High molecular weight sodium hyaluronate improves survival of syndecan-1-deficient septic mice by inhibiting neutrophil migration.

METHODS: Sepsis was induced by cotton smoke inhalation followed by intranasal administration of Pseudomonas aeruginosa in female (> 6 months) Balb/c and syndecan-1 knockout mice. Survival of mice, lung capillary endothelial glycocalyx integrity, lung water content, and vascular hyper-permeability were determined with or without HMW-SH treatment in these mice. Effects of HMW-SH on endothelial permeability and neutrophil migration were tested in in vitro setting. RESULTS: In septic wildtype mice, we found a severely damaged pulmonary microvascular endothelial glycocalyx and elevated levels of shed syndecan-1 in the circulation. These changes were associated with significantly increased pulmonary vascular permeability. In septic syndecan-1 knockout mice, extravascular lung water content was higher, and early death was observed. The administration of HMW-SH significantly reduced mortality and lung water content in septic syndecan-1 knockout mice, but not in septic wildtype mice. In in vitro setting, HMW-SH inhibited neutrophil migration and reduced cultured endothelial cell permeability increases. However, these effects were reversed by the addition of recombinant syndecan-1 ectodomain. CONCLUSIONS: HMW-SH reduced lung tissue damage and mortality in the absence of syndecan-1 protein, possibly by reducing vascular hyper-permeability and neutrophil migration. Our results further suggest that increased shed syndecan-1 protein levels are linked with the inefficiency of HMW-SH in septic wildtype mice.

Alterations in airway microbiota in patients with PaO2/FiO2 ratio ≤ 300 after burn and inhalation injury.

BACKGROUND: Injury to the airways after smoke inhalation is a major mortality risk factor in victims of burn injuries, resulting in a 15-45% increase in patient deaths. Damage to the airways by smoke may induce acute respiratory distress syndrome (ARDS), which is partly characterized by hypoxemia in the airways. While ARDS has been associated with bacterial infection, the impact of hypoxemia on airway microbiota is unknown. Our objective was to identify differences in microbiota within the airways of burn patients who develop hypoxemia early after inhalation injury and those that do not using next-generation sequencing of bacterial 16S rRNA genes. RESULTS: DNA was extracted from therapeutic bronchial washings of 48 patients performed within 72 hours of hospitalization for burn and inhalation injury at the North Carolina Jaycee Burn Center. DNA was prepared for sequencing using a novel molecule tagging method and sequenced on the Illumina MiSeq platform. Bacterial species were identified using the MTToolbox pipeline. Patients with hypoxemia, as indicated by a PaO2/FiO2 ratio ≤ 300, had a 30% increase in abundance of Streptococcaceae and Enterobacteriaceae and 84% increase in Staphylococcaceae as compared to patients with a PaO2/FiO2 ratio > 300. Wilcoxon rank-sum test identified significant enrichment in abundance of OTUs identified as Prevotella melaninogenica (p = 0.042), Corynebacterium (p = 0.037) and Mogibacterium (p = 0.048). Linear discriminant effect size analysis (LefSe) confirmed significant enrichment of Prevotella melaninognica among patients with a PaO2/FiO2 ratio ≤ 300 (p<0.05). These results could not be explained by differences in antibiotic treatment. CONCLUSIONS: The airway microbiota following burn and inhalation injury is altered in patients with a PaO2/FiO2 ratio ≤ 300 early after injury. Enrichment of specific taxa in patients with a PaO2/FiO2 ratio ≤ 300 may indicate airway environment and patient changes that favor these microbes. Longitudinal studies are necessary to identify stably colonizing taxa that play roles in hypoxemia and ARDS pathogenesis.

Airway obstruction and bacterial invasion in autopsy tissue of pediatric burn victims.

This study measured airway obstruction and bacterial invasion in systematically sampled lung tissue of burn victims at autopsy. Lung tissue from victims of combined smoke inhalation and burn injury (n = 5) and burn injury alone (n = 9) was examined histologically and the degree of bronchial and bronchiolar obstruction was measured. The walls of both bronchi and bronchioles were examined for bacterial invasion. Correlation analysis was performed for the association of airway obstruction with TBSA burn, number of ventilatory days, maximum inspiratory pressure, and days after injury. There was no significant difference in the mean degree of airway obstruction in smoke inhalation and burn victims compared with victims of burn-only injury (P > .05). Increased bronchiolar obstruction scores were detected in victims with pneumonia (55.3 ± 24.2%) compared with victims without pneumonia (9.3 ± 0.2%; P = .03). Bacterial invasion of the bronchial wall was present in one case, and invasion into the walls of bronchioles was seen in five cases. Burned children who died had extensive bronchiolar obstruction whether or not they had smoke inhalation injury. There was bacterial invasion into the airway wall in six of 14 cases (43%). Improved understanding of the mechanisms of airway obstruction is important for improved care of burned children.

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.

Microbial contamination in burn patients undergoing urgent intubation as part of their early airway management.

