Clinical trial NCT00860379
Conditions: Burns
Sponsor: Shriners Hospitals for Children
Start date: 2009-01-01; Completion date: 2019-12-01
Enrollment: 14 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The selenium status of children with major burns is suboptimal which may increase the incidence of infection. Se requirements during critical illness are not known. Results from this investigation may provide a tool for recommending Se supplements during burn injury.

The hypothesis of this research is that Se supplementation will restore the depressed Se status among children with burn injuries. The secondary hypothesis is that Se status is related to the incidence of infection among pediatric patients with burns.

Detailed description:
Study Title: The effect of selenium supplementation among pediatric patients with burns

Primary Investigator: Maggie L. Dylewski, PhD, RD

Co-investigators: RL. Sheridan, MD; C Ryan, MD; K Prelack, PhD,RD; M Lydon, RN; J Weber, RN, BSN, CIC

Approved by: FDA (IND # 78963), Partners IRB (#2007-P-001176).

Funding: private grant from the Boston Burn Foundation

Background Information: Selenium, an essential dietary nutrient, is a component of glutathione peroxidase (an antioxidant) and thioredoxin reductase, an enzyme that regulates cytokine expression and thus plays a role in the immune system. Previous studies among adult burn patients showed that IV selenium supplementation was related to decreased infection and mortality. Please refer to the study protocol for further details.

Previous Research: We previously showed that children with burns (n = 20) \> 20% TBSA had low plasma selenium values compared to reference data of healthy American children. Results from this study also found a significant relationship between plasma selenium and incidence of infections.

Study Design: Randomized, double-blind, placebo-controlled clinical trial

Specific Aims:

1. to determine the impact of supplemental selenium on plasma selenium, glutathione peroxidase activity, and urine selenium among pediatric patients with burns \>20% total body surface area (TBSA) burn.
2. to determine the association between selenium supplementation, biomarkers of Se status and indicators of stress and infection.

Subjects: N = 75 pediatric patients with burns.

Inclusion criteria:

* Between 1 and 18 years of age admitted to Shriners Burns Hospital
* TBSA burn of \> 20%
* Existing IV catheter
* Enrolled into study within 3 weeks of burn injury

Treatment:

All subjects will be randomized into 1 of 3 groups and receive the treatment for 8 weeks, until 95% wound closure, or until central venous catheter access is discontinued.

1. Placebo (IV 0.9% sodium chloride)
2. 2 mcg/kg/day IV Selenium
3. 4 mcg/kg/day IV Selenium

Biological sample collection:

* 4 mL or 8 mL (8 every other week) of plasma once a week
* 24-hour urine collection once a week

Sample analyses:

* Samples will be frozen until analyses
* Samples will be sent to the outside lab for analyses.
* Plasma will also be sent to Massachusetts General Hospital every other week for plasma selenium analysis (to assess for toxicity)

Primary outcome measures:

* Plasma selenium
* Plasma glutathione peroxidase
* Urine selenium

Secondary outcome measures:

• occurrence of pneumonia or infection (bacterial or fungal) in the wound, blood, or urine

Risks:

* Supplement doses were determined using data from previous studies, current recommended dietary allowance (RDA) and upper tolerable limits, American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines for parenteral selenium, and dietary data recorded from our previous study. According to reference weights (NHANES III) supplement doses do not exceed the upper tolerable limits for children.
* Selenium toxicity is rare. However plasma will be assessed every other week for selenium levels.

Monitoring and Quality Assurance:

* All subjects will be monitored for any treatment-related adverse events for 2 weeks following discontinuation of the study therapy
* Any adverse events will be reported to the Partners Human Research Committee and the FDA per the guidelines.

An independent Data Safety Monitoring Board, consisting of 4 knowledgeable staff members, will meet 2 times per year to monitor the data for safety.

Arms: arm 1: Placebo arm 2: Subject will receive 2 ug/kg of IV selenium per day arm 3: Subject will receive 4 ug/kg of IV selenium per day
Interventions: intervention 1: Selenium1 intervention 2: Selenium2 intervention 3: Placebo
Intervention descriptions: intervention 1: 2 ug/kg intervention 2: 4 ug/kg intervention 3: IV saline as placebo

Protocol documents:
Prot_SAP_000.pdf: 
 
1 
 
The effect of selenium supplementation among pediatric patients with 
burns  
PI:  Maggie L. Dylewski, PhD,RD 
Version:  February 4, 2015 
 
I. 
Background and Significance 
 
A. Historical Background 
 
The importance of Selenium 
Selenium (Se) is an essential nutrient that is abundant in the American food 
supply. As a component of twelve mammalian selenoproteins, selenium plays an 
important role in the well being of all mammals.  For example, four types of 
glutathione peroxidase (GPx) are indispensable in the protection against 
oxidative injury (1).  In fact, these Se-containing enzymes provide antioxidant 
defense in all cell and interstititum compartments.  Thioredoxin reductase, 
another important selenoprotein, regulates cytokine expression and therefore 
plays a major role in immune defense.  These enzymes are expressed in almost 
every cell type and are dependent on the availability of Se (2). Due to its 
incorporation into proteins, Se affects all components of the immune system, 
both innate and adaptive responses (3, 4) and therefore influences the ability to 
respond to infection (5-7).  The role of Se in innate and acquired immune 
responses is mediated via its incorporation into glutathione peroxidase (8) and 
thioredoxin reductase (9).  Reduced intakes of Se produce decreases in antibody 
titres (7), T cell proliferation (10), and natural killer cell activity (11).  
 
 
Selenium Deficiency 
Although rare in developed countries, Se deficiency has been affiliated with a 
variety of cancers, rheumatic arthritis, muscular dystrophy, cystic fibrosis, 
malaria, and cardiovascular diseases (12). Additionally, low plasma Se values 
were found to be significantly associated with increased respiratory morbidity 
among very low birth weight infants (13).  
 
Selenium Toxicity 
Se toxicity is rare but can occur after high intakes over long periods of time. 
Reports of acute selenium toxicity typically involve unintentional ingestions (14-
19) and suicides (18, 20-25).  Most of these cases were fatal and 3 involved 
children who ingested gun-bluing solution (14, 16, 18).  Studies from South 
China, where Se in the soil is particularly high, toxicity is only associated with 
intakes greater than 850 ug/day (26, 27). In a recent case series published in 
2012 (28), the others retrospectively examined 9 patients who presented to a 
medical toxicology clinic with symptoms of selenosis after consuming a nutritional 
supplement. Analyses revealed that the supplement contained 200 times the 
reported amount of selenium. This resulted in an average Se intake of 1.3 g over 


 
2 
10-60 days. Symptoms of selenium toxicity began within 1 week of supplement 
intake and included alopecia, fingernail changes, GI symptoms, and memory 
loss. All patients survived and none required hospitalization.  
 
