E Clinical Care
Anesthesia for Potts Shunt in a Child with Severe Refractory Idiopathic Pulmonary Arterial Hypertension Ashley Eggers, MD,* Gregory J. Latham, MD,* Jeremy Geiduschek, MD,* Delphine Yung, MD,† Jonathan M. Chen, MD,‡ and Denise C. Joffe, MD* Childhood idiopathic pulmonary arterial hypertension is a progressive and fatal disease. When pulmonary artery pressures become suprasystemic and refractory to medical management, atrial septostomy can be recommended for bridging patients to lung transplantation. Recently, a surgical Potts shunt has been recommended as an alternative rescue therapy, and initial outcome data are promising. The placement of a Potts shunt converts the child to Eisenmenger physiology, which is anticipated to provide an improved quality and duration of life. We present the first description of anesthetic management of a child undergoing surgical Potts shunt for pulmonary arterial hypertension and summarize the multiple, unique intraoperative considerations. (A&A Case Reports. 2016;6:56–60.)
I
diopathic pulmonary arterial hypertension (IPAH) is an uncommon but progressive and fatal disease in children. Natural progression of the disease leads to increasing pulmonary vascular resistance (PVR), right ventricular (RV) failure, and death. Although the advent of specific pulmonary vasodilator medical therapy in the past decade has increased survival at the time of diagnosis from months to years, the mortality rate remains high, with an estimated 5-year survival of approximately 74% in the pediatric population.1 Adult studies have shown that Eisenmenger syndrome carries a significantly increased life expectancy compared with the poor prognosis of IPAH.2 The former have pulmonary arterial hypertension (PAH) as a result of a long-standing cardiac shunt, and the improved life expectancy likely results from the ability of the RV to decompress into the systemic circulation through a right-to-left shunt. First described in 1946, a Potts shunt is a surgically created window between the left pulmonary artery and the descending aorta. It was used to provide needed pulmonary blood flow in children with certain forms of cyanotic congential heart disease such as pulmonary atresia and tetralogy of Fallot. Other methods of creating more regulated pulmonary blood flow for surgical palliation of cyanotic heart disease became more common, and the frequency of Potts shunt placement has since declined. In a 2004 letter, Blanc et al.3 first reported use of the Potts shunt to palliate 2 children with IPAH, which has sparked interest in several centers to resume use of the Potts shunt. Rather than providing blood flow to the lungs in a left-to-right manner, blood flows from the higher pressure pulmonary artery to the lower pressure aorta in a right-to-left manner. In the setting of suprasystemic pulmonary artery pressures (PAPs), From the Departments of *Anesthesiology and Pain Medicine, †Pediatric Cardiology, and ‡Pediatric Cardiovascular Surgery, Seattle Children’s Hospital, University of Washington, Seattle, Washington. Accepted for publication August 19, 2015. Funding: None. The authors declare no conflicts of interest. Address correspondence to Ashley Eggers, MD, Department of Anesthesiology and Pain Medicine, Seattle Children’s Hospital, University of Washington, MB.11.500, Sand Point Way NE, Seattle, WA 98105. Address e-mail to [email protected]. Copyright © 2015 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000268
56 cases-anesthesia-analgesia.org
the shunt serves as a pop-off from the pressure-loaded RV into the systemic circulation, thus improving RV function (Fig. 1). This partially mimics Eisenmenger physiology and can serve as a means of maintaining systemic circulation during an acute pulmonary hypertensive crisis, the major cause of sudden mortality in patients with IPAH. The application of a Potts shunt as an alternative means of palliation of IPAH can possibly serve as a long-term alternative to either balloon atrial septostomy (BAS) or lung transplantation, the current options for end-stage IPAH. Long-term outcome data are still limited; however, early reports of Potts shunt for this patient population have shown encouraging results.4 We report the first description of anesthetic management of a child undergoing surgical placement of a Potts shunt for the treatment of advanced IPAH.
CONSENT FOR PUBLICATION
The patient’s family provided written permission for publication of this report.
CASE DESCRIPTION
A 7-year-old girl weighing 25 kg with severe IPAH presented for surgical Potts shunt. She was asymptomatic until age 3 years when she developed dyspnea and exertional chest pain. Cardiac catheterization confirmed IPAH, which was nonresponsive to nitric oxide and minimally responsive to oxygen. This procedure was complicated by pulmonary hypertensive crises and cardiac arrest requiring chest compressions. She underwent emergent BAS. Sildenafil, warfarin, and epoprostenol therapy was initiated. Over the next 4 years, she exhibited increased fatigue and escalating right-sided heart pressures, despite multidrug therapy. At 7 years of age, she began having episodes of dizziness and syncope (New York Heart Association class IV heart failure). Because of increasing cyanosis, repeat cardiac catheterization was performed and was remarkable for suprasystemic PAP, severe RV dilation, and hypertrophy with mildly decreased RV function (Fig. 2). The decision was made to proceed with the Potts shunt. At the time of surgery, her IPAH medication therapy included epoprostenol, bosentan, and tadalafil. Warfarin had been discontinued 2 months earlier in the setting of bruising and thrombocytopenia, and she was not chronically February 1, 2016 • Volume 6 • Number 3
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Figure 1. Schematic of this patient’s heart after the Potts shunt. The Potts shunt directs flow from the left pulmonary artery down the descending aorta. Note that the most oxygenated blood is directed to the upper body, and more deoxygenated blood crosses the Potts shunt to the lower body. The previous atrial septostomy is also seen. IVC = inferior vena cava; LA = left atrium; LPA = left pulmonary artery; LPV = left pulmonary vein; LV = left ventricle; MPA = main pulmonary artery; RA = right atrium; RPA = right pulmonary artery; RPV = right pulmonary vein; RV = right ventricle; SVC = superior vena cava.
