Impact of Disease on Amikacin Pharmacokinetics and Dosing in Children.

BACKGROUND: Amikacin is widely used to treat severe Gram-negative bacterial infections. Its peak concentration in plasma is associated with treatment efficacy. Amikacin pharmacokinetics (PK) is influenced by disease conditions, in addition to other patient characteristics. In this retrospective study, we evaluated the impact of clinical characteristics and disease condition on amikacin PK in children with burn injuries and those with cancer. METHODS: Amikacin PK data from 66 children with burn injuries and 112 children with cancer were analyzed. A population PK model was developed using the nonlinear mixed-effects modeling approach. Models were developed using NONMEM 7.3 (ICON Development Solutions, LLC, Ellicott City, MD). Data processing and visualization was performed using R packages. RESULTS: The amikacin PK data were best described by a 2-compartment model. The parameters were estimated with mean values (95% confidence intervals) as follows: central volume of distribution (V1), 5.70 L (4.64-6.76 L); central clearance, 2.12 L/h (1.79-2.46 L/h); peripheral volume of distribution (V2), 4.79 L (2.36-7.22 L); and distribution clearance (Q), 0.71 L/h (0.25-1.16 L/h). The final model identified the disease condition as a significant covariate and indicated 55% (28%-82%) higher central clearance and 17% (1%-34%) higher V1 in burn patients compared with cancer patients. Volume of distribution was significantly influenced by age and body weight. Clearance was significantly influenced by age, body weight, and creatinine clearance. Using the final PK model, we developed a workflow for selecting optimal dosing strategies for 3 representative pediatric patient profiles. CONCLUSIONS: Disease condition was significant in influencing amikacin PK in children. To reach the same target concentrations (64 mg/L peak concentration) with a daily-dose plan, burn patients need higher doses than cancer patients. Future investigations are needed to explore the impact of other diseases on amikacin disposition in children, and to prospectively validate the proposed dosing strategy.

Application of a method used to deconstruct a single dose pharmacokinetic profile from multiple dose data.

With traditional non-compartmental methods, it is challenging to deconstruct plasma concentration versus time curves to assess the influence of individual doses. This study describes the application of a mathematical approach used to deconstruct a single dose curve using data derived from the second, third, fourth or nth dosing interval. Using data from a prospective clinical trial it is demonstrated that this approach reliably estimates pharmacokinetic parameters measured following two doses of zolpidem tartrate. Additionally, the study demonstrates the application of this approach using previously published data from a single- and multiple-dose pharmacokinetic study of the antibiotic gatifloxacin. Copyright © 2015 John Wiley & Sons, Ltd.

Zolpidem and Sleep in Pediatric Burn Patients with Attention Deficit/Hyperactivity Disorder.

Existing research shows that hospitalized patients, especially pediatric burn patients, are often sleep deprived. A pre-existing diagnosis of attention deficit/hyperactivity disorder (ADHD) further compounds a burn patient's inability to sleep. This retrospective study compared the effectiveness of zolpidem on patients with acute burns with ADHD (n = 23) and patients with acute burns without ADHD (n = 23). Effectiveness was defined based on the need for a change in the sleep medication or an increase in the zolpidem dose during the first 12 days of treatment. This study found that sleep dysfunction was similar in pediatric burn patients with and without a concurrent diagnosis of ADHD. Sixteen (69.6%) patients with and 13 (56.5%) patients without ADHD required a sleep medication change (p = 0.541). Further, while patients with ADHD required a sleep medication change (median = 5 days) sooner than those without ADHD (median = 9 days), it appears that zolpidem is not an effective drug for managing sleep in pediatric burn patients with or without ADHD.

Preliminary assessment of zolpidem pharmacokinetics in pediatric burn patients.

