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Venkatesh K, Glenn H, Delaney A, Andersen CR, Sasson SC. Fire in the belly: A scoping review of the immunopathological mechanisms of acute pancreatitis. Front Immunol 2023; 13:1077414. [PMID: 36713404 PMCID: PMC9874226 DOI: 10.3389/fimmu.2022.1077414] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 12/21/2022] [Indexed: 01/13/2023] Open
Abstract
Introduction Acute pancreatitis (AP) is characterised by an inflammatory response that in its most severe form can cause a systemic dysregulated immune response and progression to acute multi-organ dysfunction. The pathobiology of the disease is unclear and as a result no targeted, disease-modifying therapies exist. We performed a scoping review of data pertaining to the human immunology of AP to summarise the current field and to identify future research opportunities. Methods A scoping review of all clinical studies of AP immunology was performed across multiple databases. Studies were included if they were human studies of AP with an immunological outcome or intervention. Results 205 studies met the inclusion criteria for the review. Severe AP is characterised by significant immune dysregulation compared to the milder form of the disease. Broadly, this immune dysfunction was categorised into: innate immune responses (including profound release of damage-associated molecular patterns and heightened activity of pattern recognition receptors), cytokine profile dysregulation (particularly IL-1, 6, 10 and TNF-α), lymphocyte abnormalities, paradoxical immunosuppression (including HLA-DR suppression and increased co-inhibitory molecule expression), and failure of the intestinal barrier function. Studies including interventions were also included. Several limitations in the existing literature have been identified; consolidation and consistency across studies is required if progress is to be made in our understanding of this disease. Conclusions AP, particularly the more severe spectrum of the disease, is characterised by a multifaceted immune response that drives tissue injury and contributes to the associated morbidity and mortality. Significant work is required to develop our understanding of the immunopathology of this disease if disease-modifying therapies are to be established.
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Affiliation(s)
- Karthik Venkatesh
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
| | - Hannah Glenn
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
| | - Anthony Delaney
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- Division of Critical Care, The George Institute for Global Health, Newtown, NSW, Australia
| | - Christopher R. Andersen
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
- Division of Critical Care, The George Institute for Global Health, Newtown, NSW, Australia
| | - Sarah C. Sasson
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
- Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia
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Herrera Vielma F, Valenzuela R, Videla LA, Zúñiga-Hernández J. N-3 Polyunsaturated Fatty Acids and Their Lipid Mediators as A Potential Immune-Nutritional Intervention: A Molecular and Clinical View in Hepatic Disease and Other Non-Communicable Illnesses. Nutrients 2021; 13:3384. [PMID: 34684386 PMCID: PMC8539469 DOI: 10.3390/nu13103384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/11/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
In recent years, the beneficial effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) intake on human health has been widely accepted in the field of immunonutrition. Today, we find a diversity of supplements based on n-3 PUFAs and/or minerals, vitamins and other substances. The main objective of this review is to discuss the importance of n-3 PUFAs and their derivatives on immunity and inflammatory status related to liver disease and other non-communicable illnesses. Based on the burden of liver diseases in 2019, more than two million people die from liver pathologies per year worldwide, because it is the organ most exposed to agents such as viruses, toxins and medications. Consequently, research conducted on n-3 PUFAs for liver disease has been gaining prominence with encouraging results, given that these fatty acids have anti-inflammatory and cytoprotective effects. In addition, it has been described that n-3 PUFAs are converted into a novel species of lipid intermediaries, specialized pro-resolving mediators (SPMs). At specific levels, SPMs improve the termination of inflammation as well as the repairing and regeneration of tissues, but they are deregulated in liver disease. Since evidence is still insufficient to carry out pharmacological trials to benefit the resolution of acute inflammation in non-communicable diseases, there remains a call for continuing preclinical and clinical research to better understand SPM actions and outcomes.
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Affiliation(s)
- Francisca Herrera Vielma
- Department of Biomedical Basic Sciences, School of Health Sciences, University of Talca, Talca 3460000, Chile;
| | - Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Luis A. Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Jessica Zúñiga-Hernández
- Department of Biomedical Basic Sciences, School of Health Sciences, University of Talca, Talca 3460000, Chile;
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The Effect of Amino Acids on Wound Healing: A Systematic Review and Meta-Analysis on Arginine and Glutamine. Nutrients 2021; 13:nu13082498. [PMID: 34444657 PMCID: PMC8399682 DOI: 10.3390/nu13082498] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 07/16/2021] [Accepted: 07/20/2021] [Indexed: 01/08/2023] Open
Abstract
Under stress conditions, the metabolic demand for nutrients increases, which, if not met, may slow down or indeed stop the wound from healing, thus, becoming chronic wounds. This study aims to perform a systematic review and meta-analysis of the effect of arginine and glutamine supplementation on wound healing. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for the systematic review and ten electronic databases were used. Five and 39 human studies met the inclusion criteria for arginine and glutamine, respectively. The overall meta-analysis demonstrated a significant effect of arginine supplementation on hydroxyproline content (MD: 4.49, 95% CI: 3.54, 4.45, p < 0.00001). Regarding glutamine supplementation, there was significant effect on nitrogen balance levels (MD: 0.39, 95% CI: 0.21, 0.58, p < 0.0001), IL-6 levels (MD: −5.78, 95% CI: −8.71, −2.86, p = 0.0001), TNFα levels (MD: −8.15, 95% CI: −9.34, −6.96, p < 0.00001), lactulose/mannitol (L/M) ratio (MD: −0.01, 95% CI: −0.02, −0.01, p < 0.00001), patient mortality (OR: 0.48, 95% CI: 0.32, 0.72, p = 0.0004), C-reactive protein (CRP) levels (MD: −1.10, 95% CI: −1.26, −0.93, p < 0.00001) and length of hospital stay (LOS) (MD: −2.65, 95% CI: −3.10, −2.21, p < 0.00001). Regarding T-cell lymphocytes, a slight decrease was observed, although it failed to reach significance (MD: −0.16, 95% CI: −0.33, 0.01, p = 0.07). Conclusion: The wound healing might be enhanced in one or at various stages by nutritional supplementation in the right dose.
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Gholamalizadeh M, Tabrizi R, Rezaei S, Badeli M, Shadnoush M, Jarrahi AM, Doaei S. Effect of glutamine supplementation on inflammatory markers in critically ill patients supported with enteral or parenteral feeding. JPEN J Parenter Enteral Nutr 2021; 46:61-68. [PMID: 34213769 DOI: 10.1002/jpen.2217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 06/24/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Glutamine plays an important role in acute catabolic conditions in critically ill patients. This meta-analysis aimed to investigate the effect of glutamine supplementation on inflammatory markers in critically ill patients supported with enteral feeding (EN) or parenteral feeding (PN). METHODS PubMed, Web of Science, Scopus, and Embase were explored to identify the studies investigating the effect of glutamine on serum inflammatory markers in intensive care unit patients. All randomized clinical trials that assessed the effect of glutamine supplementation on "inflammatory markers" in EN or PN were included in the study. Because a small number of studies were included, SE was adjusted for overall effect size by using the Knapp-Hartung method. RESULTS In this study, 2728 eligible studies were initially included, and 10 eligible case-control studies were finally enrolled for further investigations. There was a statistical reduction between preintervention and postintervention CRP levels (standardized mean difference [SMD] = -0.38 mg/L; 95% CI, -0.72 to -0.03). No significant association was found between L-glutamine supplementation in the EN/PN and interleukin 6 (IL-6) (SMD = -0.58 pg/ml; 95% CI, -2.15 to 0.99) and tumor necrosis factor alpha (TNF-α) (SMD = 2.69 pg/ml; 95% CI, -9.66 to 15.03) compared with the control group. CONCLUSIONS This study identified that glutamine supplementation might have an important effect on CRP in acute conditions and no significant effect on IL-6 and TNF-α in acute conditions.
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Affiliation(s)
- Maryam Gholamalizadeh
- Student Research Committee, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Tabrizi
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Shahla Rezaei
- Department of Clinical Nutrition, Student Research Committee, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.,Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mostafa Badeli
- Department of Nutrition, Urmia University of Medical Science, Urmia, Iran
| | - Mahdi Shadnoush
- Department of Clinical Nutrition, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Saeid Doaei
- Reproductive Health Research Center, Department of Obstetrics & Gynecology, Al-zahra hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
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Jabłońska B, Mrowiec S. Nutritional Support in Patients with Severe Acute Pancreatitis-Current Standards. Nutrients 2021; 13:1498. [PMID: 33925138 PMCID: PMC8145288 DOI: 10.3390/nu13051498] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/20/2021] [Accepted: 04/25/2021] [Indexed: 12/14/2022] Open
Abstract
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.
