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Three Part Question

In [an infant with severe RSV+ bronchiolitis requiring ventilation] does [endotracheal surfactant] [improve ventilation/gas exchange parameters and shorten the duration of ventilation or intensive care stay]?

Clinical Scenario

You are an intensive care registrar who has taken over the care of a three week old baby boy diagnosed as having clinical bronchiolitis (now found to be RSV +). He was initially admitted and ventilated because of increasing respiratory distress and apnoeas. His ventilatory requirements are increasing and gas exchange is getting worse. You have just finished your stint on neonates and recall hearing that surfactant has been used on infants with bronchiolitis in trials. You wonder if it may help this child.

Search Strategy

Cochrane database, PubMed, SUMSearch.
A search string of a. [bronchiolitis] and [surfactant] and b. [respiratory syncytial virus] and [bronchiolitis] was used.

Search Outcome

Cochrane database: Topic registered only.
PubMed: 3 relevant papers. 85 hits.
SUMSearch: Nil else other than the above.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Tibby SM et al, 2000,	19 infants 9 receiving 2 doses of surfactant with ventilation, 10 ventilation plus placebo.	Randomised controlled trial (1b)	Ventilation index (VI) and oxygenation index (OI) up to 60hrs	Improved OI at 60 hrs (p<0.01) and VI (p< 0.001)	Small study Mean age of treated children 9 wks Values for the changes in OI/VI not tabulated or given in the text All RSV + cases Blinding carried out. Method not stated Randomisation method not clear Insufficient power to detect clinically significant changes in outcomes regarding ventilation times etc.
			Mean ventilation time	Surfactant v. placebo 126 v 170 hrs (p=0.4)
			Mean length of stay in PICU	Surfactant v. placebo 161 v 213 hrs (p= 0.3)
Luchetti et al, 1998,	20 children 10 ventilated and given surfactant. 10 ventilated only	Randomised controlled trial (1b)	paCO2 up to 24 hrs (mean +/- SD)	Surfactant v control 5.0+/- 0.4 v 6.0+/- 0.4 at 24 hrs p<0.05	Mean age of 10.4 months for treated cases No blinding RSV+ cases= only 4 individuals 50mg/kg curosurf used
			paO2:FiO2 ratio up to 24 hrs (mean +/-SD)	Surfactant v control 30.8 +/- 2.7 v 19.4 +/- 1.6 kPa
			Peak inspiratory pressures up to 24hrs (mean +/-SD)	Surfactant v control.28.5 +/- 3.5 v 40.4 +/- 2.4 cmH2O p<0.01
			Ventilation time (days) (mean +/- SD)	Surfactant v control 4.4 +/- 0.4 v 8.9 +/- 1.0 P<0.05
			ICU stay (days) mean +/- SD (days)	Surfactant v control 10.1 +/- 1.2 v 15.7+/- 1.5 p<0.05
Vos GD et al, 1996,	2 infants Both ventilated and given surfactant	Case series	lung compliance and fiO2	Increased lung compliance and decreased fiO2	Case series

Comment(s)

To date no systematic review has been performed on this topic.but the number of trials published to date is very small. Thus there is limited evidence available on the therapeutic merit of surfactant in bronchiolitis. Both trials summarised above show an improvement in ventilation and gas exchange parameters with surfactant. However other than these (surrogate) end points there is a lack of evidence to demonstrate that an infant with severe bronchiolitis will either require a shorter period of ventilation, or a reduced time in an intensive care setting. The earlier trial (Vos et al.) while showing statistically significant reductions in ventilation time and intensive care stay had some limiting factors. Blinding was not carried out and only four cases were shown to be RSV +. Given that bronchiolitis can be due to different viruses and these all could affect children with varying severities this is an important point to bear in mind when considering RSV + bronchiolitis. Interestingly the average age of the cases in Blanco et al's trial was 10.4 months and this may not reflect the typical PICU bronchiolitic "intake" in many other units, bronchiolitis usually being more severe in younger babies. It is worth asking therefore how generalisable this papers findings are given that they relate to infants who are not all RSV+ and who are older than those usually seen in a PICU. The more recent trial by Tibby et al. was a blinded trial but was of insufficient power to show statistically significant changes in ventilation and PICU stay. There were several differences between this trial (Tibby et al.) and the previous one which warrant consideration. This trial comprised younger patients (mean age <10 weeks) , all of whom were RSV+ and were treated with larger doses of surfactant. (100mg/kg v 50 mg/kg ). Thus as well as knowing their RSV status we know they were more representative of a PICU population of bronchiolitics.. However with two trials both using different doses we can ask which dose has the optimal efficacy? No complications were reported in these studies but it is worth reflecting upon the fact that surfactant treatment does not go without its own hazards such as a small increase in the rate of pulmonary haemorrhage. Furthermore surfactant is not cheap and there needs to be evidence showing real clinical improvements rather than improved short term physiological parameters to recommend its use. More or larger trials (including phase 2 trials or trials with multiple arms to look at surfactant doses) are needed to look at the role of surfactant in improving time based outcomes such as ventilation duration and length of hospital/ PICU stay and survival.

Clinical Bottom Line

The use of surfactant in ventilated infants with severe bronchiolitis has been associated with improved oxygenation and ventilatory parameters in the short term Surfactant has not been shown to decrease the duration of ventilation, or the length of admission to a paediatric intensive care unit. Surfactant treatment for bronchiolitis remains an experimental intervention to be used as part of a clinical trial.

References

1. Tibby SM, Hatherill M, Wright SM et al. Exogenous surfactant supplementation in infants with respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med 2000;162(4 Pt 1):1251-1256.
2. Luchetti M, Casiraghi G, Valsecchi R et al. Porcine-derived surfactant treatment of severe bronchiolitis. Acta Anaesthesiol Scand 1998;42(7):805-10.
3. Vos GD, Rijtema MN, Blanco CE. Treatment of respiratory failure due to respiratory syncytial virus pneumonia with natural surfactant. Pediatr Pulmonol 1996;22(6):412-5.