Inhalation injuries occur in approximately one third of all major burns and account for a significant number of deaths in burn patients each year. Previous studies have examined ventilator-associated pneumonia in patients with inhalation injury, but no study to date has evaluated the incidence of bacterial contamination of the airways on admission in patients with inhalation injuries. Because pulmonary complications have been found to cause or directly contribute to mortality in as high as 77% of patients, with combined inhalation injury and thermal injury, early detection of community-acquired pneumonia may significantly alter treatment outcomes. The authors conducted a retrospective review of all burn patients with early intubation and inhalation injury admitted between January 1, 2004 and December 31, 2006 who underwent bronchoscopy with bronchoalveolar lavage (BAL) within 24 hours of admission. Seventy-four consecutive patients fulfilled the inclusion criteria. Age, sex, percentage of total body surface area (%TBSA), presence of alcohol, site of intubation, grade of injury, and BAL results were examined. Analysis revealed a patient population that was 67.6% male, with a 42.0 +/- 17.1-year-old mean age, 27.0 +/- 24.7 %TBSA average burn, 1.6 +/- 1.2 inhalation grade, 17.8 +/- 24.4 ventilator days requirement, 27.3 +/- 31.4 days of length of stay, and 21.6% mortality. BAL results were grouped into four categories: 1) No growth, 2) Normal flora, 3) <100,000 colony-forming units (cfu), and 4) >100,000 cfu. By this criteria, 13 patients (17.6%) had no growth, 22 (29.7%) had normal flora, 27 (36.5%) had <100,000 cfu, and 12 (16.2%) had >100,000 cfu on the initial BAL. Therefore, 53% grew pathogenic organisms and 16% had >100,000 cfu on BAL with initial bronchoscopy. The predominant organisms were gram-positive cocci, with Streptococcus viridans found in 15 patients (20%), Staphylococcus aureus in eight (11%), and Streptococcus pneumonia in four (6%). Analysis of the patients with the highest bacterial loads revealed that they were 75% female and had a trend toward an increased ventilator requirement and longer length of stay. Patients with combined thermal and inhalation injury requiring urgent intubation have a high incidence of bacterial bronchial contamination. Inhalation injury creates a damaged tracheobronchial mucosa and early intubation provides a portal for bacterial contamination. Further studies with a larger patient population and randomization to treatment and nontreatment of the BAL culture results may show statistically significant differences in ventilator days, length of stay, and mortality.

Early complications and value of initial clinical and paraclinical observations in victims of smoke inhalation without burns.

OBJECTIVE: To evaluate the incidence of early pulmonary complications and the value of initial clinical signs and paraclinical investigations in victims of smoke inhalation not suffering from burns following structural fires. DESIGN: Retrospective chart review. SETTING: Thirteen-bed ICU. PATIENTS: Sixty-four victims of smoke inhalation following household fires were admitted to the ICU between January 1987 and December 1992. Exclusion criteria from the study were patients with cutaneous burns or multiple trauma or blast injury, and patients found in cardiac arrest. METHODS: Clinical, biological, and radiologic parameters were collected over a 5-day period. RESULTS: The mortality rate in relation to progressive respiratory failure was 3.1%. Mean ICU stay was 5.8 days (range, 1 to 33 days), and was longer in the patients presenting with soot deposits in the oropharynx (p = 0.02), dysphonia (D) (p = 0.05), or ronchi (R) (p = 0.0004) at the first examination, and in those having a positive sputum bacteriologic analysis (p = 0.003) or requiring parenteral bronchodilator agents for more than 24 h (p = 0.04). Thirty-five patients underwent mechanical ventilation (MV) for a mean of 101.2 h (range, 8 to 648 h). Mean MV duration was higher in the patients presenting initially with R (p = 0.003), high carbon monoxide (but not cyanide) levels (p = 0.02), or a positive bacteriologic sample (p = 0.0001). Positive bacteriologic sampling correlated with the presence of D (p = 0.02) or R (p = 0.04) and with immediate intubation (p = 0.0003). No correlation was found with chest radiograph. CONCLUSIONS: In this selected series of fire victims without cutaneous burns, respiratory injury was frequent. The initial clinical signs may be helpful to predict pulmonary complications.

A comparison of effects of thermal injury and smoke inhalation on bacterial translocation.

Thermal injury as well as smoke inhalation injury results in serious morbidity and high mortality. In a chronic ovine model, we studied the development of bacterial translocation to the mesenteric lymph node, liver, spleen, kidney, and lung following: 1) sham injury (N = 6), 2) cutaneous thermal injury (N = 5), 3) cotton smoke inhalation injury (N = 4), 4) combined thermal injury and smoke inhalation injury (N = 7). Cardiac output, mean arterial pressure, and plasma protein concentration were maintained within 10% of preinjury values. Urine output was maintained above 1 ml/kg/hour with fluid and plasma resuscitation. A wide-beam ultrasonic flow probe was chronically implanted to allow serial measurement of cephalic mesenteric arterial blood flow throughout the 48-hour experimental period. Sheep were sacrificed 48 hours following injury for quantitative organ culture of mesenteric lymph node, liver, spleen, kidney, and lung. Measurements of mesenteric blood flow demonstrated a decrease to 48 +/- 8%, 80 +/- 5%, and 64 +/- 9% of preinjury levels in sheep receiving thermal injury, smoke inhalation injury, and combination injury, respectively. The sham animals maintained mesenteric blood flow at 102 +/- 7% of control levels. Thermal injury, as well as combination thermal and smoke inhalation injury, resulted in higher levels of translocation than smoke inhalation injury alone.

Branhamella catarrhalis pneumonia with bacteremia in a pediatric patient with smoke inhalation.

Branhamella catarrhalis, a common inhabitant of the upper respiratory tract, has been identified recently as a cause of lower airway infection. In this report we present a case of B. catarrhalis pneumonia and bacteremia in a child with smoke inhalation as the first description of invasive disease involving this organism in a traumatized airway. In addition, other pediatric cases of B. catarrhalis bacteremia are reviewed, suggesting immunocompromise as a risk factor.