This trial involving critically ill adults with multiorgan failure who were receiving mechanical ventilation showed that early provision of glutamine and antioxidants did not improve clinical ...outcomes. Furthermore, the use of glutamine appeared to increase mortality.
Critically ill patients have oxidative stress. The most seriously ill patients in intensive care units (ICUs) have increased mediators of oxidant stress and a higher incidence of multiorgan failure than less seriously ill patients.
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Meta-analyses of randomized trials suggest that glutamine and antioxidant supplementation in critically ill patients may be associated with improved survival.
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However, recent large studies have not confirmed such an effect.
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The objective of the present trial was to evaluate the effect of early glutamine and antioxidant supplementation in critically ill patients. Our a priori hypothesis was that supplementation with these nutrients would reduce . . .
Background: While consent exists, that nutritional status has prognostic impact in the critically ill, the optimal feeding strategy has been a matter of debate. Methods: Narrative review of the ...recent evidence and international guideline recommendations focusing on basic principles of nutrition in the ICU and the treatment of specific patient groups. Covered topics are: the importance and diagnosis of malnutrition in the ICU, the optimal timing and route of nutrition, energy and protein requirements, the supplementation of specific nutrients, as well as monitoring and complications of a Medical Nutrition Therapy (MNT). Furthermore, this review summarizes the available evidence to optimize the MNT of patients grouped by primarily affected organ system. Results: Due to the considerable heterogeneity of the critically ill, MNT should be carefully adapted to the individual patient with special focus on phase of critical illness, metabolic tolerance, leading symptoms, and comorbidities. Conclusion: MNT in the ICU is complex and requiring an interdisciplinary approach and frequent reevaluation. The impact of personalized and disease-specific MNT on patient-centered clinical outcomes remains to be elucidated.
Patients in the intervention group had 10% higher lactate levels, were more often in shock and mechanically ventilated already at baseline. ...compared to placebo, patients receiving vitamin C ...appeared to be sicker, overall contributing to the higher risk of organ dysfunction. ...numerous RCTs assessing the effects of IV vitamin C have been performed in critically ill patients followed by several systematic reviews and meta-analyses (SRMA) 7. ...in most of the trials, patients were included largely based on undifferentiated phenotypes, likely having a different mortality risk and also different treatment response 12, 13. ...imbalances in sepsis phenotypes may have contributed to the heterogeneity in response to vitamin C in the different trials. ...no surrogate markers of vitamin C were measured and the average vitamin C level (measured in a sub-cohort) was in the normal range, whereas patients with vitamin C deficiency are known to most likely to benefit from a supplementation.
Enteral nutrition (EN) is recommended as the preferred route for early nutrition therapy in critically ill adults over parenteral nutrition (PN). A recent large randomized controlled trial (RCT) ...showed no outcome differences between the two routes. The objective of this systematic review was to evaluate the effect of the route of nutrition (EN versus PN) on clinical outcomes of critically ill patients.
An electronic search from 1980 to 2016 was performed identifying relevant RCTs. Individual trial data were abstracted and methodological quality of included trials scored independently by two reviewers. The primary outcome was overall mortality and secondary outcomes included infectious complications, length of stay (LOS) and mechanical ventilation. Subgroup analyses were performed to examine the treatment effect by dissimilar caloric intakes, year of publication and trial methodology. We performed a test of asymmetry to assess for the presence of publication bias.
A total of 18 RCTs studying 3347 patients met inclusion criteria. Median methodological score was 7 (range, 2-12). No effect on overall mortality was found (1.04, 95 % CI 0.82, 1.33, P = 0.75, heterogeneity I(2) = 11 %). EN compared to PN was associated with a significant reduction in infectious complications (RR 0.64, 95 % CI 0.48, 0.87, P = 0.004, I(2) = 47 %). This was more pronounced in the subgroup of RCTs where the PN group received significantly more calories (RR 0.55, 95 % CI 0.37, 0.82, P = 0.003, I(2) = 0 %), while no effect was seen in trials where EN and PN groups had a similar caloric intake (RR 0.94, 95 % CI 0.80, 1.10, P = 0.44, I(2) = 0 %; test for subgroup differences, P = 0.003). Year of publication and methodological quality did not influence these findings; however, a publication bias may be present as the test of asymmetry was significant (P = 0.003). EN was associated with significant reduction in ICU LOS (weighted mean difference WMD -0.80, 95 % CI -1.23, -0.37, P = 0.0003, I(2) = 0 %) while no significant differences in hospital LOS and mechanical ventilation were observed.
