An evaluation of the neuroendocrine response to sleep in pediatric burn patients.

INTRODUCTION: Previous work demonstrated reduced stage 3+4 and rapid eye movement (REM) sleep following burn injury. This study evaluated the hormonal effects of drug intervention on measures of endocrine status. A secondary objective examined the relationship between hormones and sleep stage distribution. METHODS: Forty patients 3-18 years of age with a mean percent total body surface area burn of 50.1 +/- 2.9 were randomly assigned to zolpidem or haloperidol utilizing a blinded crossover design. Polysomnography was performed 6 nights, 3/week over 2 weeks. Each week's first night of monitoring was conducted without medication, serving as a baseline. Hormonal levels (epinephrine, norepinephrine, growth hormone, melatonin, dehydroepiandrosterone [DHEA], serotonin, cortisol) were obtained at 0600 h each study day. RESULTS: Both drugs were associated with increased DHEA levels (P < .03); no other hormones were affected by medication. Significant inverse correlation was observed between REM sleep and epinephrine (r = -.34, P = .004) and norepinephrine levels (r = -.45, P = .02). A positive relationship existed between serotonin and sleep stage 3+4 (r = 0.24, P = .01) and REM (r = 0.48, P = .01). No other significant associations were identified between hormones and sleep. CONCLUSIONS: This work characterizes the relationship between sleep deprivation and select endocrine parameters postburn. Drug interventions utilized in this study were either ineffective or insufficient in modulating improved hormonal response. Significance of zolpidem's and haloperidol's effect on serum levels of DHEA is unclear. The inverse correlation of epinephrine with REM may suggest that hypermetabolism associated with burns is partly due to lack of REM sleep. Questions remain regarding the effects of sleep deprivation on metabolism and clinical outcome.

Are topical antimicrobials effective against bacteria that are highly resistant to systemic antibiotics?

An increasing number of bacteria are resistant to multiple systemic antibiotics. The purpose of this study was to determine if topical antimicrobials are still effective against multi-drug resistant organisms (MDROs). MDROs, including Acinetobacter, Pseudomonas, Klebsiella, Staphylococcus, and Enterococcus, were collected from four burn hospitals. The sensitivity of 47 MDROs to 11 commonly used topical agents (mafenide acetate, nystatin, mafenide + nystatin, silver nitrate, Dakin's, polymyxin B, neomycin, polymyxin + neomycin, silver sulfadiazine, bacitracin, silver sulfadiazine + bacitracin) was tested using the agar well diffusion assay and compared with the sensitivity of 27 non-MDROs of similar genera. Overall 88% of the tests of the non-MDROs showed susceptibility to the topicals compared with 80% for the MDROs (P < .05). Specific findings included: all of the gram-positive non-MDROs were sensitive to bacitracin compared with only 67% of the MDROs (P < .05); 74% of the non-MDROs were sensitive to neomycin vs 26% of the MDROs (P < .01). Even for the susceptible isolates, the zones of inhibition were smaller for the MDROs than for the non-MDROs (P < .002), indicating decreased susceptibility of the MDROs. Specifically, while the MDRO Acinetobacter were sensitive to most of the topicals, the zones of inhibition for silvadene, silvadene + bacitracin, neomycin, and neomycin + polymyxin were significantly smaller (P < .001) for the Acinetobacter MDROs than the non-MDROs. Although many topicals are still effective against some MDROs, MDROs are more resistant to topicals than are non-MDROs. Some treatment assumptions based historically on the efficacy of topical antimicrobial agents against non-MDROs need to be re-evaluated for MDROs.

An 18-year experience in the management of congenital nevomelanocytic nevi.

