** SURFACTANT THERAPY** Full Title of Guideline: Surfactant Therapy Author (include email and role): Stephen Wardle (V4) Reviewed by Dushyant Batra Consultant Neonatologist Division & Speciality: Division: Family Health - Children Specialty: Neonatology Version: 5 Ratified by: Scope (Target audience, state if Trust wide): Review date (when this version goes out of date): Explicit definition of patient group to which it applies (e.g. inclusion and exclusion criteria, diagnosis): Changes from previous version (not applicable if this is a new guideline, enter below if extensive): Summary of evidence base this Neonatal Guidelines Committee Guideline for use by Nottingham Neonatal service staff January 2023 Preterm and term neonates where surfactant therapy considered for prophylactic or rescue treatment Inclusion of recent evidence but no change in overall management strategies from the last version of the guideline See evidence table below guideline has been created from: This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date or outside of the Trust. Key Points Curosurf at a dose of 200mg/kg (see dosing table) is used Give surfactant prophylactically on delivery suite to all babies born at 26 completed weeks (i.e. up to and including 26 +6 ) Give surfactant treatment to all babies 27-32 weeks who require ventilation for symptoms of respiratory distress during the first day after birth Give surfactant treatment to all babies > 32 weeks who require ventilation for symptoms of respiratory distress who also have radiological evidence of RDS Consider using surfactant after birth in other conditions: meconium aspiration syndrome, pulmonary haemorrhage, pneumonia
1. Introduction and Rationale: Respiratory distress syndrome (RDS) occurs due to surfactant deficiency and lung immaturity in preterm infants. Surfactant therapy has revolutionised neonatal respiratory care. Most aspects of its use have been tested in multicentre randomised controlled trials, many of which have been subjected to systematic review 1. Surfactant therapy, whether given prophylactically 2 or as rescue therapy 3 to babies with or at risk of developing RDS, reduces the risk of pneumothorax and neonatal death. Clinical trials have focused on determining the optimal dose, the timing of dosing, the best method of administration and the best surfactant preparation although many of the initial studies were conducted in an era of low antenatal steroid and CPAP use. Some studies have shown that early initiation of CPAP and selective surfactant administration rather than routine prophylaxis babies may do better, with some avoiding intubation altogether and reduced rates of death or chronic lung disease in the CPAP group 3 5. However, it must be borne in mind, that babies in these trials were recruited antenatally and were therefore delivered in optimal condition, with a high rate of antenatal steroid use. These results may not be generalisable to all babies 6. In addition, this approach requires significant expertise at maintaining CPAP in the delivery suite and on route to the NICU and it still requires a significant proportion of babies to be intubated and may increase the risk of pneumothorax 6. Recent studies have shown feasibility of delivering surfactant in spontaneously breathing infants using less invasive methods including thin tubes 7 and laryngeal mask airways 8. More evidence is required before such practices can be routinely adopted. In Nottingham, therefore, we have chosen to continue the routine use of prophylactic natural surfactant in preterm infants requiring ventilation at very low gestations (see Early Care Guideline A8). Natural surfactant is given as early as possible after assessment when more mature babies need ventilation. There are other conditions which occur in newborn infants in which surfactant deficiency or inactivation are also likely to play important roles. These include: Meconium aspiration syndrome (see Neonatal Guideline B16) Congenital pneumonia Pulmonary haemorrhage (see Neonatal Guideline B13) Select cases of congenital diaphragmatic hernia (premature babies with suspected surfactant deficiency, see Neonatal Guideline B4) The use of surfactant has been examined in meconium aspiration syndrome 9. A meta-analysis of four studies has shown that there is a significant improvement in respiratory outcomes when surfactant is used with fewer infants requiring ECMO, although there was no significant effect on mortality 9. There are anecdotal reports of success following pulmonary haemorrhage in preterm infants 10 and in congenital pneumonia 11,12 and in select preterm infants with CDH 13 (see guideline B4). Discuss with the consultant. 1.1 Surfactant Choice There are two options regarding choice of natural surfactant currently available in the UK. Curosurf is a porcine surfactant and Survanta is a bovine surfactant. These two surfactants differ in a number of respects. 1. The volume of administration is different with a volume of 4ml / kg for Survanta and 1-2 ml / kg for Curosurf. This results in Curosurf being much easier to administer particularly in small babies where large volumes of liquid being put down the endotracheal tube are poorly tolerated. 2
