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Reversal of Acute Right Ventricular Failure Early Post Left Ventricular Assist Device Placement by Intratracheal Milrinone Administration

Case Report
      A 58-year-old man with medical history of hypertension and pulmonary sarcoidosis presented with palpitation and syncope. At arrival in the ED, multiple episodes of nonsustained ventricular tachycardia have been recorded. Transthoracic echocardiography (TTE) showed severe left ventricular dysfunction with suspected cardiac sarcoidosis. Shortly after admission, the patient went into cardiac arrest due to refractory ventricular tachycardia. CPR was performed, and venous-arterial extracorporeal membrane oxygenation was inserted through a femoral approach without complication. After 10 days of extracorporeal membrane oxygenation support, despite high doses of steroids and immunosuppressive therapy with cyclophosphamide, electrical myocardial irritability persisted with recurrent episodes of ventricular tachycardia that required external defibrillation. A TTE was performed and showed persistent severe left ventricular dysfunction and normal right ventricular function. The patient was assigned for left ventricular assist device (LVAD) placement set at 9000 rounds per minute that resulted in optimal cardiac output and stable hemodynamics with normal pulmonary artery pressure. Shortly after LVAD implantation, the patient had signs of profound cardiogenic shock with severe hypotension.
      High-dose vasoactive support with epinephrine and norepinephrine was started. An LVAD low pump flow alarm was engaged, and a suction event was suspected. Bedside transesophageal echocardiography (TEE) was performed (Video 1). Despite decreasing the pump speed from 9000 to 8000 rounds per minute, the patient’s condition remained unstable (Video 2). A bolus of milrinone (2.5 mg) was administered directly into the endotracheal tube with a syringe under continuous TEE monitoring. Shortly after the instillation, hemodynamics rapidly improved, and the LVAD suction event alarm stopped (Video 3). The instillation of 2.5-mg milrinone was repeated, and the patient’s hemodynamics were restored completely after 10 minutes (Video 4) (Fig 1). Continuous TEE monitoring showed improved right ventricle load and contractility, optimized left ventricular filling and function, and restoration of the ventricular interdependence (Video 3).
      Figure thumbnail gr1
      Figure 1A-D: A, Transesophageal echocardiography midesophageal 0-degree view shows severe right ventricular dilatation and an underfilled left ventricle with biventricular dysfunction at a pump speed of 9000 rounds per minute (). B, Transesophageal echocardiography 0-degree view shows similar findings decreased pump speed to 8000 rounds per minute. Intratracheal milrinone 2.5 mg was administered (). C, After the first dose, transesophageal echocardiography 0-degree view shows partial unloading of the right ventricle and an increase of left ventricle filling. A repeated dose was administered (). D, Transesophageal echocardiography 0-degree view shows complete reversal of right ventricle failure and adequate left ventricle filling, with improved left ventricle function (). LV = left ventricle; RV = right ventricular.
      Question: What is your diagnosis based on the TEE findings? (Videos 1, 2)
      Answer: Video 1 (midesophageal 4-chamber view) revealed severe right ventricular dilatation and right ventricular failure, which led to leftward deviation of the interventricular septum and an underfilled and dysfunctional left ventricle that was not improving, despite the changes in pump speed (Video 2)
      Right ventricular failure (RVF) frequently is observed after LVAD placement. Perioperative factors such as cytokine releases, systemic inflammation, increases in pulmonary vascular resistance, hypoxemia, arrhythmias, myocardial ischemia, air embolism, or tamponade may all impact right ventricular function.
      • Denault A.Y.
      • Couture P.
      • Beaulieu Y.
      • et al.
      Right ventricular depression after cardiopulmonary bypass for valvular surgery.
      Physiologic changes after implantation of the LVAD leads to increased venous return and right ventricular preload. Paradoxical septal motion and loss of septal contribution to right ventricular contraction may lead to further deterioration of preexisting right ventricular dysfunction with consecutive RVF and dilatation (Video 1). Left-ward shift of the interventricular septum can be exacerbated by aggressive left ventricular unloading, pulling of the interventricular septum toward the left ventricle, which in turn worsens right heart dimension and function.
      • Raina A.
      • Patarroyo-Aponte M.
      Prevention and treatment of right ventricular failure during left ventricular assist device therapy.
      In our case, decreasing the pump speed did not help to improve right heart dimension and function (Video 2).
      Therefore, immediate treatment to optimize myocardial contractility and pulmonary vascular resistance was initiated by bolus administration of milrinone into the endotracheal tube, which restored right ventricular function and stabilizing hemodynamics within 10 minutes (Videos 3, 4, Fig 1). Instillation of milrinone directly into the endotracheal tube has been reported previously in cardiac surgical patients and represents a rapid method of milrinone administration.
      • Gebhard C.E.
      • Desjardins G.
      • Gebhard C.
      • Gavra P.
      • Denault A.Y.
      Intratracheal milrinone bolus administration during acute right ventricular dysfunction after cardiopulmonary bypass.
      • Gavra P.
      • Denault A.Y.
      • Theoret Y.
      • Perrault L.P.
      • Varin F.
      Pharmacokinetics and pharmacodynamics of nebulized and intratracheal milrinone in a swine model of hypercapnia pulmonary hypertension.
      • Gebhard C.E.
      • Rochon A.
      • Cogan J.
      • et al.
      Acute right ventricular failure in cardiac surgery during cardiopulmonary bypass separation: a retrospective case series of 12 years’ experience with intratracheal milrinone administration.