anticoagulated at the time of surgery. She did not require home oxygen. Her preinduction vital signs were Spo2 95% on room air, arterial blood pressure 107/55, heart rate 91 beats per minute, and respiratory rate 23 bpm. She was very apprehensive at the possibility of IV placement while awake. After placement of routine monitors, the patient had a very slowly titrated sevoflurane induction with concurrent placement of a peripheral IV catheter. Her trachea was intubated, and a left bronchial blocker was placed. Cerebral and renal near-infrared spectroscopy (NIRS), upper and lower extremity pulse oximeters, a right radial arterial line, a central venous catheter, and a transesophageal echocardiography (TEE) probe were placed before incision. Anesthesia was maintained with isoflurane and high-dose fentanyl. Her epoprostenol infusion was continued, and 40 ppm nitric oxide was prophylactically started. The operation was performed through a left thoracotomy without cardiopulmonary bypass. She remained hemodynamically stable during the dissection and single-lung ventilation with ventilation variables carefully adjusted to maintain baseline values of oxygenation and ventilation. After heparin administration, an aortic side clamp was placed for 25 minutes, while a 10-mm interposition graft was placed between the left pulmonary artery and descending aorta. A graft, rather than direct anastomosis, was necessary to bridge the distance between both arteries. A blood gas analysis on single-lung ventilation
February 1, 2016 • Volume 6 • Number 3
Figure 2. A, Midesophageal 4-chamber view in diastole and (B) modified transgastric short-axis view in systole taken at the time of the Potts shunt. The right ventricular apex is equal to or slightly larger than the left ventricular apex, and there is significant right ventricular hypertrophy and flattening of the interventricular septum in diastole (A) and systole (B), consistent with a volume and pressure-loaded right ventricle. CVP = central venous pressure = 19 mm Hg.
after placement of the aortic side clamp showed pH 7.23, Paco2 59, Pao2 47, base excess −3.3, and hematocrit 31%. Ventilation was adequately adjusted. With aortic clamp release, her systolic blood pressure decreased to the mid 80s, and ST segment changes were noted, which were treated with phenylephrine boluses and initiation of a norepinephrine infusion. Once stabilized, the cerebral NIRS increased to 70 to 75 (65–70 preshunt), renal NIRS decreased to 50 to 58 (60–70 preshunt), and central venous pressure decreased to 16 to 22 mm Hg (20–30 preshunt). TEE demonstrated a patent shunt with right-to-left flow from the pulmonary artery into the descending aorta (Figs. 3–5). Continuous wave Doppler velocity across the right-to-left shunt was 2.8 m/s (Fig. 5), and RV function appeared mildly improved. These clinical and echocardiographic variables indicated appropriate RV decompression across the Potts shunt. One unit of packed red blood cells and a unit of platelets were administered because of moderate bleeding. She was transported to the cardiac intensive care unit, remaining heavily sedated, intubated, and receiving 40 ppm nitric oxide. Infusions of epoprostenol, norepinephrine, and morphine were continued. Postoperatively, her upper and lower extremity oxygen saturations were 85% to 92% and 65% to 70%, respectively, while receiving 100% oxygen.
cases-anesthesia-analgesia.org
57
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Figure 3. Descending aortic long-axis color compare view. The descending aorta is visualized in the near field. The Potts shunt connects the pulmonary artery (not seen) and the descending aorta. On the right, the color flow Doppler image shows turbulent flow (multicolored jet) from the Potts shunt entering the descending aorta. Laminar, low velocity flow (red color) in the descending aorta proximal to the shunt is clearly seen. The direction of flow is right to left (pulmonary artery to aorta).
Figure 5. Continuous wave Doppler of Potts shunt in descending aorta long-axis view. High velocity flow from the Potts shunt into the descending aorta (right to left) is demonstrated. The peak measured velocity is 2.85 m/s.
pressures. In addition, a reversal to left-to-right flow across the atrial septal defect suggests improved RV diastolic function, and RV systolic function has remained qualitatively low normal. Laboratory values of hepatic and renal function remain excellent, negating acute concerns of chronic lower body cyanosis. Eventual atrial septal defect closure may be required to limit left-to-right atrial shunt and progressive RV dilation.
DISCUSSION
Figure 4. Pulse wave Doppler of the main pulmonary artery in midesophageal ascending aorta short-axis view. Forward (systolic) flow into the main pulmonary artery (asterisk) and abnormal diastolic flow reversal (arrow) is demonstrated. The flow reversal is caused by flow into the Potts shunt in diastole.
In the 24 hours after surgery, she remained hemodynamically stable despite continued bleeding per chest tube output and requiring transfusion of blood products. She returned to the operating room for exploratory thoracotomy, and 500 mL of clotted blood was evacuated with no evidence of surgical bleeding. She was tracheally extubated the second postoperative day and was supported with noninvasive ventilatory support for 5 days. She was discharged home on postoperative day 8 with an epoprostenol infusion, tadalafil, bosentan, and diuretics. Three months later, she reported significantly improved energy and activity levels consistent with New York Heart Association class I to II heart failure. Subsequent echocardiographic examinations have shown continued right-to-left shunt across the Potts shunt and systemic rather than suprasystemic RV
58 cases-anesthesia-analgesia.org
Among the first surgeries ever performed for congenital heart disease were palliative procedures to provide stable pulmonary blood flow in the setting of pulmonary stenosis or pulmonary atresia. After successful placement of a Blalock-Taussig shunt in 1944, Willis J. Potts reported successful palliation of 3 children with severe cyanosis through a descending aorta to left pulmonary artery shunt in 1946, the Potts shunt.5 The Waterston shunt (ascending aorta to the right pulmonary artery) was reported in 1962. As techniques for corrective repair of cyanotic lesions improved and the modified Blalock-Taussig shunt was introduced, the Potts and Waterston shunts became obsolete after recognizing that they often resulted in unpredictable and excessive pulmonary artery blood flow and early pulmonary vascular disease.6 However, on recognition that Eisenmenger physiology might confer improved survival compared with the natural course of IPAH, the Potts shunt has been recently reintroduced as a novel treatment option for children with severe IPAH failing maximal medical therapy.4,7,8 In the largest pediatric cohort studied of Potts shunt for IPAH, 3 of 24 children suffered early death.7 One death was intraoperative, and 2 children who had postoperative cessation of PAH vasodilator therapy died of a hypertensive crisis. The 21 survivors, all of whom had perioperative continuation of PAH therapy, improved to and remained World Health Organization functional class I or II. None had recurrence of syncope or RV failure, and all had dramatic improvement in their functional status at a median followup of 2 years (range, 3 months to 14 years).7
