Ventilation practices in burn patients-an international prospective observational cohort study.

BACKGROUND: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). METHODS: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. RESULTS: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O. CONCLUSION: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28. TRIAL REGISTRATION: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.

Nebulized Heparin in Burn Patients with Inhalation Trauma-Safety and Feasibility.

BACKGROUND: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. METHODS: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. RESULTS: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. CONCLUSION: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients.

Changes in ventilator settings and ventilation-induced lung injury in burn patients-A systematic review.

OBJECTIVE: Ventilation strategies aiming at prevention of ventilator-induced lung injury (VILI), including low tidal volumes (VT) and use of positive end-expiratory pressures (PEEP) are increasingly used in critically ill patients. It is uncertain whether ventilation practices changed in a similar way in burn patients. Our objective was to describe applied ventilator settings and their relation to development of VILI in burn patients. DATA SOURCES: Systematic search of the literature in PubMed and EMBASE using MeSH, EMTREE terms and keywords referring to burn or inhalation injury and mechanical ventilation. STUDY SELECTION: Studies reporting ventilator settings in adult or pediatric burn or inhalation injury patients receiving mechanical ventilation during the ICU stay. DATA EXTRACTION: Two authors independently screened abstracts of identified studies for eligibility and performed data extraction. DATA SYNTHESIS: The search identified 35 eligible studies. VT declined from 14 ml/kg in studies performed before to around 8 ml/kg predicted body weight in studies performed after 2006. Low-PEEP levels (<10 cmH2O) were reported in 70% of studies, with no changes over time. Peak inspiratory pressure (PIP) values above 35 cmH2O were frequently reported. Nevertheless, 75% of the studies conducted in the last decade used limited maximum airway pressures (≤35 cmH2O) compared to 45% of studies conducted prior to 2006. Occurrence of barotrauma, reported in 45% of the studies, ranged from 0 to 29%, and was more frequent in patients ventilated with higher compared to lower airway pressures. CONCLUSION: This systematic review shows noticeable trends of ventilatory management in burn patients that mirrors those in critically ill non-burn patients. Variability in available ventilator data precluded us from drawing firm conclusions on the association between ventilator settings and the occurrence of VILI in burn patients.

HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial.

BACKGROUND: Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma. METHODS: The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours. DISCUSSION: As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma. TRIAL REGISTRATION: NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013.Recruiting. Randomisation commenced on 1 January 2014.

Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study.

INTRODUCTION: Soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a biologic marker of fibrinolysis and inflammation. The aim of this study was to investigate the diagnostic and prognostic value of systemic and pulmonary levels of suPAR in burn patients with inhalation trauma who need mechanical ventilation. METHODS: suPAR was measured in plasma and nondirected lung-lavage fluid of mechanically ventilated burn patients with inhalation trauma. The samples were obtained on the day of inhalation trauma and on alternate days thereafter until patients were completely weaned from the mechanical ventilator. Mechanically ventilated patients without burns and without pulmonary disease served as controls. RESULTS: Systemic levels of suPAR in burn patients with inhalation trauma were not different from those in control patients. On admission and follow up, pulmonary levels of suPAR in patients with inhalation trauma were significantly higher compared with controls. Pulmonary levels of suPAR highly correlated with pulmonary levels of interleukin 6, a marker of inflammation, and thrombin-antithrombin complexes, markers of coagulation, but not plasminogen activator activity, a marker of fibrinolysis. Systemic levels of suPAR were predictive of the duration of mechanical ventilation and length of intensive care unit (ICU) stay. Duration of mechanical ventilation and length of ICU stay were significantly longer in burn-injury patients with systemic suPAR levels > 9.5 ng/ml. CONCLUSIONS: Pulmonary levels of suPAR are elevated in burn patients with inhalation trauma, and they correlate with pulmonary inflammation and coagulation. Although pulmonary levels of suPAR may have diagnostic value in burn-injury patients, systemic levels of suPAR have prognostic value.

Increase in early mechanical ventilation of burn patients: an effect of current emergency trauma management?

