Colleen M. Ryan

Objective Estimates of the Probability of Death from Burn Injuries

BACKGROUND Over the past 20 years, there has been remarkable improvement in the chances of survival of patients treated in burn centers. A simple, accurate system for objectively estimating the probability of death would be useful in counseling patients and making medical decisions. METHODS We conducted a retrospective review of all 1665 patients with acute burn injuries admitted from 1990 to 1994 to Massachusetts General Hospital and the Shriners Burns Institute in Boston. Using logistic-regression analysis, we developed probability estimates for the prediction of mortality based on a minimal set of well-defined variables. The resulting mortality formula was used to determine whether changes in mortality have occurred since 1984, and it was tested prospectively on all 530 patients with acute burn injuries admitted in 1995 or 1996. RESULTS Of the 1665 patients (mean [+/-SD] age, 21+/-20 years; mean burn size, 14+/-20 percent of body-surface area), 1598 (96 percent) lived to discharge. The mean length of stay was 21+/-29 days. Three risk factors for death were identified: age greater than 60 years, more than 40 percent of body-surface area burned, and inhalation injury. The mortality formula we developed predicts 0.3 percent, 3 percent, 33 percent, or approximately 90 percent mortality, depending on whether zero, one, two, or three risk factors are present. The results of the prospective test of the formula were similar. A large increase in the proportion of patients who chose not to be resuscitated complicated comparisons of mortality over time. CONCLUSIONS The probability of mortality after burns is low and can be predicted soon after injury on the basis of simple, objective clinical criteria.

Multicenter postapproval clinical trial of Integra dermal regeneration template for burn treatment.

The safety and effectiveness of Integra Dermal Regeneration Template was evaluated in a postapproval study involving 216 burn injury patients who were treated at 13 burn care facilities in the United States. The mean total body surface area burned was 36.5% (range, 1-95%). Integra was applied to fresh, clean, surgically excised burn wounds. Within 2 to 3 weeks, the dermal layer regenerated, and a thin epidermal autograft was placed. The incidence of invasive infection at Integra-treated sites was 3.1% (95% confidence interval, 2.0-4.5%) and that of superficial infection 13.2% (95% confidence interval, 11.0-15.7%). Mean take rate of Integra was 76.2%; the median take rate was 95%. The mean take rate of epidermal autograft was 87.7%; the median take rate was 98%. This postapproval study further supports the conclusion that Integra is a safe and effective treatment modality in the hands of properly trained clinicians under conditions of routine clinical use at burn centers.

A 10-year experience with toxic epidermal necrolysis

Toxic epidermal necrolysis is a devastating medication-induced desquamation disorder with a reported mortality rate of 30% to 60% in adults. Data from previously reported series suggest that age, delay in referral to a burn center, total body surface area (TBSA) involvement, and systemic steroid treatment are poor prognostic indicators. We reviewed the records of 39 patients treated in our burn center over the past 10 years and found that the mortality rate was significantly correlated with age, thrombocytopenia, and delay in presentation. Steroid treatment and TBSA involvement were not significantly related to the mortality rate. Thirty-nine adult patients with greater than 20% TBSA epithelial necrosis were cared for in our center from January 1987 to March 1998. Wounds were treated with topical antimicrobial medications and porcine xenografts in a bacteria-controlled nursing unit. We reviewed the records of these patients for 28 clinical characteristics and looked for clinical correlates of mortality by single analysis of variance. The mortality rate was 44% (17 of 39 patients); the cause of death was most commonly multiple-organ dysfunction syndrome, for which a microbial etiologic agent was not always identified. Autopsies were performed on 11 of the 17 patients who died; there was evidence of multiple-organ damage. The patients who survived and the patients who died did not differ significantly in TBSA epithelial necrosis (66%+/-6% vs 72%+/-5%, respectively), admission platelets, number of nosocomial infections, number of complications, preadmission exposure to steroids, or extent of mucosal involvement. When compared with the patients who died, the patients who survived were (1) 20 years younger (47.5+/-4.2 years vs 64.5+/-5.3 years), (2) admitted to the hospital sooner after the onset of their rash (3.5+/-0.4 days vs 5.9+/-1.0 days), (3) much less likely to experience early thrombocytopenia (platelet nadir, 154+/-24 vs 70+/-18), (4) more likely to be febrile on presentation, and (5) less likely to have been treated with antibiotics before referral to our unit. These differences were statistically significant. The most common etiologic agents were antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs. Our results for a group of older patients with toxic epidermal necrolysis with extensive skin involvement suggest that age, delay in hospitalization, thrombocytopenia, and early empiric antibiotic treatment are associated with a poor prognosis.

