The oral/enteral route of supplementation is preferable to the parenteral route in most burn patients as it maintains the trophism of the gastrointestinal tract. It promotes the release of intestinal hormones and growth factors, directly nourishes the gastrointestinal tract, and may help reverse the defective gut barrier accompanying burn shock. For these reasons, the oral/enteral route is associated with a decrease in morbidity and mortality in the adult burn population [
Additionally, enteral nutrition allows the administration of more balanced and individualized nutritional support. Not only is it associated with lowering infection complications by eliminating catheter contamination, but it is also less costly than parenteral nutrition [
In the prognosis of burn patients, the time when nutritional enteral support is started is also paramount. In animal studies, early initiation of enteral feeding decreased high catabolic responses, as well as preventing malnutrition and hypotrophic changes of the gut [
In a patient with a poor nutritional status, nonthyroidal illness syndrome (NTIS), or euthyroid sick syndrome (ESS), has to be considered. The most common feature of ESS is low-T3 syndrome.
Low-T3 syndrome is frequently observed during caloric restriction, after surgery and after myocardial infarction [
Recent studies have shown that ESS is a prognostic indicator of worse outcomes, not only in critically ill patients, but also in burn patients [
Although the American Burn Association practice guidelines state that enteral feedings should be initiated as soon as practical, there is no consensus among physicians concerning the best time to initiate oral/enteral nutrition. Currently, the decision is based on haphazard and subjective criteria developed around the clinical status of the patient. We think this lack of cohesive criteria could result in a longer hospitalization, and a more severe case of ESS or T3 drop. For this reason, we decided to investigate the influence of delayed initiation of oral/enteral nutrition in thyroid hormone levels and the length of hospitalization.
The information was compiled from clinical histories gathered from the databases of burn patients in Birmingham (Alabama, USA) and Córdoba (Córdoba, Spain) from January 2000 to December 2009. We were looking for patients who fit the inclusion criteria and we grouped them in 3 groups according to the first initiation of oral/enteral nutrition after the burn injury: Group 1 (<24 h), Group 2 (24–48 h), and Group 3 (>48 h).
The chart review was performed by a trained plastic surgeon with long standing experience in chart reviews.
152 burn patients (93 from Birmingham and 59 from Cordoba) from January 2000 to December 2009 met the inclusion criteria and were selected for our study. All of them survived their injuries. The inclusion criteria were as follows: no preexisting thyroid disease or use of thyroid medications, patients with partial and full thickness burns ranging from 5–20% TBSA (total body surface area), patients under intensive glucose control, age >18 and ≤50 years, no electrical, chemical, or burn associated with major trauma or serious illness, no presence of inhalation injury, Curreri formula applied for the nutrition of the patient, patients that ingested this formula calories prescribed per day, no administration of parenteral nutrition, no administration of dopamine or corticosteroids, samples analyzed over the time with the same thyroid method described ahead for each hospital, and at least two complete thyroid analytical determination at both 2–5 days and 9–12 days after the burn injury. If a patient received more than one thyroid analytical determination during that period, we calculated the mean of those measurements for the collection and analysis of the data.
We considered a minimum of 5% TBSA and a maximum of 20% TBSA, as this was the size threshold capable of being treated at the burn unit of the University Hospital of Reina Sofia.
We did not include people under 18 years of age since the ethics committee from UAB did not permit it.
It was not necessary to obtain the authorization of an ethics committee from the University Hospital of Reina Sofia as this was a retrospective study that fulfilled all the terms this institution considered necessary to be excluded from such obligation. Those terms are as follows: the privacy and confidentiality of the patients will be guaranteed, no contact will be made with patients during or after completion of study, all data will be stored on password-protected institutional computers, and no money compensation granted to the research or ownership interest. For the American arm of the study we applied for and received authorization from the institutional review board (IRB) of the University of Alabama at Birmingham (protocol number: X100615005).
Patient anonymity was preserved in both arms of the study.
