A Fat-Modified Enteral Formula Improves Feeding ...

601858

research-article2015

PENXXX10.1177/0148607115601858Journal of Parenteral and Enteral NutritionQiu et al

Original Communication

A Fat-Modified Enteral Formula Improves Feeding Tolerance in Critically Ill Patients: A Multicenter, Single-Blind, Randomized Controlled Trial

Journal of Parenteral and Enteral Nutrition Volume XX Number X Month 201X 1–11 © 2015 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607115601858 jpen.sagepub.com hosted at online.sagepub.com

Chunfang Qiu, MSc1,*; Chuanxi Chen, MSc1,*; Weixing Zhang, MD, PhD2; Qiuye Kou, MD, PhD3; Shengnan Wu, MSc4; Lixin Zhou, MSc5; Jiyun Liu, BD6; Gang Ma, MSc7; Juan Chen, BD1; Minying Chen, MD, PhD1; Hua Luo, MSc2; Xiaofei Zhang, MSc3; Jianbo Lai, MSc4; Zhihui Yu, MSc5; Xiaochun Yu, BD6; Wei Liao, MSc7; Xiangdong Guan, MD, PhD1; and Bin Ouyang, MD, PhD1

Abstract Background: Improvement of fat digestion and absorption was supposed to relieve feeding intolerance. This trial aimed to evaluate the effect of a fat-modified enteral formula on feeding tolerance in critically ill patients. Materials and Methods: This trial was conducted in 7 hospitals in China. In total, 144 intensive care unit (ICU) patients with estimated need of enteral nutrition (EN) for at least 5 days were randomly given fat-modified enteral formula containing medium-chain triglycerides (MCT), carnitine, and taurine (interventional feed group, n = 71) or standard enteral formula (control feed group, n = 73). EN intake, feeding intolerance (diarrhea, vomiting, gastric retention, and abdominal distension) and outcomes (mechanical ventilator-free days of 28 days, length of ICU stay, length of hospital stay, and inhospital mortality) were collected. Results: Daily calories and protein intake were increased in the interventional feed group compared with the control feed group (P < .01). Total incidence of feeding intolerance was 42.3% in the interventional feed group and 65.7% in the control feed group (P < .001). Daily incidence of feeding intolerance was 11.3%, 18.3%, 14.1%, 25.4%, and 26.1% in the interventional feed group and 31.5%, 32.9%, 34.2%, 34.2%, and 30.4% in the control feed group from study days 1–5 (P = .0083). Incidence of feeding intolerance without abdominal distention was 32.9% in the interventional feed group and 49.3% in the control feed group (P = .047), while the incidence of abdominal distension was 26.8% in the interventional feed group and 43.8% in the control feed group (P = .03). No significant differences existed in outcomes between the 2 groups. Conclusions: The fat-modified enteral formula containing MCT, carnitine, and taurine may improve feeding tolerance in critically ill patients. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx)

Keywords feeding intolerance; enteral nutrition; critically ill patients; fat-modified enteral formula

Clinical Relevancy Statement Malnutrition is a widespread and serious problem for critically ill patients. Enteral nutrition (EN) is the preferred route for treatment because it alleviates malnutrition while keeping the integrity of the gastrointestinal (GI) barrier. The biggest challenge with maintaining EN in critically ill patients is feeding intolerance. In this study, we investigated the effect of a fatmodified enteral formula on GI tolerance in critically ill patients by comparing it with a standard enteral formula to find the most suitable enteral formula for critically ill patients.

