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Differences and Similarities Among COVID-19 Patients Treated in Seven ICUs in Three Countries Within One Region: An Observational Cohort Study.
Mesotten, D, Meijs, DAM, van Bussel, BCT, Stessel, B, Mehagnoul-Schipper, J, Hana, A, Scheeren, CIE, Strauch, U, van de Poll, MCG, Ghossein-Doha, C, et al
Critical care medicine. 2022;(4):595-606
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Abstract
OBJECTIVES To investigate healthcare system-driven variation in general characteristics, interventions, and outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU within one Western European region across three countries. DESIGN Multicenter observational cohort study. SETTING Seven ICUs in the Euregio Meuse-Rhine, one region across Belgium, The Netherlands, and Germany. PATIENTS Consecutive COVID-19 patients supported in the ICU during the first pandemic wave. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Baseline demographic and clinical characteristics, laboratory values, and outcome data were retrieved after ethical approval and data-sharing agreements. Descriptive statistics were performed to investigate country-related practice variation. From March 2, 2020, to August 12, 2020, 551 patients were admitted. Mean age was 65.4 ± 11.2 years, and 29% were female. At admission, Acute Physiology and Chronic Health Evaluation II scores were 15.0 ± 5.5, 16.8 ± 5.5, and 15.8 ± 5.3 (p = 0.002), and Sequential Organ Failure Assessment scores were 4.4 ± 2.7, 7.4 ± 2.2, and 7.7 ± 3.2 (p < 0.001) in the Belgian, Dutch, and German parts of Euregio, respectively. The ICU mortality rate was 22%, 42%, and 44%, respectively (p < 0.001). Large differences were observed in the frequency of organ support, antimicrobial/inflammatory therapy application, and ICU capacity. Mixed-multivariable logistic regression analyses showed that differences in ICU mortality were independent of age, sex, disease severity, comorbidities, support strategies, therapies, and complications. CONCLUSIONS COVID-19 patients admitted to ICUs within one region, the Euregio Meuse-Rhine, differed significantly in general characteristics, applied interventions, and outcomes despite presumed genetic and socioeconomic background, admission diagnosis, access to international literature, and data collection are similar. Variances in healthcare systems' organization, particularly ICU capacity and admission criteria, combined with a rapidly spreading pandemic might be important drivers for the observed differences. Heterogeneity between patient groups but also healthcare systems should be presumed to interfere with outcomes in coronavirus disease 2019.
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Achieving enteral nutrition during the acute phase in critically ill children: Associations with patient characteristics and clinical outcome.
Eveleens, RD, Hulst, JM, de Koning, BAE, van Brakel, J, Rizopoulos, D, Garcia Guerra, G, Vanhorebeek, I, Van den Berghe, G, Joosten, KFM, Verbruggen, SCAT
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1911-1919
Abstract
BACKGROUND & AIMS In the absence of methodologically sound randomized controlled trials (RCTs), current recommendations for timing and amount of enteral nutrition (EN) in critically ill children are based on observational studies. These studies have associated achievement of a higher EN intake in critically ill children with improved outcome. Inherent to the observational design of these underlying studies, thorough insight in possible confounding factors to correct for is essential. We evaluated the associations between EN intake and 1) patient and daily clinical characteristics and 2) clinical outcomes adjusted for these patient and clinical characteristics during the first week of critical illness with a multivariable mixed model. METHODS This secondary analysis of the multicentre PEPaNIC RCT investigated a subgroup of critically ill children with daily prospectively recorded gastrointestinal symptoms and EN intake during the first week with multivariable analyses using two-part mixed effect models, including multiple testing corrections using Holm's method. These models combined a mixed-effects logistic regression for the dichotomous outcome EN versus no EN, and a linear mixed-effects model for the patients who received any EN intake. EN intake per patient was expressed as mean daily EN as % of predicted resting energy expenditure (% of EN/REE). Model 1 included 40 fixed effect baseline patient characteristics, and daily parameters of illness severity, feeding, medication and gastrointestinal symptoms. Model 2 included these patient and daily variables as well as clinical outcomes. RESULTS Complete data were available for 690 children. EN was provided in 503 (73%) patients with a start after a median of 2 (IQR 2-3) days and a median % of EN/REE of 38.8 (IQR 14.1-79.5) over the first week. Multivariable mixed model analyses including all patients showed that admission after gastrointestinal surgery (-49%EN/REE; p = 0.002), gastric feeding (-31% EN/REE; p < 0.001), treatment with inotropic agents (-22%EN/REE; p = 0.026) and large gastric residual volume (-64%EN/REE; p < 0.001) were independently associated with a low mean EN intake. In univariable analysis, low mean EN intake was associated with new acquired infections, hypoglycaemia, duration of PICU and hospital stay and duration of mechanical ventilation. However, after adjustment for confounders, these associations were no longer present, except for low EN and hypoglycaemia (-39%EN/REE; p = 0.018). CONCLUSIONS Several patient and clinical characteristics during the first week of critical illness were associated with EN intake. No independent associations were found between EN intake and clinical outcomes such as mortality, new acquired infection and duration of stay. These data emphasize the necessity of adequate multivariable adjustment in nutritional support research and the need for future RCTs investigating optimal EN intake.
