Introduction

Osteoporosis is the most common metabolic bone disease characterized by low bone mineral density and microarchitectural deterioration of bone tissue1. Patients with osteoporosis have high risks of fragility and fracture. Given the rising aging population, cases of osteoporosis and osteoporotic fractures have become a serious public health problem. Each year, approximately 8.9 mn fractures due to osteoporosis are reported worldwide2. Vertebral body is the most common site of osteoporotic fractures, and it accounts for approximately 50% of all osteoporotic fractures. Nonoperative treatment may not effectively relief pain and its usage has been shown to induce complications due to prolonged bedrest. Consequently, there is a growing demand for effective vertebral augmentation of osteoporotic fractures, such as percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP). PVP is a minimally invasive surgical technique developed in 1987 by Galibert to treat vertebral hemangioma. The technique involves injection of polymethyl methacrylate (PMMA) into affected vertebrae using a transpedicular approach. This technique effectively stabilizes the weakened vertebral body and relieves pain from various vertebral disorders, including osteoporotic vertebral compression fractures, osteolytic metastases, and myeloma. Currently, PVP is widely applied in the treatment of osteoporotic fractures.

Although PVP is a safe and minimally invasive procedure, it is associated with several serious complications linked to cement leakage. For patients with osteoporotic vertebral compression fractures, the incidence of cement leakage after PVP is in the range of 30% to 65%3. One of the most serious complications is cement escape into the venous system causing cardiac embolism, pulmonary embolism, and cerebral embolism. Previous studies have reported that cement in a semi-fluid state may enter the inferior vena cava via vertebral veins system and migrate to the right side of the heart. The cement solidifies in the heart leading to cardiac embolism. The needle-shaped cement embolus potentially increases the risk of cardiac perforation, which is a fatal condition that requires urgent management.

Here, we describe two elderly patients with cardiac perforation caused by cement escape into the venous system following PVP and propose several recommendations to reduce the risk of cement leakage. Surgeons should more cautiously perform PVP procedure by ensuring appropriate timing of surgical operation, meticulous surgical procedures, early intraoperative and postoperative monitoring of cement leakage. This would improve clinical outcomes of PVP.

This case report received ethical approval by the Affiliated Hospital of Jining Medical University ethics committee. Written informed consent for publication was obtained from the patients and their families.

Discussion

PVP is a procedure through which vertebral disorders like osteoporotic vertebral compression fractures, osteolytic metastases, and myeloma are treated by injecting PMMA into affected vertebrae. However, in rare cases, PVP may result in serious complications due to cement leakage. It is estimated that the risk of cement leakage after PVP in patients with malignant lesions or osteoporotic vertebral compression fractures is 38%–72.5%4, 5 or 30%–65%3, respectively. Cement may escape into various anatomical sites, including needle track, the prevertebral soft tissue in 6%–52.5% of patients, the spinal canal in up to 37.5% of patients, the intervertebral disc in 5%–25% of patients, and the venous system in up to 24% of patients. The vertebral veins system, a widespread venous network that includes internal vertebral venous plexus and external vertebral plexus, surrounds and permeates the vertebral body. Its diameter and blood-flow largely depend on changing position, as well as intraabdominal and intrathoracic pressure6. Thus, if an operation causes high pressure in the vertebral body, cement may leak into it. CT scan and chest X-ray (Fig. 2E) of the second showed that retained cement (63.5 mm) was attached to the T11 vertebral body and revealed leakage into the hemiazygos vein. To the best of our knowledge, this is the first reported case of cement escape into the hemiazygos vein.

A meta-analysis found that cement leakage was associated with severe vertebral collapse, cortical disruption, cement viscosity, and high volume of injected cement. Age, sex, fracture type, and operation level are not significant risk factors7. In the cases presented here, both patients had a history of severe osteoporosis, and the vertebral bodies formed had a degree of vertebral collapse. In the first patient, 6 mL of PMMA cement with toothpaste-like consistency was injected into the L4 vertebral body. In the second patient, 2 and 5 mL of PMMA were injected into the T7 and T11 vertebral bodies, respectively. Two of the vertebrae were injected with >4 mL cement. There are few known cardiac perforation cases caused by cement escape into the venous system upon PVP. A study involving >1500 patients and >3500 vertebral bodies identified intracardiac cement embolisms in 72 patients (3.9%) and found that having many treated vertebral bodies in a single PVP is an independent risk factor for intracardiac cement embolism8. This is probably due to use of a larger amount of cement and the increased complexity and duration of the operation. Even if cement escaped into venous system and caused slight pulmonary embolism, most patients are asymptomatic. Early identification of asymptomatic patients is challenging, and symptoms vary with migration of leaked cement into the right heart and pulmonary arteries via the vertebral veins system. Symptoms range from asymptomatic to symptomatic and include sudden chest pain or syncope and life-threatening events like cardiac tamponade due perforation and acute respiratory distress syndrome (ARDS) due to pulmonary embolism9. Although the two cases reported here were of cardiac perforation upon PVP, symptoms did not indicate this. The first patient had sudden retrosternal pain, epigastric pain, severe dyspnea, and cardiac tamponade. The second had sudden syncope followed by cardiogenic shock, including hypotension, hypoxemia, and moist cold skin. Relatively small round endocardial cement can be removed by percutaneous endovascular procedure10. Thomas et al. reported a case of cement in the pericardium being removed using an endoscopic robotic-assisted approach11. Park et al. reported a case of embolus in which a 2.1 × 6.3-cm long cement was removed via inferior vena cava exploration12. Here, CT found hyperechoic linear foreign objects in right atria of both patients and open-heart surgery was unavoidable given that the sizes and positions of the cement also caused cardiac perforation.

