burns 41 (2015) 65–70
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/burns
High-frequency percussive ventilation and initial biomarker levels of lung injury in patients with minor burns after smoke inhalation injury P. Reper *, W. Heijmans Critical Care Department, Queen Astrid Hospital and Free University of Brussels, Brussels, Belgium
article info
abstract
Article history:
Background: Several biological markers of lung injury are predictors of morbidity and
Accepted 9 May 2014
mortality in patients with acute respiratory distress syndrome (ARDS). Some lung-protective ventilation strategies, such as low tidal volume, are associated with a significant
Keywords:
decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy.
Smoke inhalation injury
The primary objective of this study was to test whether the institution of high-frequency
Burn
percussive ventilation (HFPV) to patients with respiratory distress after smoke inhalation
Respiratory distress
injury influenced initial biomarker levels of lung injury (just before and after using percus-
Biomarkers
sive ventilation). Materials and methods: A prospective observational cohort study was conducted in the intensive care unit of the Brussels Burn Center. Fifteen intubated, mechanically ventilated patients with minor burns and ARDS following smoke inhalation were enrolled in our study. Physiologic data and serum samples were collected before intubation and at four different time points within the first 48 h after intubation to measure the concentration of interleukin (IL)-6, IL-8, and tumor necrosis factor-a (TNF alpha). The differences in biomarker levels before and after starting HFPV were analyzed using repeated measure analysis of variance and a paired t test with correction for multiple comparisons. Results: Before starting HFPV under endotracheal intubation, all biological markers (IL-6, IL-8, and TNF alpha) were elevated in the spontaneously breathing patients with acute lung injury (ALI). After intubation and institution of a positive pressure ventilation with HFPV (tidal volume 5.6–6.6 ml/kg per ideal body weight), none of the biological markers were increased significantly at either an early (3 2 h) or a later point in time. However, the levels of IL-8 had decreased significantly after intubation at a later point in time. During the post-intubation period, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio increased significantly and the plateau airway pressure decreased significantly. Conclusion: Levels of IL-6, IL-8, and TNF alpha are elevated in spontaneously ventilating patients with minor burns and ARDS following smoke exposition prior to endotracheal intubation. The institution of HFPV with percussive positive pressure ventilation enhances blood oxygenation and could not further increase the initial levels of these biological markers of lung injury after smoke inhalation injury. # 2014 Elsevier Ltd and ISBI. All rights reserved.
* Corresponding author at: University Hospital Brugmann, Van Gehuchtensquare 4, 1120 Brussels, Belgium. E-mail address: [email protected] (P. Reper). http://dx.doi.org/10.1016/j.burns.2014.05.007 0305-4179/# 2014 Elsevier Ltd and ISBI. All rights reserved.
66
1.
burns 41 (2015) 65–70
Introduction
2.
Materials and methods
surrogates. Patients with acute respiratory distress syndrome (ARDS) due to smoke exposure admitted to the adult intensive care unit were eligible for the study and HFPV use as initial respiratory support. The following inclusion criteria were used in our study: age of 18 years or older, positive pressure ventilation via an endotracheal tube following smoke inhalation injury, diagnosis of respiratory distress following smoke inhalation diagnosis, and no previous conventional mechanical ventilation. ARDS was defined according to the Berlin definition: ‘‘PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio less than 300 for mild, less than 200 for moderate and less than 100 for severe ARDS, acute onset of bilateral infiltrates on a chest radiograph,’’ following a known risk factor such as smoke exposure of a few hours before respiratory failure in this population. By definition, patients could not be diagnosed with ARDS until they required intubation and the fraction of inspired oxygen was precisely known. However, most patients enrolled in the study had had severe smoke inhalation injury before intubation, based on accident circumstances and clinical signs such as tachypnea, hypoxemia, and, in some cases, bilateral chest X-ray infiltrates. HFPV was delivered by a highfrequency pulse generator (Bird Space Technologies, Percussionaire Corporation, Sand Point, ID, USA). Gas from a pulse generator was administered through a non-gated venturi connected to an endotracheal tube; the venturi entrains humidified gas from the ventilator. The system combines high-frequency volume breaths with a variable I:E ratio; periodically, the flow is interrupted to return to baseline continuous positive airway pressure (CPAP). The ratio between percussive-phase and baseline CPAP is adjusted following the results of blood oxygenation and CO2 elimination. Peak airway pressure can be adjusted and also influences minute ventilation and CO2 level. The HFPV frequency periods were between 450 and 650 cycles/min; FiO2 was adapted following O2 saturation and blood gases results. Full humidification was performed through the ventilator system to prevent tracheobronchial injury. All ventilatory parameters, including plateau pressure, were measured with a respirator-independent monitoring device (Bicore Monitoring Systems, Irvine, CA, USA, using a flow transducer and an esophageal transducer) for the two ventilatory modes; the flow transducer was inserted between the phasitron piece of the ventilator circuit and the proximal end of the endotracheal tube. The ventilation strategy of the patients was determined in concordance with the ARDS Network protocol, which reduced the tidal volume/ideal body weight towards a target of 6 ml/kg as tolerated, maintaining the plateau pressure at < 30 cm H2O. Patients were excluded if they had had a history of severe chronic pulmonary disease or extended burnt surface areas other than facial burns (total burn surface area (TBSA) > 10%).