On arrival at the burn center, a thorough evaluation was performed and a treatment plan was developed. A thorough history of the burn was obtained, which included the location of the injury, type of agent involved in the burn, duration of exposure to the agent, as well as details of the patient’s other comorbidities. The TBSA was calculated and fluids, analgesia, tetanus vaccine, gastrointestinal protection, and subcutaneous heparin were administered.
When calculating TBSA, we only included those areas of partial and full-thickness dermal injury (2° and 3° degree). Superficial burns involving only the epidermis were not included in the calculation. The rule of nines was the most frequent method used for calculating the extent of the burn as it is the most familiar. The fluid resuscitation formula during the first 24 hours following burn injury was the Parkland Formula [
At the conclusion of the first 24 hours, we continued fluids to achieve a goal urine output of at least 30 cc/hr until the patient initiated oral tolerance and we considered it clinically indicated to discontinue fluids.
The administration of fixed amounts of energy to critically ill burn patients based on standardized equations or on the preestablished range of 167–188 kJ/kg day [
Patients received a high protein diet with at least 2 grams of protein per kilogram per day and were supplemented with polyvitamins, minerals, vitamins A, C, and zinc.
The caloric and protein intake was increased by the daily intake of high calorie protein shakes. The minimum number of shakes ingested by each patient was calculated by the hospital nutritionist. From that minimum shakes the patient could consume as many shakes as he wanted to ingest.
At least 2 blood samples (weekly measurement) were collected from each patient after admission to the burn center according to the inclusion criteria: at 2–5 days and 9–12 days after the burn injury.
For the American arm of the study serum fT3, fT4, and TSH levels were measured by chemiluminescent microparticle immunoassay (Architect System, Abbott Laboratories, Diagnostics Division, Abbott Park, IL 60064, USA). Normal ranges in the laboratory were fT3 2.15–4.91 pg/mL; fT4 0.85–1.52 ng/dL; TSH 0.31–4.92 mIU/L.
For the Spanish arm of the study, chemiluminescence (ADVIA Centaur, Bayer Diagnostics) was used to measure serum fT3 (fT3, normal 1.71–3.71 pg/mL), fT4 (fT4, normal 0.70–1.48 ng/dL), and TSH (normal 0.35–4.94 mIU/L).
Both hospital laboratories guaranteed that the hormonal determinations were not affected by serum albumin levels, nonesterified fatty acids, or thyroid binding globulin for these laboratory tests described but not for the tests previously used. These lab tests were validated and implemented in the American arm of the study in 2006 and in the Spanish arm in 2008. For this reason, the samples prior to these dates were not included in this study.
We studied nonthyroid parameters (Table
Nonthyroid parameters.
Parameters | Group 1 | Group 2 | Group 3 | Overall mean | *Significance |
---|---|---|---|---|---|
1st sample collection (days) |
|
|
|
|
*
|
2nd sample collection (days) |
|
|
|
|
*
|
Age (18–50 years old) |
|
|
|
|
*
|
TBSA |
|
|
|
|
*
|
LHS |
|
|
|
|
*
|
Sex: male/female | 0.75/0.25 | 0.76/0.24 | 0.80/0.20 | 0.76/0.24 |
*
|
|
71 (53/18) | 46 (35/11) | 35 (28/7) |
Thyroid parameters.