PURPOSE: Severely burned patients frequently experience sleep fragmentation and insomnia. This study evaluated the population pharmacokinetics of the sleep-enhancing agent zolpidem among burned children. METHODS: Zolpidem was administered according to the following age-based dosing schedule: 2.5 mg per dose for 2-4 year olds, 5.0 mg per dose for 5-10 year olds, and 10 mg per dose for older than 10 years. Serum samples were collected before and 1, 2, 4, 5, 6, and 8 hours after dosing. The population pharmacokinetic analysis modeled zolpidem concentrations using nonlinear mixed effects models. RESULTS: Eleven patients with a mean (±SD) age of 8.3 ± 4.0 years and a mean total burn surface area of 56% ± 22% were recruited. Seventy-three zolpidem concentrations were measured with a mean Cmax of 291 ± 140 ng/mL. A 2-compartment model with first-order absorption best described the data. Zolpidem clearance was estimated at 0.03 L·h(-1)·kg(-1) (relative standard error, 55%) and increased with body weight (P < 0.05). The central compartment volume of distribution was estimated at 0.05 L/kg (relative standard error, 25%), which was inversely related to the proportion of the body surface with third-degree burns (P < 0.001). CONCLUSIONS: A population pharmacokinetic model has been developed that reliably characterized the pharmacokinetic parameters of zolpidem when used as a sleep-enhancing agent among pediatric burn patients. Additional studies are needed to link this pharmacokinetic model with pharmacodynamic data, which may include an assessment of the effects of higher zolpidem doses and/or more frequent administration upon sleep architecture.

Composition and Performance of Autologous Engineered Skin Substitutes for Repair or Regeneration of Excised, Full-Thickness Burns.

Prompt and permanent wound closure after burn injuries remains a requirement for patient recovery. Historically, split-thickness skin autograft (STAG) has served as the prevailing standard of care for closure of extensive, deep burns. Because STAG availability may be insufficient in life-threatening burns, alternatives have been evaluated for safety and efficacy of wound closure. Since the 1970s, alternatives consisting of cultured epidermal keratinocytes, and/or acellular dermal substitutes were studied and translated into services and devices that facilitated wound closure, survival, and recovery after major burns. Cultured epithelial autografts (CEA) promoted epidermal closure of wounds but were not stable during long-term recovery. An acellular dermal substitute consisting of collagen and glycosaminoglycans (C-GAG) provided more uniform dermal repair, and reduced needs for epidermal harvesting but was subject to loss from microbial contamination. More recently, an autologous engineered skin substitute (ESS) has been reported and includes a C-GAG polymer populated with fibroblasts and keratinocytes which form basement membrane. ESS can be applied clinically over a vascularized dermal substitute and generates stable wound closure that is smooth, soft, and strong. Despite these advances, no current alternatives for permanent wound closure restore the anatomy and physiology of uninjured skin. Current alternatives act by mechanisms of wound healing, not by developmental biology by which skin forms in utero with pigment, hair, sweat and sebaceous glands, microvasculature, and nerve. Until full-thickness burns are restored with all of the normal structures and functions of uninjured skin, regenerative medicine of skin will remain an ambitious aspiration for future researchers and engineers to achieve.

Exploring the Past to Inform the Future to Optimize the Pharmacokinetics of Vancomycin in Children With Severe Burn Injuries.

Sepsis remains one of the leading causes of death among pediatric patients with burn injuries. Despite limited vancomycin pharmacokinetic (PK) information within this population, it is widely used to treat severe burn injuries. Those with severe burns are at risk of nephrotoxicity, with an incidence of acute kidney injury (AKI) over 50%. Delivering an effective vancomycin dose and avoiding unnecessary toxicity is essential for improved patient outcomes. This was a retrospective analysis of 115 children aged 0.2 months to 18 years with severe burns, >10% total body surface area. Vancomycin was given via intravenous infusion; blood samples were drawn between 6- and 12-hour postinfusion. A population pharmacokinetic model was developed using nonlinear mixed-effect modeling (Monolix, version 2016R1). A one-compartment model described a steady-state volume of distribution (V), dependent on weight. Vancomycin clearance (CL) was influenced by age and estimated creatinine clearance (CrCL). The study population's (median age = 4 years, median weight = 20 kg, median total body surface area (%TBSA) = 40%) median V and CL were calculated to be 1.25 L/kg (95% CI, 1.04-1.46) and 0.15 L/h/kg (95% CI, 0.126-0.165), respectively. The PK model was explicitly developed to characterize the impact of physiological changes in children under 18 years of age and the percentage of the burn surface area using limited data. The analysis determined that weight, age, and estimated CrCL were important covariates in predicting vancomycin PK with high variability in CL and V.

