- Can extreme low birth weight infants be treated with BLES®?
- Yes. BLES® has been clinically evaluated in controlled trials with infants weighing between 380 grams to 4460 grams. The recommended dose of BLES® is 5 mL per kilogram of body weight. Therefore the volume of a dose is proportional to the weight of the infant; a smaller infant receives a smaller dosing volume of BLES®. For example, a 1 kg infant would receive 5 mL of BLES®, however an infant weighing 400 g would receive only 2 mL of BLES®.
- What are the advantages of the relatively high volume dose of BLES®?
- When given rapidly as a bolus dose, larger volumes of surfactant containing relatively high amounts of SP-B and SP-C have been found in pre-clinical studies to produce a more uniform distribution throughout the lungs, improving the response to treatment.1,2
- Why is rapid bolus dosing recommended during administration of BLES®?
- Homogenous distribution of surfactant over the large surface area of the lung is critical to the success of therapy.3 Pre-clinical studies have shown that rapid bolus dosing helps ensure meniscus formation, filling the trachea and bronchi with the bolus, from which a more uniform dispersal process can proceed.1
- Should I use a slow drip method when administering BLES®?
- No. A slow drip administration technique is less likely to form a meniscus in the trachea. In the absence of a liquid meniscus, surfactant distribution becomes dependent on the orientation of the airways with respect to gravity. This may lead to over-inflation of certain portions of the lung4, potentially resulting in uneven lung compliance.
- Should I use test aliquots when administering BLES®?
- No. Test aliquots could lead to uneven distribution throughout the lungs. This may lead to over-inflation of certain portions of the lung4, potentially resulting in uneven lung compliance. Furthermore, Rubin et al found that small test aliquots may promote mobilization of resident mucous that can result in ETT obstruction.5 Please see below.
- How often is endotracheal tube (ETT) blockage experienced during administration of BLES®? What is the recommended method to address ETT blockage?
- BLES® has low viscosity which contributes to a low rate of ETT blockage. Since market approval, only 0.04% of estimated patients treated have been reported to experience ETT complications. Specifically, regarding acute airway obstruction, Rubin et al. found that airway obstruction in RDS may be due, in part, to abnormal mucous properties and impaired ciliary transport, and that surfactant therapy may enhance mucous clearance from the lungs5. Therefore, BLES® may promote the movement of resident mucous which could cause obstruction. Infants may experience mucous plugging, particularly if pulmonary secretions were prominent prior to BLES® administration. Infants whose ventilation becomes markedly impaired during or shortly after dosing may have mucous plugging of the ETT. Suctioning of all infants prior to dosing may lessen the chance of mucous plugs obstructing the ETT. If ETT obstruction from such plugs is suspected, and suctioning is unsuccessful in removing the obstruction, the blocked ETT should be replaced immediately.
- How does the low viscosity of BLES® affect the distribution of surfactant throughout the lungs?
- When administered via rapid bolus dosing, the high volume and low viscosity of BLES®, in combination with relatively high concentrations of SP-B and SP-C, may contribute to the efficacy of the surfactant.6 Proper ventilation can deliver the low viscosity surfactant to the terminal airways resulting in quicker spreading in a few breaths and a more uniform distribution of surfactant throughout the lungs.7 For these reasons, surfactants with lower surface viscosity may be preferred for endotracheal application. In addition, lower surface viscosity means that less surfactant is lost to coating of the upper airways.7,8
- How quickly can I expect the patient to respond after receiving BLES®?
- Because BLES® acts rapidly in improving oxygenation and lung compliance, it is very important that the patient is closely monitored after administration, with ventilator settings being adjusted in response to changes. Recent clinical experience has found that the majority of patients treated with BLES® are weaned to room air within 30 minutes; however, infants have been reported to wean to room air in as little as 1 minute.9
- When can I administer a repeat dose of BLES®?
- Neonates can receive up to 3 additional doses of BLES® within the first 5 days of life. The criteria for an additional dose are a positive response to the previous dose, and an increase in respiratory support as signalled by a gradual increase in FiO2. This increase must be at least 10% greater than the FiO2 required after the initial response to the previous dose of BLES®. There is no minimum time requirement between doses.
- How do I warm BLES® prior to administration?
- BLES® should be warmed to at least room temperature, but no higher than body temperature before being administered. Warming can be accomplished in the following ways (times are approximate):
Method of Warming Refrigerated Vials Frozen Vials In the hand 5 min. 10 to 15 min. On the counter 20 min. 60 min. In a 37°C water bath 2 min. 5 min.
Once at room temperature, gently swirl or invert the vial to suspend the lipid and disperse any agglomerates. Inspect the vial for homogeneity. It is normal for warmed vials to have an even dispersion of fine but visible flecks of lipid. Contents should appear as an off-white to light yellow suspension.
- What if the product does not change phase in the freezer?
- Some “frozen” vials may not solidify. This is a normal occurrence that does not affect product quality.
- BLES® has a very long frozen shelf-life, why is the refrigerated shelf-life only 10 months?
- This is because the biophysical and chemical stability specifications are the same as the release specifications for these attributes. This means at the end of its 36-month frozen shelf-life or 10-month refrigerated shelf-life, the quality of the drug product is identical to that of a recently manufactured batch.
1 Espinosa, F.F., Kamm, R.D. Meniscus formation during tracheal instillation of surfactant. J Appl Physiol 85: 266-272, 1998
2 Nouraeyan, Lambrinakos-Raymond, A., Leone, M., Sant’Anna, G. Surfactant administration in neonates: A review of delivery methods. Can J Respir Ther. 2014 Autumn; 50(3):91-95
3 Guttentag, S., Foster, C. Update in Surfactant Therapy. NeoReviews V. 12 No. 11 November 2011: 625-633
4 Ueda, T., Ikegami, M., Rider, E. D., Jobe, A. H. Distribution of surfactant and ventilation in surfactant-treated preterm lambs. J. Appl. Physiol. 76(1):45-55, 1994.
5 Rubin, B.K., Ramirez, O., King, M. Mucus rheology and transport in neonatal respiratory distress syndrome and the effect of surfactant therapy. Chest. 101;1080-1085, 1992.
6 Lewis, J. F., Goffin, J., Yue, P., McCaig, L. A., Bjarneson, D., Veldhuizen, R. A. W. Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury. J. Appl. Physiol. 80(4):1156-1164, 1996. And in-house testing
7 Nouraeyan, et al. Surfactant administration in neonates: A review of delivery methods. Can J Respir Ther. 2014 Autumn; 50(3):91-95
8 Lewis, et al. Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury. J. Appl. Physiol. 80(4):1156-1164, 1996.
9 Stockley, E., Valotaire, R., Miller, M., da Silva, O. Effects of bovine lipid extract surfactant administration in preterm infants treated for respiratory distress syndrome. Health Sci Rep. 2018;e34.