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.

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.

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.

[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.

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.

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.

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.

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.

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 excretion of hydroxylysine and its glycosides as an index of collagen degradation.

Urimary excretion of hydroxyprolin (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hy1[Gl)cGa1]), and galactosyl hydroxylysine (Hyl[Ga)]), more accurately reflects collagen metabolism since these products occur in specificratios in different tissue collagens and are themselves metabolized only to a minor degree. The ratios of total Hy1/Hyp and Hyl(GlcGal)/Hyl(Ga1) were measured in the urine of norma. subjects and of patients with Paget's disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal burns the pattern of urinary Hy1 and its glycosides was consistent with degradation of collagen in dermis and fascia. When bone collagen degradation was dominant, the pattern of urinary metabolites reflected that source. Pagetic bone collagen has an amino acid composition similar to normal bone and Hy1(G1cGa1/Hyl(G1) of 0.396-0.743,vs. normal of 0.474+/-0.088. In untreated patients with severe Paget's disease of bone or hyperphosphatasia (urinary Hyp greater than 2.0 micronmol/mg creatinine) urinary Hyl/Hyp averaged 0.052+/-0.042 (0.042+/-0.009 in normal bone) and Hy1(G1cGa1)/Hy1(Ga1) 0.601+/-0.017 (0.47+/-0.009 in normal bone). When bone resorption was decreased sufficiently with calcitonin or disodium etidronate in these patients, both the urinary ratios of Hy1/Hyp and Hy1(G1cGa1)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hy1/H)P approached 0.7 and Hy1(G1ycGa1)/Hy1(Ga1) approached 3.5. There increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcompoent of complement, Clq, which has collagen-like sequences, relatively high amounts of Hy1, and most of the glycosylated Hy1 as Hy1(G1cGa1), could be the source of these metabolites.

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.

Microalbuminuria: a marker of endothelial dysfunction in thermal injury.

INTRODUCTION: Systemic endothelial dysfunction (SED) and capillary leak occur following severe burn. SED can be assessed as low-level albuminuria (microalbuminuria) detectable only by sensitive immunoassay. This study compared the magnitude and duration of microalbuminuria with burn surface area and associated aggravating factors. METHODS: Serial urine specimens were collected from 2 to 36 h after injury from 43 adult burn patients with a mean total body surface area (TBSA) of 32% (range 15-68%) and during 44 episodes of wound manipulation within the same period. Urinary albumin was expressed as the albumin/creatinine ratio (ACR, normal <2.3 mg/mmol). RESULTS: Median ACR was highest 2h after injury (12.3 range 1.8-118 mg/mmol) returning to normal within 6 h. Full thickness burns (mean 17%) showed a significant association with ACR between 3 and 7h after burn. ACR was higher for up to 8 h in the presence of inhalation injury, alcohol intoxication or accelerant (p<0.05). ACR rose within 30 min of escharotomy or wound scrubbing (p<0.01). CONCLUSION: Severe burn produces variable SED which recurs with wound manipulation. Inhalation injury, alcohol intoxication and accelerant all showed a stronger association with SED than TBSA. Microalbuminuria provides a means of monitoring microvascular integrity during the early after injury period.

[The clinical course of microalbumiuria in 4 burn patients].

BACKGROUND: In burn patients, microvascular permeability is increased. It is difficult to decide the time to administer albumin because it may induce pulmonary edema in the re-filling period. One report shows that microalbuminuria is correlated with endothelial injury and systemic microvascular permeability. METHODS: We measured urinary albumin/creatinine ratio (ACR) in 4 burn patients for 48 hours after injury. RESULTS: In all patients, ACR was elevated in the early period after injury. Moreover, ACR in 2 severe burn patients with burn total body area of over 30% was above the normal range. CONCLUSIONS: The present results show that ACR seems to be correlated with the level of microvascular permeability in 4 burn patients. We conclude that ACR may be a useful indicator to decide the time to administer albumin to a burn patient. However, further investigation is required to decide the threshold value of ACR in a severe burn patient whose ACR are kept above the normal range in the long-term.

Prebiotic ingestion does not improve gastrointestinal barrier function in burn patients.

