A Multicentre Randomized-Controlled Trial of Inhaled Milrinone in High-Risk Cardiac Surgical Patients

Denault, André; Bussières, J. S.; Arellano, R.; Finegan, Barry A.; Gavra, Paul; Haddad, François; Nguyen, Andrew; Varin, F.; Fortier, Annik; Lévesque, Sylvie; Shi, Yugen; Elmi-Sarabi, Mahsa; Tardif, J.; Perrault, Louis P.; Lambert, Jeffrey

doi:10.1097/01.sa.0000513505.81349.d8

Cited by 5 publications

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“…The reduction in right atrial dimension is consistent with previous observations where iMil was associated with an increase in atrial contractions in animals, 40,41 in human atrial tissues, 42 and in clinical trials 4 with reduced atrial dimension post-CPB. 17 Therefore iMil could also improve atrial contractile performance.…”

Section: Discussionmentioning

confidence: 99%

“…Based on our previous study, 17 we expected that the proportion of difficult and complex weaning from CPB would be 30% in the placebo group and 10% in the iMil group. Accordingly, a sample size of 124 patients (62 in each group) would have a power of 0.8 to detect a 20% absolute reduction in difficult and complex weaning from CPB between the inhaled placebo and iMil groups with an alpha of 0.05 (nQuery Advisor Ò version 4.0; Statistical Solutions Ltd., Cork, Ireland).…”

Section: Discussionmentioning

confidence: 99%

“…Both agents were administered through an ultrasonic mesh nebulizer (Aeroneb Ò Professional Nebulizer System; Aerogen Ltd., Galway, Ireland) attached to the inspiratory branch of the respiratory limb of the ventilator near the endotracheal tube, with filters on the expiratory limb, as previously described. 17 The iMil and placebo were identical in appearance. The 5-mg dose selected (resulting in a range of 50-80 lgÁkg -1 ) was based on previous studies, our experience in using iMil, 10,11,14,17 and various pharmacokinetic (PK) studies.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

“…17 The iMil and placebo were identical in appearance. The 5-mg dose selected (resulting in a range of 50-80 lgÁkg -1 ) was based on previous studies, our experience in using iMil, 10,11,14,17 and various pharmacokinetic (PK) studies. 22,29,30 Concomitant medications were permitted according to local standards of care, with the exception of iMil.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

“…7 The use of inhaled milrinone (iMil) has been described in several animal 8,9 and human reports. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Compared with its alternatives [i.e., inhaled nitric oxide (iNO) and inhaled prostacyclin (iPGI 2 )], iMil possesses inotropic properties, is less expensive, does not require a complex administration system, and does not have toxic metabolites. Furthermore, contrasted with iPGI 2 , iMil is readily available in most cardiac operating rooms and needs no special preparation.…”

Section: Résumémentioning

confidence: 99%

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A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

Denault

Bussières

Arellano

et al. 2016

Can J Anesth/J Can Anesth

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Purpose Inhaled milrinone (iMil) has been used for the treatment of pulmonary hypertension (PH) but its efficacy, safety, and prophylactic effects in facilitating separation from cardiopulmonary bypass (CPB) and preventing right ventricular (RV) dysfunction have not yet been evaluated in a clinical trial. The purpose of this study was to investigate if iMil administered before CPB would be superior to placebo in facilitating separation from CPB.Methods High-risk cardiac surgical patients with PH were randomized to receive iMil or placebo after the induction of anesthesia and before CPB. Hemodynamic parameters and RV function were evaluated by means of pulmonary artery catheterization and transesophageal echocardiography. The groups were compared for the primary outcome of the level of difficulty in weaning from CPB. Among the secondary outcomes examined were the reduction in the severity of PH, the incidence of RV failure, and mortality. Results Of the 124 patients randomized, the mean (standard deviation [SD]) EuroSCORE II was 8.0 (2.6), and the baseline mean (SD) systolic pulmonary artery pressure (SPAP) was 53 (9) mmHg. The use of iMil was associated with increases in cardiac output (P = 0.03) and a reduction in SPAP (P = 0.04) with no systemic hypotension. Nevertheless, there was no difference in the combined incidence of difficult or complex separation from CPB between the iMil and control groups (30% vs 28%, respectively; absolute difference, 2%; 95% confidence interval [CI], -14 to 18; P = 0.78). There was also no difference in RV failure between the iMil and control groups (15% vs 14%, respectively; difference, 1%; 95% CI, -13 to 12; P = 0.94). Mortality was increased in patients with RV failure vs those without (22% vs 2%, respectively; P \ 0.001). Conclusion In high-risk cardiac surgery patients with PH, the prophylactic use of iMil was associated with favourable hemodynamic effects that did not translate into improvement of clinically relevant endpoints. This trial was registered at ClinicalTrials.gov; identifier: NCT00819377. RésuméObjectif La milrinone inhalée est utilisée pour traiter l'hypertension pulmonaire (HP) mais son efficacité, son innocuité et ses effets prophylactiques pour faciliter le sevrage de la circulation extracorporelle (CEC) et prévenir la dysfonction ventriculaire droite (VD) n'ont pas encore été évalués dans le cadre d'une étude clinique. L'objectif de cette étude était d'examiner si la milrinone inhalée avant la CEC serait supérieure à un placebo pour faciliter le sevrage de la CEC. Méthode Des patients de chirurgie cardiaque à risque élevé et souffrant d'HP ont été randomisés à recevoir de la milrinone inhalée ou un placebo après l'induction de l'anesthésie et avant la CEC. Les paramètres hémodynamiques et la fonction VD ont été évalués à l'aide d'un cathéter de l'artère pulmonaire et d'une échocardiographie transoesophagienne. Les groupes ont été comparés selon notre critère d'évaluation principal, soit le niveau de difficulté du sevrage de la CEC. Parmi les critères...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Pharmacological Treatmentmentioning

confidence: 99%

Section: Pharmacological Treatmentmentioning

confidence: 99%

Section: Résumémentioning

confidence: 99%

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A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