2.1.
Study design and patient selection
2.2.
Acute respiratory failure, following smoke inhalation injury, can contribute to significant complications in the presence of severe burn injury [1,2]. High-frequency percussive ventilation (HFPV) is known for representing an interesting alternative to ventilatory support after respiratory distress due to smoke inhalation injury. The mechanisms by which the HFPV strategy could confer some benefits after smoke exposure are understood incompletely. However, a reduction of lung injury leading to the release of pro-inflammatory cytokines could be one possible mechanism [3–5]. The structural disruption of lung, caused by mechanical ventilation (barotraumas and volutrauma), includes a component of associated mediator release (biotrauma), which can further aggravate lung injury and potentially lead to systemic multiorgan failure [6–10]. Surfactant protein D and soluble tumor necrosis factor (TNF) receptors are highin patients with respiratory failure; their levels change in response to different ventilation strategies, and, interestingly, this response is rather fast [11–15]. Furthermore, baseline levels of TNF alpha, IL-6, IL-8, intercellular adhesion molecule-1, and von Willebrand factor in patients with ARDS are often associated with worse clinical outcomes [12–14,16–18]. However, for patients showing a lung injury after a smoke inhalation injury and who are ventilating with supplemental oxygen spontaneously, it is not known whether the institution of HFPV influences biomarker levels that were detected after a lung injury and it tends to exacerbate the preexisting lung damage. It is possible that endotracheal intubation followed by HFPV would not worsen an already established lung injury. On the other hand, it is also possible that a possible lungprotective positive pressure ventilation strategy could worsen lung injury, and this is due to the fact that the injured alveoli are exposed to some levels of positive airway pressure like in HFPV. Stuber et al. [15] reported that the levels of plasma cytokine in patients with ARDS change within 1 h of a change in ventilation strategy. In this study, because direct assessment of extravascular lung water, lung vascular permeability, and histology is not easy in most spontaneously ventilating patients with smoke inhalation, we measured biological markers that have been shown to change in patients with respiratory failure [11–15]. If HFPV increased the severity of lung injury, the levels of proinflammatory cytokines (TNF alpha, IL-6, and IL-8) [14] would increase in the next 24–72-h period after percussive ventilation initiation. Therefore, we measured initial biomarker levels before and after endotracheal intubation. Biochemical and physiologic indices measurements were extended to include 48 h after HFPV.
A prospective observational cohort study was conducted in the intensive care unit of the Brussels Burn Center. The protocol was approved by the Institutional Ethic Committee and informed consent was obtained from patients or
Clinical data collection
The medical record of each patient was reviewed, and clinical data were collected using a standardized data collection form. Smoke inhalation injury was confirmed by classic criteria which were based on a detailed review of the clinical history
67
burns 41 (2015) 65–70
including closed-space fire, on the presence of facial burns and soot on face, and on the carboxyhemoglobin being >10% and finally confirmed by a fiber optic examination after intubation. Demographic data were recorded on day 1, and relevant physiologic data were collected at several times during the first 72 h after intubation and inclusion in the study. APACHE II (acute physiology and chronic health) scores were also calculated at the time of admission to the intensive care unit. Patients with severe burns (TBSA > 10%) and patients ventilated with conventional mechanical ventilation before admission were excluded from the study. Cardiac function had to be evaluated by echocardiographic examination to exclude cardiac causes of pulmonary edema with hypoxemia.
