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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 4  |  Issue : 1  |  Page : 35-39

Comparison of hemodynamic effects of inhaled milrinone and inhaled nitroglycerin in patients with pulmonary hypertension undergoing mitral valve surgery


Department of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, University of Alexandria, Alexandria, Egypt

Date of Submission11-Jun-2016
Date of Acceptance22-Oct-2016
Date of Web Publication22-Mar-2017

Correspondence Address:
Hussein W Hussein
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Alexandria University Elkhartoom square, Alex
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2356-9115.202698

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  Abstract 

Introduction
Pulmonary hypertension (PH) frequently complicates the perioperative management of patients undergoing mitral valve surgery and has been shown to be a significant independent predictor of postoperative morbidity and mortality. The aim of this work is to compare the effects of inhaled milrinone and inhaled nitroglycerin on pulmonary and systemic hemodynamic responses in patients with PH undergoing mitral valve surgery.
Patients and methods
A total of 50 patients with PH were randomly divided into two groups with 25 patients in each group: group I patients received inhaled nitroglycerin (5 mg, 1 mg/ml) over 15 min and group II patients received inhaled milrinone (5 mg, 1 mg/ml) over 15 min through an ultrasonic nebulizer connected to the inspiratory limb of the ventilator circuit near the endotracheal tube immediately after separation from cardiopulmonary bypass. Hemodynamic parameters were measured after induction of anesthesia (T1), immediately after the end of cardiopulmonary bypass (T2), 30 min after the start of treatment, and 90 min after the start of treatment (T4). The hemodynamic variables were as follows: heart rate, mean arterial blood pressure (MAP), mean pulmonary artery blood pressure (MPAP), cardiac index (CI), systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), and right ventricular stroke work index (RVSWI).
Results
At 30 min after the start of treatment, both groups showed a significant comparable decrease in MPAP, PVRI, and RVSWI, with no significant changes in MAP, CI, and SVRI. At 90 min after the start of treatment, MPAP, PVRI, and RVSWI returned to their values in the inhaled nitroglycerin group but remained at significantly lower values in the inhaled milrinone group.
Conclusion
Inhalation of nitroglycerin and milrinone produces a comparable decrease in MPAP, PVRI, and RVSWI without significant changes in heart rate, MAP, CI, and SVRI. Inhaled milrinone has a longer duration of action than inhaled nitroglycerin.

Keywords: cardiopulmonary bypass, inhaled milrinone, inhaled nitroglycerin, mitral valve surgery, pulmonary hypertension


How to cite this article:
Fikry DM, Ramadan ME, Elhadedy MS, Hussein HW. Comparison of hemodynamic effects of inhaled milrinone and inhaled nitroglycerin in patients with pulmonary hypertension undergoing mitral valve surgery. Res Opin Anesth Intensive Care 2017;4:35-9

How to cite this URL:
Fikry DM, Ramadan ME, Elhadedy MS, Hussein HW. Comparison of hemodynamic effects of inhaled milrinone and inhaled nitroglycerin in patients with pulmonary hypertension undergoing mitral valve surgery. Res Opin Anesth Intensive Care [serial online] 2017 [cited 2020 May 31];4:35-9. Available from: http://www.roaic.eg.net/text.asp?2017/4/1/35/202698


  Introduction Top


Pulmonary hypertension (PH) is a hemodynamic and pathophysiological condition defined as an increase in mean pulmonary artery blood pressure (MPAP) greater than and equal to 25 mmHg at rest, as assessed by right heart catheterization [1].

PH is a common complication of mitral valve disease and may affect as many as 73% of patients depending on disease severity [2],[3]. The left-sided rheumatic valvular pathology over a period results in pulmonary venous hypertension followed by pulmonary arterial hypertension. Compared with patients with primary forms of PH, those secondary to valvular heart disease have significantly elevated pulmonary artery pressure and pulmonary vascular resistance (PVR), but lesser cardiac output [4].

PH frequently complicates the perioperative management of patients undergoing mitral valve surgery [5]. Preexisting secondary PH (mainly as a result of increased left atrial pressure and pulmonary vascular remodeling) may be aggravated following mitral valve surgery because of a variety of pathophysiologic processes, including ischemia–reperfusion injury of the pulmonary vascular endothelium and the release of vasoactive substances during cardiopulmonary bypass (CPB) [6]. Exacerbation of pH may result in acute right ventricular failure, which has been demonstrated in cardiac surgical patients to be independently associated with high morbidity and mortality [7].

