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.

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.

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.

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.

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.

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.

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.

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.

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.

Determination of Optimal Amikacin Dosing Regimens for Pediatric Patients With Burn Wound Sepsis.

This study aimed to develop optimal amikacin dosing regimens for the empirical treatment of Gram-negative bacterial sepsis in pediatric patients with burn injuries. A pharmacodynamic (PD) target in which the peak concentration (Cmax) is ≥8 times the minimum inhibitory concentration (MIC) (Cmax/MIC ≥ 8) is reflective of optimal bactericidal activity and has been used to predict clinical outcomes. Population pharmacokinetic modeling was performed in NONMEM 7.2 for pediatric patients with and without burn injuries. Amikacin pharmacokinetic parameters were compared between the two groups and multiple dosing regimens were simulated using MATLAB to achieve the PD target in ≥90% of patients with burn injuries. The pharmacokinetic analysis included 282 amikacin concentrations from 70 pediatric patients with burn injuries and 99 concentrations from 32 pediatric patients without burns. A one-compartment model with first-order elimination described amikacin pharmacokinetics well for both groups. Clearance (CL) was significantly higher in patients with burn injuries than in patients without (7.22 vs 5.36 L/h, P < .001). The volume of distribution (V) was also significantly increased in patients with burn injuries (22.7 vs 18.7 L, P < .01). Weight significantly influenced amikacin CL (P < .001) and V (P < .001) for both groups. Model-based simulations showed that a higher amikacin dose (≥25 mg/kg) achieved a Cmax/MIC ≥8 in ≥90% of patients with assumed infections of organisms with an MIC = 8 mg/L. Amikacin pharmacokinetics are altered in patients with burn injuries, including a significant increase in CL and V. In simulations, increased doses (≥25 mg/kg) led to improved PD target attainment rates. Further clinical evaluation of this proposed dosing regimen is warranted to assess clinical and microbiological outcomes in pediatric patients with burn wound sepsis.

Relationship between zolpidem concentrations and sleep parameters in pediatric burn patients.

Zolpidem is a short-acting non-benzodiazepine hypnotic that is used to improve sleep architecture in patients with burn injuries. This study evaluated the relationship between zolpidem administration and sleep parameters in a cohort of children with severe burn injuries. Standard age-based zolpidem dosing practices were employed. Polysomnography data were recorded at 30-second intervals throughout the night. Serum concentrations of zolpidem were measured at 0, 1, 2, 4, 5, 6, and 8 hours after administration of the first dose. The relationship between zolpidem concentrations and sleep parameters was evaluated using Markov mixed-effects pharmacodynamic models. Ten children received two doses of zolpidem at 22:00 and 02:00 hours. The median total amount of sleep was 361.0 (interquartile range [IQR]: 299.0-418.5) minutes; approximately 65% of the normal reference value for an 8-hour period. Slow-wave and rapid eye movement (REM) sleep were also dramatically reduced (18-37% of normal). With two doses of zolpidem, stage 2 sleep was 99% of normal levels. Higher peak zolpidem concentrations were associated with increased stage 2 sleep (r = .54; P = .04). Despite this, a median of 120.0 (IQR: 99.5-143.5) transitions between nocturnal sleep stages were recorded, with a median of 55.5 (IQR: 36-75) night-time awakenings per patient. In pediatric burn patients, higher zolpidem serum concentrations were associated with restoration of stage 2 sleep to normal levels. Nonetheless, slow-wave and REM sleep were profoundly depressed with frequent transitions between sleep stages, suggesting that alternative hypnotic agents may be required to restore normal sleep architecture in severely burned children.

The effect of diphenhydramine on sleep in pediatric burn patients: a secondary analysis.

