Successful Treatment of Acute Postoperative Pulmonary Hypertension With Nifedipine Deborah A. Davis, MD, and Pierantonio RUSSO, MD Pediatric Heart Institute, Temple University School of Medicine and St. Christopher's Hospital for Children, Philadelphia, Pennsylvania
We report the successful use of nifedipine in the treatment of acute pulmonary hypertension in an infant after a cardiac operation. This patient had undergone total surgical correction of his truncus arteriosus malformation. He had signs of severe pulmonary artery hypertension unresponsive to hyperventilation, oxygenation, se-
dation, and a myriad of vasodilators. Nifedipine, 0.2 mg/kg every 4 hours, effectively treated his pulmonary artery hypertension and allowed for a smooth postoperative course and positive outcome.
P
intubated using pancuronium bromide (Pavulon; Organon Inc, West Orange, NJ) for neuromuscular blockade. Invasive monitoring consisted of a right femoral arterial line and a double-lumen right internal jugular vein. Maintenance anesthesia was provided with incremental boluses of fentanyl for a total of 65 pgkg. The operation was performed with the patient on hypothermic cardiopulmonary bypass at periods of low flow and consisted of patch closure of the ventriculoseptal defect and truncus repair using a pulmonic homograft. At the completion of the operation, a left atrial and a pulmonary arterial line were placed by the surgeon. The patient was weaned off cardiopulmonary bypass on infusions of 10 p g kg-' min-' of dopamine and 5 pg kg-' min-' of amrinone. In anticipation of pulmonary hypertension in the postoperative period, a dose of 10 pgkg of fentanyl was given to the patient before transport to the intensive care unit. In the immediate postoperative period, the pulmonary artery pressures ranged from 25% to 30% of the systemic pressure. During the night of operation, the patient was hyperventilated with 100% 0, to maintain arterial CO, levels between 20 and 25 mm Hg. The patient continued to receive fentanyl, 10 pg . kg-' . h-'. When the pulmonary artery pressures began to increase to approximately 50% of the systemic pressures, vasoactive drugs were used to manipulate the pulmonary artery pressures. The dosage of dopamine was lowered to 4 pg kg-' min-', and amrinone administration was continued at 5 pg kg-' . min-'. Prostaglandins were given at a dose of 0.05 pg . kg-' . min-' through the pulmonary artery catheter, a n d the dose was increased to 0 . 1 p g kg-' min-'. Nitroglycerin was added at a dose of 1 pg kg-' . min-'. Using these drugs, the systemic pressures remained stable and the pulmonary artery pressures decreased from 30% to 50% systemic. That evening, the patient had stable vital signs and a urine output of 2 to 3 mL . kg-' * h-'. On the first postoperative day, the pulmonary artery pressures began to rise to 60% systemic. Elevations in
ulmonary hypertension is a serious cause of morbidity and mortality after surgical correction of congenital heart defects. Postoperative pulmonary hypertension is likely to develop in infants who have excessive pulmonary blood flow or pulmonary venous obstruction. Elevated pulmonary resistance may occur as a result of this pulmonary vascular overload. The high pulmonary resistance may impose an impedance load on the right ventricle, causing it to fail and, through its interdependence with the left ventricle, produce a low cardiac output state. The decreased systemic pressure lowers coronary perfusion and a vicious cycle of biventricular failure may ensue. Oxygen, hyperventilation, alkalinization, and sedation are the mainstays of therapy for pulmonary hypertension in infants [l].The lack of specific pulmonary vasodilators makes management of postoperative pulmonary hypertension difficult. If nonspecific vasodilators are used to lower pulmonary vascular pressure, systemic pressure may be simultaneously lowered, negatively affecting coronary perfusion to a hypertensive right ventricle. We report the successful use of the calcium channel blocker nifedipine to treat pulmonary hypertension without affecting systemic pressure. A 4-month-old male infant with Type 1 truncus arteriosus underwent complete repair of his cardiac lesion. He had first been seen at the age of 3 months with a history of poor weight gain, tachypnea, and failure to thrive. Diagnosis was made by cardiac catheterization and he was placed on a regimen of digoxin and furosemide (Lasix; Hoechst-Roussel Pharmaceuticals, Somerville, NJ). The patient was brought to the operating room and noninvasive monitors were placed. Anesthesia was induced with nitrous oxide, oxygen, and 0.5% halothane. Venous access was obtained and he was nasotracheally Accepted for publication June 24, 1991. Address reprint requests to Dr Davis, Pediatric Heart Institute, St. Christopher's Hospital for Children, Erie Ave at Front St, Philadelphia, PA 19134-1095.
