Nutrition in the intensive care unit: from the acute phase to beyond.

Recent randomized controlled trials (RCTs) have shown no benefit but  dose-dependent harm by early full nutritional support in critically ill patients. Lack of benefit may be explained by anabolic resistance, suppression of cellular repair processes, and aggravation of hyperglycemia and insulin needs. Also early high amino acid doses did not provide benefit, but instead associated with harm in patients with organ dysfunctions. However, most studies focused on nutritional interventions initiated during the first days after intensive care unit admission. Although the intervention window of some RCTs extended into the post-acute phase of critical illness, no large RCTs studied nutritional interventions initiated beyond the first week. Hence, clear evidence-based guidance on when and how to initiate and advance nutrition is lacking. Prolonged underfeeding will come at a price as there is no validated metabolic monitor that indicates readiness for medical nutrition therapy, and an adequate response to nutrition, which likely varies between patients. Also micronutrient status cannot be assessed reliably, as inflammation can cause redistribution, so that plasma micronutrient concentrations are not necessarily reflective of total body stores. Moreover, high doses of individual micronutrients have not proven beneficial. Accordingly, current evidence provides clear guidance on which nutritional strategies to avoid, but the ideal nutritional regimen for individual patients remains unclear. In this narrative review, we summarize the findings of recent studies, discuss possible mechanisms explaining the results, point out pitfalls in interpretation of RCTs and their effect on clinical practice, and formulate suggestions for future research.

Incidence, diagnosis, management and outcome of acute mesenteric ischaemia: a prospective, multicentre observational study (AMESI Study).

BACKGROUND: The aim of this multicentre prospective observational study was to identify the incidence, patient characteristics, diagnostic pathway, management and outcome of acute mesenteric ischaemia (AMI). METHODS: All adult patients with clinical suspicion of AMI admitted or transferred to 32 participating hospitals from 06.06.2022 to 05.04.2023 were included. Participants who were subsequently shown not to have AMI or had localized intestinal gangrene due to strangulating bowel obstruction had only baseline and outcome data collected. RESULTS: AMI occurred in 0.038% of adult admissions in participating acute care hospitals worldwide. From a total of 705 included patients, 418 patients had confirmed AMI. In 69% AMI was the primary reason for admission, while in 31% AMI occurred after having been admitted with another diagnosis. Median time from onset of symptoms to hospital admission in patients admitted due to AMI was 24 h (interquartile range 9-48h) and time from admission to diagnosis was 6h (1-12 h). Occlusive arterial AMI was diagnosed in 231 (55.3%), venous in 73 (17.5%), non-occlusive (NOMI) in 55 (13.2%), other type in 11 (2.6%) and the subtype could not be classified in 48 (11.5%) patients. Surgery was the initial management in 242 (58%) patients, of which 59 (24.4%) underwent revascularization. Endovascular revascularization alone was carried out in 54 (13%), conservative treatment in 76 (18%) and palliative care in 46 (11%) patients. From patients with occlusive arterial AMI, revascularization was undertaken in 104 (45%), with 40 (38%) of them in one site admitting selected patients. Overall in-hospital and 90-day mortality of AMI was 49% and 53.3%, respectively, and among subtypes was lowest for venous AMI (13.7% and 16.4%) and highest for NOMI (72.7% and 74.5%). There was a high variability between participating sites for most variables studied. CONCLUSIONS: The overall incidence of AMI and AMI subtypes varies worldwide, and case ascertainment is challenging. Pre-hospital delay in presentation was greater than delays after arriving at hospital. Surgery without revascularization was the most common management approach. Nearly half of the patients with AMI died during their index hospitalization. Together, these findings suggest a need for greater awareness of AMI, and better guidance in diagnosis and management. TRIAL REGISTRATION: NCT05218863 (registered 19.01.2022).

Diagnostic accuracy of biomarkers to detect acute mesenteric ischaemia in adult patients: a systematic review and meta-analysis.

