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Brief Reports

Indian Pediatrics 2001; 38: 640-646  

Surfactant Therapy for Hyaline Membrane Disease: The Chandigarh Experience


Anil Narang,
Praveen Kumar, Sourabh Dutta, Rajesh Kumar

From the Division of Neonatology, Department of Pediatrics, Advanced Pediatrics Center, PGIMER, Chandigarh 160 012, India.
Correspondence to: Dr. Anil Narang, Professor (Neonatology), Department of Pediatrics, PGIMER, Sector-12, Chandigarh 160 012, India.
E-mail: anilnarang@yahoo.com

Manuscript received: June 1, 2000; Initial review completed: July 2, 2000; Revision accepted: January 18, 2001.

Surfactant replacement therapy (SRT) is now accepted as the standard of care for premature babies with hyaline membrane disease (HMD). In India, the drug is however still not licensed for import. Even then, its use and availability has increased in the last couple of years(1,2). We have been using this drug since November 1997 on the basis of affordability by the family. In this commu-nication, we report our experience with the use of surfactant from November 1997 to September 1999.

Subjects and Methods

During the study period, the pediatricians and obstetricians were made aware about the possibility of using surfactant. For women likely to deliver at <32 weeks, the family was counseled about the possibility of using prophylactic surfactant based on their obstetric history, affordability, and the avail-ability of drug in local market. Prophylactic surfactant was also used in some of the babies with gestational age <34 weeks if they had additional risk factors for HMD, i.e. infant of diabetic mothers, previous sibling having HMD, Rh incompatibility. For women deli-vering at ³32 weeks, SRT was considered as ‘rescue’ therapy based on same factors as above, if the baby developed HMD and required mechanical ventilation.

Two types of surfactant were used depending on availability: Survanta (Abbott Laboratories, USA; Dose - 4 ml/kg) and Exosurf (Burroughs Wellcome Co., USA; Dose - 5 ml/kg). The surfactant was adminis-tered intratracheally according to standard procedures. ‘Prophylactic’ surfactant was administered in the delivery room within few minutes of life as soon as baby had been stabilized. ‘Rescue’ surfactant was given as early as possible once the diagnosis of HMD had been made. The average age of administration of rescue surfactant was 9 (1.5-20) hours. Repeat doses were considered after 12 hours in babies who continued to be on ventilator and family could afford. All babies whether they received surfactant or not were ventilated on SIMV mode with Babylog 8000 ventilator (Drager). The ventilation strategy and sedation/analgesia was similar in all babies.

Prophylactic indomethacin was given to babies with birth weight <1250 grams and in others, indomethacin was given if PDA was diagnosed clinically and supported by M-mode echocardiography (LA/Ao ratio >1.4). Ultrasound of head was done in all babies on day 1, 3, and 7 of life and whenever IVH was clinically suspected. Chronic lung disease (CLD) was diagnosed when baby was requiring oxygen on or beyond day 28 of life and chest X-ray was suggestive. The most important cause of death was assigned based on clinical course, laboratory results and autopsy findings.

Results

During the study period 207 babies with HMD requiring mechanical ventilation were admitted in NICU. Out of these, 88 babies received surfactant. Amongst those who received surfactant, 65% received 1 dose only, 25% received 2 doses and 10% received 3 doses. The babies in both groups had comparable characteristics except for delivery by Cesarean section, which was significantly higher in the surfactant group (Table I).

The early neonatal mortality was signi-ficantly lower in surfactant (25%) than in the no surfactant group (38.7%). Septicemia was the commonest cause of death in both the groups, but it was significantly lower in the surfactant group (17%) compared to no surfactant group (28.6%). Other causes of death included air-leaks, IVH, pulmonary hemorrhage and were comparable in the two groups. The overall survival till discharge in surfactant group (62.5%) was significantly higher than in no surfactant groups (43.7%). The survival rates were also significantly higher in the babies who received surfactant across 28-33 weeks gestation (Table II). When survival was analyzed according to birth weight, significantly better survival was observed only in birth weight group of 1000-1249 grams (Table III).