0 1992 by The Society of Thoracic Surgeons
(Ann Thorac Surg 1992;53:148-50)
-
0003-4975/92/$3.50
CASE REPORT DAVIS AND RUSSO NIFEDIPINE IN PULMONARY HYPERTENSION
Ann Thorac Surg 1992;53:14a50
systemic pressure. Nitroglycerin ointment was substituted for nitroglycerin. By the fifth postoperative day, the patient had no further episodes of pulmonary hypertension, he was further weaned from the drugs, and he was discharged home 2 weeks later, receiving 3 cm of nitroglycerin ointment every 3 hours.
HR
120 30 11:45
12:w
149
12:15 \
I
Comment
-20 11:45
DAD S
"1
12:w
12:lS
12:w
12:15
A h
- 1 PAP D
'
11:45
A
'
Nihdlplne
Fig 1 . Simultaneous measurements of heart rate (HR), arterial blood pressure (ABP), and pulmonary artery pressure (PAP). (D = diastolic; M = mean; S = systolic.)
pulmonary artery pressure occurred in response to tracheal suctioning and spontaneously without a precipitating event. The fentanyl infusion was increased to 50 pg kg-' h-' and the patient was further sedated with chloral hydrate and midazolam. Arterial carbon dioxide tension was kept in the range of 20 to 25 mm Hg. Arterial oxygen tension was kept greater than 200 mm Hg. Despite these pharmacologic manipulations, the patient's pulmonary artery pressures continued to rise and approached systemic pressures. Nifedipine, 0.2 mgkg every 6 hours through the nasogastric tube, was given. The nifedipine was aspirated from a 10-mg capsule and diluted to a concentration of 1 mg/mL. The pulmonary artery pressures decreased by 50% with no impact on the systemic pressures, as shown in Figure 1.Throughout the evening, it later became necessary to increase the nifedipine dosing interval to every 4 hours to keep the pulmonary artery pressures less than 50%of the systemic pressure. On the second postoperative day, the patient would intermittently have a pulmonary hypertensive crisis as evidenced by pulmonary artery pressures that became 60% systemic. The nifedipine dose was increased to 0.5 mgkg every 4 hours, and the prostaglandin infusion was increased to 0.15 pg kg-' min-'. Captopril was added at a dose of 2.5 mg three times a day through the nasogastric tube. On the third postoperative day, the patient was weaned off dopamine and nitroglycerin. He continued to receive captopril, nifedipine, prostaglandin, and fentanyl infusion while we continued to monitor pulmonary and
-
Postoperative pulmonary hypertension with right ventricular failure is a particular problem in infants with increased pulmonary blood flow. Large systemic to pulmonary artery shunts occur in a variety of congenital heart defects including ventriculoseptal defects, transposition of the great vessels, atrioventricular canal, or truncus arteriosus. In other congenital defects such as mitral stenosis, cor triatriatum, and obstructed pulmonary veins, pulmonary hypertension is secondary to elevated pulmonary venous pressure. Pulmonary hypertension may complicate the postoperative course of patients with these defects despite adequate surgical repair [l]. A pulmonary hypertensive crisis is characterized by a rapid rise in pulmonary artery pressure. These episodes may occur randomly or may be triggered by specific factors such as agitation or tracheal suctioning. The elevated pulmonary artery pressures strain the right ventricle and, if left untreated, can evolve to ventricular failure and death. Often the pulmonary crisis can be effectively treated with oxygen, hyperventilation, and sedation. When these therapies do not suffice, vasoactive drugs such as tolazine hydrochloride (Priscoline; CIBA Pharmaceutical Co, Summit, NJ), prostaglandin, or