A & A case reports
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
The placement of a Potts shunt may thus be preferable to BAS as a first-step palliation while awaiting transplantation and potentially could prove to be preferable to transplantation. The challenges of lung transplantation include organ shortages in this age group and a median survival of only 45 months.9 BAS in severely symptomatic children can reduce the rate of syncope and improve quality of life by creating a right-to-left interatrial shunt, thus decreasing RV filling pressures and augmenting left ventricular filling. However, 3 issues relegate BAS as a short-term bridge to transplantation10,11: (1) periods of excessive right-to-left shunting resulting in severe hypoxemia, (2) a high incidence of spontaneous septal closure, and (3) the pretricuspid shunt does not allow RV decompression until the RV fails, and RV end-diastolic pressure exceeds that of the left ventricle. In contrast to BAS, a Potts shunt creates a permanent postcardiac right-to-left shunt for continuous RV decompression into the systemic circulation, a predictable degree of cyanosis, and has significantly less risk of spontaneous closure. Furthermore, a Potts shunt maintains highly oxygenated blood to the brain and myocardium and markedly reduces the risk of paradoxical cerebral emboli. The impact of potential long-term issues, such as creating chronic lower body cyanosis in young children, is not yet clear. There are numerous anesthetic considerations during evaluation and care of the child with PAH undergoing Potts shunt. Compared with the general population, anesthetizing children with severe PAH carries a significantly increased risk of cardiac arrest and death.12,13 Risk factors for overall mortality include syncope, progression of symptoms, failure to thrive, World Health Organization functional status III or IV, increased brain natriuretic peptide levels, severe RV enlargement or dysfunction, and mean PAP more than 3-quarters systemic.14 Risk factors for major complications under anesthesia in children with PAH include younger patient age, severity of PAH, longer procedure duration, leftward septal bowing on echocardiogram, and home oxygen therapy.13 Children with IPAH being considered for Potts shunt likely fulfill many or most of these risk factors for morbidity and mortality. Notably, children presenting for Potts shunt have suprasystemic RV pressures and risk for acute or chronic RV failure, placing them at the highest risk of children with PAH undergoing anesthesia. The key to managing anesthesia for these patients is an understanding of the underlying physiology of the child with IPAH and suprasystemic RV pressures. In the initial stages of the disease, the RV successfully adapts to the increased afterload with hypertrophy to maintain perfusion pressure of the pulmonary vasculature, thus maintaining cardiac output. Appropriate medical management often ameliorates symptoms for a time. As the disease progresses and PVR continues to increase, remodeling of the RV results in dilation, systolic and diastolic dysfunction, and eventual fibrosis.10 The RV struggles to adequately perfuse the pulmonary vasculature to ensure sufficient left ventricular preload and output, and a tenuous oxygen supply:demand relationship of the coronary circulation and RV is then reached. Either in the setting of an acute increase in RV afterload or low diastolic pressure at the aortic root, the RV is prone to sudden ischemia, acute failure, and cardiovascular collapse.
February 1, 2016 • Volume 6 • Number 3
The presumed benefit of surgical placement of a Potts shunt is to prevent this downward spiral. The aortopulmonary communication provides a “pop-off” in the setting of an acute increase in RV pressure, thus unloading the RV and preventing acute failure. Systemic perfusion is also maintained; if an acute increase in PVR limits left atrial filling and preload, accentuated right-to-left shunt occurs at the Potts shunt to preserve systemic and coronary perfusion, albeit at the expenses of systemic desaturation. With this physiology in mind, anesthetic care of these children must be meticulous. In short, anesthetic goals in children with severe PAH are to maintain cardiac contractility, cardiac output, systemic vascular resistance, and normal sinus rhythm while assiduously avoiding increases in PVR. Severely restrictive RV physiology mandates that sinus rhythm at a moderate rate be maintained to maximize ventricular filling. Mild hypertension is typically well tolerated, but hypotension must be avoided. Hypotension reduces coronary perfusion pressure to an already stressed RV, risking acute RV failure. Decreased left ventricular afterload may contribute to an increase in the leftward ventricular septal position, thus further limiting left ventricular function and coronary perfusion. A feared and potentially fatal complication during the anesthetic care of these children is a pulmonary hypertensive crisis, whereby an acute increase in PVR can culminate with acute RV failure and subsequent cardiovascular collapse. Hypoxia, hypercarbia, acidosis, and noxious stimuli under light anesthesia must be avoided to prevent any further increase in PVR. Any continuously infusing pulmonary vasodilators (e.g., prostacyclin analogs) must be continued uninterrupted, and inhaled nitric oxide should be immediately available or even prophylactically used for prevention and prompt treatment of a pulmonary hypertensive crisis. Cardiopulmonary bypass or extracorporeal life support should be readily available in the event of circulatory collapse during anesthesia induction or surgery. If conditions permit, an IV induction allows careful titration of anesthetic agents to maintain baseline physiologic variables. Vasoactive medications must be immediately available to treat hypotension. A high-dose opiate technique has the advantage of blunting noxious stimuli and subsequent increases in PAP and PVR during intubation and surgery. Standard monitors, arterial line, and central venous access should be placed. Placement of the arterial line in the right upper extremity allows measurement of preshunt Pao2 after the procedure. Preductal and postductal saturation probes are then placed to assess saturation variation after placement of the shunt. For the same reason, cerebral and renal NIRS can aid assessment of oxygen delivery. Regional anesthesia (e.g., paravertebral or epidural block) could arguably allow lower doses of other anesthetic agents and provide steady hemodynamics, but additional time under anesthesia, preexisting coagulopathy related to cyanosis, and possible hypotension from sympathectomy are valid concerns. The use of TEE allows continuous assessment of cardiac filling, acute increase of PAP, and evidence of RV dysfunction. One-lung ventilation is ideal for maximal surgical exposure and can be accomplished with multiple techniques. The possibility of acute deterioration during establishment
