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Nutrition therapy in critically ill patients with severe acute pancreatitis
Abstract
A significant proportion of patients (10%–20%) with acute pancreatitis develop severe acute pancreatitis characterized by pancreatic necrosis, systemic inflammation, and organ failure, commonly requiring intensive care unit (ICU) admission. In this specific population, nutrition therapy is more challenging than that in the general ICU population, primarily because of inevitable gastrointestinal involvement by pancreatic inflammation. In this review, we discussed several key aspects of nutrition therapy in this population, including key pathophysiology that may impede nutrition therapy, the timing and implementation of enteral nutrition and parenteral nutrition, the importance of specific nutrient supplements, and the long‐term outcomes that may be addressed by nutrition therapy.
... Despite the enhanced understanding of AP pathogenesis, no specific therapies are currently approved by the Food and Drug Administration for its treatment (Zaman and Gorelick 2024;Trikudanathan et al. 2024). Management of this disease is limited to supportive care with fluid resuscitation, pain control, and nutrition, reinforcing the need to develop new therapeutic compounds (Sun et al. 2024). Plants have evolved complex defense systems to counteract harmful microbial pathogens and undesirable environmental stresses (Mishra et al. 2024). ...
Acute pancreatitis is a potentially life-threatening inflammatory disorder of the exocrine pancreas characterized by early activation of pancreatic enzymes followed by macrophage-driven inflammation, and pancreatic acinar cell death. The most common causes are gallstones and excessive alcohol consumption. Inflammation and oxidative stress play critical roles in its pathogenesis. Despite increasing incidence, currently, no specific drug therapy is available to treat or prevent acute pancreatitis, in particular severe acute pancreatitis. New therapeutic agents are very much needed. Plant polyphenols have attracted extensive attention in the field of acute pancreatitis due to their diverse pharmacological properties. In this review, we discuss the potential of plant polyphenols in inhibiting the occurrence and development of acute pancreatitis via modulation of inflammation, oxidative stress, calcium overload, autophagy, and apoptosis, based on the currently available in vitro, in vivo animal and very few clinical human studies. We also outline the opportunities and challenges in the clinical translation of plant polyphenols for the treatment of the disease. We concluded that plant polyphenols have a potential therapeutic effect in the management and treatment of acute pancreatitis. Knowledge gained from this review will hopefully inspire new research ideas and directions for the development and application of plant polyphenols for treating this disease.
Background
It is unknown whether increasing dietary protein to 1.2–2.0 g/kg/day as recommended in international guidelines compared to current practice improves outcomes in intensive care unit (ICU) patients. The TARGET Protein trial will evaluate this.
Objective
To describe the study protocol for the TARGET Protein trial.
Design, setting, and participants
TARGET Protein is a cluster randomised, cross-sectional, double cross-over, pragmatic clinical trial undertaken in eight ICUs in Australia and New Zealand. Each ICU will be randomised to use one of two trial enteral formulae for three months before crossing over to the other formula, which is then repeated, with enrolment continuing at each ICU for 12 months. All patients aged ≥16 years in their index ICU admission commencing enteral nutrition will be eligible for inclusion. Eligible patients will receive the trial enteral formula to which their ICU is allocated. The two trial enteral formulae are isocaloric with a difference in protein dose: intervention 100g/1000 ml and comparator 63g/1000 ml. Staggered recruitment commenced in May 2022.
Main outcomes measures
The primary outcome is days free of the index hospital and alive at day 90. Secondary outcomes include days free of the index hospital at day 90 in survivors, alive at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination.
Conclusion
TARGET Protein aims to determine whether augmented enteral protein delivery reduces days free of the index hospital and alive at day 90.
Trial registration
Australian New Zealand Clinical Trials Registry (ACTRN12621001484831).
Background:
Severe acute pancreatitis, the most severe form of acute pancreatitis, can alter pancreatic morphology, physiology, and function resulting in long-term morbidity, even after a single episode. This review assesses long-term outcomes and quality of life of severe acute pancreatitis.
Methods:
A comprehensive literature review was conducted across MEDLINE, Embase, Scopus, and PubMed electronic databases on 18 January 2021 and updated on 26 April 2022 to ensure no new literature had been omitted. All studies were prospective or retrospective, included adult patients (>18 years) presenting with acute pancreatitis for whom data on long-term outcomes specifically after severe acute pancreatitis were reported. Quantitative and qualitative data extraction and synthesis were carried out and no meta-analysis was performed. Outcome measures included aetiology and mortality of severe acute pancreatitis, length of stay, endocrine and exocrine pancreatic insufficiency, chronic symptoms, and quality of life compared with healthy controls as assessed by validated questionnaires.
Results:
Fourteen retrospective cohort studies were included, for a total of 779 patients, using quality of life questionnaires. The most common aetiology of severe acute pancreatitis was biliary (36 per cent) followed by alcoholic (29 per cent). Mortality rate ranged from 5 to 35 per cent and length of stay ranged from 2 to 367 days. Quality of life was somewhat lower in patients with exocrine insufficiency, but unaffected by endocrine insufficiency or chronic symptoms. Quality of life was more likely to be reduced in the first 4 years but normalize thereafter and was more likely to be negatively affected where alcohol was the aetiology. In four studies, the relationship between disease severity and lower quality of life was investigated, and a significant correlation was found.
Conclusion:
The review shows how a single episode of severe acute pancreatitis can have a variable effect on long-term quality of life, which is different to previous studies showing a strong reduction in quality of life. This could indicate that in current times treatment modalities are more effective.
Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out during the last decade, its recognition has increased. However, much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis (AP). Recent prospective cohort studies show that its incidence is about 23% globally and 34.5% in patients with severe AP. With the overall increase in the incidence of AP this complication will be certainly seen more frequently. Due to its high morbidity, mortality and difficult control, early detection and treatment are essential. However, its risk factors and pathophysiological mechanisms are not clearly defined. Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes. This review will show the evidence published so far on the incidence and prevalence, risk factors, possible pathophysiological mechanisms, clinical outcomes, clinical characteristics and preventive and corrective management of PAPD. Some important gaps needing to be clarified in forthcoming studies will also be discussed.
Following the new ESPEN Standard Operating Procedures, the previous 2019 guideline to provide best medical nutritional therapy to critically ill patients has been shortened and partially revised. Following this update, we propose this publication as a practical guideline based on the published scientific guideline, but shortened and illustrated by flow charts. The main goal of this practical guideline is to increase understanding and allow the practitioner to implement the Nutrition in the ICU guidelines. All the items discussed in the previous guidelines are included as well as special conditions.
The nutritional management of acute pancreatitis (AP) patients has widely changed over time. The “pancreatic rest” was the cornerstone of the old paradigm, and nutritional support was not even included in AP management. Traditional management of AP was based on intestinal rest, with or without complete parenteral feeding. Recently, evidence-based data underlined the superiority of early oral or enteral feeding with significantly decreased multiple-organ failure, systemic infections, surgery need, and mortality rate. Despite the current recommendations, experts still debate the best route for enteral nutritional support and the best enteral formula. The aim of this work is to collect and analyze evidence over the nutritional aspects of AP management to investigate its impact. Moreover, the role of immunonutrition and probiotics in modulating inflammatory response and gut dysbiosis during AP was extensively studied. However, we have no significant data for their use in clinical practice. This is the first work to move beyond the mere opposition between the old and the new paradigm, including an analysis of several topics still under debate in order to provide a comprehensive overview of nutritional management of AP.
Background
The optimal timing of enteral nutrition (EN) initiation in predicted severe acute gallstone pancreatitis (SAGP) and its influence on disease outcomes are not well known.
Methods
We conducted a retrospective study of patients with predicted SAGP treated with endoscopic retrograde cholangiopancreatography and EN. The patients were classified into two groups according to the timing of EN initiation after admission: within 48 h, and more than 48 h. The primary outcome was in-hospital mortality. The secondary outcomes were length of hospital stay, need for intensive care admission, need for surgical intervention, improvements in blood test results after 7-10 days of EN, incidence of pancreatic necrosis and infection, and hospital care costs. The microbiological profiles of infectious complications were also evaluated.