prostacycline are added. An ideal drug for the treatment of acute pulmonary hypertension would act selectively on the pulmonary vasculature, increasing cardiac output with minimal effects on systemic pressures or the relationship between ventilation and pulmonary perfusion. Nifedipine inhibits the transmembrane influx of extracellular calcium ions across myocardial and vascular smooth muscle cells, thereby promoting vasodilatation. As a pulmonary vasodilator, nifedipine may act locally within the lung vasculature or indirectly through the sympathetic nervous system, inhibiting hypoxic vasoconstriction [2]. Changes in vascular resistance induced by nifedipine are inversely related to the degree of arterial hypoxemia [3]. Nifedipine's efficacy as a selective pulmonary vasodilator is controversial. Prielipp and associates [4], studying the hemodynamic effects of a variety of vasodilators, found nifedipine to decrease systemic pressure more than pulmonary pressure. Other investigators refute this, showing that pulmonary artery pressures and resistance are preferentially reduced, particularly in adults and children with chronic obstructive lung disease and cor pulmonale [5-71. Nifedipine has been proven beneficial in children, in whom chronic administration lowered pulmonary artery resistance, increased pulmonary performance, and produced subjective improvement [8].Less is known about acute postoperative pulmonary vasculature effects of nifedipine in children. The only
150
CASE REPORT DAVIS AND RUSSO NIFEDIPINE IN PULMONARY HYPERTENSION
generalization that can be made regarding nifedipine as a pulmonary vasodilator is that patient response is variable. In the case we report, nifedipine exhibited the properties of an ideal pulmonary vasodilator: it selectively lowered pulmonary artery pressure yet preserved systemic pressure and, indirectly, coronary perfusion, thus improving cardiac function. Nifedipine should be considered a therapeutic option in the treatment of acute postoperative pulmonary hypertension in children.
Addendum Since the submission of this report, 6 additional patients with pulmonary hypertension after cardiac surgical repair were treated with nifedipine with good results. Nifedipine is currently the pulmonary vasodilator of choice at our institution.
References 1. Hickey PR, Hansen DD. Pulmonary hypertension in infants: postoperative management. In: Yacoub M, ed. Annual of cardiac surgery. Philadelphia: Current Science, 1989:16-22.
Ann Thorac Surg 1992~53: 14S50
2. Kennedy T, Summer W. Inhibition of hypoxic pulmonary vasoconstriction by nifedipine. Am J Cardiol 1982;50:864-8. 3. Simmoneau G, Escourrou P, Duroux P, Lockhart A. Inhibitor of hypoxic pulmonary vasoconstriction by nifedipine. N Engl J Med 1981;304:1582-85. 4. Prielipp R, Rosenthal M, Pearl R. Hemodynamic profile of prostaglandin E, isoproterenol, prostacyclin, and nifedipine in vasoconstrictor pulmonary hypertension in sheep. Anesth Analg 1988;67722-9. 5. Berisha S. Acute hemodynamic effects of nifedipine in patients with ventricular septa1 defect. Br Heart J 1988;60:149-55. 6. Brownlee J, Beekman R, Rosenthal A. Acute hemodynamic effects of nifedipine in infants with bronchopulmonary dysplasia and pulmonary hypertension. Pediatr Res 1988;24: 186-90. 7. Rozkovec A. Prediction of favorable responses to long term vasodilator treatment of pulmonary hypertension by short term administration of epoprostenof or nifedipine. Br Heart J 1988;59:696-705. 8. Wimmer M. Experience with long-term nifedipine therapy in paediatric cardiologicalpatients. Padiatr Padol1990;25:181-93.