cases-anesthesia-analgesia.org
59
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
of lung isolation should be anticipated with a rescue plan in place. Management of 1-lung ventilation (or at least significant retraction and collapse of 1 lung) in a patient with suprasystemic PAP requires meticulous attention to ventilation goals. Compression or collapse of the lung decreases the cross-sectional area of the pulmonary vascular bed and thus substantially increases the PAP. Furthermore, a ventilation:perfusion mismatch results in worsening pulmonary venous desaturation and thus worsening hypoxia, hypercarbia, and acidosis. Ventilation management must be carefully and dynamically managed to achieve and maintain normoxia and normocapnia throughout surgery. Placement of the pulmonary and aortic clamps will increase afterload to the respective ventricles and may provoke hemodynamic instability. A test occlusion may be wise to assess tolerability. Removal of the aortic side clamp risks sudden and significant hypotension via several mechanisms. The side clamp can be removed slowly, and if poorly tolerated, digital compression or reclamping of the aorta may be required. Clear communication between surgeon and anesthesiologist is key before declamping. Vasopressor and inotropic medications should be immediately ready. As mentioned earlier, tachycardia must be avoided, and thus, the treatment should focus on vasoconstriction and then mild inotropic support as needed. Once the aortic side clamp is removed, it is helpful to perform a formal TEE assessment of the cardiac function, shunt flow, and RV and pulmonary pressures. Doppler measurements of the Potts shunt velocity can quantitate the pressure and provide an estimate of systolic PAP. If there is any tricuspid or pulmonary regurgitation on TEE, that can also help estimate systolic PAP and diastolic PAP, respectively. Preshunt and postshunt saturation measurements also quantify the degree of right-to-left shunt occurring at the level of the proximal descending aorta. Higher right heart pressures will cause greater right-to-left shunt and thus greater saturation differences between upper and lower extremities. In the same manner, the variation between cerebral and renal NIRS allows determination of adequate oxygen delivery to both tissue beds during this new physiology. Intraoperative and postoperative bleeding should be expected. In personal communication with other centers, the rate of intraoperative bleeding and return to the operating room for reexploration is very high. More than normal bleeding should be expected because of cyanosis-induced coagulopathy, prostacyclin-induced platelet dysfunction, and highly pressurized arterial and venous vasculature.10 In conclusion, the results of early outcome data have caused some to suggest that Potts shunt may be preferable to BAS and preferable to lung transplantation in children with severe, drug refractory IPAH.7 Anesthetic care of these fragile children undergoing Potts shunt requires that the anesthesiologist inherently understands the child’s physiology and be prepared to quickly and effectively manage the intraoperative dynamic cardiopulmonary changes. E
60 cases-anesthesia-analgesia.org
REFERENCES 1. Barst RJ, McGoon MD, Elliott CG, Foreman AJ, Miller DP, Ivy DD. Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation 2012;125:113–22 2. Hopkins WE, Ochoa LL, Richardson GW, Trulock EP. Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome. J Heart Lung Transplant 1996;15:100–5 3. Blanc J, Vouhé P, Bonnet D. Potts shunt in patients with pulmonary hypertension. N Engl J Med 2004;350:623 4. Baruteau AE, Serraf A, Lévy M, Petit J, Bonnet D, Jais X, Vouhé P, Simonneau G, Belli E, Humbert M. Potts shunt in children with idiopathic pulmonary arterial hypertension: long-term results. Ann Thorac Surg 2012;94:817–24 5. Potts WJ, Smith S, Gibson S. Anastomosis of the aorta to a pulmonary artery; certain types in congenital heart disease. J Am Med Assoc 1946;132:627–31 6. Murphy JG, Gersh BJ, Mair DD, Fuster V, McGoon MD, Ilstrup DM, McGoon DC, Kirklin JW, Danielson GK. Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot. N Engl J Med 1993;329:593–9 7. Baruteau AE, Belli E, Boudjemline Y, Laux D, Lévy M, Simonneau G, Carotti A, Humbert M, Bonnet D. Palliative Potts shunt for the treatment of children with drug-refractory pulmonary arterial hypertension: updated data from the first 24 patients. Eur J Cardiothorac Surg 2015;47:e105–10 8. Labombarda F, Maragnes P, Dupont-Chauvet P, Serraf A. Potts anastomosis for children with idiopathic pulmonary hypertension. Pediatr Cardiol 2009;30:1143–5 9. Schaellibaum G, Lammers AE, Faro A, Moreno-Galdo A, Parakininkas D, Schecter MG, Solomon M, Boyer D, Conrad C, Frischer T, Wong J, Boehler A, Benden C. Bilateral lung transplantation for pediatric idiopathic pulmonary arterial hypertension: a multi-center experience. Pediatr Pulmonol 2011;46:1121–7 10. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, Harrington RA, Anderson JL, Bates ER, Bridges CR, Eisenberg MJ, Ferrari VA, Grines CL, Hlatky MA, Jacobs AK, Kaul S, Lichtenberg RC, Lindner JR, Moliterno DJ, Mukherjee D, Pohost GM, Rosenson RS, Schofield RS, Shubrooks SJ, Stein JH, Tracy CM, Weitz HH, Wesley DJ; ACCF/AHA. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 2009;119:2250–94 11. Micheletti A, Hislop AA, Lammers A, Bonhoeffer P, Derrick G, Rees P, Haworth SG. Role of atrial septostomy in the treatment of children with pulmonary arterial hypertension. Heart 2006;92:969–72 12. Carmosino MJ, Friesen RH, Doran A, Ivy DD. Perioperative complications in children with pulmonary hypertension undergoing noncardiac surgery or cardiac catheterization. Anesth Analg 2007;104:521–7 13. Taylor K, Moulton D, Zhao XY, Laussen P. The impact of targeted therapies for pulmonary hypertension on pediatric intraoperative morbidity or mortality. Anesth Analg 2015;120:420–6 14. Ivy DD, Abman SH, Barst RJ, Berger RM, Bonnet D, Fleming TR, Haworth SG, Raj JU, Rosenzweig EB, Schulze Neick I, Steinhorn RH, Beghetti M. Pediatric pulmonary hypertension. J Am Coll Cardiol 2013;62:D117–26
A & A case reports
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Anesthesia for Potts Shunt in a Child with Severe Refractory Idiopathic Pulmonary Arterial Hypertension Ashley Eggers, MD,* Gregory J. Latham, MD,* Jeremy Geiduschek, MD,* Delphine Yung, MD,† Jonathan M. Chen, MD,‡ and Denise C. Joffe, MD* Childhood idiopathic pulmonary arterial hypertension is a progressive and fatal disease. When pulmonary artery pressures become suprasystemic and refractory to medical management, atrial septostomy can be recommended for bridging patients to lung transplantation. Recently, a surgical Potts shunt has been recommended as an alternative rescue therapy, and initial outcome data are promising. The placement of a Potts shunt converts the child to Eisenmenger physiology, which is anticipated to provide an improved quality and duration of life. We present the first description of anesthetic management of a child undergoing surgical Potts shunt for pulmonary arterial hypertension and summarize the multiple, unique intraoperative considerations. (A&A Case Reports. 2016;6:56–60.)
