Biomarkers In Prediction of Acute Mesenteric Ischaemia: a prospective multicentre study (BIPAMI study): a study protocol.

BACKGROUND: Acute mesenteric ischaemia (AMI) is a life-threatening disease where early diagnosis is critical to avoid morbidity and mortality from extensive irreversible bowel necrosis. Appropriate prediction of presence of bowel necrosis is currently not available but would help to choose the optimal method of treatment. The study aims to identify combinations of biomarkers that can reliably identify AMI and distinguish between potentially reversible and irreversible bowel ischaemia. METHODS: This is a prospective multicentre study. Adult patients with clinical suspicion of AMI (n = 250) will be included. Blood will be sampled on admission, at and after interventions, or during the first 48 h of suspicion of AMI if no intervention undertaken. Samples will be collected and the following serum or plasma biomarkers measured at Tartu University Hospital laboratory: intestinal fatty acid-binding protein (I-FABP), alpha-glutathione S-transferase (Alpha- GST), interleukin 6 (IL-6), procalcitonin (PCT), ischaemia-modified albumin (IMA), D-lactate, D-dimer, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and lipopolysaccharide-binding protein (LBP). Additionally, more common laboratory markers will be measured in routine clinical practice at study sites. Diagnosis of AMI will be confirmed by computed tomography angiography, surgery, endoscopy or autopsy. Student's t or Wilcoxon rank tests will be used for comparisons between transmural vs. suspected (but not confirmed) AMI (comparison A), confirmed AMI of any stage vs suspected AMI (comparison B) and non-transmural AMI vs transmural AMI (comparison C). Optimal cut-off values for each comparison will be identified based on the AUROC analysis and likelihood ratios calculated. Positive likelihood ratio > 10 (> 5) and negative likelihood ratio < 0.1 (< 0.2) indicate high (moderate) diagnostic accuracy, respectively. All biomarkers with at least moderate accuracy will be entered as binary covariates (using the best cutoffs) into the multivariable stepwise regression analysis to identify the best combination of biomarkers for all comparisons separately. The best models for each comparison will be used to construct a practical score to distinguish between no AMI, non-transmural AMI and transmural AMI. DISCUSSION: As a result of this study, we aim to propose a score including set of biomarkers that can be used for diagnosis and decision-making in patients with suspected AMI. TRIAL REGISTRATION: NCT06212921 (Registration Date 19-01-2024).

Current practice of gastric residual volume measurements and related outcomes of critically ill patients: A secondary analysis of the intestinal-specific organ function assessment study.

BACKGROUND: Gastric residual volume (GRV) measurement to detect gastrointestinal (GI) dysfunction is a common diagnostic procedures in critical care, albeit still not well standardized being operator-, patient-, and tube-dependent. Our aim was to describe current practice of GRV measurements and its association with clinical outcomes in critically ill patients. METHODS: This was a secondary analysis of an international prospective observational cohort study (intestinal-specific organ function assessment). Eligibility criteria were defined as ≥1 GRV measurement during the 7-day study period. Data collection included GRV measurement practices, tube diameters and volumes, symptoms of GI dysfunction, and clinical outcomes. The primary aim was to describe current practices of GRV measurements, and the secondary aim was to test the association of high (>200 ml) vs. low GRV with symptoms of GI dysfunction and clinical outcomes using generalized linear regression and survival models. RESULTS: Two hundred fifty-eight patients with 2422 GRV measurements on 875 study days were analyzed. GRV was mainly measured via passive drainage twice daily using large diameter tubes. There was no significant association between tube size or measurement technique and high GRV. High GRV occurred in 34% of patients and was associated with other GI symptoms and with increased disease severity but not with 28-day or 90-day mortality, intensive care unit-free and ventilator-free days. CONCLUSION: There was substantial variability of GRV measurement techniques, but this had no impact on the amount of GRV. High GRV was not associated with mortality or ventilator-free days but may serve as a marker of GI dysfunction and disease severity.

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.

Deepening of sedation with propofol has limited effect on intra-abdominal pressure - An interventional study in mechanically ventilated adult patients with intra-abdominal hypertension.