2. There is a marked difference in the speed of action. In all comparisons Curosurf produces a more rapid response with a change in SaO 2 and pulmonary compliance seen within seconds of administration, whereas Survanta's effects tend to occur over a period of a few hours. 3. The smaller volume of administration, more rapid improvement in respiratory status, and reduced need for repeat doses with Poractant Alfa(Curosurf ) more suitable than Beractant (Survanta ) 14. In Nottingham therefore Curosurf is the surfactant used. 2. Patient Group and Indications: All infants 26 completed weeks (i.e. up to and including 26 +6 ) Babies 27-32 weeks who require ventilation for symptoms of respiratory distress during the first day after birth. Babies > 32 weeks who require ventilation for symptoms of respiratory distress who also have radiological evidence of RDS. Infants ventilated with meconium aspiration syndrome Other infants ventilated with significant parenchymal lung disease e.g. pneumonia Preterm infants following massive pulmonary haemorrhage Discuss with consultant as appropriate 3. Dosage and Administration: There is evidence that a dose of 200mg/kg is of additional benefit over a dose of 100mg/kg. There is a small decrease in mortality when 200mg/kg is used compared to 100mg/kg 15 and this dose has been recommended in the European Consensus Guideline on the Management of Respiratory Distress Syndrome in Preterm Infants 16. There is likely to be a reduction in the number of second doses required when a higher first dose is used, although this is difficult to quantify. 3.1 Dosage In Nottingham therefore a dose of 200mg/kg is used although a whole dosing system is used to prevent wastage / over use. One vial contains either 120mg or 240mg (100mg/ml) therefore to avoid wastage and because the infant s weight is not known at birth the following table can act as a guide to the dose required:- Birth weight or gestational age Dose of Curosurf On delivery suite 26 completed weeks gestation one whole vial of 120mg 27-32 weeks one whole vial of 240mg <900g 120mg 901-1500g 240mg 1501-2000 360mg On NICU 2001-2600 480mg 2601-3300 600mg 3301-4000 720mg 4001-4600 840mg 4601-5000 960mg Two doses of Curosurf 12 hours apart, the second given only if the child remains intubated. For babies of 26 weeks and less the first dose should be given immediately after intubation, on delivery suite. Using the doses above most babies will get 200mg/kg or close to it. Always try to use whole vials. 3
The second dose can be given at 12 hours of age or before if considered necessary (discuss with consultant) if the infant remains ventilated in 30% oxygen and / or Mean Airway Pressure 8 cm H 2 O (equivalent to an Oxygenation Index (OI) of approximately 7 (See Mechanical Ventilation guideline B1) In severe RDS, which has been only partially sensitive to the first two doses of surfactant, a further dose may be considered (after discussion with the duty consultant neonatologist). If there is a chance that the surfactant dose may have not been administered into the trachea or if there is clear evidence on the CXR that surfactant only entered one lung consider repeating the dose after appropriate correction of the endotracheal tube position. In the non-rds indications there may be inhibitors of surfactant present in the tracheal/bronchial tree, making any effect of surfactant short-lived: initially 6 hourly dosing may be necessary, again discuss with the Consultant. 3.2 Administration: Surfactant should be prescribed on the usual drug prescription chart even when given in delivery suite. Surfactant is stored in the fridge and should be gently warmed (keeping the vial in incubator or within palm of hands for few minutes). It must be administered with the surfactant giving set (Figure 1) Also always document in the notes and record on the daily activity form on the Badger database. Only draw up the surfactant if it is definitely going to be used to avoid wastage. Figure 1: Surfactant vials and giving set For administration on delivery suite:- Resuscitate the baby according to Resuscitation Guideline / Early Care Guideline Intubate to stabilise the airway when HR and colour are satisfactory Ensure adequate chest movement and auscultate to check for bilateral air entry Stabilise the ETT in the usual way Have an assistant draw up and rapidly give the Curosurf into the ETT via the administration set Continue positive pressure ventilation via the ETT Record in clinical notes response to treatment and any difficulties encountered 4