Groups: parameters | 2–5 days after | Duncan | 9–12 days after | Duncan |
---|---|---|---|---|
USA 2.15–4.91 pg/mL | USA 2.15–4.91 pg/mL | |||
fT3 reference interval | SPAIN 1.71–3.71 pg/mL | SPAIN 1.71–3.71 pg/mL | ||
Mean 1.98–4.44 pg/mL | Mean 1.98–4.44 pg/mL | |||
| ||||
USA 2.42 ± 0.16 pg/mL | A | USA 2.76 ± 0.20 pg/mL | A | |
Group 1: fT3 | SPAIN 1.86 ± 0.22 pg/mL | A | SPAIN 2.40 ± 0.23 pg/mL | A |
Mean 2.20 ± 0.20 pg/mL | A | Mean 2.62 ± 0.21 pg/mL | A | |
| ||||
USA 2.31 ± 0.17 pg/mL | B | USA 2.57 ± 0.15 pg/mL | B | |
Group 2: fT3 | SPAIN 1.82 ± 0.21 pg/mL | B | SPAIN 1.95 ± 0.20 pg/mL | B |
Mean 2.12 ± 0.19 pg/mL | B | Mean 2.33 ± 0.17 pg/mL | B | |
| ||||
USA *1.63 ± 0.19 pg/mL | C | USA 2.27 ± 0.16 pg/mL | C | |
Group 3: fT3 | SPAIN *1.26 ± 0.23 pg/mL | C | SPAIN 1.83 ± 0.20 pg/mL | C |
Mean *1.49 ± 0.21 pg/mL | C | Mean 2.10 ± 0.18 pg/mL | C | |
| ||||
USA 0.85–1.52 ng/dL | USA 0.85–1.52 ng/dL | |||
fT4 reference interval | SPAIN 0.70–1.48 ng/dL | SPAIN 0.70–1.48 ng/dL | ||
Mean 0.79–1.50 ng/dL | Mean 0.79–1.50 ng/dL | |||
| ||||
USA 1.20 ± 0.20 ng/dL | A | USA 1.27 ± 0.14 ng/dL | A | |
Group 1: fT4 | SPAIN 0.85 ± 0.30 ng/dL | A | SPAIN 1.10 ± 0.18 ng/dL | A |
Mean 1.07 ± 0.25 ng/dL | A | Mean 1.21 ± 0.16 ng/dL | A | |
| ||||
USA 1.18 ± 0.17 ng/dL | A | USA 1.26 ± 0.8 ng/dL | A | |
Group 2: fT4 | SPAIN 0.83 ± 0.22 ng/dL | A | SPAIN 1.07 ± 0.13 ng/dL | A |
Mean 1.04 ± 0.19 ng/dL | A | Mean 1.19 ± 0.10 ng/dL | A | |
| ||||
USA 1.14 ± 0.10 ng/dL | A | USA 1.25 ± 0.10 ng/dL | A | |
Group 3: fT4 | SPAIN 0.80 ± 0.16 ng/dL | A | SPAIN 1.05 ± 0.14 ng/dL | A |
Mean 1.01 ± 0.13 ng/dL | A | Mean 1.17 ± 0.12 ng/dL | A | |
| ||||
USA 0.31–4.92 mIU/L | USA 0.31–4.92 mIU/L | |||
TSH reference interval | SPAIN 0.35–4.94 mIU/L | SPAIN 0.35–4.94 mIU/L | ||
Mean 0.33–4.93 mIU/L | Mean 0.33–4.93 mIU/L | |||
| ||||
USA 4.13 ± 0.18 mIU/L | A | USA 3.05 ± 0.15 mIU/L | A | |
Group 1: TSH | SPAIN 4.15 ± 0.24 mIU/L | A | SPAIN 3.10 ± 0.21 mIU/L | A |
Mean 4.14 ± 0.21 mIU/L | A | Mean 3.07 ± 0.18 mIU/L | A | |
| ||||
USA 4.21 ± 0.14 mIU/L | A | USA 3.08 ± 0.18 mIU/L | A | |
Group 2: TSH | SPAIN 4.10 ± 0.20 mIU/L | A | SPAIN 3.12 ± 0.23 mIU/L | A |
Mean 4.17 ± 0.17 mIU/L | A | Mean 3.08 ± 0.21 mIU/L | A | |
| ||||
USA 4.27 ± 0.6 mIU/L | A | USA 3.14 ± 0.07 mIU/L | A | |
Group 3: TSH | SPAIN 4.06 ± 0.15 mIU/L | A | SPAIN 3.17 ± 0.14 mIU/L | A |
Mean 4.19 ± 0.10 mIU/L | A | Mean 3.15 ± 0.10 mIU/L | A |
The non-thyroid parameters considered were (Table
The study included 152 patients. Table
Having in mind that different fT3 and fT4 assays may report significantly different results, the major concern for this study was the justification for combining results from different assays for fT3 and fT4 depending on the time and the hospital laboratory where the samples were analyzed. For this reason, the results in thyroid parameters for both hospitals during the 3 measurements were compared separately, inside each hospital. As there were no significant differences in both arms of the study for all the parameters examined (
The results in thyroid parameters (Table
As we show in Table
We can see in Table
Low serum total T3 is the most common abnormality in ESS. It can be observed in about 70% of hospitalized patients [
Mechanisms in the pathogenesis of ESS are not yet well understood. Increased levels of endogenous or exogenous glucocorticoids [