Table 1 – Clinical characteristics of 15 patients with acute lung injury following smoke inhalation injury. Clinical characteristics Age Males APACHE II score on admission Diagnosis of smoke inhalation Close space fire Soot on face Facial burns Carboxyhemoglobin >10% on admission Positive bronchoscopy TBSA
44 20 yearsa 10 (66) 18 8a No. of patients (percentage of total) 7 (41) 12 (75) 12 (75) 13 (86) 15 (100) 8 1,9%a
a
Data shown as means standard deviation. APACHE II, acute physiology and chronic health evaluation.
2.3. Serum sample collection and biomarker measurements Blood, obtained from traditional laboratory draws, was used to measure lung injury biomarkers. It facilitated pre-intubation sample acquisition while keeping a collection of blood samples and processing consistently between pre- and postintubation samples. Serum samples were centrifuged at 3000 g by the laboratory for 10 min at 4 8C and stored at 4 8C according to the research laboratory protocol. The supernatant was aspirated from serum samples within 24 h, aliquoted, and stored at 70 8C in our research laboratory. All serum samples were assayed for IL-6, IL-8, and TNF alpha. Commercially available enzyme-linked immunosorbent assays were used to measure serum levels of TNF alpha, IL-6, and IL-8 (Innogenetics Inc., Gent, Belgium). All enzymelinked immunosorbent assay analyses were performed with strict adherence to the manufacturers’ guidelines. Preintubation biomarker levels were measured from a serum sample collected within a 2-h period before intubation (mean, 2 0.4 h). Post-intubation biomarker levels were measured from samples collected within an 8-h period after intubation (mean, 3 2 h) and within 72 h after intubation.
2.4.
Statistical analysis
Data analysis was conducted using STATA 12 (StataCorp LP, TX, USA). The values for the cytokine concentrations for IL-6, IL-8, and TNF alpha were not distributed normally. This explains why we carried out natural log transformation to
achieve normal distribution and it allowed the use of parametric statistical tests. To evaluate the differences over time of cytokine values within each group, we used repeated measures of analysis of variance and paired t test with Bonferroni correction for multiple post hoc comparisons as appropriate. All tests of significance were two-tailed, and a p value of
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/burns
High-frequency percussive ventilation and initial biomarker levels of lung injury in patients with minor burns after smoke inhalation injury P. Reper *, W. Heijmans Critical Care Department, Queen Astrid Hospital and Free University of Brussels, Brussels, Belgium
article info
abstract
Article history:
Background: Several biological markers of lung injury are predictors of morbidity and
Accepted 9 May 2014
mortality in patients with acute respiratory distress syndrome (ARDS). Some lung-protective ventilation strategies, such as low tidal volume, are associated with a significant
Keywords:
decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy.
Smoke inhalation injury
The primary objective of this study was to test whether the institution of high-frequency
Burn
percussive ventilation (HFPV) to patients with respiratory distress after smoke inhalation
Respiratory distress
injury influenced initial biomarker levels of lung injury (just before and after using percus-
Biomarkers
sive ventilation). Materials and methods: A prospective observational cohort study was conducted in the intensive care unit of the Brussels Burn Center. Fifteen intubated, mechanically ventilated patients with minor burns and ARDS following smoke inhalation were enrolled in our study. Physiologic data and serum samples were collected before intubation and at four different time points within the first 48 h after intubation to measure the concentration of interleukin (IL)-6, IL-8, and tumor necrosis factor-a (TNF alpha). The differences in biomarker levels before and after starting HFPV were analyzed using repeated measure analysis of variance and a paired t test with correction for multiple comparisons. Results: Before starting HFPV under endotracheal intubation, all biological markers (IL-6, IL-8, and TNF alpha) were elevated in the spontaneously breathing patients with acute lung injury (ALI). After intubation and institution of a positive pressure ventilation with HFPV (tidal volume 5.6–6.6 ml/kg per ideal body weight), none of the biological markers were increased significantly at either an early (3 2 h) or a later point in time. However, the levels of IL-8 had decreased significantly after intubation at a later point in time. During the post-intubation period, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio increased significantly and the plateau airway pressure decreased significantly. Conclusion: Levels of IL-6, IL-8, and TNF alpha are elevated in spontaneously ventilating patients with minor burns and ARDS following smoke exposition prior to endotracheal intubation. The institution of HFPV with percussive positive pressure ventilation enhances blood oxygenation and could not further increase the initial levels of these biological markers of lung injury after smoke inhalation injury. # 2014 Elsevier Ltd and ISBI. All rights reserved.