Results
Of the 98 patients, 31 and 67 started EN within 48 h, and more than 48 h after admission, respectively. Early EN was associated with a decrease in in-hospital mortality (0 vs. 11.9%; p=0.045), length of hospital stay (median:18 vs. 27 days; p=0.001), need for intensive care admission (3.2% vs. 20.9%; p=0.032), and hospital care costs (median:9,289 vs. 13,518 US$; p=0.007), compared to delayed EN. Moreover, early EN for 7-10 days had more beneficial effects on blood test results than delayed EN, including total protein (p=0.03) and CRP (p=0.006) levels. However, the need for surgical intervention and incidence of pancreatic necrosis did not differ between the two groups. In our study, Gram-negative bacteria were the main responsible pathogens (50.5%). Infection with multidrug-resistant organisms (MDRO) was found in 19.4% of the patients. The most common MDRO was MDR Enterococcus faecium. Early EN was not superior in reducing incidence of infected pancreatic necrosis, bacteremia, polymicrobial infection, or MDROs.
Conclusions
In patients with predicted SAGP, early EN is associated with a decrease in in-hospital mortality, length of hospital stay, need of intensive care admission, and hospital care costs, compared to delayed EN. There are no significant benefits of early EN in reducing the rate of infection-related complications. Further studies with larger sample sizes are warranted.
Background
The importance of enteral nutrition (EN) in acute pancreatitis (AP) has been emphasised. Nasogastric (NG) feeding has been the preferred route for EN delivery in most AP patients intolerant to oral intake. However, gastric feeding intolerance (GFI) was frequently reported, especially in patients with more severe diseases. This study aimed to investigate the incidence and risk factors for GFI in moderately-severe to severe AP.
Methods
This is a single-centre, retrospective study. All the data were extracted from an electronic database from April 2020 to May 2021. Data were prospectively collected during hospitalisation. Patients diagnosed with moderately-severe to severe AP and admitted within seven days from the onset of abdominal pain were assessed for eligibility. Patients who showed signs of intolerance to gastric feeding and required switching to nasojejunal (NJ) feeding were deemed GFI. Multivariable logistic regression was performed to assess potential risk factors of GFI.
Results
A total of 93 patients were analysed, of whom 24 were deemed GFI (25.8%), and the rest tolerated NG feeding well ( n = 69). In patients with GFI, the median time of switching to NJ feeding was five days (interquartile range: 4–7 days) after admission. The multivariable analysis showed that respiratory failure (odds ratio = 3.135, 95% CI: 1.111–8.848, P = 0.031) was an independent risk factor for GFI.The mean daily energy delivery in the following three days after switching to NJ feeding was significantly higher than the first three days after initiation of NG feeding in patients with GFI [920.83 (493.33–1326) vs. 465 (252.25–556.67) kcal, P < 0.001].
Conclusion
GFI is common in moderately-severe to severe AP patients with an incidence of 25.8%, and the presence of respiratory failure may increase the risk of GFI.
Patients with severe acute pancreatitis (SAP) present complications and organ failure, which require treatment in critical care units. These extrapancreatic complications determine the clinical outcome of the disease. Intra-abdominal hypertension (IAH) deteriorates the prognosis of SAP. In this paper, relevant recent literature was reviewed, as well as the authors’ own experiences, concerning the clinical importance of IAH and its treatment in SAP. The principal observations confirmed that IAH is a frequent consequence of SAP but is practically absent in mild disease. Common manifestations of AP such as pain, abdominal distension, and paralytic ileus contribute to increased abdominal pressure, as well as fluid loss in third space and aggressive fluid replacement therapy. A severe increase in IAP can evolve to abdominal compartment syndrome and new onset organ failure. Conservative measures are useful, but invasive interventions are necessary in several cases. Percutaneous drainage of major collections is preferred when possible, but open decompressive laparotomy is the final possibility in some cases in order to definitively reduce abdominal pressure. Intra-abdominal pressure should be measured in all SAP cases that worsen despite adequate treatment in critical care units. Conservative measures must be introduced to treat IAH, including negative fluid balance, digestive decompression by gastric–rectal tube, and prokinetics, including neostigmine. In the case of insufficient responses to these measures, minimally invasive interventions should be preferred.
With extended life expectancy, the older population is constantly increasing, and consequently, so too is the prevalence of age-related disorders. Sarcopenia, the pathological age-related loss of muscle mass and function; and malnutrition, the imbalance in nutrient intake and resultant energy production, are both commonly occurring conditions in old adults. Altered nutrition plays a crucial role in the onset of sarcopenia, and both these disorders are associated with detrimental consequences for patients (e.g., frailty, morbidity, and mortality) and society (e.g., healthcare costs). Importantly, sarcopenia and malnutrition also share critical molecular alterations, such as mitochondrial dysfunction, increased oxidative stress, and a chronic state of low grade and sterile inflammation, defined as inflammageing. Given the connection between malnutrition and sarcopenia, nutritional interventions capable of affecting mitochondrial health and correcting inflammageing are emerging as possible strategies to target sarcopenia. Here, we discuss mitochondrial dysfunction, oxidative stress, and inflammageing as key features leading to sarcopenia. Moreover, we examine the effects of some branched amino acids, omega-3 PUFA, and selected micronutrients on these pathways, and their potential role in modulating sarcopenia, warranting further clinical investigation.
Background: Oxidative stress has been implicated in the pathogenesis of acute pancreatitis (AP), and ascorbic acid (AA), as an important endogenous antioxidant substance, has been shown to reduce AP severity in preclinical studies. However, the effects of AA supplementation in clinical settings remain controversial.
Methods: PubMed, EMBASE, MEDLINE, and SCOPUS databases were searched, and both preclinical and clinical studies were included. For clinical trials, the primary outcome was incidence of organ failure, and for preclinical studies, the primary outcome was histopathological scores of pancreatic injuries.
Results: Meta-analysis of clinical trials showed that compared with controls, AA administration did not reduce the incidence of organ failure or mortality during hospitalization but was associated with significantly reduced length of hospital stay. Meta-analysis of preclinical studies showed that AA supplementation reduced pancreatic injury, demonstrated as decreased histological scores and serum amylase, lipase levels.
Conclusion: AA administration has no effect on survival or organ failure in patients with AP but may reduce the length of hospital stay. However, the evidence to date remains sparse, scattered, and of suboptimal quality, making it difficult to draw any firm conclusion on the clinical benefits of AA in AP.
Severe acute pancreatitis (SAP) leads to numerous inflammatory and nutritional disturbances. All SAP patients are at a high nutritional risk. It has been proven that proper nutrition significantly reduces mortality rate and the incidence of the infectious complications in SAP patients. According to the literature, early (started within 24–48 h) enteral nutrition (EN) is optimal in most patients. EN protects gut barrier function because it decreases gastrointestinal dysmotility secondary to pancreatic inflammation. Currently, the role of parenteral nutrition (PN) in SAP patients is limited to patients in whom EN is not possible or contraindicated. Early versus delayed EN, nasogastric versus nasojejunal tube for EN, EN versus PN in SAP patients and the role of immunonutrition (IN) in SAP patients are discussed in this review.
Background:
This study aims to assess the effect of early enteral nutrition support (EENS) for the management of acute severe pancreatitis (ASP).
Methods:
This study will search Cochrane Library, PUBMED, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, CNKI, and WANGFANG from their inception to the present without language limitations. In addition, this study will also search clinical trial registry and reference lists of included trials. Eligible comparators will be standard care, medications, and any other interventions. Two authors will independently scan all citations, titles/abstracts, and full-text studies. The study methodological quality will be appraised using Cochrane risk of bias tool. If it is possible, we will pool out data and perform meta-analysis. Strength of evidence for each main outcome will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation.