Denault

Bussières

Arellano

et al. 2016

Can J Anesth/J Can Anesth

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Pulmonary Vasodilator Response of Combined Inhaled Epoprostenol and Inhaled Milrinone in Cardiac Surgical Patients

Elmi-Sarabi

Jarry

Couture

et al. 2022

Anesthesia &Amp; Analgesia

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BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. Intraoperative management of patients at high risk of RV failure should aim to reduce RV afterload and optimize RV filling pressures, while avoiding systemic hypotension, to facilitate weaning from cardiopulmonary bypass (CPB). Inhaled epoprostenol and inhaled milrinone (iE&iM) administered in combination before CPB may represent an effective strategy to facilitate separation from CPB and reduce requirements for intravenous inotropes during cardiac surgery. Our primary objective was to report the rate of positive pulmonary vasodilator response to iE&iM and, second, how it relates to perioperative outcomes in cardiac surgery. METHODS: This is a retrospective cohort study of consecutive patients with PH or RV dysfunction undergoing on-pump cardiac surgery at the Montreal Heart Institute from July 2013 to December 2018 (n = 128). iE&iM treatment was administered using an ultrasonic mesh nebulizer before the initiation of CPB. Demographic and baseline clinical data, as well as hemodynamic, intraoperative, and echocardiographic data, were collected using electronic records. An increase of 20% in the mean arterial pressure (MAP) to mean pulmonary artery pressure (MPAP) ratio was used to indicate a positive response to iE&iM. RESULTS: In this cohort, 77.3% of patients were responders to iE&iM treatment. Baseline systolic pulmonary artery pressure (SPAP) (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24-2.16 per 5 mm Hg; P = .0006) was found to be a predictor of pulmonary vasodilator response, while a European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score >6.5% was a predictor of nonresponse to treatment (≤6.5% vs >6.5% [reference]: OR, 5.19; 95% CI, 1.84-14.66; P = .002). Severity of PH was associated with a positive response to treatment, where a higher proportion of responders had MPAP values >30 mm Hg (42.4% responders vs 24.1% nonresponders; P = .0237) and SPAP values >55 mm Hg (17.2% vs 3.4%; P = .0037). Easier separation from CPB was also associated with response to iE&iM treatment (69.7% vs 58.6%; P = .0181). A higher proportion of nonresponders had a very difficult separation from CPB and required intravenous inotropic drug support compared to responders, for whom easy separation from CPB was more frequent. Use of intravenous inotropes after CPB was lower in responders to treatment (8.1% vs 27.6%; P = .0052). CONCLUSIONS: A positive pulmonary vasodilator response to treatment with a combination of iE&iM before initiation of CPB was observed in 77% of patients. Higher baseline SPAP was an independent predictor of pulmonary vasodilator response, while EuroSCORE II >6.5% was a predictor of nonresponse to treatment. (Anesth Analg 2023;136:282-94) KEY POINTS• Question: Can a combination of inhaled epoprostenol and inhaled milrinone (iE&iM) administered before cardiopulmonary bypass (CPB) provide a positive pulmonary vasodilator response? • Findings: A positive pul...

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Inhaled pulmonary vasodilators: a narrative review

Li¹,

Wang²,

Yu³

et al. 2021

Ann Transl Med

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Pulmonary hypertension (PH) is a severe disease that affects people of all ages. It can occur as an idiopathic disorder at birth or as part of a variety of cardiovascular and pulmonary disorders. Inhaled pulmonary vasodilators (IPV) can reduce pulmonary vascular resistance (PVR) and improve RV function with minimal systemic effects. IPV includes inhaled nitric oxide (iNO), inhaled aerosolized prostacyclin, or analogs, including epoprostenol, iloprost, treprostinil, and other vasodilators. In addition to pulmonary vasodilating effects, IPV can also be used to improve oxygenation, reduce inflammation, and protect cell.Off-label use of IPV is common in daily clinical practice. However, evidence supporting the inhalational administration of these medications is limited, inconclusive, and controversial regarding their safety and efficacy. We conducted a search for relevant papers published up to May 2020 in four databases: PubMed, Google Scholar, EMBASE and Web of Science. This review demonstrates that the clinical using and updated evidence of IPV. iNO is widely used in neonates, pediatrics, and adults with different cardiopulmonary diseases. The limitations of iNO include high cost, flat dose-response, risk of significant rebound PH after withdrawal, and the requirement of complex technology for monitoring. The literature suggests that inhaled aerosolized epoprostenol, iloprost, treprostinil and others such as milrinone and levosimendan may be similar to iNO. More research of IPV is needed to determine acceptable inclusion criteria, long-term outcomes, and management strategies including time, dose, and duration.

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A Multicentre Randomized-Controlled Trial of Inhaled Milrinone in High-Risk Cardiac Surgical Patients

Cited by 5 publications

References 0 publications

A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

Pulmonary Vasodilator Response of Combined Inhaled Epoprostenol and Inhaled Milrinone in Cardiac Surgical Patients

Inhaled pulmonary vasodilators: a narrative review

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