Annals of Thoracic Medicine
GUIDELINES
Year
: 2014  |  Volume : 9  |  Issue : 5  |  Page : 98--107

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Perioperative management in patients with pulmonary hypertension


Adriano R. Tonelli, Omar A. Minai 
 Department of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, Ohio, USA

Correspondence Address:
Omar A. Minai
MD, Associate Professor of Medicine, Respiratory Institute, Cleveland Clinic, Ohio, 9500 Euclid Avenue A-90, Cleveland, Ohio, 44195
USA

Abstract

Patients with pulmonary hypertension (PH) are being encountered more commonly in the perioperative period and this trend is likely to increase as improvements in the recognition, management, and treatment of the disease continue to occur. Management of these patients is challenging due to their tenuous hemodynamic status. Recent advances in the understanding of the patho-physiology, risk factors, monitoring, and treatment of the disease provide an opportunity to reduce the morbidity and mortality associated with PH in the peri-operative period. Management of these patients requires a multi-disciplinary approach and meticulous care that is best provided in centers with vast experience in PH. In this review, we provide a detailed discussion about oerioperative strategies in PH patients, and give evidence-based recommendations, when applicable.



How to cite this article:
Tonelli AR, Minai OA. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Perioperative management in patients with pulmonary hypertension.Ann Thorac Med 2014;9:98-107


How to cite this URL:
Tonelli AR, Minai OA. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Perioperative management in patients with pulmonary hypertension. Ann Thorac Med [serial online] 2014 [cited 2023 Mar 30 ];9:98-107
Available from: https://www.thoracicmedicine.org/text.asp?2014/9/5/98/134048


Full Text

Patients with pulmonary hypertension (PH) are being encountered more commonly in the perioperative period and this trend is likely to increase as improvements in the recognition, management, and treatment of the disease continue to occur. Management of these patients is challenging due to their tenuous hemodynamic status. Recent advances in the understanding of the pathophysiology, risk factors, monitoring, and treatment of the disease provide an opportunity to reduce the morbidity and mortality associated with PH in the perioperative period. Management of these patients requires a multi-disciplinary approach and meticulous care that is best provided in centers with vast experience in PH. [1] Current management is aimed at minimizing risk factors, optimizing hemodynamics (right ventricular [RV] preload, afterload, and contractility), and aggressively treating complications. [1],[2]

The number of patients with PH has increased because of increased awareness, better diagnostic techniques, and longer survival with the development of more effective treatment options. [3],[4],[5] Thus, more patients with PH are likely to require elective or emergency surgery. Notably, surgeries in PH patients carry higher morbidity and mortality. [1],[6] In fact, PH represents one of the most important risk factors for complications during the perioperative or peripartum period. [7],[8],[9],[10],[11],[12]

In spite of this increased risk, little information exists on the appropriate risk assessment and management of PH (including disease-specific therapies) in the perioperative period. [1] Controlled trials are lacking and most recommendations are based on case series or expert opinion. [13] In this review, we will summarize the scope of the problem and available evidence, as well as propose recommendations regarding the management of PH in the perioperative period.

 Definition



Pulmonary hypertension is a disease characterized by an increase in pulmonary pressures caused by different etiologies that can lead to RV failure and death. [14] The 4 th World Symposium on PH defined the presence of this condition when the mean pulmonary artery pressure (mPAP) is ≥25 mm Hg during right heart catheterization (RHC). [15],[16]

In order to make the diagnosis of PH a high level of suspicion is of outmost importance. The Registry to Evaluate Early and Long-term pulmonary arterial hypertension (PAH) Disease Management found that 21% of PH patients experienced a diagnostic delay of >2 years. This delay in PH diagnosis predominantly occurred in younger patients and those who had concomitant respiratory diseases, less severe RV dysfunction, or covered <250 m during the 6-min walk testing. [17]

 Need for Surgery in Pulmonary Hypertension Patients



As it occurs in the general population, PH patients may require a variety of cardiac or noncardiac surgeries that are associated with a broad range of inherent morbidity and mortality risks. In addition, female patients with PH may become pregnant and opt for delivery. Although PH patients have traditionally been counseled against having elective surgeries or becoming pregnant, it is not uncommon, in recent years, to evaluate and manage PH patients before, during, and after surgical interventions.