Results:
This study will summarize the most recent evidence to assess the effect of EENS for the management of ASP.
Conclusion:
The findings of this study will help to determine whether EENS is effective for patients with ASP.
Study registration:
INPLASY202070009.
Background:
Nutrition is an important aspect of management in severe acute pancreatitis. Enteral nutrition has advantages over parenteral nutrition and is the preferred method of feeding. Enteral feeding via nasojejunal tube is often recommended, but its benefits over nasogastric feeding are unclear. The placement of a nasogastric tube is technically simpler than the placement of a nasojejunal tube.
Objectives:
To compare the mortality, morbidity, and nutritional status outcomes of people with severe acute pancreatitis fed via nasogastric tube versus nasojejunal tube.
Search methods:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS on 17 October 2019 without using any language restrictions. We also searched reference lists and conference proceedings for relevant studies and clinical trial registries for ongoing trials. We contacted authors for additional information.
Selection criteria:
We included randomised controlled trials (RCTs) and quasi-RCTs comparing enteral feeding by nasogastric and nasojejunal tubes in participants with severe acute pancreatitis.
Data collection and analysis:
Two review authors independently screened studies for inclusion, assessed risk of bias of the included studies, and extracted data. This information was independently verified by the other review authors. We used standard methods expected by Cochrane to assess the risk of bias and perform data synthesis. We rated the certainty of evidence according to GRADE.
Main results:
We included five RCTs that randomised a total of 220 adult participants from India, Scotland, and the USA. Two of the trial reports were available only as abstracts. The trials differed in the criteria used to rate the severity of acute pancreatitis, and three trials excluded those who presented in severe shock. The duration of onset of symptoms before presentation in the trials ranged from within one week to four weeks. The trials also differed in the methods used to confirm the placement of the tubes and in what was considered to be nasojejunal placement. We assessed none of the trials as at high risk of bias, though reporting of methods in four trials was insufficient to judge the risk of bias for one or more of the domains assessed. There was no evdence of effect with nasogastric or nasojejunal placement on the primary outcome of mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.36 to 1.17; I2 = 0%; 5 trials, 220 participants; very low-certainty evidence due to indirectness and imprecision). Similarly, there was no evidence of effect on the secondary outcomes for which data were available. These included organ failure (3 trials, 145 participants), rate of infection (2 trials, 108 participants), success rate (3 trials, 159 participants), complications associated with the procedure (2 trials, 80 participants), need for surgical intervention (3 trials, 145 participants), requirement of parenteral nutrition (2 trials, 80 participants), complications associated with feeds (4 trials, 195 participants), and exacerbation of pain (4 trials, 195 participants). However, the certainty of the evidence for these secondary outcomes was also very low due to indirectness and imprecision. Three trials (117 participants) reported on length of hospital stay, but the data were not suitable for meta-analysis. None of the trials reported data suitable for meta-analysis for the other secondary outcomes of this review, which included days taken to achieve full nutrition requirement, duration of tube feeding, and duration of analgesic requirement after feeding tube placement.
Authors' conclusions:
There is insufficient evidence to conclude that there is superiority, inferiority, or equivalence between the nasogastric and nasojejunal mode of enteral tube feeding in people with severe acute pancreatitis.
Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and may require nutritional support. Acute necrotizing pancreatitis is encountered in 20% of patients with acute pancreatitis, is associated with increased morbidity and mortality, and may require artificial nutrition by enteral or parenteral route, as well as additional endoscopic, radiological or surgical interventions. Chronic pancreatitis represents a chronic inflammation of the pancreatic gland with development of fibrosis. Abdominal pain leading to decreased oral intake, as well as exocrine and endocrine failure are frequent complications of the disease. All of the above represent risk factors related to malnutrition. Therefore, patients with chronic pancreatitis should be considered at risk, screened and supplemented accordingly. Moreover, osteoporosis and increased facture risk should be acknowledged in patients with chronic pancreatitis, and preventive measures should be considered.
Background
Vascular complications of severe acute pancreatitis are well known and largely described unlike non-occlusive mesenteric ischemia, which is a rare and potentially fatal complication. Non-occlusive mesenteric ischemia is an acute mesenteric ischemia without thrombotic occlusion of blood vessels, poorly described as a complication of acute pancreatitis.
Methods
We retrospectively reviewed a prospectively maintained registry of all pancreatic diseases referred to our center from 2013 to 2018, in order to determine the causes of early death. We identified three patients who died within 48 h after hospital admission from severe acute pancreatitis complicated by irreversible non-occlusive mesenteric ischemia. Their clinical presentation, management, and outcomes were herein reported.
Results
Three consecutive patients with severe acute pancreatitis developed non-occlusive mesenteric ischemia within the first 5 days after onset of symptoms and died 48 h after non-occlusive mesenteric ischemia diagnosis despite optimal intensive care management and surgery, giving a prevalence of 3/609 (0.5%). Symptoms were unspecific with consequently potential delayed diagnosis and management. High doses of norepinephrine required for hemodynamic support (n = 3) potentially leading to splanchnic vessels vasoconstriction, transient hypotension (n = 3), and previous severe ischemic cardiomyopathy (n = 1) could be involved as precipitating factors of non-occlusive mesenteric ischemia.
Conclusion
Non-occlusive mesenteric ischemia can be a fatal complication of acute pancreatitis but is also challenging to diagnose. Priority is to reestablish a splanchno-mesenteric perfusion flow. Surgery should be offered in case of treatment failure or deterioration but is still under debate in early stage, to interrupt the vicious circle of intestinal hypoperfusion and ischemia.
Exocrine pancreatic insufficiency (EPI) is a condition caused by reduced or inappropriate secretion or activity of pancreatic juice and its digestive enzymes, pancreatic lipase in particular. EPI can result in clinical manifestation and biochemical alterations causing reduced quality of life and life-threating complications. EPI is common in pancreatic disorders, where it should be suspected and actively investigated, and in many extrapancreatic conditions. There are various tests available to diagnose EPI, with indirect, noninvasive ones, such as concentration of fecal elastase being more commonly employed. Administration of pancreatic enzymes replacement therapy remains the mainstay of EPI treatment. The present review article will discuss current evidence regarding the prevalence of EPI, the available tests to diagnose it and its treatment.
Background:
In the critically ill, energy delivery from enteral nutrition (EN) is often less than the estimated energy requirement. Parenteral nutrition (PN) as a supplement to EN may increase energy delivery. We aimed to determine if an individually titrated supplemental PN strategy commenced 48-72 hours following ICU admission and continued for up to 7 days would increase energy delivery to critically ill adults compared to usual care EN delivery.
Methods:
This study was a prospective, parallel group, phase II pilot trial conducted in six intensive care units in Australia and New Zealand. Mechanically ventilated adults with at least one organ failure and EN delivery below 80% of estimated energy requirement in the previous 24 hours received either a supplemental PN strategy (intervention group) or usual care EN delivery. EN in the usual care group could be supplemented with PN if EN remained insufficient after usual methods to optimise delivery were attempted.
Results:
There were 100 patients included in the study and 99 analysed. Overall, 71% of the study population were male, with a mean (SD) age of 59 (17) years, Acute Physiology and Chronic Health Evaluation II score of 18.2 (6.7) and body mass index of 29.6 (5.8) kg/m2. Significantly greater energy (mean (SD) 1712 (511) calories vs. 1130 (601) calories, p < 0.0001) and proportion of estimated energy requirement (mean (SD) 83 (25) % vs. 53 (29) %, p < 0.0001) from EN and/or PN was delivered to the intervention group compared to usual care. Delivery of protein and proportion of estimated protein requirements were also greater in the intervention group (mean (SD) 86 (25) g, 86 (23) %) compared to usual care (mean (SD) 53 (29) g, 51 (25) %, p < 0.0001). Antibiotic use, ICU and hospital length of stay, mortality and functional outcomes were similar between the two groups.
