The Pre-Hospital Initial Fluid Therapy Estimate in Early Nasty Burns (PHIFTEEN B, 15-B) Guideline applied to a retrospective cohort of Intensive Care Unit patients with major burns.

BACKGROUND: Appropriate fluid administration in severe burns is a cornerstone of early burns management. The American Burns Association's (ABA) recommendation is to administer 2 mL-4 mL × burnt Body Surface Area (BSA) × weight in the first 24 h with half administered in the first eight hours. Unfortunately, the calculations involved are complex and clinicians do not estimate the BSA or weight well, which can lead to errors in the amount of fluid administered. To simplify cognitive load to calculate the fluid resuscitation of early burns, the investigators derived the PHIFTEEN B (15-B) guideline. The 15-B guideline estimates the initial hourly fluid for adults ≥ 50 kg to be: 15 mL × BSA (to the nearest 10%) AIMS: To model and determine the accuracy of the 15-B calculated based on the characteristics of a retrospective cohort of patients admitted with ≥ 20% BSA to the Royal Brisbane and Women's Hospital (RBWH) Intensive Care Unit (ICU). METHODS: The 15-B formula was retrospectively calculated on the prehospital BSA estimate on patients admitted to the RBWH ICU. In addition, the 15-B guideline was modelled against a variety of weights and BSAs. The fluid volume was deemed to be clinically significant if it was greater than 250 mL/h outside the ABA's recommendations. RESULTS: The ICU cohort consisted of 107 patients (63.2% male, median age 37 years), with a median ICU estimated BSA of 40% and a median ICU weight estimation of 80 kg. In 43.9% of the cohort, the magnitude of the proportional difference between prehospital and ICU BSA estimate was greater than 25%. The 15-B formula accurately estimated the hourly fluid for all BSA (20%-100%) and weight combinations (50 kg-140 kg) in a BSA- weight matrix. When prehospital BSA estimate was utilized, 15-B guideline accurately estimated the fluid to be given within clinically significant limits for 97.2% of cases. CONCLUSIONS: The 15-B formula is a simple, easy to calculate guideline which approximates the early fluid estimates in severely burned patients despite inaccuracy in prehospital BSA estimates.

Changes of para-, meta- and ortho-tyrosine over time in burned patients.

PURPOSE: Serious burn injury leads to oxidative stress resulting in production of meta- and ortho-tyrosine, while para-tyrosine is the physiological isoform. Our aim was to investigate the metabolism of these tyrosine isoforms following major burn injury. METHODS: Fifteen patients requiring intensive care were followed for 5 consecutive days after major burn injury. Serum and urine concentrations of para-, meta-, and ortho-tyrosine were measured with high performance liquid chromatography. Fifteen healthy matching individuals were invited as control group. RESULTS: Median serum concentration of normal isoform para-tyrosine decreased in burned patients between days 2 and 5 (p < 0.01). Mean meta-, and ortho-tyrosine levels were significantly higher in patients compared to controls in the same time period (p < 0.05). Renal excretion of para-tyrosine increased significantly in our observation period (p < 0.01). CONCLUSIONS: Pathologic isoforms of tyrosine accumulate in serum meanwhile the level of normal isoform decreases possibly due to belated enhanced renal excretion or, to decreased synthesis after major burn injury.

Cutaneous Burn Injury Modulates Urinary Antimicrobial Peptide Responses and the Urinary Microbiome.

OBJECTIVES: Characterization of urinary bacterial microbiome and antimicrobial peptides after burn injury to identify potential mechanisms leading to urinary tract infections and associated morbidities in burn patients. DESIGN: Retrospective cohort study using human urine from control and burn subjects. SETTING: University research laboratory. PATIENTS: Burn patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urine samples from catheterized burn patients were collected hourly for up to 40 hours. Control urine was collected from "healthy" volunteers. The urinary bacterial microbiome and antimicrobial peptide levels and activity were compared with patient outcomes. We observed a significant increase in urinary microbial diversity in burn patients versus controls, which positively correlated with a larger percent burn and with the development of urinary tract infection and sepsis postadmission, regardless of age or gender. Urinary psoriasin and ß-defensin antimicrobial peptide levels were significantly reduced in burn patients at 1 and 40 hours postadmission. We observed a shift in antimicrobial peptide hydrophobicity and activity between control and burn patients when urinary fractions were tested against Escherichia coli and Enterococcus faecalis urinary tract infection isolates. Furthermore, the antimicrobial peptide activity in burn patients was more effective against E. coli than E. faecalis. Urinary tract infection-positive burn patients with altered urinary antimicrobial peptide activity developed either an E. faecalis or Pseudomonas aeruginosa urinary tract infection, suggesting a role for urinary antimicrobial peptides in susceptibility to select uropathogens. CONCLUSIONS: Our data reveal potential links for urinary tract infection development and several morbidities in burn patients through alterations in the urinary microbiome and antimicrobial peptides. Overall, this study supports the concept that early assessment of urinary antimicrobial peptide responses and the bacterial microbiome may be used to predict susceptibility to urinary tract infections and sepsis in burn patients.