Although at the second period collection, the fT3 levels were higher in all the groups comparing with the first period. The lowest levels in fT3 for both periods were in Group 3 and the highest in Group 1. Despite this quantifiable drop in fT3, ESS was present just at the first period determination in Group 3, but there was no group with ESS one week later. Maybe the delayed initiation of oral/enteral nutrition in our patients was not long enough to generate a long-term ESS. Based on our findings, we suggest that early initiation of oral/enteral nutrition may diminish the effects of the pathological mechanisms, previously explained, in the pathogenesis of ESS in burn patients.
Moreover, there were not any deaths in any group. We think this could be due to the inclusion criteria applied; specifically the fact that the severity of injury in the patients assessed was not very high (TBSA
Recent studies in the paediatric burn population have shown a relationship between later initiation of enteral nutrition and a worsened prognosis [
The American Burn Association practice guidelines state that enteral feedings should be initiated as soon as practical. Thus, Mosier et al. after their findings, advocate that initiation of enteral nutrition by 24 hours should be used as a formal recommendation in nutrition guidelines for severe burns, and that nutrition guidelines should be actively disseminated to individual burn centers to permit a change in practice [
Our results show that burn patients should have to be fed as soon as possible, preferably in the first 24 hours, since it is a cheap measure that would reduce the catabolic changes induced by the burn state and the fasting added, in addition to improve the patient's condition and prognosis, represented by a shorter length of hospital stay. Nevertheless, we have to consider as a limitation of the study that only patients with a modest severity of burns were included in this study. As fasting, itself, can result in the nonthyroidal illness syndrome, even in normal individuals and is rapidly reversed by eating, the decline in thyroid hormone levels in the population of burn patients selected for this analysis may have been primarily due to their nutritional status rather than to the burn injury, itself. Or maybe there was an additive catabolic effect of the fasting and the burn injury, in spite of the fact that it was not severe. Accordingly, the mechanism for nonthyroidal illness in the population of patients selected in this study may not actually be pathological as we suggested, but a normal, physiological, compensatory mechanism. With more severe burn injury, the mechanism for the decline in thyroid function may be much more complicated and under these circumstances, may be seen as pathological. It would be of interest to know whether early nutritional support rapidly recovers thyroid hormone levels in patients with more severe burn injury.
Another potential limitation of the study is that the second measurement was obtained relatively late (mean
In conclusion, our results point to a decrease in duration of hospitalization with the early initiation of oral/enteral nutrition, as well as a decrease in fT3 serum concentration depression. By doing so, early oral/enteral nutrition counteracts ESS and improves the short-term prognosis of burn patients.
This paper contains original material. Neither the paper nor any part of its essential substance has been or will be published elsewhere before appearing in this journal. No financial support or benefits have been received by me or any coauthor, by any member of my (our) immediate family or any individual or entity with whom or with which I (we) have a relationship from any commercial source which is related directly or indirectly to the scientific work which is reported here.
The authors gratefully acknowledge the help of Maclenan Ph.D., for assisting for IRB review of the research.