Conclusions:
This individually titrated supplemental PN strategy applied over 7 days significantly increased energy delivery when compared to usual care delivery. Clinical and functional outcomes were similar between the two patient groups.
Trial registration:
Clinical Trial registry details: NCT01847534 (First registered 22 April 2013, last updated 31 July 2016).
The loss of lean body mass, muscle strength and physical function causes significant problems in older adults. Protein and amino acid supplements can preserve muscle strength but the effect on function is variable. We conducted a systematic literature review and meta-analysis to investigate the effect of protein and amino acid supplementation on fat-free mass, muscle strength and physical function in malnourished, frail, sarcopenic, dependent or elderly with acute or chronic conditions, with or without rehabilitation exercise. Databases searched included Medline, BIOSIS, CINAHL, Cochrane Library, EBM Reviews, Embase, Pre-Medline, ProQuest, PubMed and Scopus. Retrieved articles were assessed by two reviewers using the Cochrane Risk of Bias (ROB) Tool. In all, thirty nine randomised controlled trails ( n 4274) were included. The studies used a range of protein or essential amino acid (EAA) supplements in a variety of settings, including hospital, community and long-term care. Only seven studies had low ROB and no effect of supplementation was found on any outcomes. Analysis of all thirty-nine studies suggest protein and EAA supplements may improve fat-free mass, muscle strength and physical function (standardised mean difference 0·21–0·27, all P <0·005), but significant heterogeneity and ROB was evident. Predetermined subgroup analysis found undernourished elderly benefitted most; EAA were the most effective supplements and small beneficial effects were seen without rehabilitation exercise. The high heterogeneity and few studies with low ROB limits the conclusions and more high quality studies are needed to determine the best nutritional strategies for the maintenance of strength and function with increasing age.
Background
Providing supplemental amino acids to ICU patients during a 3-h period results in improved whole-body net protein balance, without an increase in amino acid oxidation. The primary objective was to investigate if a 24-h intravenous amino acid infusion in critically ill patients has a sustained effect on whole-body protein balance as was seen after 3 h. Secondary objectives were monitoring of amino acid oxidation rate, urea and free amino acid plasma concentrations.
Methods
An infusion of [1-¹³C]-phenylalanine was added to ongoing enteral nutrition to quantify the enteral uptake of amino acids. Primed intravenous infusions of [ring-²H5]-phenylalanine and [3,3-²H2]-tyrosine were used to assess whole-body protein synthesis and breakdown, to calculate net protein balance and to assess amino acid oxidation at baseline and at 3 and 24 hours. An intravenous amino acid infusion was added to nutrition at a rate of 1 g/kg/day and continued for 24 h.
Results
Eight patients were studied. The amino acid infusion resulted in improved net protein balance over time, from -1.6 ± 7.9 μmol phe/kg/h at 0 h to 6.0 ± 8.8 at 3 h and 7.5 ± 5.1 at 24 h (p = 0.0016). The sum of free amino acids in plasma increased from 3.1 ± 0.6 mmol/L at 0 h to 3.2 ± 0.3 at 3 h and 3.6 ± 0.5 at 24 h (p = 0.038). Amino acid oxidation and plasma urea were not altered significantly.
Conclusion
We demonstrated that the improvement in whole-body net protein balance from a supplemental intravenous amino acid infusion seen after 3 h was sustained after 24 h in critically ill patients.
Trial registration
This trial was prospectively registered at Australian New Zealand Clinical Trials Registry. ACTRN, 12615001314516. Registered on 1 December 2015.
Abstract Background Nutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of 35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone). Methods In this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of
The early diagnosis of pancreatic exocrine insufficiency (PEI) is hindered because many of the functional diagnostic techniques used are expensive and require specialized facilities, which prevent their widespread availability. We have reviewed current evidence in order to compare the utility of these functional diagnostic techniques with the fecal elastase-1 (FE-1) test in the following three scenarios: screening for PEI in patients presenting with symptoms suggestive of pancreatic disease, such as abdominal pain or diarrhea; determining the presence of PEI in patients with an established diagnosis of pancreatic disease, such as chronic pancreatitis or cystic fibrosis; determining exocrine status in disorders not commonly tested for PEI, but which have a known association with this disorder. Evidence suggests the FE-1 test is reliable for the evaluation of pancreatic function in many pancreatic and non-pancreatic disorders. It is non-invasive, is less time-consuming, and is unaffected by pancreatic enzyme replacement therapy. Although it cannot be considered the gold-standard method for the functional diagnosis of PEI, the advantages of the FE-1 test make it a very appropriate test for screening patients who may be at risk of this disorder.
PurposeTo provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. Methods
We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined “early” EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. ResultsWe formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. Conclusions
We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.
Previous studies have shown that the nasogastric (NG) route seems equivalent to the nasojejunal (NJ) route in patients with severe acute pancreatitis (SAP). However, these studies used a small sample size and old criteria for diagnosing SAP, which may include some patients with moderate SAP, according to the newly established SAP criteria (Atlanta 2012 classification). Based on the changes in the criteria for classifying SAP, we performed an up-to-date meta-analysis.
Method.
We reviewed the PubMed, EMbase, China National Knowledge Infrastructure, Wanfang Database, and Cochrane Central Register of Controlled Trials electronic databases. We included randomized controlled trials comparing NG and NJ nutrition in patients with SAP. We performed the meta-analysis using the Cochrane Collaborations’ RevMan 5.3 software.
Results.
We included four randomized controlled trials involving 237 patients with SAP. There were no significant differences in the incidence of mortality, infectious complications, digestive complications, achievement of energy balance, or length of hospital stay between the NG and NJ nutrition groups.
Conclusions.
NG nutrition was as safe and effective as NJ nutrition in patients with SAP. Further studies are needed to confirm our results.
Introduction
Severe acute pancreatitis may be complicated by intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and intestinal ischemia. The aim of this retrospective study is to describe the incidence, treatment, and outcome of patients with severe acute pancreatitis and ACS, in particular the occurrence of intestinal ischemia.
Methods
The medical records of all patients admitted with severe acute pancreatitis admitted to the ICU of a tertiary referral center were reviewed. The criteria proposed by the World Society of the Abdominal Compartment Syndrome (WSACS) were used to determine whether patients had IAH or ACS.
Results
Fifty-nine patients with severe acute pancreatitis were identified. Intra-abdominal pressure (IAP) measurements were performed in 29 patients (49.2 %). IAH was present in all patients (29/29). ACS developed in 13/29 (44.8 %) patients. Ten patients with ACS underwent decompressive laparotomy. A large proportion of patients with ACS had intra-abdominal ischemia upon laparotomy: 8/13 (61.5 %). Mortality was high in both the ACS group and the IAH group.
Conclusion
This study confirms that ACS is common in severe acute pancreatitis. Intra-abdominal ischemia occurs in a large proportion of patients with ACS. Swift surgical intervention may be indicated when conservative measures fail in patients with ACS. National and international guidelines need to be updated so that routine IAP measurements become standard of care for patients with severe acute pancreatitis in the ICU.
Evidence behind the recommendations for protein feeding during critical illness is weak. Mechanistic studies are needed to elucidate the effects of amino acid/protein supplementation on protein metabolism before larger clinical trials with higher protein feeding are initiated.
Here we study the effects of parenteral amino acid supplementation (equivalent to 1 g/kg/day) over 3 h on whole body protein turnover in critically ill patients in the ICU during the first week after admission. Patients were studied at baseline during ongoing nutrition and during extra amino acid supplementation. If the patient was still in the ICU 2-4 days later, these measurements were repeated. Protein kinetics were measured using continuous stable isotope labeled phenylalanine and tyrosine infusions.