For administration on the neonatal unit:- The baby should be in the supine position (There is no reason to move position during administration.) Draw up appropriate dose for baby using surfactant administration kit. Disconnect ETT from ventilator circuit. Pass administration tube through the ETT and instil surfactant rapidly into the trachea. Reconnect to the ventilator. It may be necessary to increase the ventilator settings transiently whilst administering the surfactant. Curosurf has a rapid action and you should see an almost immediate change in the arterial oxygen saturation (or PaO 2 ). It may be necessary to decrease the FiO2 and the peak inspiratory pressure to prevent over-ventilation. Volume guided ventilation is preferable as appropriate (guideline B1) 3.3 Monitoring Remain at the bedside until you are satisfied that the clinical condition is stable, monitoring the clinical condition of patient, bedside parameters including oxygen saturation, heart rate, respiratory rate and blood pressure, and information from ventilator including tidal volume/ peak pressures and pulmonary graphics (See guideline B1). Measure a blood gas within 30-60 minutes of giving surfactant and alter the ventilation accordingly. Record in clinical notes response to treatment and any difficulties encountered 4. Audit: Data points Source of information 1. Time of administration of the first dose Drug chart 2. Number of doses Drug chart 3. Adverse events during dosing Clinical notes (always record administration and clinical course during and after dose) 4. Frequency and duration of hyperoxia/ Gas chart/nursing observation chart hypocarbia post administration 5. Use for non-rds applications Record number of doses and blood gas results before and within 1 hour after installation 5. Allied Guidelines Mechanical Ventilation (B1), Early Care (A8), Meconium Aspiration Syndrome (B16), High Frequency Oscillation Ventilation guideline (B9) 6. References 1. Singh, N. et al. Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants. Cochrane Database of Systematic Reviews 1 69 (2015). doi:10.1002/14651858.cd010249.pub2 2. Soll, R. & Ozek, E. Prophylactic protein free synthetic surfactant for preventing morbidity and mortality in preterm infants. The Cochrane database of systematic reviews (John Wiley & Sons, Ltd, 2010). doi:10.1002/14651858.cd001079.pub2 3. Rojas-Reyes, M. X., Morley, C. J. & Soll, R. Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants. Cochrane Database of Systematic Reviews CD000510, 1 69 (2012). 4. Network, S. S. G. of the E. K. S. N. N. R. Early CPAP versus Surfactant in Extremely Preterm Infants. N. Engl. J. Med. 362, 1970 1979 (2010). 5. Sandri, F. et al. Prophylactic or Early Selective Surfactant Combined With ncpap in Very 5
Preterm Infants. Pediatrics 125, e1402 e1409 (2010). 6. Stevens, T. P., Blennow, M., Myers, E. W. & Soll, R. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database of Systematic Reviews CD003063 (2007). doi:10.1002/14651858.cd003063.pub3 7. Aldana-Aguirre, J. C., Pinto, M., Featherstone, R. M. & Kumar, M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch. Dis. Child. Fetal Neonatal Ed. 102, F17 F23 (2017). 8. Pinheiro, J. M. B., Santana-Rivas, Q. & Pezzano, C. Randomized trial of laryngeal mask airway versus endotracheal intubation for surfactant delivery. J. Perinatol. 36, 196 201 (2016). 9. El Shahed, A. I., Dargaville, P. A., Ohlsson, A. & Soll, R. Surfactant for meconium aspiration syndrome in term and late preterm infants. Cochrane database Syst. Rev. 12, 1 36 (2014). 10. Pandit, P. B., Dunn, M. S. & Colucci, E. A. Surfactant therapy in neonates with respiratory deterioration due to pulmonary hemorrhage. Pediatrics 95, 32 6 (1995). 11. Auten, R. L., Notter, R. H., Kendig, J. W., Davis, J. M. & Shapiro, D. L. Surfactant Treatment of Full-Term Newborns With Respiratory Failure. Pediatrics 87, 101 107 (1991). 12. Davis, J. M., Richter, S. E., Kendig, J. W. & Notter, R. H. High-frequency jet ventilation and surfactant treatment of newborns with severe respiratory failure. Pediatr. Pulmonol. 13, 108 12 (1992). 13. Snoek, K. G. et al. Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update. Neonatology 110, 66 74 (2016). 14. Ramanathan, R. et al. A Randomized, Multicenter Masked Comparison Trial of Poractant Alfa (Curosurf) versus Beractant (Survanta) in the Treatment of Respiratory Distress Syndrome in Preterm Infants. Am. J. Perinatol. 21, 109 119 (2004). 15. Singh, N., Hawley, K. L. & Viswanathan, K. Efficacy of Porcine Versus Bovine Surfactants for Preterm Newborns With Respiratory Distress Syndrome: Systematic Review and Metaanalysis. Pediatrics 128, e1588 e1595 (2011). 16. Sweet, D. G. et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology 111, 107 125 (2017). 7. Summary of Evidence Summary of Evidence Level of evidence Natural Surfactant prophylaxis improves survival of preterm infants (1,2,3) A Surfactant treatment decreases need for ECMO in babies with meconium aspiration syndrome (MAS) (9) A Surfactant deficiency and / or inactivation has been associated with MAS, pneumonia, PPHN, and TTN (10-12) C 6
Its use can be considered in pulmonary haemorrhage, pneumonia (10-12) D 200 mg/kg of Curosurf rather than 100mg/kg may have advantages (15-16) B 7