Supporting the use of sildenafil infusions in paediatric and neonatal intensive care - A compatibility study

Intravenous (IV) sildenafil, a phosphodiesterase type 5 inhibitor, is increasingly being used for the treatment of pulmonary hypertension (PH) in the paediatric population. Sildenafil (Revatio®) is approved for the treatment of pH in adults where it is administered as a bolus injection. However, in paediatrics it is used off-label and administered by continuous IV infusion. In the critically unwell child, limited IV access necessitates the administration of multiple IV infusions through a single IV lumen. The absence of compatibility data between sildenafil and other IV medications commonly used in this context necessitates the use of a dedicated IV line for sildenafil. The overall aim of this study was to establish the physical and chemical compatibility of sildenafil with commonly administered infusions in the paediatric and neonatal intensive care setting.

This study evaluated the chemical and physical compatibility of binary and multiple combinations (n = 42) of sildenafil with adrenaline, noradrenaline, milrinone, vasopressin and heparin. These were tested using three diluents (NaCl 0.9%w/v, Glucose 5%w/v, and Glucose 10%w/v) and two environmental conditions (room temperature and 37 °C) frequently encountered in paediatric or neonatal intensive care units. Prior to drug combination analysis, HPLC methods were developed and optimised to allow for the quantification of drugs in accordance with current pharmaceutical guidance. Binary and multiple drug mixtures of sildenafil were examined for physical and chemical compatibility to establish compatibility.

Of the drug combinations not containing heparin, all were deemed compatible with the exception of the five drug mix of Sildenafil 800 μg/mL, Milrinone 200 μg/mL, Vasopressin 0.4Units/mL, Noradrenaline 60 μg/mL, Adrenaline 60 μg/mL at 37 °C, in 10%w/v glucose. All binary or multi drug combinations containing heparin were deemed incompatible.

This research provides support and information to clinicians looking to co-administer sildenafil with other IV medicines thus removing the requirement to subject their patients to multiple intravenous cannula insertion points where IV access is restricted.

New evidence to support administration of sildenafil infusions in #PedsICU and #nicu- collaboration between @RCSIPharBioMol@FionaSOBrien1 and @OLCHCrumlin @RCSI_Irl @MoninneHowlett #CHI.