Perioperative management of pulmonary thromboendarterectomy in a patient with life-threatening acute-on-chronic pulmonary thromboembolism secondary to nephrotic syndrome: A case report

Abstract

A previously healthy 44-year-old man presented with acute severe dyspnea. Laboratory evaluation revealed severe hypoalbuminemia, elevated low-density lipoprotein cholesterol and D-dimer levels, and marked proteinuria, suggesting nephrotic syndrome (NS). Imaging demonstrated bilateral pulmonary emboli with right ventricular strain. Since he developed progressive shock, veno-arterial extracorporeal membrane oxygenation (VA ECMO) and thrombolytic therapy were initiated. Persistent thrombi and failed ECMO weaning due to poor oxygenation prompted urgent pulmonary thromboendarterectomy on day 8, confirming both fresh and organized clots and intimal thickening. The patient was extubated on postoperative day (POD) 3, transferred from intensive care on POD 6, and discharged ambulatory on POD 63. This case represented acute-on-chronic pulmonary thromboembolism (PTE) secondary to previously undiagnosed NS, a condition that predisposes patients to hypercoagulability, including asymptomatic PTE. The case underscores the hazards of NS in acute care settings. Successful management was achieved through coordinated efforts between multidisciplinary specialists and interprofessional collaboration.

Introduction

Nephrotic syndrome (NS) is a relatively common disease that typically does not progress rapidly to a life-threatening state. Nevertheless, it induces a hypercoagulable state, predisposing individuals to thromboembolic complications. ¹ Pulmonary thromboembolism (PTE) is not uncommon in NS patients, ² although most are reportedly asymptomatic. ³ We describe a previously healthy patient with undiagnosed NS and subclinical chronic PTE, who presented to the emergency department with signs of life-threatening acute PTE. Our patient achieved a favorable outcome through multidisciplinary perioperative management, including prompt veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and urgent pulmonary thromboendarterectomy (PTEA).

Case presentation

A 44-year-old man (height, 181 cm; weight, 87 kg) with no significant medical history developed cough and fever approximately 12 days before presentation. About 5 days before admission, he began to experience progressive dyspnea. On the day of presentation, his dyspnea worsened markedly, rendering him unable to ambulate independently; consequently, he was transported to the emergency department. Laboratory findings showed severe hypoalbuminemia (1.1 g/dL), elevated low-density lipoprotein (LDL) cholesterol (214 mg/dL), high D-dimer (54.1 mcg/mL), and marked proteinuria. Transthoracic echocardiography demonstrated left ventricular compression and an estimated right ventricular systolic pressure (eRVSP) of 69 mmHg. Contrast-enhanced computed tomography (CT) revealed large emboli in both main pulmonary arteries (Figure 1(a)) and left common iliac vein thrombosis, suggesting acute NS-induced PTE. Therefore, 10,000 units of heparin were administered intravenously at the emergency department. Due to progressive shock, VA-ECMO was initiated 4 h after admission, and catheter-directed thrombolysis was concurrently performed. This, however, achieved only partial restoration of perfusion to the lower lung lobes bilaterally. Following admission to the intensive care unit (ICU), a single bolus dose of 2 million international units of monteplase, a recombinant tissue plasminogen activator commonly used in Japan, was administered. ⁴ Thereafter, continuous heparin infusion was commenced, targeting an activated clotting time of 150–200 s. Sedation with dexmedetomidine was also initiated. After the establishment of VA-ECMO support, hemodynamic stability was achieved without the need for vasoactive agents. During ECMO support, the patient was managed under spontaneous respiration without tracheal intubation. Attempts to wean the patient from ECMO on hospital days 3 and 6 were unsuccessful because of recurrent oxygen desaturation. Furthermore, chest CT on hospital day 6 (Figure 1(b)) demonstrated only minimal radiological improvement. Consequently, urgent surgical intervention was scheduled for hospital day 8.

Figure 1.

Transverse CT of the chest.

Severe hypoalbuminemia persisted throughout the patient’s clinical course. On the day of admission, 1000 mL of 5% albumin solution and 200 mL of 20% albumin solution were administered. From hospital days 2 through 6,200 mL of 20% albumin solution was infused daily. Despite this, the serum albumin level on the day of surgery (hospital day 8) remained low, at 1.0 mg/dL. At the time of surgery, general anesthesia was induced with fentanyl and midazolam, followed by tracheal intubation. Anesthesia was maintained with remifentanil and sevoflurane. A pulmonary artery catheter was inserted via the right internal jugular vein, with the catheter tip positioned in the right ventricle. The patient’s intraoperative course was uneventful until the initiation of cardiopulmonary bypass, and vasoactive support was not required. During cardiopulmonary bypass, anesthesia was maintained with propofol and remifentanil.