Development of a Differential Assessment Guide to Improve Engagement with Youths & Families Living with Chronic Trauma.

Youths and parents/caregivers who have experienced multiple forms of severe interpersonal trauma may demonstrate severe and persistent symptoms of complex trauma including high-risk behaviors. Engagement, and sustaining engagement, of these youths and parents/caregivers in evidence-supported trauma treatment is a critical challenge, especially when youths or parents/caregivers have experienced chronic traumas that may be expected to continue into the foreseeable future. An extensive literature review was conducted leading to development of an assessment framework that could increase engagement of youths and parents/caregivers in trauma treatment based on research on chronic trauma, complex trauma, Developmental Trauma Disorder (DTD), and factors that promote engagement. A multi-dimensional assessment guide was developed to enable clinicians to differentiate types of chronic trauma based on a continuum of past, current and expected exposure over time and then to use this guide collaboratively with youths and parents/caregivers to develop priorities for treatment and service planning that matches their needs and strengths. The assessment guide incorporates exposure to intra-familial and community forms of interpersonal trauma, attachment disruptions, established symptoms of PTSD, Complex PTSD and DTD, as well as social-emotional development. The assessment and treatment planning guides proposed in this article expand applicability of evidence-supported trauma-informed therapy to youths and families who have not been engaged by programs offering treatments that are focused on past or single incident traumas or do not address disrupted attachments, multi-generational experiences of adversity, discrimination and community violence, life-threatening dangers or the impact of chronic trauma on youth, parent/caregiver and family development.

Assessment of replication rates of human keratinocytes in engineered skin substitutes grafted to athymic mice.

Stable closure of skin wounds with engineered skin substitutes (ESS) requires indefinite mitotic capacity to generate the epidermis. To evaluate whether keratinocytes in ESS exhibit the stem cell phenotype of label retention, ESS (n = 6-9/group) were pulsed with 5-bromo-2'-deoxyuridine (BrdU) in vitro, and after grafting to athymic mice (n = 3-6/group). Pulse and immediate chase in vitro labeled virtually all basal keratinocytes at day 8, with label uptake decreasing until day 22. Label retention in serial chase decreased more rapidly from day 8 to day 22, with a reorganization of BrdU-positive cells into clusters. Similarly, serial chase of labeled basal keratinocytes in vivo decreased sharply from day 20 to day 48 after grafting. Label uptake was assessed by immediate chases of basal keratinocytes, and decreased gradually to day 126, while total labeled cells remained relatively unchanged. These results demonstrate differential rates of label uptake and retention in basal keratinocytes of ESS in vitro and in vivo, and a proliferative phenotype with potential for long-term replication in the absence of hair follicles. Regulation of a proliferative phenotype in keratinocytes of ESS may improve the biological homology of tissue-engineered skin to natural skin, and contribute to more rapid and stable wound healing.

Multimodal quantitative analysis of early pulsed-dye laser treatment of scars at a pediatric burn hospital.

BACKGROUND: The pulsed-dye laser (PDL) is a potential adjunctive therapy for treatment of hyperemic and hypertrophic scars. OBJECTIVE: To compare the effects of early PDL treatment plus compression therapy (CT) with those of CT alone in patients undergoing burn scar reconstruction with split-thickness grafts on an extremity. METHODS: Laser treatments were applied to one half of the graft seam. Standard CT was applied to both halves. Laser treatment was repeated at 6-week intervals until one half reached sufficient clinical improvements. Each half was evaluated just before treatments using quantitative measures of color, scar height, biomechanical properties and clinical features using the Vancouver Scar Scale (VSS). RESULTS: Less quantitative scar erythema and height and greater tissue elasticity were observed after two or three treatments for PDL plus compression than with compression alone. VSS scores showed greater improvement for vascularity, pliability, pigmentation, and height for PDL plus compression than for compression alone. CONCLUSION: PDL treatment in combination with CT appears to reduce scar hyperemia and height and normalize the biomechanical properties of burn-related scars.

Update on the critical care management of severe burns.