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TICACOS international: A multi-center, randomized, prospective controlled study comparing tight calorie control versus Liberal calorie administration study.
Singer, P, De Waele, E, Sanchez, C, Ruiz Santana, S, Montejo, JC, Laterre, PF, Soroksky, A, Moscovici, E, Kagan, I
Clinical nutrition (Edinburgh, Scotland). 2021;(2):380-387
Abstract
UNLABELLED Since the first TICACOS study, 3 additional studies have been published comparing a medical nutrition therapy guided by indirect calorimetry to a regimen prescribed on the basis of predictive equations. A recent guidelines document included a meta-analysis including these 4 papers and found a trend for improvement (OR 0.98-1.48) in favor of medical nutrition therapy guided by indirect calorimetry in terms of survival. The aim of our study was to perform a multicenter prospective, randomized, controlled non blinded study in critically patients to assess the added value for measuring daily resting energy expenditure as a guide for nutritional support. The primary objective was to decrease infectious rate of these critically ill patients. MATERIAL AND METHODS This phase III, multi-center, randomized, controlled non blinded study was planned to include 580 newly-admitted, adult ventilated ICU patients that were planned to stay more than 48 h in the ICU departments. The nutritional support was aimed to meet 80-100% of energy requirement measured by indirect calorimetry. The calorie needs were determined by IC in the Study group and by an equation (20-25 kcal/kg ideal body weight/day) in the Control Group. The ICU staff was trained to strive to supply 80-100% of a patient's energy requirements through artificial nutrition, preferably enteral feeding. Primary endpoint was infection rate and secondary endpoints included other morbidities and mortality during ICU, at 90 and 180 days. Comparison between the study and the control group was performed using T test for equality of means (independent samples test). Correlations were performed using the Pearson correlation test. A p level of 0.05 or below was considered as significant. Cross tabs procedure used Chi-square test for testing differences in complication rates, length of stay and length of ventilation. Correlations between energy balances and complications was also be tested using one way analysis as well as ANOVA analysis between groups and within groups. Kaplan Meir curves assessed the proportion of surviving patients in the 2 groups. RESULTS Seven centers with a calorimeter available participated to the study. Due to slow inclusion rate, the study was stopped after 6 years and after inclusion of 417 patients only. From the 417 intended to treat patients, 339 followed the protocol. There was no differences between control and study groups in terms of age, sex BMI, SOFA (7.1 ± 3.1 vs 7.4 ± 3.3) and APACHE II scores (22.4 ± 7.9 vs 22.2 ± 7.4). The rate of infection (40 vs 31), including pneumonia rate, need for surgery, dialysis requirement, length of ventilation, ICU length of stay, and hospital length of stay were not different between groups. Mortality (30 in the control vs 21 in the study group) was not significantly different between groups. The decreased mortality observed in the study group when added to previous studies may have a positive effect on the meta-analysis previously published. CONCLUSION Tight Calorie Control guided by indirect calorimetry decreased the rate of infection and mortality but not significantly. This may be explained by the not relatively small sample size. There results together with the previous 4 prospective randomized studies, may improve the results of the meta-analysis exploring the effects of IC guided nutrition on mortality.
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Nocturnal Hypoglycemia in Patients With Diabetes Discharged From ICUs: A Prospective Two-Center Cohort Study.
