mitral valve disease with pulmonary arterial hypertension ( pah ) is characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular ( rv ) failure and mortality . the goal of long - term therapy is to reduce pulmonary vasoconstriction , cause regression of vascular remodeling , and prevent thrombosis . pulmonary vascular resistance can be lowered by enhancing cyclic adenosine monophosphate ( camp ) using -agonist or with the phosphodiesterase type iii inhibitor , milrinone . vascular resistance can also be lowered with nitroso vasodilators ( nitroglycerine ( gtn ) , sodium nitroprusside , and inhaled nitric oxide ) . although inhaled nitric oxide is extremely efficacious , its use is complicated by the requirement for an inhaled delivery system and rebound pulmonary hypertension upon its withdrawal . oral sildenafil phosphodiesterase type 5 ( pde5 ) inhibitor increases cyclic guanosine monophosphate ( cgmp ) levels and has been shown to be effective for primary pulmonary hypertension . it has been shown that sildenafil can be used to manage secondary pulmonary hypertension in perioperative period in patients undergoing cardiac surgeries . this prospective double - blind randomized control study was planned to evaluate the efficacy of oral sildenafil preoperatively in patients with severe pulmonary hypertension undergoing mitral valve replacement surgeries . the patients were enrolled for the study after approval from institutional ethics committee after obtaining written consent . a total of 40 patients who were scheduled for mitral valve replacement surgery with severe pah , rv systolic pressure ( rvsp ) 50mmhg , as measured by preoperative transthoracic echocardiography , were included in the study . the patients were randomly allocated to either sildenafil ( in routine hospital supply ) or placebo ( multivitamin tablets similar in appearance to sildenafil were used in placebo group , as no other effective oral alternative is available to treat pah ) using a computerized randomization table . patients with associated cardiac disease ( coronary artery occlusive disease , aortic valve disease , tricuspid regurgitation requiring tricuspid repair , and left ventricular systolic dysfunction ejection fraction < 50% ) , previous cardiac operation , lung disease , liver disease , and renal disease were excluded . patients in group s ( sildenafil , in routine hospital supply ) and group c ( control group ) were administered oral sildenafil 25 mg ( penegra , zydus healthcare , india ) three times a day in 24 h preoperative period and placebo in the same fashion , respectively . nursing staff who were administering the drugs to the patients were blinded during the study . all the patients were administered tablet alprazolam 0.25 mg and tablet pantoprazole 40 mg the night before surgery . on the day of surgery after arrival to preparation room , patients received 4 - 5 l of oxygen with mask . vital parameters were monitored with ecg ( electrocardiogram ) , nibp ( non - invasive blood pressure ) , and pulse oximeter . after infiltration of local anesthesia ( 2% lidocaine ) , a peripheral venous cannula ( 16 or 18 g ) and 20 g arterial cannula in the radial artery of nondominant hand were inserted . injection clonidine 1 g / kg and injection midazolam 0.03 mg / kg intravenously were administered 20 min before surgery as a premedication in all patients . anesthesia was induced with injection midazolam ( 0.1 mg / kg ) , fentanyl ( 7 - 10 g / kg ) , and injection vecuronium ( 0.08 - 0.12 mg / kg ) and maintained with intermittent bolus doses of fentanyl ( 2 g / kg ) and vecuronium ( 0.04 mg / kg ) with sevoflurane ( 1 - 2% ) . after induction of anesthesia , the lungs were ventilated with tidal volume of 8 ml / kg at a rate of 12 breaths / min in 50% oxygen - air mixture . after that , ventilatory parameters were adjusted to maintain pao2 between 150 - 250 mmhg , paco2 between 33 - 38 mmhg , and ph 7.35 - 7.45 . after induction of anesthesia and under all aseptic and antiseptic precautions , pulmonary artery catheter ( pac ) ( edwards lifescience , irvine , ca , usa ) was inserted in the right internal jugular vein to monitor pulmonary artery pressure , pulmonary capillary wedge pressure ( pcwp ) and cardiac indices ( cis ) ,   svri ( systemic vascular resistance index ) , and pvri ( pulmonary vascular resistance index ) . cpb ( cardio pulmonary bypass ) was performed with stockert pump ( germany ) , using membrane oxygenator with standard institutional protocol . during weaning from cpb , gtn and dobutamine ( 5 - 10 g / kg / min ) was administered in all patients after achieving body temperature greater than 36c and normalizing acid - base and electrolyte balance . after 10 min of weaning from cpb , inotropes were titrated according