HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yoan Lamarche Louis P. Perrault Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lamarche, Y. Articles by Denault, A. Y. Search for Related Content PubMed PubMed Citation Articles by Lamarche, Y. Articles by Denault, A. Y. Related Collections Anesthesia Cerebral protection Extracorporeal circulation

Eur J Cardiothorac Surg 2007;31:1081-1087. doi:10.1016/j.ejcts.2007.02.019
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Preliminary experience with inhaled milrinone in cardiac surgery

^a Research Center, Montreal Heart Institute and Université de Montréal, 5000 Belanger Street, Montreal, Quebec H, Canada
^b Department of Cardiac Surgery, Montreal Heart Institute and Université de Montréal, 5000 Belanger Street, Montreal, Quebec H, Canada
^c Department of Anesthesia, Montreal Heart Institute and Université de Montréal, 5000 Belanger Street, Montreal, Quebec H, Canada
^d Department of Biostatistics, Montreal Heart Institute and Université de Montréal, 5000 Belanger Street, Montreal, Quebec H, Canada

Received 27 September 2006; received in revised form 21 February 2007; accepted 23 February 2007.

^_* Corresponding author. Tel.: +1 514 376 3330x3732; fax: +1 514 376 8784. (Email: denault{at}videotron.ca).

	Abstract

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

 
Background: Inhaled administration of milrinone reduces pulmonary artery pressure. Pulmonary hypertension (PH) and right heart failure are associated with difficult separation from cardiopulmonary bypass (CPB). Therefore, inhaled milrinone could facilitate separation from CPB. Objective: To determine the impact and timing of administration of inhaled milrinone. Methods: A retrospective analysis of our experience on high-risk patients receiving inhaled milrinone was conducted to evaluate the postoperative course after administration of the drug. Results: Seventy-three patients received inhaled milrinone from June 2002 to February 2005. Mean age was 64 ± 13 years, with a mean preoperative Parsonnet score of 27 ± 14. Inhaled milrinone (5 mg) was administered before (n = 30) or after (n = 40) CPB, three patients had off-pump procedures and were excluded. CPB time was 145 ± 78 min with cross-clamping times of 91 ± 56 min without any significant difference between groups. Fifty-four patients (74%) had difficult separation from CPB, 14 patients (19%) required an intra-aortic balloon pump and 10 patients (14%) needed emergency reinitiation of CPB for hemodynamic instability. Ten patients died in the perioperative period (13.7%). Patients receiving inhaled milrinone prior to CPB initiation had a lowering pulmonary artery pressure after CPB (p < .01) and had less emergency reinitiation of CPB after weaning (3% vs 23%, p = .02) as compared to those with administration after CPB. No detectable side effects were directly linked to the administration of the drug. Conclusion: In this high-risk cohort, use of inhaled milrinone was well tolerated. Administration before initiation of CPB could help weaning from CPB.

Key Words: Pulmonary hypertension • Milrinone • Cardiopulmonary bypass

	1. Introduction

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

 
Pulmonary hypertension (PH) is a frequent and morbid condition at the time of cardiac surgery [1,2]. Several preoperative conditions increase the risk of developing perioperative PH, including pre-existing PH, mitral stenosis or regurgitation and left ventricular dysfunction. Clinical strategies used clinically to treat perioperative PH include inhaled nitric oxide (iNO) [3–5], inhaled epoprostenol (iPGI2) [6–8] and intravenous phosphodiesterase inhibitors [9].