Introduction The incidence of malnutrition in critically ill patients prior to this report’s findings was up to 43%–50%, which resulted in a higher risk of severe complications and mortality.1–3 Enteral nutrition (EN) is the preferred route in critically ill patients. However, feeding intolerance still exists in 30.5%–75% of

patients and is considered the main cause of resistance of EN in critically ill patients.4–7 Feeding intolerance manifests itself as gastrointestinal (GI) symptoms, which include abdominal distension, diarrhea, vomiting, gastric retention, and inadequate enteral calories intake.6 Feeding intolerance not only exacerbates malnutrition but also leads to worse clinical outcomes, including fewer ventilator-free days, longer length of intensive care unit (ICU) stay, and higher mortality.7 Hence, improving GI tolerance during EN is an important issue when treating critically ill patients. Several international nutrition societies recommend paying special attention to the subject of feeding intolerance. European Society for Clinical Nutrition and Metabolism (ESPEN), American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), and the Canadian critical care nutrition guidelines recommend several measures to deal with feeding intolerance, such as treating the primary diseases, optimizing the EN regimen, elevating the head of bed, and administering GI dynamic medicine, all of which improved feeding tolerance to

Downloaded from pen.sagepub.com at JOHNS HOPKINS UNIVERSITY on June 16, 2016

2

Journal of Parenteral and Enteral Nutrition XX(X)

a large extent.8–11 However, the incidence of feeding intolerance is still high at 30.5%–75% despite all of the countermeasures mentioned above.5–7 The application of a proper EN formula may have an impact on feeding intolerance in critically ill patients. However, previous studies have showed controversial results in critically ill patientspecific formula. The effect of protein predigested enteral formula on feeding intolerance and its nutrition outcome were investigated but failed to show a significant difference in comparison with standard enteral formula in critically ill patients.12–14 Studies conducted by Mowatt-Larssen et al13 and Heimburger et al14 even showed that protein predigested enteral formula had a negative effect on diarrhea and nitrogen balance. Heyland and colleagues proposed a PEP uP protocol, which contained several steps, including (1) starting feeds at a higher initial target rate, (2) using “trophic feeds” for patients who were deemed unsuitable for high-volume intragastric feeds, (3) using a semi-elemental feeding solution as initiation of feeding and transferring to a standard polymeric diet if the patient had no problems with tolerance, (4) prescribing protein supplements at initiation of EN, (5) giving motility agents as routine, and (6) raising the gastric residual volume threshold from 250–300 mL. With the PEP uP protocol described in Heyland et al, the energy and protein intake delivered by EN was greater than in the control group. However, it was a mixed effect with all 6 measures in the PEP uP protocol. No causal relationship between the semi-elemental feeding and feeding tolerance could be drawn in their study.15 On the other hand, fat maldigestion and malabsorption turned out to be more remarkable in critically ill patients in recent studies. Ali Abdelhamid and colleagues16 infused a liquid nutrient containing 13C-triolein and 3-O-methylglucose (3-OMG) directly into the duodenum of critically ill patients and healthy volunteers, and then they measured the exhaled 13CO2 and serum 3-OMG concentrations and found that the lipid absorption in the small intestine was markedly reduced in critically ill patients compared with healthy volunteers. Taurine and carnitine, which are essential nutrients for fat digestion and absorption, were at lower levels in critically ill patients than in healthy subjects.17,18

In addition, the gastric emptying of fat was the slowest in comparison with carbohydrates and protein. A study conducted by Homko et al19 compared the effects of a high-fat diet and a lowfat diet on the overall symptoms among patients with gastroparesis. It demonstrated that a high-fat diet significantly increased the overall symptoms, whereas a low-fat diet decreased the overall symptoms among patients with gastroparesis. No previous study has investigated the effect of the fatmodified enteral formula on feeding intolerance in critically ill patients. In this study, a fat-modified enteral formula that contained medium-chain triglycerides (MCTs), L-carnitine, and taurine was used to improve the fat digestion and absorption in critically ill patients. The effect of this fat-modified formula on feeding intolerance in critically ill patients was determined by comparing these results with a standard EN formula in a multicenter, single-blind, randomized controlled trial.

Materials and Methods Patients Patients admitted to ICUs were assessed for eligibility on the admission day. Inclusion criteria included the following: (a) 18–85 years old, (b) Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥12, and (c) an estimated clinical need for EN for ≥5 days. The exclusion criteria included unstable hemodynamic status, allergy to any ingredients of the EN formula, and contraindications of EN, which included active GI bleeding, paralytic ileus, early stage of abdominal compartment syndrome (ACS), acute exacerbation of inflammatory bowel disease, and severe acute pancreatitis. Patients who were participating or had participated in other clinical trials within 2 months were also excluded.

