidney transplant. The primary outcome was the occurrence of DGF (need for renal replacement therapy between transplantation and day 7). Secondary outcome was the occurrence of complications (i.e., death, vascular thrombosis, hemorrhagic shock, urological complications (hematoma, urinoma), local or systemic infection) between transplant and day 7. RESULTS: Two hundred 12 patients were included, and 38 (17.9%) developed DGF. Venous lactate variation between H0 and H4 was higher in patients who developed DGF (-30 (IQR -83, -6)% vs. -15 (IQR -62, -11)%, p = .037), but the variation of level was more often positive (corresponding to an increased lactate production over time between H0 and H4) in patients who developed DGF ((28(85%) vs. 94(62%), p = .011). In multivariate logistic regression, positive venous lactate level variation between H0 and H4 was strongly associated with a reduced risk of developing DGF (OR .30 [.09-.79], p = .024). We did not find any association between post-operative hyperlactatemia and occurrence of complications between transplant and day 7. DISCUSSION: DGF is a frequent complication following kidney transplantation. Its early prediction could help physicians optimize treatment and protect the kidney. Early venous lactate variation after kidney transplant could help to predict the occurrence of DGF.

Evolution, control and success of combination therapy with Ampicilin-sulbactam/Ceftazidime-Avibactam during a Carbapenem-Resistant Acinetobacter baumannii outbreak in burn Intensive Care Unit.

We present our findings on interpatient transmission, epidemic control measures, and the outcomes of a series of ten critically ill burn patients who were either colonized or infected with carbapenem-resistant Acinetobacter baumannii (CRAB). None of the five infected patients achieved clinical cure, and all experienced relapses. Microbiological failure was observed in 40% of the infected patients. The isolated CRAB strains were found to carry blaOXA-23 and armA resistance genes. Despite the lack of clinical cure, all five infected patients survived and were discharged from the Burn Intensive Care Unit.

Combination of Mycological Criteria: a Better Surrogate to Identify COVID-19-Associated Pulmonary Aspergillosis Patients and Evaluate Prognosis?

Diagnosis of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remains unclear especially in nonimmunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. All successive patients (n = 176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a 1-year period. Direct examination, culture, Aspergillus quantitative PCR (Af-qPCR), and galactomannan testing were performed on all respiratory samples (n = 350). Serum galactomannan, ß-d-glucan, and plasma Af-qPCR were also assessed. The criteria were analyzed alone or in combination in relation to mortality rate. Mortality was significantly different in patients with 0, ≤2, and ≥3 positive criteria (log rank test, P = 0.04) with death rate of 43.1, 58.1, and 76.4%, respectively. Direct examination, plasma qPCR, and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46 of 350) with significantly lower quantitative cycle (Cq) when associated with at least one other criterion (30.2 versus 35.8) (P < 0.001). A combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. Af-qPCR may help identifying false-positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately.

A universal predictive and mechanistic urinary peptide signature in acute kidney injury.

BACKGROUND: The delayed diagnosis of acute kidney injury (AKI) episodes and the lack of specificity of current single AKI biomarkers hamper its management. Urinary peptidome analysis may help to identify early molecular changes in AKI and grasp its complexity to identify potential targetable molecular pathways. METHODS: In derivation and validation cohorts totalizing 1170 major cardiac bypass surgery patients and in an external cohort of 1569 intensive care unit (ICU) patients, a peptide-based score predictive of AKI (7-day KDIGO classification) was developed, validated, and compared to the reference biomarker urinary NGAL and NephroCheck and clinical scores. RESULTS: A set of 204 urinary peptides derived from 48 proteins related to hemolysis, inflammation, immune cells trafficking, innate immunity, and cell growth and survival was identified and validated for the early discrimination (< 4 h) of patients according to their risk to develop AKI (OR 6.13 [3.96-9.59], p < 0.001) outperforming reference biomarkers (urinary NGAL and [IGFBP7].[TIMP2] product) and clinical scores. In an external cohort of 1569 ICU patients, performances of the signature were similar (OR 5.92 [4.73-7.45], p < 0.001), and it was also associated with the in-hospital mortality (OR 2.62 [2.05-3.38], p < 0.001). CONCLUSIONS: An overarching AKI physiopathology-driven urinary peptide signature shows significant promise for identifying, at an early stage, patients who will progress to AKI and thus to develop tailored treatments for this frequent and life-threatening condition. Performance of the urine peptide signature is as high as or higher than that of single biomarkers but adds mechanistic information that may help to discriminate sub-phenotypes of AKI offering new therapeutic avenues.

