Background: Gastrointestinal (GI) motility disorders in intensive care patients remain relatively unexplored. Nowadays, the frequency, risk factors and complications of GI dysfunction during enteral nutrition (EN) become more questionable. Aim: To evaluate the frequency, risk factors and complications of GI dysfunction during EN in the first 2 weeks of the intensive care unit (ICU) stay and to identify precautions to prevent the development of GI dysfunction and avoid complications. Methods: In this prospective observational study, we deliberately targeted at-risk patients. A total of 137 patients who received nasogastric tube feeding in an ICU of a tertiary hospital were enrolled. Results: The incidence of GI dysfunction that was found to be 63% which was associated mainly between MDR bacteria positivity and negative fluid balance. Diarrhea was observed in 36 patients (26%) and on 147 patient-days (incidence rate, 5.5 per 100 patient-days). The median day of diarrhea onset was 6 days after the initiation of EN. Forty patients (29%) presented with constipation (85% during the first week). Fifty patients (36%) exhibited upper digestive intolerance on 212 patient-days (incidence rate, 7.9 per 100 patient-days), after a median EN duration of 6 days (range, 2–14 days). Logistic regression analysis revealed MDR bacteria growth in the culture (OR, 1.75; 95% CI, 1.15–2.67; P=0.008) and negative fluid balance (OR, 0.57; 95% CI, 0.34–0.94; P=0.03) as the risk factors for GI dysfunction. We also showed that GI dysfunction was associated with high SOFA score, hypo-albuminemia, catecholamine use, and prolonged length of stay (LOS). GI dysfunction, on the other hand, can cause some complications including inadequate nutrition, and newly developed decubitus ulcers. Conclusion: GI dysfunction should be considered a clinical predictor of inadequate nutrition and prolonged LOS. In addition, the most dramatic risk for GI dysfunction was observed in patients with MDR bacteria growth in the culture and patients in negative fluid balance. Intensivists provide appropriate nutrition for patients, as well as prompt intervention and the development of treatment strategies in the event of GI dysfunction.

Intravenous (IV) immunoglobulin (Ig) treatment is known to alleviate behavioral deficits and increase survival in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Sepsis was induced by cecal ligation perforation (CLP) in rats. The animals were divided into five groups: sham, control, CLP + saline, CLP + immunoglobulin G (IgG) (250 mg/kg, iv), and CLP + immunoglobulins enriched with immunoglobulin M (IgGAM) (250 mg/kg, iv). Blood and brain samples were taken in two sets of experiments to see the early (24 h) and late (10 days) effects of treatment. Total complement activity, complement 3 (C3), and soluble complement C5b-9 levels were measured in the sera of rats using ELISA-based methods. Cerebral complement, complement receptor, NF-κB, Bax, and Bcl-2 expressions were analyzed by western blot and/or RT-PCR methods. Immune cell infiltration and gliosis were examined by immunohistochemistry using CD3, CD4, CD8, CD11b, CD19, and glial fibrillary acidic protein antibodies. Apoptotic neuronal death was investigated by TUNEL staining. IVIgG and IgGAM administration significantly reduced systemic complement activity and cerebral C5a and C5a receptor expression. Likewise, both treatment methods reduced proapoptotic NF-κB and Bax expressions in the brain. IVIgG and IgGAM treatment induced considerable amelioration in glial cell proliferation and neuronal apoptosis which were increased in non-treated septic rats. We suggest that IVIgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. In both treatment methods, these beneficial effects might be mediated through reduction of anaphylatoxic C5a activity and subsequent inhibition of inflammation and apoptosis pathways.

Objectives: To evaluate the effect of adjunct treatment with Octagam, an intravenous immunoglobulin (IVIG) product, on clinical outcomes and biomarkers in critically ill COVID-19 patients. Methods: Data from a single center was analyzed retrospectively. Patients had received preliminary standard of intensive care (SIC) according to a local treatment algorithm, either alone or along with Octagam 5% at 30 g/day for 5 days. Both groups were compared regarding baseline characteristics, survival, and changes in inflammation markers. Imbalance in baseline APACHE II scores was addressed by propensity score matching. Otherwise, Kaplan-Meier and multiple logistic regression models were used. Results: Out of 93 patients, 51 had received Octagam and 42 had not. About 75% of patients were male and both groups had comparable body mass index and AB0 blood type distribution. Octagam-treated patients were younger (mean 65 ± 15 versus 71 ± 15 years, p = 0.066) and had slightly lower baseline disease scores (APACHE II: 20.6 versus 22.4, p = 0.281; SOFA: 5.0 versus 7.0, p = 0.006). Overall survival was 61% in the SIC + Octagam and 38% in the SIC only group (odds ratio: 2.2, 95% confidence interval: 0.9-5.4, p = 0.091 after controlling for baseline imbalances). Octagam significantly prolonged median survival time (68 versus 18 days, p = 0.014) and significantly reduced plasma levels of C-reactive protein (median change from baseline -71.5 versus -0.3 mg/L, p = 0.049). Conclusion: Clinically relevant benefits through adjunct Octagam treatment in COVID-19 need to be confirmed in a randomized, controlled trial.

Sepsis-induced brain dysfunction (SIBD) has been neglected until recently due to the absence of specific clinical or biological markers. There is increasing evidence that sepsis may pose substantial risks for long term cognitive impairment. To find out clinical and inflammatory factors associated with acute SIBD serum levels of cytokines, complement breakdown products and neurodegeneration markers were measured by ELISA in sera of 86 SIBD patients and 33 healthy controls. Association between these biological markers and cognitive test results was investigated. SIBD patients showed significantly increased IL-6, IL-8, IL-10 and C4 d levels and decreased TNF-α, IL-12, C5a and iC3b levels than healthy controls. No significant alteration was observed in neuronal loss and neurodegeneration marker [neuron specific enolase (NSE), amyloid β, tau] levels. Increased IL-1β, IL-6, IL-8, IL-10, TNF-α and decreased C4 d, C5a and iC3b levels were associated with septic shock, coma and mortality. Transient mild cognitive impairment was observed in 7 of 21 patients who underwent neuropsychological assessment. Cognitive dysfunction and neuronal loss were associated with increased duration of septic shock and delirium but not baseline serum levels of inflammation and neurodegeneration markers. Increased cytokine levels, decreased complement activity and increased neuronal loss are indicators of poor prognosis and adverse events in SIBD. Cognitive dysfunction and neuronal destruction in SIBD do not seem to be associated with systemic inflammation factors and Alzheimer disease-type neurodegeneration but rather with increased duration of neuronal dysfunction and enhanced exposure of the brain to sepsis-inducing pathogens.