Ubiquitin Urine Levels in Burn Patients.

The objective of this study was to determine whether urine ubiquitin levels are elevated after burns and to assess whether urine ubiquitin could be useful as a noninvasive biomarker for burn patients. Forty burn patients (%TBSA: 20 ± 22; modified Baux scores: 73 ± 26) were included (control: 11 volunteers). Urine was collected in 2-hour intervals for 72 hours, followed by 12-hour intervals until discharge from the intensive care unit. Ubiquitin concentrations were analyzed by enzyme linked immunosorbent assay and Western blot. Total protein was determined with a Bradford assay. Patient characteristics and clinical parameters were documented. Urine ubiquitin concentrations, renal ubiquitin excretion, and excretion rates were correlated with patient characteristics and outcomes. Initial urine ubiquitin concentrations were 362 ± 575 ng/ml in patients and 14 ± 18 ng/ml in volunteers (P < .01). Renal ubiquitin excretion on day 1 was 292.6 ± 510.8 µg/24 hr and 21 ± 27 µg/24 hr in volunteers (P < .01). Initial ubiquitin concentrations correlated with modified Baux scores (r = .46; P = .02). Ubiquitin levels peaked at day 6 postburn, whereas total protein concentrations and serum creatinine levels remained within the normal range. Total renal ubiquitin excretion and excretion rates were higher in patients with %TBSA ≥20 than with %TBSA <20, in patients who developed sepsis/multiple organ failure than in patients without these complications and in nonsurvivors vs survivors. These data suggest that ubiquitin urine levels are significantly increased after burns. Renal ubiquitin excretion and/or excretion rates are associated with %TBSA, sepsis/multiple organ failure, and mortality. Although these findings may explain previous correlations between systemic ubiquitin levels and outcomes after burns, the large variability of ubiquitin urine levels suggests that urine ubiquitin will not be useful as a noninvasive disease biomarker.

Urinary Biomarkers are Associated with Severity and Mechanism of Injury.

Combat-related blast trauma results in massive tissue injury and tends to involve multiple systems. Further, an acute measure of injury severity based on underlying biological mechanisms may be important for the triage and treatment of these types of patients. We hypothesized that urinary biomarkers (UBs) would reflect severity of injury and that they would be elevated for blast injuries compared with gunshot wounds (GSW) in a cohort of combat casualties. We also postulated that UBs would be higher in patients with burns compared with patients with non-burn trauma in a civilian cohort. Among 80 service members who sustained combat-related injuries, we performed generalized estimating equations to compare differences in log-transformed concentrations of the UBs by both injury severity and injury mechanism. Among 22 civilian patients, we performed Kruskal-Wallis tests to compare differences for the UBs stratified by burn and non-burn trauma. In the military cohort, with the exception of IL-18, all UBs were significantly (P <0.05) higher for patients with a severe combat-related injury (Injury Severity Score ≥25). In addition, all crude UBs concentrations were significantly higher for blast versus GSW patients (P < 0.05). After adjusting for injury severity score and time of UB draw, KIM-1 (2.80 vs. 2.31; P = 0.03) and LFABP (-1.11 vs. -1.92; P = 0.02) were significantly higher for patients with a blast mechanism of injury. There were no significant differences in UBs between burn and non-burn civilian trauma patients. Future studies are needed to understand the physiologic response to trauma and the extent that UBs reflect these underlying processes.

Assessment of urinary kidney injury molecule-1 and interleukin-18 in the early post-burn period to predict acute kidney injury for various degrees of burn injury.

