The safety and efficacy of parenteral nutrition among pediatric patients with burn injuries.

OBJECTIVE: Although enteral nutrition is the ideal mode of nutritional support following burn injury, it is often interrupted during episodes of severe sepsis and hemodynamic instability, leading to significant energy and protein deficits. Parenteral nutrition is not commonly used in burn centers due to concerns that it will lead to hyperglycemia, infection, and increased mortality. However, parenteral nutrition is often utilized in our burn unit when goal rate enteral nutrition is not feasible.To determine the safety and efficacy of a standardized protein-sparing parenteral nutrition protocol in which glucose infusion is limited to 5-7 mg/kg/hour. DESIGN: Retrospective observational study. SETTING: Pediatric burn hospital. PATIENTS: A retrospective medical record review of all children admitted to our hospital with burns ≥ 30% total body surface area was conducted. Only patients admitted within one week of injury and who survived > 24 hours after admission were included in this study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 105 patients who met the inclusion criteria, 96 (91%) received parenteral nutrition or a combination of parenteral nutrition and enteral nutrition at some point during their care. Nine patients received only enteral nutrition. Demographic data were similar between groups. Protein intake was significantly higher in the parenteral nutrition group. Incidence of catheter-related blood infections did not differ between groups. Use of parenteral nutrition was not associated with blood or respiratory infections. Overall mortality rate was low (4%), as most patients (96%) achieved wound closure and were discharged home. CONCLUSIONS: Judicious use of parenteral nutrition is a safe and effective means of nutritional support when goal enteral nutrition cannot be achieved. A hypocaloric, high-nitrogen parenteral nutrition solution can reduce energy and protein deficits while minimizing complications commonly associated with parenteral nutrition usage.

Evaluating Burn Recovery Outcomes in Children With Neurodevelopmental Symptoms.

Neurodevelopmental symptoms (NS) including attention and behavioral problems, developmental delays, intellectual disabilities, and learning problems are prevalent in children with burn injuries. The presence of NS may predispose children to poorer burn injury recovery outcomes compared to children without these symptoms (non-NS). The Multicenter Benchmarking Study (MCBS) monitored recovery outcomes in children with burn injuries in real time using the Burn Outcomes Questionnaire (BOQ). The objective of this study was to retrospectively assess the long-term burn recovery outcomes in NS patients vs non-NS patients from the MCBS population. This study assessed parent-reported BOQ outcomes in a sample of 563 patients aged 5 to 18 years who were admitted for burn injuries to a pediatric burn center. A subsample of patients had reported NS (n = 181). Analyses compared BOQ outcomes within the NS subsample and the non-NS subsample (n = 382) across three longitudinal points postdischarge. The prevalence rate of NS was 32.1% in the full sample. Findings revealed statistically significant improvement in the recovery curves in all five BOQ subscales for the non-NS group and all subscales except for Compliance for the NS group across all longitudinal points. When compared to non-NS patients, NS patients had significantly poorer burn recovery outcomes on the Satisfaction and Compliance subscales. Although it is important to educate all clinicians, parents, and children on burn prevention efforts, targeted education is necessary for children with NS because they may be at greater risk for burn injury as well as worse recovery outcomes.

Specific patterns of vital sign fluctuations predict infection and enable sepsis diagnosis in pediatric burn patients.