The incidence of septicemia, pneumonia, patent ductus arterioisus (PDA), intra-ventricular hemorrhage (IVH), and chronic lung disease (CLD) were significantly lower in babies who had received surfactant (Table IV). Air leaks however were comparable in two groups. The mean duration of ventilation was significantly shorter in the surfactant group (85.7±46 hours), compared to the no surfactant group (129.8±43 hours). The mean NICU and hospital stay were comparable in the two groups (Surfactant group - 14.5±12.1 and 27.13±17.9 days; and No surfactant group - 16.55±11.8 and 31.5±21.1 days, respectively).

A total of 65 babies received prophylactic surfactant during this period. Among these 53 (81.5%) developed HMD. Comparison of the HMD babies who received surfactant prophylactically or as ‘rescue’ treatment is depicted in Table V. Early neonatal mortality, pneumonia, PDA, and duration of hospital stay were significantly lower in the prophy-lactic surfactant group.

Table I General Characteristics of Patients

Characteristic

Surfactant
(n=88)

No surfactant
(n=119)

Gestational age (Weeks) (Mean±SD)

30.7±2.46

30.4±2.81

Birth weight (Grams) (Mean±SD)

1387±469.7

1365±407.9

Male (%)

62.5

58

Antenatal booked pregnancy (%)

27.3

21.8

Antenatal steroid (%)

78

77.3

Antenatal steroid (Last dose ³24 hours prior to delivery)(%)

12.5

8.4

Cesarean delivery* (%)

50

34.5

Severe birth asphysia (1 minute Apga  £3) (%)

13.6

15.1

Duration of rupture of membrane >12 h (%)

 18.2

21.8

*p<0.05

Table II Survival by Gestational Age

Gestational age

Surfactant

No surfactant

(weeks)

Number

Survival

Number

Survival

£27

8

1 (12.5)

18

4 (22.2)

28-29*

16

8 (50)

28

6 (21.4)

30-31**

20

13 (65)

29

14 (48.3)

32-33**

31

23 (74.2)

26

16 (61.3)

34-35

8

7 (87.5)

14

10 (71.4)

³36

5

3 (60) 

4

2 (50)

Total*

88

55 (62.5)

119

52 (43.7)

*p = 0.05, **p <0.05
Figures in parentheses represent percentages.

Table III Survival (%) by Birth Weight

Birth weight
(Grams)

Surfactant

No surfactant

 

Number

Survival

Number

Survival

 500- 749

4

25

6

16.6

 750- 999

7

22

13

15.3

1000-1249*

21

62

34

32.3

1250-1499

25

64

21

47.6

1500-1749

25

68

20

55

1750-1999

5

100

19

57.8

³2000

9

77.7

7

85.7

*p <0.05.

Table IV Morbidity Profile of the Babies

Morbidity

Surfactant
(n=88)

No surfactant
(n=119)

"p" value

Septicema

28 (31.8)

60 (50.4)

0.013

Pneumonia

18 (20.4)

39 (32.7)

0.034

Air leak

7 (7.9)

11 (9.9)

0.47

Patent ductus arteriosus

41 (46.6)

70 (58.8)

0.054

Intraventricular hemorrhage

15 (17.1)

37 (31)

0.015

Chronic lung disease*

6 (10.9)

12 (25)

0.0126

* Incidence is given among babies surviving for ³28 days.
Figures in parentheses represent percentages.

Table V Prophylactic vs Rescue Surfactant

Characterstic

Prophylactic
(n=53)

Rescue
(n=35)

P value

Gestation (wks) (mean ± SD)

31.04±2.62

31.62±2.84

0.53

Birth weight (g) (mean ± SD)

1448.42±538

1428.4±439

0.41

Death till discharge

16 (30.2)

17 (48.6)

0.08

Early neonatal mortality

10 (18.8)

13 (37.14)

0.05

Septicemia

14 (26.4)

14 (40)

0.18

Pneumonia

6 (11.3)

12 (34.2)

0.009

Air leak

4 (7.5)

3 (8.5)

0.86

PDA

20 (37.7)

21 (60)

0.04

Intraventricular hemorrhage

6 (11.3)

9 (25.7)

0.07

CLD

39 (5.6)

3 (8.5)

0.62

Hospital stay (days)

23.5±20.04

29.22±17.6

0.04

Figures in parentheses represent percentages.