We did not find any clinical trials that reported selenium toxicity during parenteral 
selenium administration.   
 
High blood levels of Se (greater than100 ug/dL) can result in a condition called 
selenosis (29). Symptoms of selenosis include gastrointestinal upsets, hair loss, 
white blotchy nails, garlic breath odor, fatigue, irritability, and mild nerve damage 
(30).   
 
The Institute of Medicine of the National Academy of Sciences (IOM) (31) has set 
a tolerable upper intake level (UL) for Se that ranges between 90 and 400 ug/day 
for healthy children 1-18 years old (Table 1).  The UL is not known with a great 
deal of certainty and is conservatively calculated.   Se UL among children is 
determined by extrapolating adult data. 
 
It is important to note that the IOM (31) state in their report that the UL does not 
apply to patients under medical supervision and that doses of Se above the UL 
should not be discouraged in clinical trials.  Se toxicity has not been reported in 
trials administering Se supplements to adults with doses up to 1000 ug per day 
for short periods of time (1-3 weeks).   
 
Table 1.  UL values for Se among children (31) 
Age Group (years) UL for Se (ug/day) 
1-3 
90 
4-8 
150 
9-14 
280 
14-18 
400 
 
Selenium Compounds 
Selenium is incorporated into selenoproteins. There are 4 naturally occurring 
oxidation states of selenium:  selenide (Se-2), elemental selenium (Se0), selenite 
(Se+4), and selenate (Se+6).  Selenite can associate with other elements to form 
selenious acid. 
 
Dietary Se (organic) exists in two compounds, selenomethionine (from plants) 
and selenocystein (from animals).  Supplemental Se (inorganic) exists as 
selenate or selenite.  A study conducted in 1995 (32) suggested that the organic 
forms of Se increased blood Se concentration to a greater extent than inorganic 
forms. However, it did not significantly improve the activity of the Se-dependent 
enzyme, glutathione peroxidase (32). 
 
Selenium Supplements 


 
3 
Organic supplements can only be administered via the enteral route, while 
inorganic supplements can be given both enterally and parenterally. No data is 
available to compare the effect of enteral and parenteral Se on biomarkers of Se 
status.     
 
Due to impaired gastric motility intravenous (IV) supplements may be preferred 
during critical illness. In fact, IV Se was used in all clinical trials involving Se 
supplementation during critical illness (33).    The dose of Se provided in critical 
illness trials among adults ranges from 250-1000ug per day (34).  Data is 
available to show that 500 ug sodium selenite significantly increased plasma Gpx 
within 3 days (35), and that higher doses did not further increase Gpx (2). 
 
Most studies continuously infused Se over 24 hours (2, 35-37) through a 
separate line.  Large boluses over a short amount of time are not recommended 
due to a rapid rise in urinary Se excretion (2). 
 
Selenium in Nutrition Support 
Enteral and parenteral formulas also include selenium, usually in the form of 
sodium selenate (38-40). Enteral nutrition, commonly referred to as tube feeding, 
is administered via the digestive tract.  All commercial brands of enteral tube 
feedings contain selenium (Table 2).   
 
Table 2.  Se content of tube feeding formulas at Shriners Hospital in Boston 
Formula 
Se Content (ug/L) 
Pediasure 
21.6 
Peptamen 
50 
Peptamen 
AF 
160 
Replete 
100 
Jevity 1-Cal 
52 
 
Parenteral nutrition is administered directly into the blood, and is used when the 
intestinal tract is damaged or nonfunctional.  The recommended amount of 
selenium via parenteral nutrition developed by the American Society for 
Parenteral and Enteral Nutrition (ASPEN) are featured in Table 3 (41).  At SBH 
all patients on PN receive 20 ug of Se each day. 
 
Table 3.  ASPEN guidelines for Se content of parenteral nutrition. 
Age Group 
Se 
Neonates 3-10 kg 
2 ug/kg/day 
Children 10 – 40 kg 
1 – 2 ug/kg/day 
Children > 40 kg 
40 – 60 ug/day 
 
Selenium Requirements 
The Third National Health and Nutrition Examination Survey (NHANES III) 
reports that Americans consume 106 micrograms of Se per day (42).  The 


 
4 
current Recommended Dietary Allowance (RDA) for Se is 20 µg/day for 1-3 year 
old children, 30 µg/day for 4-8 year old children, 40 µg/day for 9-13 year old 
children, and 55 µg for children > 13 and adults (31).  Recommendations among 
adults are based on the amount of Se needed to achieve optimal GPx activity.  
Pediatric recommendations were determined by extrapolating from adult data.  
An exact recommendation for Se during an acute illness is not known.   
 
Assessment of selenium status 
Accurate determination of Se status during critical illness should include plasma 
Se, plasma Gpx, and urine Se (43).  It is especially important to measure Gpx 
activity because it represents the functional marker of Se status.  Gpx activity 
appears to plateau after a certain Se intake has been reached (44) and is not 
affected by the form of Se ingested(44).   
 
B. Previous research to support proposed research 
 
Preliminary study:  Selenium status of pediatric patients with burns 
A prospective study, designed to assess the longitudinal Se status of pediatric 
burn patients, was conducted by this research team.  Twenty patients admitted to 
Shriners Hospital in Boston, MA with burns exceeding 15% of their total body 
surface area (TBSA) were studied longitudinally for 8 weeks following admission 
or until 95% wound closure was achieved (determined by the attending physician 
using a burn diagram). Dietary Se intake from all forms of nutrition (oral, enteral, 
parenteral) was calculated daily and plasma and urine samples were collected 
weekly.  Plasma Se, plasma glutathione peroxidase (GPx) activity and urinary Se 
were determined.  Demographic data is featured in Table 4.   
 
Table 4. Demographics  (N = 20) 
 
Mean ± Standard 
Deviation 
Range 
Gender 
15 males 
 
 
5 females 
Age (years) 
6.5  + 5.3 
0.33 – 16 
Length of Stay (days) 
50 + 40 
11  – 161 
Initial %TBSA 
42 + 21 
15 - 93 
% Full Thickness 
27 ± 27 
0-90 
Type of Burn 
15 flame 
 
 
5 scald 
 
 
The mean dietary Se intake throughout the 8 week study was 60± 39 µg/day.  
Weekly selenium intake did not change significantly over the eight-week study 


 
5 
(Figure 1).  All subjects consumed greater than the RDA for Se (Table 5).  They 
also consumed more Se than recommended by the ASPEN (27). 
 