We report the successful use of nifedipine in the treatment of acute pulmonary hypertension in an infant after a cardiac operation. This patient had undergone total surgical correction of his truncus arteriosus malformation. He had signs of severe pulmonary artery hypertension unresponsive to hyperventilation, oxygenation, se-
dation, and a myriad of vasodilators. Nifedipine, 0.2 mg/kg every 4 hours, effectively treated his pulmonary artery hypertension and allowed for a smooth postoperative course and positive outcome.
P
intubated using pancuronium bromide (Pavulon; Organon Inc, West Orange, NJ) for neuromuscular blockade. Invasive monitoring consisted of a right femoral arterial line and a double-lumen right internal jugular vein. Maintenance anesthesia was provided with incremental boluses of fentanyl for a total of 65 pgkg. The operation was performed with the patient on hypothermic cardiopulmonary bypass at periods of low flow and consisted of patch closure of the ventriculoseptal defect and truncus repair using a pulmonic homograft. At the completion of the operation, a left atrial and a pulmonary arterial line were placed by the surgeon. The patient was weaned off cardiopulmonary bypass on infusions of 10 p g kg-' min-' of dopamine and 5 pg kg-' min-' of amrinone. In anticipation of pulmonary hypertension in the postoperative period, a dose of 10 pgkg of fentanyl was given to the patient before transport to the intensive care unit. In the immediate postoperative period, the pulmonary artery pressures ranged from 25% to 30% of the systemic pressure. During the night of operation, the patient was hyperventilated with 100% 0, to maintain arterial CO, levels between 20 and 25 mm Hg. The patient continued to receive fentanyl, 10 pg . kg-' . h-'. When the pulmonary artery pressures began to increase to approximately 50% of the systemic pressures, vasoactive drugs were used to manipulate the pulmonary artery pressures. The dosage of dopamine was lowered to 4 pg kg-' min-', and amrinone administration was continued at 5 pg kg-' . min-'. Prostaglandins were given at a dose of 0.05 pg . kg-' . min-' through the pulmonary artery catheter, a n d the dose was increased to 0 . 1 p g kg-' min-'. Nitroglycerin was added at a dose of 1 pg kg-' . min-'. Using these drugs, the systemic pressures remained stable and the pulmonary artery pressures decreased from 30% to 50% systemic. That evening, the patient had stable vital signs and a urine output of 2 to 3 mL . kg-' * h-'. On the first postoperative day, the pulmonary artery pressures began to rise to 60% systemic. Elevations in
ulmonary hypertension is a serious cause of morbidity and mortality after surgical correction of congenital heart defects. Postoperative pulmonary hypertension is likely to develop in infants who have excessive pulmonary blood flow or pulmonary venous obstruction. Elevated pulmonary resistance may occur as a result of this pulmonary vascular overload. The high pulmonary resistance may impose an impedance load on the right ventricle, causing it to fail and, through its interdependence with the left ventricle, produce a low cardiac output state. The decreased systemic pressure lowers coronary perfusion and a vicious cycle of biventricular failure may ensue. Oxygen, hyperventilation, alkalinization, and sedation are the mainstays of therapy for pulmonary hypertension in infants [l].The lack of specific pulmonary vasodilators makes management of postoperative pulmonary hypertension difficult. If nonspecific vasodilators are used to lower pulmonary vascular pressure, systemic pressure may be simultaneously lowered, negatively affecting coronary perfusion to a hypertensive right ventricle. We report the successful use of the calcium channel blocker nifedipine to treat pulmonary hypertension without affecting systemic pressure. A 4-month-old male infant with Type 1 truncus arteriosus underwent complete repair of his cardiac lesion. He had first been seen at the age of 3 months with a history of poor weight gain, tachypnea, and failure to thrive. Diagnosis was made by cardiac catheterization and he was placed on a regimen of digoxin and furosemide (Lasix; Hoechst-Roussel Pharmaceuticals, Somerville, NJ). The patient was brought to the operating room and noninvasive monitors were placed. Anesthesia was induced with nitrous oxide, oxygen, and 0.5% halothane. Venous access was obtained and he was nasotracheally Accepted for publication June 24, 1991. Address reprint requests to Dr Davis, Pediatric Heart Institute, St. Christopher's Hospital for Children, Erie Ave at Front St, Philadelphia, PA 19134-1095.
