Novel Approaches to Surfactant Administration Dr.Sh.Noripour Neonatologis Semnan Medical Sciences University

RDS - Treatment Oxygen CPAP Mechanical ventilation Surfactant replacement Supportive Care The standard treatments we are all familiar with, including oxygen supplementation, Respiratory support with CPAP of mechanical ventilation and surfactant replacement therapy whilst at the same time providing good supportive care with careful fluid and nutritional management and temperature control. However within each of these areas controversies still exist. How much oxygen should we give? Who should get CPAP and who should be ventilated? When should you intubate to give surfactant etc.

Information about HMD in Late 1960’s Normal lungs contained surfactant (Clements – 1957) HMD lungs were surfactant deficient (Avery and Mead – 1959) Intubation of HMD infants abolished grunting and decreased oxygenation (Harrison, et al., 1968)

( Goran Enhorning (obstetrician). (b) Bengt Robertson (perinatal pathologist).

Goran Enhorning, an obstetrician, and Bengt Robertson, a pediatric pathologist, showed that preterm rabbits treated with natural surfactant did not die as expected soon after birth. After one year later, in 1973, they showed that pharyngeal deposition rather than tracheal instillation of natural surfactant was also effective

Historical Perspectives –cont. In 1973 CPAP using nasal catheters positioned in the midnares was used on infants weighing >1500gms who had RDS requiring >60% oxygen to maintain a PaO2 of 50-60 mmHg. These early interventions increased survival of preterm infants.

VIENNA-09

20 - Required 100% or had Apnea 1 - Ventilated from Birth 20 Infants Treated with CPAP over 16 Months 51 Infants with IRDS UA lines, O2 for Pao2 of 50-70 mmHg 20 - Required 100% or had Apnea 5 - Apnic at Birth 1 - Ventilated from Birth 25 - Increased O2 Only All Survived Bag & Mask Ventilation Ventilated 1 Survived CPAP All Died 16 Survived Data from Gregory NEJM, 1971 VIENNA-09

CPAP Device for use with Endotracheal Tube Gregory, et al., NEJM, 1971 VIENNA-09

Head Box for CPAP without Endotracheal Tube VIENNA-09 Gregory, et al., NEJM, 1971

CPAP Provided by G. Gregory This is a trash bag with gas inflow. It was closed loosely about the neck and pressure could be maintained easily and constantly. This was about the 5th or 6th patient we treated. Provided by G. Gregory

George Gregory

Fujiwara in 1980 published a seminal article in the Lancet giving the results of administration of a modified bovine surfactant (Surfactant-TA) to 10 preterm infants.

Verder et al. tested a novel approach, INSURE (intubation, surfactant administration, and extubation). This technique provides the benefits of surfactant administration but also eliminates continued mechanical ventilation. This approach, still requires skills for intubation and has the potential for trauma to the glottis and airway during intubation as well as the risks of surfactant administration enumerated above. H. Verder, B. Robertson, G. Greisen et al., “Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome,” New England Journal of Medicine, vol. 331, no. 16, pp. 1051–1055, 1994. 

Infants randomly assigned to treatment with surfactant were treated with morphine (0.1 mg per kilogram intravenously) and atropine (10 μg per kilogram intravenously) before intubation. Treatment with naloxone (10 μg per kilogram intravenously) before extubation was optional

Current recommendations vary from use in infants who are intubated and have an aAPo2 <0.22 to use in infants receiving ≥40% oxygen administered in a hood when the Pao2 is <80 TORR (aAPo2 approximately <0.36).

Guidelines for Surfactant Treatment of RDS < 28 wk 29-31 wk > 32 wk NIPPV in DR, Early Rescue (<30’) in DR or NICU with 200 mg/kg of Poractant Alfa Early CPAP/NIPPV Surfactant if intubated for resuscitation Observe CPAP/NIPPV if respiratory distress Extubate to NIPPV as soon as possible (> 24 wk). Start Caffeine Early Rescue with 100-200 mg/kg if FiO2 > 0.30 + white CXR. Delayed Rescue with 100 mg/kg if FiO2 > 0.40 + white CXR Caffeine if symptomatic Redosing: FiO2 > 0.30 How soon: 2-12 hrs from the 1st dose FiO2 > 0.35 How soon: 12 hrs from the 1st dose FiO2 > 0.40 17