BACKGROUND: Children with giant congenital nevomelanocytic nevi (CNN) are referred to our pediatric burn center for the surgical management of this disfiguring and potentially malignant skin disorder. Use of tissue expanders has contributed significantly in limiting donor site morbidity associated with treatment of giant CNN. Cultured skin substitutes (CSS) have also shown promise as an alternative wound coverage. With recent controversy regarding the effectiveness of excision in preventing melanoma risk, we wished to review our surgical management of giant CNN and to determine the incidence of malignancy in these patients. METHODS: A retrospective chart review of patients with giant CNN was performed from 1985 to 2003. Charts were reviewed for age, sex, percentage total body surface area (TBSA) involved, age at initiation and completion of treatment, surgical treatment, complications, histopathology, and length of follow-up. RESULTS: Of the 40 patients treated at our facility, the mean extent of skin involvement was 10% TBSA (range: 0.5%-75%). The mean age at initial operation was 5.1 years, and the majority of surgical interventions were completed within a mean of 1.3 years. Twenty-two patients (55%) required more than 1 surgical procedure. Excision and split-thickness skin grafting was the most common surgical procedure (n = 22) followed by excision with primary closure (n = 18). Ten patients were treated with tissue expansion, while 4 received cultured skin replacements. One patient died of extracutaneous melanoma during the course of surgical treatment. Three patients demonstrated histopathologic evidence of cytoatypia but remained clinically free of malignancy during a mean follow-up of 11 years. CONCLUSIONS: Giant CNN are both important cosmetic and medical problems. With an associated lifetime risk of melanoma in 4%-10% of patients, excision of CNN is recommended despite the fact that 50% of melanomas arise extracutaneously. Depending on the extent of body surface area involvement, wound closure can be obtained with conventional split- or full-thickness skin grafts, tissue expansion, and/or cultured autologous cultured skin substitutes. The latter 2 modalities provide improved cosmetic results, with minimal donor site morbidity.

A randomized, controlled prospective trial of zolpidem and haloperidol for use as sleeping agents in pediatric burn patients.

Children with burn injuries often require hospital treatment where they are subjected to stimuli likely to produce sleep deprivation. Previously demonstrated sleep fragmentation and significantly reduced sleep stage 3/4 and rapid eye movement in this population led to a search for sleep-enhancing interventions. The purpose of this study was to evaluate the effects of selected therapeutic interventions on sleep architecture. Forty patients with a mean (+/-SEM) age of 9.4 +/- 0.7 years, mean total burn surface area of 50.1 +/- 2.9% and full thickness burns of 43.2 +/- 3.6% were randomly assigned to one of two treatment regimens using a blinded crossover design. Continuous polysomnographic recordings were obtained for six study periods. Each patient alternately received zolpidem one week and haloperidol the next, with the first monitored night conducted without medication. Zolpidem minimally increased the proportion of 3/4 and rapid eye movement sleep (0.81 +/- 0.16 vs 0.61 +/- 0.10 hrs, P = .02) but not total sleep time (4.8 +/- 0.3 vs 4.3 +/- 0.3 hrs on control nights, P = .1). Haloperidol significantly increased total sleep (5.3 +/- 0.3 vs 4.3 +/- 0.3 hrs on control nights, P = .02) and stage 2 sleep (3.3 +/- 0.3 vs 2.4 +/- 0.2 hrs, P = .001) compared with control nights. Both drugs slightly improved average sleep and wake period duration compared with control nights. Although sleep was somewhat improved by each test drug, there were no statistically significant differences between the drugs. Additional studies are needed to identify methods for improving restorative sleep postburn.

Cultured skin substitutes reduce requirements for harvesting of skin autograft for closure of excised, full-thickness burns.

BACKGROUND: Rapid and effective closure of full-thickness burn wounds remains a limiting factor in burns of greater than 50% of the total body surface area (TBSA). Hypothetically, cultured skin substitutes (CSS) consisting of autologous cultured keratinocytes and fibroblasts attached to collagen-based sponges may reduce requirements for donor skin, and morbidity from autograft harvesting and widely-meshed skin grafts. METHODS: To test this hypothesis, CSS were prepared from split-thickness skin biopsies collected after enrollment of 40 burn patients by informed consent into a study protocol approved by the local Institutional Review Boards of three participating hospitals. CSS and split-thickness skin autograft (AG) were applied in a matched-pair design to patients with full-thickness burns involving a mean value of 73.4% of the TBSA. Data collection consisted of photographs, area measurements of donor skin and healed wounds after grafting, qualitative outcome by the Vancouver Scale for burn scar, and biopsies of healed skin. RESULTS: Engraftment at postoperative day (POD) 14 was 81.5 +/- 2.1% for CSS and 94.7 +/- 2.0 for AG. Percentage TBSA closed at POD 28 was 20.5 +/- 2.5% for CSS, and 52.1 +/- 2.0 for AG. The ratio of closed to donor areas at POD 28 was 66.2 +/- 8.4 for CSS, and 4.0 +/- 0.0 for each harvest of AG. Each of these values was significantly different between the graft types. Correlation of percent TBSA closed with CSS at POD 28 with percent TBSA full-thickness burn generated an r value of 0.37 (p < 0.0001). Vancouver Scale scores at 1 year after were not different for erythema, pliability, or scar height, but pigmentation remained deficient in CSS. CONCLUSIONS: These results demonstrate that CSS reduce requirements for donor skin harvesting for grafting of excised, full-thickness burns of greater than 50% TBSA with qualitative outcome that is comparable to meshed AG. Availability of CSS for treatment of extensive, deep burns may reduce time to wound closure, morbidity, and mortality in this patient population.