Agents that produce selective pulmonary vasodilatation and that lower pulmonary artery pressure and PVR but without affecting systemic arterial pressure are of special clinical interest in the setting of cardiothoracic anesthesiology. Their action, which is limited to the pulmonary vascular bed, largely avoids systemic vasodilatation.

The perioperative use of inhaled vasodilators to reduce pulmonary artery pressure, therefore, appears to be an ideal treatment option for achieving selective pulmonary vasodilatation [8].

Milrinone is a phosphodiesterase III inhibitor that increases intracellular levels of cyclic adenosine monophosphate and induces positive cardiac inotropy and vasorelaxation [9]. Nitroglycerin is a potent vasodilator that mediates its effects through liberation of nitric oxide [10].

The aim of this work is to compare the effects of inhaled milrinone and inhaled nitroglycerin on cardiac output, pulmonary artery pressure, PVR, and systemic vascular resistance in patients with PH undergoing mitral valve surgery.


  Patients and methods Top


After approval of the local ethics committee and after obtaining an informed written consent from patients, the present study was carried out in Alexandria University Hospitals on 50 adult patients with PH (having MPAP≥25 mmHg) scheduled for elective mitral valve surgery under general anesthesia. Exclusion criteria included patient refusal, emergency surgery, redo surgeries, history of chronic obstructive pulmonary disease, severe renal or liver dysfunction, left ventricular ejection fraction less than 40%, and post-bypass MPAPless than 25 mmHg. Patients were randomized using closed envelop method into two equal groups (25 patients each). Group I patients received inhaled nitroglycerin (5 mg, 1 mg/ml) over 15 min and group II patients received inhaled milrinone (5 mg, 1 mg/ml) over 15 min.

Anesthesia management

Anesthesia was induced with intravenous fentanyl (2–3 µg/kg), midazolam (4–5 mg), propofol (1–2 mg/kg) titrated to effect, and the trachea was intubated following rocuronium bromide (0.1 mg/kg), volume-controlled ventilation with the tidal volume adjusted to maintain normocapnia and anesthesia was maintained with intermittent fentanyl boluses, rocuronium boluses, and sevoflurane (2–3%) in oxygen and air (50 : 50). After induction of anesthesia, a 7.5-F central venous catheter and an 8.5-F introducer sheath were placed in the right internal jugular vein. Through the latter, a 7-F pulmonary artery catheter was inserted into the pulmonary artery under pressure guidance. Heparin was given in a dose of 3 mg/kg, intravenous (300 IU/kg) as a loading dose 5–10 min before aortic cannulation to reach an activated clotting time above 480 s. Incremental doses of 1 mg/kg were given guided by activated clotting time to keep its level above 480 s during CPB [11].

During CBP, anesthesia was maintained with propofol (0.05–0.1 mg/kg/h), midazolam (0.05–0.1 mg/kg/h), and rocuronium boluses. Myocardial preservation was achieved by intermittent antegrade cold blood cardioplegic solution (4°C), infused into the aortic root after aortic cross-clamping. Alpha-stat management was used for interpretation of the arterial blood gas analysis and treatment of the patients during CPB [12].

During weaning from CBP, all patients were normoventilated with 100% oxygen by volume-controlled ventilation. End-tidal CO2 was maintained between 30 and 35 mmHg, and arterial pH was maintained at 7.4±0.02 for all patients in both groups. Group I patients received inhaled nitroglycerin (5 mg, 1 mg/ml) over 15 min through an ultrasonic nebulizer [13] connected to the inspiratory limb of the ventilator circuit near the endotracheal tube immediately after separation from CPB and before heparin reversal with protamine. Group II patients received inhaled milrinone (5 mg, 1 mg/ml) over 15 min through an ultrasonic nebulizer [13] connected to the inspiratory limb of the ventilator circuit near the endotracheal tube immediately after separation from CPB and before heparin reversal with protamine. After weaning from CPB, heparin was antagonized with protamine at a dose of 1.0–1.3 mg protamine per 100 IU heparin [14].