In critically ill patients, the use of EN as compared to PN has no effect on overall mortality but decreases infectious complications and ICU LOS. This may be explained by the benefit of reduced macronutrient intake rather than the enteral route itself.
Selenium (Se) is an essential trace element with antioxidant, anti-inflammatory, and immunomodulatory effects. So far, several randomized clinical trials (RCTs) have demonstrated that parenteral Se ...may improve clinical outcomes in intensive care unit (ICU) patients. Since publication of our previous systematic review and meta-analysis on antioxidants in the ICU, reports of several trials have been published, including the largest RCT on Se therapy. The purpose of the present systematic review was to update our previous data on intravenous (IV) Se in the critically ill.
We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. We included RCTs with parallel groups comparing parenteral Se as single or combined therapy with placebo. Potential trials were evaluated according to specific eligibility criteria, and two reviewers abstracted data from original trials in duplicate independently. Overall mortality was the primary outcome; secondary outcomes were infections, ICU length of stay (LOS), hospital LOS, ventilator days, and new renal dysfunction.
A total of 21 RCTs met our inclusion criteria. When the data from these trials were aggregated, IV Se had no effect on mortality (risk ratio RR 0.98, 95 % CI 0.90-1.08, P = 0.72, heterogeneity I
= 0 %). In addition, when the results of ten trials in which researchers reported on infections were statistically aggregated, there was no significant treatment effect of parenteral Se (RR 0.95, 95 % CI 0.88-1.02, P = 0.15, I
= 0 %). There was no positive or negative effect of Se therapy on ICU and hospital LOS, renal function, or ventilator days.
In critically ill patients, IV Se as monotherapy does not improve clinical outcomes.
Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop ...a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies.
This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds.
Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness.
Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.
Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European ...intensive care units (ICU) and their importance for clinical outcomes.
Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10-20 kcal/kg, 0.8-1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV).
A total of 1172 patients with median Q1;Q3 APACHE II score of 18.5 13.0;26.0 were included, and 24% died within 90 days. Median length of ICU stay was 10.0 7.0;16.0 days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% 59;107 and 65% 41;91 of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 95% CI: 1.60;3.25 for calorie intake, 0.14 0.09;0.20 for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (- 2.74 - 3.28; - 2.21 and - 0.12 - 0.15; - 0.09, respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 95% CI: 1.5;14.09 on day 12; for protein: maximum HR 2.60 1.09;6.23 on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, 0.05;0.39 on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements.
Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registration NCT04143503 , registered on October 25, 2019.
Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use.
Using ...a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: < 0.8 g/kg per day, standard: 0.8-1.2 g/kg per day, high: > 1.2 g/kg per day) during the first 11 days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet).
Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49 g/kg IQR 0.27-0.66, standard intake 0.99 g/kg IQR 0.89- 1.09, and high intake 1.41 g/kg IQR 1.29-1.60. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95% CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95% CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome.
Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase. Study registration ID number ISRCTN17829198.
This study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to ...identify disease severity in patients with sepsis.
This is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was assessed by Cox regression analysis, area under the receiver operating characteristic and Kaplan-Meier curves. Patients were stratified into three severity groups (low, intermediate, high) for all biomarkers and scores based on cutoffs with either a 90% sensitivity or specificity.
1089 patients with a 28-day mortality rate of 26.9% were analysed. According to the Sepsis-3 definition, 41.2% and 58.8% fulfilled the criteria for sepsis and septic shock, with respective mortality rates of 20.0% and 32.1%. MR-proADM had the strongest association with mortality across all Sepsis-1 and Sepsis-3 subgroups and could facilitate a more accurate classification of low (e.g. MR-proADM vs. SOFA: N = 265 vs. 232; 9.8% vs. 13.8% mortality) and high (e.g. MR-proADM vs. SOFA: N = 161 vs. 155; 55.9% vs. 41.3% mortality) disease severity. Patients with decreasing PCT concentrations of either ≥ 20% (baseline to day 1) or ≥ 50% (baseline to day 4) but continuously high MR-proADM concentrations had a significantly increased mortality risk (HR (95% CI): 19.1 (8.0-45.9) and 43.1 (10.1-184.0)).
MR-proADM identifies disease severity and treatment response more accurately than established biomarkers and scores, adding additional information to facilitate rapid clinical decision-making and improve personalised sepsis treatment.
...recent studies have proposed that virus-induced endothelial dysfunction and damage, resulting in impaired vascular blood flow, coagulation and leakage, may partially explain the development of ...organ dysfunction and oedema 1. ...the development of endotheliitis may be a prominent, yet partly under recognised, feature of COVID-19 induced critical illness. ...ADM may also be of interest within COVID-19 induced endotheliitis.
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