BACKGROUND: Acute mesenteric ischaemia (AMI) is a disease with different pathophysiological mechanisms, leading to a life-threatening condition that is difficult to diagnose based solely on clinical signs. Despite widely acknowledged need for biomarkers in diagnosis of AMI, a broad systematic review on all studied biomarkers in different types of AMI is currently lacking. The aim of this study was to estimate the diagnostic accuracy of all potential biomarkers of AMI studied in humans. METHODS: A systematic literature search in PubMed, The Cochrane Library, Web of Science and Scopus was conducted in December 2022. Studies assessing potential biomarkers of AMI in (at least 10) adult patients and reporting their diagnostic accuracy were included. Meta-analyses of biomarkers' sensitivity, specificity, and positive and negative likelihood ratios were conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed with the QUADAS-2 tool. RESULTS: Seventy-five studies including a total of 9914 patients assessed 18 different biomarkers in serum/plasma and one in urine (each reported in at least two studies), which were included in meta-analyses. None of the biomarkers reached a conclusive level for accurate prediction. The best predictive value overall (all studies with any type and stage of AMI pooled) was observed for Ischaemia-modified albumin (2 studies, sensitivity 94.7 and specificity 90.5), interleukin-6 (n = 4, 96.3 and 82.6), procalcitonin (n = 6, 80.1 and 86.7), and intestinal fatty acid-binding protein (I-FABP) measured in serum (n = 16, 73.9 and 90.5) or in urine (n = 4, 87.9 and 78.9). In assessment of transmural mesenteric ischaemia, urinary I-FABP (n = 2, 92.3 and 85.2) and D-dimer (n = 3, 87.6 and 83.6) showed moderate predictive value. Overall risk of bias was high, mainly because of selected study populations and unclear timings of the biomarker measurements after onset of symptoms. Combinations of biomarkers were rarely studied, not allowing meta-analyses. CONCLUSIONS: None of the studied biomarkers had sufficient sensitivity and specificity to diagnose AMI, although some biomarkers showed moderate predictive accuracy. Future studies should focus on timing of measurements of biomarkers, distinguishing between early stage and transmural necrosis, and between different types of AMI. Additionally, studies on combinations of biomarkers are warranted. PROSPERO registration: CRD42022379341.

How to avoid harm with feeding critically ill patients: a synthesis of viewpoints of a basic scientist, dietitian and intensivist.

The optimal feeding strategy in critically ill patients is a matter of debate, with current guidelines recommending different strategies regarding energy and protein targets. Several recent trials have added to the debate and question our previous understanding of the provision of nutrition during critical illness. This narrative review aims to provide a summary of interpretation of recent evidence from the view of basic scientist, critical care dietitian and intensivist, resulting in joined suggestions for both clinical practice and future research. In the most recent randomised controlled trial (RCT), patients receiving 6 versus 25 kcal/kg/day by any route achieved readiness for ICU discharge earlier and had fewer GI complications. A second showed that high protein dosage may be harmful in patients with baseline acute kidney injury and more severe illness. Lastly, a prospective observational study using propensity score matched analysis suggested that early full feeding, especially enteral, compared to delayed feeding is associated with a higher 28-day mortality. Viewpoints from all three professionals point to the agreement that early full feeding is likely harmful, whereas important questions regarding the mechanisms of harm as well as on timing and optimal dose of nutrition for individual patients remain unanswered and warrant future studies. For now, we suggest giving low dose of energy and protein during the first few days in the ICU and apply individualised approach based on assumed metabolic state according to the trajectory of illness thereafter. At the same time, we encourage research to develop better tools to monitor metabolism and the nutritional needs for the individual patient accurately and continuously.

Intravenous vitamin C therapy in adult patients with sepsis: A rapid practice guideline.

BACKGROUND: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy? METHODS: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted. RESULTS: At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI -2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD -18.9 h, 95% CI -26.5 to -11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD -0.69, 95% CI -1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis. CONCLUSIONS: The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged.

Gastrointestinal function in critically ill patients.