Measurements

Hemodynamic parameters were measured after induction of anesthesia (T1), immediately after the end of CPB and before heparin reversal with protamine before starting inhaled medications (T2), 30 min after start of treatment, and 90 min after start of treatment (T4). The hemodynamic variables were heart rate (HR), mean arterial blood pressure (MAP) (mmHg), MPAP (mmHg), and cardiac index (CI) (l/min/m2) (Discontinuous measurement of cardiac output was done by thermodilution technique performed by triple bolus injections of 10 ml of saline 0.9% at room temperature into the right atrium. Injections were randomly spread over the respiratory cycle. Each value represents the average of three measurements [15].), systemic vascular resistance index (SVRI) (dynes s/cm5/m2), pulmonary vascular resistance index (PVRI) (dynes s/cm5/m2), and right ventricular stroke work index (RVSWI) (g m/m2/beat).

In addition, total CPB time, aortic cross-clamping time, the need for inotropes (their dose and duration), and time of weaning from mechanical ventilation were measured.


  Results and discussion Top


Demographic data for the inhaled milrinone and inhaled nitroglycerin groups are described in [Table 1]. There were no significant differences in age, sex, weight, or height (P>0.05). In addition, the two study groups were statistically comparable as regards total CPB time, cross-clamp time, inotropic support (dose and duration), and time of weaning from mechanical ventilation ([Table 2]).
Table 1 Demographic data of the study population

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Table 2 Clinical parameters of both groups

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In the present study, after induction of general anesthesia (T1), there were no statistically significant differences between group I and group II regarding HR, MAP, SVRI, CI, MPAP, PVRI, and RVSWI. CI increased significantly, whereas SVRI, MPAP, and PVRI decreased significantly in the two studied groups at T2 in comparison with their values at T1. There were no statistically significant differences between the two studied groups regarding the measured hemodynamic responses at T2 ([Table 3]).
Table 3 Hemodynamic data of both groups

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The pathophysiologic changes in mitral valve disease are related to increased pressure overload (in mitral stenosis (MS)) and volume overload (in mitral regurge (MR)) to the left atrium (LA). As the disease progresses, PVR increases as a consequence of increase in the LA pressure. The increased LA pressure is passively transmitted to the pulmonary vasculature. In addition, reactive pulmonary vasoconstriction and organic changes in the pulmonary vasculature also contribute to the increase in PVR [16]. After mitral valve replacement, there is a great reduction in LA pressure with subsequent decrease in pulmonary capillary wedge pressure, PVRI, and MPAP. However, PVRI and MPAP do not return to normal values because of persistence of reactive pulmonary vasoconstriction and organic changes in the pulmonary vasculature.

At 30 min after start of the inhaled medications (T3), MPAP, PVRI, and RVSWI decreased significantly without a significant decrease in MAP or SVRI in both groups in comparison with their values at T2. This indicates that both treatment strategies have a selective pulmonary vasodilator effect without ‘spillover’ of the drug in the systemic circulation. Both inhaled nitroglycerin and inhaled milrinone have similar effects on MPAP, PVRI, and RVSWI; there were no statistically significant differences in MPAP, PVRI, and RVSWI between the two groups at T3 ([Table 3]).

At 90 min after the start of the inhaled medications (T4), MPAP, PVRI, and RVSWI remained at significantly lower values in the inhaled milrinone group in comparison with their values at T2. However, MPAP, PVRI, and RVSWI were at significantly higher values in the inhaled nitroglycerin group in comparison with the inhaled milrinone group at T4 ([Table 3]). The difference in the duration of action of nitroglycerin and milrinone might be attributed to the different pharmacological profiles of the two drugs. Nitroglycerin is rapidly deactivated by reductive hydrolysis in the liver and blood by glutathione-organic nitrate reductase with a half-life of 4 min [17]. However, milrinone is partially metabolized in the liver and excreted in the kidney with a half-life of 2.5 h [18].


  Conclusion Top


Inhalation of nitroglycerin and milrinone produces a comparable decrease in MPAP, PVRI, and RVSWI without significant changes in HR, CI, MAP, or systemic vascular resistance. Inhaled milrinone has a longer duration of action than inhaled nitroglycerin.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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