0 1992 by The Society of Thoracic Surgeons
(Ann Thorac Surg 1992;53:148-50)
-
0003-4975/92/$3.50
CASE REPORT DAVIS AND RUSSO NIFEDIPINE IN PULMONARY HYPERTENSION
Ann Thorac Surg 1992;53:14a50
systemic pressure. Nitroglycerin ointment was substituted for nitroglycerin. By the fifth postoperative day, the patient had no further episodes of pulmonary hypertension, he was further weaned from the drugs, and he was discharged home 2 weeks later, receiving 3 cm of nitroglycerin ointment every 3 hours.
HR
120 30 11:45
12:w
149
12:15 \
I
Comment
-20 11:45
DAD S
"1
12:w
12:lS
12:w
12:15
A h
- 1 PAP D
'
11:45
A
'
Nihdlplne
Fig 1 . Simultaneous measurements of heart rate (HR), arterial blood pressure (ABP), and pulmonary artery pressure (PAP). (D = diastolic; M = mean; S = systolic.)
pulmonary artery pressure occurred in response to tracheal suctioning and spontaneously without a precipitating event. The fentanyl infusion was increased to 50 pg kg-' h-' and the patient was further sedated with chloral hydrate and midazolam. Arterial carbon dioxide tension was kept in the range of 20 to 25 mm Hg. Arterial oxygen tension was kept greater than 200 mm Hg. Despite these pharmacologic manipulations, the patient's pulmonary artery pressures continued to rise and approached systemic pressures. Nifedipine, 0.2 mgkg every 6 hours through the nasogastric tube, was given. The nifedipine was aspirated from a 10-mg capsule and diluted to a concentration of 1 mg/mL. The pulmonary artery pressures decreased by 50% with no impact on the systemic pressures, as shown in Figure 1.Throughout the evening, it later became necessary to increase the nifedipine dosing interval to every 4 hours to keep the pulmonary artery pressures less than 50%of the systemic pressure. On the second postoperative day, the patient would intermittently have a pulmonary hypertensive crisis as evidenced by pulmonary artery pressures that became 60% systemic. The nifedipine dose was increased to 0.5 mgkg every 4 hours, and the prostaglandin infusion was increased to 0.15 pg kg-' min-'. Captopril was added at a dose of 2.5 mg three times a day through the nasogastric tube. On the third postoperative day, the patient was weaned off dopamine and nitroglycerin. He continued to receive captopril, nifedipine, prostaglandin, and fentanyl infusion while we continued to monitor pulmonary and
-
Postoperative pulmonary hypertension with right ventricular failure is a particular problem in infants with increased pulmonary blood flow. Large systemic to pulmonary artery shunts occur in a variety of congenital heart defects including ventriculoseptal defects, transposition of the great vessels, atrioventricular canal, or truncus arteriosus. In other congenital defects such as mitral stenosis, cor triatriatum, and obstructed pulmonary veins, pulmonary hypertension is secondary to elevated pulmonary venous pressure. Pulmonary hypertension may complicate the postoperative course of patients with these defects despite adequate surgical repair [l]. A pulmonary hypertensive crisis is characterized by a rapid rise in pulmonary artery pressure. These episodes may occur randomly or may be triggered by specific factors such as agitation or tracheal suctioning. The elevated pulmonary artery pressures strain the right ventricle and, if left untreated, can evolve to ventricular failure and death. Often the pulmonary crisis can be effectively treated with oxygen, hyperventilation, and sedation. When these therapies do not suffice, vasoactive drugs such as tolazine hydrochloride (Priscoline; CIBA Pharmaceutical Co, Summit, NJ), prostaglandin, or