BACKGROUND: Burn patients with AKI have a higher mortality, rapid diagnosis and early treatment of AKI are necessary. Recent studies have demonstrated that urinary KIM-1 and IL-18 are potential biomarkers of early-stage AKI, however, changes in urinary KIM-1 and IL-18 levels are unclear in patients with burns. The aim of our study was to determine whether combined KIM-1 and IL-18 are more sensitive than traditional markers in detecting kidney injury in patients with burns. METHODS: Ninety-five burn patients hospitalized at the Burns and Plastic Surgery Center of our hospital from April 2013 to September 2013 were enrolled into this prospective study and divided into mild- (n = 37), moderate- (n = 30) and severe-burn groups (n = 28) by burn injury surface area. In the moderate- and severe-burn groups, patients were subcategorized to either the acute kidney injury (AKI) group, in which serum creatinine (Scr) increased to ≥ 26.5 µmol/L within 48 h, or the non-AKI group. Fifteen healthy subjects were selected as a control group. Blood specimens were collected to determine blood urea nitrogen (BUN), Scr, and other biochemical indicators. Urine samples collected at admission and 48 h after admission were analyzed for KIM-1 and IL-18. Correlations among urinary KIM-1 and IL-18, burn degree, and clinical biochemical indicators were investigated. RESULTS: AKI occurred in 11.2 % of burn patients (none in the mild-burn group). AKI developed 48 h after admission in 10.0 % of the moderate- and 28.6 % of the severe-burn groups. Urinary KIM-1 concentration in the moderate- and severe-burn groups was significantly higher than that in the control group; urinary IL-18 concentrations did not differ significantly among the burn and control groups. The AKI group had significantly higher concentrations of urinary KIM-1 and IL-18 than the non-AKI group, both at admission (p = 0.001 and p < 0.001, respectively) and 48 h later (p = 0.001 and p < 0.001, respectively). Both urinary KIM-1 and IL-18 increased before Scr. Receiver operating-curve (ROC) analysis demonstrated that KIM-1 combined with IL-18 predicted AKI with 72.7 % sensitivity and 92.8 % specificity. The area under the ROC curve was 0.904. CONCLUSIONS: Our results suggest that urinary KIM-1 and IL-18 may be used as early, sensitive indicators of AKI in patients with burns of varying degrees and provide clinical clues that can be used in early prevention of AKI.

Serum cystatin C and microalbuminuria in burn patients with acute kidney injury.

BACKGROUND: This study was aimed at evaluating the effectiveness of serum cystatin C and microalbuminuria as diagnostic markers for acute kidney injury (AKI) in major burn patients. MATERIALS AND METHODS: Major burn adult patients admitted to the burn intensive care unit within 24 h from the onset of injury were enrolled. Serum cystatin C and microalbuminuria (albumin-creatinine ratio, ACR) were obtained at postburn days 1, 3, 7, 14, 21 and 28. The patients were divided into two groups of the AKI group and the nonacute kidney injury group. RESULTS: A total of 97 patients were enrolled in this study. Acute kidney injury was diagnosed in 40 patients (41.2%) at postburn day 17.3 ± 7.9. The area under the curve of the receiver operating characteristic curve for serum cystatin C was 0.808 (95% CI, 0.711-0.905, P < 0.001) at postburn day 7 and 0.908 (95% CI, 0.843-0.973, P < 0.001) at postburn day 14. The results were 0.610 (95% CI, 0.497-0.724, P = 0.069) for ACR at postburn day 7 and 0.694 (95% CI, 0.589-0.798, P = 0.001) at postburn day 14. The optimal cut-off value of serum cystatin C at postburn day 14 and ACR at postburn day 14 were 0.85 mg/L (sensitivity, 89.5%; specificity, 82.5%) and 41.51 mg/g cre (sensitivity, 60.5%; specificity, 61.4%), respectively. Serum cystatin C at postburn day 14 was the only significant factor in relation to AKI. CONCLUSIONS: Serum cystatin C is a valuable diagnostic marker, whereas microalbuminuria is a relatively less significant marker for AKI in major burn patients.

The utility of microalbuminuria measurements in pediatric burn injuries in critical care.