 
Table 5.  Dietary Se Intake and % AI According to Age  
Age (years) 
Number of 
Subjects 
Mean Se 
Intake 
(ug/day) 
Mean Se 
Intake 
(ug/kg/day) 
% RDA 
1-3 
8 
40 
2.9 
200 
5-8 
2 
62 
2.5 
201 
9-13 
7 
75 
1.6 
183 
14-18 
2 
83 
1.4 
151 
 
 
Plasma Se (mean = 1.08± 0.34 µmol/L) did not change throughout the entire 
study.  However, 82% of the total weekly samples were below the 1.35 μmol/L 
plasma selenium level reported in healthy American children ages 1-18yrs 
(Figure 2).  Higher plasma selenium was also correlated with a lower incidence of 
infection (p = 0.043). 
 
The mean plasma glutathione peroxidase (GPx) level over the eight weeks was 
3.29 Units/mg protein ± 1.42.  Furthermore, 40% of all weekly plasma GPx 
samples were below the 2.8-3.4 U/g protein range established in healthy 
American girls ages 11-14 (34) .  No statistical differences were found throughout 
the eight weeks. 
 
There was no significant change in urinary selenium levels between weeks. The 
mean urinary selenium level throughout the eight-week study was 65.9 μg/L ± 50, 
which is higher than the mean selenium intake from diet 60 μg/L ± 39.   A 
majority of the observed urinary selenium levels were higher than those reported 
(28.7 μg/L ± 8.3) in healthy American children ages 5-18 years (35). 
 
In summary, these results indicate that selenium status in pediatric burn patients, 
as measured by plasma and urine selenium concentrations and plasma GPx 
activity, was inadequate throughout the eight weeks following thermal injury.  
Additionally, these results suggest that maintaining normal blood concentrations 
of selenium and GPx activity following burn injury reduce the incidence of 
infection.  This data was presented at the American Burn Association Annual 
meeting in March 2007 and published in the Journal of Trauma in 2010. 
 
     
 
 
 
 
 


 
6 
 
Figure 1.  Dietary Selenium. Selenium intake did not change significantly over 
the eight week study.  Intake ranged from 100-400% the AI/RDA (based on 
age). 
 
 
Figure 2.  Plasma Selenium. There was no significant difference in weekly 
plasma selenium levels throughout the eight weeks of the study. However, 82% 
of the total weekly samples were below the 1.35 μmol/L plasma selenium level 
reported in healthy American children ages 1-18yrs. 
 
 
 
Selenium supplementation in children  
Few clinical trials have studied the impact of Se among sick children.  The few 
studies available include various populations and methodologies (Table 6).   
 
0.0
20.0
40.0
60.0
80.0
100.0
120.0
140.0
1
2
3
4
5
6
7
8
µg Selenium/day
Week
Average Weekly Selenium Intake
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
1
2
3
4
5
6
7
8
Plasma Selenium µmol/L
Weeks
Average Weekly Plasma Selenium Values


 
7 
 
Table 6.  Selenium supplementation trials among non-critically ill children. 
Reference Region 
Subjects 
Se supplement 
Se dose 
Outcome 
(45)  
South 
Malawi 
2372 children 
(1-4 years) with 
malnutrition 
Sodium selenate 
(MVI powder) 
55 ug/day 
for 20 
weeks 
Se not related 
to risk of 
Kwashiorkor 
(46) 
USA 
94 Latino 
children 
(6mos – 5 years) 
Sodium selenate 
(MVI tablet) 
1 tablet for 
5-6 months 
Se decreased 
Upper 
respiratory 
tract visits to 
pediatrician 
(47) 
Tibet 
324 children 
(5-15 years) with 
Kashin-Beck 
disease 
Sodium selenate 
(oral) 
100 ug/day 
for 12 
months 
Se not related 
to Kashin-
Beck disease 
(48) 
France 
27 children 
(7-20 years) with 
cystic fibrosis 
Sodium selenite 
(oral) 
2.8 ug/kg 
for 2 
months 
Se not related 
to lipid 
peroxidation 
markers 
 
Only one study was found in the literature pertaining to pediatric Se 
supplementation during burn injuries.  Borner et al. (49) studied 65 children aged 
1 to 16 years with severe inflammatory surgical diseases as well as widespread 
burns.  All subjects received either a Se supplement (n =34) or no selenium 
supplement (n = 31). Selenium was administered intravenously for the first seven 
days of the maintenance period, and orally for an additional seven to 14 days.   
The initial Se dose was based on body weight.  A one-time dose of 200 μg was 
administered to children weighing less than 15 kg.  Likewise, a 500 μg dose was 
given to subjects weighing 15 – 30 kg, and a 1000 μg dose was given to subjects 
weighing greater than 30 kg.  Subsequently the experimental group received 3 
doses of 2 ug/kg Se everyday for 7-14 days.  Blood samples were drawn on 
study days 1, 2, 3, 6, and on the final day of the trial. Results showed that the 
control group had lower plasma Se and GPx activity compared to the 
experimental group.  The authors also reported that lipid peroxidation declined 
following Se supplementation, indicating increased cell protection.   
 
Selenium supplementation during adult burn injuries 
There is more data regarding Se supplementation among critically ill adults.  A 
meta-analysis completed several years ago showed that Se supplementation 
alone or in combination with other antioxidants was associated with a reduced 
trend in mortality (p=0.09) (33). Although this data was not significant, high dose 
Se (500 or 1000 ug/day IV sodium selenite) had the best results. 
 
In 2006 Angstwurm et al. (2) published the first trial on high-dose Se 
supplementation among adults in the intensive care unit.  Patients (n=249) in this 
study were randomized to treatment (1000 ug IV sodium-selenite continuous 
infusion over 24 hours for 14 days) or placebo.  Results showed that high dose 
Se supplementation reduced mortality among patients with severe sepsis.  
 


 
8 
In a slightly smaller study (n = 150) published in 2011, Valenta et al. (50) 
reported contradictory results. This study was a prospective, randomized, open-
label, trial that investigated the impact of Se supplementation (1500 ug/day x 14 
days) on patients with SIRS/sepsis. Although plasma Se and GPx activity were 
higher among the supplemented patients, mortality was similar among groups. 
 
There is data among critically ill patients that suggests that Se reduces 
infections. In 2011, Andrews et al. (51) studied 502 adult ICU patients with 
gastrointestinal failure. In this randomized, double-blind study, subjects received 
parenteral glutamine, selenium (500 ug/day), or both for up to 7 days.  Patients 
who received IV Se for > 5 days had less new infections compared to other 
groups (OR: 0.53(0.30-0.93). This data was supported by a prospective, 
randomized, placebo-control, single-blinded study published in 2011 (52).  Thirty-
one ICU patients were included in this study. The authors showed that a daily 
infusion of 1600 ug Se, following an initial bolus of 2000 ug, lowered the 
incidence of hospital-acquired pneumonia among patients in the intensive care 
unit.  
 
Over the past 15 years, a research team led by Berger et al. conducted several 
studies that examined Se supplementation combined with other trace minerals 
during adult burn injuries (Table 7).  In general, studies showed a reduction in 
infection rates among supplemented groups.  However, it is not known if the 
results are due to selenium, another trace mineral, or a combination of the 3 
trace minerals provided.  
 
