**6.2 Combination therapy**

118 Perioperative Considerations in Cardiac Surgery

into the systemic circulation. Moreover, abrupt withdrawal of inhaled PGI2 may cause

Variable dose delivery, alteration of ventilation volumes, pressures, FiO2, and solvent evaporation with drug-concentrating effect are other obvious disadvantages. Plasma half-

Iloprost is a more stable carbacyclin derivative of prostacyclin and can be administered intermittently, as the hemodynamic effects of a single dose are sustained for approximately 60-120 min, although the plasma half-life time of intravenously administered iloprost is known to be between 20-30 min (Theodoraki et al., 2002). This form of treatment appears to be promising combining the advantages of NO and the lack of problems of intravenous administration. Iloprost causes a significant reduction in MPAP and PVR and a significant increase in cardiac output after its administration since there is a substantial reduction in right ventricular afterload. It cannot be ruled out that a decrease in systemic vascular resistance (SVR) may occur during its administration but not to a degree that can affect

Aerosolized iloprost has been described as a more potent pulmonary vasodilator than NO in patients with PH (Winterhalter et al., 2008). Its longer half-life firstly confers effective protection against the rebound phenomenon and, secondly, may facilitate the pharmacological effective transfer of the inhaler material from the pulmonary into the

Iloprost remains stable at room temperature and does not undergo any molecular changes on exposure to light, in comparison to PGI2 (Fattouch et al., 2003). Also, inhaler iloprost can be rapidly and simply administered intraoperatively, irrespective of ventilator type. Unlike the situation with NO, inhaled iloprost treatment can also be continued with an ultrasonic

Episodes of PH during heart transplantation procedures can be successfully treated with the administration of iloprost without unwanted side effects or significant systemic impact

Right heart failure after left ventricular assist device (LVAD) implantation is an acute lifethreatening event. In patients with intraoperative severe acute right heart failure after implantation of a LVAD, successful weaning from CPB was possible after inhaled iloprost

In addition to its beneficial hemodynamic profile, aerosolized iloprost also exerted beneficial effects on arterial oxygenation, which probably reflected the more potent effects of iloprost on the pulmonary vascular bed and the more pronounced increase of mixed-venous oxygen

Inhaled NTG decreases PH without producing systemic vasodilatation (Yurtseven et al., 2003). Further studies are warranted to define their potential utility because nebulization of these drugs does not require an expensive apparatus like the one required for NO

Milrinone inhibits the breakdown of cAMP, thereby promoting pulmonary vasodilatation. There are few recent studies which demonstrated the beneficial effects of inhaled milrinone

nebulizer during weaning from the ventilator and after extubation.

rebound increases in PH. (Lowson, 2002)

life of prostacyclin is 3 to 6 minutes.

arterial blood pressure dramatically.

systemic arterial circulation.

(Theodoraki et al., 2006).

was added (Winterhalter et al., 2006).

**Phosphodiesterase – 3 inhibitors** 

on PH during weaning of patients from CPB.

saturation (Hoeper et al., 2000).

**NO donors** 

nebulization.

**Iloprost** 

NO and PGI2 / iloprost cause vasodilatation via two different intracellular signal pathways by relaxing smooth muscle cells. After diffusion into the smooth muscle cells, NO causes vascular smooth muscle cell relaxation by stimulating guanylate cyclase, leading to an increase in 3,5-cGMP and a reduction in intracellular calcium concentration. By contrast, PGI2 / iloprost result in an increase in intracellular cyclic 3,5 cAMP concentrations, causing calcium-activated potassium channels to open through activation of adenyl-cyclase. However these drugs can be administered as combination therapy.