Milrinone is a type III phosphodiesterase inhibitor that increases intracellular concentration of cyclic adenosine monophosphate (cAMP) in the vascular smooth muscle cell and cardiomyocyte [10]. The effects of intravenous milrinone include pulmonary vasodilatation, systemic vasodilatation and increased inotropy. Milrinone is more efficient than placebo in facilitating weaning from cardiopulmonary bypass (CPB) [11] and is widely used in post-CPB left ventricular dysfunction and low cardiac output [12,13]. However, intravenous milrinone is associated with systemic hypotension and increased vasoactive drug requirements [14]. Moreover, in the largest randomized controlled trial studying the use of intravenous milrinone in the coronary care unit [15], no significant benefit in ischemic cardiomyopathy was observed [16]. The use of the inhaled route for milrinone was recently published in animal [17,18] and human studies [19,20]. As an alternative to nitric oxide and epoprostenol, inhaled milrinone does not require a complex setup, is less expensive, and no toxic metabolites need monitoring [21]. Furthermore, inhaled milrinone is readily available in any operating room and needs no special preparation as opposed to inhaled epoprostenol as it only requires a simple nebulizer for administration to lower the pulmonary artery pressure without inducing systemic hypotension. In addition, administration of inhaled milrinone before and during CPB has been shown to be superior to the intravenous administration in reducing the pulmonary reperfusion syndrome [17], preventing pulmonary arterial endothelial dysfunction and improving oxygenation in a porcine model [17]. Only two studies describe the use of inhaled milrinone after cardiac surgery and in heart transplant candidates undergoing catheterization [19,20] with no significant side effect. However, in these studies, the timing of administration was constant and the effect on ventricular function using echocardiography was not evaluated. This report describes our preliminary experience with intraoperative use of inhaled milrinone and its effect on clinical outcome and ventricular function in 70 high-risk cardiac surgical patients. The main working hypothesis was that inhaled milrinone administered before CPB could be helpful for weaning of CPB in high-risk patients.

	2. Methods

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

 
After approval from the local ethics and research committee and with the permission of Health Canada, a retrospective review of all the transesophageal echocardiograms of consecutive patients having received inhaled milrinone from June 2002 to February 2005 during cardiac surgery in a tertiary cardiac surgery center was conducted. All patients had preoperative risk assessment by Parsonnet and ASA scoring systems. Parsonnet scores of 0–4, 5–9, 10–14, 15–19, and >20 indicate progressively higher risks of mortality ranging from minimal (1%), mild (2%), and moderate (3%) to high (5%) and very high (5–10%) [2]. All patients were monitored by pulmonary artery catheter, electrocardiogram, pulse oximetry, capnography, and radial artery catheter. Anesthesia was inducted with a fentanyl or sufentanil combination with midazolam and isoflurane according to the anesthesiologist's preference. Blood cardioplegia was used in all patients. Induction and maintenance were cold to tepid (10–29 °C). The blood to crystalloid ratio was 4:1. The pump flow was adjusted to obtain an adjusted output of 2.2 l/m² of BSA. The pump flow was reduced to 0.5 l/min for aortic clamping and unclamping. The pumps for all patients were SIII (Stockert, Munchen, Germany) roller pumps. Oxygenator were Sorin Monolyth (Mirandola (MO, Italy). For coronary artery bypass procedures, temperature was allowed to drift to 34 °C. Valve and complex procedures were done with temperatures of 32–34 °C. Aortic procedures with circulatory arrest were done at 15–18 °C. Selective antegrade and retrograde cerebral perfusion were used on a case by case basis. Weaning from cardiopulmonary bypass was attempted after systemic temperature (central and vesical) was >36 °C.