Ali Abdelhamid, Y, Bernjak, A, Phillips, LK, Summers, MJ, Weinel, LM, Lange, K, Chow, E, Kar, P, Horowitz, M, Heller, S, et al
Critical care medicine. 2021;(4):636-649
Abstract
OBJECTIVES There is very limited information about glycemic control after discharge from the ICU. The aims of this study were to evaluate the prevalence of hypoglycemia in ICU survivors with type-2 diabetes and determine whether hypoglycemia is associated with cardiac arrhythmias. DESIGN Prospective, observational, two-center study. Participants underwent up to 5 days of simultaneous blinded continuous interstitial glucose monitoring and ambulatory 12-lead electrocardiogram monitoring immediately after ICU discharge during ward-based care. Frequency of arrhythmias, heart rate variability, and cardiac repolarization markers were compared between hypoglycemia (interstitial glucose ≤ 3.5 mmol/L) and euglycemia (5-10 mmol/L) matched for time of day. SETTING Mixed medical-surgical ICUs in two geographically distinct university-affiliated hospitals. PATIENTS Patients with type-2 diabetes who were discharged from ICU after greater than or equal to 24 hours with greater than or equal to one organ failure and were prescribed subcutaneous insulin were eligible. MEASUREMENTS AND MAIN RESULTS Thirty-one participants (mean ± sd, age 65 ± 13 yr, glycated hemoglobin 64 ± 22 mmol/mol) were monitored for 101 ± 32 hours post-ICU (total 3,117 hr). Hypoglycemia occurred in 12 participants (39%; 95% CI, 22-56%) and was predominantly nocturnal (40/51 hr) and asymptomatic (25/29 episodes). Participants experiencing hypoglycemia had 2.4 ± 0.7 discrete episodes lasting 45 minutes (interquartile range, 25-140 min). Glucose nadir was less than or equal to 2.2 mmol/L in 34% of episodes. The longest episode of nocturnal hypoglycemia was 585 minutes with glucose nadir less than 2.2 mmol/L. Simultaneous electrocardiogram and continuous interstitial glucose monitoring recordings were obtained during 44 hours of hypoglycemia and 991 hours of euglycemia. Hypoglycemia was associated with greater risk of bradycardia but did not affect atrial or ventricular ectopics, heart rate variability, or cardiac repolarization. CONCLUSIONS In ICU survivors with insulin-treated type-2 diabetes, hypoglycemia occurs frequently and is predominantly nocturnal, asymptomatic, and prolonged.
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Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.
Dixon, B, Smith, RJ, Campbell, DJ, Moran, JL, Doig, GS, Rechnitzer, T, MacIsaac, CM, Simpson, N, van Haren, FMP, Ghosh, AN, et al
The Lancet. Respiratory medicine. 2021;(4):360-372
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Abstract
BACKGROUND Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS. METHODS The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO2/FiO2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 109/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0·9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk patients, deterioration of the Murray Lung Injury Score (MLIS) to day 5, mortality at day 60, residence of survivors at day 60, and serious adverse events. Analyses followed the intention-to-treat principle. There was no imputation of missing data. The trial is registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612000418875 . FINDINGS Between Sept 4, 2012, and Aug 23, 2018, 256 patients were randomised. Final follow-up was on Feb 25, 2019. We excluded three patients who revoked consent and one ineligible participant who received no intervention. Of 252 patients included in data analysis, the mean age was 58 years (SD 15), 157 (62%) were men, and 118 (47%) had ARDS. 128 (51%) patients were assigned to the heparin group and 124 (49%) to the placebo group, all of whom received their assigned intervention. Survivors in the heparin group (n=97) had similar SF-36 Physical Function Scores at day 60 compared to the placebo group (n=94; mean 53·6 [SD 31·6] vs 48·7 [35·7]; difference 4·9 [95% CI -4·8 to 14·5]; p=0·32). Compared with the placebo group, the heparin group had fewer cases of ARDS develop to day 5 among the at-risk patients (nine [15%] of 62 patients vs 21 [30%] of 71 patients; hazard ratio 0·46 [95% CI 0·22 to 0·98]; p=0·0431), less deterioration of the MLIS to day 5 (difference -0·14 [-0·26 to -0·02]; p=0·0215), similar day 60 mortality (23 [18%] of 127 patients vs 18 [15%] of 123 patients; odds ratio [OR] 1·29 [95% CI 0·66 to 2·53]; p=0·46), and more day 60 survivors at home (86 [87%] of 99 patients vs 73 [73%] of 100 patients; OR 2·45 [1·18 to 5·08]; p=0·0165). A similar number of serious adverse events occurred in each group (seven [5%] of 128 patients in the heparin group vs three [2%] of 124 patients in the placebo group; OR 2·33 [0·59 to 9·24]; p=0·23), which were a transient increase in airway pressure during nebulisation (n=3 in the heparin group), major non-pulmonary bleeding (n=2 in each group), haemoptysis (n=1 in the heparin group), tracheotomy site bleeding (n=1 in the heparin group), and hypoxaemia during nebulisation (n=1 in the placebo group). INTERPRETATION In patients with or at risk of ARDS, nebulised heparin did not improve self-reported performance of daily physical activities, but was well tolerated and exploratory outcomes suggest less progression of lung injury and earlier return home. Further research is justified to establish if nebulised heparin accelerates recovery in those who have or are at risk of ARDS. FUNDING Rowe Family Foundation, TR and RB Ditchfield Medical Research Endowment Fund, Patricia Madigan Charitable Trust, and The J and R McGauran Trust Fund.