Thirteen patients were studied on the first study occasion only and 7 were studied twice. Parenteral amino acid supplementation significantly improved protein balance on both occasions; from median -4 to +7 μmol phenylalanine/kg/h (P = 0.001) on the first study day and from median 0 to +12 μmol phenylalanine/kg/h (P = 0.018) on the second study day. The more positive protein balance was attributed to an increased protein synthesis rate which reached statistical significance during the first measurement (from 58 to 65 μmol phenylalanine/kg/h; n = 13; P = 0.007) but not during the second measurement (from 58 to 69 μmol phenylalanine/kg/h; n = 7; P = 0.09). Amino acid oxidation rates, estimated by phenylalanine hydroxylation, did not increase during the 3 h amino acid infusion. A positive correlation (r = 0.80; P < 0.0001)) between total amino acids/protein given to the patient and whole body protein balance was observed.
Extra parenteral amino acids infused over a 3 hour period improved whole body protein balance and did not increase amino acid oxidation rates in critically ill patients during the early phase (first week) of critical illness.
Background:
On the basis of low-quality evidence, international critical care nutrition guidelines recommend a wide range of protein doses. The effect of delivering high-dose protein during critical illness is unknown. We aimed to test the hypothesis that a higher dose of protein provided to critically ill patients would improve their clinical outcomes.
Methods:
This international, investigator-initiated, pragmatic, registry-based, single-blinded, randomised trial was undertaken in 85 intensive care units (ICUs) across 16 countries. We enrolled nutritionally high-risk adults (≥18 years) undergoing mechanical ventilation to compare prescribing high-dose protein (≥2·2 g/kg per day) with usual dose protein (≤1·2 g/kg per day) started within 96 h of ICU admission and continued for up to 28 days or death or transition to oral feeding. Participants were randomly allocated (1:1) to high-dose protein or usual dose protein, stratified by site. As site personnel were involved in both prescribing and delivering protein dose, it was not possible to blind clinicians, but patients were not made aware of the treatment assignment. The primary efficacy outcome was time-to-discharge-alive from hospital up to 60 days after ICU admission and the secondary outcome was 60-day morality. Patients were analysed in the group to which they were randomly assigned regardless of study compliance, although patients who dropped out of the study before receiving the study intervention were excluded. This study is registered with ClinicalTrials.gov, NCT03160547.
Findings:
Between Jan 17, 2018, and Dec 3, 2021, 1329 patients were randomised and 1301 (97·9%) were included in the analysis (645 in the high-dose protein group and 656 in usual dose group). By 60 days after randomisation, the cumulative incidence of alive hospital discharge was 46·1% (95 CI 42·0%-50·1%) in the high-dose compared with 50·2% (46·0%-54·3%) in the usual dose protein group (hazard ratio 0·91, 95% CI 0·77-1·07; p=0·27). The 60-day mortality rate was 34·6% (222 of 642) in the high dose protein group compared with 32·1% (208 of 648) in the usual dose protein group (relative risk 1·08, 95% CI 0·92-1·26). There appeared to be a subgroup effect with higher protein provision being particularly harmful in patients with acute kidney injury and higher organ failure scores at baseline.
Interpretation:
Delivery of higher doses of protein to mechanically ventilated critically ill patients did not improve the time-to-discharge-alive from hospital and might have worsened outcomes for patients with acute kidney injury and high organ failure scores.
Funding:
None.
Background
The timing of oral refeeding can affect length of stay (LOS) and recovery of acute pancreatitis (AP). However, the optimal timing for oral refeeding is still controversial for AP. This meta-analysis investigated the effects of immediate or early versus delayed oral feeding on mild and moderate AP, regardless of improvement in clinical signs or laboratory indicators.
Methods
This systematic review and meta-analysis of randomized controlled trials (RCTs) based on data from Embase, Cochrane Library, PubMed, Web of science, and CBM before August 2021. Two researchers independently used Stata16 to extract and analyse study data. Random effect model was performed for meta-analysis to calculate the risk ratio (RR) and standardized mean difference (SMD).
Results
8 RCTs were selected, including 748 patients with mild to moderate AP. Patients in IOR (Immediate or early Oral Refeeding) group had less costs [SMD -0.83, 95%CI (−1.17, −0.5), P < 0.001] and shorter LOS [SMD -1.01, 95%CI (−1.17, −0.85), P < 0.001] than the DOR (Delayed Oral Refeeding) group patients. However, there was no difference in mortality [RR 0.54, 95%CI (0.11, 2.62), P = 0.44], pain relapse rate [RR 0.58, 95%CI (0.25, 1.35), P = 0.27], feeding intolerance rate [RR 0.61, 95%CI (0.28, 1.3), P = 0.2], AP progression rate [RR 0.21, 95%CI (0.04, 1.07), P = 0.06] and overall complications rate [RR 0.41, 95%CI (0.17, 1.01), P = 0.05] between the IOR and DOR groups.
Conclusions
Limited data suggest that IOR could reduce LOS and costs without increasing adverse events in mild to moderate AP.
Background:
New randomized controlled trials have been conducted since publication of the 2016 ASPEN/SCCM critical care nutrition guideline. This guideline updates recommendations for foundational questions central to critical care nutrition support.
Methods:
The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process was used to develop and summarize evidence for clinical practice recommendations. Clinical outcomes were assessed for (1) higher vs lower energy dose (2) higher vs lower protein dose (3) exclusive isocaloric PN vs EN (4) supplemental PN (SPN) plus EN vs EN alone (5a) mixed oil lipid injectable emulsions (ILE) vs soybean oil, and (5b) Fish oil (FO) containing ILE vs non-FO ILE. To assess safety, weight based energy intake was plotted against hospital mortality when study heterogeneity precluded meaningful Forest plot inferences.
Results:
Between 1/1/2001 and 07/15/2020, 2,320 citations were identified and data were abstracted from 39 trials, including 20,578 participants. Patients receiving FO had decreased pneumonia rates of uncertain clinical significance. Otherwise, there were no differences for any outcome in any question. Due to lack in certainty regarding harm, the energy prescription recommendation was decreased to 12-25kcal/kg/day.
Conclusion:
No differences in clinical outcomes were identified among numerous nutritional interventions, including higher energy or protein intake, isocaloric PN or EN, supplemental PN, or different ILEs. As more consistent critical care nutrition support data become available, more precise recommendations will be possible. In the meantime, clinical judgment and close monitoring are needed. This paper was approved by the ASPEN Board of Directors. This article is protected by copyright. All rights reserved.
Background & aims:
Acute pancreatitis is a common disease with significant associated morbidity and mortality. We performed a systematic review and meta-analysis of population-based studies to explore the changing temporal trends of acute pancreatitis incidence globally.
Methods:
We performed a systematic literature search to identify population-based studies reporting the annual incidence of acute pancreatitis. Abstracts were independently assessed to identify applicable papers for full-text review and data extraction. Joinpoint temporal trend analyses were performed to calculate the average annual percent change (AAPC) with 95% confidence intervals (CI). The AAPCs were pooled in a meta-analysis to capture the overall and regional trends in acute pancreatitis incidence over time. Temporal data were summarized in a static map and an interactive, web-based map.
Results:
Forty-four studies reported the temporal incidence of acute pancreatitis (online interactive map: https://kaplan-acute-pancreatitis-ucalgary.hub.arcgis.com/). The incidence of acute pancreatitis has increased from 1961 to 2016 (AAPC = 3.07%; 95% CI: 2.30, 3.84; n=34). Increasing incidence was observed in North America (AAPC = 3.67%; 95% CI: 2.76, 4.57; n=4) and Europe (AAPC = 2.77%; 95% CI: 1.91, 3.63; n=23). The incidence of acute pancreatitis was stable in Asia (AAPC = -0.28%; 95% CI: -5.03, 4.47; n=4).
Conclusion:
This meta-analysis provides a comprehensive overview of the global incidence of acute pancreatitis over the last 56 years and demonstrates a steadily rising incidence over time in most countries of the Western world. More studies are needed to better define the changing incidence of acute pancreatitis in Asia, Africa, and Latin America.
Objective:
To explore the effect of intra-abdominal pressure monitoring in early enteral nutrition therapy after abdominal surgery.