CPB was established in 70 patients and 3 patients had off-pump procedures and were not included in the analysis. Postoperative management of pulmonary hypertension included intravenous nitroglycerine and milrinone and, in more severe cases, inhaled milrinone, epoprostenol or nitric oxide. Preoperative and operative characteristics were collected and postoperative hemodynamic status, events, weaning from CPB support, intensive care unit (ICU) and hospital stay, extubation time and mortality were analyzed according to the timing of the milrinone bolus. Difficult separation from bypass (DSB) was defined as systolic blood pressure <80 mmHg, confirmed by central measurement (femoral or aortic); pulmonary artery diastolic pressure (PADP) or pulmonary artery capillary wedge pressure (PCWP) >15 mmHg during progressive weaning from CPB; and the use of inotropic or vasopressive support (norepinephrine >4 µg/min, epinephrine >2 µg/min, dobutamine >2 µg/kg/min) for at least 1 h, intra-aortic balloon pump or CPB reinitiation [22]. Extreme difficult weaning from CPB was defined as the use of more than two inotropes, need for introduction of an intraaortic balloon pump (IABP) or reinitiation of CPB. The notion of extreme difficult weaning from cardiopulmonary bypass was introduced to identify very high-risk patients. Complex procedures were defined as reoperation, combined procedure, double valve procedure, operation for aortic dissection or endocarditis. The preoperative characteristics of the two groups were compared, and outcomes were analyzed to compare the effects of administration of inhaled milrinone before and after CPB.

2.1 Transesophageal echocardiography
After anesthesia induction, a multiplane TEE probe (Hewlett-Packard Sonos 5500, Andover, MA; Vivid 7 Imaging System, GE Healthcare, Amersham, USA) was inserted to obtain a standard sequence of cardiac images during a period of hemodynamic stability before pericardiotomy and again after sternal closure. Baseline and postoperative values were obtained according to published guidelines [23]. All TEE were performed by two anesthesiologists with more than 10 years experience and with National Board Certification. Global LV systolic function was evaluated by determining the fractional area change (FAC) which is equal to the difference between the end-diastolic and end-systolic area divided by the end-diastolic area obtained in a transgastric midpapillary view. Normal LV function was defined as FAC >50%. The FAC was collected as a categorical variable (above 50, 35–50 and below 35) and each patient was then compared to his preoperative status and classified as having an unchanged, worsened or improved FAC. To assess regional LV systolic function, the regional wall motion score index (RWMSI), using the 16 segments recommended by the American Society of Echocardiography, was measured using midesophageal 4-chamber, 2-chamber, and long-axis views as well as the transgastric midpapillary view (24). A rise in the RWMSI signifies a deterioration of the LV function.

2.2 Drug administration
Inhaled milrinone (Primacor, Sanofi-Synthelabo Canada Inc., Markham, ON, Canada) was administered through the endotracheal tube preceding the initiation of CPB [6,19] or upon discontinuation of CPB according to the surgical and anesthesiology team preference. Five milligrams (1 mg/ml) was administered, resulting in a dose ranging from 50 to 80 µg/kg, over 5 min. The study drug was administered through a jet nebulizer (Salter Labs, Arvin, CA) attached to the inspiratory limb of the ventilator near the endotracheal tube. Nebulization was achieved with a bypass flow of oxygen at 10 l/min. This high flow was used to achieve a high proportion of small particles. Since this added a secondary flow to the patient, the minute ventilation was adjusted to maintain peak inspiratory pressures of less than 30 cm H₂O.

2.3 Study groups
The patients were divided in two groups: those having received the inhaled milrinone before (BE, n = 30) and those receiving it after (AF, n = 40) CPB.

2.4 Statistical analysis
Patient characteristic results were expressed as mean ± SD or simple frequencies and percentages. A logarithmic transformation was used when a continuous variable was not normally distributed. For continuous variables, comparison of groups was performed using the parametric (Student's t-test) or nonparametric (Wilcoxon) test depending on the distribution. For categorical variables, comparison of groups was performed using Pearson chi-square test. Hemodynamic and regional wall motion score index values were measured before (BE) and after (AF) CPB. To test variation between groups and over time, repeated measures ANOVA with GROUP, TIME (before CPB and after CPB) and GROUP x TIME interaction were performed. In case of statistically significant findings, appropriate contrasts were tested following the ANOVA results. For categorical variables (FAC), marginal homogeneity was tested to compare pre and postoperative responses by using log-linear models in each group. To determine the risk factors associated with extreme difficult weaning from CPB and mortality, a logistic regression analysis was performed. Univariate logistic regression analysis was used to identify which baseline variables were significantly associated with the two outcomes. Due to the limited number of events, a stepwise multivariate logistic regression model was performed only with variables with p-values <.10 in the univariate analysis. Statistical analysis was done with the computer software SAS version 8.02 (SAS Institute Inc., Cary, NC). A p-value <.05 was considered statistically significant.