Care of the severely injured patient with burn requires correct diagnosis, appropriately tailored resuscitation, and definitive surgical management to reduce morbidity and mortality. Currently, mortality rates related to severe burn injuries continue to steadily decline due to the standardization of a multidisciplinary approach instituted at tertiary health care centers. Prompt and accurate diagnoses of burn wounds utilizing Lund-Browder diagrams allow for appropriate operative and nonoperative management. Coupled with diagnostic improvements, advances in resuscitation strategies involving rates, volumes, and fluid types have yielded demonstrable benefits related to all aspects of burn care. More recently, identification of comorbid conditions such as inhalation injury and malnutrition have produced appropriate protocols that aid the healing process in severely injured patients with burn. As more patients survive larger burn injuries, the early diagnosis and successful treatment of secondary and tertiary complications are becoming commonplace. While advances in this area are exciting, much work to elucidate immune pathways, diagnostic tests, and effective treatment regimens still remain. This review will provide an update on the critical care management of severe burns, touching on accurate diagnosis, resuscitation, and acute management of this difficult patient population.

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.

Energy requirements of pediatric patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

INTRODUCTION: The primary purpose of this study was to compare the measured resting energy requirements (MREE) of children with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) with that of children with burns of similar size. A secondary goal was to develop a predictive equation useful in estimating the energy of children with SJS/TEN. METHODS: This retrospective study included 30 patients admitted to our pediatric burn unit between 12/91 and 03/06. All patients were admitted within 10 days of injury and had at least 1 metabolic cart measurement. Fifteen patients with SJS/TEN comprised group 1. Group 2 consisted of 15 burn patients matched for total wound size, age, preinjury weight, and gender. Caloric intake and discharge weight (percent of preburn weight) were recorded. RESULTS: The energy needs of the SJS/TEN group were 22% less than the burn group. Correlation between MRE x 1.3 and caloric intake was 0.89 for the SJS/TEN group and 0.92 for the burn group (P < .0001). Both the SJS/TEN and burn groups were managed by nutrition goals based on the MREE x 1.3, and patients were 95.1% +/- 6.3% and 98.9% +/- 6% of preinjury weight at discharge, respectively, in each group. An equation for the estimation of energy requirements in pediatric SJS/TEN patients was statistically generated: (24.6 x weight in kg) + (% wound x 4.1) + 940. CONCLUSION: The energy requirement in pediatric SJS/TEN patients is less than that following burn injury. The application of a 30% factor to MREE is supported in SJS/TEN and thermal injury.

Development of clinical process measures for pediatric burn care: Understanding variation in practice patterns.

BACKGROUND: There has been little systematic examination of variation in pediatric burn care clinical practices and its effect on outcomes. As a first step, current clinical care processes need to be operationally defined. The highly specialized burn care units of the Shriners Hospitals for Children system present an opportunity to describe the processes of care. The aim of this study was to develop a set of process-based measures for pediatric burn care and examine adherence to them by providers in a cohort of pediatric burn patients. METHODS: We conducted a systematic literature review to compile a set of process-based indicators. These measures were refined by an expert panel of burn care providers, yielding 36 process-based indicators in four clinical areas: initial evaluation and resuscitation, acute excisional surgery and critical care, psychosocial and pain control, and reconstruction and aftercare. We assessed variability in adherence to the indicators in a cohort of 1,076 children with burns at four regional pediatric burn programs in the Shriners Hospital system. The percentages of the cohort at each of the four sites were as follows: Boston, 20.8%; Cincinnati, 21.1%; Galveston, 36.0%; and Sacramento, 22.1%. The cohort included children who received care between 2006 and 2010. RESULTS: Adherence to the process indicators varied both across sites and by clinical area. Adherence was lowest for the clinical areas of acute excisional surgery and critical care, with a range of 35% to 48% across sites, followed by initial evaluation and resuscitation (range, 34%-60%). In contrast, the clinical areas of psychosocial and pain control and reconstruction and aftercare had relatively high adherence across sites, with ranges of 62% to 93% and 71% to 87%, respectively. Of the 36 process indicators, 89% differed significantly in adherence between clinical sites (p < 0.05). Acute excisional surgery and critical care exhibited the most variability. CONCLUSION: The development of this set of process-based measures represents an important step in the assessment of clinical practice in pediatric burn care. Substantial variation was observed in practices of pediatric burn care. However, further research is needed to link these process-based measures to clinical outcomes. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients.