Capillary refill time for the management of acute circulatory failure: a survey among pediatric and adult intensivists.

INTRODUCTION: Recent studies have shown the prognostic value of capillary refill time (CRT) and suggested that resuscitation management guided by CRT may reduce morbidity and mortality in patients with septic shock. However, little is known about the current use of CRT in routine clinical practice. This study aimed to assess the modalities of CRT use among French adult and pediatric intensivists. METHODS: A cross-sectional survey exploring CRT practices in acute circulatory failure was performed. The targeted population was French adult and pediatric intensivists (SFAR and GFRUP networks). An individual invitation letter including a survey of 32 questions was emailed twice. Descriptive and analytical statistics were performed. RESULTS: Among the 6071 physicians who received the letter, 418 (7%) completed the survey. Among all respondents, 82% reported using CRT in routine clinical practice, mainly to diagnose acute circulatory failure, but 45% did not think CRT had any prognostic value. Perfusion goal-directed therapy based on CRT was viewed as likely to improve patient outcome by 37% of respondents. The measurement of CRT was not standardized as the use of a chronometer was rare (3%) and the average of multiple measurements rarely performed (46%). Compared to adult intensivists, pediatric intensivists used CRT more frequently (99% versus 76%) and were more confident in its diagnostic value and its ability to guide treatment. CONCLUSION: CRT measurement is widely used by intensivists in patients with acute circulatory failure but most often in a non-standardized way. This may lead to a misunderstanding of CRT reliability and clinical usefulness.

Galectin-3 in Kidney Diseases: From an Old Protein to a New Therapeutic Target.

Galectin-3 (Gal-3) is a 30KDa lectin implicated in multiple pathophysiology pathways including renal damage and fibrosis. Gal-3 binds ß-galactoside through its carbohydrate-recognition domain. From intra-cellular to extra-cellular localization, Gal-3 has multiple roles including transduction signal pathway, cell-to-cell adhesion, cell to extracellular matrix adhesion, and immunological chemoattractant protein. Moreover, Gal-3 has also been linked to kidney disease in both preclinical models and clinical studies. Gal-3 inhibition appears to improve renal disease in several pathological conditions, thus justifying the development of multiple drug inhibitors. This review aims to summarize the latest literature regarding Gal-3 in renal pathophysiology, from its role as a biomarker to its potential as a therapeutic agent.

Incidence and Outcome of Subclinical Acute Kidney Injury Using penKid in Critically Ill Patients.

Rationale: Subclinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically ill patients remain, however, largely unknown. Plasma proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of glomerular function.Objectives: In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid.Methods: A prospective observational study in ICUs was conducted. FROG-ICU (French and European Outcome Registry in ICUs) enrolled 2,087 critically ill patients, and AdrenOSS-1 (Adrenomedullin and Outcome in Severe Sepsis and Septic Shock-1) enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e., >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate above 60 ml/min/1.73 m2 at ICU admission.Measurements and Main Results: In total, 6.1% (122/2,004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high estimated glomerular filtration rate, penKid was associated with higher mortality (adjusted standardized hazard ratio [HR], 1.4 [95% confidence interval, 1.1-1.8]; P = 0.010; and HR, 1.6 [95% confidence interval, 1.3-1.8]; P < 0.0001, respectively) after adjustment for age, sex, comorbidities, diagnosis, creatinine, diuresis, and study. Patients with sub-AKI had higher mortality compared with no AKI (HR, 2.4 [95% confidence interval, 1.5-3.7] in FROG-ICU and 2.5 [95% confidence interval, 1.1-5.9] in AdrenOSS-1).Conclusions: Sub-AKI defined using penKid occurred in 11.6-17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.

Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients.

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 < 0.0001). Patients with a sustained elevated DPP3 had an increased risk of death compared to patients with high DPP3admin 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.

Monitoring tissue perfusion: a pilot clinical feasibility and safety study of a urethral photoplethysmography-derived perfusion device in high-risk patients.

Continuous monitoring of tissue perfusion in patients with hemodynamic instability remains challenging because of the lack of tools available. Through using urethral photoplethysmography, the urethral perfusion index (uPI) could allow tissue perfusion monitoring through a modified urinary catheter. The first objective of our study was to evaluate the feasibility and safety of the IKORUS UP (Advanced Perfusion Diagnostics, Villeurbanne, France), a new device in the field. The secondary objectives were to evaluate the performance (duration and signal quality) of the IKORUS UP probe and to assess the uPI variations during hemodynamic events during major abdominal surgery. "STEP UP" was a prospective, multicenter, observational study. The inclusion criteria were age 18 years or older with signed informed consent and admitted to intensive care unit (ICU) with hemodynamic instability or high-risk surgical patient. Thirty patients were included in the study, 26 in the operating room, and four in the ICU. Of these patients, 28 were analyzed. For the primary outcome, six (21%) patients had pain scores assessed at insertion of and 22 (79%) at withdrawal of the catheter. The mean EVA score was 1.5 (IQ 1-2) and 0.7 (IQ 0-1), respectively, with the highest score being 3. One (4%) minor urethral bleeding and one (4%) catheter-associated urinary tract infection were reported. The IKORUS UP probe remained in the urethra for an average of 172 h (IQ40-328). The median signal measurement time was 33 h (IQ 5.2-46). The signal quality was recorded as good or excellent for 99% (IQ 82-100) of the insertion duration. The signal quality index was 93% (IQ 87-96) with a signal-to-noise ratio of 26 (IQ 21-36). We observed clinically relevant variations in the uPI over time during hemodynamic events or therapeutic interventions, with a strong cross-correlation with macrohemodynamic variables in some patients, while others did not display macrohemodynamic changes. The IKORUS UP probe was well tolerated and allowed urethral perfusion monitoring. Clinically relevant changes in tissue perfusion could be recorded during the observational period. Trial Registration: ( www.clinicaltrials.gov NCT03410069) registered January 25, 2018.

Contributing factors and outcomes of burn-associated cholestasis.

BACKGROUND & AIMS: Cholestasis often occurs after burn injuries. However, the prevalence of cholestasis and its effect on outcomes in patients with severe burn injuries are unknown. The aim of this study was to describe the course and the burden of cholestasis in a cohort of severely burned adult patients. METHODS: We investigated the relationship between burn-associated cholestasis (BAC) and clinical outcomes in a retrospective cohort of patients admitted to our unit for severe burn injuries between 2012 and 2015. BAC was defined as an increased level of serum alkaline phosphatase (ALP) ≥1.5x the upper limit of normal (ULN) with an increased level of gamma-glutamyltransferase (GGT) ≥3x ULN, or as an increased level of total bilirubin ≥2x ULN. RESULTS: A total of 214 patients were included: 111 (52%) patients developed BAC after a median (IQR) stay of 9 (5-16) days. At 90 days, the mortality rate was 20%, including 34 and 9 patients with and without BAC (p <0.001), respectively, which corresponded to a 2.5-fold higher (95% CI 1.2-5.2, p = 0.012) risk of 90-day mortality for patients with BAC. After being adjusted for severity of illness, patients with BAC, hyperbilirubinemia and without elevated ALP and GGT levels had a hazard ratio of 4.51 (95% CI 1.87-10.87) for 90-day mortality. BAC was associated with the severity of the burn injury, shock and bacteraemia. BAC was present in 38 (51%) patients at discharge, and 7 (18%) patients had secondary sclerosing cholangitis. These patients maintained elevated levels of ALP and GGT that were 5.8x (1.7-15) the ULN and 11x the ULN (4.5-22), respectively, 20 months (3.5-35) after discharge. CONCLUSION: BAC is prevalent among patients with severe burn injuries and is associated with worse short-term outcomes, especially when total bilirubin levels were increased without elevated ALP and GGT levels. BAC survivors are at risk of developing sclerosing cholangitis. LAY SUMMARY: Cholestasis is common after burn injuries and is associated with burn severity, sepsis, organ failure and mortality. Patients with hyperbilirubinemia without elevated alkaline phosphatase and gamma-glutamyltransferase levels after the burn injury have a poor prognosis. Patients with burn-associated cholestasis may develop sclerosing cholangitis and secondary biliary cirrhosis.