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Affiliation(s)
- Beata Jabłońska
- Department of Digestive Tract Surgery, Medical University of Silesia, Medyków 14 St., 40752 Katowice, Poland;
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Hasani M, Mansour A, Asayesh H, Djalalinia S, Mahdavi Gorabi A, Ochi F, Qorbani M. Effect of glutamine supplementation on cardiometabolic risk factors and inflammatory markers: a systematic review and meta-analysis. BMC Cardiovasc Disord 2021; 21:190. [PMID: 33865313 PMCID: PMC8053267 DOI: 10.1186/s12872-021-01986-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 04/06/2021] [Indexed: 01/16/2023] Open
Abstract
Background Evidence exists that glutamine plays multiple roles in glucose metabolism, insulin sensitivity, and anti-inflammatory effects. This systematic review and meta-analysis of controlled trials aimed to assess the effect of glutamine supplementation on cardio-metabolic risk factors and inflammatory markers. Methods The processes of systematic reviews and meta-analyses were performed according to the PRISMA checklist. PubMed, Web of Sciences, Cochrane library, and Scopus databases were search for relevant studies without time or language restrictions up to December 30, 2020. All randomized clinical trials which assessed the effect of glutamine supplementation on “glycemic indices”, “level of triglyceride, “and “inflammatory markers” were included in the study. The effect of glutamine supplementation on cardio-metabolic risk factors and inflammatory markers was assessed using a standardized mean difference (SMD) and 95% confidence interval (CI). Heterogeneity between among studies was assessed using Cochran Q-statistic and I-square. Random/fixed-effects meta-analysis method was used to estimate the pooled SMD. The risk of bias for the included trials was evaluated using the Cochrane quality assessment tool. Results In total, 12 studies that assessed the effect of glutamine supplementation on cardio-metabolic risk factors were included in the study. Meta-analysis showed that glutamine supplementation significantly decreased significantly serum levels of FPG [SMD: − 0.73, 95% CI − 1.35, − 0.11, I2: 84.1%] and CRP [SMD: − 0.58, 95% CI − 0.1, − 0.17, I2: 0%]. The effect of glutamine supplementation on other cardiometabolic risk factors was not statistically significant (P > 0.05). Conclusion Our findings showed that glutamine supplementation might have a positive effect on FPG and CRP; both of which are crucial as cardio-metabolic risk factors. However, supplementation had no significant effect on other cardio-metabolic risk factors.
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Affiliation(s)
- Motahareh Hasani
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Asieh Mansour
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute Shahid Beheshti University of Medical Science, Tehran, Iran.,Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Asayesh
- Department of Medical Emergencies, Qom University of Medical Sciences, Qom, Iran.
| | - Shirin Djalalinia
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.,Development of Research and Technology Center, Deputy of Research and Technology, Ministry of Health and Medical Education, Tehran, Iran
| | - Armita Mahdavi Gorabi
- Social Determinants of Health Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Fatemeh Ochi
- Students Research Committee, Alborz University of Medical Sciences, Karaj, Iran
| | - Mostafa Qorbani
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. .,Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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Zhou J, Xue Y, Liu Y, Li X, Tong Z, Li W. The effect of immunonutrition in patients with acute pancreatitis: a systematic review and meta‐analysis. J Hum Nutr Diet 2020; 34:429-439. [PMID: 33001472 DOI: 10.1111/jhn.12816] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/08/2020] [Accepted: 08/17/2020] [Indexed: 12/20/2022]
Affiliation(s)
- J. Zhou
- Surgical Intensive Care Unit (SICU) Department of General Surgery Jinling Hospital Medical School of Southeast University Nanjing China
- Department of Clinical Medicine School of Medicine Southeast University Nanjing China
| | - Y. Xue
- Department of Clinical Medicine School of Medicine Southeast University Nanjing China
| | - Y. Liu
- Surgical Intensive Care Unit (SICU) Department of General Surgery Jinling Hospital Medical School of Nanjing University Nanjing China
| | - X.K. Li
- Department of Clinical Medicine School of Medicine Southeast University Nanjing China
| | - Z.H. Tong
- Surgical Intensive Care Unit (SICU) Department of General Surgery Jinling Hospital Medical School of Nanjing University Nanjing China
| | - W.Q. Li
- Surgical Intensive Care Unit (SICU) Department of General Surgery Jinling Hospital Medical School of Southeast University Nanjing China
- Surgical Intensive Care Unit (SICU) Department of General Surgery Jinling Hospital Medical School of Nanjing University Nanjing China
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Studying the effect of parenterally administered l-alanyl l-glutamine dipeptide in diabetes and new onset diabetes in liver transplantation. EGYPTIAN JOURNAL OF ANAESTHESIA 2019. [DOI: 10.1016/j.egja.2015.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
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Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee. J Pediatr Gastroenterol Nutr 2018; 66:159-176. [PMID: 29280782 PMCID: PMC5755713 DOI: 10.1097/mpg.0000000000001715] [Citation(s) in RCA: 149] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. RESULTS The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastro-duodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. CONCLUSIONS This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP.
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Pan LL, Li J, Shamoon M, Bhatia M, Sun J. Recent Advances on Nutrition in Treatment of Acute Pancreatitis. Front Immunol 2017; 8:762. [PMID: 28713382 PMCID: PMC5491641 DOI: 10.3389/fimmu.2017.00762] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 06/16/2017] [Indexed: 12/12/2022] Open
Abstract
Acute pancreatitis (AP) is a common abdominal acute inflammatory disorder and the leading cause of hospital admission for gastrointestinal disorders in many countries. Clinical manifestations of AP vary from self-limiting local inflammation to devastating systemic pathological conditions causing significant morbidity and mortality. To date, despite extensive efforts in translating promising experimental therapeutic targets in clinical trials, disease-specific effective remedy remains obscure, and supportive care has still been the primary treatment for this disease. Emerging evidence, in light of the current state of pathophysiology of AP, has highlighted that strategic initiation of nutrition with appropriate nutrient supplementation are key to limit local inflammation and to prevent or manage AP-associated complications. The current review focuses on recent advances on nutritional interventions including enteral versus parenteral nutrition strategies, and nutritional supplements such as probiotics, glutamine, omega-3 fatty acids, and vitamins in clinical AP, hoping to advance current knowledge and practice related to nutrition and nutritional supplements in clinical management of AP.
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Affiliation(s)
- Li-Long Pan
- School of Medicine, Jiangnan University, Wuxi, China
| | - Jiahong Li
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- Nutrition and Immunology Laboratory, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Muhammad Shamoon
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- Nutrition and Immunology Laboratory, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Madhav Bhatia
- Inflammation Research Group, Department of Pathology, University of Otago, Christchurch, New Zealand
| | - Jia Sun
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- Nutrition and Immunology Laboratory, School of Food Science and Technology, Jiangnan University, Wuxi, China
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Pakula MM, Maier TJ, Vorup-Jensen T. Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism. Expert Opin Ther Targets 2017; 21:611-626. [PMID: 28441889 DOI: 10.1080/14728222.2017.1323879] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.
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Affiliation(s)
| | - Thorsten J Maier
- a Department of Biomedicine , Aarhus University , Aarhus , Denmark
| | - Thomas Vorup-Jensen
- a Department of Biomedicine , Aarhus University , Aarhus , Denmark.,b Center for Neurodegenerative Inflammation Prevention (NEURODIN) , Aarhus University , Aarhus , Denmark.,c Interdisciplinary Nanoscience Center , Aarhus University , Aarhus , Denmark.,d The Lundbeck Foundation Nanomedicine Center for Individualized Management of Tissue Damage and Regeneration (LUNA) , Aarhus University , Aarhus , Denmark.,e MEMBRANES Research center , Aarhus University , Aarhus , Denmark
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Márta K, Farkas N, Szabó I, Illés A, Vincze Á, Pár G, Sarlós P, Bajor J, Szűcs Á, Czimmer J, Mosztbacher D, Párniczky A, Szemes K, Pécsi D, Hegyi P. Meta-Analysis of Early Nutrition: The Benefits of Enteral Feeding Compared to a Nil Per Os Diet Not Only in Severe, but Also in Mild and Moderate Acute Pancreatitis. Int J Mol Sci 2016; 17:1691. [PMID: 27775609 PMCID: PMC5085723 DOI: 10.3390/ijms17101691] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Revised: 09/10/2016] [Accepted: 09/27/2016] [Indexed: 12/12/2022] Open
Abstract
The recently published guidelines for acute pancreatitis (AP) suggest that enteral nutrition (EN) should be the primary therapy in patients suffering from severe acute pancreatitis (SAP); however, none of the guidelines have recommendations on mild and moderate AP (MAP). A meta-analysis was performed using the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). The following PICO (problem, intervention, comparison, outcome) was applied: P: nutrition in AP; I: enteral nutrition (EN); C: nil per os diet (NPO); and O: outcome. There were 717 articles found in Embase, 831 in PubMed, and 10 in the Cochrane database. Altogether, seven SAP and six MAP articles were suitable for analyses. In SAP, forest plots were used to illustrate three primary endpoints (mortality, multiorgan failure, and intervention). In MAP, 14 additional secondary endpoints were analyzed (such as CRP (C-reactive protein), WCC (white cell count), complications, etc.). After pooling the data, the Mann-Whitney U test was used to detect significant differences. Funnel plots were created for testing heterogeneity. All of the primary endpoints investigated showed that EN is beneficial vs. NPO in SAP. In MAP, all of the six articles found merit in EN. Analyses of the primary endpoints did not show significant differences between the groups; however, analyzing the 17 endpoints together showed a significant difference in favor of EN vs. NPO. EN is beneficial compared to a nil per os diet not only in severe, but also in mild and moderate AP.
