Pancreatic Exocrine Insufficiency and Pancreatic Enzyme Supplementation in Critically Ill Adult Patients

Study Overview
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Brief Summary
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Malnutrition is a frequent problem in critically ill patients that is associated with detrimental clinical outcomes. To provide adequate nutritional support, current studies focused mostly on the choice of delivery timing, formula selection and the route of administration, little attention was paid to malnutrition related to exocrine pancreatic insufficiency (EPI). In fact, malnutrition is also a major consequence of pancreatic exocrine insufficiency and pancreatic damage is commonly observed in critically ill patients without prior pancreatic diseases. Hence, EPI associated malnutrition should be concerned due to the high prevalence of pancreatic damage in critically ill patients. The aims of this study is to evaluate the incidence of EPI in critically ill adult patients and explore its potential risk factors. Moreover, the efficacy of pancreatic enzyme supplementation therapy on malnutrition in ICU patients with specific clinical characteristics will be investigated.

Detailed Description
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Critically ill patients who is able to receive early enteral nutrition and estimated to stay in ICU at least four days are considered to enroll into this study. Exclusion criteria are age under 18 or over 80 years, pregnancy or breastfeeding, known exocrine pancreatic insufficiency due to pancreatitis, unresectable pancreatic cancer, cystic fibrosis, celiac disease, Zollinger-Ellison syndrome, pancreatectomy, gastrectomy and medications of somatostatin or aprotinin that directly influence pancreatic exocrine function. Informed consent documents are signed by immediate family members of the recruited patients. All study procedures are performed in accordance with the institutional guidelines for the conduct of research on human beings and approved by the Human Ethics Committee of Shanghai Tenth People's Hospital. Once the enrolled patients are admitted to the ICU, they are inserted either a nasogastric tube or a nasojejunal tube guided by electronic gastroscope according to the expected feeding time, and the position of feeding tubes is confirmed by plain abdominal radiograph. Enteral nutrition will be initiated at a rate of 25 ml/h within 24h of admission, and the infusion rate increases steadily until the prescribed nutritional requirements are achieved within 3 days. Daily nutritional requirements are calculated mainly based on the patient's body mass index. During the study, the details of each patient such as age, sex, BMI, admission diagnosis, and Acute Physiology and Chronic Health Evaluation II score are collected. All clinical characteristics that may cause pancreatic damage, including shock (systolic blood pressure < 90 mmHg), tissue hypoxia (serum lactate > 2 mmol/L), respiratory failure (PaO2 < 60 mmHg), anemia (hemoglobin < 90 g/L), obesity (BMI > 30 kg/m2), biliary sludge (total bilirubin > 17.5 μmol/L), hypertriglyceridemia (> 1.7 mmol/L), sepsis, cardiac arrest, cardiopulmonary bypass (CPB), severe head injury, acute stroke, post-neurosurgery, diabetes, inflammatory bowel disease (IBS), mechanical ventilation and continuous renal replacement therapy (CRRT) are recorded prospectively. Medications such as propofol, valproate, metronidazole and morphine-derived drugs, which are applied for more than 24 h and might induce pancreatic damage, are also documented. Arterial blood samples are taken 3 days after admission to determine biochemical parameters. Stool samples are collected 3-5 days after the beginning of enteral nutrition and frozen at -20℃ until analysis. Some patients will undergo CT scanning and magnetic resonance cholangio-pancreatography (MRCP)to acquire histological evidence of exocrine pancreatic insufficiency.