Early recognition of the clinical signs of bloodstream infection in pediatric burn patients is key to improving survival rates in the burn unit. The objective of this study was to propose a simple scoring criteria that used readily available temperature, heart rate (HR) and mean arterial pressure (MAP) data to accurately predict bloodstream infection in pediatric burn patients. A retrospective chart review included 100 patients admitted to the pediatric burn unit for >20% total body surface area (TBSA) burn injuries. Each patient had multiple blood culture tests, and each test was treated as a separate and independent "infection event" for analysis. The time at each blood culture draw was time 0 for that event, and temperature, HR and MAP data was collected for 24 hours after the blood culture was drawn. "Infection events" included in this study had at least six complete sets of temperature, HR and MAP data entries. Median temperature, HR and MAP, as well as mean fever spikes, HR spikes and MAP dips, were compared between infection group (positive blood cultures) and control group (negative blood cultures). These vital sign fluctuations were evaluated individually and as a combination of all three as timely predictors of bloodstream infection. In addition, we tested the prediction of Gram-negative bacteria versus Gram-positive or fungi present in blood cultures. Patients in the infection group had significantly higher median temperatures (p<0.001), mean fever spikes (p<0.001) and mean HR spikes (p<0.001), compared to the control group. Using the combination scoring criteria to predict bloodstream infection, the strongest predictive values in the 24-hour timeframe had high sensitivity (93%) and specificity (81%). The predictive test metric based on vital sign spikes predicted Gram-negative bacteria, but with limited sensitivity (57%) and specificity (44%). A simple scoring criteria using a combination of fever spikes, HR spikes and MAP dips predicted bloodstream infection in pediatric burn patients, and can be feasibly implemented in routine clinical care. There is also potential to use the predictive metric to detect a few select organisms based on vital signs, however further work is necessary to enhance accuracy to levels that would allow consideration for clinical use.

Reconstruction of the Upper Extremity High-Voltage Electrical Injury: A Pediatric Burn Hospital's 13-Year Experience.

High-voltage electrical injury is a rare yet destructive class of burn injury that persists as a serious public health issue. High-voltage exposure is commonly associated with complex wounds to the upper extremities, which can be a significant challenge for burn and plastic surgeons to reconstruct. This intensive and multistage reconstructive process is especially difficult in the growing child. Maximizing upper extremity function is a top priority, as it can have a significant impact on a patient's quality of life. Therefore, the purpose of this retrospective review was to describe lessons learned during a 13-year experience at a specialized pediatric burn hospital with reconstruction of the upper extremity after severe high-voltage injury in 37 children. We found that adherence to the following principles can help promote meaningful functional recovery. These include 1) frequent assessment during early acute care for the evolving need of decompression or amputation; 2) serial surgical debridement that follows a tissue-sparing technique; 3) wound closure by skin grafting or use of flaps (particularly groin or abdominal pedicled flaps) when deep musculoskeletal structures are involved; 4) early multidisciplinary intervention for contracture prevention and management, including physical and occupational therapy, splinting, and fixation; 5) reconstructive care that focuses on the simplest possible techniques to repair chronic skin defects such as laser therapy, local tissue rearrangements, and skin grafting; 6) complex reconstruction to address deeper tissue contractures or tendon and peripheral nerve deficits; and 7) amputation with preservation of growth plates, tissue transfer, and long-term prosthetic management when limb salvage is unlikely.

Appearance Concerns, Psychosocial Outcomes, and the Feasibility of Implementing an Online Intervention for Adolescents Receiving Outpatient Burn Care.

The current study assessed the prevalence of appearance concerns, psychosocial difficulty, and use of an appearance-focused social and psychological support resource (Young Person's Face IT; YPF) within a population of teens (12-17 year-olds) receiving outpatient burn care with the goal to assess the feasibility of routine use of the resource in outpatient burn care. The study sample included 78 patients ages 12 to 17 receiving outpatient care for burns at one hospital. Appearance concerns were measured via the Burn Outcomes Questionnaire Appearance Subscale, the Appearance Subscale of the Body Esteem Scale for Adolescents, and a 2-part question which asked participants directly about appearance concerns related to the burn injury. A large majority (70.0%) of study participants reported appearance concerns on at least one appearance measure and girls reported more burn-related appearance concerns compared with boys. Psychosocial difficulty was measured via the Pediatric Symptom Checklist-17 (PSC-17) and measures of social functioning were collected and compared within the sample by burn size, burn location, sex, and appearance concerns. Internalizing symptoms were prevalent on the PSC-17 (18.6% risk) and decreased self-worth and increased social anxiety symptoms were significantly associated with having appearance concerns. Although interest in YPF was high (78.3%), actual use of the resource among those who signed up to pilot it (n = 46 participants) was low (19.4% use). Results indicate that there is a need for and interest in appearance-focused social anxiety resources for adolescents with burn injuries such as YPF, but more research is needed to understand its feasibility in clinical practice.

