Long-term reduction in bone mass after severe burn injury in children.

OBJECTIVE: Because burn victims are at risk of having bone loss, a cross-sectional study was undertaken to determine whether severe burn injury had acute and long-term effects on bone mass or on the incidence of fractures in children. METHODS: Dual-energy x-ray absorptiometry of the lumbar portion of the spine was performed on 68 children: 16 moderately burned (15% to 36% of total body surface area) and 52 age-matched severely burned (> or = 40% of total body surface area). Twenty-two severely burned children were hospitalized and studied within 8 weeks of their burn, and 30 others were studied approximately 5 years after discharge. In the severely burned group, both hospitalized and discharged, serum and urine were analyzed for calcium, phosphorus, intact parathyroid hormone, osteocalcin, and type I collagen telopeptide. RESULTS: Sixty percent of severely burned patients had age-related z scores for bone density less than -1, and 27% of severely burned patients had age-related z scores for bone density less than -2 (p < 0.005, for each). In the moderately burned group, 31% of patients had z scores less than -1 (p < 0.005 vs normal distribution), but only 6% had z scores less than -2 (p value not significant). There was evidence of increased incidence of fractures after discharge in the severely burned patients. Biochemical studies were compatible with a reduction in bone formation and an increase in resorption initially, and with a long-term persistence of low formation. CONCLUSION: We conclude that acute burn injury leads to profound and long-term bone loss, which may adversely affect peak bone mass accumulation.

Risk of aluminum accumulation in patients with burns and ways to reduce it.

Severely burned patients experience a bone lesion consisting of markedly reduced bone formation and evidence of decreased resportion. The cause of the lesion may be multifactorial, but aluminum loading, which also occurs in patients with burns, has been documented to produce this type of injury in both humans and animals. To assess the risk of aluminum loading with patients with burns, we analyzed fluids, creams, and medication used in the management of acute burn injury for aluminum content. These substances were classified according to route of administration: cutaneous, enteral, or parenteral, to assess the risk of aluminum loading. Cutaneous exposure to aluminum is greatest from baths, which may provide up to 8 mg aluminum. However, the dynamics of aluminum entry into the blood via a damaged skin barrier are unclear. Enteral exposure to aluminum is no greater than daily dietary exposure. Parenteral sources of aluminum, especially 25% human serum albumin and calcium gluconate, provide the most significant risk of loading because of direct introduction of aluminum into the circulation. Substitution with a different brand of albumin and calcium chloride can reduce the parenteral aluminum load by as much as 95% and minimize any role aluminum may play in the pathogenesis of this bone lesion.

Effect of thermal injury and sepsis on neutrophil function.

Burn injury and sepsis have been repeatedly demonstrated to impair the function of circulating (blood) neutrophils. As a result of the difficulty in harvesting and purifying neutrophils from the burn wound, there have been minimal investigations to date on the effect of burn injury and sepsis on the function of neutrophils which have reached the wound. We utilized a sponge matrix model in order to obtain neutrophils from burned and burned-infected rats. Despite having a higher concentration of neutrophils in the blood, both the burned and burned-infected rats were noted to have a decreased number of neutrophils infiltrating the sponge compared with the controls (1.91 +/- 0.30 x 10(6), 2.31 +/- 0.47 x 10(6), and 4.82 +/- 0.64 x 10(6) neutrophils per sponge, respectively). Blood neutrophils from both the burned and burned-infected rats had a greater chemiluminescence capacity than neutrophils from the control group (p < 0.0001). This enhanced capacity was not present with sponge neutrophils obtained from the burned-infected group. The diminished capacity may have been the result of a decreased concentration of prostaglandin E in the sponge fluid of the burned-infected rats compared with that of the burned or control rats (52 +/- 9, 135 +/- 15, and 114 +/- 13 pg/mL of sponge fluid, respectively).

Bone disease in burn patients.