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Affiliation(s)
- Katalin Márta
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Nelli Farkas
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
- Institute of Bioanalysis, University of Pécs, Pécs H-7624, Hungary.
| | - Imre Szabó
- Department of Gastroenterology, First Department of Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Anita Illés
- Department of Gastroenterology, First Department of Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Áron Vincze
- Department of Gastroenterology, First Department of Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Gabriella Pár
- Department of Gastroenterology, First Department of Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Patrícia Sarlós
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
- Department of Gastroenterology, First Department of Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Judit Bajor
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
- Department of Gastroenterology, First Department of Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Ákos Szűcs
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
- First Department of Surgery, Semmelweis University, Budapest H-1085, Hungary.
| | - József Czimmer
- Department of Gastroenterology, First Department of Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Dóra Mosztbacher
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
- First Department of Pediatrics, Semmelweis University, Budapest H-1083, Hungary.
| | - Andrea Párniczky
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
- Heim Pál Children's Hospital, Budapest H-1089, Hungary.
| | - Kata Szemes
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
- Department of Gastroenterology, First Department of Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Dániel Pécsi
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
| | - Péter Hegyi
- Institute for Translational Medicine, University of Pécs, Pécs H-7624, Hungary.
- Translational Gastroenterology Research Group, Hungarian Academy of Sciences, University of Szeged, Szeged H-6720, Hungary.
- First Department of Medicine, University of Szeged, Szeged H-6720, Hungary.
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Castro-Gutiérrez V, Rada G. Is there a role for glutamine supplementation in the management of acute pancreatitis? Medwave 2016; 16 Suppl 3:e6512. [PMID: 27580296 DOI: 10.5867/medwave.2016.6512] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
There is no consensus about the effects of glutamine supplementation for acute pancreatitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified 15 systematic reviews including 31 randomized controlled trials addressing the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded glutamine supplementation might decrease infectious complications in acute pancreatitis, but it is not clear if it affects mortality or length of hospital stay because the certainty of the evidence is very low.
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Affiliation(s)
- Victoria Castro-Gutiérrez
- Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Proyecto Epistemonikos, Santiago, Chile. Address: Facultad de Medicina, Pontificia Universidad Católica de Chile, Lira 63, Santiago Centro. Chile
| | - Gabriel Rada
- Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Proyecto Epistemonikos, Santiago, Chile; Programa de Salud Basada en Evidencia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; GRADE working group; The Cochrane Collaboration
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Gooshe M, Abdolghaffari AH, Nikfar S, Mahdaviani P, Abdollahi M. Antioxidant therapy in acute, chronic and post-endoscopic retrograde cholangiopancreatography pancreatitis: An updated systematic review and meta-analysis. World J Gastroenterol 2015; 21:9189-9208. [PMID: 26290647 PMCID: PMC4533052 DOI: 10.3748/wjg.v21.i30.9189] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 04/15/2015] [Accepted: 06/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the efficacy and adverse effects of antioxidant therapy in acute pancreatitis (AP), chronic pancreatitis (CP) and post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). METHODS PubMed, Scopus, Google Scholar, Cochrane library database, and Evidence-based medicine/clinical trials published before August 2014 were searched. Clinical and laboratory outcomes of randomized trials of antioxidant therapy in patients with AP, CP and PEP were included. The methodological quality of the trials was assessed by the Jadad score based on the description of randomization, blinding, and dropouts (withdrawals). The results of the studies were pooled and meta-analyzed to provide estimates of the efficacy of antioxidant therapy. RESULTS Thirty four trials out of 1069 potentially relevant studies with data for 4898 patients were eligible for inclusion. Antioxidant therapy significantly reduced the length of hospital stay in AP patients {mean difference -2.59 d (95%CI: -4.25-(-0.93)], P = 0.002}. Although, antioxidant therapy had no significant effect on serum C reactive protein (CRP) after 5-7 d in AP patients [mean difference -9.57 (95%CI: -40.61-21.48, P = 0.55], it significantly reduced serum CRP after 10 d {mean difference -45.16 [95%CI: -89.99-(-0.33)], P = 0.048}. In addition, antioxidant therapy had no significant effect on CP-induced pain [mean difference -2.13 (95%CI: -5.87-1.6), P = 0.26]. Antioxidant therapy had no significant effects on the incidence of all types of PEP [mean difference 1.05 (95%CI: 0.74-1.5), P = 0.78], severe PEP [mean difference 0.92 (95%CI: 0.43-1.97), P = 0.83], moderate PEP [mean difference 0.82 (95%CI: 0.54-1.23), P = 0.33], and mild PEP [mean difference 1.33 (95%CI: 0.99-1.78), P = 0.06]. Furthermore, while antioxidant therapy had no significant effect on serum amylase after less than 8 h sampling [mean difference -20.61 (95%CI: -143.61-102.39), P = 0.74], it significantly reduced serum amylase close to 24-h sampling {mean difference -16.13 [95%CI: -22.98-(-9.28)], P < 0.0001}. CONCLUSION While there is some evidence to support antioxidant therapy in AP, its effect on CP and PEP is still controversial.
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Oldani M, Sandini M, Nespoli L, Coppola S, Bernasconi DP, Gianotti L. Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials. Medicine (Baltimore) 2015; 94:e1319. [PMID: 26252319 PMCID: PMC4616616 DOI: 10.1097/md.0000000000001319] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Revised: 06/25/2015] [Accepted: 07/02/2015] [Indexed: 12/17/2022] Open
Abstract
The role of glutamine (GLN) supplementation in critically ill patients is controversial. Our aim was to analyze its potential effect in patients admitted to intensive care unit (ICU).We performed a systematic literature review through Medline, Embase, Pubmed, Scopus, Ovid, ISI Web of Science, and the Cochrane-Controlled Trials Register searching for randomized clinical trials (RCTs) published from 1983 to 2014 and comparing GLN supplementation to no supplementation in patients admitted to ICU. A random-effect meta-analysis for each outcome (hospital and ICU mortality and rate of infections) of interest was carried out. The effect size was estimated by the risk ratio (RR).Thirty RCTs were analyzed with a total of 3696 patients, 1825 (49.4%) receiving GLN and 1859 (50.6%) no GLN (control groups). Hospital mortality rate was 27.6% in the GLN patients and 28.6% in controls with an RR of 0.93 (95% CI = 0.81-1.07; P = 0.325, I = 10.7%). ICU mortality was 18.0 % in the patients receiving GLN and 17.6% in controls with an RR of 1.01 (95% CI = 0.86-1.19; P = 0.932, I = 0%). The incidence of infections was 39.7% in GLN group versus 41.7% in controls. The effect of GLN was not significant (RR = 0.88; 95% CI = 0.76-1.03; P = 0.108, I = 56.1%).These results do not allow to recommend GLN supplementation in a generic population of critically ills. Further RCTs are needed to explore the effect of GLN in more specific cohort of patients.
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Affiliation(s)
- Massimo Oldani
- From the Department of Surgery and Translational Medicine, Milano-Bicocca University, San Gerardo Hospital, Monza (MO, MS, LN, LG); Department of Surgery, Humanitas Gavazzeni, Bergamo (SC); and Department of Health Sciences, Center of Biostatistics for Clinical Epidemiology, Milano-Bicocca University, Monza, Italy (DPB)
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Ye BD. [Parenteral Nutritional Support in Gastrointestinal and Liver Diseases]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2015; 65:346-53. [PMID: 26087689 DOI: 10.4166/kjg.2015.65.6.346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Protein-calorie malnutrition and deficiencies of specific nutrients could commonly occur in various types of gastrointestinal diseases. These nutritional problems could delay recovery from diseases, resulting in increased morbidity and mortality, and impairment of quality of life. Parenteral nutrition (PN) is one of the methods of nutritional support through which macronutrients (glucose, amino acids, and triglycerides), micronutrients (vitamins and trace elements), water, and electrolytes are administered via peripheral or central venous route. PN could play an important role for patients for whom enteral/oral feeding is contraindicated or cannot meet the patients' requirement for adequate nutrition due to anatomical and/or functional problems. Since insufficient and excessive PN supplement could both be harmful for patients, it is very important to adhere to correct indication, optimal timing, and dosage/composition of PN. In this article, the current role of PN for various gastrointestinal diseases will be reviewed and discussed.
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Affiliation(s)
- Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
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Jeurnink SM, Nijs MM, Prins HAB, Greving JP, Siersema PD. Antioxidants as a treatment for acute pancreatitis: A meta-analysis. Pancreatology 2015; 15:203-8. [PMID: 25891791 DOI: 10.1016/j.pan.2015.03.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 03/10/2015] [Accepted: 03/16/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To assess the efficacy of antioxidants in acute (AP) pancreatitis. METHODS 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. RESULTS 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). CONCLUSION 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.
