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.

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.

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.

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.

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.

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.

Grease fryers: a significant danger to children.

Scald injuries in children often occur as the result of them pulling a container of hot liquid off a countertop or stove. To date, there have been no studies that have specifically examined the impact of the burning agent after this mechanism of injury on the magnitude of injury or the hospital resources consumed in caring for these patients. In this study, we sought to compare the extent and depth of injury, hospital resources consumed, and outcomes of children burned by pulling a container of grease or other liquid onto themselves. We retrospectively reviewed all cases of children who were admitted to our pediatric burn center from January 1995 through December 2001 who sustained scald injuries as the result of pulling a container of hot liquid onto himself or herself. Patients were evaluated for extent TBSA burned, depth of injury, the need for skin grafts, and the number of ventilator, days in the intensive care unit, and total hospital days (length of stay). We identified 196 children admitted with scald injuries caused by this mechanism. Fifty-four (27.6%) were caused by grease or oil, and 142 (72.6%) were caused by other liquids. The mean age of children burned by this mechanism was approximately 3 years, and slightly more than half were males. The mean TBSA and full-thickness burn was 18.3% and 8.1% for the grease group and 14.4% and 4.5% for the no-grease group, respectively (P <.05). Fifty-six percent of those children burned with grease required skin grafting compared with only 34% of those burned by other liquids. Twenty percent of the patients burned by grease required ventilator support compared with only 6.3% of those burned by other liquids (P <.01). Of those burned by grease, 22.2% required care in the intensive care unit compared with only 6.3% of those burned by other liquids (P <.005). Mean length of stay was 16.8 +/- 2.5 days and 9.1 +/- 1.0 days for the grease and nongrease groups, respectively (P <.001). Scalds caused by children pulling a grease fryer onto themselves result in more extensive and deeper injuries and greater consumption of hospital resources than those from other liquids. These findings support the need for safer product design and more specific warnings in product labeling and instructions as to the danger of severe scald injury to minimize the occurrence of such injuries.