Esophageal Doppler Can Predict Fluid Responsiveness Through End-Expiratory and End-Inspiratory Occlusion Tests.

OBJECTIVES: To assess whether, in patients under mechanical ventilation, fluid responsiveness is predicted by the effects of short respiratory holds on cardiac index estimated by esophageal Doppler. DESIGN: Prospective, monocentric study. SETTING: Medical ICU. PATIENTS: Twenty-eight adult patients with acute circulatory failure and a decision of the clinicians in charge to administer fluids. INTERVENTIONS: Before and after infusing 500 mL of saline, we measured cardiac index estimated by esophageal Doppler before and during the last 5 seconds of successive 15-second end-inspiratory occlusion and end-expiratory occlusion, separated by 1 minute. Patients in whom volume expansion increased cardiac index measured by transpulmonary thermodilution greater than or equal to 15% were defined as "fluid responders." Cardiac index measured by the Pulse Contour Cardiac Output device (from pulse contour analysis or transpulmonary thermodilution) was used as the reference. MEASUREMENTS AND MAIN RESULTS: End-expiratory occlusion increased cardiac index estimated by esophageal Doppler more in responders than in nonresponders (8% ± 2% vs 3% ± 1%, respectively; p < 0.0001) and end-inspiratory occlusion decreased cardiac index estimated by esophageal Doppler more in responders than in nonresponders (-8% ± 5% vs -4% ± 2%, respectively; p = 0.0002). Fluid responsiveness was predicted by the end-expiratory occlusion induced percent change in cardiac index estimated by esophageal Doppler with an area under the receiver operating characteristic curve of 1.00 (95% CI, 0.88-1.00) and a threshold value of 4% increase in cardiac index estimated by esophageal Doppler. It was predicted by the sum of absolute values of percent changes in cardiac index estimated by esophageal Doppler during both occlusions with a similar area under the receiver operating characteristic curve (0.99 [0.86-1.00]) and with a threshold of 9% change in cardiac index estimated by esophageal Doppler, which is compatible with the esophageal Doppler precision. CONCLUSIONS: If the absolute sum of the percent change in cardiac index estimated by esophageal Doppler induced by two successive end-inspiratory occlusion and end-expiratory occlusion maneuvers is greater than 9%, it is likely that a 500 mL fluid infusion will increase cardiac output. This diagnostic threshold is higher than if only end-expiratory occlusion induced percent changes in cardiac index estimated by esophageal Doppler are taken into account.

Validation and Critical Evaluation of the Effective Arterial Elastance in Critically Ill Patients.