The selenium status of pediatric patients with burn injuries.

BACKGROUND: Dietary selenium (Se) requirements during critical illness are not well known. The objective of this study was to assess the longitudinal Se status of pediatric patients with burns. METHODS: Twenty patients admitted to our hospital with burns exceeding 10% of their total body surface area were studied longitudinally during the first 8 weeks of admission or until 95% wound closure was achieved. Dietary Se intake was calculated daily, and plasma and urine samples were collected weekly for analyses of plasma Se, urinary Se, and glutathione peroxidase activity. RESULTS: Patients included in this study were individuals with an average age of 6.5 years ± 5.3 years and with burn injury of a mean total body surface area of 42% ± 21%. Dietary Se intake throughout the study (mean = 60 µg/d ± 39 µg/d) was consistent with established standards for healthy children and did not change throughout the study. Plasma Se (mean = 1.08 µmol/L ± 0.34 µmol/L) and plasma glutathione peroxidase (mean = 3.2 U/g protein ± 1.42 U/g protein) were below reported normal values for healthy American children. Mean urinary Se excretion (65.9 µg/L ± 50 µg/L) exceed dietary Se intake. Plasma Se was inversely related to incidence of total infection (p = 0.04). CONCLUSIONS: Results from this study indicate that Se status is depressed among pediatric patients with burns and that recommended Se intake for healthy children is likely insufficient for this population. Further studies are necessary to elucidate the amount of dietary Se required to maximize Se stores among pediatric patients with burn injuries.

Specific Patterns of Postoperative Temperature Elevations Predict Blood Infection in Pediatric Burn Patients.

Using readily available temperature data, we seek to propose a scoring criteria that can facilitate accurate and immediate prediction of blood infection. The standard in diagnosing blood infection is a positive blood culture result that may take up to 3 days to process, requiring providers to make a prediction about which febrile patient is actually bacteremic. This prediction is difficult in burned children as systemic inflammation can cause fever in the absence of infection. An ability to make this prediction more accurate using readily available information would be useful. A retrospective chart review was performed for 28 pediatric patients, with a burn size 20% or greater, admitted to the burn unit between 2010 and 2014. All children had blood cultures drawn. They were divided into either infection (positive blood cultures) or control (negative blood cultures) groups. Median temperature and mean number of temperature elevations were compared between the two groups. We evaluated the predictive accuracy of using temperature elevation, pattern, and timing to predict blood infection. A significant difference was seen in the mean number of temperature elevations above 39°C. This was significant for each time stage, especially in the 0- to 24-hour post-surgery period. We found the most predictive accuracy in the 0- to 12-, 12- to 38-, and 12- to 48-hour time periods. We found a strong association between mean number of fever spikes above 39°C and blood infection, especially 12 to 24 hours after surgery. This readily available data can be useful to clinicians as they access children with burns.

Usefulness of a Novel System for Feedback of Patient-Reported Outcome Measures in Children Recovering From Burns.

The Burn Outcomes Questionnaire for children ages 5-18 years (BOQ5-18) is a widely used, reliable, and valid parent-reported outcome measure designed to assess children's recovery from burn injuries in 12 physical and psychosocial domains. This study evaluated the feasibility, acceptability, and usefulness of a feedback system that delivered BOQ and Pediatric Symptom Checklist (PSC-17; a widely used measure of psychosocial functioning) results to burn care clinicians prior to an outpatient appointment or a postoperative surgical encounter. The BOQ and the PSC-17 were administered to the parents of 147 children receiving outpatient or surgical care in two pediatric burn hospitals. Clinician and parent perceptions of the feedback system were evaluated using debriefing questionnaires. Over half of all patients were at-risk on at least one BOQ subscale, and risk on three or more BOQ domains was significantly associated with a higher likelihood of poor psychological scores on the PSC-17 (P < .001). Significant differences in BOQ scores were found between the two hospital sites on four BOQ subscales, three related to physical ability and one to psychosocial well-being. Parent ratings of the feedback system were positive, with 90% of parents in both settings agreeing that the BOQ tablet experience was easy and helpful. Clinician attitudes differed across the two settings with more positive clinician ratings of the system in the outpatient setting (P < .001). Clinician interviews revealed that the data was especially useful in bringing to light psychosocial aspects of functioning relevant to long-term recovery from burn injuries.

