EAL

CI: Enteral Nutrition and Fiber (2011)

Citation:

Spapen H, Diltoer M, Van Malderen C, Opdenacker G, Suys E, Huyghens L. Soluble fiber reduces the incidence of DIARRHEA in septic patients receiving total enteral nutrition: a prospective, double-blind, randomized, and controlled trial. Clin Nutr. 2001 Aug; 20 (4): 301-305. PMID: 11478826.

PubMed ID: 11478826

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To determine the effect of early administraton of EN containing soluble fiber on occurrence of diarrhea in patients with severe sepsis and septic shock.

Inclusion Criteria:

Patient in the medical ICU
Consent by next of kin
Diagnosis of severe sepsis (sepsis associated with organ dysfunction, hypoperfusion or hypotension) or septic shock (systolic blood pressure under 90mmHg or decreased by more than 40mmHg from baseline) within four hours of clinical onset.

Exclusion Criteria:

Medical condition to be lethal or inability to stabilize patient within 24 hours after admission
Impossibility to use GI tract due to hemorrhage, obstruction, severe ileus
Pancreatitis
Known diarrheal illness (ulcerative colitis, Crohn's disease, ischemic or infectious colitis)
Diarrhea occurring within 72 hours before inclusion
Treatment modifying GI transit
Albuminemia under 2.0g per dL
Diabetes mellitus
Immunosuppressed state (steroid treatment, bone marrow or organ transplant recipient, leuko-or neutropenia, hematological malignancy, AIDS).

Description of Study Protocol:

Recruitment

Met inclusion criteria; all patients had indwelling radial and balloon-tipped pulmonary artery catheters and were mechanically ventilated in pressure-controlled modes, under continuous analgesic sedation
All patients received intravenous fluid, broad-spectrum antibiotics and goal-titrated catecholamines.

Design

RCT: Randomization scheme not described.

Blinding Used

EN formulas prepared in central pharmacy and delivered to ICU in identical brown 500-ml sterile glass containers and handled by nurse who was unaware of the study protocol.

Intervention

Isocaloric, isonitrogenous EN (lactose free, provided 1,000kcal per L, consisting of 54% carbohydrates, 17% proteins and 30% fat); osmolality 230mOsmol per L
Treatment group had 22g partially hydrolyzed guar per L added to EN.

Statistical Analysis

Mann-Whitney U-test for comparison of unpaired continuous data
All results expressed as means ±standard deviation
Significance level set at P<0.05.

Data Collection Summary:

Timing of Measurements

Assessment for diarrhea started when at least 750ml of enternal feed could be given
Three stool cultures and assay for Clostridium difficile toxin performed in all patients with diarrhea and on every fifth feeding day in patients without diarrhea
To be evaluable for data analysis, patients had to receive enteral feeding for at least six days
Study continued for maximum of 21 days or until withdrawal of EN.

Dependent Variables

Diarrhea score (Hart and Dobb method).

Independent Variables

EN was supplemented with 22g partially hydrolyzed guar per L (Benefiber).

Control Variables

EN formula isocaloric, isonitrogenous.

Description of Actual Data Sample:

Initial N

35 (13 males, 12 females).

Attrition (Final N)

Six fiber-treated and four control patients excluded from data analysis because of inadequate duration of EN
Reasons included death within five days (N=4), intractable vomiting (N=2), gastric stasis with regurgitation (N=3) and urgent abdominal surgery (N=1).

Age

NS difference in groups for age

Soluble Fiber Group: 68±11 years
Control Group: 69±15 years.

Ethnicity

Not described.

Other Relevant Demographics

NS difference in groups for APACHE II score

Soluble Fiber Group: 26±7 years
Control Group: 24±8 years.

Location

Brussels, Belgium.

Summary of Results:

Key Findings

Variables	Treatment Group (Soluble fiber)	Control Group	Statistical Significance of Group Difference
Percentage of Days with Diarrhea per Feeding Days	8.8±10.0	32.0±15.3	P=0.001
Number of Feeding Days	148	146	NS
Number (percentage) of Days with Diarrhea	16 (10.8)	46 (31.5)	P<0.001
Diarrhea Score	4.8±6.4	9.4±10.2	P<0.001

Other Findings

Author Conclusion:

EN-supplemented with soluble fiber is beneficial in reducing incidence of diarrhea in tube-fed, full-resuscitated and mechanically ventilated septic patients.

Funding Source:

Industry:

Novartis

University/Hospital:

Academic Hospital, Vrije Universiteit Brussels, Belgium

In-Kind support reported by Industry:

Yes

Reviewer Comments:

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes