Anesthetic management of children with medically refractory pulmonary hypertension undergoing surgical Potts shunt

Pulmonary hypertension in children is associated with high rates of adverse events under anesthesia. In children who have failed medical therapy, a posttricuspid shunt such as a Potts shunt can offload the right ventricle and possibly delay or replace the need for lung transplantation. Intraoperative management of this procedure, during which an anastomosis between the pulmonary artery and the descending aorta is created, is complex and requires a deep understanding of the pathophysiology of acute and chronic right ventricular failure. This retrospective case review describes the intraoperative management of children undergoing surgical creation of a Potts shunt at a single center.

Results: Twenty-nine children with medically refractory pulmonary hypertension underwent surgical Potts shunts with a median age of 12 years (range 4 months to 17.4 years).Nineteen Potts shunts (65%) were placed via thoracotomy and 10 (35%) were placed via median sternotomy with use of cardiopulmonary bypass.Ketamine was the most frequently utilized induction agent (17 out of 29, 59%), and the majority of patients were initiated on vasopressin prior to intubation (20 out of 29, 69%).
Discussion: A Potts shunt offers another palliative option for children with medically refractory pulmonary hypertension.General anesthesia in these children carries high risk for pulmonary hypertensive crises.Anesthesiologists must understand underlying physiological mechanisms responsble for acute hemodynaic decompensation during

| INTRODUC TI ON
Pediatric pulmonary hypertension (PH) is a rare, highly morbid disease characterized by progressive obstruction and obliteration of the distal muscular arteries resulting in sustained increase in right ventricular (RV) afterload. 1Subsequent RV remodeling allows a compensated physiologic state, but many children ultimately develop medically refractory symptoms and right ventricular failure. 2 Targeted medical therapies have improved survival rates in this population, 3 but ultimately fail to reverse the underlying pathogenic destruction of the pulmonary vasculature.Consequently, many children eventually develop medically refractory symptoms of right ventricular failure.Recognizing RV dysfunction as the leading cause of mortality in patients with end-stage disease, 4 methods to decompress the failing RV are a logical palliative approach.Atrial septostomy has been utilized for decades to create an atrial level shunt, although such pretricuspid valve shunts can only decompress the right ventricle in patients with high right ventricular end-diastolic pressures, hence high right atrial pressures.Additionally, atrial shunts lead to systemic desaturation, and compromise cerebral and coronary circulation. 5Another treatment option for children endstage pulmonary hypertension is lung transplantation.Rarely, heartlung transplantation may be the only option with patients with severe pulmonary hypertension and associated right ventricular failure.However, these resource-intensive interventions are offered at few medical centers and their utility remain limited due to scarcity of suitable donor organs and disappointingly low long-term survival rates. 6e use of a reverse Potts shunt, an anastomosis between the pulmonary artery and the descending aorta (Figure 1), is potentially Conclusions: Our single center expereince shows that the Potts shunt surgery, despite high short-term mortaility, may offer another option for palliation in children with medically refractory pulmonary hypertension.

K E Y W O R D S
general anesthesia, Potts shunt, pulmonary hypertension, pulmonary hypertensive crises, vasopressin F I G U R E 1 These are two posterior views, using magnetic resonance imaging, of a reverse Potts shunt (arrow) that was placed via left thoracotomy.During the operation, an anastomosis between the pulmonary artery (*) and descending aorta is created either with a direct attachment of the two vessels, or with use of a conduit as shown in these images.lower body organs, preserving oxygenation in the cerebral and coronary circulations.The rationale for the introduction of this approach is based on observations that patients with Eisenmenger syndrome have survival advantages over those with other types of pulmonary hypertension. 7th catheter-based and surgical approaches are available for the creation of reverse Potts shunts.In the cardiac catheterization laboratory, an existing patent ductus arteriosus can be stented, or radiofrequency perforation can be used to place covered stents between the pulmonary artery and the descending aorta.Surgical approaches include left thoracotomy or median sternotomy to either create direct anastomoses or to place conduits between the great vessels.Mid-term results after surgical Potts shunts are promising.