Study Design A prospective, single-blind, multicenter randomized clinical trial was conducted in 7 ICUs across 7 tertiary hospitals in

From the 1Department of Surgical Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China; 2Department of Intensive Care Unit, Peking University Shenzhen Hospital, Shenzhen, P.R. China; 3Department of Intensive Care Unit, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China; 4Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, P.R. China; 5 Department of Intensive Care Unit, The First People's Hospital of Foshan, Foshan, P.R. China; 6Department of Intensive Care Unit, The First People's Hospital of Guangzhou, Guangzhou, P.R. China; and 7Department of Intensive Care Unit, University Cancer Center, Guangzhou, P.R. China. *These authors contributed to the work equally and should be regarded as co–first authors. Financial disclosure: This study was funded by the Abbott Company. The funding body, Abbott, provided funding to the institution of The First Affiliated Hospital of Sun Yat-sen University for research management, ELISA kits purchase, statistical fee, and allowances for the participants. Abbott was not involved in project design, data collection, data analysis, and manuscript writing in this study. Neither the sites nor the investigators received any reimbursement. Conflicts of interest: All authors declared that they have no competing interests. It was an investigator-initiated and driven study. As both two formulas were from the same company, there was no interest conflict from the company side. Received for publication February 15, 2015; accepted for publication July 8, 2015. Corresponding Author: Bin Ouyang, MD, PhD, Department of Surgical Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan Rd 2, Guangzhou, Guangdong Province 510080, P.R. China. Email: [email protected]


Qiu et al

3

Table 1. Ingredients of the 2 Enteral Formulas. Ingredients Energy density, kcal/mL Protein, % of calories Carbohydrates, % of calories Lactose Fat, % of calories Taurine, mg/mL L-carnitine, mg/mL Dietary fiber, g/mL

Interventional Feed Group (TPF-FOS)

Control Feed Group (TPF-TP)

1.05 15.0 56 None 29.0 (LCT 80%, MCT 20%) 10/100 8.4/100 1.06/100; dietary fiber patent (gum arabic, oat fiber, silkool, carboxymethyl cellulose, and Nutraflora-FOS)

1.00 14.2 54 None 31.8 (LCT 100%) None None None

FOS, fructooligosaccharide; LCT, long-chain triglyceride; MCT, medium-chain triglyceride; TP, total protein; TPF, total protein formula.

Table 2. Protocol of the Adjustment of Feed Speed.a Study Day

Initial Feed Speed, mL/h

Adjustment of the Feed Speed

0

10–20

1 2–5

20–40 30–100

Monitoring the GRV every 6 hours, if: GRV .05. Values are presented as mean ± SD unless otherwise indicated.

Incidence of Feeding Intolerance The total incidence of feeding intolerance during the study feeding period in the interventional feed group was significantly lower than in the control feed group (42.3% in the interventional feed group and 65.7% in the control feed group, P = .005) (Figure 3A). Diarrhea occurred in 29.6% (21/71) of patients in the interventional feed group and 38.4% (7/73) of patients in the control feed group. Gastric retention occurred in 4.2% (3/71) of patients in the interventional feed group and 9.6% (7/73) of patients in the control feed group. Vomiting occurred in 2.8% (2/71) of patients in the interventional feed group and 8.2% (6/73) of patients in the control feed group. Abdominal distension occurred in 26.8% (19/71) of patients in the interventional feed group and 43.8% (32/73) of patients in the control feed group. The total incidence of feeding intolerance without abdominal distension (including diarrhea, gastric retention, and vomiting) was significantly lower in the interventional feed group than in the control feed group (32.9% in the