PURPOSE OF REVIEW: To summarize recent evidence regarding the diagnosis of acute gastrointestinal dysfunction and enteral feeding intolerance, and relationship of these to development of multiple organ dysfunction syndrome, during critical illness. RECENT FINDINGS: Novel gastric feeding tubes that attenuate gastroesophageal regurgitation or facilitate continuous monitoring of gastric motility have been developed. The definition of enteral feeding intolerance remains controversial, which may be resolved using a consensus process. A novel scoring system for gastrointestinal dysfunction (GIDS - GastroIntestinal Dysfunction Score) was recently developed but it is not yet validated or tested to evaluate the effect of any interventions. Studies of biomarkers to identify gastrointestinal dysfunction have yet to yield a suitable biomarker for daily clinical use. SUMMARY: The assessment of gastrointestinal function in critically ill patients continues to rely on complex daily clinical assessment. Scoring systems, consensus definitions and novel technology appear the most promising tools and interventions to improve patient care.

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.

Management of acute mesenteric ischaemia: Results of a worldwide survey.

BACKGROUND: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide. METHODS: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected. RESULTS: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity. CONCLUSIONS: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes.

The need for biomarkers to determine response to enteral nutrition during and after critical illness: an update.

PURPOSE OF REVIEW: Biomarkers proposed to provide prognosis or to determine the response to enteral nutrition have been assessed in a number of experimental and clinical studies which are summarized in the current review. RECENT FINDINGS: There are several pathophysiological mechanisms identified which could provide biomarkers to determine response to enteral nutrition. Several biomarkers have been studied, most of them insufficiently and none of them has made its way to clinical practice. Available studies have mainly assessed a simple association of a biomarker with outcomes, but are less focused on dynamic changes in the biomarker levels. Importantly, studies on pathophysiology and clinical features of gastrointestinal dysfunction, including enteral feeding intolerance, are also needed to explore the mechanisms potentially providing specific biomarkers. Not only an association of the biomarker with any adverse outcome, but also a rationale for repeated assessment to assist in treatment decisions during the course of illness is warranted. SUMMARY: There is no biomarker currently available to reliably provide prognosis or determine the response to enteral nutrition in clinical practice, but identification of such a biomarker would be valuable to assist in clinical decision-making.

Epidemiology of Acute Mesenteric Ischemia: A Population-Based Investigation.

BACKGROUND: There is a lack of population-based studies on acute mesenteric ischemia (AMI). We have therefore performed a nationwide epidemiological study in Estonia, addressing incidence, demographics, interventions and mortality of AMI. METHODS: A retrospective population-based review was conducted of all adult cases of AMI accrued from the digital Estonian Health Insurance Fund and Causes of Death Registry for 2016-2020 based on international classification of diseases (ICD-10) diagnostic codes and procedure codes (NOMESCO). RESULTS: Overall, 577 cases of AMI were identified-an annual incidence of 8.7 per 100,000. The median age was 79 (range 32-104) and 57% were female. Predominating comorbidities included hypertensive disease (81%), atherosclerosis (67%), and atrial fibrillation (52%). The majority of cases (60%) were caused by superior mesenteric artery occlusion (thrombosis 54%, embolism 12%, and unclear 34%). Inferior mesenteric artery occlusion occurred in 7%, non-occlusive mesenteric ischemia in 7%, venous thrombosis in 4%, whereas the type remained unclear in 21% of cases. 40% of patients received intervention (revascularization and/or intestinal resection) and 13% active non-operative treatment. In 21% an exploratory laparotomy or laparoscopy revealed unsalvageable bowel prompting end-of-life care, which was the only management in a further 25% of cases. CONCLUSIONS: The population-based annual incidence of AMI in Estonia was 8.7 per 100,000 during the study period. The overall hospital mortality and 1 year mortality were 64% and 74%, respectively. In the 53% of patients who received active treatment hospital mortality was 32% and 1 year all-cause mortality was 51%. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04867499.

Incidence and outcomes of acute mesenteric ischaemia: a systematic review and meta-analysis.

OBJECTIVE: To estimate the incidence of acute mesenteric ischaemia (AMI), proportions of its different forms and short-term and long-term mortality. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE (Ovid), Web of Science, Scopus and Cochrane Library were searched until 26 July 2022. ELIGIBILITY CRITERIA: Studies reporting data on the incidence and outcomes of AMI in adult populations. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment with modified Newcastle-Ottawa scale were performed using predeveloped standard forms. The outcomes were the incidence of AMI and its different forms in the general population and in patients admitted to hospital, and the mortality of AMI in its different forms. RESULTS: From 3064 records, 335 full texts were reviewed and 163 included in the quantitative analysis. The mean incidence of AMI was 6.2 (95% CI 1.9 to 12.9) per 100 000 person years. On average 5.0 (95% CI 3.3 to 7.1) of 10 000 hospital admissions were due to AMI. Occlusive arterial AMI was the most common form constituting 68.6% (95% CI 63.7 to 73.2) of all AMI cases, with similar proportions of embolism and thrombosis.Overall short-term mortality (in-hospital or within 30 days) of AMI was 59.6% (95% CI 55.5 to 63.6), being 68.7% (95% CI 60.8 to 74.9) in patients treated before the year 2000 and 55.0% (95% CI 45.5 to 64.1) in patients treated from 2000 onwards (p<0.05). The mid/long-term mortality of AMI was 68.2% (95% CI 60.7 to 74.9). Mortality due to mesenteric venous thrombosis was 24.6% (95% CI 17.0 to 32.9) and of non-occlusive mesenteric ischaemia 58.4% (95% CI 48.6 to 67.7). The short-term mortality of revascularised occlusive arterial AMI was 33.9% (95% CI 30.7 to 37.4). CONCLUSIONS: In adult patients, AMI is a rarely diagnosed condition with high mortality, although with improvement of treatment results over the last decades. Two thirds of AMI cases are of occlusive arterial origin with potential for better survival if revascularised. PROSPERO REGISTRATION NUMBER: CRD42021247148.

Fluid Management, Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome: A Narrative Review.

BACKGROUND: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. OBJECTIVES: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). METHODS: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. RESULTS: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. CONCLUSIONS: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

Acute mesenteric ischaemia.

PURPOSE OF REVIEW: To summarize the recent evidence on acute mesenteric ischaemia (AMI). RECENT FINDINGS: The overall incidence of AMI is below 10/100 000 person years but increases exponentially with age. The overall mortality of AMI remains high, exceeding 50%, despite continuing progress and increasing availability of imaging and endovascular interventions. However, patients with (early) revascularization have significantly better outcomes. The majority of patients surviving the acute event are still alive at 1 year, but evidence on quality of life is scarce.Clinical suspicion of AMI is the key to timely diagnosis, with biphasic computed tomography-angiography the diagnostic method of choice. Currently, no biomarker has sufficient specificity to diagnose AMI. SUMMARY: Improved awareness and knowledge of AMI are needed to raise the suspicion of AMI in relevant patients and thereby to achieve better outcomes.

Impact of intraabdominal hypertension on kidney failure in critically ill patients: A post-hoc database analysis.

PURPOSE: To assess whether intraabdominal hypertension (IAH) may influence kidney failure as well as mortality. METHODS: This post-hoc analysis of two databases (IROI and iSOFA study) tested the independent association between IAH and kidney failure. Mortality was assessed using four prespecified groups (IAH present, kidney failure present, IAH and kidney failure present and no IAH or kidney failure present). RESULTS: Of 825 critically ill patients, 302 (36.6%) developed kidney failure and 192 (23.7%) died during the first 90 days. Only 'Cumulative days with IAH grade II or more' was significantly associated with kidney failure (OR 1.29 (1.08-1.55), p = 0.003) while 'cumulative days with IAH grade I or more' (p = 0.135) or highest daily IAP (p = 0.062) was not. IAH combined with kidney failure was independently associated with 90-day mortality (OR 2.20 (1.20-4.05), p = 0.011), which was confirmed for higher grades of IAH (grade II or more) alone (OR 2.14 (1.07-4.30), p = 0.032) and combined with kidney failure (OR 3.25 (1.72-6.12), p < 0.001). CONCLUSIONS: This study suggest that duration as well as higher grades of IAH are associated with kidney failure and may increase mortality.

Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline.

PURPOSE: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM­RPG) was to formulate evidence­based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). METHODS: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web­based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. RESULTS: The ICM­RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". CONCLUSION: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.