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You are working as a pharmacist supporting a tertiary neonatal unit. A 36/40 gestation infant is transferred from another hospital. The infant had been born by normal vaginal delivery and collapsed on the postnatal ward at 3 hours of age. The child is hypoxic despite high pressures and 100% oxygen. The diagnosis of persistent pulmonary hypertension (PPH) is suggested; intravenous tolazaline had been tried without significant improvement. Nebulised tolazaline is mentioned, and you are asked to find out more.
Structured clinical question
In severe PPH of the newborn [patient], is nebulised tolazoline [intervention] an option when intravenous tolazoline [comparator] has failed to produce an improvement in oxygenation [outcome]?
Search strategy and outcome
Medicines for children: information on intravenous tolazoline but not on nebulised.
Guy’s formulary: no information
LTH neonatal formulary: no information.
Northern neonatal network formulary: intratracheal instillation experimental, when formulary written.
Medline: “tolazoline” and “nebulised/nebuliser/vapourisers/aerosols /inhalation” (two relevant studies). See table 2.
There is no good quality study addressing the use of nebulised tolazoline in PPH, and none addressing the use after intravenous tolazoline has failed. The only study that has been conducted to date was a case series of only 12 infants. It is difficult to attach significance to a treatment group so small. The study concluded that the endotracheal route is preferred because it is devoid of significant side effects (for example, hypotension and flushing), but it is worth noting that tolazoline is acid in solution and may cause some alveolar injury. The case report concluded that in their case the endotracheal use of tolazoline was life saving and warrants further clinical trials.
CLINICAL BOTTOM LINE
Nebulised tolazaline may be effective, but no data reliably compare it to the intravenous route or other drugs.
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