Is monitoring milrinone therapy useful in advanced heart failure?

Vazir, Ali; Leaver, Neil; Lyster, Haifa; Alexanian, A.; Wilton, P.; Banner, Nicholas R.

doi:10.1016/j.ijcard.2011.02.068

Cited by 7 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since inhalation is being considered as an alternative therapeutic route of administration for milrinone in cardiac surgical patients, it was important to determine the early systemic exposure after nebulization in order to verify whether these plasma concentrations were susceptible to exceed the therapeutic range (100-300 ng•ml −1 ) 5,30,31 and cause systemic hypotension [5][6][7] . In agreement with their respective inhaled dose determined during in vitro experiments, milrinone early systemic exposure was influenced by the type of nebulizer, which resulted in plasma concentrations 2-3 fold greater with mesh compared to jet nebulization.…”

Section: Discussionmentioning

confidence: 99%

Inhaled milrinone in cardiac surgical patients: a pilot randomized controlled trial of jet vs. mesh nebulization

Nguyen

Denault

Théôret

et al. 2020

Sci Rep

View full text Add to dashboard Cite

inhaled milrinone administered before cardiopulmonary bypass (cpB) reduces the severity of pulmonary hypertension during cardiac surgery. However, milrinone pharmacokinetics has not been determined for this route of administration. the objective of this study was to investigate inhaled milrinone dosing in vitro and early plasma concentrations in vivo after jet and mesh nebulization. twelve pulmonary hypertensive patients scheduled for cardiac surgery were randomized to receive milrinone (5 mg) by inhalation before CPB using a jet or mesh nebulizer. In vitro experiments were conducted to determine the inhaled dose delivered with either jet or mesh nebulization. In vivo experiments involved hemodynamic monitoring and blood samples drawn from patients for the first 15 min after the end of inhalation to determine early plasma concentrations. After mesh nebulization, the mean in vitro inhaled dose was almost 3-fold higher compared to jet nebulization (46.4% vs 16.6% for mesh and jet, respectively; mean difference, 29.8%; 95% CI, 14.1 to 45.5; P = 0.006). Consistent with this, the early plasma concentrations in vivo were also 2-3 fold higher after mesh nebulization (P = 0.002-0.005). After inhalation (jet or mesh nebulization), milrinone early plasma concentrations remained within the therapeutic range. no systemic hypotension was reported in our patients. Intravenous milrinone, a phosphodiesterase inhibitor and inodilator, has been extensively used in cardiac surgery for the treatment of pulmonary hypertension (PH), particularly during difficult separation from cardiopulmonary bypass (CPB) 1-4. An important drawback of intravenous milrinone is its association with systemic hypotension 5-7. To avoid this side effect, inhalation has been proposed as an alternative therapeutic route of administration for milrinone 8-10. Pulmonary drug delivery presents advantages such as rapid absorption, high bioavailability, and high local concentrations 11. Consequently, a hypothesis was put forward in the past decade that inhaled milrinone administered prior to CPB would have a protective effect against the exacerbation of PH in cardiac surgical patients 12,13 by minimizing CPB-related inflammation 14 , preventing pulmonary endothelial dysfunction 15 , and facilitating separation from CPB 16. More recently, a multicenter randomized controlled trial demonstrated the clinical efficacy of inhaled milrinone in reducing the degree of PH; however, it was not associated with a reduction in difficulty separating from CPB 17. Several factors could explain those results, including suboptimal drug delivery 18. Nebulizers are commonly used drug delivery devices in aerosol therapy for patients with pulmonary diseases. These devices operate by converting liquid formulations into fine breathable droplets. There are three types of nebulizers: jet, ultrasonic and mesh 19. Apart from four clinical studies using ultrasonic 9,14 or mesh nebulizers 17,20 , jet nebulizers have been the standard drug delivery devices for inhaled milrinone in adult cardiac ...

show abstract

Section: Discussionmentioning

confidence: 99%

Inhaled milrinone in cardiac surgical patients: a pilot randomized controlled trial of jet vs. mesh nebulization

Nguyen

Denault

Théôret

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…This included patients who had undergone general cardiac surgery or cardiac transplantation in the early post operative period and preoperative patients awaiting surgery or procedures such as left ventricular device (LVAD) implantation. This data was used to confirm therapeutic ranges within these groups and retrospective analysis of the data used to determine the potential for a dose optimization strategy Vazir et al, 2011. There are a number of major advantages of HPLC-MS for monitoring milrinone compared with HPLC-UV. Figure 2(a and b) illustrates the higher specificity of the MS detector by the virtual elimination of baseline variability and noise.…”

Section: Discussionmentioning

confidence: 99%

A clinical assay for the measurement of milrinone in plasma by HPLC mass spectrometry

Chihoho

Sage

Smolenski³

et al. 2011

Biomedical Chromatography

Self Cite

View full text Add to dashboard Cite

Milrinone is a bipyridine phosphodiesterase inhibitor with positive inotropic and vasodilatory effects. As interest in longer term use of intravenous therapy increases, it becomes essential to monitor its plasma concentration owing to a narrow therapeutic range, an increased half-life in renal failure and toxicity associated with high levels. A high-performance liquid chromatography (HPLC) method with mass (MS) detection using a triple quadrupole mass spectrometer is presented. The method was compared with the UV/HPLC method and validated according to current international guidelines. Coefficients of variation of less than 7.5% were obtained across the therapeutic range and 18.3% at 2.4 ng/mL, the lower limit of quantitation. Plasma from 13 cardiac surgery patients receiving standard intravenous doses of milrinone were measured. Eight patients achieved therapeutic milrinone levels within 3-4 h post start of infusion, one was borderline sub-therapeutic and four patients achieved levels that were above the upper limit of the therapeutic range and potentially toxic. This method offers high sensitivity, is rapid, easy to use and requires minimal amount of sample. We believe this method could become the reference procedure for clinical monitoring of milrinone and help to improve the safety of the use of this drug in patients with cardiac failure.

show abstract

“…The remarkable response induced by milrinone in our patient resulted in an institutional policy change: all patients with a DNR order on file and refractory symptoms related to ESHF may now receive inotropes in the PCU. Monitoring of milrinone blood levels has been advocated as a surrogate for telemetric monitoring (Vazir et al, 2011), but it is largely unpractical at the end of life, when only comfort measures are warranted. In cases of opioid-resistant dyspnea, symptom management is one of the compelling reasons to continue administering inotropes in the palliative care setting.…”

Section: Commentmentioning

confidence: 99%

Intensive symptom control of opioid-refractory dyspnea in congestive heart failure: Role of milrinone in the palliative care unit

et al. 2015

View full text Add to dashboard Cite

show abstract

Is monitoring milrinone therapy useful in advanced heart failure?

Cited by 7 publications

References 14 publications

Inhaled milrinone in cardiac surgical patients: a pilot randomized controlled trial of jet vs. mesh nebulization

Inhaled milrinone in cardiac surgical patients: a pilot randomized controlled trial of jet vs. mesh nebulization

A clinical assay for the measurement of milrinone in plasma by HPLC mass spectrometry

Intensive symptom control of opioid-refractory dyspnea in congestive heart failure: Role of milrinone in the palliative care unit

Contact Info

Product

Resources

About