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BACKGROUND: Septic shock is often treated with aggressive fluid resuscitation leading to profound fluid overload. The assessment of fluid status relies on suboptimal measures making treatment difficult. Bioelectrical impedance analysis is an alternative but the validity is unclear. The aim of this study was to determine the validity of bioelectrical impedance analysis for fluid measures in patients with septic shock.METHODS: Single-center, prospective observational cohort study. We included adult ICU patients with septic shock. We evaluated the agreement between measures on the left and right side of the patient and measures one hour apart by two bioelectrical impedance devices. Results are presented as Bland Altman plots with 95% Limits of Agreements (LoA) and as correlations between bioelectrical impedance analysis results and clinical markers of fluids.RESULTS: 49 patients were included. The agreement between measures on the left and the right side of the patient and after one hour was overall without bias, but with wide LoA's. Fluid overload one hour apart showed the most narrow 95% LoA (-2.4l - 2.9L). The same wide limits of agreements were observed when comparing devices. E.g. total body water with 95% LoA of -14.8l - 16.7l. Correlations between bioelectrical impedance analysis and clinical measures were low but statistically significant.CONCLUSIONS: In patients with septic shock bioelectrical impedance analysis had no systematic errors or bias, but wide limits of agreement, indicating that the devices have a large and uncorrectable random error. Fluid status by bioelectrical impedance analysis is not sufficiently accurate to guide treatment in this group of patients. This article is protected by copyright. All rights reserved.

Coagulation abnormalities and microthrombi contribute to septic shock, but the impact of body temperature regulation on coagulation in patients with sepsis is unknown. We tested the hypothesis that mild induced hypothermia reduces coagulation and platelet aggregation in patients with septic shock. Secondary analysis of randomized controlled trial. Adult patients with septic shock who required mechanical ventilation from eight intensive care units in Denmark were randomly assigned to mild induced hypothermia for 24 h or routine thermal management. Viscoelastography and platelet aggregation were assessed at trial inclusion, after 12 h of thermal management, and 24 h after inclusion. A total of 326 patients were randomized to mild induced hypothermia (n = 163) or routine thermal management (n = 163). Mild induced hypothermia slightly prolonged activated partial thromboplastin time and thrombus initiation time (R time 8.0 min [interquartile range, IQR 6.6–11.1] vs. 7.2 min [IQR 5.8–9.2]; p =.004) and marginally inhibited thrombus propagation (angle 68° [IQR 59–73] vs. 71° [IQR 63–75]; p =.014). The effect was also present after 24 h. Clot strength remained unaffected (MA 71 mm [IQR 66–76] with mild induced hypothermia vs. 72 mm (65–77) with routine thermal management, p =.9). The proportion of patients with hyperfibrinolysis was not affected (0.7% vs. 3.3%; p =.19), but the proportion of patients with no fibrinolysis was high in the mild hypothermia group (8.8% vs. 40.4%; p

Background: Fluid overload is a risk factor for mortality in intensive care unit (ICU) patients. Administration of loop diuretics is the predominant treatment of fluid overload, but evidence for its benefit is very uncertain when assessed in a systematic review of randomised clinical trials. The GODIF trial will assess the benefits and harms of goal directed fluid removal with furosemide versus placebo in ICU patients with fluid overload. Methods: An investigator-initiated, international, randomised, stratified, blinded, parallel-group trial allocating 1000 adult ICU patients with fluid overload to infusion of furosemide versus placebo. The goal is to achieve a neutral fluid balance. The primary outcome is days alive and out of hospital 90 days after randomisation. Secondary outcomes are all-cause mortality at day 90 and 1-year after randomisation; days alive at day 90 without life support; number of participants with one or more serious adverse events or reactions; health-related quality of life and cognitive function at 1-year follow-up. A sample size of 1000 participants is required to detect an improvement of 8% in days alive and out of hospital 90 days after randomisation with a power of 90% and a risk of type 1 error of 5%. The conclusion of the trial will be based on the point estimate and 95% confidence interval; dichotomisation will not be used. ClinicalTrials.gov identifier: NCT04180397. Perspective: The GODIF trial will provide important evidence of possible benefits and harms of fluid removal with furosemide in adult ICU patients with fluid overload.