Table 7.  Selenium supplementation trials among adult burn patients 
Reference 
Study 
Design 
Subjects 
Intervention 
Duration 
Results 
Berger et al. 
2006 (34)  
Combination 
of 2 
randomised, 
double-blind 
trial 
41 burn 
patients 
with mean 
TBSA of 
46% 
IV trace element 
cocktail vs 
Placebo. 
Cu: 2.5-3.1 mg/d 
Se: 315-380 ug/d 
Zn: 26.2-31.4 
mg/d 
8-21 days 
Plasma Se 
levels increased 
with 
supplementation; 
Reduced 
number of 
infections in 
supplemented 
pts (3.5 vs 2 
episodes per pt) 
Berger et al. 
2007 (53) 
Prospective, 
randomized, 
placebo-
controlled trial 
21 burn 
patients 
with mean 
TBSA of 
45% 
IV trace element 
cocktail vs 
Placebo. 
Cu: 3.75 mg/d 
Se: 375  ug/d 
Zn: 37.5 mg/d 
14-21 days 
Plasma Se sig 
higher in 
supplement 
group; Number 
of infect in first 
30 days was sig 
lower in 
supplement 
group (2 vs 4 
infections per 


 
9 
pt); Supplement 
group had fewer 
regrafting 
episodes. 
Berger et al. 
1998 (36) 
Prospective, 
randomized, 
placebo-
controlled trial 
20 burn 
patients 
with mean 
TBSA of  
48% 
IV trace element 
cocktail vs 
Placebo. 
Cu: 3.75 mg/d 
Se: 375  ug/d 
Zn: 37.5 mg/d 
8 days 
The number of 
infections were 
lower in 
supplement 
group 
 
Overall the data among adults is promising, but does not identify a specific 
guideline for selenium supplementation during critical illness.  The data among 
children is scarce and less impressive.  
 
 
 
 
 
C. Rationale behind proposed research/ benefits to society 
The Se status of children with major burns is suboptimal which may increase the 
incidence of infection.  Se requirements during critical illness are not known. 
Results from this investigation may provide a tool for recommending Se 
supplements during burn injury. 
 
II. 
Specific Aims 
 
The hypothesis of this research is that Se supplementation will restore the 
depressed Se status among children with burn injuries.  The secondary 
hypothesis is that Se status is related to the incidence of infection among 
pediatric patients with burns.   
The specific aims of this research are 
1. to determine the impact of supplemental Se needed on plasma Se, Gpx 
activity, and urine selenium among pediatric patients with burns >20% 
TBSA. 
2. to determine the association between Se supplementation, biomarkers of 
Se status and indicators of stress and infection.   
 
III. 
Subject Selection 
 
All subjects (n = 75) will be recruited from the Shriners Hospital for Children in 
Boston.     
 
Inclusion Criteria: 
• Between 1 and 18 years of age admitted to Shriners Burns Hospital 
• TBSA burn of > 20% 
• Existing catheter 
• Enrolled into study within 3 weeks of burn injury 
Exclusion Criteria: 
• < 1 year or > 18 years of age 
• < 20% TBSA burn 


 
10 
• No existing catheter 
• Renal disease (eGFR < 60) 
• Liver disease (bilirubin greater than 3) 
• Thyroid disorders (thyroid disease which currently requires 
treatment) 
• Cancer 
• HIV* 
• Pregnancy (as determined by routine admission labs) 
 
* Previously known HIV+ status.  An HIV test will not be administered for the 
purpose of this study. 
  
 
To ensure the safety of all patients, once every 2 weeks, blood samples will also 
be sent to the Massachusetts General Hospital Chemistry lab for analysis of 
selenium levels.  If the selenium level is greater than 100 ug/dL the patient will be 
immediately removed from the study. 
 
If the selenium level is greater than 100 ug/dL the subject will be immediately 
removed from the study. 
 
 
If a patient decided to withdraw from the study or meets the exclusion criteria 
during the study, he/she will be removed from the study immediately.  No further 
study procedures, including supplementation and blood and urine collection, will 
be completed.  However, these subjects will be followed for 2 weeks for any 
adverse events related to the study. Neurological status, per routine care from 
the medical team, will be assessed.  Additionally, lab values will be followed (if 
available from routine care) (complete blood count, serum creatinine, aspartate 
aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, 
coagulation studies). Ongoing adverse events thought to be study drug related 
will be followed until resolution or the condition stabilizes. 
 
 
IV. 
Subject Enrollment 
 
All eligible subjects will be screened using the inclusion/exclusion criteria by the 
Clinical Research Nurse or Clinical Research Specialist, who will serve as the 
primary investigator. Assessment of potential eligibility of subjects will be 
provided by the primary physician.  Subsequently, only members of the study 
staff can initiate the recruitment process.  The consent and assent will only be 
obtained by members of the study staff who are a physician, a PhD, or an RN.  
 
Following patient admission and stabilization, if the patient meets the inclusion 
criteria, a member of the clinical staff will approach the subjects/parents 
guardian/ to gain permission for the study staff to discuss the study.    If 
permission is granted, an appropriate member of the study staff will approach 


 
11 
subjects/parents/ guardians at the bedside, who meet the inclusion/exclusion 
criteria, with a brief explanation of the study. A more detailed explanation will be 
offered in a private room to those interested in participation. The alternative to 
participation is “not to participate”.  Care will not be altered for patients who do 
not participate.  Informed consent will be obtained if the patient and/or 
parent/legal guardian agrees to participate. Parents/legal guardians will be 
allowed an indefinite amount of time for questions and participation 
consideration.  Parents/legal guardian will provide consent for 0-18 year old 
children (documented in writing using the PHRC approved consent form). The 
permission of both parents is required unless one parent is deceased, unknown, 
incompetent, or not reasonably available or if only one parent has legal 
responsibility for the care and custody of the child. Any child 14 years or older, 
who is able, will consent along with parent/guardian.  The assent of each child 
(age 7 and older) who is capable of providing assent based on medical condition, 
age, maturity, and psychological state will be sought.According to a power 
analysis calculation, 75 children will be included in this study.  
 
 
B. Treatment Assignment and Randomization 
 
This is a randomized, double-blind, placebo-controlled trial.  Patients will be 
randomly assigned to receive Selenium supplementation (either 2, or 4 
ug/kg/day) or a placebo. 25 subjects will be in each group (total of 75 subjects).  
Randomization will occur by using a computerized randomization list.  A 
pharmacist, who is not a member of the study staff, will prepare the supplements 
and label them accordingly prior to distribution. 
 