BACKGROUND: Hypovitaminosis D exists postburn. However, evidence-based guidelines for vitamin D repletion are unknown. This investigation examined differences between D2 and D3 supplementation on outcome in children with burn injuries. METHODS: Fifty patients with total body surface area burn of 55.7% ± 2.6% and full-thickness injury of 40.8% ± 3.8% were enrolled, ranging in age from 0.7-18.4 years. All participants received multivitamin supplementation per standardized clinical protocol. In addition, 100 IU/kg D2, D3, or placebo was administered daily during hospitalization using a randomized, double-blinded study design. Assay of total 25-hydroxyvitamin D (D25), 1,25-dihydroxyvitamin D (D1,25), 25-hydroxyvitamin D2 (25-OH-D2), 25-hydroxyvitamin D3 (25-OH-D3), and parathyroid hormone (PTH) was performed at 4 preplanned time intervals (baseline, midpoint, discharge, and 1 year postburn). Differences in vitamin D status were compared over time and at each specific study interval. RESULTS: There were no significant differences in serum vitamin D levels between groups, but >10% of patients had low D25 at discharge, and percent deficiency worsened by the 1-year follow up for the placebo (75%), D2 (56%), and D3 (25%) groups. There were no statistical differences in PTH or clinical outcomes between treatment groups, although vitamin D supplementation demonstrated nonsignificant but clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formation. CONCLUSIONS: The high incidence of low serum D25 levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D3 beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity.

Randomized, Paired-Site Comparison of Autologous Engineered Skin Substitutes and Split-Thickness Skin Graft for Closure of Extensive, Full-Thickness Burns.

Stable closure of full-thickness burn wounds remains a limitation to recovery from burns of greater than 50% of the total body surface area (TBSA). Hypothetically, engineered skin substitutes (ESS) consisting of autologous keratinocytes and fibroblasts attached to collagen-based scaffolds may reduce requirements for donor skin, and decrease mortality. ESS were prepared from split-thickness skin biopsies collected after enrollment of 16 pediatric burn patients into an approved study protocol. ESS and split-thickness autograft (AG) were applied to 15 subjects with full-thickness burns involving a mean of 76.9% TBSA. Data consisted of photographs, tracings of donor skin and healed wounds, comparison of mortality with the National Burn Repository, correlation of TBSA closed wounds with TBSA full-thickness burn, frequencies of regrafting, and immunoreactivity to the biopolymer scaffold. One subject expired before ESS application, and 15 subjects received 2056 ESS grafts. The ratio of closed wound to donor areas was 108.7 ± 9.7 for ESS compared with a maximum of 4.0 ± 0.0 for AG. Mortality for enrolled subjects was 6.25%, and 30.3% for a comparable population from the National Burn Repository (P < .05). Engraftment was 83.5 ± 2.0% for ESS and 96.5 ± 0.9% for AG. Percentage TBSA closed was 29.9 ± 3.3% for ESS, and 47.0 ± 2.0% for AG. These values were significantly different between the graft types. Correlation of % TBSA closed with ESS with % TBSA full-thickness burn generated an R value of 0.65 (P < .001). These results indicate that autologous ESS reduce mortality and requirements for donor skin harvesting, for grafting of full-thickness burns of greater than 50% TBSA.

A microbiologic study of enteral feeding hang time in a burn hospital: can feeding costs be reduced without compromising patient safety?