Surgical treatment of hidradenitis suppurativa: a 10-year experience.

BACKGROUND: Hidradenitis suppurativa (HS) is a disease of the apocrine sweat glands resulting in chronic wounds with abscesses, sinuses, and fibrosis. Because many patients referred for treatment have both recurrent and progressive disability, we attempted to determine which factors have the greatest impact on outcome so we could develop an operative treatment algorithm. METHODS: We identified 57 patients with HS who underwent operative treatment for chronic recurrent HS from January 1994 through December 2003. Charts were reviewed for demographic, treatment, and outcome data. RESULTS: The mean age at presentation was 34 years and the average duration of symptoms was 6.7 years. Two thirds of the patients had undergone 1 or more incision and drainage procedures and 90% had received long-term antibiotic therapy. Axillary involvement was present in 88% of women and was bilateral in half of all patients. Inguinoperineal involvement was present in 87% of men and was bilateral in 92% of all patients. An algorithm for operative treatment was developed based on the extent of involvement, chronicity, and comorbid conditions. Ninety-two operative procedures were performed, 50% involved the axilla, 36% involved the perineum, and 14% involved the inguinal region. Excision and primary closure was used for localized disease; wide excision with or without skin grafting was used for diffuse disease. CONCLUSIONS: HS is a chronic relapsing disease that frequently causes disabling pain, diminished range of motion, and social isolation. Definitive treatment involves operative excision of the involved apocrine tissue and should be individualized based on the stage and location of the disease.

Evaluation of cytotoxicity and antimicrobial activity of Acticoat Burn Dressing for management of microbial contamination in cultured skin substitutes grafted to athymic mice.

Cultured skin substitutes (CSS) have become a useful adjunctive treatment for closure of burn wounds, but CSS are avascular and remain susceptible to microbial destruction longer than split-thickness skin grafts. Irrigation of CSS grafted to burn wounds with a topical antimicrobial solution (TAS) has been shown to promote engraftment of CSS, but TAS usage has potential limitations. Acticoat Burn Dressing (Acticoat; Westaim Biomedical, Exeter, NH) is a silver-coated barrier dressing reported to exhibit antimicrobial activity and to reduce infection in partial-thickness and full-thickness wounds. This study evaluated the cytotoxicity of Acticoat with CSS and the efficacy of Acticoat for the management of microbial contamination in CSS grafted to full-thickness wounds in athymic mice. The cytotoxicity of Acticoat was assessed in preliminary studies after 1 week of exposure to CSS during in vitro maturation or healing on wounds in athymic mice. Histologies were analyzed and cellular viability in the CSS was determined by MTT conversion on days 0, 1, and 7 of Acticoat exposure. At 1, 2, 3, and 4 weeks after grafting, wounds were traced, and areas of healing CSS were calculated by image analysis. At 4 weeks, wound biopsies were evaluated and scored for engraftment of human cells. In a subsequent study, wounds were inoculated with strain SBI-N of Pseudomonas aeruginosa at 1 x 10(5) cfu/wound before the application of CSS or inoculated onto the surface of Acticoat. At 4 weeks, swab cultures were collected from the surface of CSS and scored for the presence of SBI-N. Statistical significance was accepted at the 95% confidence level (P <.05). The data show that exposure in vitro of CSS to Acticoat was cytotoxic within 1 day, but 1 week of exposure in vivo did not injure CSS or inhibit wound healing. Contaminated wounds treated with Acticoat healed similarly to control treatments, with comparable rates of engraftment, and detection of SBI-N on the surface of only one graft. No SBI-N was detected on CSS after inoculation onto the surface of Acticoat. These results suggest that Acticoat may be suitable as a protective dressing to reduce environmental contamination of CSS, if used in conjunction with additional antimicrobials to control organisms present in the wound.

Protein breakdown in muscle from burned rats is blocked by insulin-like growth factor i and glycogen synthase kinase-3beta inhibitors.

