Samuel W. Jones

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.

Catechol-O-Methyltransferase Genotype Predicts Pain Severity in Hospitalized Burn Patients

Increasing evidence suggests that stress system activation after burn injury may contribute to burn-related pain. If this is the case, then genetic variations influencing the function of important stress system components, such as the enzyme catechol-O-methyltransferase (COMT), may predict pain severity after thermal burn injury. The authors evaluated the association between COMT genotype and pain intensity in 57 individuals hospitalized after thermal burn injury. Consenting participants at four burn centers were genotyped and completed daily 0 to 10 numeric rating scale pain assessments on 2 consecutive days including evaluation of waking, least, and worst pain. The association between COMT genotype and individual pain outcomes was calculated using a linear mixed model adjusting for sociodemographic and burn injury characteristics. Overall pain (combination of least, worst, and waking pain scores) was significantly higher in patients with a COMT pain vulnerable genotype (6.3 [0.4] vs 5.4 [0.4], P = .037). Individuals with a COMT pain vulnerable genotype also had significantly higher “least pain” scores (3.8 [0.5] vs 2.6 [0.4], P = .017) and significantly higher pain on awakening (6.8 [0.5] vs 5.3 [0.4], P = .004). Differences in worst pain according to genotype group were not significant. COMT pain vulnerable genotype was a stronger predictor of overall pain severity than burn size, burn depth, or time from admission to pain interview assessment. These findings suggest that genetic factors influencing stress system function may have an important influence on pain severity after burn injury. Further studies of genetic predictors of pain after burn injury are needed.

Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury

Bacterial infection is a major cause of morbidity affecting outcome following burn and inhalation injury. While experimental burn and inhalation injury animal models have suggested that mediators of cell damage and inflammation increase the risk of infection, few studies have been done on humans. This is a prospective, observational study of patients admitted to the North Carolina Jaycee Burn Center at the University of North Carolina who were intubated and on mechanical ventilation for treatment of burn and inhalational injury. Subjects were enrolled over a 2-yr period and followed till discharge or death. Serial bronchial washings from clinically indicated bronchoscopies were collected and analyzed for markers of tissue injury and inflammation. These include damage-associated molecular patterns (DAMPs) such as hyaluronic acid (HA), double-stranded DNA (dsDNA), heat-shock protein 70 (HSP-70), and high-mobility group protein B-1 (HMGB-1). The study population was comprised of 72 patients who had bacterial cultures obtained for clinical indications. Elevated HA, dsDNA, and IL-10 levels in bronchial washings obtained early (the first 72 h after injury) were significantly associated with positive bacterial respiratory cultures obtained during the first 14 days postinjury. Independent of initial inhalation injury severity and extent of surface burn, elevated levels of HA dsDNA and IL-10 in the central airways obtained early after injury are associated with subsequent positive bacterial respiratory cultures in patients intubated after acute burn/inhalation injury.

Healthcare-Associated Infections among Patients in a Large Burn Intensive Care Unit: Incidence and Pathogens, 2008–2012

Burn injuries are a common source of morbidity and mortality in the United States, with an estimated 450,000 burn injuries requiring medical treatment, 40,000 requiring hospitalization, and 3,400 deaths from burns annually in the United States. Patients with severe burns are at high risk for local and systemic infections. Furthermore, burn patients are immunosuppressed, as thermal injury results in less phagocytic activity and lymphokine production by macrophages. In recent years, multidrug-resistant (MDR) pathogens have become major contributors to morbidity and mortality in burn patients. Since only limited data are available on the incidence of both device- and nondevice-associated healthcare-associated infections (HAIs) in burn patients, we undertook this retrospective cohort analysis of patients admitted to our burn intensive care unit (ICU) from 2008 to 2012.

Overwhelming disseminated herpes simplex virus type 2 infection in a patient with severe burn injury: case report and literature review.

Viral-mediated organ disease is an infrequent but recognized complication of severe burn injury. This occurs primarily because of herpes family viruses such as cytomegalovirus, herpes simplex virus (HSV), and Epstein-Barr virus given their ability to establish lifelong latency after primary infection and reactivate in the setting of altered immune function. In this report, we describe a severely burned patient who succumbed to fulminant HSV-2 pneumonitis and hepatitis, and summarize the existing literature on HSV infections in this unique patient population. To our knowledge, this is the first report of disseminated visceral HSV-2 infection in a burn patient in the medical literature.

Timeline of health care–associated infections and pathogens after burn injuries

BACKGROUND Infections are an important cause of morbidity and mortality after burn injuries. Here, we describe the time line of infections and pathogens after burns. METHODS A retrospective study was performed in a large tertiary care burn center from 2004-2013. Analyses were performed on health care-associated infections (HAIs) meeting Centers for Disease Control and Prevention criteria and on all positive cultures. Incidence rates per 1,000 days were calculated for specific HAI categories and pathogens and across hospitalization time (week 1, weeks 2-3, and week ≥4). RESULTS Among 5,524 patients, the median burn size was 4% of total body surface area (interquartile range, 2%-10%). Of the patients, 7% developed an HAI, of whom 33% had >1 HAI episode. Gram-positive bacteria were isolated earlier, and gram-negative bacteria were isolated later during hospitalization. Of 1,788 bacterial isolates, 44% met criteria for multidrug resistance, and 23% met criteria for extensive drug resistance. Bacteria tended to become increasingly resistant to antibiotics as time from admission increased. CONCLUSIONS We observed differences in infection type, pathogen, and antibiotic-resistant bacterium risk across time of hospitalization. These results may guide infection prevention in various stages of the postburn admission.