In the second patient, pulmonary embolism caused an arterial blood pH of 7.49, PaO2 of 47 mmHg, PaCO2 of 41 mmHg, an oxygenation index (OI) of 220, and hypoxemia after surgery. According to 2019 European Society of Cardiology (ESC) guidelines for diagnosis and management of acute pulmonary embolism13, intravenous anticoagulation with unfractionated heparin is recommended for patients at high-risk of pulmonary embolism with hemodynamic instability. They should then be encouraged to continue on anticoagulants for 3–6 months, which prevents other thrombotic events and promotes reendothelialization of the embolic surface, minimizing risk of thrombosis. For patients with a SaO2 level <90% in the acute phase, supplemental oxygen is indicated. To delay pulmonary embolism progression and prevent thrombosis due to the cement retained in the hemiazygos vein, low-molecular weight heparin and aspirin were given as anticoagulation therapy and warfarin continue for 3 months as maintenance therapy.

Among the multiple risk factors for cement leakage, cement viscosity and injected cement volume are actively controllable factors14. It has been suggested that only injection of cement above a certain volume will be able to restore the strength and stiffness of the vertebra and relieve pain15, 16. But this increased volume of cement injection increased the risk of cement leakage. A recent study has suggested that injecting more than 4 mL of cement could provide good levels of pain relief and prevent vertebral body re-collapse, and it does not increase the risk of cement leakage14. Apart from that, risk of cement leakage can be minimized by using cement with a toothpaste-like consistency. Thus, injected cement should have an appropriate viscosity and volume. For cement injection, a bilateral transpedicular approach, which applies less pressure and avoids the central part where risk of leakage is higher, may be superior to the unilateral transpedicular approach in patients with severe vertebral collapse or central disk herniation3.

The timing of when PVP is optimal has been long debated17. Thus, it may also have been an additional risk factor for leakage caused by overtreatment. The role of PVP in patients with osteoporotic vertebral compression fractures and chronic pain is indisputable. A treatment plan should be selected after detailed consideration for patients in the acute phase18. Patients with milder symptoms and those without nerve compression should be treated with nonoperative treatment that consists of bedrest, orthopaedic brace, and narcotic analgesia. Elderly patients who are not suitable for prolonged bedrest and those who fail nonoperative therapy should be treated with surgical therapy as early as possible. Application of high-resolution fluoroscopy and mixing PMMA with barium or tungsten for opacification may be crucial for early detection of leakage6, and will have a positive impact on reducing the incidence of serious complications. Furthermore, single-level vertebroplasty poses lower risk of embolism relative to multilevel vertebroplasty. Thus, the number of vertebrae treated per vertebroplasty should be as low as possible. It is suggested that no more than three vertebrae should be injected in a single procedure19. If vertebral venography identifies a direct approach from the needle tip to the venous system intra-operatively, repositioning of the needle tip and pre-injection gelfoam embolization may help avoid leakage20.

Even if PVP is safe and minimally invasive, surgeons should pay more attention to leakage-associated complications as PVP use increases. PMMA cement escape into the cardiac system may trigger life-threatening complications. Thus, timely testing during the operation is crucial. For patients with chest pain and tachypnea, chest radiographs should be performed immediately to determine if there is cement leakage and begin treatment as early as possible.

Acknowledgements

This work was supported by the Teacher-Supporting Science Foundation of Jining Medical University (JYFC2018FKJ170) and Key Research and Development Program of Jining (2020JKNS007) and Natural Science Foundation of Shandong Province (ZR2021MH346)

An Authorship Declaration

All authors listed meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors. All authors read and approved this manuscript.