Neosurf is a completely natural surfactant obtained from bovine lung lavage. It is available as BLES (Bovine Lipid Extract Surfactant) in Canada, manufactured by BLES Biochemicals.

Neosurf is a natural surfactant extracted from lung lavage, and contains the same phospholipids in the same concentration as found in natural lung surfactant. These are accompanied by the hydrophobic proteins SP-B and SP-C.

Bovine minced lung extract surfactant is a modified natural surfactant prepared by extraction from bovine minced lung, then DPPC, palmitic acid and tripalmitin are added to specified concentrations. This serves to bring the concentrations of these components back to the levels found in natural surfactant. In the process of mincing, the cellular components of the lung tissue are included in the extract, which in turn, makes it more viscous. The presence of other phospholipids from cellular components of the lung and added lipid components make this a modified surfactant with a lower concentration of the hydrophobic surfactant proteins.

Neosurf contains significantly more SP-B than bovine minced lung extract surfactant which improves its surfactant qualities, and improves its resistance to inactivation by plasma proteins.

Neosurf has a lower ratio of small surfactant aggregate (SA) to large surfactant aggregate (LA) than bovine minced lung extract surfactant. Lower SA/LA ratio is associated with a superior physiological response.

Neosurf is approximately eight times less viscous than bovine minced lung extract surfactant.

Using the Ostwald Viscometer, Neosurf had a viscosity of 4.5 times that of water, and bovine minced lung extract surfactant had a viscosity of 33.3 times that of water. A more viscous material could lead to slower peripheral distribution of surfactant when instilled through the endotracheal tube, resulting in increases in PIP and PaCO₂, values due to airway obstruction.

In a comparative preclinical study of Neosurf and bovine minced lung extract surfactant, animals given instilled minced surfactant had an acute deterioration in ventilator parameters compared with those treated with the instilled Neosurf.

Neosurf was compared with bovine minced lung extract surfactant in a study published by Lam et al. (Lam, 1995). The Neosurf group had a significantly lower oxygenation index throughout the 12-hour period after dosing compared to the other surfactant group. There was no difference in secondary outcomes, including mortality, ventilator days and occurrence of chronic lung disease. This may be attributed to small sample size of study. The authors concluded that the infants with RDS responded favorably to both surfactants, but that Neosurf achieved a significantly faster clinical response in terms of improvement in oxygenation index.

No studies have been conducted between Neosurf and porcine surfactant.

The concentration of phospholipids in porcine surfactant is 80 mg/mL, which is three times concentration in Neosurf at 27 mg/mL. The higher concentration of phospholipids in porcine surfactant would make this a more viscous preparation and may lead to slower peripheral distribution. Thus, Neosurf has the advantage over porcine surfactant of being less viscous.

The porcine surfactant is manufactured from minced porcine lung, and cellular lipids dilute the amount of surfactant proteins.

SA/LA ratio denotes small surfactant aggregate/large surfactant aggregate ratio.

Large surfactant aggregate represent surface active component of surfactant and metabolic precursor of inactive small aggregate. Hence, lower SA/LA ratio is associated with better physiological response.

Neosurf has a lower SA/LA ratio as compared to that of bovine minced lung extract surfactant

Neosurf is obtained by lavage extraction. Other surfactants like bovine minced lung extract surfactant or porcine minced lung extract surfactant are obtained by mincing. It appears that mincing process dilutes amount of SP-B relative to lipids due to presence of non surfactant lipids from the tissue mass. Thus, Neosurf has higher content of SP-B relative to lipids mass.

SP- B resists the inactivation of surfactant by plasma proteins leaking into the air spaces. Thus, the need for a second dose is reduced with Neosurf due to the higher SP-B content. However, no comparative studies have been conducted specifically looking at this issue.

Recommended dose for Neosurf is 135 mg of phospholipids per kg & it is based on the results of the phase III trial conducted with Neosurf. The available data mentions that the dose of 100 mg/kg of phospholipids will cover the entire lung surface. The recommended dose for currently used surfactant varies from 50mg/kg of phospholipids to 200mg/kg of phospholipids.

There is evidence to suggest that there is dose dependent improvement in response for surfactant therapy. A publication by Metcalfe, in 1982 seems to say that volume and concentration do not matter as much as the quantity of phospholipids delivered. The availability of Neosurf in two packs of 5 ml & 3 ml leads to greater flexibility in dosing & hence save costs.

Neonates can receive up to 3 additional doses of Neosurf within the first 5 days of life. The criteria for an additional dose are a positive response to the previous dose, and an increase in respiratory support as signaled by a gradual increase in Fi02. This increase must be at least 10% greater than the Fi02 required after the initial response to the previous dose of Neosurf. There is no minimum time between doses as there is for at least some other surfactants. In the clinical trials, the decision was made to redose based on need, and not on an arbitrary time point, which may leave some patients in distress for a period of time before the next dose can be administered.

BLES Biochemicals recommends the administration of Neosurf in three bolus aliquots with the infant in three positions: supine, lying on left side and lying on right side. This is to ensure proper distribution of Neosurf. It also recommends the administration of Neosurf as a single bolus dose in supine position in more premature infants who have not yet developed a gag reflex. This will allow less handling of very premature infants.

A Y-connector serves as an additional port of the ETT for surfactant administration. Surfactant can thus be safely instilled through the ETT, without disconnecting the ETT from the ventilator. It thus, protects the neonate from developing oxygen desaturation during surfactant administration.

In post-marketing surveillance, Neosurf has been used in MAS, but it was less effective than in NRDS. Dose used was the same i.e. 5 ml/kg.

BLES Biochemicals Inc. is unable to recommend a suitable dose for treating infants with meconium aspiration syndrome (MAS), as a definitive clinical trial has not been conducted for this indication. However, web search shows that undiluted and diluted surfactant preparations have been used.

As per the recommendations of Fetus and New Born Committee, Canadian Pediatric Society (CPS), intubated infants with Meconium Aspiration Syndrome requiring more than 50% of oxygen should receive exogenous surfactant therapy (grade A recommendation)

Though the storage recommendation for Neosurf is to be stored frozen below -10°C, Neosurf may be stored in refrigerator (2-8°C) for a maximum period of 10 months at any time during its labelled shelf life. If not used during this period, it can be returned to the freezer with no harm done, for the remaining part of its shelf life.

The colder storage temperature allows for a longer shelf life of 36 months for Neosurf as against approximately 12 months shelf life of bovine minced lung extract surfactant. Also 10 months storage period at 2-8°C gives customer an opportunity to store Neosurf in hospital settings where strict frozen storage cannot be observed.

The Product Monograph states that "Warming can be accomplished by holding the vial in the hand, allowing the vial to stand at room temperature, or placing the vial in warm water up to 37°C." Perhaps placing the vial in an incubator would be a more convenient alternative for the 37°C water bath.

As the Product Monograph specifies, the product should be warmed at least to room temperature but no higher than body temperature before being administered.