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.

Measures of Total Energy Expenditure and Its Components Using the Doubly Labeled Water Method in Rehabilitating Burn Children.

BACKGROUND: A persistent hypermetabolic state delays anabolism and growth in burned children. However, our own clinical experience has been that resting energy expenditure (REE) is not increased during the rehabilitative phase, suggesting other contributing factors. We measured total energy expenditure (TEE) and its components in rehabilitating pediatric burn patients to identify the basis for accelerated energy metabolism in this population. MATERIALS AND METHODS: Children admitted with initial burns of 20% of their total body surface area (TBSA) or greater were enrolled into this prospective, descriptive study. TEE was measured using the doubly labeled water method over a 7-day period. During that period, REE was measured on 2 days by indirect calorimetry. Activity energy expenditure (AEE) was assessed using a physical activity monitoring device for a 24-hour period. TEE and REE were compared with sex-specific, age-matched, and weight-matched norms using the Dietary Reference Intakes (DRI) standards. RESULTS: Ten children with an average burn size of 53.7% ± 20% (range, 27%-82%) of TBSA completed this study. Their mean age and weight were 10.4 ± 5.5 years and 35.8 ± 16.4 kg, respectively. Daily TEE averaged 66 kcal/kg and was 1.08% of reference DRI. REE was 92% ± 25% of predicted basal metabolic rate, not exceeding 120% as a maximum value in any child. CONCLUSIONS: TEE and REE in rehabilitating burn children are comparable to reference standards. Increased REE was not typical in our population, but measures of AEE were commonly high.

Body water in children during recovery from severe burn injury using a combined tracer dilution method.

Useful information about hydration and the size of the body cell mass (BCM) can be obtained by monitoring changes in the amount of total body water (TBW) and its components, extracellular water (ECW) and intracellular water (ICW). A combined tracer dilution method with deuterium to measure TBW and bromide to measure ECW was used to assess changes in ICW (as a proxy for the BCM) and in the ECW/ICW ratio (an indicator of water distribution) over the course of recovery in nine severely burned children. During the acute phase of recovery, ICW losses averaged (mean +/- SD) 2.2 +/- 2.0 liters (P = .02) or 18.5 +/- 0.4%. During the rehabilitative phase, mean ICW increased by 3.4 +/- 3.7 liters or 31.9 +/- 14%. The ECW/ICW ratio varied widely both between patients and during the course of the study. During the acute phase of recovery, the mean ECW/ICW ratio increased from 1.06 +/- 0.15 liters to 1.20 +/- 0.14 liters because the ECW compartment had expanded relative to the ICW compartment. During rehabilitation, the ECW/ICW ratio decreased from 1.20 +/- 0.14 liters to 0.86 +/- 0.20 liters, with a recoup of ICW and continued ECW losses. Tracking ICW and the ECW/ICW ratio using the combined tracer dilution method is practical for monitoring BCM and water distribution in severely burned children. Taken together, the indices provide useful information about hydration and nutritional status in individuals recovering from severe burn injury.

Short-term enteral glutamine does not enhance protein accretion in burned children: a stable isotope study.