There are other surgical interventions that are specifically indicated for certain groups of PH patients such as thromboendarterectomy (for individuals with chronic thromboembolic PH) or lung transplantation (for those patients with advanced PH nonresponsive to PH-targeted therapies).

 Pathophysiologic Considerations



Normal resting mPAP is 14 ΁ 3 mm Hg with the upper limit of normal of 20.6 mm Hg. [15] The normal pulmonary vascular resistance (PVR) (0.8 ΁ 0.4 Wood units) is 80-90% lower than the resistance observed in the systemic circulation. In PH, the chronic elevation of the pulmonary pressures leads to progressive dilation and hypertrophy of the RV that generates higher wall stress and limits the myocardial perfusion in diastole, increasing the risk of RV ischemia and failure in the presence of systemic hypotension. [18]

In PH, the RV does not appropriately tolerate acute increases in afterload, as a consequence the RV dilates and the stroke volume decreases due to its limited ability to increase preload or contractility. [18],[19] RV dilation can lead to a paradoxical shift of the interventricular septum toward the left ventricle (LV), compromising LV filling and reducing systemic cardiac output and coronary perfusion pressure due to ventricular interdependence. The elevated venous pressure, coupled with low systemic perfusion pressure can markedly reduce the blood supply to vital organs (kidney, liver, gastrointestinal tract, brain, etc.) leading to multiple organ system failure. [20] Patients with PH can also develop acute tricuspid regurgitation with further reduction in RV output and LV preload. In addition, the elevated RV end-diastolic pressure associated with RV failure may open a patent foramen ovale leading to right-to-left shunt and deterioration of the underlying hypoxemia. These events could in turn worsen RV myocardial ischemia and right heart failure. [18],[21]

Factors that impair RV contractility, RV preload, or RV afterload can precipitate right-sided circulatory failure during the perioperative or peripartum period. RV contractility can be affected by ischemia or medications used during surgery. RV preload can be reduced by arrhythmias, positive intrathoracic pressure during mechanical ventilation, and excessive use of diuretics or fluid restriction. Increases in RV afterload may be precipitated by sympathetic stimulation (e.g., pain and endotracheal intubation), hypoxemia, hypercapnia, hypothermia, acidemia, or high airway pressures in mechanically ventilated patients. [21],[22],[23],[24],[25],[26] PH can also be aggravated by the occurrence of thromboembolism, carbon dioxide or fat embolism, use of protamine, or extracorporeal circulation. [27]

Marked cardiopulmonary changes occur during pregnancy and puerperium. During pregnancy the intravascular volume and cardiac output increase by approximately 50%. Cardiac output may increase even further during labor and the immediate postpartum period, [28],[29] meanwhile the return to baseline values may take up to 6 months after delivery. [29] These large hemodynamic changes in PH patients are poorly tolerated, since they have a fixed resistance of the pulmonary vasculature with limited ability to compensate. Increases in heart rate and circulatory volume can lead to RV failure, especially when associated with hypoxemia, hypercapnia, and acidemia. [29],[30] In addition, an increase in venous return following delivery (uterine contraction and relief of the inferior vena cava compression) as well as pulmonary embolism can worsen PH during pregnancy and the postpartum period.

 Pulmonary Hypertension in Noncardiac Surgery



Pulmonary hypertension is a risk factor for worse outcomes in noncardiac surgery predominantly in the early postoperative period. [1],[31],[32] However, the guidelines on perioperative cardiovascular evaluation for noncardiac surgery from the American College of Cardiology and American Heart Association (2007) do not include PH in the risk stratification of these patients. These guidelines emphasize that most experts agree that PH poses an increased risk for noncardiac surgery; however, no major study has been performed to prove this concept. [33] We summarized the studies on PH in noncardiac surgery, as shown in [Table 1]. [9],[10],[11],[12],[34] {Table 1}

It is important to mention that the results presented in this table are applied to PH patients that underwent surgeries in referral centers. It is unclear if similar outcomes will be observed in centers with less experience in the management of this disease.