I
diopathic pulmonary arterial hypertension (IPAH) is an uncommon but progressive and fatal disease in children. Natural progression of the disease leads to increasing pulmonary vascular resistance (PVR), right ventricular (RV) failure, and death. Although the advent of specific pulmonary vasodilator medical therapy in the past decade has increased survival at the time of diagnosis from months to years, the mortality rate remains high, with an estimated 5-year survival of approximately 74% in the pediatric population.1 Adult studies have shown that Eisenmenger syndrome carries a significantly increased life expectancy compared with the poor prognosis of IPAH.2 The former have pulmonary arterial hypertension (PAH) as a result of a long-standing cardiac shunt, and the improved life expectancy likely results from the ability of the RV to decompress into the systemic circulation through a right-to-left shunt. First described in 1946, a Potts shunt is a surgically created window between the left pulmonary artery and the descending aorta. It was used to provide needed pulmonary blood flow in children with certain forms of cyanotic congential heart disease such as pulmonary atresia and tetralogy of Fallot. Other methods of creating more regulated pulmonary blood flow for surgical palliation of cyanotic heart disease became more common, and the frequency of Potts shunt placement has since declined. In a 2004 letter, Blanc et al.3 first reported use of the Potts shunt to palliate 2 children with IPAH, which has sparked interest in several centers to resume use of the Potts shunt. Rather than providing blood flow to the lungs in a left-to-right manner, blood flows from the higher pressure pulmonary artery to the lower pressure aorta in a right-to-left manner. In the setting of suprasystemic pulmonary artery pressures (PAPs), From the Departments of *Anesthesiology and Pain Medicine, †Pediatric Cardiology, and ‡Pediatric Cardiovascular Surgery, Seattle Children’s Hospital, University of Washington, Seattle, Washington. Accepted for publication August 19, 2015. Funding: None. The authors declare no conflicts of interest. Address correspondence to Ashley Eggers, MD, Department of Anesthesiology and Pain Medicine, Seattle Children’s Hospital, University of Washington, MB.11.500, Sand Point Way NE, Seattle, WA 98105. Address e-mail to [email protected]. Copyright © 2015 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000268
56 cases-anesthesia-analgesia.org
the shunt serves as a pop-off from the pressure-loaded RV into the systemic circulation, thus improving RV function (Fig. 1). This partially mimics Eisenmenger physiology and can serve as a means of maintaining systemic circulation during an acute pulmonary hypertensive crisis, the major cause of sudden mortality in patients with IPAH. The application of a Potts shunt as an alternative means of palliation of IPAH can possibly serve as a long-term alternative to either balloon atrial septostomy (BAS) or lung transplantation, the current options for end-stage IPAH. Long-term outcome data are still limited; however, early reports of Potts shunt for this patient population have shown encouraging results.4 We report the first description of anesthetic management of a child undergoing surgical placement of a Potts shunt for the treatment of advanced IPAH.
CONSENT FOR PUBLICATION
The patient’s family provided written permission for publication of this report.
CASE DESCRIPTION
A 7-year-old girl weighing 25 kg with severe IPAH presented for surgical Potts shunt. She was asymptomatic until age 3 years when she developed dyspnea and exertional chest pain. Cardiac catheterization confirmed IPAH, which was nonresponsive to nitric oxide and minimally responsive to oxygen. This procedure was complicated by pulmonary hypertensive crises and cardiac arrest requiring chest compressions. She underwent emergent BAS. Sildenafil, warfarin, and epoprostenol therapy was initiated. Over the next 4 years, she exhibited increased fatigue and escalating right-sided heart pressures, despite multidrug therapy. At 7 years of age, she began having episodes of dizziness and syncope (New York Heart Association class IV heart failure). Because of increasing cyanosis, repeat cardiac catheterization was performed and was remarkable for suprasystemic PAP, severe RV dilation, and hypertrophy with mildly decreased RV function (Fig. 2). The decision was made to proceed with the Potts shunt. At the time of surgery, her IPAH medication therapy included epoprostenol, bosentan, and tadalafil. Warfarin had been discontinued 2 months earlier in the setting of bruising and thrombocytopenia, and she was not chronically February 1, 2016 • Volume 6 • Number 3
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Figure 1. Schematic of this patient’s heart after the Potts shunt. The Potts shunt directs flow from the left pulmonary artery down the descending aorta. Note that the most oxygenated blood is directed to the upper body, and more deoxygenated blood crosses the Potts shunt to the lower body. The previous atrial septostomy is also seen. IVC = inferior vena cava; LA = left atrium; LPA = left pulmonary artery; LPV = left pulmonary vein; LV = left ventricle; MPA = main pulmonary artery; RA = right atrium; RPA = right pulmonary artery; RPV = right pulmonary vein; RV = right ventricle; SVC = superior vena cava.
