Continuous infusion aerosol delivery of prostacyclins during mechanical ventilation: challenges, limitations, and recent advances

ABSTRACT

Introduction

Critically ill mechanically ventilated patients routinely receive aerosol delivery of epoprostenol by continuous infusion of the nebulizer by syringe pump. This procedure is ‘off-label’ as no FDA approved drug presently exists. Without standardized protocols, therapy is based on prior experience with bronchodilators, limited studies of delivery systems and anecdotal clinical trials. Current protocols based upon patient body weight and drug concentration determines the infusion rate of drug dose delivered to the nebulizer , which is only distantly related to dose delivered to the lung and may be altered by many factors.

Areas covered

This paper reviews the background of this technique as well as current methods of managing drug delivery, technical challenges, and limitations. A recent advance in aerosol laboratory bench testing, using radiolabeled aerosols, is presented to reveal important factors defining delivery.

Expert opinion

Off-label use of continuously nebulized prostacyclin in the ICU lacks the support of large clinical trials needed for FDA clearance. However, comprehensive bench studies afford the potential for clinicians to better understand and manage therapy at a level above simple dosing of the nebulizer by body weight. New research techniques are enhancing our basic comprehension of the interaction between aerosol devices and the mechanical ventilator.

KEYWORDS:

• Aerosol delivery
• continuous drug delivery
• inhalation administration
• mechanical ventilation

Article highlights

• Continuously aerosolized epoprostenol is routinely administered ‘off label’ into the mechanical ventilator circuit in patients with pulmonary arterial hypertension (PAH) and arterial hypoxemia due to Adult Respiratory Distress Syndrome by continuously infusing the nebulizer with the drug.

• Continuous infusion aerosol delivery in critically ill intubated and ventilated patients evolved from continuous infusion bronchodilator delivery during mechanical ventilation that served as the prototype for inhaled epoprostenol and which, in turn, evolved from continuous nebulization delivery of bronchodilators by face mask in adult and children with severe reversible airways disease.

• Despite numerous clinical studies of aerosolized epoprostenol delivery by continuous infusion, with varying degrees of success, little has been published regarding assessment of the technical aspects and performance of the delivery system.

• Current methods of in vitro aerosol delivery assessment (inhaled mass, aerosol particle size determination, drugs, and radioisotopes as surrogate tracers) are useful, and have been used successfully, for example, to demonstrate in vitro to in vivo correlation. They are, however, time-consuming to conduct and results are not available until after the experiment has concluded and final analyses have been accomplished.

• Recent advances in in vitro testing using radiolabeled saline in an infusion pump have enabled a deeper understanding of the multiple factors that influence aerosol delivery and suggest exciting new possibilities for determining real-time aerosol delivery during technically challenging procedures. Behavior of the system, as well as any anomalies that may occur, can be observed in real-time so that adjustments can be made on the spot and, if desired, multiple test conditions can be explored during a single experiment.

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Declaration of interest

G Smaldone serves as a consultant to InspiRx and is a member of the advisory board. Stony Brook University holds patents on nebulizers licensed to InspiRx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This paper was not funded.