 
V. 
Study Procedures 
 
A. Study Parameters 
B. Lab studies conducted solely for the purpose of this study include 
plasma and urinary Se, plasma Gpx and dietary Se intake. Other 
parameters that will be included are demographics, medications, 
wound debridement procedures, invasive devices, mode of nutrition 
support, kilocalorie and protein intake, weekly weights, neurological 
status (as routinely assessed by the clinical team) and routine 
laboratory studies.  
C. Another parameter that will be recorded is the occurrence of 
pneumonia or infection (bacterial or fungal) in the wound, blood, or 
urine, as defined by The National Noscomial Infection Surveillance 
System (A localized or systemic condition that results from adverse 
reaction to the presence of an infectious agent(s) or toxin(s)) and 
clarified by the Infection Control Nurse.  Specific definitions are as 
follows: 
Urinary Tract Infections 


 
12 
 a) Patient has at least 1 of the following signs or symptoms with no 
other recognized cause:  fever (>38◦C), urgency, frequency, dysuria, 
or suprapubic tenderness 
 
and 
 
patient has a positive urine culture that is ≥ 105 microorganisms per 
cm3 of urine with no more than 2 species of microorganisms. 
 
     
 b) Patient has at least 2 of the following signs or symptoms with no 
other recognized cause:  fever (>38◦C), urgency, frequency, dysuria, 
or suprapubic tenderness 
 
 
 
and at least 1 of the following 
• Positive dipstick for leukocyte esterase and/or nitrate 
• Pyuria (urine specimen with ≥ 10 WBC/mm3 or ≥ WBC/high 
power field of unspun urine) 
• Organisms seen on Gram stain of unspun urine 
• At least 2 urine cultures with repeated isolation of the same 
uropathogen (gram-negative bacteria or S. saprophyticu) with 
≥ 102 colonies/mL in nonvoided specimens 
• ≤ 105 colonies/mL of a single uropathogen (gram-negative 
bacteria or S. saprophyticu) in a patient being treated with an 
effective antimicrobial agent for a urinary tract infection 
• Physician diagnosis of a urinary tract infection 
• Physician institutes appropriate therapy for a urinary tract 
infection 
 
c) Patient 1 year of age has at least 1 of the following signs or 
symptoms with no other recognized cause: fever (>38◦C), 
hypothermia (<37◦C), apnea, bradycardia, dysuria, lethargy,or 
vomiting 
     and 
 
patient has a positive urine culture that is ≥ 105 microorganisms per 
cm3 of  
urine with no more than 2 species of microorganisms 
 
d) Patient 1 year of age has at least 1 of the following signs or 
symptoms with no other recognized cause: fever (>38◦C), 
hypothermia (<37◦C), apnea, bradycardia, dysuria, lethargy,or 
vomiting 
     and at least 1 of the following: 
• Positive dipstick for leukocyte esterase and/or nitrate 
• Pyuria (urine specimen with ≥ 10 WBC/mm3 or ≥ WBC/high 
power field of unspun urine) 
• Organisms seen on Gram stain of unspun urine 
• At least 2 urine cultures with repeated isolation of the same 
uropathogen (gram-negative bacteria or S. saprophyticu) with 
≥ 102 colonies/mL in nonvoided specimens 
• ≤ 105 colonies/mL of a single uropathogen (gram-negative 


 
13 
bacteria or S. saprophyticu) in a patient being treated with an 
effective antimicrobial agent for a urinary tract infection 
• Physician diagnosis of a urinary tract infection 
• Physician institutes appropriate therapy for a urinary tract 
infection 
 
  
 
Pneumonia  
a) 2 or more serial chest radiographs with at least 1 of the 
following: new or progressive and persistent infiltrate, 
consolidation, cavitation,  
 pneumatoceles 
 
b) At least 1 of the following: 
• Fever (>38◦C) with no other recognized cause 
• Leukopenia (< 4000 WBC/mm3) or leukocytosis (≥ 12000 
WBC/mm3) 
and at least 2 of the following: 
• New onset of purulent sputum, or change in character of 
sputum, or increased respiratory secretions, or increased 
suctioning requirements 
• New onset or worsening cough, dyspnea, or tachypnea 
• Rales or bronchial breath sounds 
• Worsening gas exchange (e.g. O2 desaturations, increased 
oxygen requirements, or increased ventilation demand 
 
Burn Infection 
  
 
 a)  Patient has a change in burn wound appearance or character, 
such as  
     rapid eschar separation; dark brown, black, or 
violaceous discoloration  
    
    of the char; or edema at wound 
margin 
 
 
        and 
 
 
     histologic examination of burn biopsy shows invasion of 
organisms into    
    adjacent viable tissue. 
 
 
 
 
 
 b)  Patient has a change in burn wound appearance or character, 
such as  
     rapid eschar separation; dark brown, black, or 
violaceous discoloration  
    
     of the char; or edema at 
wound margin 
 
 
         and at least 1 of the following: 
• 
Organism cultured from blood in the absence of other 
identifiable  
 
 
infection 
• 
Isolation of herpes simplex virus, histologic identification of  
 
 
inclusions by light or electron microscopy or visualization of 
viral  
 
 
 
particles by electron microscopy in biopsies or lesion 
scrapings 


 
14 
c) Patient with a burn has at least 2 of the following signs or 
symptoms  
      with no other recognized cause: fever (>38◦C), hypothermia 
(<37◦C),  
 
 
    hypotension, oliguria (< 20 cm3/hr), 
hyperglycemia at previously    
 
      tolerated level of 
dietary carbohydrate, or mental confusion 
 
       and at least 1 of the following: 
• Histologic examination of burn biopsy shows invasion of 
organisms into adjacent viable tissue. 
• Organism cultured from blood 
• Isolation of herpes simplex virus, histologic identification of 
inclusions by light or electron microscopy, or visualization of 
viral particles electron microscopy in biopsies or lesion 
scrapings 
  
    Bloodstream Infections 
a) Patient has a recognized pathogen cultured from one or more 
blood  cultures 
 
and 
 
organism cultured from blood is not related to an infection at 
another  site. 
 
i.Patient 1 year of age has at least 1 of the following signs or 
symptoms with no other recognized cause: fever (>38◦C), chills, or 
hypotension 
 
  
and at least 1 of the following 
• Common skin contaminant (e.g. diphtheroids, Bacillus sp. 
Propionibacterium sp, coagulase-negative staphylococci, or 
micrococci) is cultured from 2 or more blood cultures drawn on 
separate occasions 
• Common skin contaminant (e.g. diphtheroids, Bacillus sp. 
Propionibacterium sp, coagulase-negative staphylococci, or 
micrococci) is cultured from at least 1 blood culture from a 
patient with an intravascular line, and the physician institutes 
appropriate antimicrobial therapy 
• Positive antigen test on blood (e.g. Haemophilus influenza, 
Streptococcus pneumoniae, Neisseria meningitides, or group 
B Streptococcus) 
 
