Surfactant Replacement Therapy for Premature Babies with Respiratory Distress

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• Dramatic First Human Surfactant Treatment
• Developing a Purified Surfactant Medication
• Immediate Effects of Surfactant Treatment
• Building a Clinical Trial Network
• The Path to Regulatory Approval
• Global Impact on Neonatology

Dramatic First Human Surfactant Treatment

Dr. Tore Curstedt, MD, recounts the pivotal moment when he and his colleague, Dr. Bengt Robertson, received an urgent call about a critically ill premature baby. The infant, born at just 27 weeks gestation and weighing approximately 700 grams, was dying from respiratory distress syndrome and was expected to survive only a few hours without intervention. The medical team had exhausted all conventional treatment options for this extremely low birth weight premature baby.

Despite having no prepared surfactant medication available, Dr. Curstedt had a purified surfactant sample in his laboratory. He immediately evaporated the organic solvents from this experimental preparation and suspended it in physiological saline, creating an emergency treatment for this specific neonatal emergency. This decision marked the first time a purified surfactant was administered to a human patient.

Developing a Purified Surfactant Medication

Dr. Tore Curstedt, MD, and Dr. Bengt Robertson had collaborated for years developing what would become the Curosurf medication. Dr. Curstedt brought expertise in phospholipid isolation and separation, while Dr. Robertson conducted in-vitro and in-vivo experiments using premature rabbit models. Their research began in 1980, focusing on creating an effective surfactant replacement therapy for respiratory distress syndrome.

The researchers developed a superior phospholipid preparation that demonstrated excellent results in both laboratory tests and animal studies. Their work showed that the surfactant medication effectively improved lung function in premature animals, providing the scientific foundation that justified the emergency human use when the critical situation arose with the dying premature infant.

Immediate Effects of Surfactant Treatment

The administration of the experimental surfactant produced dramatic and immediate clinical improvements. Within minutes of receiving the medication through tracheal instillation, the cyanotic (blue) baby turned pink as oxygenation dramatically improved. The infant had been requiring 85% oxygen concentration through mechanical ventilation just to maintain minimal oxygenation before treatment.

Remarkably, within one hour after surfactant administration, the premature baby could breathe room air (21% oxygen) without respiratory support. This rapid transformation from imminent death to stable respiration represented a breakthrough moment in neonatology. Dr. Anton Titov, MD, emphasizes the extraordinary nature of this response, noting how quickly the medication reversed the life-threatening respiratory failure.

Building a Clinical Trial Network

Following this dramatic success, Dr. Curstedt and Dr. Robertson recognized the need to establish proper clinical research structures. As laboratory doctors, they understood that transforming a single successful case into a standardized treatment required collaboration with neonatologists across Europe. They focused on creating a network of medical specialists who could participate in controlled clinical trials.

The researchers organized regular research meetings to coordinate their efforts and share findings. This collaborative approach ensured that the surfactant medication development followed rigorous scientific protocols while accelerating the collection of clinical data from multiple medical centers. Dr. Tore Curstedt, MD, emphasizes that building this professional network was essential for advancing surfactant therapy from experimental treatment to standard care.

The Path to Regulatory Approval

The development team faced the significant challenge of obtaining proper regulatory approvals for surfactant therapy. They needed to secure permissions to administer the medication to premature infants through formal clinical trials. This process involved demonstrating both safety and efficacy through controlled studies rather than individual emergency uses.

Dr. Curstedt and his colleagues worked with pharmaceutical companies to establish manufacturing processes that could produce clinical-grade surfactant medication consistently. Scaling production from laboratory samples to pharmaceutical-grade medication required developing standardized purification methods and quality control measures. This manufacturing development was crucial for obtaining regulatory approval and making the treatment widely available.