We reported previously that IGF-I inhibits burn-induced muscle proteolysis. Recent studies suggest that activation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway with downstream phosphorylation of Forkhead box O transcription factors is an important mechanism of IGF-I-induced anabolic effects in skeletal muscle. The potential roles of other mechanisms in the anabolic effects of IGF-I are less well understood. In this study we tested the roles of mammalian target of rapamycin and glycogen synthase kinase-3beta (GSK-3beta) phosphorylation as well as MAPK- and calcineurin-dependent signaling pathways in the anticatabolic effects of IGF-I by incubating extensor digitorum longus muscles from burned rats in the presence of IGF-I and specific signaling pathway inhibitors. Surprisingly, the PI3K inhibitors LY294002 and wortmannin reduced basal protein breakdown. No additional inhibition by IGF-I was noticed in the presence of LY294002 or wortmannin. Inhibition of proteolysis by IGF-I was associated with phosphorylation (inactivation) of GSK-3beta. In addition, the GSK-3beta inhibitors, lithium chloride and thiadiazolidinone-8, reduced protein breakdown in a similar fashion as IGF-I. Lithium chloride, but not thiadiazolidinone-8, increased the levels of phosphorylated Foxo 1 in incubated muscles from burned rats. Inhibitors of mammalian target of rapamycin, MAPK, and calcineurin did not prevent the IGF-I-induced inhibition of muscle proteolysis. Our results suggest that IGF-I inhibits protein breakdown at least in part through a PI3K/Akt/GSK3beta-dependent mechanism. Additional experiments showed that similar mechanisms were responsible for the effect of IGF-I in muscle from nonburned rats. Taken together with recent reports in the literature, the present results suggest that IGF-I inhibits protein breakdown in skeletal muscle by multiple mechanisms, including PI3K/Akt-mediated inactivation of GSK-3beta and Foxo transcription factors.

Hypovitaminosis D in acutely injured pediatric burn patients.

PROBLEM: The prevalence of vitamin D insufficiency, its etiology, and associated sequelae among acutely injured burn patients is unknown. OBJECTIVE: This study assessed vitamin D and endocrine status, as well as the effect of anabolic agents, in pediatric patients who had sustained burns in excess of 25% total body surface area (TBSA). SUBJECTS: Sixty-nine patients with a mean TBSA burn of 50.6+/-2.2% (range 27% to 94%) and full thickness injury of 41.3+/-3.0% (range 0% to 94%) were studied. Subjects ranged in age from 0.6 to 18 years (mean, 5.8+/-0.6 years). Main outcome measures Blood samples were obtained for serum 25-hydroxyvitamin D (D25), 1,25-dihydroxyvitamin D (D1,25), albumin, cortisol, triiodothyronine (T3), tetraiodothyronine (T(4)), thyroid stimulating hormone (TSH), and parathormone (PTH). RESULTS: Two hundred eighty morning blood samples of D25 and D1,25 demonstrated that 45% and 26.2% were low and 8.9% and 11% were very low, respectively. At least one low D25 or D1,25 level occurred in 62.3% of all subjects. Very low levels were noted in 23.2% of all patients. There was an increased incidence of hyperparathyroidism in patients with very low serum D25. Vitamin D25 and D1,25 levels were lower in subjects with larger burns or inhalation injury, as well as those treated with thyroxine or oxandrolone. Serum albumin, cortisol, T(4), and TSH were not correlated with concentration of vitamin D. CONCLUSIONS: Demonstration of a high incidence of low serum vitamin D indicates vitamin D status may be significantly compromised in burned children. It is unclear why vitamin D deficiency exists in this population. The most effective way to improve vitamin D status remains elusive at this time.

Rapid monitoring by quantitative polymerase chain reaction for pathogenic Aspergillus during carpet removal from a hospital.

Monitoring for pathogenic Aspergillus species using a rapid, highly sensitive, quantitative polymerase chain reaction technique during carpet removal in a burn unit provided data that allowed patients to be safely returned to the refloored area sooner than if only conventional culture monitoring had been used.

Procalcitonin in pediatric burn patients: an early indicator of sepsis?

