Critical & Organ Care · 1980
Exogenous surfactant therapy for neonatal respiratory distress syndrome (Fujiwara)
Hyaline membrane disease, the pathological term for what clinicians now call neonatal respiratory distress syndrome, was the leading cause of death in premature infants through the 1960s and 1970s. The underlying problem had been identified by Mary Ellen Avery and Jere Mead in 1959: lungs of affected infants lacked sufficient surfactant, the complex mixture of phospholipids and proteins that reduces alveolar surface tension and prevents alveolar collapse at end-expiration. Without it, each breath required enormous effort to reinflate collapsed alveoli, and infants fatigued quickly. Treatment was supportive, primarily supplemental oxygen and, later, mechanical ventilation, with no way to address the underlying deficiency.
Tetsuro Fujiwara at Iwate Medical University in Morioka, Japan, spent years working out whether exogenous surfactant could be delivered safely into the trachea of living infants. The preparation he used was a modified bovine lipid surfactant, extracted from bovine lungs and supplemented with synthetic lipids to approximate the composition of human surfactant. Animal experiments preceded the human work, providing both the biological rationale and safety data necessary to proceed.
In 1980, Fujiwara's team published results in the Lancet from ten very preterm infants with hyaline membrane disease who received intratracheal surfactant. Oxygenation improved within minutes of instillation, documented by rising arterial PO2 and falling inspired oxygen requirements on mechanical ventilation. Eight of the ten infants survived; five of those weighed under 1500 grams at birth. For infants in that weight range, survival with supportive care alone was substantially lower at the time.
The Lancet publication attracted immediate interest from neonatologists in Europe and North America, who began designing controlled trials to confirm the findings and establish optimal dosing and timing. Trials through the mid-1980s compared natural surfactant extracts against synthetic preparations, prophylactic versus rescue administration, and single versus multiple doses. FDA approval for the first commercial preparation, EXOSURF, came in 1990, followed by beractant (Survanta) shortly after, making surfactant available at most neonatal intensive care units in high-income countries.
Surfactant replacement therapy, used alongside antenatal corticosteroids introduced by Graham Liggins and Ross Howie in the 1970s, and continuous positive airway pressure for spontaneously breathing infants, substantially reduced RDS mortality through the 1990s. Survival for infants born between 25 and 28 weeks gestation improved markedly in the decade following widespread surfactant adoption. Subsequent research into lamellar body counts and gastric aspirate analysis for fetal lung maturity reflected the same logic: define the biochemical deficit, measure it, and target it directly.
Key People
- Tetsuro Fujiwara — Japanese neonatologist who conducted the first clinical surfactant trial
- Mary Ellen Avery — Physician who identified surfactant deficiency as the cause of hyaline membrane disease in 1959
- Graham Liggins — New Zealand obstetrician who demonstrated antenatal corticosteroids accelerate fetal lung maturity
Lancet, 1980
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