Clinical pharmacology considerations for children supported with ventricular assist devices

Abstract

The ventricular assist device is being increasingly used as a "bridge-to-transplant" option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.

Gastrointestinal Bleeding as a Complication in Continuous Flow Ventricular Assist Devices: A Systematic Review With Meta-Analysis

“…In pulsatile pumps, the diaphragm, pusher plates, and the one-way valve system establishes a pulsatile flow pattern that mimics that of the native heart. Conversely, VADs with continuous flow pumps have hydrodynamic or magnetically driven rotors within their pump unit that effectively propels blood with lesser noise [15][16][17][18][19][20][21][22][23][24][25][26][27]. They are also more portable and durable.…”

“…A power module can be used when the external battery pack is exhausted with no access to spare batteries. These modules use AC and should be connected to an AC inlet through an AC power adapter [15][16][17][18][19][20][21][22][23][24][25][26][27].…”

“…Current healthcare innovations in these devices include the development of a muscle powered VAD that can eliminate the need for a tethered driveline system by utilizing energy generated by muscle tissues like that of the latissimus dorsi muscle [15][16][17][18][19][20][21][22][23]. This may be made possible by the use of a muscle energy converter that works in unison with a controllable pacemaker-like stimulator which can synchronize the energy harnessed with the cardiac cycle and adequately power these devices at an optimum level.…”

“…Unlike ECMO, which can be used for short-term ventilatory and circulatory support; VADs are used solely for circulatory support. However, VADs require lower heparin dosing, lesser priming volume and provide better ventricular compensation [ 18 ]. Most VADs are portable and easily conveyed.…”

“…They are currently different versions of VADs. A few to be mentioned include HeartMate 3, HeartMate II, HeartMate XVE, Jarvik, HeartWare, Thoratec Paracorporeal VAD and Thoratec Implantable VAD, Tandem heart, CentriMag, and Impella 2.5 [ 15 - 18 ]. The conventional flow pumps are mainly used in adults because of their relative size which makes it difficult for them to be used in children and infants.…”