Adequate sleep is essential for maintaining homeostasis, especially when recovering from an illness; however, studies have shown that sleep disruption and sleep deprivation are common in intensive care unit patients, including children who have sustained burn injury. The purpose of this study was to evaluate the effect of diphenhydramine (DPH) on sleep in pediatric intensive care unit burn patients using Myra Levine's Conservation Model as the organizing framework. For this study, secondary analysis of polysomnography data and retrospective chart review were used. Twelve DPH patients were pair matched in terms of morphine, midazolam, and methadone with 12 non-DPH patients. The data were analyzed using paired t-tests for each dependent variable and χ analysis was used for frequency determinations. There was no difference in demographics between the two groups. DPH patients took 4.3 ± 1.6 minutes to fall asleep whereas non-DPH patients took 15.8 ± 1.6 minutes to achieve sleep onset (P = .06). Patients receiving DPH achieved 297.6 ± 29.9 minutes of total sleep time whereas those not receiving DPH achieved only 209.2 ± 29.9 minutes (P < .05). There was minimal difference in the mean percentage of sleep time in stages 3 and 4 between the two groups. The DPH group did have 50% more rapid eye movement sleep time compared with the non-DPH group. Even though DPH did not result in a statistical improvement in sleep quality, sleep quantity was increased in this study. More research is needed to find an effective sleep intervention in pediatric burn patients.

Trends in bacterial wound isolates and antimicrobial susceptibility in a pediatric burn hospital.

The purpose of this retrospective study was to collate data dealing with organisms cultured from the burn patients and evaluate trends in antimicrobial susceptibility. All cultures collected from each acute admission patient between 2004 and 2011 in the 30-bed pediatric burn hospital were evaluated for their annual frequency and antimicrobial susceptibility. Duplicate cultures were excluded. Staphylococcus aureus was isolated most frequently (25% of total isolates; range, 69-408 isolates/yr), followed by Pseudomonas aeruginosa (13%; range, 40-202 isolates/yr), coagulase-negative staphylococci (9%; range, 2-188 isolates/yr), Enterobacter cloacae (8%; range, 22-128 isolates/yr), and Escherichia coli (6%; range, 19-91 isolates/yr). This rank order remained relatively consistent during the period of study. The emergence of methicillin-resistant S. aureus increased from 20% in 2004 to about 45% in 2009 to 2011. Susceptibility to vancomycin was still 100%. In comparing periods 2004 to 2007 and 2008 to 2011, P. aeruginosa showed increased susceptibility to cefepime (from 76% to 84%) and the aminoglycosides (from 68% to 81%), whereas susceptibility to piperacillin-tazobactam remained high (from 91% to 93%). E. cloacae demonstrated 90 to 100% susceptibility to aminoglycosides, cefepime, and imipenem. E. coli showed an increased rate of resistance to ceftazidime but was still susceptible to imipenem and amikacin. S. aureus and P. aeruginosa continue to be the most prevalent organisms cultured from our pediatric burn population. Almost half of the staphylococcal isolates were methicillin-resistant S. aureus. Despite widespread use of piperacillin-tazobactam, P. aeruginosa susceptibility remained high. Several classes of antimicrobials continued to demonstrate good to excellent activity against the majority of organisms cultured from the burn patients.

Long-term posttraumatic stress symptoms vary inversely with early opiate dosing in children recovering from serious burns: effects durable at 4 years.

BACKGROUND: Children surviving serious burns are at risk for developing posttraumatic stress disorder (PTSD) as a function both of the injury and of its treatment. Short-term studies in such children have demonstrated reduced PTSD symptoms with intensive early pain control. However, the long-term impact of early pain control strategies on posttraumatic stress symptoms in children recovering from serious burn injuries has not been examined. METHODS: This was a retrospective review of a multiple time point data collection involving a cohort of 147 infants, children, and teenagers with 4 years of follow-up after serious burns conducted at 4 pediatric burn centers to examine the impact of early opiate dosing on long-term posttraumatic stress symptoms. The main outcome measure was the nine-item Short Form Child Stress Disorders Checklist, which is an established and validated assessment. The impact of total opiate dosing during the first 7 days on these scores was assessed. RESULTS: Subjects had an average age of 11 years and average injury size of 22% total body surface area burned (%TBS). The correlation between opiate units (OUs) and %TBS was 0.46 at baseline, OU increasing with increasing %TBS. OUs were strongly predictive of Child Stress Disorders Checklist scores up to 4 years, with higher OU (10 units vs. 6 and 2 units) remaining constantly different up to 4 years in predicting lower stress scores for both smaller and larger burns. CONCLUSION: Early opiate management of pain associated with acute burn wounds and burn treatment predicts the development and resolution rate of PTSD symptoms in a large multicenter sample of children hospitalized for serious burns. The effect seems to be dose related and durable at least up to 4 years in a range of burn sizes. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level II.