	3. Results

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

 
A total of 73 patients with a mean age of 64 ± 13 years old, composed of 56% males were included. Seventeen patients had CABG, 25 had valve procedures, 15 had combined valvular and CABG, and 16 had other procedures (type A aortic dissection, left ventricular assist device insertion or ventricular repairs). Twelve patients had reoperative surgery (16%). Three patients were operated off pump and were not included in the analysis.

3.1 Preoperative (Table 1), operative (Table 2) and postoperative characteristics (Table 3)
Patients from groups BE and AF had similar preoperative characteristics and risk profile except for more diabetic patients in group BE (p = .048). The Parsonnet scores (BE: 30.4 and AF: 26.1, p = .24), the type of procedures and the operative characteristics were similar among groups. Difficult weaning from CPB occurred in 73% and 80% of patients in group BE and AF, respectively. Nine patients from AF group necessitated reinitiation of CPB, as opposed to one from BE group patients (p = .023). More patients in group AF necessitated adrenaline (5 vs 1), intravenous milrinone (7 vs 2), and IABP insertion (10 vs 4) than in group BE but the differences were not statistically significant .

3.3.1 Univariate and multivariate analysis (Table 5)
Risk factors for mortality used in the univariate analysis were Parsonnet score, CPB time, aortic cross clamp time, postoperative IABP introduction and very difficult weaning from CPB. Administration of inhaled milrinone before CPB was not protective against mortality (p = .38). In the multivariate analysis, postoperative insertion of IABP was associated with increased mortality (OR = 17.7 CI: 3.7–84.5; p = .0003). Univariate analysis of risk factors for very difficult weaning from CPB showed that CPB and cross clamp times were significant predictors and that inhaled milrinone administration before CPB initiation (BE) was a protective factor (OR = 0.2, CI: 0.05–0.8; p = .02). Finally, in the multivariate analysis, only CPB time was a strong risk factor for very difficult weaning from CPB (OR = 1.02, CI: 1.007–1.03, p = .002).

	4. Discussion

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

Only two reports addressing the role of inhaled milrinone and inhaled epoprostenol in cardiac surgery have been published so far [19,20]. In the first, the mPAP, transpulmonary gradient and pulmonary vascular resistance decreased only in patients with PH, defined as a mPAP above 30 mmHg. The dosage was 2 mg based on intravenous milrinone loading doses used in heart transplantation. In the second study, the demonstrated magnitude of the effect was similar to the previous study [19]. However, in both studies, the intraoperative usage and the timing of inhaled milrinone was not explored.

The present study reports our preliminary experience in patients having received inhaled milrinone through a similar mode of administration. The same clinical findings of reduced pulmonary artery pressure and higher MAP over mPAP ratio were observed when inhaled milrinone was administered before CPB. An animal study in our laboratory has shown that the reduced pulmonary artery pressure was secondary to a preservation of pulmonary arterial endothelial function and increased cAMP content in pulmonary artery cells, favoring vasodilatation even in the setting of a reperfusion injury after CPB [17]. Administration of milrinone before and, in smaller doses, during CPB through a more uniform distribution and penetration in the lung parenchyma could protect the pulmonary vasculature during the weaning from CPB when ischemia-reperfusion injury occurs. The duration of the effect of the preoperative dose of inhaled milrinone was longer than the 20 min reported by Haraldsson et al. [19]. Administration of the drug before CPB followed by CPB initiation and diversion of the blood from the pulmonary arterial bed could explain this longer duration as the drug would diffuse in poorly irrigated lung parenchyma during the CPB run. The duration of effect of inhaled milrinone has not been described in humans but is consistent with our animal experiments in which the effect of inhaled agents on vascular tone can be quantified after CPB [17].