PURPOSE: To evaluate the effect of deepening of sedation on intra-abdominal pressure (IAP). METHODS: 37 adult mechanically ventilated ICU patients with intra-abdominal hypertension received a bolus dose and subsequent infusion of propofol (bolus: 1 mg/kg, infusion: 3 mg/kg/h). IAP, mean arterial pressure (MAP), abdominal perfusion pressure (APP), depth of sedation according to Richmond Agitation-Sedation Scale (RASS), respiratory parameters, and vasopressor dose were assessed after bolus and at 15, 30 and 60 min of infusion of propofol. RESULTS: Median IAP at baseline was 15 (13-16) mm Hg. During the intervention, median IAP decreased by 1 mm Hg at all time points. In 24% of patients IAP decreased by ≥3 mm Hg. Compared to baseline, MAP and APP were reduced at all time points. Deepening of sedation per RASS was achieved in 70% of patients at all time points. No changes in respiratory tidal volumes nor plateau pressures were observed. Vasopressor therapy with noradrenaline was started or increased in 43% of patients, whereas the increase in patients already receiving noradrenaline prior to the intervention was not significant. CONCLUSIONS: Deepening of sedation with propofol results in a small decrease in IAP and greater simultaneous decrease in MAP and APP, requiring increased vasopressor support in some cases.

Citrulline and intestinal fatty acid-binding protein as biomarkers for gastrointestinal dysfunction in the critically ill.

Currently there is no reliable tool available to monitor gastrointestinal function in the critically ill. Biomarkers are therefore of great interest in this field as the lack of monitoring tools impedes any interventional studies. The potential biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) are the present focus. Targeted literature searches were undertaken for physiology and pathophysiology, sampling, measurement methods and clinical use of citrulline and I-FABP as biomarkers of intestinal function and injury. Physiology and pathophysiology, specific aspects of sampling and different laboratory assays are summarized and respective pitfalls outlined. Studies in animals and patients outside the ICU support the rationale for these biomarkers. At the same time, evidence in critically ill patients is not yet convincing, several specific aspects need to be clarified, and methodology and interpretation to be refined. We conclude that there are good physiological rationales for citrulline as a marker of enterocyte function and for I-FABP as a marker of intestinal injury, but further studies are needed to clarify whether and how they could be used in daily practice in caring for critically ill patients.

Gastrointestinal failure affects outcome of intensive care.

PURPOSE: Goal of this study was to describe incidence and outcome of gastrointestinal failure (GIF) in ICU patients, evaluate its additive role to SOFA score in mortality prediction and describe GIF according to etiology. MATERIALS AND METHODS: A retrospective study with prospective data collection was conducted in mixed adult ICU patients admitted 2004-2015. GIF was considered present if ≥3 of following 6 symptoms occurred in 1 day: maximum gastric residual volume ≥ 500 mL; absent bowel sounds; vomiting or regurgitation; diarrhea; suspected or radiologically confirmed bowel distension; gastrointestinal bleeding. Division into primary (gastrointestinal pathology causing GIF) and secondary (due to other conditions) GIF was made based on origin of syndrome. RESULTS: GIF developed in 413 (10.4%) of 3959 patients. Primary GIF occurred in 61.3% and secondary GIF in 38.7% of patients. Development of GIF was associated with longer mechanical ventilation, ICU stay and higher ICU, 30-day and 90-day mortality. Outcomes of patients with primary and secondary GIF were similar. All SOFA sub-scores and number of gastrointestinal symptoms on admission day independently predicted 90-day mortality. CONCLUSIONS: Gastrointestinal failure, independent of origin, is associated with worse ICU outcome. Similar to other organ failures included in SOFA score, GIF independently predicts mortality.

Abdominal Compartment Syndrome: Improving Outcomes With A Multidisciplinary Approach - A Narrative Review.

Abdominal compartment syndrome (ACS) refers to a severe increase in intra-abdominal pressure associated with single or multiorgan failure. ACS with specific pathophysiological processes and detrimental outcomes may occur in a variety of clinical conditions. Patients with ACS are predominantly managed in critical care settings, however, a wide range of multidisciplinary interventions are frequently required from medical, surgical, radiological and nursing specialties. The medical management, aiming to prevent the progression of intra-abdominal hypertension to ACS, is extensively reviewed. Timing and techniques of surgical decompression techniques, as well as management of open abdomen, are outlined. In summary, the current narrative review provides data on history, definitions, epidemiology and pathophysiology of the syndrome and highlights the importance of multidisciplinary approach in the management of ACS in adults.

Implementation of enteral feeding protocol in an intensive care unit: Before-and-after study.

AIM: To determine the effects of implementing an enteral feeding protocol on the nutritional delivery and outcomes of intensive care patients. METHODS: An uncontrolled, observational before-and-after study was performed in a tertiary mixed medical-surgical intensive care unit (ICU). In 2013, a nurse-driven enteral feeding protocol was developed and implemented in the ICU. Nutrition and outcome-related data from patients who were treated in the study unit from 2011-2012 (the Before group) and 2014-2015 (the After group) were obtained from a local electronic database, the national Population Registry and the hospital's Infection Control Service. Data from adult patients, readmissions excluded, who were treated for at least 7 d in the study unit were analysed. RESULTS: In total, 231 patients were enrolled in the Before and 249 in the After group. The groups were comparable regarding demographics, patient profile, and severity of illness. Fewer patients were mechanically ventilated on admission in the After group (86.7% vs 93.1% in the Before group, P = 0.021). The prevalence of hospital-acquired infections, length of ICU stay and ICU, 30- and 60-d mortality did not differ between the groups. Patients in the After group had a lower 90-d (P = 0.026) and 120-d (P = 0.033) mortality. In the After group, enteral nutrition was prescribed less frequently (P = 0.039) on day 1 but significantly more frequently on all days from day 3. Implementation of the feeding protocol resulted in a higher cumulative amount of enterally (P = 0.049) and a lower cumulative amount of parenterally (P < 0.001) provided calories by day 7, with an overall reduction in caloric provision (P < 0.001). The prevalence of gastrointestinal symptoms was comparable in both groups, as was the frequency of prokinetic use. Underfeeding (total calories < 80% of caloric needs, independent of route) was observed in 59.4% of the study days Before vs 76.9% After (P < 0.001). Inclusion in the Before group, previous abdominal surgery, intra-abdominal hypertension and the sum of gastrointestinal symptoms were found to be independent predictors of insufficient enteral nutrition. CONCLUSION: The use of a nurse-driven feeding protocol improves the delivery of enteral nutrition in ICU patients without concomitant increases in gastrointestinal symptoms or intra-abdominal hypertension.

Postoperative complications and mortality after major gastrointestinal surgery.

BACKGROUND AND OBJECTIVE: The incidence of postoperative complications and death is low in the general population, but a subgroup of high-risk patients can be identified amongst whom adverse postoperative outcomes occur more frequently. The present study was undertaken to describe the incidence of postoperative complications, length of stay, and mortality after major abdominal surgery for gastrointestinal, hepatobiliary and pancreatic malignancies and to identify the risk factors for impaired outcome. MATERIAL AND METHODS: Data of patients, operated on for gastro-intestinal malignancies during 2009-2010 were retrieved from the clinical database of Tartu University Hospital. Major outcome data included incidence of postoperative complications, hospital-, 30-day, 90-day and 1-year mortality, and length of ICU and hospital stay. High-risk patients were defined as patients with American Society of Anesthesiologists (ASA) physical status ≥3 and revised cardiac risk index (RCRI) ≥3. Multivariate analysis was used to determine the risk factors for postoperative mortality and morbidity. RESULTS: A total of 507 (259 men and 248 women, mean age 68.3±11.3 years) were operated on for gastrointestinal, hepatobiliary, or pancreatic malignancies during 2009 and 2010 in Tartu University Hospital, Department of Surgical Oncology. 25% of the patients were classified as high risk patients. The lengths of intensive care and hospital stay were 4.4±7 and 14.5±10 days, respectively. The rate of postoperative complications was 33.5% in the total cohort, and 44% in high-risk patients. The most common complication was delirium, which occurred in 12.8% of patients. For patients without high risk (ASA130min, and positive fluid balance >1300mL after the 1st postoperative day, were identified as independent risk factors for the development of complications. CONCLUSION: The complication rate after major gastro-intestinal surgery is high. ASA physical status and revised cardiac risk index adequately reflect increased risk for postoperative complications and worse short and long-term outcome.