prostacycline are added. An ideal drug for the treatment of acute pulmonary hypertension would act selectively on the pulmonary vasculature, increasing cardiac output with minimal effects on systemic pressures or the relationship between ventilation and pulmonary perfusion. Nifedipine inhibits the transmembrane influx of extracellular calcium ions across myocardial and vascular smooth muscle cells, thereby promoting vasodilatation. As a pulmonary vasodilator, nifedipine may act locally within the lung vasculature or indirectly through the sympathetic nervous system, inhibiting hypoxic vasoconstriction [2]. Changes in vascular resistance induced by nifedipine are inversely related to the degree of arterial hypoxemia [3]. Nifedipine's efficacy as a selective pulmonary vasodilator is controversial. Prielipp and associates [4], studying the hemodynamic effects of a variety of vasodilators, found nifedipine to decrease systemic pressure more than pulmonary pressure. Other investigators refute this, showing that pulmonary artery pressures and resistance are preferentially reduced, particularly in adults and children with chronic obstructive lung disease and cor pulmonale [5-71. Nifedipine has been proven beneficial in children, in whom chronic administration lowered pulmonary artery resistance, increased pulmonary performance, and produced subjective improvement [8].Less is known about acute postoperative pulmonary vasculature effects of nifedipine in children. The only
150
CASE REPORT DAVIS AND RUSSO NIFEDIPINE IN PULMONARY HYPERTENSION
generalization that can be made regarding nifedipine as a pulmonary vasodilator is that patient response is variable. In the case we report, nifedipine exhibited the properties of an ideal pulmonary vasodilator: it selectively lowered pulmonary artery pressure yet preserved systemic pressure and, indirectly, coronary perfusion, thus improving cardiac function. Nifedipine should be considered a therapeutic option in the treatment of acute postoperative pulmonary hypertension in children.
Addendum Since the submission of this report, 6 additional patients with pulmonary hypertension after cardiac surgical repair were treated with nifedipine with good results. Nifedipine is currently the pulmonary vasodilator of choice at our institution.
References 1. Hickey PR, Hansen DD. Pulmonary hypertension in infants: postoperative management. In: Yacoub M, ed. Annual of cardiac surgery. Philadelphia: Current Science, 1989:16-22.
Ann Thorac Surg 1992~53: 14S50
2. Kennedy T, Summer W. Inhibition of hypoxic pulmonary vasoconstriction by nifedipine. Am J Cardiol 1982;50:864-8. 3. Simmoneau G, Escourrou P, Duroux P, Lockhart A. Inhibitor of hypoxic pulmonary vasoconstriction by nifedipine. N Engl J Med 1981;304:1582-85. 4. Prielipp R, Rosenthal M, Pearl R. Hemodynamic profile of prostaglandin E, isoproterenol, prostacyclin, and nifedipine in vasoconstrictor pulmonary hypertension in sheep. Anesth Analg 1988;67722-9. 5. Berisha S. Acute hemodynamic effects of nifedipine in patients with ventricular septa1 defect. Br Heart J 1988;60:149-55. 6. Brownlee J, Beekman R, Rosenthal A. Acute hemodynamic effects of nifedipine in infants with bronchopulmonary dysplasia and pulmonary hypertension. Pediatr Res 1988;24: 186-90. 7. Rozkovec A. Prediction of favorable responses to long term vasodilator treatment of pulmonary hypertension by short term administration of epoprostenof or nifedipine. Br Heart J 1988;59:696-705. 8. Wimmer M. Experience with long-term nifedipine therapy in paediatric cardiologicalpatients. Padiatr Padol1990;25:181-93.