Official Title
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The Incidence of Pancreatic Exocrine Insufficiency and the Benefits of Pancreatic Enzyme Supplementation in Critically Ill Adult Patients

Conditions
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Critical Illness, Sepsis, Diabetes, Cardiac Arrest, Acute Renal Failure, Shock

Intervention / Treatment
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* Dietary Supplement: Enteral nutrition (EN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All critically ill patients who are able to receive early enteral nutrition and estimated to stay in ICU at least four days Exclusion Criteria: age under 18 or over 80 years, pregnancy or breastfeeding, known exocrine pancreatic insufficiency due to pancreatitis, unresectable pancreatic cancer, cystic fibrosis, celiac disease, Zollinger-Ellison syndrome, pancreatectomy, gastrectomy and medications of somatostatin or aprotinin that directly influence pancreatic exocrine function

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sepsis-PEST<br>septic patients with enteral nutrition and pancreatic enzyme supplementation therapy | Dietary Supplement: Enteral nutrition (EN)<br>* All patients enrolled in this study must carry out nutritional support by enteral nutrition<br>|
| Sepsis-NPEST<br>Septic patients with enteral nutrition only | Dietary Supplement: Enteral nutrition (EN)<br>* All patients enrolled in this study must carry out nutritional support by enteral nutrition<br>|
| DM-PEST<br>Diabetic patients with enteral nutrition and pancreatic enzyme supplementation therapy | Dietary Supplement: Enteral nutrition (EN)<br>* All patients enrolled in this study must carry out nutritional support by enteral nutrition<br>|
| DM-NPEST<br>Diabetic patients with enteral nutrition only | Dietary Supplement: Enteral nutrition (EN)<br>* All patients enrolled in this study must carry out nutritional support by enteral nutrition<br>|
| PCAS-PEST<br>Patients suffering from cardiac arrest receive both enteral nutrition and pancreatic enzyme supplementation therapy | Dietary Supplement: Enteral nutrition (EN)<br>* All patients enrolled in this study must carry out nutritional support by enteral nutrition<br>|
| PCAS-NPEST<br>Patients suffering from cardiac arrest receive enteral nutrition only | Dietary Supplement: Enteral nutrition (EN)<br>* All patients enrolled in this study must carry out nutritional support by enteral nutrition<br>|
| ARF-PEST<br>Patients with acute renal failure receive both enteral nutrition and pancreatic enzyme supplementation therapy | Dietary Supplement: Enteral nutrition (EN)<br>* All patients enrolled in this study must carry out nutritional support by enteral nutrition<br>|
| ARF-NPEST<br>Patients with acute renal failure receive enteral nutrition only | Dietary Supplement: Enteral nutrition (EN)<br>* All patients enrolled in this study must carry out nutritional support by enteral nutrition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Screening and risk factors of exocrine pancreatic insufficiency in critically ill adult patients receiving enteral nutrition | The incidence of exocrine pancreatic insufficiency will be evaluated that is based on hyperamylasemia, hyperlipasemia and fecal elastase-1 concentrations. multivariate logistic regression analyses are used to estimate the correlations between exocrine pancreatic insufficiency and clinical events and characteristics, which include APACHE II score, shock, hyperlactacidemia, respiratory failure, anemia, obesity, biliary sludge, hypertriglyceridemia, sepsis, cardiac arrest, cardiopulmonary bypass, severe head injury, acute stroke, post-neurosurgery, diabetes, inflammatory bowel disease, mechanical ventilation, continuous renal replacement therapy and medications such as propofol, valproate, metronidazole and morphine-derived drugs | From 2012-1 to 2012-12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of pancreatic enzyme supplementation on nutritional status and clinical outcomes in critically ill patients with sepsis | The incidence of exocrine pancreatic insufficiency and the nutritional status are evaluated by fecal elastase-1 concentrations before pancreatic enzyme supplementation therapy is applied. Patients are assigned into two groups randomly, the control group is only receiving enteral nutrition without the addition of pancreatic enzyme(CREON), and the PEST group is given both enteral nutrition and pancreatic enzyme supplementation therapy at the same time. Following two weeks of corresponding treatments, the nutritional status and clinical outcomes are documented in both groups for statistical analysis. | From 2013-1 to 2014-12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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enteral nutrition, sepsis, diabetes, hyperlactacidemia, hemodialysis, exocrine pancreatic insufficiency, fecal elastase-1, amylase, lipase, critical illness, malnutrition, mechanical ventilation