With extracorporeal circulation established on a beating heart, both fresh and organized clots were removed from the left pulmonary artery. Under cardiac arrest and mild hypothermia (32°C), further thrombectomy and pulmonary endarterectomy were performed due to intimal thickening, followed by removal of additional clots from the right side. After return of spontaneous circulation, the catheter was advanced into the pulmonary artery. Cardiopulmonary bypass (CPB) was discontinued with minimal norepinephrine (0.04 mcg/kg/min), and ECMO was discontinued once adequate oxygenation was ensured. At this time, mean pulmonary artery pressure remained mildly elevated (approximately 25 mmHg). Aortic cross-clamp, CPB, and total operation times were 81, 128, and 307 min, respectively. Although 720 mL of fresh frozen plasma and 100 mL of 20% albumin were administered into the bypass circuit, albumin levels had increased to only 1.4 g/dL at the time of ICU admission.

Postoperatively, the continuous norepinephrine infusion was discontinued on the day of surgery, while continuous infusion of a low dose (<0.03 µg/kg/min) of carperitide, a recombinant form of human atrial natriuretic peptide preparation used in Japan, ⁵ moderate-dose nicardipine (<1.5 µg/kg/min), and low-dose epinephrine (<0.05 µg/kg/min) were continued until postoperative day (POD) 4. Additionally, during the ventilator period from POD 1 to POD 3, furosemide was administered intravenously as clinically indicated, with a cumulative total dose of 140 mg. For the perioperative management of hypoalbuminemia, the patient received 500 mL of 5% albumin on the day of surgery, followed by 1000 mL on POD 1, resulting in his serum albumin level increasing to 2.1 g/dL before it declined again. At ventilator weaning on POD 3, his albumin level was 1.6 g/dL. Although hemoptysis persisted initially, it resolved by POD 2 with 10 cmH₂O positive end-expiratory pressure, allowing ventilator weaning. The patient was transferred to the ward on POD 6.

Enteral administration of acetylsalicylic acid was initiated on POD 1. Warfarin therapy was started on POD 10, when the risk of postoperative bleeding was considered sufficiently reduced, and was continued for 5 months with a target international normalized ratio of 1.6 to 1.9. Thereafter, anticoagulation was transitioned to edoxaban and maintained until remission of NS was achieved. Although non-contrast CT on POD 10 showed residual microthrombi (Figure 1(c)), contrast-enhanced CT on POD 45 showed complete resolution (Figure 1(d)). Echocardiography on POD 6 confirmed normalization of eRVSP (23 mmHg). Thereafter, steroid therapy for NS was initiated on POD 13. By the time of his discharge on POD 63, his serum albumin level had increased to 1.7 g/dL, and LDL cholesterol had decreased to 128 mg/dL. Complete remission of NS, as determined by urinary findings, was achieved 11 months postoperatively, with a serum albumin level of 4.2 g/dL. Considering the risk of bleeding, renal biopsy was performed after discontinuation of edoxaban. Therefore, approximately 1 year elapsed after the surgery before a definitive pathological diagnosis was obtained, which revealed membranous nephropathy.

Discussion

In patients with NS, hypercoagulability is attributed to mechanisms including increased platelet activation, enhanced red cell aggregation, and an imbalance between procoagulant and anticoagulant factors. ¹ Consequently, NS predisposes individuals to venous thromboembolic events, including deep vein thrombosis, renal vein thrombosis, and PTE. A recent meta-analysis of 10 studies investigating the prevalence of PTE in NS patients indicated that approximately 8% develop PTE, despite substantial heterogeneity among reports. ² Among patients with NS, hypoalbuminemia of less than 2 g/dL is reportedly a risk factor for thrombosis, with membranous nephropathy being the most common underlying pathology. ¹ Our case met both these criteria. Another meta-analysis of 12 studies involving over 10,000 patients examined the frequency of incidentally detected asymptomatic PTE on chest CT performed for reasons other than investigating PTE, reporting a prevalence of 2.6%. ³ Meanwhile, a prospective study using CT reported that 84% of 153 NS-associated PTE cases were asymptomatic. ⁶ Thus, asymptomatic PTE is not particularly rare, and most cases of NS-associated PTE might be asymptomatic. On the other hand, life-threatening PTE has also been reported in patients with an established diagnosis of NS, and several case reports have described successful resuscitation with ECMO support.^7,8 However, to the best of our knowledge, there have been no previous reports of a patient presumed to be otherwise healthy, who developed life-threatening PTE requiring ECMO support, and who subsequently underwent urgent PTEA, and ultimately achieved full social reintegration. This aspect renders the present case noteworthy.