 
 
 
and signs and symptoms and positive laboratory results are 
not  
  
related to an infection at another site. 
 
c) Patient 1 year of age has at least 1 of the following signs or 
symptoms with no other recognized cause: fever (>38◦C), 
hypothermia (<37◦C), apnea, or bradycardia 
 
and at least 1 of the following: 


 
15 
• Common skin contaminant (e.g. diphtheroids, Bacillus sp. 
Propionibacterium sp, coagulase-negative staphylococci, or 
micrococci) is cultured from 2 or more blood cultures drawn on 
separate occasions 
• Common skin contaminant (e.g. diphtheroids, Bacillus sp. 
Propionibacterium sp, coagulase-negative staphylococci, or 
micrococci) is cultured from at least 1 blood culture from a 
patient with an intravascular line, and the physician institutes 
appropriate antimicrobial therapy 
• Positive antigen test on blood (e.g. Haemophilus influenza, 
Streptococcus pneumoniae, Neisseria meningitides, or group 
B Streptococcus) 
and signs and symptoms and positive laboratory results are 
not related to an infection at another site. 
 
 
B.    Supplements to be used 
 
 
All patients will receive routine nutrition support that includes oral, enteral, or 
parenteral nutrition or a combination of the 3 sources.  All enteral nutrition 
products contain Se in the form of sodium selenate (Table 2).  All patients who 
require parenteral nutrition receive 20 ug of IV selenious acid per day (this is 
standard therapy at SBH).  According to our previous study, despite various 
routes of nutrition support within and among subjects, Se intake remained stable 
throughout the 8 week time period and cover approximately 150 – 200% of the 
RDA for Se.  Therefore standard nutrition support, including Se, should not 
interfere with this proposed investigation (Figure 1). 
 
In addition to standard nutrition support, all patients will be randomized to receive 
IV Se supplementation or placebo.  The placebo (0.9% sodium chloride or 5% 
Dextrose solution, depending on the clinical situation) will look identical to the Se 
supplements.  Patients in the experimental groups will receive parenteral Se as 
selenouis acid (added to 25 ml of 5% Dextrose solution or 0.9% sodium chloride) 
(carrier solution will depend on clinical situation) as a 24-hour continuous infusion 
in doses 2 ug/kg/day (n = 25), or 4 ug/kg/day (n = 25).  The placebo group (n = 
25) will receive sodium chloride 0.9% in the same regimen.  These Se 
supplement amounts were determined taking into account previous studies in the 
literature, current RDAs, UTLs, ASPEN guidelines for parenteral Se, and dietary 
data recorded from our previous study.  According to reference weights adapted 
from NHANES III data, supplement doses (2 ug/kg/day and 4 ug/kg/day) do not 
exceed the upper tolerable limits for children. 
 
The Se/Placebo will be provided as a 24-hour continuous infusion.  The 
continuous infusion of Se/Placebo may be temporarily interrupted, if necessary, 
for reasons including, but not limited to, surgical procedures and drug 
compatibility issues. These temporary interruptions will not reduce the integrity of 


 
16 
the study.  However, if the Se/Placebo infusion is held for longer than 48 
consecutive hours or 72 hours in 7 days then the subject will be removed from 
the study.  At this time no further study drug will be given or biological samples 
taken.  All subjects will be monitored for any treatment-related adverse events for 
2 weeks following discontinuation of the study therapy. 
 
Prior to initiation of the study, the research nurse will hold an in-service for 
clinical staff to alert them of the study. A specific research sticker will be placed in 
the chart to alert clinical staff that the patient is enrolled in this research study. 
The MD responsible for the care of the patient will write the orders for the 
supplements.  The Pharmacy will prepare all supplements and the nurses will 
administer them. 
 
 
C. Data Collection 
 
Plasma and urine Se and plasma Gpx will be measured weekly from the time of 
admission for a maximum of 8 weeks or until the patient achieves 95% definitive 
wound closure.   
 
The research nurse will obtain 4 ml or 8ml (8 ml will be drawn instead of 4 ml 
every other week starting with week 1 for real time analysis) of whole blood off an 
existing catheter and place it into a trace-element free blood collection tube.  
 
Every other week, when 8 ml of blood is needed, 4 ml will be transferred by the 
unit assistant to the MGH laboratory for immediate analyses (the MGH lab uses 
Quest Labs for analysis of selenium). If in the unlikely event that the MGH lab 
rejects the sample for any reason, another 4 mL blood draw will be collected and 
sent to the MGH lab for real-time analyses.  
 
Weekly, the 4 ml sample will be transported by the nurse to the clinical research 
lab (in the same building).  In the lab the nurse will use a centrifuge to separate 
the blood and then pipette the plasma and whole blood into collection vials to be 
frozen prior to analyses.   A  24 hour urine will be initiated the day prior to blood 
sampling for analysis of urinary Se.  Urine will be collected via an existing 
catheter.  If no catheter exists patient will be asked to urinate into a container.  If 
the patient is unable to urinate into a container, the urine sample will not be 
collected.  Infant urine will be collected via diapers.  The research nurse will then 
bring the urine container down to the clinical research lab and aliquot it into 50 ml 
vials prior to being frozen.  Frozen samples are eventually mailed to a 
commercial laboratory for lab analyses.  The PI is certified to ship biological 
products and all appropriate regulations will be followed. 
 
Culture Data 


 
17 
Wound cultures will be obtained for all patients admitted to the acute care unit at 
Shriners Burns Hospital, per routine care, on admission.  Urine cultures will also 
be obtained upon admission if one or more of the following criteria are met: 
• Symptoms of urinary tract infection (UTI) 
• History of recurrent UTI 
• Structural abnormalities of the GU tract 
• Patient requires urinary catherization 
• Fever of unknown origin 
• Urinalysis testing indicates possible infection 
 
Subsequently wound and urine (if meets criteria above) will be obtained at least 
once a week.  Wound, urine, blood, and sputum cultures may also be obtained 
during a fever spike or when clinically appropriate per the medical team.  If 
bacteremia or fungemia is suspected, 2 sets of blood cultures will be assessed. 
 
All cultures are obtained by a trained registered nurse or a medical doctor and 
are transported to the bacteriology lab (accredited by CLSI) at Shriners Burns 
Hospital within 2 hours.  According to infection control policies at Shriners Burns 
Hospital all specimens must be labeled with patient name and medical record 
number and placed in sealed plastic bags or other suitable containers when 
being transported. If a specimen will be cultured for fungus, the specimen will be 
labeled “fungal culture”.  Methods of culture collection are described below: 
 
 
Blood:  Venipuncture is the recommended means of obtaining blood for 
cultures. However, when this is not possible blood from catheters and other 
intravascular devices may be used.   
Blood cultures are placed in a sealed plastic bag and brought to the laboratory as 
soon as possible.   
Blood is cultured in our laboratory using the Bactec automated system consisting 
of a single blood culture bottle.  
• Blood culture bottles: Plastic cap is removed from the bottle. Rubber 
stopper on top of bottle is cleaned with an alcohol pad.  
 