Prebiotics increase intestinal levels of health-promoting bacteria implicated in decreasing pathogen colonization, stimulating immune functions and stabilizing gut barrier functions, parameters which are altered in burn patients. We propose that regular intake of a prebiotic, oligofructose (OF), might help to improve the altered gastrointestinal (GI) permeability observed in burn patients. A randomized, double-blind, controlled clinical trial was carried out in 41 burn patients (mean burn surface area=17.1+/-8.2%) who ingested daily 6 g of oligofructose (OF group) or sucrose as placebo (Control group) during 15 days. Gastrointestinal permeability to sucrose and lactulose/mannitol (L/M) was evaluated on days 1 (before treatment) 3, 7, 14 and 21. A permeability test was also performed in 18 healthy subjects as controls. Thirty-one patients completed the protocol (dropout rate=24.4%). Healthy subjects had a basal sucrose excretion of 21.3 mg (14.0-32.5 mg) and a basal L/M ratio of 0.017% (0.009-0.022%). Sucrose excretion increased 5-fold and L/M ratio 4.4-fold in burn patients on day 1 and these high levels of marker excretion decreased significantly throughout the study (p=0.016 and 0.000001, respectively). No differences between the OF and Control groups were observed for sucrose excretion or L/M ratio. In conclusion, the normalization of gastrointestinal permeability is not accelerated by prebiotic intake.

[Disturbances of electrolytes in severe thermal burns]. / Intérêt du ionogramme chez le brûlé thermique grave.

Thermal burns result in severe electrolytes disturbances which are life-threatening when the percentage of burnt body surface area (BSA) is above 20% in adults and 10% in children. If electrolytes disturbances are often mentioned in the physiopathology of burns, they are less documented in the daily practice of the follow up. The objective of this work was to describe variation of blood and urine electrolytes concentrations in severe burns. The survey concerned 30 patients hospitalized in the Burn Centre of Abidjan. The patients have been followed during the first three days after the burn, including the initial phase of shock resuscitation. The results showed, in accordance with data of the literature, the incidence of hypophosphoremia, hypoprotidemia and hypocalcemia. The hypoprotidemia and the hypocalcemia were correlated with the importance of the BSA. An elevation of potassium and a decrease of sodium have been also observed, but, in contrast to data of the literature, they were not significant. Moderate variations of chloride and magnesium have been noted. All urinary parameters were decreased. The present results suggest the necessity of proteins, phosphore and calcium administration in the therapeutic protocols.

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.

Urinary excretion of D-glucaric acid by severely burned patients.

The 24-hr excretion of urinary D-glucaric acid (UGA) has been measured in 5 seriously burned adults and compared with 6 healthy adults. In the burn patients mean UGA was 14.4 +/- 5.4 (+/- SD) mumoles/day and 28.7 +/- 6.5 mumoles/day in controls (p less than 0.002). In a 6-year-old female, UGA was also found to be very low. In a seventh burn patient, an adult male taking 20 mg of fluphenazine until his injury, his UGA was still in the normal range (29 mumoles/day) on the day of admission but descended to 21 mumoles/day at 2 days, to 16 at 4 days, and to 13 at 6 days. Treatment with fluphenazine was then reinstituted and on the tenth day UGA was 28 mumoles/day, indicating that after thermal injury UGA can respond to drugs. Although the inference has not been proved that decreased UGA corresponds to a decreased activity of drug metabolism, there is evidence of a strong correlation between increased UGA and increased drug metabolism. A decrease of UGA in disorders that generally lower metabolic activity supports a possible correlation in severe burns. If drug metabolism activity is lowered in the seriously burned patient, drug overdose may well result from the usual clinical doses.

Serum copper and ceruloplasmin levels and urinary copper excretion in thermal injury.

Conflicting reports regarding copper status in thermal injury patients have been published. We determined serial serum-copper and serum-ceruloplasmin levels and 24-h urinary excretion of copper in 23 patients with second- and third-degree thermal burns. Throughout hospitalization, mean serum-copper concentration was significantly depressed; lowest levels were found in patients with greater than 40% total body surface area burns. Serum ceruloplasmin was also depressed, an unexpected finding because this protein is a positive acute-phase reactant poststress. Mean urinary excretion of copper was elevated, reaching 2.5 times the upper limit of normal 2 wk postburn. Depressed serum-copper levels paralleled the serum-ceruloplasmin levels rather than the increased urinary-copper losses. Further studies are required to determine the mechanism(s) of this altered copper metabolism and whether physiological or biochemical evidence of copper deficiency accompanies the observed hypocupremia.