Introduction

Lung contusion is a common clinical condition in patients with chest trauma. Surfactant abnormalities have been demonstrated in animal models of lung contusion [1], in trauma patients with lung contusion [2] and acute respiratory distress syndrome (ARDS) [3–5]. The impact of these abnormalities on gas exchange, lung mechanics and clinical outcome remains unclear. Although surfactantreplacement has long been studied in adult patients with acute lung injury (ALI)/ARDS [6–8], there is rather limited and incidental reporting in lung contusion and ALI [9]. The aim of the current study was to investigate the effect of exogenous surfactant on gas exchange and lung mechanics in ventilated patients with lung contusion and ALI. Preliminary results of this study were presented at the annual congress of the European Society of Intensive Care Medicine in Amsterdam, 25–28 September 2005 [10].

Materials and methods

Patients

The study population consisted of 16 ventilated patients with blunt chest trauma and fulfilling ARDS criteria [11] admitted to a 14-bed ICU during a 3-year period. Inclusion criteria were severe hypoxemia (PaO2/FIO2 < 150 mmHg 24–48 h after initiation of mechanical ventilation), intact heart function, and lung contusions manifested as areas of nonaerated lung parenchyma on computed tomography. The mechanism of injury was traffic accident in all but one (fall); baseline data are presented in Table 1. Exclusion criteria were high intracranial pressure and/or need for neurosurgical intervention, hemodynamic instability, massive transfusion (> 4 blood units), massive hemoptysis and tracheobronchial tree rupture. Seventeen consecutive patients fulfilling the inclusion and exclusion criteria were identified and all but one entered the study. The institutional ethics committee approved the study, and written informed consent was obtained from the patients' next of kin.

Table 1 Baseline demographics and ventilatory data (APACHE Acute Physiology and Chronic Health Evaluation, Crs respiratory system compliance)
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All patients were ventilated with tidal volume of 6–7 ml/kg and positive end-expiratory pressure (PEEP) set above the lower inflection point. FIO2 was set at the minimal level to achieve SaO2 greater than 90%. Tidal volume and PEEP were kept unchanged for the first 72 h after randomization, and changes were allowed only in frequency and FIO2. The ventilatory target was an end-inspiratory pressure less than 30 cmH2O in all patients and a PaCO2 less than 40 mmHg in the case of head-injury patients. Recruitment maneuvers were applied to all patients at baseline and at 6, 12, 24, 48, and 72 h. Each time two maneuvers were conducted, one 60 s after the other, by applying 40 cmH2O for 30 s. Blood gases 10 min after the second recruitment maneuver were considered as reflecting recruitment effect.

Study protocol

On admission all patients underwent a fiberoptic bronchoscopy to visualize the bronchial tree and remove secretions. Patients were then subjected to either surfactant administration (surfactant group) or standard treatment (control group) on a random basis using a computer-generated list. Natural bovine surfactant (Alveofact; Dr. K. Thomae, Biberach, Germany) was administered by a repeat bronchoscopy. Surfactant was instilled in any of the nonaerated 19 segments (ten right, nine left); each segmental bronchus received (200/19) mg/kg body weight. The following variables were assessed at baseline and every 6 h: blood gases, ventilatory parameters, routine hemodynamic variables, net fluid balance, sedation requirements, volume of secretions suctioned (closed circuit) and abdominal pressure. Patients were weaned and extubated according to predefined criteria [12]. The primary study end-point was oxygenation and compliance, while the secondary end-points included response to recruitment, changes in ventilatory parameters, duration of mechanical ventilation and adverse effects. Adverse effects included desaturation, hypotension and arrhythmias and during the 28-day monitoring period mortality, pulmonary complications, and any other undesired event. At baseline there were no significant differences between the two groups regarding age, comorbidities, Acute Physiology and Chronic Health Evaluation II and Injury Severity Score, Lung Injury Score, number of involved bronchopulmonary segments, initial gas exchange, lung mechanics, net fluid balance, or blood transfusion requirements.

Statistics

Statistical analysis was performed using the GraphPad Prism version 4. Data were tested for normality using the Kolmogorov–Smirnov test and are presented as mean ± SD. The groups were compared using repeated-measures two-way analysis of variance followed by Bonferroni's test for post-hoc comparisons. In all tests differences at the level of p < 0.05 were considered statistically significant.

Results

Gas exchange

Arterial oxygenation (PaO2/FIO2) increased significantly in the surfactant group patients as early as 6 h after surfactant administration and continued improving at 12 and 24 h without any further rise beyond the 24 h (Table 2). The improvement in PaO2/FIO2 allowed the decrease in FIO2 (from 79% at baseline to 50% at 24 h, p ≤ 0.004) in all surfactant group patients. Control patients demonstrated greater oxygenation at 48 and 72 h than at baseline (p ≤ 0.011 and 0.002, respectively). Oxygenation was significantly higher in the surfactant than in the control group from 6 h until 48 h (Table 2, Fig. 1). This difference was not significant at 72 h (p ≤ 0.87). There were no differences in PaCO2 or pH between or within groups.