Burn patients are at risk for bone disease due to aluminum (Al) exposure from use of antacids and albumin, partial immobilization, and increased production of endogenous glucocorticoids. Moreover, severely burned children are growth impaired up to 3 years after the burn. To determine the extent of bone disease, we studied nine men and three women, ages 18-41 years, with greater than 50% body surface area burn. Seven patients underwent iliac crest bone biopsy following double tetracycline labeling, one additional patient expired after a single label, and three others had postmortem specimens obtained for quantitative Al only. Serial serum and urine samples were obtained weekly until biopsy or death. All biopsied patients had reduced bone formation and osteoid area, surface, and width, with mineral apposition rate, osteoblast surface, and osteoclast number with normal eroded surfaces compared to age- and sex-matched normal ambulatory volunteers. Burn patients also had reduced bone formation, mineral apposition rate, osteoid area, and surface compared to age-matched volunteers at short-term bed rest. Serum levels of osteocalcin were low. Most patients had mild hypercalcemia but only a third had hypercalciuria. All patients had elevated Al in blood or urine; urine Al correlated inversely with serum osteocalcin. In 60% significant bone Al was detectable by stain or quantitation. Our data are compatible with burn patients having markedly reduced bone turnover. Al loading, partial immobilization, endogenous corticosteroids, and cytokine production may be among the etiologic factors.

Management of the pediatric patient with burns.

Two million people in the United States receive medical treatment each year for burn injuries. One hundred thousand of these patients are hospitalized, and 7800 die as a direct result of their injuries. Of the patients that are hospitalized 30% to 40% are under 15 years of age. Sixty-seven percent are male. The average age of children with burns is 32 months. Flame burns account for approximately 13% of accidents, scalds account for 85%, and electrical and chemical burns account for approximately 2%. The majority of scald injuries are small. Sixteen percent of burn injuries are not accidental, and approximately half of these are a result of documentable, inflicted abuse.

Effect of exogenous growth hormone on glucose utilization in burn patients.

The treatment of burn patients with recombinantly derived human growth hormone (rHGH) appears effective in counteracting protein catabolism. However, exogenous growth hormone is frequently associated with hyperglycemia, an aspect which may limit its usefulness. Therefore, to assess the affect of rHGH on glucose utilization, 13 severely burned patients (65% +/- 4 TBSA burn; mean +/- SEM) began receiving on admission either placebo or rHGH (0.2 mg/kg.d) in a double-blind randomized fashion. While hypermetabolic (percentage REE/predicted REE 1.41 +/- 0.11) fasting oxygen consumption and CO2 production were measured using indirect calorimetry prior to and then during a hyperinsulinemic euglycemic clamp. This experiment demonstrated that rHGH significantly reduced glucose uptake and inhibited glucose oxidation compared to the placebo patients. Since the decreases in glucose oxidation and uptake were proportional, glucose utilization (percentage glucose uptake oxidized) remained similar in both patient groups. Furthermore, the hyperinsulinemic clamp lowered the plasma amino acid concentrations in the control patients while rHGH-treated patients had no significant alterations. In conclusion, exogenous growth hormone therapy induces an insulin resistance in burn patients. Furthermore, since the glucose utilization did not change, it is likely that the mechanism of insulin resistance is due to a deficiency in glucose transport.

Elevated serum aluminum levels in severely burned patients who are receiving large quantities of albumin.

Aluminum contaminates various fluids that are used in intravenous therapy, and it is associated with bone disease and encephalopathy. Albumin is highly contaminated with aluminum, which is eliminated primarily by renal excretion. Patients with burns receive large quantities of albumin and have impaired renal function, which puts them at hypothetical risk for aluminum loading. To assess the risk of aluminum loading we analyzed sera from 12 patients with burns for aluminum concentrations. Serum aluminum concentration was elevated in 8 of the 12 patients, and levels were at or near toxicity in 3 of the 8. Serum aluminum and serum creatinine levels directly correlated, r = 0.71 and p less than 0.005. No relation was found between serum aluminum and amount of albumin received. However, patients with the highest serum aluminum levels were the most severely burned and none survived. Thus patients with burns who are receiving albumin are at risk for aluminum loading. Impaired renal function contributes to aluminum retention.

Increased mortality with intravenous supplemental feeding in severely burned patients.

Patients with large cutaneous burns are characterized by an elevated metabolic rate and lose up to 25% of their body weight within 3 weeks. A previous study suggested that intravenous supplementation to attain nutritional requirements was of no benefit in patients with cutaneous burns covering greater than 50% of their total body surface area. In this study 39 patients with burns greater than 50% of their total body surface area were randomly assigned to receive intravenous supplementation of enteral calories (n = 16) or enteral calories alone (n = 23). Intravenous supplementation decreased the amount of enteral calories that patients with burns could tolerate. The mortality rate was significantly higher (p less than 0.05) in the intravenously supplemented group at 63% as compared with 26% in the group receiving enteral calories alone. Both groups showed significant decrease in natural killer cell activity when compared with controls at both 0 to 7 and 7 to 14 days after injury. T cell helper/suppressor ratios were depressed in both groups when compared with controls; however, the intravenously supplemented group was significantly depressed at 7 to 14 days after burn. Both groups demonstrated hepatomegaly, moderate fatty infiltration, and cholestasis. It is suggested that intravenous supplementation should be carefully evaluated and used only in patients with total enteral failure.