Isolators are processed within 16 hours.  Bottles are held for 5 days. A separate 
plate is routinely used to assess for fungus.  Please note that regarding fungal 
cultures, many of the opportunistic fungi (Aspergillus, Penicillium and Mucor) are 
rapid growers and colonies will be seen within the first 24-48 hours (mature 
within 4-5 days) and identified down to the species level when possible.  Candida 
will usually grow in 24-48 hours and can be identified at this time.  Speciation 
requires 72 hours.     


 
18 
 
The pathogenic fungi (Histoplasma and Blastomyces) cultures will be referred to 
the MGH laboratory for speciation. Results are confidentially reported to the 
medical team at Shriners Burns Hospital.    
 
Contaminates may be found among blood cultures.  The decision on whether or 
not it is a contaminate is based on the clinical judgment of the medical doctors 
and clinical team.  If a culture is deemed a   “contaminant” it will be reported as 
such in the data collection sheet.   
 
 
Burn:  Wound cultures for patients include the following anatomical areas: 
head, chest, back, buttocks, groin, upper extremities, hands, and lower 
extremities (approximately 1 culture for every 10% burn surface injury). Open 
wound areas as well as donor sites are cultured.  These cultures are usually 
obtained by swab.  Occasionally, wound cultures will be obtained by biopsy if 
requested by the surgical physician.  Wound site is cleaned and then gently 
rubbed in a circular motion to swab areas most likely to harbor pathogenic 
organisms (under eschar, purulent drainage etc.)   Areas of normal tissue are 
avoided to reduce contamination with skin flora.   Ampule at the bottom of the 
culture tube is crushed and the specimen is placed in a plastic bag and sealed. 
 The culture is brought to the laboratory as soon as possible, but no longer than 2 
hours after collection. Wounds are planted on two plates: TSA with 5% sheep 
blood and Levine EMB.  The swab is then put into a thioglycolate broth which will 
support the growth of most anaerobes.  Plates are incubated for 24 hours.  If 
there is no growth they are reincubated for another 24 hours.  Tubes are kept 
until growth is seen or 7 days, which ever comes first.   
 
 
A separate plate is routinely used to assess for fungus.  Please note that 
regarding fungal cultures, many of the opportunistic fungi (Aspergillus, 
Penicillium and Mucor) are rapid growers and colonies will be seen within the first 
24-48 hours (mature within 4-5 days) and identified down to the species level 
when possible.  Candida will usually grow in 24-48 hours and can be identified at 
this time.  Speciation requires 72 hours.  .   
 
 
The pathogenic fungi (Histoplasma and Blastomyces) cultures will be referred to 
the MGH laboratory for speciation. Results are confidentially reported to the 
medical team at Shriners Burns Hospital.    
Histological exams are not routinely completed, but may be ordered by the 
physician. 
 


 
19 
 
Urine:  Urine is collected in a sterile leak proof container.  If the patient has 
a foley catheter, the injection port at junction of drainage tubing is cleaned with 
betadine. Needle is inserted and urine aspirated into the syringe. Urine is then 
transferred into the urine container.  If a urine collection bag is used, the urinary 
meatus is cleansed and the urine bag is applied to collect the urine. 
 
Urine specimen is sealed and transported to the laboratory as soon as possible, 
no longer than 1 hr.  Samples are inoculated on BAP and EMB plates with a 
calibrated loop and incubated for 24 hours.  
 
A separate plate is routinely used to assess for fungus.  Please note that 
regarding fungal cultures, many of the opportunistic fungi (Aspergillus, 
Penicillium and Mucor) are rapid growers and colonies will be seen within the first 
24-48 hours (mature within 4-5 days) and identified down to the species level 
when possible.  Candida will usually grow in 24-48 hours and can be identified at 
this time.  Speciation requires 72 hours.  .   
 
The pathogenic fungi (Histoplasma and Blastomyces) cultures will be referred to 
the MGH laboratory for speciation. Results are confidentially reported to the 
medical team at Shriners Burns Hospital.    
 
Contaminates may be found among urine cultures.  The decision on whether or 
not it is a contaminate is based on the clinical judgment of the medical doctors 
and clinical team.  .  If a culture is deemed a   “contaminant” it will be reported as 
such in the data collection sheet.   
 
 
Sputum:  Sputum and aspirates are collected in a sterile cup or suction 
trap.  Non-bacteriostatic normal saline may be instilled into the airway to aid in 
procurement of culture. Specimen container is placed in a plastic bag, sealed 
and brought to the laboratory as soon as possible. Sputum is plated onto 3 
different agar plates:  TSA with 5%sheep blood, Levine EMB and Chocolate 
plates.  Plates are incubated in a CO2 incubator for 24 hours and if no organisms 
are seen (or scant growth) they are reincubated for another 24 hours.    
 
A separate plate is routinely used to assess for fungus.  Please note that 
regarding fungal cultures, many of the opportunistic fungi (Aspergillus, 
Penicillium and Mucor) are rapid growers and colonies will be seen within the first 
24-48 hours (mature within 4-5 days) and identified down to the species level 
when possible.  Candida will usually grow in 24-48 hours and can be identified at 
this time.  Speciation requires 72 hours.  .   
 


 
20 
The pathogenic fungi (Histoplasma and Blastomyces) cultures will be referred to 
the MGH laboratory for speciation. Results are confidentially reported to the 
medical team at Shriners Burns Hospital.    
Normal flora cultured from the sputum (viridians strep Neisseria species, 
coagulase negative Staphylococcus and rare amounts of yeast, enteric gram 
negatives, Staph. aureus.) will be documented as normal flora) 
 
Dietary Data 
Dietary data (enteral nutrition, parenteral nutrition, oral intake) will be collected 
daily from the medical record.  Total Se intake via supplements and/or enteral 
feedings will be calculated based on daily intake and output sheets as recorded 
by the bedside nurse.  Dietary Se intake from food will be determined using the 
Nutrient Database System for Research version 2005. 
 
 
Other Data 
Weights will be obtained as part of routine care by the bedside nurse, and 
recorded twice a week. Demographic data will be obtained from the medical 
record.  Please see data collection sheet for details.  
 
As part of routine care by the medical team neurological status will be assessed 
and several laboratory values will be monitored closely (including total protein, 
albumin, prealbumin and C-reactive protein complete blood count, serum 
creatinine, AST, ALT, alkaline phosphatase, total bilirubin, and coagulation 
studies) will be recorded from the medical record.   
 
