Association between enterocyte injury and fluid balance in patients with septic shock: a post hoc exploratory analysis of a prospective observational study

Background: The required fluid volume differs among patients with septic shock. Enterocyte injury caused by shock may increase the need for fluid by triggering a systematic inflammatory response or an ischemia-reperfusion injury in the presence of intestinal ischemia/necrosis. This study aimed to evaluate the association between enterocyte injury and positive fluid balance in patients with septic shock.Methods: This study was a post hoc exploratory analysis of a prospective observational study that assessed the association between serum intestinal fatty acid-binding protein, a biomarker of enterocyte injury, and mortality in patients with septic shock. Intestinal fatty acid-binding protein levels were recorded on intensive care unit admission, and fluid balance was monitored from intensive care unit admission to Day 7. The association between intestinal fatty acid-binding protein levels at admission and the infusion balance during the early period after intensive care unit admission was evaluated. Multiple linear regression analysis, with adjustments for severity score and renal function, was performed.Results: Overall, data of 57 patients were analyzed. Logarithmically transformed intestinal fatty acid-binding protein levels were significantly associated with cumulative fluid balance per body weight at 24 and 72 h post-intensive care unit admission both before (Pearson’s r = 0.490 [95% confidence interval: 0.263–0.666]; P < 0.001 and r = 0.479 [95% confidence interval: 0.240–0.664]; P < 0.001, respectively) and after (estimate, 14.4 [95% confidence interval: 4.1–24.7]; P = 0.007 and estimate, 26.9 [95% confidence interval: 11.0–42.7]; P = 0.001, respectively) adjusting for severity score and renal function.Conclusions: Enterocyte injury was significantly associated with cumulative fluid balance at 24 and 72 h post-intensive care unit admission. Enterocyte injury in patients with septic shock may be related to excessive fluid accumulation during the early period after intensive care unit admissio

Usefulness of intestinal fatty acid-binding protein in predicting strangulated small bowel obstruction.

BACKGROUND: The level of intestinal fatty acid-binding protein (I-FABP) is considered to be useful diagnostic markers of small bowel ischemia. The purpose of this retrospective study was to investigate whether the serum I-FABP level is a predictive marker of strangulation in patients with small bowel obstruction (SBO). METHODS: A total of 37 patients diagnosed with SBO were included in this study. The serum I-FABP levels were retrospectively compared between the patients with strangulation and those with simple obstruction, and cut-off values for the diagnosis of strangulation were calculated using a receiver operating characteristic curve. In addition, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Twenty-one patients were diagnosed with strangulated SBO. The serum I-FABP levels were significantly higher in the patients with strangulation compared with those observed in the patients with simple obstruction (18.5 vs. 1.6 ng/ml p<0.001). Using a cut-off value of 6.5 ng/ml, the sensitivity, specificity, PPV and NPV were 71.4%, 93.8%, 93.8% and 71.4%, respectively. An I-FABP level greater than 6.5 ng/ml was found to be the only independent significant factor for a higher likelihood of strangulated SBO (P =  0.02; odds ratio: 19.826; 95% confidence interval: 2.1560 - 488.300). CONCLUSIONS: The I-FABP level is a useful marker for discriminating between strangulated SBO and simple SBO in patients with SBO

Association between endotoxemia and enterocyte injury and clinical course in patients with gram-positive septic shock

Endotoxemia often occurs in patients with gram-positive infections. The possible mechanism is thought to be bacterial translocation after enterocyte hypoperfusion injury. However, the association between endotoxemia and enterocyte injury among patients with gram-positive septic shock has never been assessed. The aim of this study was to evaluate the association between endotoxemia and enterocyte injury in gram-positive septic shock patients and to evaluate the association among endotoxemia, subsequent clinicalcourse, and other related factors.This was a posthoc analysis of a prospective observational study that evaluated the capability of intestinal fatty acid-binding protein(I-FABP), an indicator of enterocyte injury, to predict mortality. Among 57 patients in septic shock, those whose causative microorganisms were gram positive were included. The correlation between endotoxin activity (EA), which indicates endotoxemia,and I-FABP levels upon admission to the intensive care unit (ICU), the clinical course, and other related factors were evaluated.A total of 21 patients were examined. One-third of the patients presented with high EA levels at the time of ICU admission.However, there was no significant correlation between EA and I-FABP levels (Spearman r=0.002, P=.993). Additionally, high EA levels were not associated with abdominal complications after ICU admission or mortality. Similarly, high EA levels were not associated with severity scores, inotropic scores, or lactate levels upon ICU admission, which were previously reported to be factorsrelated to high EA levels.In this posthoc analysis, no correlation was observed between endotoxemia and enterocyte injury among patients in gram-positiveseptic shock. Additionally, high EA levels were not associated with the clinical course and reported factors related to endotoxemia.Although our results need to be validated in a large prospective cohort study, hypoperfusion enterocyte injury might not be a cause of endotoxemia in these patients. Thus, if there is no correlation between EA and I-FABP levels, other mechanisms that induce high EA levels among patients with gram-positive septic shock should be elucidated

Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy.

We investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n = 34) or efavirenz (EFV) containing ART (n = 37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72).The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p = 0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p = 0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (Δ = -0.47 µg/ml; p = 0.015).Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT.ClinicalTrials.gov NCT01445223

Flow diagram of the patients included in this study.

<p>Forty-seven of 281 patients with acute abdomen were diagnosed with bowel obstruction. Ten patients with large bowel obstruction were excluded, and finally 37 patients with small bowel obstruction (SBO) were included in this study. According to the findings of enhanced computed tomography, they were divided into the two groups, those with strangulated bowel obstruction or those with simple bowel obstruction.</p

Results of the blood examinations.

<p>a: SBO indicates small bowel obstruction</p><p>WBC: white blood cell; Plt: platelet; ALP: alkaline phosphatase; LDH: lactic dehydrogenase; CK: creatine phosphokinase; CRP: C-reactive protein; LA: lactic acid; I-FABP: intestinal fatty acid-binding protein.</p

Comparison of the diagnostic usefulness of the blood biochemical markers for predicting strangulated small bowel obstruction.

<p>Numbers in parentheses represent 95% confidence intervals.</p>a<p>ROC indicates receivor operating characteristics.</p>b<p>PPV indicates the positive predictive value.</p>c<p>NPV indicates the negative predictive value.</p><p>WBC: white blood cell; Plt: platelet; ALP: alkaline phosphatase; LDH: lactic dehydrogenase;</p><p>CK:creatine phosphokinase; CRP: C-reactive protein; LA:lactic acid; I-FABP: intestinal fatty acid-binding protein</p

Clinical characteristics (n = 37).

<p>a: CT indicates computed tomography</p><p>b: SBO indicates small bowel obstruction</p