A comparison of conservative versus early excision. Therapies in severely burned patients.

Early excision and grafting of small burn wounds is a generally accepted treatment. Early excision of burn injuries greater than 30% total body surface area (TBSA) in adults, however, has not been universally accepted. In this study, 85 patients whose ages ranged from 17 to 55 years with greater than 30% total body surface area (TBSA) burns were randomly assigned to either early excision or topical antimicrobial therapy and skin grafting after spontaneous eschar separation. Mortality from burns without inhalation injury was significantly decreased by early excision from 45% to 9% in patients who were 17 to 30 years of age (p less than 0.025). No differences in mortality could be demonstrated between therapies in adult patients older than 30 years of age or with a concomitant inhalation injury. Children (n = 259) with similar large burns treated by early excision showed a significant increase in mortality with increasing burn size and with concomitant inhalation injury (p less than 0.05). The mean length of hospital stay of survivors was less than one day per per cent of TBSA burn in both children and adults.

Longitudinal assessment of breast development in adolescent female patients with burns involving the nipple-areolar complex.

Long-term follow-up of breast development in adolescent female patients with burns of the anterior chest wall is poorly documented. Between 1971 and 1976, 28 female patients with photographic documentation of burns to the anterior chest wall involving the nipple-areolar complex were reviewed. All patients were followed at least until their early teens. The mean age at the time of thermal injury was 5.9 +/- 2.5 years, with a mean follow-up time of 8.9 +/- 2.6 years. Thirteen patients (46 percent) were admitted to the Shriners Burns Institute in Galveston for acute care of their burns. Fifteen patients (54 percent) were referred for long-term follow-up or specific reconstructive procedures following care of the acute burns. In spite of significant thermal injury to the anterior chest wall with involvement of the nipple-areolar complex, no patient failed to develop breasts. Twenty patients (71 percent) required releases of the anterior chest wall to assist breast development. All anterior chest wall releases were accomplished with the use of skin grafts or local skin flaps.

Effect of propranolol administration on hemodynamic and metabolic responses of burned pediatric patients.

Hypermetabolism, increased heart rate, and lipolysis are responses to high catecholamine levels associated with burn injury. This study tests the hypothesis that adrenergic beta blockade in burns could reduce myocardial work, lipolysis, and negative nitrogen balance without adversely affecting cardiac or metabolic function. Eighteen patients with burns of 70 +/- 3% total burn surface area (TBSA) (Mean +/- SEM), were studied after a 5-day infusion of 2 mg/Kg of intravenous (I.V.) propranolol infusion every 24 hours without their cardiac output or resting energy expenditure being adversely reduced. Heart rate, left ventricular work, and rate pressure product were significantly reduced by 20, 22, and 36%, respectively (P less than 0.05). Plasma glucose, free fatty acids, triglycerides, and insulin levels remained unchanged. The rate of urea production, however, was significantly increased by 54 +/- 12% in fasted patients, and to a much lesser 12 +/- 2% in fed patients. The marked decrease in myocardial work afforded by propranolol administration may be of clinical benefit in the treatment of large burns. Variations in drug dosage and feeding regimens will, however, need to be perfected to limit catabolic effects.

Extravascular lung water changes following smoke inhalation and massive burn injury.

During a 3-year period (1984 through 1987), 40 patients with smoke inhalation, cutaneous burns, or a combination of both injuries were studied. Injuries were assigned to the three categories on the basis of bronchoscopic findings and clinical history. Eleven patients had simultaneously sustained a common smoke-inhalation injury without burns while trapped in a burning ship; twelve patients had massive cutaneous burns over 50% of the total body surface area (TBSA); and seventeen patients had cutaneous burns over more than 30% of the TBSA and inhalation injury. Colloid oncotic pressure was maintained with salt-poor albumin infusion. Central venous pressure, arterial saturation, inspired oxygen, arterial pressure, and urine output were continuously monitored. Extravascular lung water (EVLW) and cardiac output were measured by the double indicator (thermal dye dilution) technique. EVLW remained normal throughout the study period in the group of patients with burns alone. In the first 24 hours after injury, EVLW increased in both groups with smoke injury and remained elevated for more than 48 hours after injury in patients with smoke injury only. The group with both smoke-inhalation and burn injuries showed an early increase in EVLW, which returned to normal by 28 hours after injury and which remained normal until 5 days after injury. The EVLW level then increased again until the end of the study period. In this study, lung edema formation is attributed to the toxic effect of smoke inhalation.