OBJECTIVE: Glutamine is a nonessential amino acid that, in recent years, has been found to play important roles in several metabolic and immunologic processes. It has been theorized that, in a stressed state, it may become "conditionally essential" because the patient's ability to manufacture glutamine may not be adequate to meet their needs under this condition. We chose to evaluate the ability of 48 hours of enteral glutamine to enhance immediate nitrogen accretion in stressed pediatric burn patients. METHODS: Nine children with serious burns who were tolerating tube feedings were enrolled in a human studies committee-approved protocol in which they received 48 hours of enteral feedings with glutamine replacing 20% of essential and nonessential amino acids and 48 hours of isonitrogenous, isocaloric standard enteral feedings. This interval was chosen to help ensure that the study periods were comparable from a metabolic perspective. At the end of each period, protein kinetics were determined by a primed constant infusion of L-[1-(13)C] leucine tracer. The order of the studies was randomized. Seven children completed both phases of the study. Results were compared by paired t test and are presented as mean +/- standard error of the mean. RESULTS: During the glutamine feeding period, the leucine flux and leucine oxidation rate were significantly lower than those in the conventional feeding period. This reflects a reduction in total leucine intake from 80 +/- 11 to 62 +/- 10 micromol/kg per hour. However, there was no significant difference in the net balance of leucine accretion into proteins between these 2 dietary periods, which indicated that enriched glutamine feeding for 48 hours did not result in an immediate whole body protein gain in this group of pediatric patients. In addition, plasma glutamine concentration showed a moderate increase after 48 hours of supplementation but did not reach significance. CONCLUSION: Rapid protein accretion does not occur with short-term enteral glutamine supplementation. Several days of glutamine supplementation may be required to restore plasma glutamine levels and stimulate protein synthesis.

Sodium bromide by instrumental neutron activation analysis quantifies change in extracellular water space with wound closure in severely burned children.

BACKGROUND: The ability to measure extracellular water (ECW) in critically ill patients can significantly enhance current methods of assessing fluid homeostasis, body composition, and response to nutritional therapy. We measured corrected bromide space to determine change in ECW with wound closure among acutely burned children. METHODS: Fifteen children with burns over 30% of their total body surface area had their ECW determined following hemodynamic stabilization and when wound closure was complete. Plasma samples were obtained at baseline and 4 hours after receiving 25 mg/kg of sodium bromide. Plasma bromide was quantified by instrumental neutron activation analysis. RESULTS: Mean CBS decreased with wound closure (9.1 +/- 4.1 vs 7.9 +/- 3.9 liters; P =.04), indicating a significant decrease in ECW over the course of recovery. A decline in weight also occurred over the same period (32.4 +/- 15.2 vs 29.1 +/- 13.5 kg; P =.007); however, change in corrected bromide space as a proportion of weight was not statistically significant. CONCLUSION: A significant decrease in ECW accompanies the weight loss observed in patients following wound closure. Measurement of bromide dilution space is a convenient method for monitoring ECW that can be done at the bedside.

In vivo imaging of human burn injuries with polarization-sensitive optical coherence tomography.

The accurate determination of burn depth is critical in the clinical management of burn wounds. Polarization-sensitive optical coherence tomography (PS-OCT) has been proposed as a potentially non-invasive method for determining burn depth by measuring thermally induced changes in the structure and birefringence of skin, and has been investigated in pre-clinical burn studies with animal models and ex vivo human skin. In this study, we applied PS-OCT to the in-vivo imaging of two pediatric burn patients. Deep and superficial burned skins along with contralateral controls were imaged in 3D. The imaging size was 8 mm × 6 mm × 2 mm in width, length, and depth in the air respectively, and the imaging time was approximately 6 s per volume. Superficially burned skins exhibited the same layered structure as the contralateral controls, but more visible vasculature and reduced birefringence compared to the contralateral controls. In contrast, a deeply burned skin showed loss of the layered structure, almost absent vasculature, and smaller birefringence compared to superficial burns. This study suggested the vasculature and birefringence as parameters for characterizing burn wounds.

Measuring the cost of care for children with acute burn injury.