 

Discussion

Respiratory distress due to variety of causes afflict 5-12% of neonates in our country(3-4). Hyaline membrane disease (HMD) is a major cause of respiratory distress in preterm newborns. The incidence of HMD is reported to be 6.8-14.1% of preterm livebirths in our country(4-6). At gestational ages of 29-30 weeks, the incidence is as high as 32% while at £28 weeks the incidence is not well documented(4). HMD is the commonest indication of ventilation in neo-nates in our country(7). The reported survival of babies ventilated for HMD has varied from 25% to 64% in our country(5-8).

The survival in the babies who did not receive surfactant (43.7%) was comparable to other reported studies from India(5-8). The survival in the surfactant group was signi-ficantly higher. The maximum impact on survival was seen in babies of 28-33 weeks gestation and 1000-1249 grams birth weight. The survival was not significantly different in babies gestation age £27 weeks and ³34 weeks due to small numbers of babies in these groups. It has been mentioned before that in our country the priority area in the care of very premature babies is to increase the survival of babies with birth weight between 1000 to 1250 grams(9). Surfactant replace-ment therapy can be one modality to achieve this.

Sepsis is the commonest complication in ventilated babies, as high as 67% incidence has been reported(7). Septicemia has been reported as the commonest cause of mortality in ventilated babies(5). Occurrence of infection is directly related to the duration of ventilation and duration of hospital stay. Forty nine per cent of total deaths in this study were directly attributed to septicemia. The lower incidence of septicemia in the surfactant group may be related to the lesser duration of ventilation in the surfactant group.

The incidence of PDA was significantly higher in the babies who did not receive surfactant. However, studies from developed countries have shown the incidence of PDA to be higher in the babies who received surfactant(10,11). The increased incidence of PDA in the babies who did not receive surfactant could be explained based on the known association of PDA and septicemia in the premature neonates(12,13).

Although, surfactant therapy appears very expensive initially, its impact on reducing the duration of ventilation, NICU stay and various morbidities actually decreases the total cost of care. There is lesser duration of hospital stay and 16-22% decrease in the total hospital charges with the use of surfactant(14,15). In this study, the mean duration of ventilation was 44.1 hours less in the surfactant group. The mean duration of hospital stay and NICU stay in survivors were 4.37 days and 2.15 days less in surfactant group as compared to babies who did not receive surfactant. We did not assess the difference in the cost of treatment being a government run hospital where charges are grossly subsidized.

When we compared the baies who had received prophylactic surfactant to those who received ‘rescue’ surfactant, the outcome - both mortality and morbidity was better with the prophylactic approach. Exogenous surfac-tant administered to surfactant-depleted lungs reduces both protein leak and epithelial lesions and the protective effect may be significantly lessened by delays of administra-tion of as short as 15-30 minutes(16). Systematic review of prophylactic vs rescue surfactant has shown an odds ratio of 0.55 (95% CI: 0.41 - 0.73) for neonatal mortality in favor of prophylactic surfactant(17). In this systematic review, the incidence of air leaks was significantly reduced with prophylactic approach but there were no differences in the occurrence of CLD, PDA, ROP, PVL and brain hemorrhage.

Antenatal care and intrapartum care tends to be better in the higher socio-economic status than lower socio-economic status. Type of antenatal care and intrapartum care tends to influence the neonatal outcome. Since in this study use of surfactant was dependant on the affordability of parents, the difference in the socio-economic status may have some influence on the results of this study.

In summary, the use of surfactant improved the survival and decreased the associated morbidities in babies with HMD who required mechanical ventilation. The maximum impact was seen among the babies of 28-33 weeks gestation and birth weight group 1000-1249 grams. It has been shown that a single dose of surfactant at birth followed by CPAP significantly reduced the subsequent need for mechanical ventila-tion(18). Hence, it may be worth considering prophylactic surfactant therapy in high-risk neonates between 28-32 weeks gestation even in the absence of elaborate level III care setup in our country.