To determine whether changes in procalcitonin (PCT) could be used to predict the onset of sepsis, daily PCT levels were monitored in 20 burned children. Analysis indicated a PCT rise of 5 ng/ml or greater as the best indication of sepsis. We compared the surgeons' determination of sepsis, which was based on changes in platelet count, C-reactive protein (CRP), and other clinical manifestations, with the prediction of sepsis from PCT. There were 26 septic episodes and 36 nonseptic episodes in the 20 patients. PCT results were classified as to true positives, false positives, true negatives, and false negatives. As an indicator of sepsis, the PCT assay had a sensitivity of 42%, a specificity of 67%, and an efficiency of 57%. Even when the assay correctly identified sepsis, the determination was made an average of 0.8 days after the surgeon had already made the diagnosis based on CRP and/or platelet count. We conclude that PCT is not as effective as CRP and/or platelet count in the early detection of sepsis in burned children.

Insulin-like growth factor-I blocks dexamethasone-induced protein degradation in cultured myotubes by inhibiting multiple proteolytic pathways: 2002 ABA paper.

In previous studies, insulin-like growth factor-I (IGF-I) inhibited glucocorticoid-induced muscle protein breakdown, but the intracellular mechanisms of this effect of IGF-I are not well understood. The purpose of the present study was to test the hypothesis that IGF-I inhibits multiple proteolytic pathways in dexamethasone-treated cultured L6 myotubes. Myotubes were treated with 1 microM dexamethasone for 6 hours in the absence or presence of 0.1 microg/ml of IGF-I. Protein degradation was determined by measuring the release of trichloroacetic acid-soluble radioactivity from proteins prelabeled with 3H-tyrosine. The contribution of lysosomal, proteasomal-dependent, and calpain-dependent proteolysis to the inhibitory effect of IGF-I on protein degradation was assessed by using inhibitors of the individual proteolytic pathways (methylamine, beta-lactone, and E64, respectively). In addition, the influence of IGF-I on cathepsin B, proteasome, and calpain activities was determined. Treatment of L6 myotubes with dexamethasone resulted in an approximately 20% increase in protein degradation. This effect of dexamethasone was completely blocked by IGF-I. When the different protease inhibitors were used, results showed that IGF-I inhibited lysosomal, proteasomal-dependent, and calpain-dependent proteolysis by 70, 44, and 41%, respectively. Additionally, IGF-I blocked the dexamethasone-induced increase in cathepsin B, proteasome, and calpain activities. The present results suggest that IGF-I inhibits glucocorticoid-induced muscle proteolysis by blocking multiple proteolytic pathways.

Home oxygen therapy: adjunct or risk factor?

The use of home oxygen therapy has become increasingly commonplace and is frequently prescribed by medical specialists. In this study, we have identified a generally unexpected risk of home oxygen therapy. We performed a retrospective review of 3673 consecutive patients treated at our adult burn center over a 10-year period from 1992 to 2001. We identified 27 patients with burns directly attributable to oxygen therapy and also noted an increased incidence of these injuries over the study period. The average age of the patients was 68.1 +/- 9.2 years (range, 40-82 years). Twenty-three were using oxygen at home, three in nursing homes, and one was an inpatient in an acute care facility. Twenty-five patients (93%) were receiving oxygen therapy for the diagnosis of chronic obstructive pulmonary disease. Twenty-four patients (89%) were smoking while using oxygen, two were lighting pilot lights, and one was lighting his wife's cigarette. Four patients (15%) sustained burns greater than 10% TBSA. Seventeen patients (63%) had only partial thickness burns. Thirteen patients (48%) required admission for treatment of their burn injuries. The average length of stay for those admitted was 4.4 days. The average hospital charge for admitted patients was US dollars 8055. There were four deaths (15%), all of which were correlated only with the extent of injury. Although intuitively obvious to most health care professionals, not all patients understand that oxygen therapy and cigarettes or open flame can result in a significant injury. Although some practitioners have advocated not prescribing home oxygen for those who continue to smoke, an alternative means of reducing the incidence of this preventable complication appears warranted. Prevention efforts should focus on the counseling of patients and their caregivers as well as educating primary care physicians, nurses, and home health providers as to the dangers of oxygen use.

Four-year review of burns as an etiologic factor in the development of long bone fractures in pediatric patients.