In comparison to lung transplantation, patients receiving Potts shunt have similar 3-year survival rates (76%), but experience a lower incidence of major perioperative complications (35% vs. 81%). 8Additionally, because of sustained improvements in functional status and biomarkers of disease severity after Potts shunt surgery, 9 this treatment option is also being considered as destination therapy.However, general anesthesia in children with systemic or supra-systemic right ventricular pressure remains a high-risk endeavor.Severe pulmonary hypertension is a well-known risk factor for serious adverse events under anesthesia including cardiac arrest and death, 10 and the risk for major adverse events may be further elevated during complex surgeries such as creation of Potts shunt and lung transplantation.The principles of anesthetic management of children with pulmonary hypertension has been previously described in excellent review articles. 4,11In this paper, we describe a single-center experience with the anesthetic management of children with severe pulmonary hypertension who underwent surgical placement of Potts shunts.Data were summarized using descriptive statistics.Continuous variables were expressed as median and range or interquartile range, and categorical variables were described as numbers and percentages.

| Evolution of surgical approach
The use of Potts shunt for palliation in pulmonary hypertension was first reported as a salvage treatment for two children in 2004. 12Subsequently, the same group published their midterm outcomes and demonstrated long-term improvement in clinical symptoms of the survivors with a mean follow-up of 63.7 ± 16.1 months. 13In 2013, our institute performed Potts shunt, also as a salvage treatment, for two children with medically refractory pulmonary hypertension and who were considered ineligible for lung transplant surgery.These procedures were performed through a left posterior thoracotomy and with elective use of extracorporeal membrane oxygenator support (ECMO). 14Between 2013 and 2019, 16 more surgeries were performed using a thoracotomy approach.Since 2019, a median sternotomy approach with use of cardiopulmonary bypass has been adopted. 8The current surgical approach connects the main pulmonary artery and the descending aorta using a unidirectional valved conduit.A thoracotomy approach is still used for smaller patients, in whom the use of artificial conduits could limit future growth potential.

| RE SULTS
Twenty-nine Potts shunt surgeries were performed during the study period; 19 were placed via thoracotomy (66%) and 10 (34%) were placed via median sternotomy and use of cardiopulmonary bypass.

A summary of demographics and patient characteristics is presented
in Table 1 (additional information in Appendix S1).The median age was 12.8 years (IQR 6.5-14.Four patients, all in the thoracotomy group, suffered major intraoperative or early postoperative complications unrelated to the anesthetic care.One patient suffered from intraoperative pulmonary hemorrhage following the release of cross clamp.Two patients required reexploration in the intensive care unit for postoperative bleeding.One patient developed persistent weakness in the lower limb which was attributed to spinal cord ischemia due to aortic cross clamp.There were four mortalities (13.8%) during the entire hospital stay (Table 3).The remaining 25 patients (86%) were successfully discharged from the hospital.Median length of stay in the intensive care unit was 5 days (range 2-31) and median length of stay in the hospital was 9 days (range 6-34).

| DISCUSS ION
The Potts shunt is being reintroduced as an effective palliation for children with medically refractory pulmonary hypertension.However, general anesthesia in this patient population carries high risks for pulmonary hypertensive crises, intraoperative cardiac arrest and intraoperative death. 15Published comparative intraoperative data for Potts shunt are sparse but two small case series reported intraoperative cardiac arrests which lead to death in 4%-20% patients. 16,17ile some patients experienced moderate to severe hypoxemia, there were no intraoperative cardiac arrests and only one patient in thoracotomy group required unplanned extracorporeal support.
