Heart and lung transplantation

Pulmonary hypertension and right ventricular failure after heart transplantation: usefulness of nitric oxide

Caring for the critically ill patient with acute right ventricle (RV) failure is a diagnostic and management challenge. A thorough understanding of normal RV anatomy and physiology is essential to manage RV failure. Despite the fact that the RV is essentially a volume chamber that ejects into a low-pressure system, the left ventricle contributes significantly to RV function through maintenance of the transseptal gradient (TSG). Preserving systemic mean arterial pressure maintains the TSG and RV perfusion. Various pathological states cause acute RV failure by decreasing the TSG and RV perfusion and/or increasing pulmonary vascular resistance. Early diagnosis prevents rapid progression of RV failure due to the “double hit phenomenon,” which is acute intra-abdominal multiple organ system failure as a result of a reduced blood pressure and elevated central venous pressure. Management includes hemodynamic support and reversal of the precipitating cause through optimizing RV rate and rhythm, determining ideal RV filling pressure, reducing RV afterload through nonpharmacologic and pharmacological means, and selecting the appropriate RV inotrope or mechanical support.

La prise en charge d'un patient dans un état critique en raison d'une insuffisance ventriculaire droite (VD) aiguë constitue un véritable défi diagnostique et thérapeutique. Une connaissance approfondie de l'anatomie et de la physiologie normales du ventricule droit est essentielle à la prise en charge appropriée d'un tel cas. Même si le ventricule droit constitue essentiellement un compartiment de retenue qui permet d’éjecter le sang dans un système à faible pression, le ventricule gauche contribue de manière significative à la fonction du ventricule droit par le maintien du gradient de pression transseptal (GPTS). Pour préserver le GPTS et la perfusion VD, il faut maintenir la pression artérielle générale moyenne dans des valeurs acceptables. Divers états pathologiques entraînent une insuffisance VD aiguë en diminuant le GPTS et la perfusion VD et/ou en augmentant la résistance vasculaire pulmonaire. Un diagnostic précoce permet d’éviter l’évolution rapide de l'insuffisance VD attribuable au « double phénomène délétère », soit une insuffisance pluriorganique intra-abdominale aiguë causée par une baisse de la pression artérielle et une hausse de la pression veineuse centrale. La prise en charge comprend le soutien hémodynamique et l’élimination de la cause sous-jacente par l'optimisation du rythme et du débit VD, la détermination de la pression de remplissage idéale du ventricule droit, la réduction de la postcharge VD par des interventions pharmacologiques ou non pharmacologiques et la sélection de l'agent inotrope ou du dispositif de soutien mécanique approprié.

We sought to directly compare the effects of prostaglandin E₁ (PGE₁) and nitric oxide (NO) in testing for pulmonary hypertension reversibility in heart transplant candidates.

We included 19 heart transplant candidates who fulfilled at least 1 of 3 criteria: pulmonary vascular resistance (PVR) of >4 Wood units; transpulmonary gradient (TPG) of >12 mm Hg; or systolic pulmonary artery pressure (PAP) of >60 mm Hg. Patients randomly received either PGE₁ (0.05, 0.2 and 0.5 μg/kg/min) or NO (40, 60 and 80 ppm) and were crossed-over to the second medication after receiving the maximal dose of the first.

With PGE₁, TPG decreased by 21% (baseline 20.3 ± 6.8 mm Hg; final 16.0 ± 7.0 mm Hg) compared to a 34% decrease with NO (baseline 20.8 ± 6.2 mm Hg; final 13.8 ± 5.4 mm Hg) (p = 0.13). PVR decreased by 42% with PGE₁ (baseline 6.2 ± 4.0 Wood units; final 3.6 ± 1.8 Wood units) and by 47% with NO (baseline 6.0 ± 3.9 Wood units; final 3.2 ± 1.6 Wood units) (p = 0.87). Mean systemic pressure decreased with PGE₁ (baseline 76.1 ± 10.5 mm Hg; final 69.4 ± 12.2 mm Hg; –9%) but not with NO administration (baseline 70.2 ± 14.7 mm Hg; final 71.6 ± 10.9 mm Hg; +2%) (p = 0.01). TPG was lowered to <12 mm Hg in 14 patients. Of these, 6 (46%) responded to both PGE₁ and NO, 4 (27%) responded only to PGE₁, and 4 (27%) responded only to NO.

The effects of PGE₁ and NO on pulmonary hypertension are comparable, with PGE₁ having more systemic hypotensive effects. Due to variability of patient responses, we recommend multiple rather than single-agent pharmacologic testing for the reversibility of pulmonary hypertension.