* Corresponding author at: University Hospital Brugmann, Van Gehuchtensquare 4, 1120 Brussels, Belgium. E-mail address: [email protected] (P. Reper). http://dx.doi.org/10.1016/j.burns.2014.05.007 0305-4179/# 2014 Elsevier Ltd and ISBI. All rights reserved.
66
1.
burns 41 (2015) 65–70
Introduction
2.
Materials and methods
surrogates. Patients with acute respiratory distress syndrome (ARDS) due to smoke exposure admitted to the adult intensive care unit were eligible for the study and HFPV use as initial respiratory support. The following inclusion criteria were used in our study: age of 18 years or older, positive pressure ventilation via an endotracheal tube following smoke inhalation injury, diagnosis of respiratory distress following smoke inhalation diagnosis, and no previous conventional mechanical ventilation. ARDS was defined according to the Berlin definition: ‘‘PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio less than 300 for mild, less than 200 for moderate and less than 100 for severe ARDS, acute onset of bilateral infiltrates on a chest radiograph,’’ following a known risk factor such as smoke exposure of a few hours before respiratory failure in this population. By definition, patients could not be diagnosed with ARDS until they required intubation and the fraction of inspired oxygen was precisely known. However, most patients enrolled in the study had had severe smoke inhalation injury before intubation, based on accident circumstances and clinical signs such as tachypnea, hypoxemia, and, in some cases, bilateral chest X-ray infiltrates. HFPV was delivered by a highfrequency pulse generator (Bird Space Technologies, Percussionaire Corporation, Sand Point, ID, USA). Gas from a pulse generator was administered through a non-gated venturi connected to an endotracheal tube; the venturi entrains humidified gas from the ventilator. The system combines high-frequency volume breaths with a variable I:E ratio; periodically, the flow is interrupted to return to baseline continuous positive airway pressure (CPAP). The ratio between percussive-phase and baseline CPAP is adjusted following the results of blood oxygenation and CO2 elimination. Peak airway pressure can be adjusted and also influences minute ventilation and CO2 level. The HFPV frequency periods were between 450 and 650 cycles/min; FiO2 was adapted following O2 saturation and blood gases results. Full humidification was performed through the ventilator system to prevent tracheobronchial injury. All ventilatory parameters, including plateau pressure, were measured with a respirator-independent monitoring device (Bicore Monitoring Systems, Irvine, CA, USA, using a flow transducer and an esophageal transducer) for the two ventilatory modes; the flow transducer was inserted between the phasitron piece of the ventilator circuit and the proximal end of the endotracheal tube. The ventilation strategy of the patients was determined in concordance with the ARDS Network protocol, which reduced the tidal volume/ideal body weight towards a target of 6 ml/kg as tolerated, maintaining the plateau pressure at < 30 cm H2O. Patients were excluded if they had had a history of severe chronic pulmonary disease or extended burnt surface areas other than facial burns (total burn surface area (TBSA) > 10%).
2.1.
Study design and patient selection
2.2.
Acute respiratory failure, following smoke inhalation injury, can contribute to significant complications in the presence of severe burn injury [1,2]. High-frequency percussive ventilation (HFPV) is known for representing an interesting alternative to ventilatory support after respiratory distress due to smoke inhalation injury. The mechanisms by which the HFPV strategy could confer some benefits after smoke exposure are understood incompletely. However, a reduction of lung injury leading to the release of pro-inflammatory cytokines could be one possible mechanism [3–5]. The structural disruption of lung, caused by mechanical ventilation (barotraumas and volutrauma), includes a component of associated mediator release (biotrauma), which can further aggravate lung injury and potentially lead to systemic multiorgan failure [6–10]. Surfactant protein D and soluble tumor necrosis factor (TNF) receptors are highin patients with respiratory failure; their levels change in response to different ventilation strategies, and, interestingly, this response is rather fast [11–15]. Furthermore, baseline levels of TNF alpha, IL-6, IL-8, intercellular adhesion molecule-1, and von Willebrand factor in patients with ARDS are often associated with worse clinical outcomes [12–14,16–18]. However, for patients showing a lung injury after a smoke inhalation injury and who are ventilating with supplemental oxygen spontaneously, it is not known whether the institution of HFPV influences biomarker levels that were detected after a lung injury and it tends to exacerbate the preexisting lung damage. It is possible that endotracheal intubation followed by HFPV would not worsen an already established lung injury. On the other hand, it is also possible that a possible lungprotective positive pressure ventilation strategy could worsen lung injury, and this is due to the fact that the injured alveoli are exposed to some levels of positive airway pressure like in HFPV. Stuber et al. [15] reported that the levels of plasma cytokine in patients with ARDS change within 1 h of a change in ventilation strategy. In this study, because direct assessment of extravascular lung water, lung vascular permeability, and histology is not easy in most spontaneously ventilating patients with smoke inhalation, we measured biological markers that have been shown to change in patients with respiratory failure [11–15]. If HFPV increased the severity of lung injury, the levels of proinflammatory cytokines (TNF alpha, IL-6, and IL-8) [14] would increase in the next 24–72-h period after percussive ventilation initiation. Therefore, we measured initial biomarker levels before and after endotracheal intubation. Biochemical and physiologic indices measurements were extended to include 48 h after HFPV.