BACKGROUND: Data relating to patients admitted with extensive burn injuries in the Netherlands have revealed a marked increase in patients whose initial care included mechanical ventilation (MV). The increase was abrupt, dating from 1997, and has been sustained since. The aim of this study is to quantify this observation and to discuss possible causes. METHODS: The study included 258 consecutive patients with burns >30% total body surface area admitted to the Beverwijk burns center. Patients were divided into two groups based on admission date: group 1 from 1987 to 1996 (n=135) and group 2 from 1997 to 2006 (n=123). Data were analyzed using χ or analysis of variance. RESULTS: There were no differences between groups in demographics, facial burns, inhalation injury, and % total body surface area. However, the number of patients subjected to MV at admission increased from 38% to 76% (group 1 vs. 2; p<0.001). In 57% of patients who were intubated based on the suspicion of inhalation injury, this condition could not be confirmed (p<0.05 vs. 9% [1987-1996]). CONCLUSIONS: This study has confirmed that a higher proportion of patients were treated with MV since 1997, whereas the severity of burn injury remained unchanged throughout the study period. In the absence of a clinical explanation, we surmise that there has been a change within Dutch casualty departments in the initial management of major burn injury. The change coincides with the implementation of the Advanced Life Trauma Support training course as the accepted standard of trauma care in Dutch hospitals.

Pulmonary activation of coagulation and inhibition of fibrinolysis after burn injuries and inhalation trauma.

BACKGROUND: Pulmonary coagulopathy is intrinsic to pneumonia and other forms of acute lung injury. We hypothesized patients with burn injuries and inhalation trauma to have similar alterations in pulmonary coagulation and fibrinolysis. METHODS: We performed a prospective study on changes in pulmonary and systemic thrombin generation and fibrinolytic activity in patients with burn injuries and inhalation trauma requiring mechanical ventilation. Nondirected bronchial lavage was performed on alternate days. Patients requiring mechanical ventilation for nonpulmonary reasons who did not meet the North American European Consensus Conference criteria for acute lung injury functioned as control patients. RESULTS: We studied 13 patients with burn injuries and inhalation trauma and 15 control patients. On admission, patients with burn injuries and inhalation trauma showed a significant increase in thrombin generation in the airways compared with control patients, as reflected by increased lavage fluid levels of thrombin-antithrombin complexes and fibrin degradation products, and decreased lavage fluid levels of activated protein C and antithrombin. Simultaneously, burn patients showed a significant decrease in fibrinolytic activity, as reflected by decreased lavage fluid levels of plasminogen activator activity. Pulmonary coagulopathy persisted throughout the period of mechanical ventilation and was accompanied by similar changes in systemic coagulation and fibrinolysis. There was no significant correlation between changes in coagulation and fibrinolysis and the extent of burn injury. CONCLUSIONS: Patients with burn injuries and inhalation trauma requiring mechanical ventilation show a distinct and sustained procoagulant and antifibrinolytic shift in the pulmonary compartment. Pulmonary coagulopathy could be an important therapeutic target in these patients.

Mechanical ventilation and fluid retention in burn patients.

BACKGROUND: Burn patients with inhalation injury (INHI) require more fluid resuscitation than patients without INHI. However, the relation between INHI and fluid resuscitation may be confounded by a ventilation-induced increase in fluid retention. We therefore evaluated whether INHI was independently of continuous positive pressure ventilation (CPPV) associated with increased fluid retention. METHODS: One hundred eighty-six patients with burns of >20% of total body surface area admitted to the Beverwijk Burns Center (1995-2006) were retrospectively studied. Cumulative fluid balance, defined as the total volume of fluids administered from the time of admission minus the total volume of fluids collected from each patient, was calculated at the end of days 3 (FB3) and 7 (FB7) postburn. The population was divided into three groups: (1) INHI-CPPV- (no INHI, no ventilation; n = 75); (2) INHI-CPPV+ (no INHI with ventilation; n = 62); and (3) INHI+CPPV+ (INHI with ventilation; n = 49). Analyses were corrected for differences in age, weight, and % total body surface area. RESULTS: Patients who were mechanically ventilated were older and had more extensive burns than those who were not ventilated. Baseline characteristics of patients without INHI who were treated by CPPV were similar to patients with INHI, also treated by CPPV. FB3 was significantly higher in patients without INHI who were ventilated compared with nonventilated patients (13.4 +/- 5.8 L vs. 23.1 +/- 10.6 L for INHI-CPPV- and INHI-CPPV+ respectively, p = 0.001). However, fluid balance was not additionally affected by the presence of INHI. The difference in fluid retention between nonventilated and ventilated patients was also seen on day 7 (22.1 +/- 9.4 L vs. 34.2 +/- 15.9 L for INHI-CPPV- and INHI-CPPV+, respectively, p = 0.001). CONCLUSION: These results suggest that increased fluid retention, which is conventionally associated with INHI, is due to the effects of ventilation and not to the effects of INHI itself. This warrants a closer evaluation of patients who are ventilated in the absence of INHI, with a view to early extubation.