anticoagulated at the time of surgery. She did not require home oxygen. Her preinduction vital signs were Spo2 95% on room air, arterial blood pressure 107/55, heart rate 91 beats per minute, and respiratory rate 23 bpm. She was very apprehensive at the possibility of IV placement while awake. After placement of routine monitors, the patient had a very slowly titrated sevoflurane induction with concurrent placement of a peripheral IV catheter. Her trachea was intubated, and a left bronchial blocker was placed. Cerebral and renal near-infrared spectroscopy (NIRS), upper and lower extremity pulse oximeters, a right radial arterial line, a central venous catheter, and a transesophageal echocardiography (TEE) probe were placed before incision. Anesthesia was maintained with isoflurane and high-dose fentanyl. Her epoprostenol infusion was continued, and 40 ppm nitric oxide was prophylactically started. The operation was performed through a left thoracotomy without cardiopulmonary bypass. She remained hemodynamically stable during the dissection and single-lung ventilation with ventilation variables carefully adjusted to maintain baseline values of oxygenation and ventilation. After heparin administration, an aortic side clamp was placed for 25 minutes, while a 10-mm interposition graft was placed between the left pulmonary artery and descending aorta. A graft, rather than direct anastomosis, was necessary to bridge the distance between both arteries. A blood gas analysis on single-lung ventilation
February 1, 2016 • Volume 6 • Number 3
Figure 2. A, Midesophageal 4-chamber view in diastole and (B) modified transgastric short-axis view in systole taken at the time of the Potts shunt. The right ventricular apex is equal to or slightly larger than the left ventricular apex, and there is significant right ventricular hypertrophy and flattening of the interventricular septum in diastole (A) and systole (B), consistent with a volume and pressure-loaded right ventricle. CVP = central venous pressure = 19 mm Hg.
after placement of the aortic side clamp showed pH 7.23, Paco2 59, Pao2 47, base excess −3.3, and hematocrit 31%. Ventilation was adequately adjusted. With aortic clamp release, her systolic blood pressure decreased to the mid 80s, and ST segment changes were noted, which were treated with phenylephrine boluses and initiation of a norepinephrine infusion. Once stabilized, the cerebral NIRS increased to 70 to 75 (65–70 preshunt), renal NIRS decreased to 50 to 58 (60–70 preshunt), and central venous pressure decreased to 16 to 22 mm Hg (20–30 preshunt). TEE demonstrated a patent shunt with right-to-left flow from the pulmonary artery into the descending aorta (Figs. 3–5). Continuous wave Doppler velocity across the right-to-left shunt was 2.8 m/s (Fig. 5), and RV function appeared mildly improved. These clinical and echocardiographic variables indicated appropriate RV decompression across the Potts shunt. One unit of packed red blood cells and a unit of platelets were administered because of moderate bleeding. She was transported to the cardiac intensive care unit, remaining heavily sedated, intubated, and receiving 40 ppm nitric oxide. Infusions of epoprostenol, norepinephrine, and morphine were continued. Postoperatively, her upper and lower extremity oxygen saturations were 85% to 92% and 65% to 70%, respectively, while receiving 100% oxygen.
cases-anesthesia-analgesia.org
57
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Figure 3. Descending aortic long-axis color compare view. The descending aorta is visualized in the near field. The Potts shunt connects the pulmonary artery (not seen) and the descending aorta. On the right, the color flow Doppler image shows turbulent flow (multicolored jet) from the Potts shunt entering the descending aorta. Laminar, low velocity flow (red color) in the descending aorta proximal to the shunt is clearly seen. The direction of flow is right to left (pulmonary artery to aorta).
Figure 5. Continuous wave Doppler of Potts shunt in descending aorta long-axis view. High velocity flow from the Potts shunt into the descending aorta (right to left) is demonstrated. The peak measured velocity is 2.85 m/s.
pressures. In addition, a reversal to left-to-right flow across the atrial septal defect suggests improved RV diastolic function, and RV systolic function has remained qualitatively low normal. Laboratory values of hepatic and renal function remain excellent, negating acute concerns of chronic lower body cyanosis. Eventual atrial septal defect closure may be required to limit left-to-right atrial shunt and progressive RV dilation.
DISCUSSION
Figure 4. Pulse wave Doppler of the main pulmonary artery in midesophageal ascending aorta short-axis view. Forward (systolic) flow into the main pulmonary artery (asterisk) and abnormal diastolic flow reversal (arrow) is demonstrated. The flow reversal is caused by flow into the Potts shunt in diastole.
In the 24 hours after surgery, she remained hemodynamically stable despite continued bleeding per chest tube output and requiring transfusion of blood products. She returned to the operating room for exploratory thoracotomy, and 500 mL of clotted blood was evacuated with no evidence of surgical bleeding. She was tracheally extubated the second postoperative day and was supported with noninvasive ventilatory support for 5 days. She was discharged home on postoperative day 8 with an epoprostenol infusion, tadalafil, bosentan, and diuretics. Three months later, she reported significantly improved energy and activity levels consistent with New York Heart Association class I to II heart failure. Subsequent echocardiographic examinations have shown continued right-to-left shunt across the Potts shunt and systemic rather than suprasystemic RV
58 cases-anesthesia-analgesia.org
Among the first surgeries ever performed for congenital heart disease were palliative procedures to provide stable pulmonary blood flow in the setting of pulmonary stenosis or pulmonary atresia. After successful placement of a Blalock-Taussig shunt in 1944, Willis J. Potts reported successful palliation of 3 children with severe cyanosis through a descending aorta to left pulmonary artery shunt in 1946, the Potts shunt.5 The Waterston shunt (ascending aorta to the right pulmonary artery) was reported in 1962. As techniques for corrective repair of cyanotic lesions improved and the modified Blalock-Taussig shunt was introduced, the Potts and Waterston shunts became obsolete after recognizing that they often resulted in unpredictable and excessive pulmonary artery blood flow and early pulmonary vascular disease.6 However, on recognition that Eisenmenger physiology might confer improved survival compared with the natural course of IPAH, the Potts shunt has been recently reintroduced as a novel treatment option for children with severe IPAH failing maximal medical therapy.4,7,8 In the largest pediatric cohort studied of Potts shunt for IPAH, 3 of 24 children suffered early death.7 One death was intraoperative, and 2 children who had postoperative cessation of PAH vasodilator therapy died of a hypertensive crisis. The 21 survivors, all of whom had perioperative continuation of PAH therapy, improved to and remained World Health Organization functional class I or II. None had recurrence of syncope or RV failure, and all had dramatic improvement in their functional status at a median followup of 2 years (range, 3 months to 14 years).7
