Benny L. Joyner

Bronchoscopy-Derived Correlates of Lung Injury following Inhalational Injuries: A Prospective Observational Study

Background Acute lung injury (ALI) is a major factor determining morbidity following burns and inhalational injury. In experimental models, factors potentially contributing to ALI risk include inhalation of toxins directly causing cell damage; inflammation; and infection. However, few studies have been done in humans. Methods We carried out a prospective observational study of patients admitted to the NC Jaycees Burn Center who were intubated and on mechanical ventilation for burns and suspected inhalational injury. Subjects were enrolled over an 8-month period and followed till discharge or death. Serial bronchial washings from clinically-indicated bronchoscopies were collected and analyzed for markers of cell injury and inflammation. These markers were compared with clinical markers of ALI. Results Forty-three consecutive patients were studied, with a spectrum of burn and inhalation injury severity. Visible soot at initial bronchoscopy and gram negative bacteria in the lower respiratory tract were associated with ALI in univariate analyses. Subsequent multivariate analysis also controlled for % body surface area burns, infection, and inhalation severity. Elevated IL-10 and reduced IL-12p70 in bronchial washings were statistically significantly associated with ALI. Conclusions Independently of several factors including initial inhalational injury severity, infection, and extent of surface burns, high early levels of IL-10 and low levels of IL-12p70 in the central airways are associated with ALI in patients intubated after acute burn/inhalation injury. Lower airway secretions can be collected serially in critically ill burn/inhalation injury patients and may yield important clues to specific pathophysiologic pathways.

DNA and Inflammatory Mediators in Bronchoalveolar Lavage Fluid From Children With Acute Inhalational Injuries

The aim of this study was to assess the feasibility of using serial bronchoalveolar lavage fluids (BALFs) to characterize the course of cell damage and inflammation in the airways of pediatric patients with acute burn or inhalation injury. This was a prospective, longitudinal, descriptive pilot study conducted at the Burn and Pediatric Intensive Care Units in a tertiary care medical center. Six consecutively intubated and mechanically ventilated pediatric patients with acute inhalational injuries were studied. Serial BALF specimens from clinically indicated bronchoscopies were used to measure DNA and cytokine levels. BALF DNA levels for the six pediatric burn subjects were the highest within the first 72 hours after burn injury and declined thereafter. At the early stages after injury, BALF DNA levels (median [min, max] 3789 [1170, 11,917] ng/ml) were similar to those in adult burn patients and pediatric cystic fibrosis or bronchiectasis patients and was higher than those in pediatric recurrent pneumonia patients. BALF DNA levels in children and adults with inhalation injury correlated significantly with BALF interleukin-6, interleukin-8, and transforming growth factor-&bgr;1 levels. The patient with the most severe early visible airway mucosal damage and soot pattern at bronchoscopy, as well as the most extensive burns, also had the highest average early BALF DNA level (11,917ng/ml) and the longest ventilator course and hospital stay. Procedures were well tolerated. In children with acute burn and inhalational injury, airway cellular damage and inflammation (reflected in high BALF DNA levels) appear to peak during the first 72 hours after burn or inhalation injury followed by a slow decline. Serial analysis of factors in airway secretions is feasible and has the potential to reveal important pathophyisiologic pathways and therapeutic targets for the treatment of acute inhalational injuries.

Mortality after fluid bolus in African children with sepsis.

To the Editor: The Fluid Expansion as Supportive Therapy (FEAST; Current Controlled Trials number, ISRCTN69856593) Trial Group (June 30 issue)1 performed a meticulous study of fluid resuscitation in children with sepsis. We note that the excess mortality in the intervention group was most pronounced among severely anemic children but not statistically significant among children with a hemoglobin level of 5 g per deciliter or more (Fig. 3 of the article). This finding suggests that acute hemodilution in children with preexisting anemia may have caused the increased mortality in the resuscitation group. Assuming a circulating blood volume of 80 ml per kilogram of body weight, a child with a hemoglobin level of 5 g per deciliter on admission would undergo hemodilution to 4 g per deciliter. The most comprehensive pediatric literature on anemia in children with sepsis and in pediatric intensive care unit (ICU) populations has studied a transfusion threshold hemoglobin level of 7.0 g per deciliter.2,3 Below this level, evidence is anecdotal.4 The physiological effect of severe dilutional anemia is predictable and detrimental: impaired oxygen delivery leading to organ failure. This is not a criticism of the trial per se, but it is a possible mechanism for the apparent harm of fluid resuscitation with an agent other than blood in children with anemia and sepsis seen in this study.