The important findings in our series show that the physiological per- Anesthetic management for all patients with severe pulmonary hypertension must ensure adequate depth of anesthesia to prevent significant releases of catecholamines and the resulting increase in PVR.However, it is also critical to preserve SVR and myocardial contractility.Intravenous induction, with anesthetic agents such as ketamine and etomidate, in combination with opioids, can provide adequate anesthetic depth for intubation and was preferred over inhaled anesthetic agent due to fewer effects on myocardial function, and systemic or pulmonary vasculature. 19,20e second component of intraoperative management is to avoid sudden decrease in systemic vascular resistance, as de-  differential effects on pulmonary vasculature.In animal models 22 and small human studies 23 vasopressin was shown to produce mild decrease in pulmonary vasculature resistance.In an animal model of hypoxia-induced pulmonary hypertension crisis, vasopressin boluses significantly improved arterial blood pressure, myocardial function, and restored left ventricular morphology by reversing the leftward shift of interventricular septum. 22The exact mechanism of its vasodilatory action on pulmonary vasculature is not well established but it is postulated to be mediated though release of intrinsic nitric oxide or prostaglandins. 24nally, the support for the right and left ventricular function re- Following a Potts shunt, the expected physiology is that oxygen delivery is preserved to the branches of the ascending aorta with some degree of desaturation of the lower body.While we observed oxygen saturation gradient of 5%-15% between the upper and lower extremities, most patients experienced systemic severe oxygen desaturation.These desaturation events, which resolved prior to completion of surgery in all but five patients, could be attributed to alveolar atelectasis, or an inflammatory response to bypass.Other groups have suggested that decreases in LV preload and high systemic vascular resistance following the Potts shunt may contribute towards hemodynamic instability and hypoxemia during postoperative period. 17rprisingly, a number of patients met the criteria for extubation at the conclusion of surgery and were successfully extubated in the operating room or soon after arrival in the intensive care unit.Extubation goals were consistent with the aim of minimizing noxious stimulation of the airway to avoid increasing PVR.Use of regional analgesia assists with limiting pain and the associated pulmonary vasoconstriction.Continuous erector spinae block or single shot pectoral nerve blocks are good alternatives to thoracic epidural catheters in patients where partial or complete heparinization is necessary.
The four mortalities occurred during second to fifth week after surgery.All four patients had required ECMO support at some point of their treatment and had some amount of RV dysfunction.
Of interest, two patients died from suspected postoperative pulmonary hypertensive crises including one during reintubation attempts.These observations reenforce the palliative, rather than curative, nature of the Potts shunt and highlight that the above mentioned strategies for preventing and treating pulmonary hypertensive crises must be used for while caring for these patients.
The role of Potts shunt in the treatment algorithm for children with end-stage pulmonary hypertension, continues to evolve. 8,25recent multicenter review of 110 surgeries performed across 13 institutions, including some patients from this series, suggests that the creation of this posttricuspid valve shunt offers a durable palliation, improvement in clinical symptoms, and in some patients, eliminates the need for cumbersome intravenous prostacyclin therapy. 6Recently, 5-year survival after Potts shunt was assessed to be noninferior to survival after lung transplantation, with lower perioperative morbidity. 8Still, our experience and previously published reports suggest that placement of Potts shunt is still associated with high perioperative mortality. 17 a more effective approach to reduce right ventricular afterload.Because the shunt is beyond the tricuspid valve, it decompresses the right ventricle in all patients with suprasystemic pressure.The resulting right to left shunt selectively sends desaturated blood to the acute pulmonary hypertneisve crises.Severe physiological perturbations imposed by thoracic surgery and use of cardiopulmonay bypass can be mitigated by aggresive heodynamic support of ventricle function and maintainence of systemic vascular resistance.Early use of vasopressin, before or immidiately after anesthesia induction, in combination with other inotropes is a useful agent during the perioperative care of thes.Early use of vasopressin during anesthesia induction, and aggressive inotropic support of right ventricular function can help mitigate effects of induction and intubation, single-lung ventilation, and cardiopulmonary bypass.
This retrospective study was approved by the Human Resource Protection Office at Washington University School of Medicine in St. Louis with a waiver of informed consent.All patients younger than 18 years of age who underwent surgical Potts shunt between April 2013 and June 2022 were included in the study.Electronic medical records were reviewed and data were manually extracted.Preoperative data included patient demographics, markers of severity of the PH, and prior treatment of pulmonary hypertension.Intraoperative variables included medications and blood products administered, vital signs, procedural and anesthetic duration, and need for extracorporeal support.Postoperative outcomes included immediate postoperative vital signs and blood product administration, duration of postoperative ventilation, need for reintubation, intensive care unit (ICU), and hospital length of stay.
