Abstract

Acute respiratory distress syndrome (ARDS) is characterized by damage to the arteriolar-capillary endothelium and alveolar epithelium that leads to surfactant deficiency and atelectasis.  Alveolar collapse and pulmonary edema will further induce surfactant inactivation. Surfactant supplementation has been suggested but results are unpredictable. Poor response may be due to inhibition of administered surfactant by plasma components filling the alveolar space, severity of lung injury, time of surfactant application and inadequate dose. We report the course of gas exchange and pulmonary mechanics after instillation  of surfactant in 14 children (3 months-7 years) with severe ARDS, defined as an oxygenation index (OI) > 30 and a partial pressure of oxygen/ fraction of Inspired oxygen (PaO2/FiO2) 200 for more than 12 hours.  Diluted surfactant lung lavages were able to increase blood gas exchange in all our patients despite previously severe gas exchange impairment.

Keywords: ARDS, pulmonary surfactant, bronchoalveolar lavages, child

 

Introduction

Acute respiratory distress syndrome (ARDS) is a lung pathology induced by diverse injuries, including trauma, sepsis, liquid aspiration, inhaled gases, radiation, pneumonitis and many others. Despite the introduction of new treatments, the mortality from ARDS in the pediatric age group remains high (about 40%). (1) ARDS is characterized by damage to the arteriolar-capillary endothelium and alveolar epithelium, including type I and type II pneumocytes. (2) Damage to the latter results in surfactant deficiency and atelectasis. Even though surfactant abnormalities in ARDS are not the primary pathogenic factor, surfactant deficiency, either in the presence or absence of type II pneumocyte alterations, may result from primary or secondary inhibition or inactivation of pulmonary surfactant in the alveolar space. (2,3) Surfactant deficiency and inactivation will further induce alveolar collapse and pulmonary edema, leading to the characteristic pathophysiology of ARDS. (2,3) Surfactant supplementation has been suggested but the treatment is unpredictable. (4,5) Poor response may be due to inhibition of administered surfactant by plasma components filling the alveolar space related to the severity of lung injury. Therefore, the timing and modality of surfactant application seems very important. (3-5) In our study we report the course of gas exchange and pulmonary mechanics in 15 children with severe ARDS treated with repeated bronchoalveolar lavages of diluted natural porcine surfactant (Curosurf).

Material and methods

We enrolled all children admitted between January 2005 and December 2007 to the Pediatric Intensive Care Units of A. Gemelli University Hospital and Bambino Gesù Hospital of Rome with severe ARDS, defined as an OI > 20 and a PaO2/FiO2 92% and end –tidal CO2 in the range between 40-50 mmHg. Pulmonary function tests were performed before, and 30 min, 1 hr ,4 hr, 8 hr,12 hr, 24 hr, 48 hr and 72 hr after treatment.

Results

The sample consists of fourteen (n=14) children. The age of our children ranged between 3 months and 7 years, and the origin of ARDS was very different: burn, septic shock, bronchiolitis, pulmonary thromboembolism, trauma and pleuropneumonia (table 1). Pediatric risk of mortality (PRISM) score ranged between 10 and 13 points (table 1). Mechanical ventilation was set in order to reduce baro and volutrauma using small tidal volume, high respiratory rate, permissive hypercapnia and prone position. Two children were under high frequency oscillation ventilation (HFOV). All patients were receiving corticosteroid treatment. Every child showed a dramatic response to surfactant with rapid and progressive increase in compliance from a mean of 0.43 (range 0.38-0.51) before surfactant treatment to 0.97(range 0,85-1.2) cmH2O/ml/kg 12 hours after treatment (figure 1). Mean OI dropped under 15 (range 5-18) and mean PaO2/FiO2 increased over 250 (range 216-260) in less than 6 hours (figure 2). Mechanical ventilation set was rapidly reduced obtaining a mean (mean arterial pressure) MAP < 10 cmH2O and this improvement in gas exchange was kept for more than 12 hours (figure 2). After that, all patients recorded progressive pulmonary deterioration characterized by an increase in oxygen supplementation. In 6 out of 14 children the PaO2/FiO2 ratio returned to below 150 and we re-treated them with a new course of diluted surfactant. The response to the second dose was less impressive and more delayed, but in 48 hours all babies increased their PaO2/FiO2 over 250. All patients were extubated and discharged from the intensive care unit (ICU) without major complications. Only 1 patient, who had severe tuberculosis pleuropneumonia and was under HFOV, developed a bilateral pneumothorax and pneumomediastinum in the first hours after surfactant treatment (which required surgical drainage).

Table 1. General clinical characteristics of studied children.

GENERAL CLINICAL CHARACTERISTICS Age Gender ARDS etiology PRISM OI
1 5 yr F Burn 13 36
2 1yr F Sepsis 12 33
3 4mo M Bronchiolitis 10 30
4 6mo M Pneumonia 11 30
5 2yr M DIC, Meningitis 13 31
6 6yr F Disseminated TBC 12 31
7 3yr M Tonsillectomy 13 32
8 4yr M Aspiration pneumonia 13 33
9 5mo M Bronchiolitis 10 30
10 3mo F Bronchiolitis 11 30
11 4yr M Pneumonia 11 31
12 10mo F Aspiration pneumonia 13 34
13 3mo M Bronchiolitis 12 32
14 7yr F Trauma 10 30

ARDS, acute respiratory distress syndrome; DIC, disseminated intravascular coagulation; F, female; M, male; mo, months; OI, oxygenation index; PRISM, Pediatric Risk of Mortality; TBC, tuberculosis; yr, years.

{webgallery}Figure 1. Lung compliance before and after treatment.{/webgallery}{webgallery}Figure 2. Gas exchange (mean ± sd) in treated children.{/webgallery}

Discussion

Diluted surfactant lung lavages were able to increase blood gas exchange in all our patients despite all of them suffering from severe ARDS with OI > 30. This improvement was faster and more impressive right after the first than the second dose. Experimental animal data have shown strong evidence that tracheobronchial lavages with surfactant are extremely efficacious in the most severe forms of ARDS in which alveolar ventilation is extremely heterogenic and the majority of the alveoli are filled with edema proteins. (6-8) When regular instillation of exogenous surfactant is performed, this distribution is less homogenic and the small amount of surfactant that reaches the alveoli surface is rapidly inactivated by inflammatory and edema proteins. (6-8) This is one of the main reasons why the majority of randomized controlled trials on surfactant treatment in children with ARDS failed to find a beneficial effect. A recent meta-analysis pointed out that trials paid special attention to the selection of the population, type, dosage, timing and ways of administration of surfactant achieving a statistical significant effect in surfactant treated children in term of reduction of days of mechanical ventilation, days of ICU stay and one study also in mortality. (9) Despite the limitations of our study (we didn’t have a control population), it demonstrates very clearly the improved distribution and efficacy of diluted surfactant using lung lavages. A larger, randomized controlled trial is needed to confirm this important finding.

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