Kaw et al. described that PH patients undergoing noncardiac surgery were more likely to develop heart failure, hemodynamic instability, sepsis and respiratory failure when compared with patients without PH on RHC. Furthermore, the authors noted that PH patients needed longer mechanical ventilatory support, intensive care unit (ICU) stay, and had more 30-day hospital readmissions. [10] A recent international prospective survey found that the risk factors for major complications in noncardiac nonobstetric surgery in patients with PAH were an elevated right atrial pressure (>7 mm Hg), a 6-min distance walked <399 m, the perioperative use of vasopressors and the need for emergency surgery. [35]

Factors reported to increase the operative risk in PH patients are summarized in [Table 2]. High-risk surgery is defined as a procedure with significant perioperative systemic inflammatory response, rapid blood loss, risk of venous air, CO 2 , fat or cement emboli, loss of pulmonary vasculature, or exposure to factors that can acutely increase PVR. [20] At present, no study was able to determine whether the anesthetic approach (regional versus general), type of anesthetic used and treatment with advanced PH therapies have an impact in the perioperative morbidity or mortality.{Table 2}

 Pulmonary Hypertension in Cardiac Surgery



Pulmonary hypertension is a recognized risk factor for morbidity and mortality in cardiac surgery. [1],[36] Among 2,149 patients that underwent coronary artery bypass grafting, PH was an independent predictor for postoperative mortality. [7] Similarly, PH was an independent risk factor for mortality in patients that underwent heart surgery in the EuroSCORE study. [37] Other studies have also shown that a mPAP ≥25 or >30 mm Hg is a useful predictor of perioperative morbidity, mortality, and ICU length of stay in patients undergoing cardiac surgery. [38],[39] Similarly, the risk of mitral valve replacement is increased in patients with PH, especially when the pulmonary pressures are above systemic levels. [40],[41] Even though the early mortality is high, the long-term results are comparable to patients without PH. [41] PH has also been found to be a strong and independent predictor of mortality in severe aortic stenosis. [42],[43],[44] In fact, aortic valve replacement in PH patients is associated with higher mortality; nevertheless, it is associated with a marked survival benefit when compared to conservative management, since the latter has a dismal prognosis. [42],[45],[46] Interestingly, persistent moderate or severe PH after aortic valve replacement is associated with reduced long-term survival. [43]

A lower mean systemic-to-pulmonary artery pressure (PAP) ratio after anesthesia induction predicts hemodynamic complications after surgery. [1],[47] A favorable response to inhaled nitric oxide (iNO) may identify patients at low risk for perioperative complications. Those PH patients with a ratio of pulmonary over systemic vascular resistance (on ~100% oxygen and iNO) <0.33, or a decrease of 20% when compared to baseline had a lower risk of complications. [48]

 Pulmonary Hypertension in Pregnancy



The estimated overall maternal mortality for individuals with PH (≥25 mm Hg) has traditionally been between 30% and 56%. Most of the maternal fatalities occur in the early postpartum period (1 st month) and are due to sudden or progressive heart failure. [30],[49] Mortality depends on the etiology of PH, time to recognition, and medical treatment received during pregnancy, delivery, and postpartum. [32],[49],[50] Patients with Eisenmenger's syndrome have higher maternal mortality (40-52%) than other groups, although most of the evidence comes from studies performed before the introduction of PH-specific therapies. [51],[52] A late diagnosis and delayed hospitalization are strong predictors of maternal mortality. [49]

Recent studies using advanced PH therapies and a multi-disciplinary approach showed a lower maternal mortality (11-33%) than historical controls. [30],[53],[54] Nevertheless, maternal mortality remains prohibitively high especially in those with uncontrolled PH. [30],[32],[54] Thus, pregnancy is discouraged and contraception advice becomes critical in women of child bearing potential who have PH. [32] In pregnant women with PH, the risks of pregnancy should be carefully discussed with the patient including the option of early termination of pregnancy, especially in the event of PH deterioration. [32],[55] If the pregnancy is to be continued, early hospitalization with careful multi-disciplinary management is the standard of practice.