This may explain why patients in the BE group had a lower mPAP after separation from CPB. These findings were not observed when the administration of the drug occurred after CPB. The administration of milrinone before CPB could be advantageous as the drug would be distributed in mechanically ventilated lungs, without any significant atelectasis before CPB. In addition, as demonstrated in the animal model, inhaled milrinone could prevent the post-CPB reperfusion injury associated with PH [17]. This could explain the lower mPAP values and the improved left ventricular function after separation from CPB. Furthermore, the left ventricular preload may have been enhanced in patients receiving inhaled milrinone before CPB as it was reported with other vasodilators such as nitric oxide [25] and inhaled epoprostenol [19], however no changes in pulmonary capillary wedge pressure was observed after inhaled milrinone in the Haraldsson et al. [19] or Sablotzki et al. pilot study [20]. The improved left ventricular function could also be explained by a partial intravenous absorption of the drug even though no signs of systemic hypotension were reported. The improved LV function and lower right ventricular afterload have led to a lower proportion of reinitiation of CPB in patients receiving inhaled milrinone before CPB. A lower rate of IABP insertion was also observed in this group (13% vs 25% p = NS), supporting an easier weaning from CPB. The total mortality was 13.7% and was not statistically different between groups (10% vs 18%). The predicted mortality for patients with Parsonnet scores from 26 to 30 is 6–16% [2].

Univariate and multivariate analysis were performed to determine risk factors for very difficult weaning from cardiopulmonary bypass and mortality. The timing of administration of inhaled milrinone was not identified as a predictor of mortality in this limited number of high-risk patients in whom several other factors played a role. Univariate and multivariate analysis to examine the risk factors for extreme difficult weaning from cardiopulmonary bypass identified CPB time and cross clamp time as risk factors and inhaled milrinone administered before CPB was a protective factor. However, in the multivariate analysis, the small number of patients and events allowed identification of increased CPB time as only risk factor for extreme difficult weaning from CPB.

	5. Limitations

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

 
This study represents a retrospective analysis of patients in whom inhaled milrinone was used as it was introduced in our practice. With growing experience, our indications for administration were refined and patients with preoperative pulmonary hypertension receive inhaled milrinone on a more regular basis. Although both groups were statistically similar in terms of preoperative risk, there is a potential selection bias as clinical judgment and experience influenced the decision for using the drug before or after CPB. The anesthesiologists performing TEE were not blinded to the timing of administration. However, this study is so far the largest experience with the clinical use of inhaled milrinone in cardiac surgery. Our data support its efficacy and suggest that it may be advantageous to administer inhaled milrinone before CPB. Nitric oxide and epoprostenol are other inhaled agents that can be used in patients to treat PH in cardiac surgery [3–6,8]. The nebulized administration of milrinone has the advantage of being simpler and cheaper than nitric oxide and epoprostenol inhalation. These issues make inhaled milrinone an attractive option in a cardiac operating room environment. Several issues must be clarified including the ideal timing, the duration of the effect, the optimal dosages, the maintenance administration and the advantages of the inhaled compared to the intravenous route. Randomized controlled trials will seek to answer these options.

	6. Conclusion

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

 
In summary, administration of inhaled milrinone before CPB in high-risk patients facilitates separation from CPB. When PH is present and difficult weaning from CPB is anticipated, inhaled milrinone before CPB may represent a promising approach as an adjunct in the treatment of RV dysfunction and low cardiac output syndrome.

	Footnotes

 
^\#9734; Supported by the Montreal Heart Institute Research Foundation, the Fonds de la recherche en santé du Québec and the Canadian Institutes of Health Research.