Table 2 Gas exchange and ventilatory parameters for the first 72 h after surfactant treatment (RM recruitment maneuvers)
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Fig. 1
figure 1

PaO2/FIO2 in surfactant group patients (dashed line) and control (solid line). Points values; bars SD; * p < 0.05 vs. baseline; † p < 0.05 between groups. Statistical significance of difference between time points and baseline for the two groups: in the surfactant group, p < 0.001 6 h vs. baseline, p < 0.001 for the other time points; in the control group, all time points nonsignificant vs. baseline except 48 h (p < 0.011) and 72 h (p < 0.002)

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Lung mechanics and recruitment maneuvers

Compliance increased from 30 to 36 ml/cmH2O 6 h after surfactant administration (p < 0.05), and this increase was maintained at 48 and 72 h. The surfactant group patients demonstrated greater compliance than controls at all time points, although the baseline compliance of control group tended to be better at baseline. The control group patients showed significantly greater compliance at 72 h than at baseline (p < 0.05). Surfactant group patients demonstrated a greater response to recruitment than controls at 6 h (p < 0.05) but not at 12 h.

Complications, outcome

There were no significant adverse events during the study. No new cases of barotrauma were diagnosed in the ICU. There was no significant difference in the duration of mechanical ventilation, although there was a trend toward fewer days on the ventilator for surfactant patients (5.6 ± 2.6 days in the surfactant and 8.1 ± 2.4 days in the control group, p ≤ 0.16). All patients in the surfactant group survived, while one patient from the control group died.

Discussion

This prospective randomized study assessed the effect of surfactant replacement in mechanically ventilated trauma patients with lung contusion and ALI. The main finding of the study was improved oxygenation in surfactant group patients 6 h after surfactant replacement, which was maintained for at least 72 h. The clinical significance of this finding remains unclear. Previous studies in adult ALI have demonstrated improved oxygenation following surfactant replacement, though not linked to an outcome benefit [8]. Furthermore, improved oxygenation has not been associated with survival in recent clinical ARDS trials [13]. Nevertheless there are three interesting differences between our results and those of previous studies. First, oxygenation improvement after surfactant administration was associated with a significant and persistent increase in compliance, a novel finding in adult surfactant replacement area. Second, the oxygenation improvement was noted soon after replacement and lasted longer than expected from previous studies [9]. Third, surfactant instillation was combined with the use of a lung protective strategy.

The mechanism for this acute improvement in oxygenation is not clear. The stabilizing effect of surfactant on alveoli may have played a significant role either by recruitment of nonventilated alveoli or by prevention of end-expiratory collapse. Recent experimental datasupport the idea that surfactant administration, especially in conjunction with recruitment maneuvers, can significantly modify the distribution of ventilation [14]. Furthermore lung protective strategy seems to enhance the effect of exogenous surfactant, resulting in improved oxygenation [15]. Improved compliance after surfactant replacement has been demonstrated in pigs with unilateral lung contusion [16] as well as in human neonates with ALI receiving surfactant [17, 18], but this is the first adult study that reports such a finding. The synergistic effect of recruitment should be considered. Recent experimental data have demonstrated improved compliance, when a recruitment maneuver was performed after surfactant replacement [16]. The response to recruitment was rather poor at baseline. This may have been due to the level of applied pressure, the duration of the maneuver or the level of PEEP afterwards, the unilateral character of lung injury, or the clinical condition per se. Although starting from a higher oxygenation point before recruitment, patients in the surfactant group demonstrated a marked response to recruitment at 6 h compared to controls.

The real clinical impact of these findings is difficult to determine. The improvement in oxygenation allowed the significant reduction in FIO2. Furthermore minute ventilation and respiratory rate were significantly lower in surfactant group patients for the same PaCO2 than in controls, exposing the acutely injured lung to diminished repetitive stress. On the other hand, no improved clinical outcome was demonstrated, probably for two reasons. First, the size of patient sample was small; although a reduction of 30% in ventilation time was observed, the study was underpowered to detect any difference in the duration of mechanical ventilation. Second, we have used a single and reduced surfactant dose, in contrast to recent trials that tend to use repeated and large surfactant doses [9, 19]. However, this low-dose effect could be partially offset by direct administration of surfactant to the damaged area.

In conclusion, a single dose of bronchoscopically instilled natural bovine surfactant resulted in acutely improved oxygenation and compliance in patients with lung contusion and ALI. Surfactant replacement was not associated with serious adverse events. There was no difference in clinical outcome, although a trend to shorter duration of ventilatory support was observed.