The main goals are to recognize and manage PH, prevent its progression, and minimize side-effects of various therapies. [56] The optimal mode of delivery (vaginal versus caesarean section) and best anesthetic approach (epidural versus general) remain controversial. [30],[32],[50],[53],[54],[55],[57] Although promising, the effects of advanced PH therapies on pregnancy outcomes remain largely unknown. [30] Endothelin receptor antagonists (including bosentan, ambrisentan and macitentan) are contraindicated during pregnancy due to potential teratogenic effects. [58] Similarly, riociguat, a soluble guanylate cyclase stimulator showed evidence of fetal abnormalities in animal reproduction studies, therefore its use is contraindicated in women how are or may become pregnant. Although the data are insufficient, epoprostenol and sildenafil appear to be well tolerated during pregnancy without any reported adverse consequence to the fetus. [29],[57],[59] NO has also been used effectively in the peripartum management of patients with PH. [60] Pregnancy in PAH patients who are long-term responders to calcium channel blockers appears to have a particularly good outcome. [54]

In patients who desire to become pregnant despite the recommendation against it, a year of successful PH therapy with the goal of improving the RV function to near-normal is usually suggested. [57]

 Management



Preoperative

Preoperative evaluation starts by obtaining a thorough history and physical examination with special attention to symptoms of PH. [1],[61] Complementary studies may show signs of RV hypertrophy on electrocardiogram or dilated pulmonary arteries on imaging studies. The best initial screening modality when PH is clinically suspected is echocardiography, but a definitive diagnosis requires RHC. [15] In addition, RHC narrows potential etiologies, provides prognostic information, and guides the therapeutic decisions. [16]

The presence of PH (mPAP ≥25 mm Hg) should prompt a re-evaluation of the need for surgery. The risk assessment should take into account the type of surgery, co-morbidities and PH severity [Table 2]. [6],[62] In patients with unacceptably high-risk for the surgical intervention, it is essential to consider other alternatives to surgery or the administration of advanced PH therapies. [63] If the decision is to proceed with surgery, a multi-disciplinary approach in a center with experience in the management of PH is recommended.

The preoperative management encompasses general measurements and consideration of advanced PH therapies. Oxygen is indicated when the oxygen saturation is below 90%. [64] Diuretics are considered in the presence of RV volume overload, but they should be used judiciously, as excessive diuresis can hazardously reduce RV preload. [22] Digoxin may modestly improve cardiac output in patients with PH and RV failure; however, limited data is available. [65]

Bridging with heparin is recommended in patients with indications for oral anticoagulation beyond PAH. [66]

Calcium channel blockers (diltiazem, nifedipine and amlodipine) need to be continued in PAH patients who are vasoreactive and have a long-term response to these medications. [67] Calcium channel blockers are contraindicated in subjects with hemodynamic instability, heart failure (cardiac index below 2 L/min/m 2 and right atrial pressure above 20 mm Hg) or previous adverse reactions to the medication. [67]

Advanced PH therapies should be continued in the perioperative period. If the patient is "nil per mouth," sildenafil can be given in intravenous (IV) form. Patients treated with subcutaneous treprostinil may continue the infusion for short procedures, however for prolonged interventions this medication should be converted to IV treprostinil or epoprostenol. [63] Similarly, in patients that cannot continue inhaled iloprost or treprostinil, like those requiring mechanical ventilation, iNO, IV or nebulized epoprostenol should be considered. [6]

Intraoperative

The main goals for the intraoperative management of patients with PH [Table 3] are based on:

Maintenance of adequate systemic perfusion, RV preload, and optimal contractility. [1] Aggressive control of PH triggers and prevention of the PH crisis and RV failure. [1],[66] Careful monitoring is critical to avoid and correct PH triggers such as hypoxia, hypercapnia, acidosis, hypothermia, sympathetic activation, and hyperinflation.{Table 3}

There are no validated data to help define the best monitoring approach for PH patients undergoing surgery, thus the extent of monitoring required should be determined on a "case by case" basis. Most patients with PH benefit from arterial and central venous catheters, to allow continuous blood pressure monitoring, frequent arterial blood gases analysis, and assessment of fluid volume status. The need for perioperative insertion of a pulmonary arterial catheter is controversial due to lack of evidence on improving outcomes and concern for potential complications. [68] An approach to systemic hypotension using information derived from the pulmonary artery catheterization is shown in [Figure 1]. Trans-esophageal echocardiography is a promising diagnostic modality to evaluate preload and ventricular function in this group of patients.{Figure 1}