	References

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations 6. Conclusion References

 

1. Roques F, Nashef SA, Michel P, Michel P, Gauducheau E, de Vincentiis C, Baudet E, Cortina J, David M, Faichney A, Gabrielle F, Gams E, Harjula A, Jones MT, Pintor PP, Salamon R, Thulin L. Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19,030 patients. Eur J Cardiothorac Surg 1999;15:816-822.[Abstract/Free Full Text]
2. Bernstein AD, Parsonnet V. Bedside estimation of risk as an aid for decision-making in cardiac surgery. Ann Thorac Surg 2000;69:823-828.[Abstract/Free Full Text]
3. Rich GF, Murphy Jr. GD, Roos CM, Johns RA. Inhaled nitric oxide. Selective pulmonary vasodilation in cardiac surgical patients. Anesthesiology 1993;78:1028-1035.[Medline]
4. Kieler-Jensen N, Lundin S, Ricksten SE. Vasodilator therapy after heart transplantation: effects of inhaled nitric oxide and intravenous prostacyclin, prostaglandin E1, and sodium nitroprusside. J Heart Lung Transplant 1995;14:436-443.[Medline]
5. Steudel W, Hurford WE, Zapol WM. Inhaled nitric oxide: basic biology and clinical applications. Anesthesiology 1999;91:1090-1121.[CrossRef][Medline]
6. Hache M, Denault AY, Belisle S, Robitaille D, Couture P, Sheridan P, Pellerin M, Babin D, Noel N, Guertin MC, Martineau R, Dupuis J. Inhaled epoprostenol (prostacyclin) and pulmonary hypertension before cardiac surgery. J Thorac Cardiovasc Surg 2003;125:642-649.[Abstract/Free Full Text]
7. Fortier S, DeMaria RG, Lamarche Y, Malo O, Denault A, Desjardins F, Carrier M, Perrault LP. Inhaled prostacyclin reduces cardiopulmonary bypass-induced pulmonary endothelial dysfunction via increased cyclic adenosine monophosphate levels. J Thorac Cardiovasc Surg 2004;128:109-116.[Abstract/Free Full Text]
8. De Wet CJ, Affleck DG, Jacobsohn E, Avidan MS, Tymkew H, Hill LL, Zanaboni PB, Moazami N, Smith JR. Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg 2004;127:1058-1067.[Abstract/Free Full Text]
9. Monrad ES, McKay RG, Baim DS, Colucci WS, Fifer MA, Heller GV, Royal HD, Grossman W. Improvement in indexes of diastolic performance in patients with congestive heart failure treated with milrinone. Circulation 1984;70:1030-1037.[Abstract/Free Full Text]
10. Baim DS, McDowell AV, Cherniles J, Monrad ES, Parker JA, Edelson J, Braunwald E, Grossman W. Evaluation of a new bipyridine inotropic agent – milrinone – in patients with severe congestive heart failure. N Engl J Med 1983;309:748-756.[Abstract]
11. Doolan LA, Jones EF, Kalman J, Buxton BF, Tonkin AM. A placebo-controlled trial verifying the efficacy of milrinone in weaning high-risk patients from cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997;11:37-41.[CrossRef][Medline]
12. Solina A, Papp D, Ginsberg S, Krause T, Grubb W, Scholz P, Pena LL, Cody R. A comparison of inhaled nitric oxide and milrinone for the treatment of pulmonary hypertension in adult cardiac surgery patients. J Cardiothorac Vasc Anesth 2000;14:12-17.[CrossRef][Medline]
13. Feneck RO, Sherry KM, Withington PS, Oduro-Dominah A. Comparison of the hemodynamic effects of milrinone with dobutamine in patients after cardiac surgery. J Cardiothorac Vasc Anesth 2001;15:306-315.[CrossRef][Medline]
14. Jaski BE, Fifer MA, Wright RF, Braunwald E, Collucci WS. Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose–response relationships and comparison to nitroprusside. J Clin Invest 1985;75:643-649.[Medline]