A performance improvement initiative to determine the impact of increasing the time interval between changing centrally placed intravascular catheters.

Existing practice guidelines designed to minimize invasive catheter infections and insertion-related complications in general intensive care unit patients are difficult to apply to the burn population. Burn-specific guidelines for optimal frequency for catheter exchange do not exist, and great variation exists among institutions. Previously, the authors' practice was to follow a new site insertion at 48 hours by an exchange over a guidewire, which was followed 48 hours later by a second guidewire exchange (48h group). As a performance improvement initiative, the authors attempted to determine whether there would be any advantage or disadvantage to extending these intervals to 72 hours (72h). All patients with centrally placed intravascular catheters from October 2007 to August 2008 were included in the 48h group, and all patients with catheters placed from September 2008 to December 2009 comprised the 72h group. Catheter infection rates were determined using the National Healthcare Safety Network definition for central line-associated bloodstream infections (CLABSIs) and calculated as CLABSIs/1000 catheter days. The two groups were not significantly different for age, sex, burn etiology, total burn size, or percent third-degree burn. There were 3.1 CLABSIs/1000 catheter days for the 48h group and 2.8 CLABSIs/1000 catheter days for the 72h group (NS). The authors conclude that increasing the central catheter change interval from 48 to 72 hours did not result in any increase in their CLABSI rate. Implementation of this change in practice is expected to decrease supply costs by $28,000 annually in addition to reducing clinical support services needed to perform these procedures.

Amish burn ointment and burdock leaf dressings: assessments of antimicrobial and cytotoxic activities.

Amish burn wound ointment (ABO) contains honey, lanolin, oils, glycerin, bees wax, and other natural additives. Although there are many anecdotal reports that this ointment covered with a burdock leaf (BL) dressing promotes burn wound healing, little scientific testing of this treatment has occurred. The goal of this study was to evaluate in vitro some of the components of this treatment modality for antimicrobial and cytotoxic activities. The ABO was tested for sterility using standard microbiological techniques. Because of the semisolid, lipid-based nature of the salve, the at-use product could not be tested in bioassays. Samples of BL and the dry ingredients (DI) used in the ointment were provided by the Amish vendor. Aqueous extracts of the DI and of the BL were prepared and freeze dried. The freeze-dried extracts were reconstituted, filtered, and tested separately on keratinocyte and fibroblast cell cultures for cytotoxicity (growth inhibition assay) and against a panel of susceptible and resistant microbes for antimicrobial activity (Nathan's agar-well diffusion assay) in a series of concentrations (% wt/vol). Neither DI nor BL extracts demonstrated antimicrobial activity against any of organisms tested. The DI extract inhibited growth of both keratinocytes and fibroblasts at the 0.1% concentration. The 0.1 and 0.03% concentrations of the BL extract were cytotoxic to both keratinocytes and fibroblasts. Although tests for microbial growth from the at-use preparation of the ABO were negative, extracts of the DI and BL did not demonstrate any antimicrobial activity. Additionally, both extracts inhibited the growth of skin cells in vitro at higher concentrations. These results suggest caution in the use of ABO and BL dressings if there is more than a minimal risk of complications from the burn injury.

Amikacin population pharmacokinetics among paediatric burn patients.

INTRODUCTION: The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates. METHODS: Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10-20mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis. RESULTS: The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean Cmax was 33.2±9.4µg/mL and the mean Cmin was 3.8±4.6µg/mL. The final covariate model estimated clearance as 5.98L/h/70kg (4.97-6.99, 95% CI), the volume of distribution in the central compartment as 16.7L/70kg (14.0-19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1L/70kg (15.0-80.4, 95% CI), and the inter-compartmental clearance as 3.38L/h/70kg (2.44-4.32, 95% CI). In multivariate analyses, current weight (P<0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics. DISCUSSION: Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.