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Affiliation(s)
- S M Jeurnink
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands.
| | - M M Nijs
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
| | - H A B Prins
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
| | - J P Greving
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
| | - P D Siersema
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
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Jafari T, Feizi A, Askari G, Fallah AA. Parenteral immunonutrition in patients with acute pancreatitis: a systematic review and meta-analysis. Clin Nutr 2015; 34:35-43. [PMID: 24931755 DOI: 10.1016/j.clnu.2014.05.008] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2013] [Revised: 04/01/2014] [Accepted: 05/15/2014] [Indexed: 01/10/2023]
Abstract
BACKGROUND & AIMS Acute pancreatitis is a systemic immunoinflammatory response to auto-digestion of the pancrease and peri-pancreatic organs. Patients with acute pancreatitis can rapidly develop nutritional deficiency; hence nutritional support is important and critical. Sometimes parenteral nutrition (PN) is inevitable in acute pancreatitis. Due to immunosuppressive and inflammatory nature of the disease, it seems that immunonutrients like glutamine and omega-3 fatty acids (ω-3 FAs) added to parenteral formulas may improve the conditions. We conducted a meta-analysis to evaluate the effects of parenteral immunonutrition on clinical outcomes (infectious complications, length of hospital stay (LOS) and mortality) in patients with acute pancreatitis. METHODS A computerized literature search on four databases (PubMed, Cochrane, ISI Web of Science, and Iran Medex) was performed to find all the randomized controlled trials (RCTs) assessed the effects of parenteral immunonutrition in acute pancreatitis. Necessary data were extracted and quality assessment of RCTs was performed with consensus in the study team. Fixed effects model was used to conduct the meta-analysis. RESULTS One hundred and ninety four references were found via our search in which 7 articles matched our criteria for enrolling the meta-analysis. Parenteral immunonutrition significantly reduced the risk of infectious complications (RR = 0.59; 95% CI, 0.39-0.88; p ≤ 0.05) and mortality (RR = 0.26; 95% CI, 0.11-0.59; p ≤ 0.001). LOS was also shorter in patients who received immunonutrition (MD = -2.93 days; 95% CI, -4.70 to -1.15; p ≤ 0.001). CONCLUSION Immunonutrients like glutamine and ω-3 FAs added to parenteral formulas can improve prognoses in patients with acute pancreatitis.
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Affiliation(s)
- Tina Jafari
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Awat Feizi
- Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran; Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan 81745-319, Iran
| | - Gholamreza Askari
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Aziz A Fallah
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord 34141, Iran
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Hu J, Huang Q, Lin XS, Liu CH, Yang J, Li RY, Wang C. Parenteral immunonutrition in patients with acute pancreatitis: A meta-analysis of randomized controlled trials. Shijie Huaren Xiaohua Zazhi 2014; 22:4647-4653. [DOI: 10.11569/wcjd.v22.i30.4647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effects of parenteral immunonutrition on clinical outcomes [infectious complications, length of hospital stay (LOS) and mortality] in patients with acute pancreatitis.
METHODS: Pubmed, Medline, Embase, Science Direct, CBM, Springer link, VIP and CNKI were electronically searched before 31st May 2014 to collect the articles on parenteral immunonutrition in acute pancreatitis. The quality of the included trials was assessed according to the inclusive and exclusive criteria, and the data were extracted and analyzed using RevMan 5.2.7 software.
RESULTS: A total of seven randomized controlled trials studies with 264 pancreatitis patients were included. The number of patients receiving parenteral immunonutrition was 130 and the number of patient receiving standard parenteral nutrition was 134. Meta-analysis showed that parenteral immunonutrition significantly reduced the risk of infectious complications (RR = 0.56, 95%CI: 0.39-0.82, P = 0.002) and mortality (RR = 0.23, 95%CI: 0.10-0.52, P < 0.001). LOS was also shorter in patients who received immunonutrition (RR = -5.63, 95%CI: -9.69--1.57, P = 0.007).
CONCLUSION: Immunonutrients like glutamine and omega-3 fatty acids added to parenteral formulas can improve prognoses in patients with acute pancreatitis. Our findings still need to be verified by large, multicenter prospective randomized controlled trials.
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Abstract
BACKGROUND Glutamine is a non-essential amino acid which is abundant in the healthy human body. There are studies reporting that plasma glutamine levels are reduced in patients with critical illness or following major surgery, suggesting that glutamine may be a conditionally essential amino acid in situations of extreme stress. In the past decade, several clinical trials examining the effects of glutamine supplementation in patients with critical illness or receiving surgery have been done, and the systematic review of this clinical evidence has suggested that glutamine supplementation may reduce infection and mortality rates in patients with critical illness. However, two recent large-scale randomized clinical trials did not find any beneficial effects of glutamine supplementation in patients with critical illness. OBJECTIVES The objective of this review was to:1. assess the effects of glutamine supplementation in critically ill adults and in adults after major surgery on infection rate, mortality and other clinically relevant outcomes;2. investigate potential heterogeneity across different patient groups and different routes for providing nutrition. SEARCH METHODS We searched the Cochrane Anaesthesia Review Group (CARG) Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 5); MEDLINE (1950 to May 2013); EMBASE (1980 to May 2013) and Web of Science (1945 to May 2013). SELECTION CRITERIA We included controlled clinical trials with random or quasi-random allocation that examined glutamine supplementation versus no supplementation or placebo in adults with a critical illness or undergoing elective major surgery. We excluded cross-over trials. DATA COLLECTION AND ANALYSIS Two authors independently extracted the relevant information from each included study using a standardized data extraction form. For infectious complications and mortality and morbidity outcomes we used risk ratio (RR) as the summary measure with the 95% confidence interval (CI). We calculated, where appropriate, the number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH). We presented continuous data as the difference between means (MD) with the 95% CI. MAIN RESULTS Our search identified 1999 titles, of which 53 trials (57 articles) fulfilled our inclusion criteria. The 53 included studies enrolled a total of 4671 participants with critical illness or undergoing elective major surgery. We analysed seven domains of potential risk of bias. In 10 studies the risk of bias was evaluated as low in all of the domains. Thirty-three trials (2303 patients) provided data on nosocomial infectious complications; pooling of these data suggested that glutamine supplementation reduced the infectious complications rate in adults with critical illness or undergoing elective major surgery (RR 0.79, 95% CI 0.71 to 0.87, P ＜ 0.00001, I² = 8%, moderate quality evidence). Thirty-six studies reported short-term (hospital or less than one month) mortality. The combined rate of mortality from these studies was not statistically different between the groups receiving glutamine supplement and those receiving no supplement (RR 0.89, 95% CI 0.78 to 1.02, P = 0.10, I² = 22%, low quality evidence). Eleven studies reported long-term (more than six months) mortality; meta-analysis of these studies (2277 participants) yielded a RR of 1.00 (95% CI 0.89 to 1.12, P = 0.94, I² = 30%, moderate quality evidence). Subgroup analysis of infectious complications and mortality outcomes did not find any statistically significant differences between the predefined groups. Hospital length of stay was reported in 36 studies. We found that the length of hospital stay was shorter in the intervention group than in the control group (MD -3.46 days, 95% CI -4.61 to -2.32, P < 0.0001, I² = 63%, low quality evidence). Slightly prolonged intensive care unit (ICU) stay was found in the glutamine supplemented group from 22 studies (2285 participants) (MD 0.18 days, 95% CI 0.07 to 0.29, P = 0.002, I² = 11%, moderate quality evidence). Days on mechanical ventilation (14 studies, 1297 participants) was found to be slightly shorter in the intervention group than in the control group (MD - 0.69 days, 95% CI -1.37 to -0.02, P = 0.04, I² = 18%, moderate quality evidence). There was no clear evidence of a difference between the groups for side effects and quality of life, however results were imprecise for serious adverse events and few studies reported on quality of life. Sensitivity analysis including only low risk of bias studies found that glutamine supplementation had beneficial effects in reducing the length of hospital stay (MD -2.9 days, 95% CI -5.3 to -0.5, P = 0.02, I² = 58%, eight studies) while there was no statistically significant difference between the groups for all of the other outcomes. AUTHORS' CONCLUSIONS This review found moderate evidence that glutamine supplementation reduced the infection rate and days on mechanical ventilation, and low quality evidence that glutamine supplementation reduced length of hospital stay in critically ill or surgical patients. It seems to have little or no effect on the risk of mortality and length of ICU stay, however. The effects on the risk of serious side effects were imprecise. The strength of evidence in this review was impaired by a high risk of overall bias, suspected publication bias, and moderate to substantial heterogeneity within the included studies.
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Affiliation(s)
- Kun‐Ming Tao
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityDepartment of AnesthesiologyRoom 404, Building 3, Eastern Hepatobiliary Surgery Hospital, 225 Changhai RoadShanghaiShanghaiChina200438
| | - Xiao‐Qian Li
- Changhai Hospital, Second Military Medical UniversityDepartment of Traditional Chinese MedicineRoom 2201, School of TCM, No.800 Xiangyin RoadShanghaiShanghaiChina200433
| | - Li‐Qun Yang
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityDepartment of AnesthesiologyRoom 404, Building 3, Eastern Hepatobiliary Surgery Hospital, 225 Changhai RoadShanghaiShanghaiChina200438
| | - Wei‐Feng Yu
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityDepartment of AnesthesiologyRoom 404, Building 3, Eastern Hepatobiliary Surgery Hospital, 225 Changhai RoadShanghaiShanghaiChina200438
| | - Zhi‐Jie Lu
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityDepartment of AnesthesiologyRoom 404, Building 3, Eastern Hepatobiliary Surgery Hospital, 225 Changhai RoadShanghaiShanghaiChina200438
| | - Yu‐Ming Sun
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityDepartment of AnesthesiologyRoom 404, Building 3, Eastern Hepatobiliary Surgery Hospital, 225 Changhai RoadShanghaiShanghaiChina200438
| | - Fei‐Xiang Wu
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical UniversityDepartment of AnesthesiologyRoom 404, Building 3, Eastern Hepatobiliary Surgery Hospital, 225 Changhai RoadShanghaiShanghaiChina200438
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Effect of oral glutamine supplementation on gut permeability and endotoxemia in patients with severe acute pancreatitis: a randomized controlled trial. Pancreas 2014; 43:867-73. [PMID: 24809408 DOI: 10.1097/mpa.0000000000000124] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE The aim of this study is to evaluate the effect of oral glutamine (GL) supplementation on gut permeability and endotoxemia (surrogate end point) in patients with severe acute pancreatitis. METHODS In a randomized controlled trial, patients were randomized to be given placebo or GL for 7 days. The primary outcome measures include the effect on gut permeability (assessed by lactulose/mannitol excretion in urine and endotoxemia assessed by endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM). The secondary outcome measures include infectious complications, mortality, total hospital/intensive care unit stay, C-reactive protein, and prealbumin levels. RESULTS Patients were assigned to GL (n = 41) and placebo (n = 39) groups. There was no change in gut permeability after the intervention. However, the EndoCab IgM levels increased significantly (33 [4, 175] to 40 [8, 350] GMU/mL; P = 0.0164) and the C-reactive protein levels decreased significantly (133 [1, 287] to 88 [1, 267] ng/mL; P = 0.0236) in the GL group. No difference was observed in infectious complication, prealbumin value, hospital/intensive care unit stay, and mortality in both groups. CONCLUSIONS No significant trend was identified for an effect of GL on gut permeability. Decreased inflammation and endotoxemia did not translate into reduced infectious complications in severe acute pancreatitis. However, the study was underpowered to detect the aforementioned difference (trial registration: CTRI/2009/000945).