OBJECTIVES: First, to validate bedside estimates of effective arterial elastance = end-systolic pressure/stroke volume in critically ill patients. Second, to document the added value of effective arterial elastance, which is increasingly used as an index of left ventricular afterload. DESIGN: Prospective study. SETTING: Medical ICU. PATIENTS: Fifty hemodynamically stable and spontaneously breathing patients equipped with a femoral (n = 21) or radial (n = 29) catheter were entered in a "comparison" study. Thirty ventilated patients with invasive hemodynamic monitoring (PiCCO-2; Pulsion Medical Systems, Feldkirchen, Germany), in whom fluid administration was planned were entered in a " dynamic" study. INTERVENTIONS: In the "dynamic" study, data were obtained before/after a 500 mL saline administration. MEASUREMENTS AND MAIN RESULTS: According to the "cardiocentric" view, end-systolic pressure was considered the classic index of left ventricular afterload. End-systolic pressure was calculated as 0.9 × systolic arterial pressure at the carotid, femoral, and radial artery level. In the "comparison" study, carotid tonometry allowed the calculation of the reference effective arterial elastance value (1.73 ± 0.62 mm Hg/mL). The femoral estimate of effective arterial elastance was more accurate and precise than the radial estimate. In the "dynamic" study, fluid administration increased stroke volume and end-systolic pressure, whereas effective arterial elastance (femoral estimate) and systemic vascular resistance did not change. Effective arterial elastance was related to systemic vascular resistance at baseline (r = 0.89) and fluid-induced changes in effective arterial elastance and systemic vascular resistance were correlated (r = 0.88). In the 15 fluid responders (cardiac index increases ≥ 15%), fluid administration increased end-systolic pressure and decreased effective arterial elastance and systemic vascular resistance (each p < 0.05). In the 15 fluid nonresponders, end-systolic pressure increased (p < 0.05), whereas effective arterial elastance and systemic vascular resistance remained unchanged. CONCLUSIONS: In critically ill patients, effective arterial elastance may be reliably estimated at bedside (0.9 × systolic femoral pressure/stroke volume). We support the use of this validated estimate of effective arterial elastance when coupled with an index of left ventricular contractility for studying the ventricular-arterial coupling. Conversely, effective arterial elastance should not be used in isolation as an index of left ventricular afterload.

One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study.

OBJECTIVES: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge. DESIGN: Ancillary investigation of a prospective observational study. SETTING: Twenty-one ICUs with 1-year follow-up. PATIENTS: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included. INTERVENTIONS: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors. MEASUREMENTS AND MAIN RESULTS: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease). CONCLUSIONS: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

Tailoring treatment of hyperkalemia.

Hyperkalemia is a common electrolyte disorder that may be rapidly life-threatening because of its cardiac toxicity. Hyperkalemia risk factors are numerous and often combined in the same patient. Most of the strategies to control serum potassium level in the short term have been used for decades. However, evidence for their efficacy and safety remains low. Treatment of hyperkalemia remains challenging, poorly codified, with a risk of overtreatment, including short-term side effects, and with the priority of avoiding unnecessary hospital stays or chronic medication changes. Recently, new oral treatments have been proposed for non-life-threatening hyperkalemia, with encouraging results. Their role in the therapeutic arsenal remains uncertain. Finally, a growing body of evidence suggests that hyperkalemia might negatively impact outcomes in the long term in patients with chronic heart failure or kidney failure through underdosing or withholding of cardiovascular medication (e.g. renin-angiotensin-aldosterone system inhibitors). Recognition of efficacy and potential side effects of treatment may help in tailoring treatments to the patient's status and conditions. In this review we discuss how treatment of hyperkalemia could be tailored to the patient's conditions and status, both on the short and mid term.

What is the lowest change in cardiac output that transthoracic echocardiography can detect?

BACKGROUND: In critically ill patients, changes in the velocity-time integral (VTI) of the left ventricular outflow tract, measured by transthoracic echocardiography (TTE), are often used to non-invasively assess the response to fluid administration or for performing tests assessing fluid responsiveness. However, the precision of TTE measurements has not yet been investigated in such patients. First, we aimed at assessing how many measurements should be averaged within one TTE examination to reach a sufficient precision for various variables. Second, we aimed at identifying the least significant change (LSC) of these variables between successive TTE examinations. METHODS: We prospectively included 100 haemodynamically stable patients in whom TTE examination was planned. Three TTE examinations were performed, the first and the third by one operator and the second by another one. We calculated the precision and LSC (1) within one examination depending on the number of averaged measurements and (2) between measurements performed in two successive examinations. RESULTS: In patients in sinus rhythm, averaging three measurements within an examination was enough for obtaining an acceptable precision (interquartile range highest value < 10%) for VTI. In patients with atrial fibrillation, averaging five measurements was necessary. The precision of some other common TTE variables depending on the number of measurements is provided. Between two successive examinations performed by the same operator, the LSC was 11 [5-18]% for VTI. If two operators performed the examinations, the LSC for VTI significantly increased to 14 [8-26]%. The LSC between two examinations for other TTE variables is also provided. CONCLUSIONS: Averaging three measurements within one TTE examination is enough for obtaining precise measurements for VTI in patients in sinus rhythm but not in patients with atrial fibrillation. Between two TTE examinations performed by the same operator, the LSC of VTI is compatible with the assessment of the effects of a 500-mL fluid infusion but is not precise enough for assessing the effects of some tests predicting preload responsiveness.