Methods:
164 patients who underwent elective abdominal surgery in our hospital from January 2019 to January 2020 were selected and divided into an observation group and a control group according to the random number table method, with 82 cases in each group. On the basis of conventional enteral nutrition nursing, the control group received conventional gastric residual monitoring, and the observation group received intra-abdominal pressure monitoring. The clinical treatment effect, intra-abdominal pressure, incidence of intra-abdominal hypertension, APACHE-II score, and enteral nutrition tolerance were compared. Correlation of early enteral nutrition intolerance and intra-abdominal pressure was analyzed in the ROC curve.
Results:
The time of abdominal pain relief, adjusted enteral nutrition, and hospitalization were significantly shorter in the observation group (P < 0.05). The intra-abdominal pressure, intra-abdominal hypertension rate, and APACHE-II scores were comparable before treatment (P > 0.05) and all were significantly reduced after treatment in the two groups (P < 0.05). After treatment, the above items were significantly lower in the observation group (P < 0.05). The enteral nutrition's tolerance level of the observation group was significantly higher than that of the control group (P < 0.05). The Pearson correlation analysis revealed that the early enteral nutrition tolerance of patients after abdominal surgery was correlated with the level of intra-abdominal pressure (P < 0.05). The ROC reveled that the baseline level of intra-abdominal pressure and the average level of intra-abdominal pressure 3 days before enteral nutrition were of diagnostic values in predicting the intolerance during enteral nutrition.
Conclusion:
Intraperitoneal pressure monitoring can significantly improve patients' symptoms, and it should be accurately measured for doctors to make timely diagnoses and provide proper treatments.
Objectives:
In patients with severe acute pancreatitis (SAP), early enteral nutrition (EN) is recommended by major clinical practice guidelines, but the exact timing for the initiation of EN is unknown.
Methods:
We conducted a post hoc analysis of the database for a multicenter (44 institutions) retrospective study of patients with SAP in Japan. The patients were classified into 3 groups according to the timing of EN initiation after the diagnosis of SAP: within 24 hours, between 24 and 48 hours, and more than 48 hours. The primary outcome was in-hospital mortality.
Results:
Of the 1094 study patients, 176, 120, and 798 patients started EN within 24 hours, between 24 and 48 hours, and more than 48 hours after SAP diagnosis, respectively. On multivariable analysis, hospital mortality was significantly better with EN within 48 hours than with more than 48 hours (adjusted odds ratio, 0.49; 95% confidence interval, 0.29-0.83; P < 0.001) but did not significantly differ between the groups with EN starting within 24 hours and between 24 and 48 hours (P = 0.29).
Conclusions:
Enteral nutrition within 24 hours may not confer any additional benefit on clinical outcomes compared with EN between 24 and 48 hours.
Importance:
In the United States, acute pancreatitis is one of the leading causes of hospital admission from gastrointestinal diseases, with approximately 300 000 emergency department visits each year. Outcomes from acute pancreatitis are influenced by risk stratification, fluid and nutritional management, and follow-up care and risk-reduction strategies, which are the subject of this review.
Observations:
MEDLINE was searched via PubMed as was the Cochrane databases for English-language studies published between January 2009 and August 2020 for current recommendations for predictive scoring tools, fluid management and nutrition, and follow-up and risk-reduction strategies for acute pancreatitis. Several scoring systems, such as the Bedside Index of Severity in Acute Pancreatitis (BISAP) and the Acute Physiology and Chronic Health Evaluation (APACHE) II tools, have good predictive capabilities for disease severity (mild, moderately severe, and severe per the revised Atlanta classification) and mortality, but no one tool works well for all forms of acute pancreatitis. Early and aggressive fluid resuscitation and early enteral nutrition are associated with lower rates of mortality and infectious complications, yet the optimal type and rate of fluid resuscitation have yet to be determined. The underlying etiology of acute pancreatitis should be sought in all patients, and risk-reduction strategies, such as cholecystectomy and alcohol cessation counseling, should be used during and after hospitalization for acute pancreatitis.
Conclusions and relevance:
Acute pancreatitis is a complex disease that varies in severity and course. Prompt diagnosis and stratification of severity influence proper management. Scoring systems are useful adjuncts but should not supersede clinical judgment. Fluid management and nutrition are very important aspects of care for acute pancreatitis.
Objectives: To determine the incidence of enteral feed intolerance, identify factors associated with enteral feed intolerance, and assess the relationship between enteral feed intolerance and key nutritional and clinical outcomes in critically ill patients.
Design: Analysis of International Nutrition Survey database collected prospectively from 2007 to 2014.
Setting: Seven-hundred eighty-five ICUs from around the world.
Patients: Mechanically ventilated adults with ICU stay greater than or equal to 72 hours and received enteral nutrition during the first 12 ICU days.
Interventions: None.
Measurement and main results: We defined enteral feed intolerance as interrupted feeding due to one of the following reasons: high gastric residual volumes, increased abdominal girth, distension, subjective discomfort, emesis, or diarrhea. The current analysis included 15,918 patients. Of these, 4,036 (24%) had at least one episode of enteral feed intolerance. The enteral feed intolerance rate increased from 1% on day 1 to 6% on days 4 and 5 and declined daily thereafter. After controlling for site and patient covariates, burn (odds ratio 1.46; 95% CIs, 1.07-1.99), gastrointestinal (odds ratio 1.45; 95% CI, 1.27-1.66), and sepsis (odds ratio 1.34; 95% CI, 1.17-1.54) admission diagnoses were more likely to develop enteral feed intolerance, as compared to patients with respiratory-related admission diagnosis. enteral feed intolerance patients received about 10% less enteral nutrition intake, as compared to patients without enteral feed intolerance after controlling for important covariates including severity of illness. Enteral feed intolerance patients had fewer ventilator-free days and longer ICU length of stay time to discharge alive (all p < 0.0001). The daily mortality hazard rate increased by a factor of 1.5 (1.4-1.6; p < 0.0001) once enteral feed intolerance occurred.
Conclusions: Enteral feed intolerance occurs frequently during enteral nutrition delivery in the critically ill. Burn and gastrointestinal patients had the highest risk of developing enteral feed intolerance. Enteral feed intolerance is associated with lower enteral nutrition delivery and worse clinical outcomes. Identification, prevention, and optimal management of enteral feed intolerance may improve nutrition delivery and clinical outcomes in important "at risk" populations.
Acute pancreatitis is a common disorder of the pancreas. It is the most frequent gastrointestinal cause for hospitalization and one of the leading causes of in-hospital deaths. Its severity ranges from mild self-limited disease to severe acute necrotizing pancreatitis characterized by systemic complications and multiorgan failure. Severe acute pancreatitis develops in about 20% of patients with acute pancreatitis and may be associated with multiorgan failure (respiratory, cardiovascular, and kidney). AKI is a frequent complication of severe acute pancreatitis and develops late in the course of the disease, usually after the failure of other organs. It carries a very poor prognosis, particularly if kidney replacement therapy is required, with mortality rates exceeding 75%. The exact pathophysiology of AKI in acute pancreatitis remains unclear but appears to result from initial volume depletion followed by complex vascular and humoral factors. Here, we provide an overview of the epidemiology, pathogenesis, causes, and management of AKI in patients with severe acute pancreatitis.
Background:
Loss of skeletal muscle mass and muscle weakness are common in a variety of clinical conditions with both wasting and weakness associated with an impairment of physical function. β-Hydroxy-β-methylbutyrate (HMB) is a nutrition supplement that has been shown to favorably influence muscle protein turnover and thus potentially plays a role in ameliorating skeletal muscle wasting and weakness.
Objectives:
The aim of this study was to investigate the efficacy of HMB alone, or supplements containing HMB, on skeletal muscle mass and physical function in a variety of clinical conditions characterized by loss of skeletal muscle mass and weakness.
Methods:
A systematic review and meta-analysis of randomized controlled trials reporting outcomes of muscle mass, strength, and physical function was performed. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment. Outcome data were synthesized through meta-analysis with the use of a random-effects model and data presented as standardized mean differences (SMDs).