Evaluation of a caloric requirement formula in burned children treated with early excision.

This study was undertaken to evaluate the effectiveness of a standard caloric requirement formula, as determined by retrospective analysis of weight gain of patients treated by serial debridement, for patients treated by early excision. The caloric intakes of 61 patients with more than 40% third-degree burn, 27 treated with serial debridement of the burn wound and 34 treated with early massive excision, were reviewed and compared to their calculated requirements. Nutritional support in both groups was similar. Of the 48 survivors there was no difference in their age, % TBSA burn, and per cent meeting caloric requirement. The early excision survivors had a greater percentage third-degree burn and weight change but a decreased length of stay. It was concluded that even though the formula, previously developed at our institution, may lead to a slight overestimation in determination of the caloric needs of early excision patients, it is an acceptable means of determining their requirements.

Determinants of mortality in pediatric patients with greater than 70% full-thickness total body surface area thermal injury treated by early total excision and grafting.

Recent advancements in burn care have improved the survival rates of victims with severe burn injuries. The total mortality rate in a series of 1,057 pediatric patients admitted to Shriners Burns Institute Galveston Unit between 1982 and 1986 was 2.7%. The burn size resulting in a 50% death rate was 95% of the total body surface area (TBSA). In this study 19 survivors and 13 nonsurvivors with greater than 70% full-thickness TBSA burn injuries were compared. All survivors were adequately resuscitated upon arrival 11% sustained an inhalation injury. Forty-six per cent of the nonsurvivors sustained an inhalation injury; 31% were not initially adequately resuscitated. The presence of preadmission shock and inhalation injury were early determinants of mortality with secondary renal, pulmonary, or cardiovascular collapse being the later predictors of mortality in these massively burned pediatric patients.

Effect of early excision on patients with major thermal injury.

A randomized study was carried out to determine the effect on mortality of early massive excision of large burns. Fifty consecutive adult patients admitted to our hospital burn unit between December 1983 and January 1986 with 2 degrees and 3 degrees burns totaling at least 30% total body surface area (TBSA) were randomized on admission to one of two groups. The patients received either conservative therapy or early massive excision of all full-thickness burns. The two groups were similar in average size of burn but differed in their average age. In the patients with burns greater than 50% TBSA and no inhalation injury, mortality was decreased with early excision, which can be explained entirely by age differences alone. There was not a significant difference in length of stay, blood requirements, or in mortality in other groups of patients.

Failure of TPN supplementation to improve liver function, immunity, and mortality in thermally injured patients.

Hypermetabolism with negative nitrogen balance and immune deficiencies characterize the systemic response to major thermal injury. Patients with burns greater than 50% of the total body surface area (TBSA) initially have poor gastrointestinal function, making it difficult to deliver sufficient enteral calories to meet nutritional requirements. Controversy has developed over whether to supplement oral alimentation with total parenteral nutrition (TPN) early in their treatment. This study randomly assigned 28 patients with burns greater than 50% TBSA to receive TPN supplementation or no TPN supplementation in the first 10 days postburn. Patients receiving TPN supplementation had significantly lower T-cell helper-to-suppressor cell ratios than the unsupplemented group. However, there was no difference in mortality between the groups (eight in each). All patients who died developed hepatomegaly associated with fatty infiltration cholestasis and antemortem liver function abnormalities, indicating that this syndrome is the result of burn injury itself, not TPN.

Fungal sepsis: an increasing problem in major thermal injuries.

In major thermal burns there has been an alarming emergence of fungal sepsis as defined by involvement of three or more organs and/or repeated positive blood cultures. During an 18-month period, we treated 72 patients (aged 18 +/- 2 years; TBSA burn, 57 +/- 3%; percent of third-degree burn, 45 +/- 3) with fungal sepsis. In all patients with documented three-organ involvement, treatment was with intravenous amphotericin (0.5 mg/kg body weight/day), immediate wound debridement, and early wound closure. The mortality was 32% (23 patients); 49 (68%) survived infection. Sixty-two variables were reviewed retrospectively using multiple regression analysis to ascertain specific factors associated with fungal sepsis and their relationship to survival. In burn patients, fungal sepsis is a strong determinant of survival, and its occurrence overshadows traditional factors presently utilized to predict clinical outcome.