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.

Noninvasive continuous detection of arterial hypotension during induction of anaesthesia using a photoplethysmographic signal: proof of concept.

BACKGROUND: During general anaesthesia, intraoperative hypotension (IOH), defined as a mean arterial pressure (MAP) reduction of > 20%, is frequent and may lead to complications. Pulse oximetry is mandatory in the operating room, making the photoplethysmographic signal and parameters, such as relative dicrotic notch height (Dicpleth) or perfusion index (PI), readily available. The purpose of this study was to investigate whether relative variations of Dicpleth and PI could detect IOH during anaesthesia induction, and to follow their variations during vasopressor boluses. METHODS: MAP, Dicpleth, and PI were monitored at 1-min intervals during target control induction of anaesthesia with propofol and remifentanil in 61 subjects. Vasopressor infusion (norepinephrine or phenylephrine) was performed when hypotension occurred according to the decision of the physician. RESULTS: The delta in Dicpleth and PI accurately detected IOH, with areas under the receiver operating characteristic curves (AUC) of 0.86 and 0.83, respectively. The optimal thresholds were -19% (sensitivity 79%; specificity 84%) and 51% (sensitivity 82%; specificity 74%) for ΔDicpleth and ΔPI, respectively. There was no difference between the ROC of ΔDicpleth and ΔPI (P=0.22). Combining both ΔDicpleth and ΔPI further improved the hypotension detection power (AUC=0.91) with a sensitivity and specificity of 84%. MAP variations were correlated with ΔDicpleth and ΔPI during vasopressor infusion (r=0.73 and -0.62, respectively; P<0.001). CONCLUSIONS: The relative variation in Dicpleth and PI derived from the photoplethysmographic signal can be used as a non invasive, continuous, and simple tool to detect intraoperative hypotension, and to track the vascular response to vasoconstrictor drugs during induction of general anaesthesia. CLINICAL TRIAL REGISTRATION: NCT03756935.

Outcome and potentially modifiable risk factors for candidemia in critically ill burns patients: A matched cohort study.

BACKGROUND: Patients with extensive burns are at risk of developing candidemia. OBJECTIVES: To identify potentially modifiable risk factors and outcomes of candidemia in critically ill burns patients. PATIENTS AND METHODS: Retrospective matched cohort study including adult burns patients. Patients who developed candidemia were matched with burns patients with Candida spp colonisation and sepsis or septic shock without candidemia in a ratio of 1:3 (same severity scores and colonisation index). Univariate and multiple regression analyses were performed. RESULTS: Of 130 severely burned patients with Candida spp colonisation and at least one episode of sepsis or septic shock, 14 were diagnosed with candidemia. In the candidemia group, patients had a median (IQR) total burns surface area (TBSA) of 57 (38-68)%, SAPSII of 43 (36-58) and ABSI of 11 (8-13). Multiple regression analysis showed that only duration of prior antibiotic therapy was independently associated with candidemia. ICU mortality was higher in the candidemia group (71% vs 35% [P = 0.02]). The log-rank test for 28-day mortality comparing patients with candidemia treated with an empirical strategy vs a curative strategy did not reach significance (P = 0.056). CONCLUSIONS: Burns patients having received recent antibiotherapy have a higher risk of candidemia. Antifungal strategies did not influence outcome in this series.