 
D. Selenium Analysis 
 
Blood (4 ml or 8 ml) and urine samples will be obtained weekly.  De-identified 
samples will be sent to a commercial laboratory for analyses. Results will be sent 
to Shriners Burns Hospital in Boston.  Additionally, to ensure the safety of all 
patients, once every 2 weeks, blood samples (4 ml) will also be sent to the 
Massachusetts General Hospital Chemistry lab for analysis.  These results are 
typically available after 24-48 hours. 
The study endpoint will be whichever of the following factors happens first: 
• 8 weeks 
• discontinuation of central venous catheter 
• a stop in Se/Placebo infusion lasting longer than 48 consecutive 
hours or 72 hours in 1 week, 
• when the patient achieves 95% definitive wound closure 
determined by the attending physician.   
 


 
21 
No interim analyses are planned.  Data obtained from our previous investigation 
on Se and pediatric burns was used for the power analysis calculation:   
 
 
n = (2 x [Z (1- a/2) + Z (1- b)]2) / D2     
 
where Z (1- a/2)  and  Z (1- b) represent percentage points of the normal distribution 
for statistical significance level and power, respectively.  The values used were 
1.96 for a significance level of 5% and 0.8416 for a power of 80%.  The  D 
represents the standardized difference (the treatment difference divided by its 
standard deviation).  This was calculated by subtracting the mean plasma Se 
determined in our pilot study (1.08  µmol/L) from the average plasma Se of 
healthy American children 1.35 (µmol/L) and dividing by the standard deviation 
(0.34). This calculation revealed that 25 subjects are needed per group to obtain 
80% power and a significance level of 5%. 
 
All subjects enrolled will be included in the statistical analyses (intent-to treat).  A 
2-sided statistical test will be used for all analyses and the overall type-I error 
rate will be controlled at the 5% level.   For each dependent variable (plasma 
selenium, urinary selenium, plasma GPx activity) a 2-way repeated measures 
ANOVA will be used to examine the difference among groups and over time 
(primary hypothesis).  Tukey’s will be utilized as the post-hoc test. 
 
An ordinal logistic regression will performed to determine the relationship 
between the incidence of infection (categorized by burn, bloodstream, urinary 
tract infection, and PNA) and plasma selenium, urinary selenium, plasma GPX, 
age, initial percent TBSA burned, and treatment group (secondary hypothesis). 
 
Appropriate confounding factors (including but not limited to dietary Se intake, 
age, sex, race, initial %TBSA, and length of time from burn injury to study 
enrollment) will be included in the statistical models.  All statistics will be 
completed using SAS software. 
 
 
VI. 
Risks and Discomforts 
 
Phlebotomy will be minimal (4 or 8 ml/wk) and will be obtained painlessly through 
existing catheters or during operative procedures. 
Se toxicity is rare.  Symptoms include: 
• memory loss 
• gastrointestinal upset, 
• hair loss,  
• weakened nails, 
• white blotchy nails,  
• garlic breath odor, 
• metallic taste, 
• vomiting, 


 
22 
• sweat 
• dermatitis, 
• dental defects, 
• nervousness, 
• mental depression, 
•  fatigue, 
•  irritability, 
•  mild nerve damage, 
• Peripheral vascular collapse, 
• Internal vascular congestion, 
• Hemorrhage, 
• Congested and edemmatus lungs, 
• Brick-red color gastric mucosa 
• Coma 
• Death 
 
Some symptoms of Se toxicity are not specific to Se toxicity and would be difficult 
to monitor in a pediatric burn patient.  Additionally, blood and urine Se values will 
not be immediately available (being sent to an outside facility for analyses).  To 
assess for toxicity, hair and nails will be monitored weekly for loss, change of 
appearance, and brittleness.  Additionally, to ensure the safety of all patients, 
once every 2 weeks, blood samples will also be sent to the Massachusetts 
General Hospital Chemistry lab for analysis of selenium levels.  If the selenium 
level is greater than 100 ug/dL the patient will be immediately removed from the 
study. 
 
It is important to note that the IOM (31) state in their report that the UL does not 
apply to patients under medical supervision and that doses of Se above the UL 
should not be discouraged in clinical trials.  Se toxicity has not been reported in 
trials administering Se supplements to adults with doses up to 1500 ug per day 
(approximately 25 times the RDA) for short periods of time (1-3 weeks).   
 
 
VII. 
Potential Benefits 
 
This study will provide enhanced understanding of Se requirements during burn 
injury. 
 
 
VIII. 
Monitoring and Quality Assurance 
 
All subjects will be monitored for any treatment-related adverse events for 2 
weeks following discontinuation of the study therapy.  Ongoing adverse events 
thought to be study drug related will be followed until resolution or the condition 
stabilizes. Any adverse events will be reported to the Partners Human Research 
Committee per the guidelines.   


 
23 
 
 
Per FDA reporting requirements, serious and unexpected adverse experiences, 
as well as, unexpected fatal and life-threatening experiences related to this study 
will be reported to the FDA no later than 7 days after the initial receipt of the 
information.   A complete written report of the unexpected fatal or life-threatening 
experience will be provided to the FDA within 15 calendar days.   
 
According to the FDA, all “Expected” and “Unexpected” adverse events related to 
this study will be: (1) classified by relation to study treatment, severity, action 
taken in response to the adverse event, and clinical outcome; (2) collected and 
recorded in patient case report forms and adverse event datasets; and (3) 
reported to the Food and Drug Administration (FDA) 
 
An independent Data Safety Monitoring Board, consisting of 3 knowledgeable 
staff members, will meet 2 times per year to monitor the data for safety.  
Members include Carol Scott RN, MS; Derrick Hursey PharmD; Yong Ming Yu, 
MD, PhD. This board will perform the following duties: 
 
• Verify that the investigators have adequate qualifications. 
• Verify that the facilities are adequate to safely and properly conduct the 
trial. 
• Verify that the IV selenium is properly stored and expired drugs are not 
used. 
• Verify that the utilization of the IV selenium is properly documented. 
• Verify that all subjects enrolled in the study meet the inclusion criteria 
throughout the study. 
• Verify that written informed consent was obtained before each subject’s 
participation in the trial. 
• Verify that the approved protocol was followed. 
• Data safety monitoring (review accumulated data to ensure all current and 
future subjects are safe and to make sure that the study still has scientific 
merit).  All Adverse Events, and Serious Adverse Event reports will be 
discussed. 
• Verify that the study staff is adequately informed about the trial. 
• Verify that unauthorized individuals are not participating in the trial. 
• Verify that all research records and essential documents are accurate 
complete, up-to-date, and maintained. 


 
24 
• Verify that the PI provides all required reports, notifications, applications, 
and submissions to the FDA and the IRB (including adverse events, 
withdrawals) 
• The Board will provide a written report to the PI after each meeting.   
 
 
 
 
 


 
25 
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