Reduced bone density has been documented in children after burns. This loss of bone may place children at heightened risk for fractures. The medical records of all acutely injured patients with burns in excess of 40% TBSA burn admitted to our institution between January 1, 1997, through December 31, 2000, were reviewed for fracture incidence. Patients with fractures sustained during the course of initial trauma were not included in the review. One hundred four records were reviewed. These patients had a mean age of 6.7 +/- 0.51 years, (range, 0.2 to 18.0) and a mean %TBSA burn of 59.9 +/- 1.60 (range, 40 to 98) with a mean full-thickness %burn of 51.7 +/- 2.16 (range, 0 to 95). Fifteen long bone fractures were documented in six patients during the review time frame. All fractures were initially suspected by physical therapy personnel upon regularly scheduled therapy sessions and subsequently verified by x-ray. All fractures identified by this review occurred in children less than 3 years of age. Most fractures were noted during the rehabilitation phase of injury (range, 73 to 283 days after burn) once wounds were more than 95% healed, except for one child, who sustained multiple fractures during the acute recovery phase at a referring hospital. A 5.8% incidence of fractures was noted in patients with burns in excess of 40% (6 of 104 admissions). The etiology of the fractures is unknown, although the hormonal milieu postburn, depressed vitamin D status, inadequate protein intake, and decreased weight-bearing activity are potential contributory factors. In addition, infants and toddlers tend to provide more resistance to therapy because of an inherent lack of cognition. This may account for the increased breaks in this population.

Multicenter postapproval clinical trial of Integra dermal regeneration template for burn treatment.

The safety and effectiveness of Integra Dermal Regeneration Template was evaluated in a postapproval study involving 216 burn injury patients who were treated at 13 burn care facilities in the United States. The mean total body surface area burned was 36.5% (range, 1-95%). Integra was applied to fresh, clean, surgically excised burn wounds. Within 2 to 3 weeks, the dermal layer regenerated, and a thin epidermal autograft was placed. The incidence of invasive infection at Integra-treated sites was 3.1% (95% confidence interval, 2.0-4.5%) and that of superficial infection 13.2% (95% confidence interval, 11.0-15.7%). Mean take rate of Integra was 76.2%; the median take rate was 95%. The mean take rate of epidermal autograft was 87.7%; the median take rate was 98%. This postapproval study further supports the conclusion that Integra is a safe and effective treatment modality in the hands of properly trained clinicians under conditions of routine clinical use at burn centers.

The 2002 Clinical Research Award. An evaluation of the safety of early vs delayed enteral support and effects on clinical, nutritional, and endocrine outcomes after severe burns.

Early enteral support is believed to improve gastrointestinal, immunological, nutritional, and metabolic responses to critical injury; however, this premise is in need of further substantiation by definitive data. The purpose of this prospective study was to examine the effectiveness and safety of early enteral feeding in pediatric patients who had burns in excess of 25% total body surface area. Seventy-seven patients with a mean percent total body surface area burn of 52.5 +/- 2.3 (range 26-91), percent full thickness injury of 44.7 +/- 2.8 (range 0-90), and age ranging from 3.1 to 18.4 (mean 9.3 +/- 0.5) were randomized to two groups: early (feeding within 24 hours of injury) vs control (feeding delayed at least 48 hours postburn). Nutrient intake was measured daily, indirect calorimetry was performed biweekly, and blood and urine samples were obtained for the assay of cortisol, glucagon, insulin, gastrin, epinephrine, norepinephrine, dopamine, triiodothyronine, tetraiodothyronine, albumin, transferrin, prealbumin, retinol-binding protein, glucose, nitrogen balance, and 3-methylhistidine throughout the study period. Three protocol violations occurred, and two patients were transferred to another hospital; these patients were excluded from the study. No patient in either group experienced tube feeding aspiration. No differences were evident in infection, diarrhea, hospital length of stay, or mortality outcomes. A higher incidence of reportable adverse events coincided with early feeding (22 vs 8%), but this was not statistically significant. The delayed feeding group demonstrated a significant caloric deficit during postburn week (PBW) 1 (P <.0001) and PBW2 (P =.0022). Serum insulin (P =.0004) and triiodothyronine (P =.0162) were higher in the early fed group during PBW1. A decrease in 3-methylhistidine output (suggesting a decrease in protein breakdown) was also evident during PBW1 (P =.0138). No other significant trends in study outcome variables were noted. In conclusion, provision of enteral nutrients shortly after burn injury reduces caloric deficits and may stimulate insulin secretion and protein retention during the early phase postburn. These data, however, do not necessarily reaffirm the safety of early enteral feeding, nor do they associate earlier feeding with a direct improvement in endocrine status or a reduction in morbidity, mortality, hypermetabolism, or hospital stay. Future studies are needed to establish precise feeding implementation times that maximize clinical benefit while minimizing morbidity in the critically injured burn patient.