Intraoperative findings in this case revealed organized pulmonary arterial thrombi and thickening of the pulmonary arterial intima, indicating that the patient had experienced prior episodes of PTE that had progressed to a chronic stage before the current cardiac event. Among patients with an acute presentation of PTE, some already have underlying undiagnosed chronic thromboembolic pulmonary hypertension (CTEPH), with the new episode precipitating decompensation. Cases such as ours are termed acute-on-chronic PTE.

Therapeutic options for CTEPH can be broadly categorized into PTEA, balloon pulmonary angioplasty, and medical therapy. The choice of treatment is determined by the anatomical distribution of the thromboembolic lesions (central versus peripheral), patient preference, and the presence of comorbid conditions.^9,10 In the present case, since the primary lesion was located in the main pulmonary artery trunk, PTEA was selected, and a surgeon with extensive experience in the management of CTEPH was invited to participate as a member of the operative team. In cases of acute-on-chronic PTE, similar favorable outcomes have been reported when these therapeutic modalities are selected on an individualized basis.^{11 –13}

Ultimately, the surgical intervention promptly reduced pulmonary vascular resistance and improved the ventilation- perfusion ratio. However, PTEA, as performed in this case, is associated with several procedure-specific complications.^{14 –17} One of the most important is reperfusion pulmonary edema, for which preventive management strategies aimed at limiting cardiac output have been advocated. Accordingly, after separation from cardiopulmonary bypass, the use of inotropes and vasodilators should generally be minimized; instead, hemodynamic support primarily based on norepinephrine, together with ventilatory management using high positive end-expiratory pressure, is recommended.^{14 –16} In the present case, a continuous infusion of low-dose inotropes and moderate-dose vasodilators was administered postoperatively in the ICU, with no clinically significant adverse events attributable to these agents observed.

In patients with NS, the administration of albumin preparations to increase serum albumin levels or to manage edema is generally discouraged,^18,19 since the therapeutic effect is typically transient and may further compromise glomerular and tubular function. Moreover, expansion of the intravascular plasma volume may predispose patients to hypertension and pulmonary edema. Conversely, a study using pulmonary ultrasound in patients with NS has shown that lower serum albumin levels are associated with more severe asymptomatic pulmonary congestion. ²⁰ In the present case, a substantial amount of albumin preparation was administered perioperatively. By the day of weaning from mechanical ventilation, the patient’s serum albumin level had increased modestly to 1.6 g/dL, compared with the admission value of 1.1 g/dL. Therefore, whether or not limited, short-term correction of hypoalbuminemia should be considered as a preventive strategy against reperfusion pulmonary edema in patients with severe hypoalbuminemia—an important feature in this case—remains controversial. We speculate that the combined use of albumin infusion and furosemide administration partially contributed to the prevention of pulmonary edema in this patient.

Another potential complication of PTEA is alveolar hemorrhage, arising from disruption of the blood-airway barrier following adventitial injury. There are reports recommending the intraoperative use of a larger-bore endotracheal tube in anticipation of the potential need for bronchoscopy or the placement of a bronchial blocker.^16,17 In this case, a standard endotracheal tube was used perioperatively, and the hemorrhage resolved by POD 2. Further, PTEA sometimes causes persistent pulmonary hypertension, particularly in distal-type lesions. In this case, however, the pulmonary artery pressure had normalized by POD 1, and echocardiographic evaluation on POD 6 demonstrated normalization of eRVSP. Thus, residual pulmonary hypertension was considered absent.

Conclusion

We described here the perioperative care of a previously apparently healthy middle-aged man who developed life-threatening PTE secondary to nephrotic syndrome with severe hypoalbuminemia. Following treatment with ECMO and PTEA, he ultimately recovered and was discharged in good condition. The successful management of this educational case was achieved through coordinated efforts by multidisciplinary experts and effective interprofessional collaboration. However, the appropriateness of perioperative albumin administration to prevent postoperative reperfusion pulmonary edema in such patients remains a matter of debate. This case also raises awareness of the potential dangers of NS among those involved in acute care.