Global Impact on Neonatology

The successful development of surfactant replacement therapy revolutionized the treatment of respiratory distress syndrome in premature infants. Before surfactant therapy, respiratory distress syndrome was a leading cause of mortality in preterm infants, particularly those born before 32 weeks gestation. The introduction of effective surfactant medications dramatically improved survival rates for extremely premature babies.

Today, surfactant replacement therapy remains a cornerstone of neonatal intensive care worldwide. Medications like Curosurf, developed from the pioneering work of Dr. Tore Curstedt, MD, and Dr. Bengt Robertson, continue to save countless premature infants annually. Dr. Anton Titov, MD, highlights how this breakthrough demonstrates the profound impact that translational research can have on clinical medicine and patient outcomes.

Full Transcript

Dr. Anton Titov, MD: You were working for more than a decade on the medication in the laboratory, then one day you received a phone call from a doctor who cared for a dying, prematurely born baby. They asked you to use this medication on a human for the first time. It was a very dramatic experience. Could you please tell more about that experience of bringing your medication from the bench to the bedside?

Dr. Tore Curstedt, MD: I and my colleague Bengt Robertson were both laboratory doctors. He worked as a pathologist and he worked with in-vitro and in-vivo experiments. I worked with phospholipid isolation and separation.

We started to talk about making the surfactant in 1980. I had my skills in phospholipids and he did in-vitro and in-vivo experiments. We worked together. We got a good phospholipid preparation. We tested it in vitro and in vivo in premature rabbits and it worked very well.

That made one of many rabbit experiments. Then they called us at the site. Said, "We have a little boy, he weighs 785 grams, about that. He was born in week 27 of pregnancy. We have done everything we can do. He will die in a couple of hours. Do you have any surfactant? We know that you work with that, do you have any?"

At that time, we had no surfactant. But I had in the tube some purified surfactant and I had it in an organic solution. I evaporated the organic solvents.

Dr. Anton Titov, MD: Specifically for that baby?

Dr. Tore Curstedt, MD: For that baby. You could not smell any chloroform in that purified form. Bengt Robertson and I discussed, is it possible for us to give the medication? What will happen if the baby will die? "But we take this chance", he said.

I suspended it in the physiological saline and we said to the boss of the pediatric department, "Give this to the little boy." Within a couple of minutes, they gave the medication into the trachea. Within a couple of minutes, the blue baby became pink and it started at 85% oxygen in the respirator and after one hour, it could breathe room air.

Dr. Anton Titov, MD: This was dramatic change within minutes and in one hour. It was a very dramatic effect. It was a boy born at 27 weeks, weighing just 700 grams, couple of hours from death, being blue. Then you give first time ever, your just-purified surfactant, of course. The chief of the hospital gives. But it is your co-invented medication, with your collaborator Dr. Robertson. It is a dramatic change. Within a few minutes, the baby becomes pink. An hour later can breathe normal air instead of 85% oxygen. This is very dangerous.

Dr. Tore Curstedt, MD: Yes.

Dr. Anton Titov, MD: That is an absolutely dramatic effect. How did you feel?

Dr. Tore Curstedt, MD: It is very difficult to say. It was so dramatic. I have never seen something like that in all my life. I was near tears at that time to see this change in a little, little boy that expected to die in a couple of hours.

Dr. Anton Titov, MD: You observed the boy with your own eyes, sitting next to the clock in the ICU?

Dr. Tore Curstedt, MD: Yes, yes.

Dr. Anton Titov, MD: Chief of surgery, chief of the hospital was probably there. Who else was there?

Dr. Tore Curstedt, MD: But you see, at that time, we thought we had good product. But we were laboratory doctors. Sometimes we could have this to the rest of the world, we must have a network.

We had two, three things that are very important. A good medication is very important. We also said, we must have a network of neonatologists. In Europe, we must have that in all Europe.

We must have the company that can produce this medication in the future. We must have meetings, research meetings. That continue every year at least. That we started at that time. Then we must also of course have all permission to give this medication to these premature children.