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Jensen KB, Chan DL. Nutritional management of acute pancreatitis in dogs and cats. J Vet Emerg Crit Care (San Antonio) 2014; 24:240-50. [PMID: 24690138 DOI: 10.1111/vec.12180] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 02/17/2014] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To review current and emerging nutritional approaches in the management of acute pancreatitis (AP) in people, dogs, and cats, and to provide a framework for further investigation in this field. DATA SOURCES Veterinary retrospective studies and reviews, human prospective clinical trials and reviews, and experimental animal studies focusing on nutritional management during AP. SUMMARY Nutritional management is an important part of the treatment plan for patients with AP. In human medicine, the general approach for providing nutrition in patients with AP has changed in recent years and favors enteral over parenteral nutrition with an emphasis on early enteral nutrition (EN). Although there are limited data available, there is increasing evidence in the veterinary literature that supports the beneficial role of EN in AP and contradicts previous assumptions about poor tolerance to enteral feeding in this patient population. Parenteral nutrition may be appropriate alone or in combination with EN as a temporary measure in malnourished patients that do not tolerate adequate EN; however, enteral feeding should be attempted first in most cases. Immunonutrition is being investigated for its positive role in modulating pancreatic inflammation and improving gut barrier function in cases of human AP. CONCLUSIONS The nutritional management of veterinary patients with AP remains challenging. Based on clinical evidence in people, experimental animal studies, and preliminary studies in dogs and cats, the choice of EN over parenteral nutritional support during AP in dogs and cats appears to be beneficial and well tolerated. Optimization of nutritional therapies in dogs and cats including the use of immunonutrition during AP warrants further investigation.
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Affiliation(s)
- Kristine B Jensen
- Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, Hertfordshire, United Kingdom
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Asrani V, Chang WK, Dong Z, Hardy G, Windsor JA, Petrov MS. Glutamine supplementation in acute pancreatitis: a meta-analysis of randomized controlled trials. Pancreatology 2013; 13:468-74. [PMID: 24075510 DOI: 10.1016/j.pan.2013.07.282] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 07/11/2013] [Accepted: 07/20/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND There is emerging evidence that glutamine supplementation should be considered in patients with acute and critical illness associated with a catabolic response. There are reports of glutamine supplementation in acute pancreatitis but the results of these studies are conflicting. The aim of this study was to systematically review the randomised controlled trials (RCT) of glutamine in patients with acute pancreatitis. METHODS The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SCOPUS and 3 major Chinese databases were searched. The outcomes studied were mortality, total infectious complications, and length of hospital stay. A random effects model was used for meta-analysis of the outcomes in the included trials. A number of pre-specified subgroup analyses were also conducted. The summary estimates were reported as risk ratio (RR) for categorical variables and mean difference (MD) for continuous variables together with the corresponding 95% confidence interval. RESULTS Twelve RCT that enrolled 505 patients with acute pancreatitis were included in the final analysis. Overall, glutamine supplementation resulted in a significantly reduced risk of mortality (RR 0.30; 95% CI, 0.15 to 0.60; P < 0.001) and total infectious complications (RR 0.58; 95% CI, 0.39 to 0.87; P = 0.009) but not length of hospital stay (MD -1.35; 95% CI, -3.25 to 0.56, P = 0.17). In the subgroup analyses, only patients who received parenteral nutrition and those who received glutamine in combination with other immunonutrients demonstrated a statistically significant benefit in terms of all the studied outcomes. CONCLUSIONS This meta-analysis demonstrates a clear advantage for glutamine supplementation in patients with acute pancreatitis who receive total parenteral nutrition. Patients with acute pancreatitis who receive enteral nutrition do not require glutamine supplementation. Further studies are warranted to determine whether patients who receive combined enteral and parenteral nutrition need glutamine supplementation.
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Affiliation(s)
- Varsha Asrani
- Department of Surgery, University of Auckland, Auckland, New Zealand; Nutrition Services, Auckland City Hospital, Auckland, New Zealand
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Zhong X, Liang CP, Gong S. Intravenous glutamine for severe acute pancreatitis: A meta-analysis. World J Crit Care Med 2013; 2:4-8. [PMID: 24701410 PMCID: PMC3953862 DOI: 10.5492/wjccm.v2.i1.4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2012] [Revised: 01/29/2013] [Accepted: 03/27/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy of intravenous glutamine on the patients with severe acute pancreatitis (SAP).
METHODS: The Cochrane Library, PubMed, EMBASE, and EBM review databases were searched up to June 2012. Randomized controlled trials (RCTs) that compared non-glutamine nutrition with intravenous glutamine supplemented nutrition in patients with SAP were included. A method recommended by the Cochrane Collaboration was used to perform a meta-analysis of those RCTs.
RESULTS: Four RCTs involving a total of 190 participants were included. Analysis of these RCTs revealed the presence of statistical homogeneity among them. Results showed that glutamine dipeptide has a positive effect in reducing the mortality rate (OR = 0.26, 95%CI: 0.09-0.73, P = 0.01), length of hospital stay (weighted mean difference = -4.85, 95%CI: 6.67--3.03, P < 0.001), and the rate of complications (OR = 0.41, 95%CI: 0.22-0.78, P = 0.006). No serious adverse effects were found.
CONCLUSION: Current best evidence demonstrates that glutamine is effective for SAP. Further high quality trials are required and parameters of nutritional condition and hospital cost should be considered in future RCTs with sufficient size and rigorous design.
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Choi JH, Lim KH, Park E, Kim JY, Choi YK, Baek KH. Glutamate-ammonia ligase and reduction of G0 population in PANC-1 cells. J Cell Biochem 2012; 114:303-13. [DOI: 10.1002/jcb.24370] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Accepted: 08/13/2012] [Indexed: 12/18/2022]
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Bollhalder L, Pfeil AM, Tomonaga Y, Schwenkglenks M. A systematic literature review and meta-analysis of randomized clinical trials of parenteral glutamine supplementation. Clin Nutr 2012. [PMID: 23196117 DOI: 10.1016/j.clnu.2012.11.003] [Citation(s) in RCA: 98] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND & AIMS Glutamine supplementation has been associated with reduced mortality, infections and hospital length of stay in critically ill patients and patients undergoing major surgery. We carried out a meta-analysis to examine randomized clinical trial (RCT)-based evidence of these effects. METHODS Based on a systematic database search, RCTs published since 1990 were included if they evaluated the effect of parenteral glutamine supplementation against a background of parenteral nutrition. Enteral (tube) feeding in a proportion of patients was allowable. Information on RCT methodology, quality and outcomes was extracted. Random effects meta-analysis followed the DerSimonian-Laird approach. RESULTS Forty RCTs were eligible for meta-analysis. Parenteral glutamine supplementation was associated with a non-significant 11% reduction in short-term mortality (RR = 0.89; 95% CI, 0.77-1.04). Infections were significantly reduced (RR = 0.83; 95% CI, 0.72-0.95) and length of stay was 2.35 days shorter (95% CI, -3.68 to -1.02) in the glutamine arms. Meta-analysis results were strongly influenced by one recent trial. An element of publication bias could not be excluded. CONCLUSION Parenteral glutamine supplementation in severely ill patients may reduce infections, length of stay and mortality, but substantial uncertainty remains. Unlike previous meta-analyses, we could not demonstrate a significant reduction in mortality.
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Affiliation(s)
- Lea Bollhalder
- Institute of Social and Preventive Medicine, Medical Economics Unit, University of Zurich, Hirschengraben 84, 8001 Zurich, Switzerland.