BACKGROUND: Procedural changes for hospitalized patients must always balance safety with fiscal constraints. Microbiologic contamination of enteral feeding solutions has been previously associated with nosocomial infections. Formula manipulation and hang time contribute to microbial load, and there is considerable variation in hang time recommendations in the medical literature. With cost containment in mind, the purpose of this performance improvement study was to determine if an increase in hang time of a modular tube feeding product would increase microbial load or affect the nosocomial infection rate in pediatric burn patients. METHODS: This biphasic trial initially evaluated the microbial load of the feeding after delivery of two 4-hour aliquots into a container using the same delivery set (total hang time of 8 hours; number of tests = 20). Second, once this feeding procedure was deemed microbiologically safe, tube feedings were administered to patients, and both microbial load and nosocomial infection rate were monitored for 1 year. RESULTS: Contamination levels at the end of the 8-hour period using the same feeding set with 2 consecutive 4-hour feeding aliquots (number of tests = 38) were lower than standard recommendations. The hospital's nosocomial infection rate was not altered by this procedural change, and feeding-set expenses were reduced. CONCLUSIONS: The hang time of our enteral feeding administration set can be increased safely from 4 hours to 8 hours, with the tube feeding preparation added as two 4-hour aliquots without a significant change in microbial load or nosocomial infection rate, thus promoting simultaneous fiscal responsibility and patient safety.

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.

Investigation of Bone Health Subsequent to Vitamin D Supplementation in Children Following Burn Injury.

BACKGROUND: The effect of supplemental vitamin D on fracture occurrence following burn injuries is unclear. The objective of this study was to evaluate postintervention incidence of fractures in children during the rehabilitative phase postburn (PB) following participation in a randomized clinical trial of vitamin D supplementation. MATERIALS AND METHODS: Follow-up for fracture evaluation was obtained in 39 of 50 patients randomized to daily enteral vitamin D2, D3, or placebo throughout the acute burn course. Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, D2, D3, calcitonin, and bone alkaline phosphatase (BAP) measurements were obtained PB day 7, midpoint, discharge, and 1-year PB. Urinary calcium was obtained PB day 7 and midpoint. Dual-energy x-ray absorptiometry (DXA) was performed at discharge and 1-year PB. RESULTS: Fractures were reported in 6 of 39 respondents. Four fractures occurred in the placebo group, 2 in the D2 group, and none in the D3 group. Serum vitamin D, calcitonin, BAP, and urinary calcium were similar between fracture groups. The group with fracture morbidity had larger burn size (83.8% ± 4.9% vs 53.0% ± 2.9%, P < .0001), greater full-thickness burn (69.7% ± 9.4% vs 39.4% ± 4.1%, P = .02), and increased incidence of inhalation injury (33% vs 6%, P = .04). Decreased bone mineral density z score was noted at discharge in the placebo fracture compared with no-fracture group (P < .05). CONCLUSION: This preliminary report suggests there may be benefit of vitamin D3 in reducing postdischarge fracture risk. Results reaffirm the importance of monitoring bone health in pediatric patients postburn.

Clinical safety and efficacy of probiotic administration following burn injury.

Provision of probiotics has been limited postburn by questionable potential for bacterial translocation and risk of infection in an immune-compromised population. The purpose of this study was to evaluate the safety of probiotic administration in acutely burned, pediatric patients. Subjects were randomized to receive probiotic (n = 10) vs placebo (n = 10) twice daily. The investigational product was initiated within 10 days of burn, and daily supplementation continued until wound closure. Nursing staff was provided education regarding optimal procedures to minimize potential for study product cross contamination. Clinical outcomes (infection, antibiotic, antifungal, and operative days, tolerance, and mortality) were recorded. Length of stay was modified for burn size. Student's t-test, χ test, and nonparametric Wilcoxon's rank-sum test were used for comparative analysis. No differences were noted (probiotic; placebo) for age (7.1 ± 2.2; 6.9 ± 1.7), burn size (38.0 ± 5.9; 45.5 ± 4.45), full thickness (24.6 ± 5.6; 32.1 ± 5.4), postburn day admit (0.8 ± 0.4; 1.1 ± 0.4), or inhalation injury (10%; 20%). Infection days, antibiotic use, constipation, and emesis were similar between groups. Trends toward increased antifungal and laxative use as well as diarrhea incidence were evident in the controls (P < .30). Flatulence was statistically higher with probiotics. The control group trended toward higher requirement for excision/graft procedure. Medical length of stay was not significantly different between groups; however, time required to complete wound healing was shortened with probiotics. This study documents safety and provides preliminary efficacy data relative to probiotic supplementation postburn.