PURPOSE: Microalbuminuria, as measured by urinary albumin-creatinine ratios (ACRs), has been shown to be a marker of systemic inflammation and an indicator of the potential severity of trauma and critical illness. Severe pediatric burns represent the best model in which to investigate the clinical utility of microalbuminuria. This study aims to ascertain whether ACR measurements have any role in predicting the severity or the intensive care requirements in the critically unwell pediatric burn population. MATERIALS AND METHODS: A retrospective observational study was undertaken within a regional burn center with a dedicated 8-bed burn intensive care unit (ICU). This looked at 8 years of consecutive pediatric burns requiring intensive care support-a total of 63 patients after exclusions. Daily urinary ACR measurements were acquired from all patients. RESULTS: All patients had greater than or equal to 1 ACR measurement out with the reference range, and only 8% (5/63) presented to the ICU with a normal ACR. The median day for the peak ACR measurement was day 4. The relative lack of mortalities (3/63) precluded adequate correlations between ACR and outcomes. Peak and mean ACR values correlate well with length of ICU stay, and the peak ACR also correlates with total length of hospital stay and severity of burn injury as measured by total body surface area burnt and number of organ systems requiring support. No significant differences were found when the patients were stratified by age. The peak ACR measurement was found to be independently predictive of the length of the ICU stay. As such, we have created a predictive model to prove that an ACR that remains less than 12 mg/mmol is predicative of an ICU stay of less than or equal to 7 days. CONCLUSIONS: The clinical utilities of ACR measurements are demonstrated by their correlation with the severity of injury, length of ICU stay, and requirements for multiple organ support. Albumin-creatinine ratios raised over certain thresholds highlight to the clinician the need for closer observation and the potential deterioration of patients.

Routine use of urinary hCG test in adult burn females to detect "hidden" pregnancies: a review.

Burns occurring in conjunction with pregnancy can be a potentially life threatening scenario as it may lead to a rapid depletion of the already diminished maternal reserves. The management protocol in a pregnant burn female has to be tailored, taking into consideration the additional factor of fetal well being and the fetal susceptibility to various agents. For such alterations to be incorporated, it is imperative on part of the treating doctor to correctly ascertain the pregnant/non-pregnant status of an adult burn female. Though most cases of pregnancy can be straightforwardly diagnosed on basis of history/examination but it is not a totally reliant method. Ours is a prospective study which reveals the inadequacy of history/examination as the only method of diagnosing pregnancy in adult burnt female group. We also found routine urinary hCG usage as a viable method of picking up these "hidden" cases of pregnancy and thus avert the potential catastrophe of not altering the management in accordance with pregnancy and subsequent endangering of maternal and fetal life. An ancillary observation of our study was the need of the attending doctor to be well versed in his obstetrical knowledge and skills and if not so, then an effort be taken on part of the institution to undertake a reorientation program which will help the attending resident/doctor to brush up his obstetrical attainments.

Contributions of severe burn and disuse to bone structure and strength in rats.

Burn and disuse results in metabolic and bone changes associated with substantial and sustained bone loss. Such loss can lead to an increased fracture incidence and osteopenia. We studied the independent effects of burn and disuse on bone morphology, composition and strength, and microstructure of the bone alterations 14days after injury. Sprague-Dawley rats were randomized into four groups: Sham/Ambulatory (SA), Burn/Ambulatory (BA), Sham/Hindlimb Unloaded (SH) and Burn/Hindlimb Unloaded (BH). Burn groups received a 40% total body surface area full-thickness scald burn. Disuse by hindlimb unloading was initiated immediately following injury. Bone turnover was determined in plasma and urine. Femur biomechanical parameters were measured by three-point bending tests and bone microarchitecture was determined by micro-computed tomography (uCT). On day 14, a significant reduction in body mass was observed as a result of burn, disuse and a combination of both. In terms of bone health, disuse alone and in combination affected femur weight, length and bone mineral content. Bending failure energy, an index of femur strength, was significantly reduced in all groups and maximum bending stress was lower when burn and disuse were combined. Osteocalcin was reduced in BA compared to the other groups, indicating influence of burn. The reductions observed in femur weight, BMC, biomechanical parameters and indices of bone formation are primarily responses to the combination of burn and disuse. These results offer insight into bone degradation following severe injury and disuse.

Detection of microalbuminuria: a simple test for prognosis in severe burns.

PURPOSE: To evaluate the effectiveness of microalbuminuria monitoring in the management of patients with severe burns. METHODS: Consecutive patients admitted to the burn unit with total body surface area burn between 20% and 50% were examined for microalbuminuria during the hospitalisation. The findings were correlated to different clinical variables usually encountered in this patient category. RESULTS: Microalbuminuria was found in patients with inhalation injuries (100%), systemic inflammatory response syndrome (SIRS, 88.4%), burn sepsis (95.1%) and postoperatively (94.9%). CONCLUSION: Microalbuminuria is the only simple, non-invasive, bedside, immediate and cost-effective test to indicate for occurrence of SIRS, if the other variables were stabilised. It can be measured with every urine void or more often when a urinary catheter is inserted. This will affect our management of patients with severe burns.