The Metabolic Basis of the Increase in Energy Expenditure in Severely Burned Patients

Background: Severe burn trauma is characterized by an elevated rate of whole-body energy expenditure. Approach: In this short review, we have attempted to assess the metabolic characteristics of and basis for the persistent increase in energy expenditure during the flow phase of the injury. We consider some aspects of normal energy metabolism, including the contribution of the major adenosine triphosphate (ATP)-consuming reactions to the standard or basal metabolic rate. Rate estimates are compiled from the literature for a number of these reactions in healthy adults and burned patients, and the values are related to the increased rates of whole-body energy expenditure with burn injury. Results: Whole-body protein synthesis, gluconeogene sis, urea production, and substrate cycles (total fatty acid and glycolytic-gluconeogenic) account for approximately 22% 11%, 3%, 17%, and 4%, respectively, of the burn-induced increase in total energy expenditure. Conclusions: These ATP consuming reactions, therefore, se...

Increased gut permeability early after burns correlates with the extent of burn injury

ObjectiveTo determine if increased gut permeability within 48 hrs after burn injury correlates with the extent of injury, before sepsis and pulmonary disorders have complicated the clinical course. DesignNonrandomized, controlled study. PatientsConsecutive patients admitted with burn injuries on >20% of body surface area. InterventionsIntestinal absorption and renal excretion of polyethylene glycol 3350 was used as the macromolecule to determine gut permeability; polyethylene glycol 400 intestinal absorption was used as an internal control for abnormal motility and malabsorption. Polyethylene glycol 3350 (40 g) and polyethylene glycol 400 (5 g) were administered enterally. Measurements and Main ResultsGut permeability was significantly increased early after the injury. The patients excreted 0.56 ± 0.34% (n = 11) of polyethylene glycol 3350, compared with the amount (0.12 ± 0.04%) (p < .05) previously reported in normal volunteers. There was no significant difference in the excretion of polyethylene glycol 400 in the patients (27.0 ± 4.6%, n = 11) vs. the normal volunteers previously reported (26.3 ± 5.1%, n = 12), suggesting normal intestinal motility and absorption. The percentage of excretion of polyethylene glycol 3350 correlated with the percentage body surface burned; patients with smaller injuries excreted 0.32 ± 0.17% (n = 6), which was greater than normal and less than those values from patients with larger injuries, 0.84 ± 0.25% (n = 5) (p < .001 by Tukey test). ConclusionsUsing our newly developed method to separate and quantify polyethylene glycols in urine, gut permeability was found to be increased early after burn injury, which confirms a previous study using lactulose as the permeability probe. Furthermore, this increased gut permeability to polyethylene glycol 3350 correlated with the extent of the burn injury.

Gut Macromolecular Permeability in Pancreatitis Correlates With Severity of Disease in Rats

BACKGROUND Increased intestinal macromolecular permeability could allow absorption of substances from the bowel into the systemic circulation and contribute to multiple organ system failure. METHODS Mild, intermediate, and severe grades of pancreatitis were induced in rats using intravenous caerulein and intraductal glycodeoxycholic acid. [14C]polyethylene glycol (molecular weight, 3350 daltons; 1.1 microCi/142 mg) was instilled into the distal duodenum. At 24 hours, the animals were killed, ascitic fluid was collected for trypsinogen activation peptide measurement, and pancreatic specimens were collected and scored for based on the degree of necrosis, inflammation, and hemorrhage. RESULTS Gut permeability to polyethylene glycol 3350 (PEG 3350) was increased in animals with early experimental pancreatitis (5.4% +/- 1.2%, n = 20) when compared with control animals (1.8% +/- 0.2%; n = 6) (P = 0.0005). Furthermore, intestinal macromolecular permeability to PEG 3350 correlated with severity of disease as predicted by the method of induction of pancreatitis (P = 0.0003), the histological findings (P = 0.0002), and total ascitic trypsinogen activation peptides content (P = 0.029). CONCLUSIONS Increased gut permeability in experimental pancreatitis can be correlated with pancreatitis severity.

