Late Exogenous Surfactant Therapy In Preterm Neonates With Respiratory Distress Syndrome By Dr. Mohamed El- Sherbini

Introduction The most common cause of RD in the preterm infant is RDS. The incidence of RDS is from 5% in infants of Ws GA to >50% in infants of Ws GA.

Pathophysiology Of RDS The stiff atelectatic lung of the preterm infant with RDS does not inflate easily. With the deficiency of surfactant in RDS, the alveoli resist inflation because of the high surface tension at the air- fluid interface.

Role Of Surfactant Therapy In IRDS Surfactant lowers the surface tension at the air- fluid interface of the atelectatic alveoli allowing them to remain inflated. It markedly reduced mortality rate of premature infants and is now established as a safe and effective standard of care.

Aim Of The Work To assess the effect and outcome of late first dose of rescue bovine surfactant therapy administered to preterm infants with RDS on mechanical ventilation (between 24 –48 hr post- natal age).

Patients & Methods The study included 30 preterm infants admitted to NICU and divided into 2 equal groups (1&2) Inclusion criteria: preterm infants with RDS on MV, not suffering from any cong. anomalies, their mothers didn’t receive corticosteroids or other medications and with no history of PROM or hypoxia- ischemia.

Patients & Methods (cont.) Group (1) : The surfactant group: Each received a single bolus therapy of a bovine extract surfactant (beractant) in a dose of 4 ml/kg/dose at a mean age of hr. Group (2) : The comparison group : They were gestational age, sex and weight matched with group (1) but with no surfactant therapy.

Patients & Methods ( cont.) Both groups were subjected to: 1.Full perinatal history& postnatal examination. 2.Plain CXR and ABG analysis. 3.MV, SIMV mode (with a back- up rate of 30 bpm). 4.Full record of clinical picture, CX R, ABGs, ventilation parameters at 24& 48 hr of age. 5.Outcome study (including investigations). 6.Statistical analysis of results.

Results & Discussion Table 1. Baseline characteristics of the two groups. Characteristic Surfactant Group (n = 15) Comparison Group (n = 15) P value Birth weight (Kg) mean±SD1.31± ±0.09>0.05 Gestational age (wks) mean±SD 29.93± ±2.05>0.05 Presence of maternal disease (n, %) 9 (60)8 (53.3)>0.05 C.S. delivery (n, %)13 (86.7) >0.05 Gender Males (n, %) Females (n, %) 8 (53.3) 7 (46.7) 8 (53.3) 7 (46.7) >0.05 N.B. The mean age at which surfactant was administered to group (1) patients = (± 4.13)hr

Results & Discussion(cont.) Table 2. Clinical outcome and X-ray improvement of the two groups at 24 and 48 hours of life. Surfactant Group (n = 15) Comparison group (n = 15) P value Respiratory rate at 24 hr Mean ± SD 60.67± ± 6.05>0.05 Respiratory rate at 48 hr Mean ± SD 51.13± ± 5.18<0.001** Retractions at 24 hr (n, %) 15 (100) -- Retractions at 48 hr (n, %) 2 (13.3)15 (100)<0.001**  Air entry at 24 hr (n, %) 15 (100) --  Air entry at 48 hr (n, %) 2 (13.3)15 (100)<0.001** X-ray improvement at 48 hr (n,%) 13 (86.7)0 (0)<0.001** ** Highly significant

Results & Discussion(cont.) Fig. (1):Comparison between the surfactant and the non surfactant groups in X-ray improvement at 48 hr of age

Results & Discussion(cont.) Fig.(2): Chest X-ray of a case of the surfactant group before and after surfactant administration AfterBefore

Results & Discussion(cont.) Table 3. Outcome of arterial blood gases at 24 and 48 hours of life of the two groups. Surfactant group (n = 15) Mean±SD Comparison group (n = 15) Mean±SD P value pH at 24 hr7.23 ± ±0.034>0.05 pH at 48 hr7.29± ± 0.03<0.001** PaO 2 at 24 hr (mmHg)55.82± ± 3.63>0.05 PaO 2 at 48 hr (mmHg)63.9± ± 3.41<0.001** PaCO 2 at 24 hr (mmHg)57.13± ± 5.55>0.05 PaCO 2 at 48 hr (mmHg)46.93± ± 4.24<0.001** HCO 3 at 24 hr (mmol/L)22.13± ± 2.11>0.05 HCO 3 at 48 hr (mmol/L)21.6± ± 1.72>0.05 ** Highly significant

Results & Discussion(cont.) Table 4. Outcome of ventilatory parameters at 48 hours of life of the two groups. Surfactant group (n = 15) Mean±SD Comparison group (n =15) Mean±SD P value PIP (cm H 2 O)18.73± ± 1.28<0.001** PEEP (cm H 2 O)4.13± ± 0<0.001** FiO ± ± 0.08<0.001** Ti at (sec)0.5± ± 0.06<0.05* Te at (sec)1.41± ± 0.11>0.05 MAP (cm H 2 O)7.99± ± 0.613<0.001** OI5.16± ± 2.02<0.001** * significant ** Highly significant

Results & Discussion(cont.) Mean Airway Pressure: Oxygenation Index : MAP = PEEP + (PIP – PEEP) × Ti Ti + Te OI = MAP × FiO 2 × 100 Pa O 2

Results & Discussion(cont.) Fig.(3): Mean airway pressure at 24 and 48 hr of age

Results & Discussion(cont.) Fig. (4): Oxygenation index at 24 and 48 hr of age

Results & Discussion(cont.) Table 5. Median duration of hospitalization and mechanical ventilation in surfactant and comparison groups. Surfactant group (n = 15) Mean±SD Comparison group (n = 15) Mean±SD P value Duration of hospitalization (days) ± ±14.22<0.05* Duration of mechanical ventilation (days) 7.13 ± ± 9.47<0.001* * * Significant ** Highly significant

Results & Discussion(cont.) Fig. (5):Duration of hospitalization and mechanical ventilation

Results & Discussion(cont.) Table 6. Outcome comparison between surfactant and non- surfactant groups. CLD = chronic lung disease; ICH = intracranial hemorrhage PDA=patent ductus arteriosus; NEC =necrotizing enterocolitis Surfactant group (n = 15) n (%) Comparison group (n = 15) n (%) P value Death due to RDS 0 (0)2 (13.3)>0.05 CLD 0 (0)3 (20)>0.05 Air leak 0 (0)3 (20)>0.05 Pulmonary hemorrhage 1 (6.67) --- ICH 1 (6.67) --- PDA 1 (6.67) --- Sepsis 2 (13.3)3 (20)>0.05 NEC 1 (6.67) ---

Results & Discussion(cont.) Fig. (6): Outcome of the two study groups

Summary & Conclusion 1.Late (24 – 48 hr of age) single dose of rescue therapy of bovine surfactant administered to preterms with RDS on MV has shown effectiveness. 2.The improvement was obvious clinically, in CXR, ABGs, needs and parameters of ventilation. 3.Highly significant  in MAP, OI and duration of MV and a significant  in duration of hospitalization were obvious in the surfactant group. 4.No mortality, CLD and air leak were detected among surfactant-treated preterms.

Recommendation The use of a single dose of bovine surfactant replacement therapy, (even appears to be late after the first 24 hr of age), is beneficial and recommended in cases of preterm infants with RDS on mechanical ventilation.