Effects of restrictive fluid therapy on the time to resolution of hyperlactatemia in ICU patients with septic shock. A secondary post hoc analysis of the CLASSIC randomized trial.

PURPOSE: The aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of fluid overload. METHODS: We conducted a post hoc analysis of serial plasma lactate concentrations in a sub-cohort of 777 patients from the international multicenter clinical CLASSIC trial (restriction of intravenous fluids in intensive care unit (ICU) patients with septic shock). Adult ICU patients with septic shock had been randomized to restrictive (n = 385) or standard (n = 392) intravenous fluid therapy. The primary outcome, time to resolution of hyperlactatemia, was analyzed with a competing-risks regression model. Death and discharge were competing outcomes, and administrative censoring was imposed 72 h after randomization if hyperlactatemia persisted. The regression analysis was adjusted for the same stratification variables and covariates as in the original CLASSIC trial analysis. RESULTS: The hazard ratios (HRs) for the cumulative probability of resolution of hyperlactatemia, in the restrictive vs the standard group, in the unadjusted analysis, with time split, were 0.94 (confidence interval (CI) 0.78-1.14) at day 1 and 1.21 (0.89-1.65) at day 2-3. The adjusted analyses were consistent with the unadjusted results. CONCLUSION: In this post hoc retrospective analysis of a multicenter randomized controlled trial (RCT), a restrictive intravenous fluid strategy did not seem to affect the time to resolution of hyperlactatemia in adult ICU patients with septic shock.

[Insights from creating a covid-19 biobank in Sweden]. / Så skapades covid-19-biobanken.

Biobanks function as important repositories for biological samples collected in health care. As such, they play an important role in enabling important medical research over time. In response to the covid-19 outbreak in Stockholm, Sweden, a group of specialists in intensive care, infectious diseases, and clinical microbiology, as well as scientists with experience in immunology and viral diseases, rapidly gathered. The group discussed how to cope with the prevailing situation, both from a clinical and a research-oriented perspective. Among strategies decided was an attempt to rapidly organize a biological sample collection organized in a biobank for immediate but also long-term research purposes. Given the pandemic conditions with a new virus, the biobank project and associated immediate immunological research tasks turned out to be challenging. In the following months, many lessons were learned from the systematic collection of clinical samples and associated immunological research. Many insights were gained of value for future pandemic preparedness.

Enteral nutrition and dynamics of citrulline and intestinal fatty acid-binding protein in adult ICU patients.

BACKGROUND AND AIMS: Plasma citrulline and intestinal fatty acid binding protein (I-FABP) are biomarkers reflecting enterocyte function and intestinal mucosal injury. The aim was to describe daily dynamics of citrulline and I-FABP concentrations in association with enteral nutrition (EN) in adult ICU patients. We hypothesized that success or failure of EN is reflected by differences in citrulline and I-FABP levels at admission, as well as in daily dynamics over the first week. METHODS: The present study was a planned sub-study of the iSOFA study (ClinicalTrials.gov Identifier: NCT02613000). With delayed informed consent we included adult (18 years or older) patients admitted for unlimited care to 5 ICUs in Europe. Citrulline and I-FABP were assessed and nutritional data recorded daily during the first week of the patients' ICU stay. RESULTS: The study included 224 patients with 693 plasma samples analyzed for citrulline and 695 for I-FABP. The median ICU stay was 2 (IQR 1-4) days and 35 patients (15.6 %) stayed in the ICU for ≥ 7 days. The majority of patients (184/224; 82.1 %) received EN or oral nutrition (ON) during their ICU stay, in 164 patients (73.2 %) nutrition was started within 48 h of admission (early enteral or oral nutrition, EEN/ON). Median biomarker concentrations on admission were: citrulline 24.5 (IQR 18.1-31.7) µmol/L and I-FABP 2763 (1326-4805) pg/mL. Reference range for citrulline was 17-46 µmol/L and for I-FABP 377-2049 pg/mL. Patients with EEN/ON demonstrated an increase in citrulline concentrations over the first week in ICU unlike those not receiving EEN/ON (P = 0.049 for the mean log-citrulline values over time between groups) as well as higher average citrulline concentrations. Success of EEN/ON (80 % of caloric target achieved by day 4) was associated with citrulline values increasing from day 4, whereas a slight decrease was observed with unsuccessful EEN/ON. However, these dynamics over time were not statistically significantly different (P = 0.654). Patients with EEN/ON unexpectedly had I-FABP values higher than those without (average values for all days P = 0.004). Median I-FABP values on day 3 were higher with successful EEN/ON (646 (IQR 313-1116) vs 278 (IQR 190-701) pg/mL, P = 0.022). CONCLUSIONS: EEN/ON was associated with higher values and different dynamics of citrulline over the first week in ICU. No clear difference of measured biomarkers was seen when patients were compared according to success of EEN/ON. Our study does not allow suggesting certain thresholds of citrulline nor I-FABP that could be used for bedside decision-making with regard to EN. This study was a planned sub-study of the iSOFA study (ClinicalTrials.gov Identifier: NCT02613000).

Development of the Gastrointestinal Dysfunction Score (GIDS) for critically ill patients - A prospective multicenter observational study (iSOFA study).

BACKGROUND & AIMS: To develop a five grade score (0-4 points) for the assessment of gastrointestinal (GI) dysfunction in adult critically ill patients. METHODS: This prospective multicenter observational study enrolled consecutive adult patients admitted to 11 intensive care units in nine countries. At all sites, daily clinical data with emphasis on GI clinical symptoms were collected and intra-abdominal pressure measured. In five out of 11 sites, the biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) were measured additionally. Cox models with time-dependent scores were used to analyze associations with 28- and 90-day mortality. The models were estimated with stratification for study center. RESULTS: We included 540 patients (224 with biomarker measurements) with median age of 65 years (range 18-94), the Simplified Acute Physiology Score II score of 38 (interquartile range 26-53) points, and Sequential Organ Failure Assessment (SOFA) score of 6 (interquartile range 3-9) points at admission. Median ICU length of stay was 3 (interquartile range 1-6) days and 90-day mortality 18.9%. A new five grade Gastrointestinal Dysfunction Score (GIDS) was developed based on the rationale of the previously developed Acute GI Injury (AGI) grading. Citrulline and I-FABP did not prove their potential for scoring of GI dysfunction in critically ill. GIDS was independently associated with 28- and 90-day mortality when added to SOFA total score (HR 1.40; 95%CI 1.07-1.84 and HR 1.40; 95%CI 1.02-1.79, respectively) or to a model containing all SOFA subscores (HR 1.48; 95%CI 1.13-1.92 and HR 1.47; 95%CI 1.15-1.87, respectively), improving predictive power of SOFA score in all analyses. CONCLUSIONS: The newly developed GIDS is additive to SOFA score in prediction of 28- and 90-day mortality. The clinical usefulness of this score should be validated prospectively. TRIAL REGISTRATION: NCT02613000, retrospectively registered 24 November 2015.