Contributors : AN coordinated the study and helped in the preparation of the manuscript; he will also act as the guarantor for the paper. PK and SD were involved in the data collection and the preparation of the manuscript. RK was involved in the data collection, analyzed the data and prepared the manuscript.

Funding: None.
Competing interests:
None stated.

Key Messages

  • The survival rates of the neonates with hyaline membrane disease requiring ventilation were significantly higher in babies who received surfactant.

  • The mean duration of ventilation was 44.1 hours lesser, and the hospital stay was 4.37 days lesser in babies who received surfactant.

  • The incidence of septicemia, pneumonia, patent ductus arteriosus, intraventricular hemorrhage and chronic lung disease was lower in babies who received surfactant.

  • Babies who received ‘prophylactic’ surfactant had a better outcome than those who received ‘rescue’ doses only.
 References

1. Nagesh K, Bhat V, Kunikullya S, Rajesh N. Surfactant therapy in neonatal respiratory distress syndrome. Indian Pediatr 1994; 31: 971-977.

2. Sanghvi KP, Merchant RH. Single dose surfactant rescue therapy in neonatal respira-tory distress syndrome. Indian Pediatr 1998; 35: 533-536.

3. Neonatal morbidity and mortality: Report of the National Neonatal Perinatal Database. Indian Pediatr 1997; 34: 1089-1092.

4. Kumar P, Kumar R, Narang A. Spectrum of neonatal respiratory distress at PGI. Bull NNF 1999; 13(4): 8-12.

5. Singh M, Deorari K, Aggarwal R, Paul VK. Assisted ventilation for hyaline membrane disease. Indian Pediatr 1995; 32: 1267-1274.

6. Bhakoo ON, Narang A, Ghosh K. Assisted ventilation in neonates: An experience with 120 cases. Paper presented at IX Annual Conference, National Neonatology Forum, Manipal, February 17-20, 1990.

7. Bhakoo ON. Assisted ventilation in neonates: The Indian perspective. Indian Pediatr 1995; 32: 1261-1264.

8. Maiya PP, Viswanath D, Hegde S, Srinivas TP, Shivaprasad, Shantala CC, et al. Mechanical ventilation of newborns: Expe-rience from a level II NICU. Indian Pediatr 1995; 32: 1275-1280.

9. Narang A. Tiny neonates: Management and follow-up. Indian Pediatr 1993; 30: 1393-1395..

10. Soll RF, McQueen MC. Respiratory distress syndrome. In: Effective Care of the Newborn. Eds. Sinclair JC, Bracken MB. Oxford; Oxford University Press, 1992; pp 325-352.

11. Schwartz RM, Luby AM, Scanlon JW, Kellogg RJ. Effect of surfactant on morbidity, mortality, and resource use in newborn infants weighing 500-1500g. N Engl J Med 1994; 330: 1476-1480.

12. Hammerman G. Patent ductus arteriosus: Clinical relevance of prostaglandins and prostaglandin inhibitors in PDA patho-physiology treatment. Clin Perinatol 1995; 22: 457-479.

13. Saez-Liorens X, McCracken GH Jr. Sepsis syndrome and septic shock in pediatrics: Current concept in terminology, patho-physiology, and management. J Pediatr 1993; 123: 497-508.

14. Tubman TRJ, Halliday HL, Normand C. Cost of Surfactant replacement treatment for severe neonatal respiratory distress syndrome: A randomized controlled trial. Brit Med J 1990; 301: 842-845.

15. Al-Umran K, yaseen K. Cost-effectiveness of surfactant replacement therapy in a develop-ing country. J Trop Pediatr 1997; 43: 167-169.

16. Sidner SR, Ikegami M, Yamada T. Rider ED, Castror, Jobe AH. Decreased surfactant dose response after delayed administration to preterm rabbits. Am J Respir Crit Care Med 1995; 152: 113-120.

17. Morley CJ. Systematic review of prophylactic vs rescue surfactant. Arch Dis Child 1997; 77: F70-F77.

18. Verder H, Robertson B, Grisen G, Ebbesen F, Albertson P, Windstron K, et al. Surfactant therapy and nasal CPAP for newborn with RDS. N Engl J Med 1994; 331: 1051-1055.

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