15. Cuffe MS, Califf RM, Adams Jr. KF, Benza R, Bourge R, Colucci WS, Massie BM, O’Connor CM, Pina I, Quigg R, Silver MA, Gheorghiade M. For the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) Investigators. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA 2002;287:1541-1547.[Abstract/Free Full Text]
16. Felker GM, Benza RL, Chandler AB, Leimberger JD, Cuffe MS, Califf RM, Gheorghiade M, O’Connor CM, for the OPTIME-CHF Investigators Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study. J Am Coll Cardiol 2003;41:997-1003.[Abstract/Free Full Text]
17. Lamarche Y, Malo O, Thorin E, Denault A, Carrier M, Roy J, Perrault LP. Inhaled but not intravenous milrinone prevents pulmonary endothelial dysfunction after cardiopulmonary bypass. J Thorac Cardiovasc Surg 2005;130:83-92.[Abstract/Free Full Text]
18. Hentschel T, Yin N, Riad A, Habbazettl H, Weimann J, Koster A, Tschope C, Kuppe H, Kuebler WM. Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary hypertension in a rat model of congestive heart failure. Anesthesiology 2007;106:124-131.[CrossRef][Medline]
19. Haraldsson s A, Kieler-Jensen N, Ricksten SE. The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension. Anesth Analg 2001;93:1439-1445table.[Abstract/Free Full Text]
20. Sablotzki A, Starzmann W, Scheubel R, Grond S, Czeslick EG. Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates: [La vasodilatation pulmonaire selective avec l’inhalation de milrinone en aerosol chez des candidats a la greffe cardiaque]. Can J Anaesth 2005;52:1076-1082.[Abstract/Free Full Text]
21. Denault AY, Lamarche Y, Couture P, Haddad F, Lambert J, Tardif JC, Perrault LP. Inhaled milrinone: a new alternative in cardiac surgery?. Semin Cardiothorac Vasc Anesth 2006;10:346-360.[Abstract/Free Full Text]
22. Costachescu T, Denault AY, Guimond JG, Couture P, Carignan S, Sheridan P, Hellou G, Blair L, Normandin L, Babin D, Allard M, Harel F, Buithieu J. The hemodynamically unstable patient in the intensive care unit: hemodynamic vs. transesophageal echocardiographic monitoring. Crit Care Med 2002;30:1214-1223.[CrossRef][Medline]
23. Shanewise JS, Cheung AT, Aronson S, Stewart WJ, Weiss RL, Mark JB, Savage RM, Sears-Rogan P, Mathew JP, Quinones MA, Cahalan MK, Savino JS. ASE/SCA guidelines for performing a comprehensive intraoperative multiplane transesophageal echocardiography examination: recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography. Anesth Analg 1999;89:870-884.[Free Full Text]
24. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ, Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee: European Association of Echocardiography Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440-1463.[CrossRef][Medline]
25. Bocchi EA, Bacal F, Auler Junior JO, Carmone MJ, Bellotti G, Pileggi F. Inhaled nitric oxide leading to pulmonary edema in stable severe heart failure. Am J Cardiol 1994;74:70-72.[CrossRef][Medline]

This article has been cited by other articles:

				A. Q. N. Nguyen, A. Denault, Y. Theoret, C. Chen, Y. Lamarche, L. Perrault, and F. Varin 475500 - PLASMA CONCENTRATIONS OF INHALED MILRINONE IN CARDIAC PATIENTS Can J Anesth, June 1, 2008; 55(suppl_1): 475500 - 475500. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yoan Lamarche Louis P. Perrault Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lamarche, Y. Articles by Denault, A. Y. Search for Related Content PubMed PubMed Citation Articles by Lamarche, Y. Articles by Denault, A. Y. Related Collections Anesthesia Cerebral protection Extracorporeal circulation