Downes’ Scoring system 0   1 2  Cyanosis None In room air  In 40% FIO2  Retractions Mild Severe Grunting Audible with stethoscope Audible without stethoscope Air entry Clear Decreased or delayed Barely audible Respiratory rate <60 60-80 >80 or apnea  Score:  > 4 = Clinical respiratory distress; monitor arterial blood gases > 8 = Impending respiratory failure

Failure of InSurE was associated with severity of RDS and extremely low birth weight < 750g

MISurf: Minimally invasive intratracheal surfactant application without mechanical ventilation by feeding tube device InSurE: Surfactant application by InSurE strategy (Intubation - surfactant - extubation sequence).

Minimally invasive surfactant application (MISurf) via feeding tube or IV cannula device is a recently described innovative method of surfactant administration without the need for positive pressure ventilation

Several techniques, collectively labeled “minimally invasive surfactant therapy” (MIST), have been described in which surfactant is delivered without tracheal intubation.

strategies include (1)intra-amniotic instillation (2)pharyngeal instillation (3)administration via laryngeal mask airway (4)administration via thin endotracheal catheter without IPPV (5)aerosolized/nebulized surfactant administration in spontaneously breathing infants.

Intra-Amniotic Instillation of Surfactant There is only one feasibility report describing endoscopic delivery of surfactant directly to the fetus during active preterm labor Using this approach the investigators injected surfactant into the mouths of 3 preterm fetuses through a catheter placed through the biopsy channel of the fiberscope it has not been incorporated into clinical practice.

Pharyngeal Instillation of Surfactant The pharyngeal instillation of surfactant before delivery has the potential to replicate the physiologic process. While the chest remains compressed in the birth canal, fetal lung fluid can be suctioned from the upper airway and replaced with a surfactant-containing solution. Then, as the chest expands, the baby is stimulated to aspirate the surfactant-containing solution providing surfactant at the advancing air-fluid interface. This process can be further facilitated by the application of mask CPAP.

Surfactant administered within the nasopharynx before delivery of the shoulders after suctioning of the nasopharynx. Newborns received CPAP at 10 cm H2O by mask as they initiated breathing, and this was continued at 6 cm H2O for at least 48 hours this approach requires a cephalic delivery and a spontaneously breathing infant. Cesarean section, malpresentation (breech or transverse), or perinatal compromise limit the application of this approach.

Administering via Laryngeal Mask Airway (LMA) A protocol for LMA surfactant administration suggested by Trevisanuto involves positioning the LMA, followed by instilling the surfactant in two to four aliquots via the LMA. Each aliquot is usually followed by brief IPPV until the surfactant disappears from the LMA. the LMA is removed and the baby is placed on CPAP for subsequent management.

The limitations of surfactant administration using LMA are related to the nonavailability of smaller LMA sizes for use in extremely premature infants The technique is relatively simple and seems promising, but well-designed studies are needed to confer safety and efficacy.

aerosolized/nebulized surfactant administration Use of nebulized surfactant seems to be the most sophisticated and minimally invasive technique Multiple factors are reported to influence aerosol surfactant dose delivery, including patient weight or size, minute ventilation , aerosol flow and patient peak inspiratory flow, aerosol particle size

It is classified as a “MIST” technique. Administration via Thin Endotracheal Catheter/Feeding Tube without IPPV This method of surfactant administration delivers exogenous surfactant using a thin intravascular catheter or feeding tube inserted below the vocal cords. It is classified as a “MIST” technique.

MIST/LIST – Minimally/Less Invasive Surfactant Therapy Dargaville and Gopel described the use of rescue surfactant administered in spontaneously breathing infants, via a fine tube placed into the trachea without the use of sedative or paralysing drugs

Indication for MIST worsening hyaline membrane disease in a baby on non-invasive support increased work of breathing (WOB – respiratory rate,recession, apnoea, cardiovascular stability) Increasing oxygen requirement (FiO2) (normally over 50%)

Equipment (1) Laryngoscope with appropriate sized blade (2) Surfactant administration pack – syringe, needle and administration tube (3) Magill forceps (4) 5ml syringe (5) Warmed surfactant (rub vial in hands to ensure not chilled), prescribed on drug chart