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Vanek VW, Matarese LE, Robinson M, Sacks GS, Young LS, Kochevar M. A.S.P.E.N. Position Paper. Nutr Clin Pract 2011; 26:479-94. [DOI: 10.1177/0884533611410975] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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Stein J, Boehles HJ, Blumenstein I, Goeters C, Schulz R. Amino acids - Guidelines on Parenteral Nutrition, Chapter 4. GERMAN MEDICAL SCIENCE : GMS E-JOURNAL 2009; 7:Doc24. [PMID: 20049071 PMCID: PMC2795371 DOI: 10.3205/000083] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2009] [Indexed: 12/16/2022]
Abstract
Protein catabolism should be reduced and protein synthesis promoted with parenteral nutrion (PN). Amino acid (AA) solutions should always be infused with PN. Standard AA solutions are generally used, whereas specially adapted AA solutions may be required in certain conditions such as severe disorders of AA utilisation or in inborn errors of AA metabolism. An AA intake of 0.8 g/kg/day is generally recommended for adult patients with a normal metabolism, which may be increased to 1.2-1.5 g/kg/day, or to 2.0 or 2.5 g/kg/day in exceptional cases. Sufficient non-nitrogen energy sources should be added in order to assure adequate utilisation of AA. A nitrogen calorie ratio of 1:130 to 1:170 (g N/kcal) or 1:21 to 1:27 (g AA/kcal) is recommended under normal metabolic conditions. In critically ill patients glutamine should be administered parenterally if indicated in the form of peptides, for example 0.3-0.4 g glutamine dipeptide/kg body weight/day (=0.2-0.26 g glutamine/kg body weight/day). No recommendation can be made for glutamine supplementation in PN for patients with acute pancreatitis or after bone marrow transplantation (BMT), and in newborns. The application of arginine is currently not warranted as a supplement in PN in adults. N-acetyl AA are only of limited use as alternative AA sources. There is currently no indication for use of AA solutions with an increased content of glycine, branched-chain AAs (BCAA) and ornithine-alpha-ketoglutarate (OKG) in all patients receiving PN. AA solutions with an increased proportion of BCAA are recommended in the treatment of hepatic encephalopathy (III-IV).
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Affiliation(s)
- J Stein
- Dept. Internal Medicine, University of Frankfurt, Germany
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Chan DL, Rozanski EA, Freeman LM. Relationship among plasma amino acids, C-reactive protein, illness severity, and outcome in critically ill dogs. J Vet Intern Med 2009; 23:559-63. [PMID: 19645841 DOI: 10.1111/j.1939-1676.2009.0296.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Alterations in circulating amino acids have been documented in animal models and in critically ill people but have not been evaluated in dogs with spontaneously occurring disease. HYPOTHESIS/OBJECTIVES To compare amino acid concentrations in critically ill dogs and healthy controls and to investigate potential relationships among amino acids, markers of inflammation, illness severity, and clinical outcome. ANIMALS Forty-eight critically ill dogs and 24 healthy control dogs. METHODS Plasma was analyzed for amino acids and C-reactive protein (CRP) was measured in serum. The Fischer ratio (the molar ratio of branched chain amino acids [BCAA] to aromatic amino acids [AAA]) and survival prediction index (SPI2) were calculated. RESULTS Median CRP concentrations were significantly higher in the critically ill dogs compared with controls (P < .001). Critically ill dogs had significantly lower concentrations of alanine (P= .001), arginine (P < .001), citrulline (P < .001), glycine (P < .001), methionine (P < .001), proline (P < .001), and serine (P= .001) but significantly higher concentrations of lysine (P= .02) and phenylalanine (P < .001; Table 1). This pattern resulted in a significantly lower Fischer ratio (P= .001) in the critically ill group. Median SPI2 score was significantly higher in dogs that survived (P= .03). Concentrations of arginine (P= .02), isoleucine (P= .01), leucine (P= .04), serine (P= .04), valine (P= .04), total BCAA (P= .03), and the Fischer ratio (P= .03) were significantly higher in survivors compared with nonsurvivors. CONCLUSIONS AND CLINICAL IMPORTANCE Critically ill dogs have altered amino acid profiles and additional research to investigate potential benefits of amino acid supplementation is warranted.
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Affiliation(s)
- D L Chan
- Section of Emergency and Critical Care, North Grafton, MA, USA.
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Monfared SSMS, Vahidi H, Abdolghaffari AH, Nikfar S, Abdollahi M. Antioxidant therapy in the management of acute, chronic and post-ERCP pancreatitis: a systematic review. World J Gastroenterol 2009; 15:4481-4490. [PMID: 19777606 PMCID: PMC2751992 DOI: 10.3748/wjg.15.4481] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2009] [Revised: 08/03/2009] [Accepted: 08/10/2009] [Indexed: 02/06/2023] Open
Abstract
We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis (AP) or chronic pancreatitis (CP) and in the prevention of post-endoscopic retrograde cholangio-pancreatography (post-ERCP) pancreatitis (PEP) up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous. Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PEP. Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted.
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Gianotti L, Meier R, Lobo DN, Bassi C, Dejong CHC, Ockenga J, Irtun O, MacFie J. ESPEN Guidelines on Parenteral Nutrition: pancreas. Clin Nutr 2009; 28:428-435. [PMID: 19464771 DOI: 10.1016/j.clnu.2009.04.003] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2009] [Accepted: 04/01/2009] [Indexed: 12/13/2022]
Abstract
Assessment of the severity of acute pancreatitis (AP), together with the patient's nutritional status is crucial in the decision making process that determines the need for artificial nutrition. Both should be done on admission and at frequent intervals thereafter. The indication for nutritional support in AP is actual or anticipated inadequate oral intake for 5-7 days. This period may be shorter in those with pre-existing malnutrition. Substrate metabolism in severe AP is similar to that in severe sepsis or trauma. Parenteral amino acids, glucose and lipid infusion do not affect pancreatic secretion and function. If lipids are administered, serum triglycerides must be monitored regularly. The use of intravenous lipids as part of parenteral nutrition (PN) is safe and feasible when hypertriglyceridemia is avoided. PN is indicated only in those patients who are unable to tolerate targeted requirements by the enteral route. As rates of EN tolerance increase then volumes of PN should be decreased. When PN is administered, particular attention should be given to avoid overfeeding. When PN is indicated, a parenteral glutamine supplementation should be considered. In chronic pancreatitis PN may, on rare occasions, be indicated in patients with gastric outlet obstruction secondary to duodenal stenosis or those with complex fistulation, and in occasional malnourished patients prior to surgery.
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Affiliation(s)
- L Gianotti
- Department of Surgery, Milano-Bicocca University, San Gerardo Hospital, Monza, Italy
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Symposium 4: Hot topics in parenteral nutrition Current evidence and ongoing trials on the use of glutamine in critically-ill patients and patients undergoing surgery. Proc Nutr Soc 2009; 68:261-8. [DOI: 10.1017/s0029665109001372] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
The amino acid glutamine has numerous important roles including particularly antioxidant defence, immune function, the inflammatory response, acid–base balance and N economy. The present systematic review of randomised controlled trials of nutrition support with glutamine up to August 2008 has found that parenteral glutamine in critical illness is associated with a non-significant reduction in mortality (risk ratio 0·71 (95% CI 0·49, 1·03)) and may reduce infections. However, poor study quality and the possibility of publication bias mean that these results should be interpreted with caution. There is no evidence to suggest that glutamine is harmful in terms of organ failure and parenteral glutamine may reduce the development of organ failure.
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Fuentes-Orozco C, Cervantes-Guevara G, Muciño-Hernández I, López-Ortega A, Ambriz-González G, Gutiérrez-de-la-Rosa JL, Gómez-Herrera E, Hermosillo-Sandoval JM, González-Ojeda A. L-alanyl-L-glutamine-supplemented parenteral nutrition decreases infectious morbidity rate in patients with severe acute pancreatitis. JPEN J Parenter Enteral Nutr 2008; 32:403-11. [PMID: 18596311 DOI: 10.1177/0148607108319797] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The effect of parenteral GLN on recovery from severe acute pancreatitis has not been thoroughly investigated. The aims of this study were to determine whether parenteral GLN improves nutrition status and immune function, and to determine its ability to reduce morbidity and mortality in patients with this condition. METHODS In a randomized clinical trial, 44 patients with severe acute pancreatitis were randomly assigned to receive either standard PN (n = 22) or l-alanyl-l-glutamine-supplemented PN (n = 22) after hospital admission. Nitrogen balance, counts of leukocytes, total lymphocytes, and CD4 and CD8 subpopulations, and serum levels of immunoglobulin A, total protein, albumin, C-reactive protein, and serum interleukin (IL)-6 and IL-10 were measured on days 0, 5, and 10. Hospital stay, infectious morbidity, and mortality were also evaluated. RESULTS Demographics, laboratory characteristics, and pancreatitis etiology and severity at entry to the study were similar between groups. The study group exhibited significant increases in serum IL-10 levels, total lymphocyte and lymphocyte subpopulation counts, and albumin serum levels. Nitrogen balance also improved to positive levels in the study group and remained negative in the control group. Infectious morbidity was more frequent in the control group than in the study group. The duration of hospital stay was similar between groups, as was mortality. CONCLUSION The results suggest that treatment of patients with GLN-supplemented PN may decrease infectious morbidity rate compared with those who treated with nonenriched PN.
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Affiliation(s)
- Clotilde Fuentes-Orozco
- Medical Research Unit in Clinical Epidemiology, Western Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico
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Navarro S, Amador J, Argüello L, Ayuso C, Boadas J, de Las Heras G, Farré A, Fernández-Cruz L, Ginés A, Guarner L, López Serrano A, Llach J, Lluis F, de Madaria E, Martínez J, Mato R, Molero X, Oms L, Pérez-Mateo M, Vaquero E. [Recommendations of the Spanish Biliopancreatic Club for the Treatment of Acute Pancreatitis. Consensus development conference]. GASTROENTEROLOGIA Y HEPATOLOGIA 2008; 31:366-87. [PMID: 18570814 DOI: 10.1157/13123605] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Salvador Navarro
- Servicio de Gastroenterología, Institut de Malalties Digestives i Metabóliques, Hospital Clínic, Barcelona, Spain.