interventional feed group and 49.3% in the control feed group, P = .047). The total incidence of abdominal distension was significantly lower in the interventional feed group than in the control feed group (26.8% vs 43.8%, P = .030) (Figure 3A). Daily incidence of feeding intolerance from D1–D5 was 11.3%, 18.3%, 14.1%, 25.4%, and 26.1% in the interventional feed group and 31.5%, 32.9%, 34.2%, 34.2%, and 30.4% in the control feed group, which was significantly lower in the interventional feed group than in the control feed group (P = .008) (Figure 3B). The daily incidence of feeding intolerance without abdominal distension from D1–D5 was 7.1%, 12.9%, 11.4%, 18.6%, and 14.3% in the interventional feed group and 26.8%, 18.3%, 19.7%, 15.5%, and 15.5% in the control feed group (Figure 3C), which was lower in interventional group but with no significant difference between the 2 groups (P = .078). The daily incidence of abdominal distension from D1– D5 was 5.6%, 8.5%, 8.5%, 12.6%, and 12.9% in the interventional feed group and 13.7%, 20.5%, 20.5%, 28.8%, and 21.1% in the control feed group (Figure 3D), which was significantly


Qiu et al

7

Figure 2. Daily enteral nutrition intake and adequacy. Interventional feed group (n = 71); control feed group (n = 73). D1–D5 refers to study days 1–5. Daily percentages of calories and protein adequacy were based on the energy target of 25 kcal/kg/d and protein target of 1.0 g/kg/d. **P < .01. ***P < .001.

lower in the interventional feed group than in the control feed group (P = .006). There were 78 medical patients and 66 surgical patients among the 144 patients in this study. The total incidence of feeding intolerance was 53.8% in medical patients and 45.4% in surgical patients, with no significant difference between the 2 groups (P > .05).

Outcomes of the Patients The mechanical ventilator–free days of 28 days showed no significant difference between the 2 groups (16.3 ± 8.3 days in the interventional feed group and 16.0 ± 7.8 days in the control feed group, P = .82). The length of ICU stay also showed no significant difference between the 2 groups (16.3 ± 8.5 days in the interventional feed group and 15.3 ± 8.6 days in the control feed group, P = .85). The length of hospital stay showed no significant difference between the 2 groups (35.8 ± 16.2 days in the interventional feed group and 32.1 ± 15.3 days in the control feed group, P = .42). The in-hospital mortality was 24.0% in the interventional feed group and 27.4% in the

control feed group, and no significant difference was found between the 2 groups (P = .70) (Table 4).

Nutrition-Related Parameters The concentration of blood glucose, lipid (triglyceride and total cholesterol), serum albumin, prealbumin, transferrin, and CRP showed no significant difference between the 2 groups (P > .05). The liver and renal tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood creatinine, and urea nitrogen levels, showed no significant difference between the 2 groups (P > .05) (Table 5).

Concentrations of D-Lactate and I-FABP The baseline concentration of D-lactate was 15.9 ± 14.3 nmol/L in the interventional feed group and 13.0 ± 10.1 nmol/L in the control feed group (normal range, 11.0–70.0 mmol/L22) with no significant difference between the 2 groups. The concentration of D-lactate on study day 5 was 12.0 ± 10.7 nmol/L in the interventional feed group and 11.1 ± 10.1 nmol/L in the control


8

Journal of Parenteral and Enteral Nutrition XX(X)

Figure 3. Incidence of feeding intolerance. Interventional feed group (n = 71); control feed group (n = 73). D1–D5 refers to study days 1–5. *P < .05. **P < .01. ***P < .001.

Table 4. Outcome of the Patients. Outcome Mechanical ventilator–free days of 28 days, d, mean ± SD Length of ICU stay, d, mean ± SD Length of hospital stay, d, mean ± SD In-hospital mortality, %

Interventional Feed Group (n = 71)

Control Feed Group (n = 73)

P Value

16.3 ± 8.3

16.0 ± 7.8

.82

16.5 ± 8.5 35.8 ± 16.2 24.3

15.3 ± 8.6 32.1 ± 15.3 28.2

.85 .42 .70

ICU, intensive care unit.

feed group, with no significant difference between the 2 groups. However, the concentration of D-lactate showed a significant reduction through a 5-day enteral feeding in both groups (P = .003) (Table 6). The concentration of I-FABP at baseline was 686.4 ± 541.1 pg/mL in the interventional feed group and 673.6 ± 514.5 pg/ mL in the control feed group (normal range,