7); the youngest patient was 4 months old at the time of surgery.Idiopathic pulmonary arterial hypertension was the most common diagnosis (21 out of 29, 73%).All patients had severe pulmonary hypertension; the mean right ventricular to left ventricular systolic pressure (RVp/LVp) ratio was 1.2 (range 0.8-1.7).Cardiac catheterization data measured suprasystemic pulmonary pressures (76%) in 22 patients.The Potts shunt surgery was performed on average 5 years after the diagnosis of PH (range 0-16.7 years).Two patients were critically ill at the time of their initial diagnosis and underwent the procedure prior to initiating maximal medical therapies.All other patients (27 out of 29, 93%) were receiving dual or triple drug therapy, initiated after cardiac catheterization.Four patients (14%) required mechanical ventilation prior to surgery, and two of these were on ECMO.Intraoperative variables are presented in Table 2 and expanded in Appendix S2.Intravenous ketamine (59%) was the most common anesthetic agent used for induction; propofol (6 out of 29, 21%) and etomidate (5 out of 19, 17%) were used less frequently.General anesthesia was maintained with sevoflurane, muscle relaxation, and intravenous opioids with some patients receiving intraoperative infusions of sedatives such as dexmedetomidine.Both pressure and volume controlled modes on anesthesia ventilators were used for intraoperative ventilation.Intraoperative inhaled nitric oxide (iNO) was used in 23 patients (79%).When feasible, an arterial line was placed immediately prior to induction using mild sedation and ultrasound guidance (20 out of 29, 69.0%).For the thoracotomy group, single-lung ventilation was successfully achieved in 14 patients (73.7%) using a variety of approaches (Table 2) with a median duration of 92 minutes (range 41-161).No patient required urgent reinflation of the lung during the surgical procedure.Most patients tolerated single-lung ventilation well.Only two of the thoracotomy patients (10.5%) experienced severe arterial oxygen desaturation (more than 10% below baseline) after initiating one-lung ventilation.A total of 5 patients (26%) experience severe desaturations during the period of cross clamp placement on the pulmonary artery and aorta.The average duration of cross clamp in the thoracotomy groups was 23 min (range 15-70).Almost all patients (27 out of 29, 93%) required inotropic or vasopressor support during the intraoperative period (Appendix S2).For the first 8 patients (28%), milrinone alone or in combination with dobutamine infusion was initiated on the evening prior to the surgery in the ICU.For 25 (86%) patients, additional vasoactive infusions were initiated intraoperatively.Vasopressin infusion was initiated prior to or immediately after induction of anesthesia in 20 (69%) patients.Other hemodynamic medications included epinephrine infusions (7 out of 29, 24%) and norepinephrine infusions (3 out of 29, 10%).Episodes of hypotension or hypoxemia were evaluated with transesophageal echocardiography and were aggressively treated with escalation of vasopressin or epinephrine infusion doses, boluses of epinephrine, and volume replacement.Most patients (27 out of 29, 93%) required vasoactive infusions after the opening of the shunt, and remained on hemodynamic support at the time of ICU arrival (25 out of 29, 86%).Preoperative prostacyclin infusions were continued throughout the procedure.As part of a multimodal analgesia strategy, a variety of regional analgesia techniques were utilized to provide postoperative pain relief and facilitate earlier extubation.The decision to extubate in the operating room was made at the attending physician's discretion and became more common over time.Fourteen patients (48%) were extubated in the operating room.Fifteen patients required postoperative mechanical ventilation (median duration 3.5 days, range 1-18).No patient suffered intraoperative cardiac arrest.The most common adverse intraoperative event was moderate to severe hypoxemia (SpO 2 < 80%, 21 out of 29 patients, 72%).Eight patients (28%) experienced prolonged hypoxemia (>20 min).The timing of desaturation correlated with the opening of the Potts shunt, that is, after taking pulmonary and aortic clamps off in the thoracotomy group (10 out of 19, 53%) and after separation from bypass in sternotomy group (7 out of 10, 70%).Most episodes of hypoxemia and hypotension were successfully managed with increasing doses of vasopressin or epinephrine, and volume replacement.One patient in the thoracotomy group developed severe desaturation and hypotension prior to surgical incision and was placed on ECMO support prior to TA B L E 2 Procedural variables.