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Estívariz CF, Griffith DP, Luo M, Szeszycki EE, Bazargan N, Dave N, Daignault NM, Bergman GF, McNally T, Battey CH, Furr CE, Hao L, Ramsay JG, Accardi CR, Cotsonis GA, Jones DP, Galloway JR, Ziegler TR. Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients. JPEN J Parenter Enteral Nutr 2008; 32:389-402. [PMID: 18596310 DOI: 10.1177/0148607108317880] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. METHODS This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. RESULTS Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). CONCLUSIONS Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.
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Affiliation(s)
- Concepción F Estívariz
- Emory University Hospital Nutrition and Metabolic Support Service, Department of Medicine, Atlanta, GA 30322, USA
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Efficacy of glutamine-supplemented parenteral nutrition on short-term survival following allo-SCT: a randomized study. Bone Marrow Transplant 2008; 41:1021-7. [DOI: 10.1038/bmt.2008.27] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Abstract
Nutrition support is especially important in patients who have pancreatitis, as these patients have high metabolic needs and are usually unable to ingest sufficient calories from an oral diet because of pain or intestinal dysfunction. Clinicians must assess severity of the disease carefully, as initiation and timing of nutrition support are crucial. Depending on the severity, early nutrition support may be unnecessary, while late support ultimately may lead to worse outcomes. Route of nutrition support also plays an important role in treatment. The clinician has many alternatives from which to choose, including enteral nutrition given nasogastrically or nasojejunally, or parenteral nutrition given through a central line. This article explores the role of nutrition support in the outcome of pancreatitis and provides guidelines to aid the clinician in caring for patients who have acute and chronic pancreatitis.
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Affiliation(s)
- Caitlin S Curtis
- Department of Pharmacy, University of Wisconsin-Madison Hospital and Clinics, 600 Highland Avenue, CSC-1530 F6/133, Madison, WI 53792, USA
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Xue P, Deng LH, Xia Q, Zhang ZD, Hu WM, Yang XN, Song B, Huang ZW. Impact of alanyl-glutamine dipeptide on severe acute pancreatitis in early stage. World J Gastroenterol 2008; 14:474-8. [PMID: 18200673 PMCID: PMC2679139 DOI: 10.3748/wjg.14.474] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the therapeutic effect of alanyl-glutamine dipeptide (AGD) in the treatment of severe acute pancreatitis (SAP) in early and advanced stage.
METHODS: Eighty patients with SAP were randomized and received 100 mL/d of 20% AGD intravenously for 10 d starting either on the day of (early treatment group) or 5 d after (late treatment group) admission. Groups had similar demographics, underlying diseases, Ranson score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Balthazar’s computed tomography (CT) score at the beginning of the study and underwent similar other medical and nutritional management.
RESULTS: The duration of acute respiratory distress syndrome (2.7 ± 3.3 d vs 12.7 ± 21.0 d, P < 0.01), renal failure (1.3 ± 0.5 d vs 5.3 ± 7.3 d, P < 0.01), acute hepatitis (3.2 ± 2.3 d vs 7.0 ± 7.1 d, P < 0.01), shock (1.7 ± 0.4 d vs 4.8 ± 3.1 d, P < 0.05), encephalopathy (2.3 ± 1.9 d vs 9.5 ± 11.0 d, P < 0.01) and enteroparalysis (2.2 ± 1.4 d vs 3.5 ± 2.2 d, P < 0.01) and hospital stay (28.8 ± 9.4 d vs 45.2 ± 27.1 d, P < 0.01) were shorter in the early treatment group than in the late treatment group. The 15-d APACHE II score was lower in the early treatment group than in the late treatment group (5.0 ± 2.4 vs 8.6 ± 3.6, P < 0.01). The infection rate (7.9% vs 26.3%, P < 0.05), operation rate (13.2% vs 34.2%, P < 0.05) and mortality (5.3% vs 21.1%, P < 0.05) in the early treatment group were lower than in the late treatment group.
CONCLUSION: Early treatment with AGD achieved a better clinical outcome in SAP patients.
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Petrov MS, Zagainov VE. Influence of enteral versus parenteral nutrition on blood glucose control in acute pancreatitis: a systematic review. Clin Nutr 2007; 26:514-23. [PMID: 17559987 DOI: 10.1016/j.clnu.2007.04.009] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2007] [Revised: 03/28/2007] [Accepted: 04/24/2007] [Indexed: 12/26/2022]
Abstract
BACKGROUND & AIMS There is increasing evidence that tight glucose control may reduce infectious complications and mortality in surgical critically ill patients. However, data regarding the influence of artificial nutrition on glycemic homeostasis are limited. Our aim was to review all randomized controlled trials on enteral versus parenteral nutrition in acute pancreatitis to determine whether the route of feeding can affect the glucose control in the setting of this disease. METHODS Relevant literature cited in three electronic databases (Cochrane Central Register of Controlled Trials, EMBASE and Medline) were systematically reviewed. A meta-analysis was carried out using a random-effects model. RESULTS Thirteen randomized controlled trials on enteral versus parenteral nutrition in acute pancreatitis were identified. Seven studies were excluded from analysis, leaving 6 trials in which a total of 264 non-diabetic patients with acute pancreatitis were treated. Intake of nutrients did not differ among enterally and parenterally fed patients in 5 of 6 randomized controlled trials. Enteral nutrition reduced the risk of hyperglycemia (relative risk 0.53; 95% confidence interval 0.29-0.98; p = 0.04) and insulin requirement (relative risk 0.41; 95% confidence interval 0.24-0.70; p = 0.001). CONCLUSIONS Enteral nutrition, when compared with parenteral nutrition, is associated with better blood glucose control in patients with acute pancreatitis.
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Affiliation(s)
- Maxim S Petrov
- Department of Surgery, Nizhny Novgorod State Medical Academy, PO Box 568, Nizhny Novgorod, 603000 Russia.
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Jo S, Choi SH, Heo JS, Kim EM, Min MS, Choi DW, Seo JM, Chung JC, Kim YI. Missing effect of glutamine supplementation on the surgical outcome after pancreaticoduodenectomy for periampullary tumors: a prospective, randomized, double-blind, controlled clinical trial. World J Surg 2007; 30:1974-82; discussion 1983-4. [PMID: 16927064 DOI: 10.1007/s00268-005-0678-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND The effect of glutamine (Gln) supplementation in patients undergoing a major operation has not been conclusively established. This study was designed to elucidate the effect of Gln supplementation on the surgical outcome after a pancreaticoduodenectomy (PD) for periampullary tumors. METHODS A prospective, randomized, double-blind, and controlled clinical trial was undertaken for patients who underwent a classical PD or a pylorus-preserving PD for periampullary tumors. The Gln and control groups received isonitrogenous amino acid, with a 0.2 g/kg per day Gln regimen administered to the Gln group. The surgical outcome was compared in light of length of postoperative hospital stay, nutritional and chemical profiles, and complication rate between the Gln and control groups. RESULTS Sixty of the consecutive 143 patients who were admitted to undergo operation for periampullary tumors were enrolled in our study; 32 were in the Gln group and 28 in the control group. The two groups were comparable prior to and during the operation. The median length of the postoperative hospital stay and the postoperative nutritional and chemical profiles were not different between two groups. The overall and PD-related complication rates of the Gln group (37.5% and 25.0%) and the control group (28.6% and 14.3%) were not statistically different. CONCLUSIONS No significant beneficial effect of Gln supplementation with a low-dose parenteral regimen was demonstrated on the surgical outcome after a PD for periampullary tumors. Therefore, we should be prudent in using Gln as a routine pharmacologic supplement to the standard nutrition in patients who undergo major operations.
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Affiliation(s)
- Sungho Jo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-170, South Korea
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Sahin H, Mercanligil SM, Inanç N, Ok E. Effects of glutamine-enriched total parenteral nutrition on acute pancreatitis. Eur J Clin Nutr 2007; 61:1429-34. [PMID: 17311061 DOI: 10.1038/sj.ejcn.1602664] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AIM This study was performed to determine the effects of glutamine enriched total parenteral nutrition (TPN) on the patients with acute pancreatitis (AP). METHOD Forty patients with AP, who had Ranson's score between 2 and 4 received either standard TPN (control group) or TPN with glutamine (treatment group). The patients in the treatment group received TPN containing 0.3 g/kg/days glutamine. At the end of the study, patients were evaluated for nutritional and inflammatory parameters, length of TPN and length of hospital stay. RESULTS The length of TPN applications were 10.5+/-3.6 days and 11.6+/-2.5 days, and the length of hospital stays were 14.2+/-4.4 and 16.4+/-3.9 days for the treatment and control groups (NS), and the complication rates in the treatment and control groups were 10 and 40%, respectively (P<0.05). The transferrin level increased by 11.7% in the group that received glutamine-enriched TPN (P<0.05), whereas the transferrin level decreased by 12.1% in the control group (NS). At the end of the study, slight but not significant changes were determined in both groups in fasting blood sugar, albumin, blood urea nitrogen (BUN), creatinine, total cholesterol concentrations, aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities, leukocytes, CD(4), CD(8), serum Zn, Ca and P levels compare to the baseline levels (NS). Significant decreases were determined in serum lipase, amylase activities and C-reactive protein (CRP) levels in both groups (P<0.05). CONCLUSIONS The results of this study have shown that glutamine supplementation to TPN have beneficial effects on the prevention of complications in patients with AP.