Various anesthetic techniques have been used in patients with PH, including regional (limited or neuroaxial) and general anesthesia. Limited regional anesthesia using nerve blocks should be considered when appropriate. Regional anesthesia using a low epidural dose and slow titration is well tolerated in PH patients since it minimizes the hemodynamic compromise associated with systemic afterload reduction. However, this anesthetic approach may not be appropriate for many surgeries or when cessation of anticoagulation is not possible. [34] It is uncertain if neuroaxial anesthesia is safe in patients treated with prostacyclin analogs, since these medications have antiplatelet effects, nevertheless there are no data suggesting increased risk of epidural bleeding in association with these medications. [22] Spinal anesthesia should be avoided as it may cause sudden and poorly tolerated hemodynamic changes at induction and during recovery from the block. [22]

General anesthesia can increase PVR by sympathetic tone activation during airway instrumentation, use of certain anesthetic agents, positive pressure mechanical ventilation, hypoxemia, hypercapnia, and acidemia.

During intubation, opioids and lidocaine can be used to block the cardiorespiratory response. Propofol, pentothal, and etomidate are appropriate induction medications. [6],[22] Concern existed regarding the use of ketamine in PH patients as it may increase PAP; [69] however, a recent retrospective study looking at perioperative complications in children with PH undergoing general anesthesia with ketamine, found similar rates of complications when compared to other medications. [70]

Dexmedetomidine, an alpha 2-agoinst that reduces central sympathetic outflow and induces sedation, may be beneficial in PH patients. [71],[72] Volatile anesthetic agents, regularly used for anesthesia maintenance, may adversely affect RV preload, contractility, and afterload, leading to RV dysfunction. [73],[74]

Nevertheless, the effects on the pulmonary vasculature have been conflicting and no specific agent has been proven superior. [74],[75],[76],[77] Nitrous oxide should generally be avoided as it may increase PVR and produce postoperative myocardial ischemia. [78],[79],[80] Volatile agents can also decrease systemic arterial pressure, resulting in RV ischemia. High dose opioids can blunt the cardiovascular response to surgical stimulation and reduce the dose of volatile anesthetics, limiting their potential adverse effects. [66]

Endotracheal intubation should be avoided when possible, especially in patients with evidence of RV failure. [81] In patients requiring mechanical ventilation, hyperinflation, high plateau pressure and the use of high levels of positive end-expiratory pressure (PEEP) should be avoided as they may reduce RV preload and increase PVR. [82],[83] It might be reasonable to use high FiO 2 , moderate tidal volumes (8 mL/kg) with low levels of PEEP (<12 mm Hg) and relatively high respiratory rates to prevent hypoxemia and hypercapnia. [63],[83]

Postoperative

Most PH patients that die in the perioperative period do so in the first few days after surgery. [1] Price et al. in their study have reported that 92% of the perioperative complications in PH patients occurred in the first 48 h following surgery. Meanwhile, no significant clinical or hemodynamic deterioration was observed in survivors for up to a year of postoperative follow-up. [34] Therefore, it is particularly important to closely follow individuals during the first few days after surgery to promptly detect sudden worsening of PH and RV failure [Table 3], predominantly when anesthetics wear off.

Extubation should be considered when the FiO 2 requirement is ≤40% and patients have appropriate ventilation on minimal ventilator settings. Patients should receive adequate analgesia and be hemodynamically stable. Extubation is usually performed in the ICU; however, for less invasive surgeries without complications, extubation can be done in the operating room. [12] If started intraoperatively, inotropic agents, vasopressors and pulmonary vasodilators should be weaned off gradually. Pulmonary artery catheter monitoring is removed when the patient becomes hemodynamically stable. Sildenafil has been used successfully in the postoperative management of PH after heart transplantation and congenital heart surgery. [84],[85]

Management of right ventricular failure

Right ventricular failure continues to be a common cause of death and RV function is a major determinant of morbidity and mortality in PH patients. [1],[86],[87] Acute decompensation during the perioperative period has a poor prognosis and often occurs as a result of acute RV failure. [9],[22] Therefore, it is critical to promptly identify this commonly misdiagnosed complication.