turbations imposed by thoracic surgery, single-lung ventilation, cardiopulmonary bypass can be mitigated with appropriate anesthetic management and aggressive support.Patients undergoing this surgery through thoracotomy face particular challenges.Clamping of the left pulmonary artery abruptly increases right ventricular afterload, and the RV faces additional physiologic insults during the time of onelung ventilation.18Surprisingly, most patients in our series were able to tolerate severe physiological changes imposed by intubation, singlelung ventilation, and surgical dissection and cross clamp placement.Our intraoperative management strategy evolved over time to focus on three key goals; (i) prevent significant increases in pulmonary vascular resistance (PVR) by ensuring adequate depth of anesthesia, (ii) maintain systemic vascular resistance (SVR), particularly prior to placement of the Potts shunt, and (iii) support right and left myocardial function throughout the surgery and early postoperative period.
crease in systemic vascular resistance plays a significant role in precipitating pulmonary hypertensive crises.During a crisis, increases in PVR or decreases in SVR can overwhelm the chronic compensatory mechanisms of the right ventricle and lead to progressive right ventricular dilation.As the right ventricle dilates, it shifts the interventricular septum towards left ventricle (LV), thereby decreasing LV preload and effective stroke volume, compromising systemic cardiac output. 21Loss of normal septal position also dramatically worsens RV contractility.If not immediately identified and treated, this self-propagating cycle of hypotension can rapidly progress toward cardiac arrest and death.Restoring systemic vascular resistance and hence left ventricular pressure reduces compression of the left ventricle and maintains left ventricular stroke volume.We proactively started vasopressin infusion (0.2-2 milliunits/kilogram/minute) to counter any decrease in systemic vascular resistance caused by anesthetic agents.Vasopressin, a small nano peptide, is an active mediator in cardiovascular physiology.Through its actions on V 1 receptors, mostly located in systemic peripheral vasculature, it increases intracellular calcium and systemic vasculature tone.Vasopressin is attractive in patients with severe pulmonary hypertension due to its TA B L E 3 Characteristics of patients with in-hospital mortalities.
mains critical before and after Potts shunt is established.The opening of the Potts shunt can prevent supra-systemic RV pressures, acute right ventricular dilatation and the associated leftward shift of the interventricular septum.However, even in the potts physiology, right ventricle contractility must remain robust to deal with systemic resistance.The current approach relies on use of epinephrine and milrinone infusions into the recovery period, especially in patients who underwent cardiopulmonary bypass.Use of milrinone, with its inodilatory properties, is particularly helpful, as it can decrease systemic vascular resistance and right ventricular afterload.Aggressive fluid resuscitation is often required after Potts shunt creation because the right to left shunt reduces left ventricular preload.
The evolving evidence suggests that a preserved right ventricular function is essential for better short-and long-term outcomes.The introduction of valved conduits necessitates the use of cardiopulmonary bypass and prolongs operative duration.These unidirectionally valved conduits prevent the unwanted reversal of flow through the shunt during the times when pulmonary pressures are subsystemic, and the Potts shunt may be performed earlier during the progress of the disease while the right ventricular function is preserved and pulmonary pressures are suprasystemic only during exercise or stress.8Additionally, the use of cardiopulmonary bypass allows for simultaneous repair of any intracardiac defects that may be detrimental to RV function.This retrospective study is limited by the small sample size, evolving anesthetic management, and does not allow statistical analysis of risk factors or identification of best practices.In summary, our single center experience shows that the Potts shunt surgery, despite high short-term postoperative mortality, may offer another option for palliation in children with severe pulmonary hypertension.Aggressive support of systemic vascular resistance and myocardial contractility are essential to safely anesthetize children during the extreme physiological perturbations that they experience during this surgical procedure.