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Affiliation(s)
- H Sahin
- Department of Nutrition and Dietetics, Ataturk School of Health, University of Erciyes, Kayseri, Turkey.
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Abstract
Glutamine, the most abundant amino acid in the body, is thought to become conditionally essential in critical illness. Some of the important roles for glutamine are as a carrier for inter-organ N, a preferred fuel for enterocytes and cells of the immune system, a substrate for renal NH3 formation and a precursor for glutathione. Mechanisms by which glutamine could improve recovery include attenuating oxidant damage and inflammatory cytokine production, reducing gut bacterial translocation and improving N balance. The present systematic review has found trends to suggest that parenteral and enteral glutamine supplementation reduce mortality, the development of infection and organ failure in critical illness. Trials of parenteral nutrition containing glutamine with patients after elective surgery also suggest reduction of infection, but it is unlikely that glutamine-containing parenteral nutrition would be used for such patients. The evidence base is limited by the quality of the reported trials and the suggestion that there is publication bias, with trials suggesting reduced infection being more likely to be published.
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Affiliation(s)
- Alison Avenell
- Health Services Research Unit, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD.
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de Luis D, Aller R, Culebras J. Recomendaciones para el soporte nutricional artificial del paciente crítico. Med Clin (Barc) 2006; 127:232-6. [PMID: 16938246 DOI: 10.1157/13091411] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The development of artificial nutritional support has been increased in the last years. Access routes and composition of formulas have been improved. Critic patients is a group of great controversy in this topic area. Enteral nutrition is better than parenteral nutrition in patients with inflammatory bowel disease, acute pancreatitis, burn and septic with a A level of evidence. Enteral nutrition is better than parenteral nutrition in patients with short bowel disease, chronic hepatopathy, surgery ot digestive tract in patients with cancer disease, patients with HIV infection and patients with politraumatism. Parenteral nutrition is better than enteral nutrition in patients with haematopoyetic transplantation with a B level of evidence. Some nutrients have been shown a beneficial effect in artificial nutritional support such as (diets low in fat and high in complex carbohydrates) (level A), diets with inmunonutrients in patients with surgery of digestive tract cancer (level B), diet enhanced with w3 fatty acids in patients with acute respiratory distress syndrome (level C), and patients with HIV infection (level B), diets enriched with glutamin in patients with politraumatism and haematopoyetic transplantation (level B). Specific diets have not been shown beneficial effects in some pathologies (short bowel syndrome, acute pancreatitis, renal insufficiency treated with dialysis, and respiratory insufficiency). Diets with arginine are contraindicated in septic critically ill patients (level A). In conclusion, artificial nutritional support in critic patients is a controversy topic area with a high level of change in knowledgments with new improvements in access route, diets and designs of interventional trials.
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Affiliation(s)
- Daniel de Luis
- Instituto de Endocrinología y Nutrición Clínica, Facultad de Medicina de Valladolid, Valladolid, España
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McClave SA, Chang WK, Dhaliwal R, Heyland DK. Nutrition support in acute pancreatitis: a systematic review of the literature. JPEN J Parenter Enteral Nutr 2006; 30:143-56. [PMID: 16517959 DOI: 10.1177/0148607106030002143] [Citation(s) in RCA: 206] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Failure to use the gastrointestinal (GI) tract in patients with acute pancreatitis may exacerbate the stress response and disease severity, leading to greater incidence of complications and prolonged hospitalization. The objectives of this study were to determine the optimum route for nutrition support, whether nutrition therapy is better than no artificial nutrition support, whether specific additives to enteral or parenteral therapy can further enhance their efficacy, and whether methodologic differences in delivery of enteral nutrition (EN) influence tolerance. METHODS A computerized search was performed of MEDLINE, Cochrane database, EMBASE, and reference lists of pertinent review articles for prospective randomized trials in adult patients with acute pancreatitis that evaluated interventions with nutrition therapy. Primary outcome data and surrogate endpoint parameters (for nutrition indices, stress markers, and measures of the inflammatory/immune response) were extracted in duplicate independently. Where appropriate, meta-analysis was performed by random-effects model. RESULTS From 119 articles screened, 27 randomized controlled trials were included and analyzed. In patients admitted for acute pancreatitis, meta-analysis of 7 trials showed that use of EN was associated with a significant reduction in infectious morbidity (risk ratio [RR] = 0.46; 95% confidence interval [CI], 0.29 - 0.74; p = .001) and hospital length of stay (LOS; weighted mean difference [WMD] = -3.94; 95% CI, -5.86 to -2.02; p < .0001), a trend toward reduced organ failure (RR = 0.59; 95% CI, 0.28-1.27; p = .18), with no effect on mortality (RR = 0.88; 95% CI, 0.43-1.79; p = .72) when compared with use of parenteral nutrition (PN). Results from individual studies suggest that EN in comparison to PN reduces oxidative stress, hastens resolution of the disease process, and costs less. Insufficient data exist to determine whether EN improves outcome over standard therapy (no artificial nutrition support) in patients admitted for acute pancreatitis. However, in those patients requiring surgery for complications of acute pancreatitis, meta-analysis of 2 trials indicates that provision of EN postoperatively may reduce mortality (RR = 0.26; 95% CI, 0.06 - 1.09; p = .06) compared with standard therapy. PN provided early within 24 hours of admission was shown to worsen outcome, whereas PN provided later after full-volume resuscitation appeared to improve outcome when compared with standard therapy. In early individual studies, specific supplements added to EN, such as arginine, glutamine, omega-3 polyunsaturated fatty acids, and probiotics, may be associated with a positive impact on patient outcome in acute pancreatitis, compared with EN alone without the supplements, but studies are too few to make strong treatment recommendations. Supplementation of PN with parenteral glutamine was shown to reduce oxidative stress and improve patient outcome (reduced duration of nutrition therapy and decreased hospital LOS) compared with PN alone in patients with acute pancreatis. A wide range of tolerance to EN exists, irrespective of known influences such as mode (continuous vs bolus) and level of infusion within the GI tract (gastric vs postpyloric). CONCLUSIONS Patients with acute severe pancreatitis should begin EN early because such therapy modulates the stress response, promotes more rapid resolution of the disease process, and results in better outcome. In this sense, EN is the preferred route and has eclipsed PN as the new "gold standard" of nutrition therapy. When PN is used, it should be initiated after 5 days. The favorable effect of both EN and PN on patient outcome may be further enhanced by supplementation with modulators of inflammation and systemic immunity. Individual variability allows for a wide range of tolerance to EN, even in severe pancreatitis.
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Affiliation(s)
- Stephen A McClave
- Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
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Déchelotte P, Hasselmann M, Cynober L, Allaouchiche B, Coëffier M, Hecketsweiler B, Merle V, Mazerolles M, Samba D, Guillou YM, Petit J, Mansoor O, Colas G, Cohendy R, Barnoud D, Czernichow P, Bleichner G. L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med 2006; 34:598-604. [PMID: 16505644 DOI: 10.1097/01.ccm.0000201004.30750.d1] [Citation(s) in RCA: 195] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Glutamine (Gln)-supplemented total parenteral nutrition (TPN) improves clinical outcome after planned surgery, but the benefits of Gln-TPN for critically ill (intensive care unit; ICU) patients are still debated. DESIGN Prospective, double-blind, controlled, randomized trial. SETTING ICUs in 16 hospitals in France. PATIENTS One-hundred fourteen ICU patients admitted for multiple trauma (38), complicated surgery (65), or pancreatitis (11). INTERVENTIONS Patients were randomized to receive isocaloric isonitrogenous TPN via a central venous catheter providing 37.5 kcal and 1.5 g amino acids.kg-1.day-1 supplemented with either L-alanyl-L-glutamine dipeptide (0.5 g.kg-1.day-1; Ala-Gln group, n=58) or L-alanine+L-proline (control group, n=56) over at least 5 days. MEASUREMENTS AND MAIN RESULTS Complicated clinical outcome was defined a priori by the occurrence of infectious complications (according to the criteria of the Centers for Disease Control and Prevention), wound complication, or death. The two groups were compared by chi-square test on an intention-to-treat basis. The two groups did not differ at inclusion for type and severity of injury (mean simplified acute physiology score II, 30 vs. 30.5; mean injury severity score, 44.9 vs. 42.3). Similar volumes of TPN were administered in both groups. Ala-Gln-supplemented TPN was associated with a lower incidence of complicated outcome (41% vs. 61%; p<.05), which was mainly due to a reduced infection rate per patient (mean, 0.45 vs. 0.71; p<.05) and incidence of pneumonia (10 vs. 19; p<.05). Early death rate during treatment and 6-month survival were not different. Hyperglycemia was less frequent (20 vs. 30 patients; p<.05) and there were fewer insulin-requiring patients (14 vs. 22; p<.05) in the Ala-Gln group. CONCLUSIONS TPN supplemented with Ala-Gln dipeptide in ICU patients is associated with a reduced rate of infectious complications and better metabolic tolerance.
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