Early alveolar and systemic mediator release in patients at different risks for ARDS after multiple trauma
Introduction
The Acute Respiratory Distress Syndrome (ARDS) is a devastating inflammatory disease of the lung which is characterised by the sudden onset of increased pulmonary vascular permeability, pulmonary oedema and respiratory failure. Activated neutrophils (PMN) play a major role in mediating the microvascular damage and also contribute to lung tissue injury. PMN infiltrate the lung in significant numbers and their persistence in the lungs is an important determinant of poor survival.1, 10
Interleukin-8 (IL-8) has been identified as one of the most significant chemotactic factors for PMN in the blood and bronchoalveolar lavage (BAL) fluids with ARDS.1, 10, 30, 39 Donnelly et al. studied a heterogeneous group of ICU-patients with a predisposition for ARDS due to trauma, pancreatitis or bowel perforation.10 Patients with an IL-8 concentration higher than 200 pg/ml in BAL fluids developed ARDS in the following 6–72 h10 whereas only one patient with a BAL IL-8 concentration lower than 200 pg/ml also developed ARDS. Other studies confirmed the relevance of IL-8 in populations of ICU patients with surgical trauma,42 nosocomial pneumonia,28, 39 or groups with very diverse diseases.1, 2 In addition, Pallsiter et al. demonstrated in an in vitro study that PMN isolated from multiple trauma patients have a significantly elevated migratory capacity which is directed by IL-8 concentrations.30
Apart from IL-8, also pulmonary TNF-α, IL-1β and IL-6 levels showed an increase during the development or during the early phase of ARDS.11, 27, 35, 36 Both parameters demonstrated a good negative predictive value for ARDS development, whereas IL-1 was superior in regards to sensitivity and survival specificity.2 In contrast to the proinflammatory response, ARDS patients who survived had higher alveolar anti-inflammatory cytokine levels early after ARDS development than those ARDS patients who died.11 Alveolar anti-inflammatory cytokines are already released in ARDS-predisposed patients and high concentrations were found at the onset of ARDS.28, 32
ARDS occurs in approximately 20% of major trauma admissions and therefore represents one of the most frequent complications in the clinical course of multiple trauma patients. Early identification of high risk patients is of major importance in order to adjust the surgical treatment strategies.31 The observations of Donnelly et al. in a very diverse group of intensive care patients10 indicate that measurements of BAL IL-8 might identify patients at high risk to progress to ARDS. These results have not been confirmed although there are various studies on the importance of IL-8 in lung injury.1, 2, 18, 28, 39, 42 It remains still unknown if alveolar IL-8 is also predictive for ARDS development in a homogeneous group of multiple trauma patients. Furthermore it is unclear, whether and how alveolar IL-8 is related to the alveolar and systemic release of other mediators in these patients.
We hypothesised that early alveolar IL-8 release predicts progression to ARDS after multiple trauma and that this marker is superior compared to clinical parameters or other mediators to distinguish between patients at high and low risk for ARDS. Furthermore, we expected that the alveolar IL-8 release at the initiation of lung injury might be associated with both enhanced pro- and anti-inflammatory reactions after multiple trauma. Therefore, we studied patients who were predisposed to develop ARDS due to multiple trauma.
Section snippets
Patients
The study was approved by the ethical committee of our institution and informed consent was obtained from the next-of-kin.
Trauma severity was assessed by the Injury Severity Score (ISS)3 and the Hannover Polytrauma Score (PTS).29 The illness severity was assessed at admission to the intensive care unit by determining APACHE II, III21, 22 and SAPS II.23 Lung injury was assessed using the American-European Consensus Conference criteria for ARDS.4 Furthermore, the requirements of crystalloid and
Patients
The total study group consisted of 24 patients (3 female, 21 male), who were homogeneous for ARDS risk factors. All patients required endotracheal intubation at the accident site performed by an emergency physician. According to the initially measured IL-8 levels in the BAL fluid, eight patients were assigned to the group with high risk for ARDS (H), whereas 16 patients were in the low risk group (L). Age, AISchest as well as transfusion and infusion requirements until performance of the BAL
Discussion
Pulmonary dysfunction that clinically manifests as ARDS is a major component of Multiple Organ Dysfunction Syndrome (MODS) and one of the primary causes of late mortality after multiple trauma.5, 36 An excessive local and systemic inflammatory response leading to organ dysfunction has been shown to be significantly involved in the development of ARDS.5, 28 IL-8 represents a potent neutrophil chemoattractant and the posttraumatic presence of IL-8 within the alveolar airspace is associated with
Acknowledgement
This work was supported by departmental funding.
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