Rationale: Bioimpedance may be a useful tool to guide fluid treatment and avoid organ dysfunction related to fluid overload. Objective: We examined the correlation between bioimpedance and organ dysfunction in patients with septic shock. Methods: Prospective observational study of adult intensive care unit patients fulfilling the sepsis-3 criteria. Bioimpedance was measured using a body composition monitor (BCM) and BioScan Touch i8 (MBS). We measured impedance at inclusion and after 24 h and reported the impedance, change in impedance, bioimpedance-derived fluid balance, and changes in bioimpedance-derived fluid balance. Organ markers on respiratory, circulatory, and kidney function and overall disease severity were ascertained on days 1–7. The effect of bioimpedance on the change in organ function was assessed by mixed effects linear models. We considered P

Intensive care unit (ICU) patients with acute kidney injury (AKI) who recover kidney function within 28 days experience less severe chronic kidney impairment and have increased long term survival. The aims of this study were to develop and validate a risk prediction model to identify these patients.Observational study with development and validation of a risk prediction model.Nine academic ICUs in Denmark.Development cohort of critically ill patients with AKI at ICU admission from the Procalcitonin and Survival Study cohort (n = 568), validation cohort of adult patients with AKI admitted to two university hospitals in Denmark in 2012-13 (n = 766).None.Recovery of kidney function was defined as living for 5 consecutive days with no renal replacement therapy and with creatinine plasma levels below 1.5-fold the levels determined before ICU admission.A total of 266 patients (46.8%) recovered prior kidney function in the development cohort, and 453 patients (59.1%) in the validation cohort. The prediction model included elevation in creatinine, urinary output, sex and age. In the validation cohort, 69 patients (9.0%) had a predicted chance of recovery25%, and their observed rate of recovery was 21.5%. This observed rate of recovery was 81.7% among the 325 patients who had a predicted chance75%. The area under the receiver operations curves for predicting recovery in the validation cohort was 73.1%.We constructed and validated a simple model that can predict the chance of recovery from AKI in critically ill patients.

Summary Background Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. Methods In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. Findings Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55–0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55–1·53; p=0·76). Interpretation Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication. Funding Boehringer Ingelheim and Canadian Institutes of Health Research.

Hypophosphataemia is a potentially hazardous metabolic disturbance which is common in critically ill patients. The condition is reported to be associated with severe complications and increased mortality. It is unknown, whether hypophosphataemia has a causal effect or reflects the severity of illness. There are no randomized clinical trials to support treatment of hypophosphataemia with intravenous phosphate substitution, which has resulted in large variations in monitoring and treatment of hypophosphataemia in the intensive care unit.

BACKGROUD: Hyaluronic acid (HA) is proposed as a marker of functional liver capacity. The aim of the present study was to compare a new turbidimetric assay for measuring HA with the current standard method. METHODS: HA was measured by a particle‐enhanced turbidimetric immunoassay (PETIA) and enzyme‐linked immunosorbent assay (ELISA) in a 40‐sample dilution series and 39 intensive care unit (ICU) patients. Agreement was assessed with Bland–Altman's method. RESULTS: In the ICU patients, the median HA concentration was 159.0 ng/ml (interquartile range (IQR) 117.5–362.5 ng/ml) with ELISA and 157.5 ng/ml (IQR 92.5–359.6 ng/ml) with PETIA. The mean difference was 12.88 ng/ml (95% CI, −4.3 to 30.1 ng/ml, P = 0.14) and the 95% limits of agreement were −91.17 to 116.9 ng/ml. In the dilution series, the mean difference was −59.26 ng/ml (95% CI, −74.68 to 43.84 ng/ml, P < 0.0001) and the 95% limits of agreement were 35.23 to −153.8 ng/ml. CONCLUSION: We found random variation between the PETIA and ELISA test that could affect performance in a clinical context, but only to a lesser extent in a research context. The new clinical biochemistry assay for HA determination will allow for large studies of the clinical utility of HA.