A prospective observational cohort study was conducted in the intensive care unit of the Brussels Burn Center. The protocol was approved by the Institutional Ethic Committee and informed consent was obtained from patients or
Clinical data collection
The medical record of each patient was reviewed, and clinical data were collected using a standardized data collection form. Smoke inhalation injury was confirmed by classic criteria which were based on a detailed review of the clinical history
67
burns 41 (2015) 65–70
including closed-space fire, on the presence of facial burns and soot on face, and on the carboxyhemoglobin being >10% and finally confirmed by a fiber optic examination after intubation. Demographic data were recorded on day 1, and relevant physiologic data were collected at several times during the first 72 h after intubation and inclusion in the study. APACHE II (acute physiology and chronic health) scores were also calculated at the time of admission to the intensive care unit. Patients with severe burns (TBSA > 10%) and patients ventilated with conventional mechanical ventilation before admission were excluded from the study. Cardiac function had to be evaluated by echocardiographic examination to exclude cardiac causes of pulmonary edema with hypoxemia.
Table 1 – Clinical characteristics of 15 patients with acute lung injury following smoke inhalation injury. Clinical characteristics Age Males APACHE II score on admission Diagnosis of smoke inhalation Close space fire Soot on face Facial burns Carboxyhemoglobin >10% on admission Positive bronchoscopy TBSA
44 20 yearsa 10 (66) 18 8a No. of patients (percentage of total) 7 (41) 12 (75) 12 (75) 13 (86) 15 (100) 8 1,9%a
a
Data shown as means standard deviation. APACHE II, acute physiology and chronic health evaluation.
2.3. Serum sample collection and biomarker measurements Blood, obtained from traditional laboratory draws, was used to measure lung injury biomarkers. It facilitated pre-intubation sample acquisition while keeping a collection of blood samples and processing consistently between pre- and postintubation samples. Serum samples were centrifuged at 3000 g by the laboratory for 10 min at 4 8C and stored at 4 8C according to the research laboratory protocol. The supernatant was aspirated from serum samples within 24 h, aliquoted, and stored at 70 8C in our research laboratory. All serum samples were assayed for IL-6, IL-8, and TNF alpha. Commercially available enzyme-linked immunosorbent assays were used to measure serum levels of TNF alpha, IL-6, and IL-8 (Innogenetics Inc., Gent, Belgium). All enzymelinked immunosorbent assay analyses were performed with strict adherence to the manufacturers’ guidelines. Preintubation biomarker levels were measured from a serum sample collected within a 2-h period before intubation (mean, 2 0.4 h). Post-intubation biomarker levels were measured from samples collected within an 8-h period after intubation (mean, 3 2 h) and within 72 h after intubation.
2.4.
Statistical analysis
Data analysis was conducted using STATA 12 (StataCorp LP, TX, USA). The values for the cytokine concentrations for IL-6, IL-8, and TNF alpha were not distributed normally. This explains why we carried out natural log transformation to
achieve normal distribution and it allowed the use of parametric statistical tests. To evaluate the differences over time of cytokine values within each group, we used repeated measures of analysis of variance and paired t test with Bonferroni correction for multiple post hoc comparisons as appropriate. All tests of significance were two-tailed, and a p value of