BACKGROUND: There have been few studies on costs of burn treatment. Furthermore, quantifying the actual cost of care at the patient level is hindered by anomalies of our insurance system. This article presents a practical method for determining the cost of caring for pediatric burn patients, using a cohort of patients from the Multi-Center Benchmarking Study at the Shriners Hospitals for Children-Boston and allows an estimate of resource use that may be linked to need or to best practices, without the confounding variable of inconsistent billing practices. METHODS: We estimated the cost of hospitalization for a cohort of 230 pediatric patients who sustained burn injuries. In a simulation of billing patterns of all US hospitals between 2001 and 2009, we applied Shriners Hospitals for Children use data to two external sources of cost information. For the hospital component of costs, we used the Healthcare Cost and Utilization Project Kid's Inpatient Database, and for the physician component of costs, we used the Medicare fee schedule. RESULTS: Patients had a mean of 1.9 hospitalizations over 3 to 4 years. The mean total cost of hospitalization was $83,535 per patient, and the median total cost was $16,331 in 2006 dollars. CONCLUSION: This is the first effort to estimate the early hospital costs of caring for children and young adults with burns in specialty hospitals and to establish a referent for quantifying the cost of caring for patients with acute burns. It lays the groundwork for studies relating costs of specific interventions to their effects on patient-centered outcomes.

Production of Pseudomonas aeruginosa Intercellular Small Signaling Molecules in Human Burn Wounds.

Pseudomonas aeruginosa has developed a complex cell-to-cell communication system that relies on low-molecular weight excreted molecules to control the production of its virulence factors. We previously characterized the transcriptional regulator MvfR, that controls a major network of acute virulence functions in P. aeruginosa through the control of its ligands, the 4-hydroxy-2-alkylquinolines (HAQs)-4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS). Though HHQ and PQS are produced in infected animals, their ratios differ from those in bacterial cultures. Because these molecules are critical for the potency of activation of acute virulence functions, here we investigated whether they are also produced during human P. aeruginosa acute wound infection and whether their ratio is similar to that observed in P. aeruginosa-infected mice. We found that a clinically relevant P. aeruginosa isolate produced detectable levels of HAQs with ratios of HHQ and PQS that were similar to those produced in burned and infected animals, and not resembling ratios in bacterial cultures. These molecules could be isolated from wound tissue as well as from drainage liquid. These results demonstrate for the first time that HAQs can be isolated and quantified from acute human wound infection sites and validate the relevance of previous studies conducted in mammalian models of infection.

The contribution of muscle to whole-body protein turnover throughout the course of burn injury in children.

The physiologic response to trauma results in the efflux of large amounts of amino acids from skeletal muscle. This is extreme in large burn injuries. Protein kinetic studies, although useful in determining the rates of protein synthesis and breakdown, do not provide information about muscle loss. This study determined the contribution of muscle protein to whole-body protein breakdown in children throughout their course of burn injury. Children aged 0 to 18 years with initial burn size ≥30% TBSA underwent ¹5N glycine and 3 methylhistidine (3MH) analysis during three phases of care: A, early acute; B, wound closure; and C, convalescence. Muscle protein breakdown was estimated using a factor of 4.2 µmol 3MH per 1 g of mixed protein. Twenty-two patients with a mean of 54.5 ± 20.1% TBSA burn were studied. Protein balance did not change remarkably and remained positive by 2 g/kg during hospitalization. However, muscle protein breakdown dropped from 1.1 to 0.6 g/kg with wound closure (P < .0001), representing a decrease in the contribution of muscle protein to whole-body protein breakdown from 20 to 7%. Ten patients returned for a third measurement after discharge. Although protein turnover was high, muscle breakdown was consistent with 3MH values reported in healthy children. Serial determination of 3MH excretion is a simple way to track muscle catabolism throughout burn injury. Our data suggest that despite accelerated protein turnover, muscle catabolism significantly decreases with wound closure and begins to normalize around discharge. In convalescence, 3MH excretion is comparable with normal children.