A & A case reports
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
The placement of a Potts shunt may thus be preferable to BAS as a first-step palliation while awaiting transplantation and potentially could prove to be preferable to transplantation. The challenges of lung transplantation include organ shortages in this age group and a median survival of only 45 months.9 BAS in severely symptomatic children can reduce the rate of syncope and improve quality of life by creating a right-to-left interatrial shunt, thus decreasing RV filling pressures and augmenting left ventricular filling. However, 3 issues relegate BAS as a short-term bridge to transplantation10,11: (1) periods of excessive right-to-left shunting resulting in severe hypoxemia, (2) a high incidence of spontaneous septal closure, and (3) the pretricuspid shunt does not allow RV decompression until the RV fails, and RV end-diastolic pressure exceeds that of the left ventricle. In contrast to BAS, a Potts shunt creates a permanent postcardiac right-to-left shunt for continuous RV decompression into the systemic circulation, a predictable degree of cyanosis, and has significantly less risk of spontaneous closure. Furthermore, a Potts shunt maintains highly oxygenated blood to the brain and myocardium and markedly reduces the risk of paradoxical cerebral emboli. The impact of potential long-term issues, such as creating chronic lower body cyanosis in young children, is not yet clear. There are numerous anesthetic considerations during evaluation and care of the child with PAH undergoing Potts shunt. Compared with the general population, anesthetizing children with severe PAH carries a significantly increased risk of cardiac arrest and death.12,13 Risk factors for overall mortality include syncope, progression of symptoms, failure to thrive, World Health Organization functional status III or IV, increased brain natriuretic peptide levels, severe RV enlargement or dysfunction, and mean PAP more than 3-quarters systemic.14 Risk factors for major complications under anesthesia in children with PAH include younger patient age, severity of PAH, longer procedure duration, leftward septal bowing on echocardiogram, and home oxygen therapy.13 Children with IPAH being considered for Potts shunt likely fulfill many or most of these risk factors for morbidity and mortality. Notably, children presenting for Potts shunt have suprasystemic RV pressures and risk for acute or chronic RV failure, placing them at the highest risk of children with PAH undergoing anesthesia. The key to managing anesthesia for these patients is an understanding of the underlying physiology of the child with IPAH and suprasystemic RV pressures. In the initial stages of the disease, the RV successfully adapts to the increased afterload with hypertrophy to maintain perfusion pressure of the pulmonary vasculature, thus maintaining cardiac output. Appropriate medical management often ameliorates symptoms for a time. As the disease progresses and PVR continues to increase, remodeling of the RV results in dilation, systolic and diastolic dysfunction, and eventual fibrosis.10 The RV struggles to adequately perfuse the pulmonary vasculature to ensure sufficient left ventricular preload and output, and a tenuous oxygen supply:demand relationship of the coronary circulation and RV is then reached. Either in the setting of an acute increase in RV afterload or low diastolic pressure at the aortic root, the RV is prone to sudden ischemia, acute failure, and cardiovascular collapse.
February 1, 2016 • Volume 6 • Number 3
The presumed benefit of surgical placement of a Potts shunt is to prevent this downward spiral. The aortopulmonary communication provides a “pop-off” in the setting of an acute increase in RV pressure, thus unloading the RV and preventing acute failure. Systemic perfusion is also maintained; if an acute increase in PVR limits left atrial filling and preload, accentuated right-to-left shunt occurs at the Potts shunt to preserve systemic and coronary perfusion, albeit at the expenses of systemic desaturation. With this physiology in mind, anesthetic care of these children must be meticulous. In short, anesthetic goals in children with severe PAH are to maintain cardiac contractility, cardiac output, systemic vascular resistance, and normal sinus rhythm while assiduously avoiding increases in PVR. Severely restrictive RV physiology mandates that sinus rhythm at a moderate rate be maintained to maximize ventricular filling. Mild hypertension is typically well tolerated, but hypotension must be avoided. Hypotension reduces coronary perfusion pressure to an already stressed RV, risking acute RV failure. Decreased left ventricular afterload may contribute to an increase in the leftward ventricular septal position, thus further limiting left ventricular function and coronary perfusion. A feared and potentially fatal complication during the anesthetic care of these children is a pulmonary hypertensive crisis, whereby an acute increase in PVR can culminate with acute RV failure and subsequent cardiovascular collapse. Hypoxia, hypercarbia, acidosis, and noxious stimuli under light anesthesia must be avoided to prevent any further increase in PVR. Any continuously infusing pulmonary vasodilators (e.g., prostacyclin analogs) must be continued uninterrupted, and inhaled nitric oxide should be immediately available or even prophylactically used for prevention and prompt treatment of a pulmonary hypertensive crisis. Cardiopulmonary bypass or extracorporeal life support should be readily available in the event of circulatory collapse during anesthesia induction or surgery. If conditions permit, an IV induction allows careful titration of anesthetic agents to maintain baseline physiologic variables. Vasoactive medications must be immediately available to treat hypotension. A high-dose opiate technique has the advantage of blunting noxious stimuli and subsequent increases in PAP and PVR during intubation and surgery. Standard monitors, arterial line, and central venous access should be placed. Placement of the arterial line in the right upper extremity allows measurement of preshunt Pao2 after the procedure. Preductal and postductal saturation probes are then placed to assess saturation variation after placement of the shunt. For the same reason, cerebral and renal NIRS can aid assessment of oxygen delivery. Regional anesthesia (e.g., paravertebral or epidural block) could arguably allow lower doses of other anesthetic agents and provide steady hemodynamics, but additional time under anesthesia, preexisting coagulopathy related to cyanosis, and possible hypotension from sympathectomy are valid concerns. The use of TEE allows continuous assessment of cardiac filling, acute increase of PAP, and evidence of RV dysfunction. One-lung ventilation is ideal for maximal surgical exposure and can be accomplished with multiple techniques. The possibility of acute deterioration during establishment