The management of acute RV failure is challenging and requires a multi-disciplinary approach [Table 4].{Table 4}

In patients with acute RV failure experts advocate the placement of a pulmonary artery catheter to allow measurement of right atrial pressure, cardiac output, PVR and mixed-venous oxygen saturation. [88] Factors causing a negative effect on pulmonary hemodynamics need to be corrected, such as inadequate mechanical ventilatory support or hypothermia.

Anemia may worsen RV function; hence some authors suggest a hemoglobin level of ≥10 g/dL. [88],[89] Systemic hypotension during the perioperative period should not be managed by downtitrating the PH-specific therapies. [6] Volume loading may paradoxically lead to a reduction in the left ventricular preload and worsen hypotension. On the other hand, diuresis may improve left ventricular preload and cardiac output through a reduction in the leftward septal displacement. [88],[90]

Vasopressors may need to be added to prevent or treat RV ischemia, particularly when systemic hypotension develops despite optimization of the fluid status, ventilator settings, and medications. [91],[92] It has been suggested that an increase in left ventricular afterload may optimize the ventricular interdependence. [88] Vasopressors that can potentially be used include norepinephrine and vasopressin. [93],[94],[95] Norepinephrine decreases the ratio of PAP over systemic blood pressure without a change in cardiac output; meanwhile vasopressin, which may lead to a decrease in PVR by way of releasing of NO, has been used successfully in a limited number of PH patients. [93],[94],[96],[97],[98] Dopamine and epinephrine are not ideal as they tend to increase heart rate and myocardial oxygen consumption more than norepinephrine. [11],[92] It is unknown whether these differences could have a clinically significant impact in the perioperative outcomes of PH patients. Dobutamine and milrinone are the preferred inotropic agents since they have vasodilator properties, thereby increasing RV function and reducing PVR. [99],[100],[101],[102]

Pulmonary vasodilators including iNO and other PH-specific therapies may also be initiated. iNO reduces PAPs and pulmonary vascular resistance, while it does not produce systemic vasodilation, since it is rapidly inactivated by hemoglobin binding. [67],[103],[104],[105],[106],[107] PH-specific therapies, used in the perioperative period, include oral or IV sildenafil, [13],[108],[109] IV or inhaled epoprostenol, [110],[111],[112],[113],[114],[115] inhaled iloprost, [116],[117],[118] and IV treprostinil. [119] Endothelin receptor antagonists have a limited role in the acute setting as they are considered long-term therapies for PH. [120],[121] There is lack of data to recommend any particular PH-targeted strategy. Inhaled agents are especially attractive since they are short acting and predominantly produce pulmonary vasodilation without other systemic hemodynamic effects. Nonspecific vasodilators such as calcium channel blockers should be avoided in RV failure as they may cause profound systemic hypotension leading to death. [67]

Data are promising for the use of other therapies such as inhaled milrinone (less systemic effects than the IV form), [122],[123],[124] inhaled nitroglycerin (more selective pulmonary vasodilatory effects), [125],[126] IV iloprost, [127] inhaled sildenafil, [128] and IV levosimendan (myocardial calcium sensitizer and pulmonary vasodilator). [73],[129],[130] Further studies are needed before specific recommendations regarding these therapies can be provided.

When prior therapies fail, patients may benefit from mechanical support such as veno-arterial extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or transplantation. [131],[132] ECMO decompresses the RV and improves the perfusion to other organs, especially bowel, liver, and kidneys. [88] Ideally, this mechanical support should be provided before intubation to avoid hemodynamic instability associated with the airway manipulation and mechanical ventilation. [88] Another potential intervention in severe cases is atrial septostomy, which allows decompression of the right heart chambers, decreasing wall tension and improving contractility. [18],[133] However, this intervention is discouraged as an emergency procedure in patients with RV failure, due to a higher risk of fatal complications. [134] Lung transplantation is usually not an option as patients are often unsuitable candidates due to comorbidities.

 Conclusions



As PH patients live longer and their disease is under better control, it is likely that more patients with this condition will be encountered in the perioperative setting. Management of these patients is challenging due to their tenuous hemodynamic and respiratory status. Better understanding of the pathophysiology, risk factors, monitoring, and treatment of the disease are expected to improve the outcomes of surgical interventions. The perioperative management of PH patients requires a thorough multi-disciplinary approach and meticulous care that is best provided in centers that specialize in PH management.

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