to map ( mean arterial pressure ) and   spap ( systolic pulmonary artery pressure ) . hemodynamic variables were measured 20 min after insertion of pac under anesthesia ( t1 ) , 20 min after weaning from cpb ( t2 ) , 1 , 2 , and 6 h after transferring the patient to postoperative recovery period ( t3 , t4 , t5 ) . heart rate ( hr ) , map , systolic pulmonary arterial pressure ( spap ) , mean pulmonary artery pressure ( mpap ) , pcwp , cardiac index ( ci ) , systolic vascular resistance index ( svri ) , and pvri were measured at each interval . the statistical analysis was performed using statistical package for the social sciences ( spss ) version 20.0 . hemodynamic variables were measured 20 min after insertion of pac under anesthesia ( t1 ) , 20 min after weaning from cpb ( t2 ) , 1 , 2 , and 6 h after transferring the patient to postoperative recovery period ( t3 , t4 , t5 ) . heart rate ( hr ) , map , systolic pulmonary arterial pressure ( spap ) , mean pulmonary artery pressure ( mpap ) , pcwp , cardiac index ( ci ) , systolic vascular resistance index ( svri ) , and pvri were measured at each interval . the statistical analysis was performed using statistical package for the social sciences ( spss ) version 20.0 . hemodynamic variables were measured 20 min after insertion of pac under anesthesia ( t1 ) , 20 min after weaning from cpb ( t2 ) , 1 , 2 , and 6 h after transferring the patient to postoperative recovery period ( t3 , t4 , t5 ) . heart rate ( hr ) , map , systolic pulmonary arterial pressure ( spap ) , mean pulmonary artery pressure ( mpap ) , pcwp , cardiac index ( ci ) , systolic vascular resistance index ( svri ) , and pvri were measured at each interval . the statistical analysis was performed using statistical package for the social sciences ( spss ) version 20.0 . a total of 40 patients were included in the study , 20 patients in each group . other parameters like preoperative rvsp , cpb time , and cross - clamp time were similar in both groups ( p = 0.936 , p = 0.932 , p = 0.902 , respectively ) [ table 1 ] . characteristics of patients with mitral valve disease and pulmonary hypertension treated with sildenafil versus placebo hemodynamic parameters , i. e. hr , map , and pcwp were similar in both groups after induction , after weaning from cpb , and in the postoperative period [ table 2 ] . spap and mpap were significantly lower ( p < 0.0001 ) during t1-t5 times in sildenafil group as compared with the control group [ table 2 ] . hemodynamic parameters during mitral valve replacement surgery in sildenafil versus control groups on comparison of ci and svri there was no statistical significance between the two groups . pvri was significantly lower in sildenafil group after induction , after weaning from cpb , and in the postoperative period [ table 2 ] . during the period of weaning from cpb , the number of patients who required dobutamine infusion was lower in s group ( p < 0.01 ) , whereas the number of patients requiring norepinephrine infusion was not significantly different between the two groups ( p < 0.23 ; table 3 ] . postoperative parameters like ventilation time and postoperative icu ( intensive care unit ) stay time was significantly lower in sildenafil group ( p = 0.011 ) as compared with control group [ table 3 ] . during study , there was one mortality due to low output noted in control group on second postoperative day . perioperative parameters during mitral valve replacement surgery in sildenafil and control group of patients ( n=20 ) in this prospective double - blind randomized controlled study , oral sildenafil 25 mg three times over 24 h before surgery produced significant pulmonary vasodilatation without any significant systemic effects . sildenafil has a favorable effect like lowering pulmonary vascular resistance after induction of anesthesia that extended into postoperative period . spap , mpap , and pvri were significantly lower in sildenafil group ( p < 0.0001 ) as compared with controlled group during the intraoperative period as well as in postoperative period . cardiac surgery in patients with valvular heart disease with severe pah is often complicated with rv failure with an adverse consequence on its prognosis . right ventricle is susceptible to ischemic injury , as cpb exacerbates pah , this necessitates perioperative strategy to manage pah and rv dysfunction . the final messenger for vascular smooth muscle relaxation , cgmp , is metabolized by pde5 . among the various phosphodiesterase , pde5 is the predominant type in the normal pulmonary vasculature that may be upregulated after cpb . the inhibition of pde5 is therefore a logical step to increase the bioavailability of cgmp and support endogenous vasodilation in patient with pah . pde5 is selectively inhibited by