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Effects of oral/enteral nutrition alone versus plus pantoprazole on gastrointestinal bleeding in critically ill patients with low risk factor: a multicenter, randomized controlled trial.
Gündoğan, K, Karakoc, E, Teke, T, Zerman, A, Esmaoglu, A, Temel, Ş, Güven, M, Sungur, M
Turkish journal of medical sciences. 2020;(4):776-783
Abstract
BACKGROUND/AIM: Critically ill patients are at risk of developing gastrointestinal (GI) bleeding due to stress causing mucosal damage. Aim of the study was to determine the effect of oral/enteral nutrition with or without concomitant pantoprazole on upper GI bleeding in low risk critically ill patients. MATERIALS AND METHODS This was a prospective, randomized, open-label, multicenter study conducted with intensive care unit (ICU) patients receiving oral/enteral nutritional support. Patients were randomly assigned into two groups including intervention group (received oral/EN plus pantoprazole) and control group (received only oral/EN). RESULTS A total of 300 patients (intervention group: 152, control group: 148) participated in the study. Overall, 226 (75%) patients were fed by orally and 74 (25%) patients fed by enteral tube feeding. Median duration of nutritional support 4 (range: 2–33) days. Overt upper GI bleeding was noted only in one patient (0.65%) who was in the intervention group. The overall length of ICU stay of 4 (2–105) days, while ICU stay was significantly longer in the intervention group than in the control group (P = 0.006). CONCLUSIONS Our findings seems to indicate that in patients who are at low risk for GI bleeding and under oral/enteral nutritional support, the use of PPIs may not reduce the risk of bleeding, however these results are imprecise because of low event (GI bleeding) rate and limited power.
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Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.
Wischmeyer, PE, Mintz-Cole, RA, Baird, CH, Easley, KA, May, AK, Sax, HC, Kudsk, KA, Hao, L, Tran, PH, Jones, DP, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(2):563-573
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BACKGROUND Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. OBJECTIVE Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. METHODS Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. RESULTS eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. CONCLUSION Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.
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Prophylactic Haloperidol Effects on Long-term Quality of Life in Critically Ill Patients at High Risk for Delirium: Results of the REDUCE Study.
Rood, PJT, Zegers, M, Slooter, AJC, Beishuizen, A, Simons, KS, van der Voort, PHJ, van der Woude, MCE, Spronk, PE, van der Hoeven, JG, Pickkers, P, et al
Anesthesiology. 2019;(2):328-335
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BACKGROUND Delirium incidence in intensive care unit patients is high and associated with impaired long-term outcomes. The use of prophylactic haloperidol did not improve short-term outcome among critically ill adults at high risk of delirium. This study evaluated the effects of prophylactic haloperidol use on long-term quality of life in this group of patients and explored which factors are associated with change in quality of life. METHODS A preplanned secondary analysis of long-term outcomes of the pRophylactic haloperidol usE for DeliriUm in iCu patients at high risk for dElirium (REDUCE) study was conducted. In this multicenter randomized clinical trial, nondelirious intensive care unit patients were assigned to prophylactic haloperidol (1 or 2 mg) or placebo (0.9% sodium chloride). In all groups, patients finally received study medication for median duration of 3 days [interquartile range, 2 to 6] until onset of delirium or until intensive care unit discharge. Long-term outcomes were assessed using the Short Form-12 questionnaire at intensive care unit admission (baseline) and after 1 and 6 months. Quality of life was summarized in the physical component summary and mental component summary scores. Differences between the haloperidol and placebo group and factors associated with changes in quality of life were analyzed. RESULTS Of 1,789 study patients, 1,245 intensive care unit patients were approached, of which 887 (71%) responded. Long-term quality of life did not differ between the haloperidol and placebo group (physical component summary mean score of 39 ± 11 and 39 ± 11, respectively, and P = 0.350; and mental component summary score of 50 ± 10 and 51 ± 10, respectively, and P = 0.678). Age, medical and trauma admission, quality of life score at baseline, risk for delirium (PRE-DELIRIC) score, and the number of sedation-induced coma days were significantly associated with a decline in long-term quality of life. CONCLUSIONS Prophylactic haloperidol use does not affect long-term quality of life in critically ill patients at high risk for delirium. Several factors, including the modifiable factor number of sedation-induced coma days, are associated with decline in long-term outcomes.