      Discussion

      Acute right ventricle is a commonly seen complication early after LVAD implantation. It varies from 9% to 44% and is associated with high postoperative morbidity and mortality rates.
      • Kormos R.L.
      • Teuteberg J.J.
      • Pagani F.D.
      • et al.
      Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes.
      ,
      • Lampert B.C.
      • Teuteberg J.J.
      Right ventricular failure after left ventricular assist devices.
      Immediate treatment of acute RVF is crucial to prevent further hemodynamic deterioration, often leading to multiorgan failure. IV inotropes and inhaled pulmonary vasodilators that include nitric oxide, epoprostenol, iloprost, and milrinone have been used to improve right ventricle contractility and afterload.
      Several strategies have been described regarding the use of inhaled pulmonary vasodilators in the treatment of pulmonary hypertension and prevention of acute RVF after LVAD placement.
      • Sabato L.A.
      • Salerno D.M.
      • Moretz J.D.
      • Jennings D.L.
      Inhaled pulmonary vasodilator therapy for management of right ventricular dysfunction after left ventricular assist device placement and cardiac transplantation.
      In these studies, the inhaled agent was given by nebulization via the endotracheal tube just before or shortly after the patient has been weaned from cardiopulmonary bypass in the prevention of acute RVF. The use of inhaled milrinone in cardiac surgery patients has been investigated in several clinical studies and was found to have a favorable effect on stroke volume, right-sided chamber dimension, and systolic pulmonary artery pressure while omitting significant effects on heart rate or systemic arterial pressure.
      • Sablotzki A.
      • Starzmann W.
      • Scheubel R.
      • Grond S.
      • Czeslick E.G.
      Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates.
      ,
      • Denault A.Y.
      • Bussieres J.S.
      • Arellano R.
      • et al.
      A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients.
      In addition, inhaled milrinone has been used in high-risk patients with pulmonary hypertension who have undergone coronary artery bypass graft or valve surgery for cardiopulmonary bypass weaning.
      • Sabato L.A.
      • Salerno D.M.
      • Moretz J.D.
      • Jennings D.L.
      Inhaled pulmonary vasodilator therapy for management of right ventricular dysfunction after left ventricular assist device placement and cardiac transplantation.
      ,
      • Denault A.Y.
      • Bussieres J.S.
      • Arellano R.
      • et al.
      A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients.
      In a small prospective clinical trial in ten patients with LVAD, milrinone that was nebulized continuously over 24 hours postoperatively demonstrated a positive impact on hemodynamics in addition to its simple administration and lower cost profile.
      • Haglund N.A.
      • Burdorf A.
      • Jones T.
      • et al.
      Inhaled milrinone after left ventricular assist device implantation.
      However, considering the pharmacokinetic/pharmacodynamic profile of nebulized milrinone with a peak plasma concentration within up to 20 minutes,
      • Denault A.Y.
      • Bussieres J.S.
      • Arellano R.
      • et al.
      A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients.
      ,
      • Nguyen A.Q.
      • Theoret Y.
      • Chen C.
      • Denault A.
      • Varin F.
      High performance liquid chromatography using UV detection for the quantification of milrinone in plasma: improved sensitivity for inhalation.
      this delay might not be acceptable in the setting of acute RVF and hemodynamic instability in patients with LVAD. Intratracheal milrinone bolus administration offers a much faster and simpler administration method in emergency situations, and its administration was shown to be associated with clinical improvement of RVF during difficult separation from cardiopulmonary bypass.
      • Gebhard C.E.
      • Desjardins G.
      • Gebhard C.
      • Gavra P.
      • Denault A.Y.
      Intratracheal milrinone bolus administration during acute right ventricular dysfunction after cardiopulmonary bypass.
      ,
      • Gebhard C.E.
      • Rochon A.
      • Cogan J.
      • et al.
      Acute right ventricular failure in cardiac surgery during cardiopulmonary bypass separation: a retrospective case series of 12 years’ experience with intratracheal milrinone administration.
      In a recent animal porcine model, a favorable positive hemodynamic effect with reduction of the right-sided chamber dilatation was observed with intratracheal milrinone administration.
      • Gavra P.
      • Denault A.Y.
      • Theoret Y.
      • Perrault L.P.
      • Varin F.
      Pharmacokinetics and pharmacodynamics of nebulized and intratracheal milrinone in a swine model of hypercapnia pulmonary hypertension.
      In our case, intratracheal milrinone was administered in a patient with LVAD with acute RVF and without preexisting pulmonary hypertension. We demonstrated that intratracheal milrinone administration has the potential to improve acute RVF because of its positive effect on right ventricle contractility and pulmonary vasculature in the absence of significant systemic vasodilatation (Discussion Video).
      • Denault A.Y.
      • Bussieres J.S.
      • Arellano R.
      • et al.
      A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients.

      Reverberations

      • 1.
        Acute right heart failure is a significant complication that is associated with LVAD implantation.
      • 2.
        First step in the management is to maintain adequate perfusion pressure and reduce pump speed to limit the right ventricular dilatation.
      • 3.
        If this approach is unsuccessful, treatment to increase right ventricle contractility and reduce right ventricle afterload is crucial.
      • 4.
        Intratracheal milrinone instillation has been reported to be efficacious intraoperatively in acute right ventricular failure during cardiac surgery, but this is the first report of its potential use in the ICU in a patient with LVAD.

      Acknowledgments

      Financial/nonfinancial disclosures: The authors have reported to CHEST the following: A. Y. D. is on the Speakers Bureau for CAE Healthcare and Masimo. None declared (Y. T. S., C. E. G.).
      Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.
      Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
      Additional information: To analyze this case with the videos, see the online version of this article.

      Supplementary Data

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