Brain Death
Conditions
Brief summary
The investigators propose to assess 36 donors' nutritional status using accepted parameters (prealbumin, resting energy expenditure); to assess nutrient intestinal absorption through 13Curacil breath tests; and to evaluate serum concentrations of IL-6 and TNFalpha to determine if continuing or initiating enteral feeding and nutritional supplementation is effective in restoring or maintaining nutritional parameters.
Detailed description
There are an estimated 98,000 people in need of organ transplants in the United States (OPTN). Only a fraction of the need is met with the organs that become available. Therefore interventions are needed to maximize the viability of available organs and improve donor organ procurement and successful transplantation. Improving the nutritional status of potential donors after they are declared brain dead could favorably impact subsequent organ procurement. Improved nutrition may improve organ viability by reducing the negative effects of inflammatory cytokines and catecholamines, and through reducing translocation of bacteria or endotoxin from the intestine. In our preliminary work the investigators show significantly elevated inflammatory cytokines (IL-6 and TNFalpha) in unfed donors and a correlation with improved graft survival in recipients with lower plasma concentrations of IL-6. The investigators propose to assess 36 donors' nutritional status using accepted parameters (prealbumin, resting energy expenditure); to assess nutrient intestinal absorption through 13Curacil breath tests; and to evaluate serum concentrations of IL-6 and TNFalpha to determine if continuing or initiating enteral feeding and nutritional supplementation is effective in restoring or maintaining nutritional parameters. Additionally, half of the group will be randomized to receive a nutritional supplement via naso/oro-duodenal feeding tube with a commercially available formula containing omega-3 and omega-6 fatty acids, and antioxidants plus glutamine (Oxepa® plus Glutasolve). The intervention through its anti-inflammatory and antioxidant functions has the potential to improve organ function (e.g. improved myocardial function (Wischmeyer 2003), and improved oxygenation (Pacht 2003; Pontes-Arruda 2006; Singer 2006)). Through improved organ function and/or a suppression of inflammatory cytokine production (e.g., IL-6 and TNFalpha) more organs are expected to be appropriate for procurement/transplantation. If enteral nutrition reduces the inflammatory response commonly documented after brain death and, in doing so, improves organ procurement, enteral feeding could be immediately employed toward improving donor care practices. Furthermore, reducing the level of inflammatory molecules in donor organs may reduce the risk of rejection.
Interventions
DIETARY_SUPPLEMENTenteral feeding with Oxepa® and Glutasolve®
enteral feeding with Oxepa® and RESOURCE® GLUTASOLVE®
Sponsors
Health Resources and Services Administration (HRSA)
Baylor College of Medicine
LifeGift
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Consented solid organ donor 2. Age \>14, \<65 years old 3. Donors may have received or are receiving parenteral or enteral nutrition
Exclusion criteria
1. Known gastric or small bowel resections 2. Known malabsorptive disease of the gastrointestinal tract 3. Bariatric procedures, vagotomy or pyloroplasty 4. Known acute or chronic pancreatitis 5. Requiring an FiO2 \> 60%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome Measure is IL-6 Level | 12+/-2 hours | Plasma IL-6 level measured by ELISA. The 12+/-2 hour time frame is prior to organ explantation. |
Countries
United States
Participant flow
Recruitment details
Thirty-six (36) brain dead organ donors were randomized in a 1:1 ratio to standard care (fasting) or to receive the nutritional intervention via naso/oro-duodenal feeding. Consent was obtained from family members for subject participation. Organ donors were screened and enrolled between 2/2009-6/2011.
Pre-assignment details
Inclusion criteria: consented brain-dead organ donors age 14 to 70 years; may have received parenteral/enteral nutrition prior, but were excluded for prior gastric/bowel resections, GI malabsorption, bariatric procedures, vagotomy, pyloroplasty, or pancreatitis. Donors were excluded if a FiO2 greater than 60% was required (REE).
Participants by arm
| Arm | Count |
|---|---|
| 1 Standard Care 18 organ donors receiving standard care | 18 |
| 2 Enteral Feeding 18 enteral feeding with Oxepa® and RESOURCE® GLUTASOLVE®
enteral feeding with Oxepa® and Glutasolve®: enteral feeding with Oxepa® and RESOURCE® GLUTASOLVE® | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | 1 Standard Care | 2 Enteral Feeding | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 30 Participants |
| Age, Continuous | 44.5 years STANDARD_DEVIATION 14.7 | 38.9 years STANDARD_DEVIATION 14.5 | 41.9 years STANDARD_DEVIATION 14.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 13 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Organs procured | 4.6 Solid organs procured STANDARD_DEVIATION 1.5 | 4.4 Solid organs procured STANDARD_DEVIATION 4 | 4.53 Solid organs procured STANDARD_DEVIATION 1.7 |
| Organs Transplanted | 3.5 Solid organs transplanted STANDARD_DEVIATION 1.8 | 4.1 Solid organs transplanted STANDARD_DEVIATION 2.1 | 3.8 Solid organs transplanted STANDARD_DEVIATION 2 |
| Positive Breath Test Results | 4 participants | 6 participants | 10 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 17 Participants | 34 Participants |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
| Resting energy expenditure | 1954 kcal/d STANDARD_DEVIATION 691.9 | 1773 kcal/d STANDARD_DEVIATION 778.8 | 1866 kcal/d STANDARD_DEVIATION 729.5 |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 14 Participants | 11 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Primary Outcome Measure is IL-6 Level
Plasma IL-6 level measured by ELISA. The 12+/-2 hour time frame is prior to organ explantation.
Time frame: 12+/-2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 Standard Care | Primary Outcome Measure is IL-6 Level | 565.5 pg/ml | Standard Deviation 1010 |
| 2 Enteral Feeding | Primary Outcome Measure is IL-6 Level | 264.9 pg/ml | Standard Deviation 285.6 |