Results:
Fifteen randomized controlled trials were included, involving 2137 patients. Meta-analysis revealed some evidence to support the effect of HMB alone, or supplements containing HMB, on increasing skeletal muscle mass (SMD = 0.25; 95% CI: -0.00, 0.50; z = 1.93; P = 0.05; I2 = 58%) and strong evidence to support improving muscle strength (SMD = 0.31; 95% CI: 0.12, 0.50; z = 3.25; P = 0.001; I2 = 0%). Effect sizes were small. No effect on bodyweight (SMD = 0.16; 95% CI: -0.08, 0.41; z = 1.34; P = 0.18; I2 = 67%) or any other outcome was found. No study was considered to have low risk of bias in all categories.
Conclusion:
HMB, and supplements containing HMB, increased muscle mass and strength in a variety of clinical conditions, although the effect size was small. Given the bias associated with many of the included studies, further high-quality studies should be undertaken to enable interpretation and translation into clinical practice. The trial was registered on PROSPERO as CRD42017058517.
Purpose of review:
To review recent literature on the management of patients with severe acute pancreatitis (SAP) admitted to an ICU.
Recent findings:
SAP is a devastating disease associated with a high morbidity and mortality. Recent evidence advocates adequate risk assessment and severity prediction (including intra-abdominal pressure monitoring), tailored fluid administration favoring balanced crystalloids, withholding prophylactic antibiotic therapy, and early detection and treatment of extra-pancreatic and fungal infections. Urgent (within 24-48 h after diagnosis) endoscopic retrograde cholangiopancreatography is indicated when persistent biliary obstruction or cholangitis are present. Corticosteroid therapy (mainly dexamethasone) can reduce the need for surgical interventions, length of hospital stay, and mortality. Peritoneal lavage may significantly lower morbidity and mortality. Hemofiltration may offer substantial benefit but more studies are needed to prove its efficacy. Enteral feeding using a polymeric formula and provided early through a nasogastric tube is recommended but has no survival benefit compared with parenteral nutrition. Probiotics could be beneficial, however no clear recommendations can be made.
Summary:
Management of SAP is multimodal with emphasis on monitoring, adequate fluid resuscitation, avoiding prophylactic use of antibiotics, cause-directed procedures or treatment, and organ support. There is a role for early enteral nutrition including probiotics.
Following the new ESPEN Standard Operating Procedures, the previous guidelines to provide best medical nutritional therapy to critically ill patients have been updated. These guidelines define who are the patients at risk, how to assess nutritional status of an ICU patient, how to define the amount of energy to provide, the route to choose and how to adapt according to various clinical conditions. When to start and how to progress in the administration of adequate provision of nutrients is also described. The best determination of amount and nature of carbohydrates, fat and protein are suggested. Special attention is given to glutamine and omega-3 fatty acids. Particular conditions frequently observed in intensive care such as patients with dysphagia, frail patients, multiple trauma patients, abdominal surgery, sepsis, and obesity are discussed to guide the practitioner toward the best evidence based therapy. Monitoring of this nutritional therapy is discussed in a separate document.
Objectives:
We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake.
Design:
Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome.
Setting:
ICUs of 16 hospitals throughout Australia and New Zealand.
Patients:
Adult critically ill patients expected to remain in the study ICU for longer than 2 days.
Interventions:
Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care.
Measurements and main results:
A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, -7.9%; 95% CI, -15.1 to -0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, -0.6%; 95% CI, -16.2 to 15.2; p = 0.95).
Conclusions:
In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials with low risk of bias before this treatment is recommended for routine care.
Objectives:
This study systematically explores the prevalence of pancreatic exocrine insufficiency (PEI) after acute pancreatitis in different subgroups of etiology (biliary/alcoholic/other), disease severity and follow-up time (<12, 12-36 and > 36 months after index admission).
Methods:
PubMed and EMBASE databases were searched, 32 studies were included in this study level meta-analysis.
Results:
In a total of 1495 patients with acute pancreatitis, tested at a mean of 36 months after index admission, the pooled prevalence of PEI was 27.1% (95%-confidence interval [CI]: 20.3%-35.1%). Patients from seven studies (n = 194) underwent direct tests with pooled prevalence of 41.7% [18.5%-69.2%]. Patients from 26 studies (n = 1305) underwent indirect tests with pooled prevalence of 24.4% [18.3%-31.8%]. In subgroup analyses on patients that underwent fecal elastase-1 tests, PEI occurred more often in alcoholic pancreatitis (22.7% [16.6%-30.1%]) than in biliary pancreatitis (10.2% [6.2%-16.4%]) or other etiology (13.4% [7.7%-22.4%]; P = 0.02). Pooled prevalence of PEI after mild and severe pancreatitis was 19.4% [8.6%-38.2%] and 33.4% [22.6%-46.3%] respectively in studies using fecal elaste-1 tests (P = 0.049). Similar results were seen in patients without (18.9% [9.3%-34.6%]) and with necrotizing pancreatitis (32.0% [18.2%-49.8%]; P = 0.053). Over time, the prevalence of PEI decreased in patients who underwent the fecal elastase-1 test and increased in patients who underwent the fecal fat analysis.
Conclusions:
After acute pancreatitis, a quarter of all patients develop PEI during follow-up. Alcoholic etiology and severe and necrotizing pancreatitis are associated with higher risk of PEI. The prevalence of PEI may change as time of follow-up increases.
Abstract
Purpose: We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive
care unit (ICU) patients.
Methods: We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than
3 days in the ICU. In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary
urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In
the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7,
patients were supplemented with parenteral nutrition. The primary outcome was physical component summary
(PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders.
Results: We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline variables were
reasonably balanced between the two groups. The EGDN group had less negative energy (p < 0.001) and protein
(p < 0.001) balances in the ICU as compared to the standard of care group. The PCS score at 6 months did not differ
between the two groups (mean difference 0.0, 95% CI −5.9 to 5.8, p = 0.99); neither did mortality, rates of organ failures,
serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support
at 90 days.
Conclusions: EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as
compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients.
Clinicaltrials.gov identifier no. NCT01372176.
Background & Aims
It is not clear how acute pancreatitis (AP) affects quality of life (QOL). We aimed to determine the long-term independent effect of AP on physical and mental QOL.
Methods
We analyzed data from 91 patients (mean age, 52 year; 54% female) admitted with AP to the University of Pittsburgh Medical Center from 2011 through 2015 who responded to telephone surveys at a median of 14 months after hospital discharge (interquartile range, 12–16 months). Individuals who did not answer the telephone survey were sent a questionnaire by regular mail. Patients answered questions from the SF-12, and answers were used to calculate mental (MCS) and physical (PCS) component summary scores with norm-based scoring (normal ≥50). QOL for these subjects was compared with that of age and sex matched individuals without pancreatitis (1:2) identified from the North American Pancreatitis Study. We controlled for other covariates using multivariable regression analysis.
Results
At follow-up, individuals with AP had significantly lower PCS (46.2±11.8) than controls (51.1±9.5) (P<0.01), but similar MCS. A 4-point reduction of the PCS was attributed to AP after controlling for socio-demographic factors and medical comorbidities. The only pancreatitis-related factor associated with low PCS was multisystem organ failure. Presence of abdominal pain, analgesic use, disability, and current smoking at the time of follow up were also associated with lower PCS scores. Etiology of AP, disease severity (by Revised Atlanta Classification), use of nutritional support, and performance of pancreatic interventions did not affect QOL at follow-up.
Conclusion
In a 14-month follow-up of patients hospitalized with AP, we found a meaningful, independent, and deleterious effect of AP in the physical QOL of these patients, compared to individuals without AP. Further research is needed to determine the duration of this impairment and to evaluate the effects of modifying risk factors.
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of nasogastric versus nasojejunal tube feeding for people with severe acute pancreatitis.
Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness.
To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients.
Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days.
Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care.
Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function.
474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI -0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m(2) (95 % CI 1.0-14.5 mL/min/1.73 m(2), P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145-455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21).
Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction.
anzctr.org.au Identifier: ACTRN12609001015235.
To assess the efficacy of antioxidants in acute (AP) pancreatitis.
We searched PubMed, Embase and the Cochrane library for all randomized controlled trials (RCT) involving administration of antioxidants in the therapy of AP until February 2012. AP studies were pooled to analyze the effect of antioxidants on hospital stay, mortality, and complications. Subgroup analyses were performed on the use of the antioxidant glutamine.
In total, eleven RCTs were included. Among patients with AP, antioxidant therapy resulted in a borderline significant reduction in hospital stay (mean difference -1.74; 95%CI -3.56 to 0.08), a significant decrease in complications (RR 0.66; 95%CI 0.46-0.95) and a non-significant decrease in mortality rate (RR 0.66; 95%CI 0.30-1.46). Subgroup analyses showed that glutamine significantly reduced complications (RR 0.51; 95%CI 0.34-0.78) and mortality rate (RR 0.33; 95%CI 0.13-0.85).
The present meta-analysis shows a possible benefit of glutamine supplementation in patients with acute pancreatitis. However, large randomized trials are needed to confirm these observations.
Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Background and objectivesSevere acute pancreatitis (SAP) is believed to be a major risk factor leading to acute kidney injury (AKI) among critically ill patients, but little is known about SAP-induced AKI. We study the incidence of AKI defined by the Acute Kidney Injury Network (AKIN) criteria and the risk factors associated with outcomes among SAP-induced AKI patients.Method
We conduct a multicenter retrospective study of critically ill SAP-induced AKI patients during the period August 2009 to June 2013. Data on enrolled patients were retrieved from electronic records, including age, sex, laboratory data, clinical details, along with and the ICU mortality rate. Univariate and multiple regression analyses were performed.ResultsAmong a total of 414 SAP patients admitted to intensive care units(ICU), 287 (69.3%) developed AKI during their ICU stay by the AKIN criteria, with 16.7%, 18.4%, and 34.3% classified as AKI stage I,II, and III, respectively. SAP-induced AKI patients experienced a significantly higher ICU mortality than those without AKI. The risk factors associated with ICU mortality among SAP-induced AKI patients included ACS (odds ratio (OR) 10.58), renal replacement therapy (RRT) (OR 3.31), sepsis (OR 2.46), Computed Tomography Severity Index (CTSI) (OR 3.01), APACHE II score (OR 1.82), AKI III (OR 1.38), ICU-length-of-stay (ICU-LOS) (OR 1.04), and multi-organ failure.Conclusions
The paper represents the first attempt to investigate the etiology and epidemiology of AKI following SAP under the AKIN criteria among critically ill patients. Several independent risk factors were found to be associated with ICU mortality for AKI patients. The findings may pinpoint crucial therapeutic measures for preventing AKI among a vulnerable population and for more effective management of SAP-induced AKI to improve the quality of intensive care.
Importance Systematic reviews suggest adult patients in intensive care units (ICUs) with relative contraindications to early enteral nutrition (EN) may benefit from parenteral nutrition (PN) provided within 24 hours of ICU admission.
Objective To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes.
Design, Setting, and Participants Multicenter, randomized, single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zealand. Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days.
Interventions Random allocation to pragmatic standard care or early PN.
Main Outcomes and Measures Day-60 mortality; quality of life, infections, and body composition.
Results A total of 1372 patients were randomized (686 to standard care, 686 to early PN). Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4). Patients receiving early PN commenced PN a mean of 44 minutes after enrollment (95% CI, 36 to 55). Day-60 mortality did not differ significantly (22.8% for standard care vs 21.5% for early PN; risk difference, −1.26%; 95% CI, −6.6 to 4.1; P = .60). Early PN patients rated day-60 quality of life (RAND-36 General Health Status) statistically, but not clinically meaningfully, higher (45.5 for standard care vs 49.8 for early PN; mean difference, 4.3; 95% CI, 0.95 to 7.58; P = .01). Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference, −0.47; 95% CI, −0.82 to −0.11; P = .01) and, based on Subjective Global Assessment, experienced less muscle wasting (0.43 vs 0.27 score increase per week; mean difference, −0.16; 95% CI, −0.28 to −0.038; P = .01) and fat loss (0.44 vs 0.31 score increase per week; mean difference, −0.13; 95% CI, −0.25 to −0.01; P = .04).
Conclusions and Relevance The provision of early PN to critically ill adults with relative contraindications to early EN, compared with standard care, did not result in a difference in day-60 mortality. The early PN strategy resulted in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays.
Trial Registration anzctr.org.au Identifier: ACTRN012605000704695
Background: Plasma glutamine (Gln) level has been negatively correlated with the severity of severe acute pancreatitis (SAP). Although Gln is widely used today, the results of individual randomized controlled trials of Gln-enriched nutrition support for patients with SAP are conflicting. Methods: PubMed, EMBASE, HighWire, Cochrane Central Register of Controlled Trials, Wanfang, China Journals Full-Text Database, and the Chinese Biomedical Literature Database were searched. Literature published before June 2014 was searched. Randomized controlled trials investigating the comparison of conventional and Gln-enriched nutrition support were included; a random effect model using Rev Man 5.2 software was chosen to complete this meta-analysis. The count data were analyzed using the risk ratio (RR) and 95% confidence interval (CI), and the measurement data were analyzed using the standard mean difference or weighted mean difference and 95% CI. Heterogeneity analyses were conducted by I(2) test; publication bias analyses were conducted by Begg test. Results: Ten studies were eventually chosen for analysis, including 218 patients who received conventional methods (control group) and 215 patients who received Gln-enriched nutrition support (experimental group). Compared with the control group, Gln is helpful in elevating the albumin level, decreasing C-reaction protein (standard mean difference = 1.01, -1.89; 95% CI: 0.50 to 1.51, -3.23 to -0.56; P < .05), decreasing the incidence of infectious complication and mortality (RR = 0.62, 0.36; 95% CI: 0.46 to 0.83, 0.16 to 0.83; P < .05), and shortening the hospital stay length (weighted mean difference [WMD] = -3.89; 95% CI: -4.98 to -2.81; P < .05) without increasing expenses (WMD = -0.16; 95% CI: -1.34 to 1.02; P > .05). Intravenous infusion manifested more advantages by decreasing the incidence of infectious complications and mortality. Conclusions: Gln-enriched nutrition support is superior to conventional methods for SAP, and intravenous infusion may be a better choice for drug administration.
© 2015 American Society for Parenteral and Enteral Nutrition.
Background
Although (EEN) is a relatively safer route by which to feed patients with severe acute pancreatitis (SAP) or predicted SAP (pSAP) compared to total parental nutrition (TPN), the appropriate starting time for EEN administration after admission is still controversial. This study pooled all relevant studies to assess the complications associated with EEN by stratifying relevant RCTs into subgroups according to the starting time (<24 h or between 24 and 72 h after admission).
Material/Methods
Relevant studies were searched for among 5 databases. The association between intervention and complications, including pancreatic infection, mortality, hyperglycemia, organ failure, and catheter-related septic complications, were assessed by using pooled risk ratio (RR) and the corresponding 95% confidential interval (CI).
Results
Twelve RCTs were identified through our literature search. Pooled analysis showed that EEN, but not TPN or delayed enteral nutrition (DEN), is associated with reduced risk of pancreatic infection, mortality, organ failure, hyperglycemia, and catheter-related septic complications. EEN within 24 h of admission presented significantly better outcome in morality than EEN between 24 and 72 h. However, no significant heterogeneity was observed in the risk of pancreatic infection, organ failure, hyperglycemia, and catheter-related septic complications between the 2 subgroups.
Conclusions
If the patients are reasonably expected to have high compliance to EN therapy, it could be considered as early as possible.