The acutely burned hand : management and outcome based on a ten-year experience with 1047 acute hand burns

Optimal hand function has a very positive impact on the quality of survival after burn injury. Over a 10-year period, 659 patients with 1047 acutely burned hands were managed at the Sumner Redstone Burn Center of the Massachusetts General Hospital. Our approach to acutely burned hands emphasizes ranging and splinting throughout hospitalization, prompt sheet autograft wound closure as soon as practical, and the selective use of axial pin fixation and flaps. This approach is associated with normal function in 97% of those with superficial injuries and 81% of those with deep dermal and full-thickness injuries requiring surgery. Although only 9% of those with injuries involving the extensor mechanism, joint capsule, or bone had normal functional outcomes, 90% were able to independently perform activities of daily living.

Permissive Hypercapnia as a Ventilatory Strategy in Burned Children: Effect on Barotrauma, Pneumonia, and Mortality

OBJECTIVE To document the incidence of barotrauma, pneumonia, and respiratory death associated with a mechanical ventilation protocol based on permissive hypercapnia in pediatric burn patients. DESIGN Retrospective review. MATERIALS AND METHODS Patients were managed using a mechanical ventilation protocol based on permissive hypercapnia, tolerating moderate (pH > 7.20) respiratory acidosis to keep inflating pressures below 40 cm H2O. MAIN RESULTS Over a 2.5-year interval, 54 burned children (11% of 495 acute admissions) with an average age of 6.5 years (range 5 weeks to 17 years), average burn size of 44% (range 0 to 98%), and median burn size of 46% required mechanical ventilatory support for an average of 12.5 days (range 1 to 56 days). Inhalation injury was diagnosed in 34 (63%) of the children and 72% percent were admitted within 24 hours of injury. Overt barotrauma occurred in 5.6% of the patients, pneumonia in 32%, and respiratory death in 0%. CONCLUSIONS A conventional ventilation protocol based on permissive hypercapnia is associated with acceptable rates of barotrauma and pneumonia. The low incidence of respiratory death associated with this strategy suggests that it also minimizes ventilator-induced lung injury.

Death in the burn unit: sterile multiple organ failure

It has been our impression over the years that the most common cause of death in our burn patients is multiple organ failure, despite the clinical absence of uncontrolled infection at the time of death. A six year review of all deaths in our unit confirmed this impression, revealing that multiorgan failure is indeed the most common cause of death (48 patients, 67 per cent), followed rather distantly by early withdrawal of support (15 patients, 21 per cent), resuscitation failure (4 patients, 6 per cent) and isolated pulmonary failure (4 patients, 6 per cent). Finally, we found that our patients dying of multiorgan failure, although often having had multiple small infections during their course, were indeed clinically uninfected at the time of death. These findings are consistent with the supposition that uncontrolled systemic inflammation, initially triggered by tissue injury and isolated infection, persists despite control of these infections and leads to multiple organ failure and death.

Plasma arginine and leucine kinetics and urea production rates in burn patients

We measured plasma arginine and leucine kinetics and rates of urea production (appearance) in 12 severely burned patients (mean body surface burn area, 48%) during a basal state (low-dose intravenous glucose) and while receiving routine, total parenteral nutrition ([TPN] fed state) including an L-amino acid mixture, supplying a generous level of nitrogen (mean, 0.36 g N.kg-1.d-1). The two nutritional states were studied in random order using a primed 4-hour constant intravenous tracer infusion protocol. Stable-nuclide-labeled tracers were L-[guanidino-13C]arginine, L-[1-13C]leucine, [18O]urea, and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, alpha-ketoisocaproate ([KIC] for leucine), and urea in plasma and 13CO2 in breath. Results are compared with data obtained in these laboratories in healthy adults. Leucine kinetics (flux and disappearance into protein synthesis) indicated the expected higher turnover in burn patients than in healthy controls. Mean leucine oxidation rates are also higher and compared well with values predicted from urea production rates, provided that urea nitrogen recycling via intestinal hydrolysis is taken into account. The plasma urea flux was also higher than for normal subjects. Arginine fluxes as measured in the systemic whole body, via the plasma pool, were correspondingly higher in burned patients than in healthy controls and were in good agreement with values predicted from leucine-KIC kinetics. However, systemic whole-body arginine flux measured via the plasma pool was only 20% of the arginine flux estimated from the urea flux plus the rate of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)