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[Evaluation of the degree of adherence to the nutritional recommendations of the critical care patient].
Serviá Goixart, L, López Delgado, JC, Grau Carmona, T
Nutricion hospitalaria. 2019;(3):510-516
Abstract
Background: the application of specialized nutritional support (SNE) is difficult at the organizational level due to the complexity of clinical practice guidelines and we do not know the degree of adherence to the published nutritional recommendations. The aim of this study was to assess the degree of adherence to the recommendations of high impact and "do not do" within our environment, in order to show areas for improvement. Methods: survey of nine questions agreed by experts and carried out in different ICUs of our environment, which reflected the recommendations in SNE. Data related to the organizational characteristics and the healthcare provider that indicated the nutritional support were collected. The differences regarding the degree of adherence between the level of care and the presence of an expert in these units were analyzed. Results: thirty-seven ICUs participated, which corresponded mostly to second level hospitals and polyvalent ICUs with an SNE indicated by intensivists. The adherence to the recommendations was > 80%, with three exceptions associated with issues related to the refeeding syndrome (70.3%), the caloric-protein adjustment of nutrition according to the patient's evolutionary phase (51.4%) and the adjustment of protein intake in patients with renal failure (40.5%). There were no differences according to the level of care or the presence of an expert in these ICUs. Only a greater availability of local nutrition protocols was observed in those ICUs with an expertise. Conclusions: there is a high theoretical adherence to the majority of recommendations in the nutritional field, with exceptions that could correspond to areas where there is an opportunity for improvement.
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The effect of a natural food based tube feeding in minimizing diarrhea in critically ill neurological patients.
Schmidt, SB, Kulig, W, Winter, R, Vasold, AS, Knoll, AE, Rollnik, JD
Clinical nutrition (Edinburgh, Scotland). 2019;(1):332-340
Abstract
BACKGROUND & AIMS Diarrhea has negative consequences for patients, health care staff and health care costs when neurological patients are fed enterally over long periods. We examined the effect of tube feeding with natural foods in reducing the number of fluid stool evacuations and diarrhea in critically ill neurological patients. METHODS A multicenter, prospective, open-label and randomized controlled trial (RCT) was conducted at facilities in Germany specializing in early rehabilitation after neurological damage. Patients of the INTERVENTION group were fed by tube using a commercially available product based on real foods such as milk, meat, carrots, whereas CONTROL patients received a standard tube-feed made of powdered raw materials. All received enteral nutrition over a maximum of 30 days. The number of defecations and the consistency of each stool according to the Bristol Stool Chart (BSC) were monitored. In addition, daily calories, liquids and antibiotic-use were recorded. RESULTS 118 Patients who had suffered ischemic stroke, intracerebral hemorrhage, traumatic brain injury or hypoxic brain damage and requiring enteral nutrition were enrolled; 59 were randomized to receive the intervention and 59 control feed. There were no significant differences in clinical screening data, age, sex, observation period or days under enteral nutrition between the groups. Patients in both groups received equivalent amount of calories and fluids. In both groups antibiotics were frequently prescribed (69.5% in the INTERVENTION group and 75.7% in the CONTROL group) for 10-11 days on average. In comparison to the CONTROL group, patients in the INTERVENTION group had a significant reduction of the number of watery stool evacuations (type 7 BSC) (minus 61%, IRR = 0.39, p < 0.001). Further statistical evaluations using the following corrections: major diarrhea-associated confounders (number and duration of antibiotics); shorter observation period of 15 days; excluding patients with Clostridium difficile associated diarrhea (CDAD) and the Per Protocol Population, confirmed the primary hypothesis. The number of days with diarrhea was significantly lower in the INTERVENTION group (0.8 ± 1.60 days versus 2.0 ± 3.46 days). CONCLUSIONS Tube feeding with natural based food was effective in reducing the number of watery defecations and diarrhea in long term tube-fed critically ill neurological patients, compared to those fed with standard tube feeding.