Extent and magnitude of catecholamine surge in pediatric burned patients.

Increased catecholamine (CA) levels after severe burn are associated with stress, inflammation, hypermetabolism, and impaired immune function. The CA secretion profiles in burned patients are not well described. Mechanisms, duration, and extent of CA surge are unknown. The purpose of this large unicenter study was to evaluate the extent and magnitude of CA surge after severe burn in pediatric patients. Patients admitted between 1996 and 2008 were enrolled in this study. Twenty-four-hour urine collections were performed during acute hospitalization and up to 2 years postburn. Results from the samples collected from 12 normal, healthy volunteers were compared with the data from the burned patients. Relevant demographic and clinical information was obtained from medical records. Student t-test and one-way ANOVA were used to analyze the data where appropriate. Significance was accepted at P < 0.05. Four hundred thirteen patients were enrolled in this study; 17 patients died during acute hospitalization. Burn caused a marked stress and inflammatory response, indicated by massive tachycardia and elevated proinflammatory cytokines. In burned patients, CA levels are consistently and significantly modulated after burn when compared with the levels in normal, healthy volunteers. Catecholamine levels were significantly higher in boys compared with girls, correlated with burn size in burns greater than 40%, and were increased in older children. There were differences over time in survivors versus nonsurvivors, with CA levels significantly higher in nonsurvivors at two time points. Inflammatory cytokines show a similar profile during the study period. Our study gives clinicians a useful insight into the extent and magnitude of CA elevation to better design treatment strategies.

[Pharmacokinetic evaluation of linezolid in patients with major thermal injuries]. / Pharmacocinétique du linézolide chez des patients souffrant de brûlures sévères.

The aims of this multicentre open-label study was to evaluate the pharmacokinetics of linezolid in patients with burn injury above 20 % BSA and to compare them with healthy volunteers, matched in age, sex and weight. After a single 600 mg IV dose of linezolid, multiple blood and urine samples were taken from subjects, in order to determine linezolid concentrations, using a HPLC assay. C(max) and volume of distribution at steady state were not different between the two groups. Values describing clearance were altered in burns, leading to a reduction by half in AUC in these patients (42.5 versus 98.1 mghL(-1)). The enhancement of clearance was due to which of non renal clearance (323+/-191 versus 80.4+/-27.5 mLmin(-1)). We conclude that pharmacokinetics of linezolid are altered in burn patients, in a magnitude sufficient that linezolid concentration may be subtherapeutic in some patients and we suggest that the dosage interval may need to be decreased in this patient population.

Physical and biochemical characteristics of biological fluids in rats with modeled thermal injury.

Lactate dehydrogenase activity, crystallogenic and initiator characteristics of biological substrates were evaluated by enzymological and crystalloscopic analysis of rat serum and urine. Changes in these characteristics of biological media in combined thermal injury were shown. This approach is effective for evaluation of the metabolic status in rats with experimental burn disease.

von Willebrand factor in cadaveric urine for forensic investigation.

Preliminary experimental study of urinary von Willebrand factor (VWF) concentration was undertaken to evaluate the utility of this parameter in forensic investigations. ELISA was used to measure VWF concentration. Correlations of urinary VWF with cause of death and postmortem interval (PMI) were ascertained. As PMI advanced, urinary VWF increased but plasma VWF did not. Cause of death was not significantly correlated with VWF. This study indicated the possibility that urinalysis would be helpful to estimate PMI.

Proteinuria without albuminuria: urinary protein excretion by a subset of patients with burn injuries.