Reduction in central line-associated bloodstream infections in patients with burns

2000 Enhanced education of medical staff regarding central lines; addition of 2% chlorhexidine plus 70% isopropyl alcohol for skin preparation to central line kits 2001 Mandatory training for nurses on IV line site care and maintenance 2003 Central line changes over a guidewire every 3 days with use of a new site every 6 days becomes standard practice; use of full body drape for line insertion and changes 2003–2005 Introduction of antibiotic-impregnated central venous catheters for all patients 2004 Enhanced nursing education on central line insertion and maintenance 2005 Customized catheter-insertion kits 2006 Universal glove and gown use for all patient encounters 2007 Implementation of the Institute for Healthcare Improvement bundle to prevent CLABSI 2009 Use of chlorhexidine patch at insertion site

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.

Influence of Race and Neighborhood on the Risk for and Outcomes of Burns in the Elderly in North Carolina

Risk factors for mortality and length of hospital stay in elderly burn patients are well established, but the influence of race and socioeconomic status has not been evaluated. This study evaluates the effect of neighborhood level socioeconomic indicators on burns risk, and determines whether race and neighborhood influence burn injury outcomes in the elderly. Data from the North Carolina Jaycee Burn Center was linked to United States Census Bureau block group socioeconomic data. The odds of death and increased length of hospital stay for European-Americans and Minorities were determined using logistic regression. Rates of burn were determined using Poisson regression, and multilevel modeling was used to evaluate the influence of neighborhood on outcomes. No significant differences in mortality were observed between European-American and Minority patients in individual (Minority OR 0.71; p=0.3200) and multilevel (0.72; p=0.4020) models. Minorities had significantly higher odds of increased length of hospital stay in individual (2.05; p=0.0020) and multilevel (2.55; 0.037) models. High proportions of rural households (RR=1.39; p=0.0010) and poverty (1.26; p<0.0001) were significantly associated with increased risk of burn. Additional investigation using larger databases will allow further elucidation of the contextual effects of socioeconomic status on burn in the elderly.

Intermediary Variables and Algorithm Parameters for an Electronic Algorithm for Intravenous Insulin Infusion

Background: Algorithms for intravenous insulin infusion may assign the infusion rate (IR) by a two-step process. First, the previous insulin infusion rate (IRprevious) and the rate of change of blood glucose (BG) from the previous iteration of the algorithm are used to estimate the maintenance rate (MR) of insulin infusion. Second, the insulin IR for the next iteration (IRnext) is assigned to be commensurate with the MR and the distance of the current blood glucose (BGcurrent) from target. With use of a specific set of algorithm parameter values, a family of iso-MR curves is created, each giving IR as a function of MR and BG. Method: To test the feasibility of estimating MR from the IRprevious and the previous rate of change of BG, historical hyperglycemic data points were used to compute the “maintenance rate cross step next estimate” (MRcsne). Historical cases had been treated with intravenous insulin infusion using a tabular protocol that estimated MR according to column-change rules. The mean IR on historical stable intervals (MRtrue), an estimate of the biologic value of MR, was compared to MRcsne during the hyperglycemic iteration immediately preceding the stable interval. Hypothetically calculated MRcsne-dependent IRnext was compared to IRnext assigned historically. An expanded theory of an algorithm is developed mathematically. Practical recommendations for computerization are proposed. Results: The MRtrue determined on each of 30 stable intervals and the MRcsne during the immediately preceding hyperglycemic iteration differed, having medians with interquartile ranges 2.7 (1.2–3.7) and 3.2 (1.5–4.6) units/h, respectively. However, these estimates of MR were strongly correlated (R 2 = 0.88). During hyperglycemia at 941 time points the IRnext assigned historically and the hypothetically calculated MRcsne-dependent IRnext differed, having medians with interquartile ranges 4.0 (3.0–6.0) and 4.6 (3.0–6.8) units/h, respectively, but these paired values again were correlated (R 2 = 0.87). This article describes a programmable algorithm for intravenous insulin infusion. The fundamental equation of the algorithm gives the relationship among IR; the biologic parameter MR; and two variables expressing an instantaneous rate of change of BG, one of which must be zero at any given point in time and the other positive, negative, or zero, namely the rate of change of BG from below target (rate of ascent) and the rate of change of BG from above target (rate of descent). In addition to user-definable parameters, three special algorithm parameters discoverable in nature are described: the maximum rate of the spontaneous ascent of blood glucose during nonhypoglycemia, the glucose per daily dose of insulin exogenously mediated, and the MR at given patient time points. User-assignable parameters will facilitate adaptation to different patient populations. Conclusions: An algorithm is described that estimates MR prior to the attainment of euglycemia and computes MR-dependent values for IRnext. Design features address glycemic variability, promote safety with respect to hypoglycemia, and define a method for specifying glycemic targets that are allowed to differ according to patient condition.