sildenafil , vardenafil , and tadalafil and less selectively by zaprinast and dipyridamole . oral sildenafil is widely used in treatment of patients with erectile dysfunction and shows an excellent cardiovascular safety profile . it is emerging as an effective and safe pulmonary vasodilator in primary pulmonary hypertension as well as secondary pulmonary hypertension . pde5 is abundant in lung tissue ; hence sildenafil selectively inhibits it and preferentially dilates pulmonary vascular beds . oral sildenafil selectively reduced pulmonary hypertension without any adverse systemic effects . in the present study , 25 mg of oral sildenafil was administered three times a day for 24 h with the last dose administered 3 h prior to surgery . , demonstrated that the maximal hemodynamic effects of sildenafil on pulmonary circulation could be achieved with a dose as low as 25 mg . we used three doses over 24 h to reduce pulmonary hypertension and improve rv function prior to surgery . sildenafil has a half - life of about 4 h ; it is rapidly absorbed via the stomach and its plasma levels peaks within 30 - 120 min after ingestion . considering these facts , the last dose of sildenafil was administered 3 h prior to surgery . in this study , spap , mpap , and pvri were significantly lower ( p < 0.0001 ) after induction of anesthesia , after weaning from cpb , and in immediate postoperative period in sildenafil group as compared with control group . but map , pcwp and ci , and svri were no significantly differing between two groups . during weaning from cpb , we started gtn infusion and dobutamine infusion in all patients . inotropes , dobutamine infusion ( 5 - 10 g / kg / min ) continued when map was lower than 60 mmhg and also norepinephrine infusion ( 0.05 - 0.1 g / kg / min ) was added whenever required . in sildenafil group , six ( 30% ) patients required dobutamine infusion , of these two ( 33.3% ) patients required norepinephrine infusion . in the control group , ventilation time and postoperative recovery room times were significantly lower ( p = 0.001 ) in sildenafil group as compared with control group . preoperative oral sildenafil reduces pulmonary artery pressure in the perioperative period in patients with severe pulmonary hypertension secondary to mitral valve disease undergoing mitral valve replacement . because of the predominant selective activity of sildenafil in management of pulmonary hypertension and improvement of rv function without compromising the systemic blood pressure , the use of this drug in cardiac surgical patients should be considered . elaborate studies of oral sildenafil in secondary pah in larger populations will help validate the results of this study .
aim : long standing mitral valve disease is usually associated with severe pulmonary hypertension . perioperative pulmonary hypertension is a risk factor for right ventricular ( rv ) failure and a cause for morbidity and mortality in patients undergoing mitral valve replacement . 
 phosphodiesterase 5 inhibitor - sildenafil citrate is widely used to treat primary pulmonary hypertension . 
 there is a lack of evidence of effects of oral sildenafil on secondary pulmonary hypertension due to mitral valve disease . 
 the study aims to assess the effectiveness of preoperative oral sildenafil on severe pulmonary hypertension and incidence of rv failure in patients undergoing mitral valve replacement surgery.materials and methods : a total of 40 patients scheduled for mitral valve replacement with severe pulmonary hypertension ( rv systolic pressure ( rvsp ) 60 mmhg ) on preoperative transthoracic echo were randomly treated with oral sildenafil 25 mg ( n = 20 ) or placebo ( n = 20 ) eight hourly for 24 h before surgery . 
 hemodynamic variables were measured 20 min after insertion of pulmonary artery catheter ( pac ) under anesthesia ( t1 ) , 20 min at weaning from cardiopulmonary bypass ( cpb ) ( t2 ) and after 1,2 , and 6 h ( t3 , t4 , t5 , respectively ) during the postoperative period.results:systolic and mean pulmonary artery pressure ( mpap ) and pulmonary vascular resistance index ( pvri ) were significantly lower ( p < 0.0001 ) in sildenafil group at all times . 
 ventilation time and postoperative recovery room stay were significantly lower ( p < 0.001 ) in sildenafil group.conclusion:sildenafil produces significant pulmonary vasodilatory effect as compared with placebo in mitral valve replacement patients with severe pulmonary hypertension . 
 it also reduces ventilation time and intensive care unit ( icu ) stay time as compared with placebo . 
 it is concluded that sildenafil is effective in reducing pulmonary hypertension when administered preoperatively in patients with severe pulmonary hypertension undergoing mitral valve replacement surgery .