BACKGROUND: There is disagreement regarding the utility of urinary albumin excretion as a marker for capillary injury in patients with severe burn injuries. We examined protein components in urine specimens from patients with burn injury. METHODS: Detailed analysis was performed for a set of 5 urine specimens selected based on a high ratio of albumin-sized molecules by size-exclusion HPLC (Accumin) versus albumin by immunoassay methods. Specimens were analyzed for total protein, alpha(1)-microglobulin, alpha(1)-acid glycoprotein, cystatin C, and retinol-binding protein. Urine components were analyzed by chromatographic and electrophoretic methods. Major components were identified by mass spectrometry of tryptic peptides. RESULTS: A subset of urine specimens had increased total protein with slight increases in albumin by immunoassay or by polyacrylamide gel electrophoresis. Albumin values by size-exclusion HPLC were more than 10-fold higher. Immunoassays for alpha(1)-microglobulin and alpha(1)-acid glycoprotein yielded concentrations 5-10 fold higher than for albumin. Other major components identified included zinc-alpha(2)-glycoprotein and leucine-rich-alpha(2)-glycoprotein. CONCLUSIONS: A subset of patients with burn injury had increased total urinary protein resulting primarily from increased excretion of proteins such as alpha(1)-microglobulin and alpha(1)-acid glycoprotein with little increase in albumin excretion. The unusual composition of urinary proteins in these patients may relate to decreased filtered load of albumin and increased filtered load of acute phase reactants or to alterations in renal tubular protein processing. Thus, measurement of urinary albumin may have decreased sensitivity for detecting kidney injury in burn patients.

Arterial thermodilution in burn patients suggests a more rapid fluid administration during early resuscitation.

BACKGROUND: A number of target points have been used for fluid replacement in severely burned patients. The aim of our prospective randomized study was to compare the effect of two different types of fluid resuscitation regimes on the multiple organ dysfunction score (MODS) and central venous oxygen saturation (ScvO(2)) in the first 3 days after injury. METHODS: Twenty-four patients admitted to the critical care unit of a university hospital with the presence of burn injury affecting more than 15% of the body surface area and in-hospital fluid resuscitation started within 3 h after burn injury were included. Patients were randomized into two groups. Fluid resuscitation was guided by the hourly urine output (HUO Group, n=12) or by the intrathoracic blood volume index (ITBVI Group, n=12). Invasive transpulmonary hemodynamic measurements utilizing pulse contour analysis with a single dilution technique and continuous ScvO(2) measurements were performed in both groups. RESULTS: The mean ScvO(2) was significantly lower in the HUO Group than in the ITBVI Group (P=0.024) for the first 24 h. MODS was significantly higher in the HUO Group than in the ITBVI group 48 h (P=0.024) and 72 h after injury (P=0.014). The two main outcome parameters, i.e., MODS calculated at 48 and 72 h after injury and ScvO(2) were negatively correlated on day 1 (r=-0.684, P=0.004, r=-0.677, P=0.003). There were no statistical differences in clinical outcome parameters. CONCLUSION: Our data suggest that ITBVI may be a better target parameter than HOU in the fluid resuscitation of severely burned patients after injury.

Urinary cortisol and catecholamine excretion after burn injury in children.

INTRODUCTION: A severe burn causes increased levels of urine cortisol and catecholamines. However, little is known about the magnitude of this increase or how and when the levels return to normal. The purpose of this study was to determine in a large clinical prospective trial the acute and long-term pattern of urine cortisol and catecholamine expression in severely burned children. METHODS: Pediatric patients with burns greater than 40% total body surface area (TBSA), admitted to our unit over a 6-yr period, were included into the study. Clinical data including length of stay, number of operations, and duration and number of infections were determined. Patients had regular 24-h urine collections during their acute admission and reconstructive periods. Urine collections were analyzed for cortisol, epinephrine, and norepinephrine. Each urine cortisol was compared with age-adjusted reference ranges. Ninety-five percent confidence intervals and ANOVA analysis were used where appropriate. RESULTS: Two hundred twelve patients were included in the study (75 females and 137 males), with a mean +/- sem TBSA of 58 +/- 1% (third-degree 45 +/- 2%) and mean age of 9 +/- 0.4 yr. Urinary cortisol levels were significantly increased (3- to 5-fold) up to 100 d after the burn and then approached normal levels (P < 0.05). The rise in urine cortisol was significantly higher in male than female patients (P < 0.05). Early hypercortisolemia was associated with increased duration of severe infection (P < 0.05). Persistent hypercortisolemia was associated with increases in both infection rates and duration of severe infection (P < 0.05). Urinary catecholamines showed a significant increase at 11-20 d after the burn (P < 0.05). Urinary norepinephrine levels were significantly increased up to 20 d and then returned to normal (P < 0.05). CONCLUSIONS: Urinary levels of cortisol, epinephrine, and norepinephrine are significantly increased after a major burn. Early hypercortisolemia is associated with increased duration of severe infection. Persistent hypercortisolemia is associated with increases in both infection rates and duration of severe infection.