cases-anesthesia-analgesia.org
59
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
of lung isolation should be anticipated with a rescue plan in place. Management of 1-lung ventilation (or at least significant retraction and collapse of 1 lung) in a patient with suprasystemic PAP requires meticulous attention to ventilation goals. Compression or collapse of the lung decreases the cross-sectional area of the pulmonary vascular bed and thus substantially increases the PAP. Furthermore, a ventilation:perfusion mismatch results in worsening pulmonary venous desaturation and thus worsening hypoxia, hypercarbia, and acidosis. Ventilation management must be carefully and dynamically managed to achieve and maintain normoxia and normocapnia throughout surgery. Placement of the pulmonary and aortic clamps will increase afterload to the respective ventricles and may provoke hemodynamic instability. A test occlusion may be wise to assess tolerability. Removal of the aortic side clamp risks sudden and significant hypotension via several mechanisms. The side clamp can be removed slowly, and if poorly tolerated, digital compression or reclamping of the aorta may be required. Clear communication between surgeon and anesthesiologist is key before declamping. Vasopressor and inotropic medications should be immediately ready. As mentioned earlier, tachycardia must be avoided, and thus, the treatment should focus on vasoconstriction and then mild inotropic support as needed. Once the aortic side clamp is removed, it is helpful to perform a formal TEE assessment of the cardiac function, shunt flow, and RV and pulmonary pressures. Doppler measurements of the Potts shunt velocity can quantitate the pressure and provide an estimate of systolic PAP. If there is any tricuspid or pulmonary regurgitation on TEE, that can also help estimate systolic PAP and diastolic PAP, respectively. Preshunt and postshunt saturation measurements also quantify the degree of right-to-left shunt occurring at the level of the proximal descending aorta. Higher right heart pressures will cause greater right-to-left shunt and thus greater saturation differences between upper and lower extremities. In the same manner, the variation between cerebral and renal NIRS allows determination of adequate oxygen delivery to both tissue beds during this new physiology. Intraoperative and postoperative bleeding should be expected. In personal communication with other centers, the rate of intraoperative bleeding and return to the operating room for reexploration is very high. More than normal bleeding should be expected because of cyanosis-induced coagulopathy, prostacyclin-induced platelet dysfunction, and highly pressurized arterial and venous vasculature.10 In conclusion, the results of early outcome data have caused some to suggest that Potts shunt may be preferable to BAS and preferable to lung transplantation in children with severe, drug refractory IPAH.7 Anesthetic care of these fragile children undergoing Potts shunt requires that the anesthesiologist inherently understands the child’s physiology and be prepared to quickly and effectively manage the intraoperative dynamic cardiopulmonary changes. E
60 cases-anesthesia-analgesia.org
REFERENCES 1. Barst RJ, McGoon MD, Elliott CG, Foreman AJ, Miller DP, Ivy DD. Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation 2012;125:113–22 2. Hopkins WE, Ochoa LL, Richardson GW, Trulock EP. Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome. J Heart Lung Transplant 1996;15:100–5 3. Blanc J, Vouhé P, Bonnet D. Potts shunt in patients with pulmonary hypertension. N Engl J Med 2004;350:623 4. Baruteau AE, Serraf A, Lévy M, Petit J, Bonnet D, Jais X, Vouhé P, Simonneau G, Belli E, Humbert M. Potts shunt in children with idiopathic pulmonary arterial hypertension: long-term results. Ann Thorac Surg 2012;94:817–24 5. Potts WJ, Smith S, Gibson S. Anastomosis of the aorta to a pulmonary artery; certain types in congenital heart disease. J Am Med Assoc 1946;132:627–31 6. Murphy JG, Gersh BJ, Mair DD, Fuster V, McGoon MD, Ilstrup DM, McGoon DC, Kirklin JW, Danielson GK. Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot. N Engl J Med 1993;329:593–9 7. Baruteau AE, Belli E, Boudjemline Y, Laux D, Lévy M, Simonneau G, Carotti A, Humbert M, Bonnet D. Palliative Potts shunt for the treatment of children with drug-refractory pulmonary arterial hypertension: updated data from the first 24 patients. Eur J Cardiothorac Surg 2015;47:e105–10 8. Labombarda F, Maragnes P, Dupont-Chauvet P, Serraf A. Potts anastomosis for children with idiopathic pulmonary hypertension. Pediatr Cardiol 2009;30:1143–5 9. Schaellibaum G, Lammers AE, Faro A, Moreno-Galdo A, Parakininkas D, Schecter MG, Solomon M, Boyer D, Conrad C, Frischer T, Wong J, Boehler A, Benden C. Bilateral lung transplantation for pediatric idiopathic pulmonary arterial hypertension: a multi-center experience. Pediatr Pulmonol 2011;46:1121–7 10. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, Harrington RA, Anderson JL, Bates ER, Bridges CR, Eisenberg MJ, Ferrari VA, Grines CL, Hlatky MA, Jacobs AK, Kaul S, Lichtenberg RC, Lindner JR, Moliterno DJ, Mukherjee D, Pohost GM, Rosenson RS, Schofield RS, Shubrooks SJ, Stein JH, Tracy CM, Weitz HH, Wesley DJ; ACCF/AHA. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 2009;119:2250–94 11. Micheletti A, Hislop AA, Lammers A, Bonhoeffer P, Derrick G, Rees P, Haworth SG. Role of atrial septostomy in the treatment of children with pulmonary arterial hypertension. Heart 2006;92:969–72 12. Carmosino MJ, Friesen RH, Doran A, Ivy DD. Perioperative complications in children with pulmonary hypertension undergoing noncardiac surgery or cardiac catheterization. Anesth Analg 2007;104:521–7 13. Taylor K, Moulton D, Zhao XY, Laussen P. The impact of targeted therapies for pulmonary hypertension on pediatric intraoperative morbidity or mortality. Anesth Analg 2015;120:420–6 14. Ivy DD, Abman SH, Barst RJ, Berger RM, Bonnet D, Fleming TR, Haworth SG, Raj JU, Rosenzweig EB, Schulze Neick I, Steinhorn RH, Beghetti M. Pediatric pulmonary hypertension. J Am Coll Cardiol 2013;62:D117–26
A & A case reports
Copyright © 2015 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
