Pulmonary embolism after shoulder surgery: Is it a real threat?

Abstract

Pulmonary embolism (PE) is a rare but devastating complication of shoulder surgery. Apart from increased morbidity and mortality rates, it may significantly impair postoperative recovery and functional outcome. Its frequency accounts for up to 5.7% of all shoulder surgery procedures with a higher occurrence in women and patients older than 70 years. It is most commonly associated with thrombophilia, diabetes mellitus, obesity, smoking, hypertension, and a history of malignancy. PE usually occurs secondary to upper or lower-extremity deep vein thrombosis (DVT). However, in rare cases, the source of the thrombi cannot be determined. Prophylaxis for PE following shoulder surgery remains a topic of debate, and the standard of care does not routinely require prophylactic medication for DVT prophylaxis. Early ambulation and elastic stockings are important preventative measures for DVT of the lower extremity and medical agents such as aspirin, low-molecular-weight heparin, and vitamin K antagonists are indicated for high-risk patients, long-lasting operations, or concomitant severe acute respiratory syndrome coronavirus 2 infection. The most common symptoms of PE include chest pain and shortness of breath, but PE can also be asymptomatic in patients with intrinsic tolerance of hypoxia. Patients with DVT may also present with swelling and pain of the respective extremity. The treatment of PE includes inpatient or outpatient anticoagulant therapy if the patient is hemodynamically unstable or stable, respectively. Hemodynamic instability may require transfer to the intensive care unit, and cardiovascular arrest can be implicated in fatal events. An important issue for patients with PE in the postoperative period after shoulder surgery is residual stiffness due to a delay in rehabilitation and a prolonged hospital stay. Early physiotherapy and range-of-motion exercises do not adversely affect the prognosis of PE and are highly recommended to preserve shoulder mobility and function.

Key Words: Pulmonary embolism; Venous thromboembolism; Shoulder surgery; Shoulder arthroscopy; Shoulder arthroplasty

Core Tip: Pulmonary embolism is a rare and possibly fatal complication of shoulder surgery. While venous thromboembolism, which includes pulmonary embolism and deep vein thrombosis, has been extensively studied, there is a lack of data about pulmonary embolism as a distinct pathology after shoulder surgery. This review summarizes the most important information about this condition and highlights the significance of early diagnosis and treatment.

INTRODUCTION

Venous thromboembolism (VTE) is an umbrella term of two pathologies, deep vein thrombosis (DVT) and pulmonary embolism (PE)[1]. PE is the third most common cause of cardiovascular death worldwide after stroke and heart attack[2]. Most PE events originate as DVTs of the lower extremities and approximately 50% of DVTs lead to silent PE[3].

Although PE is a rare cause of perioperative morbidity and mortality following open shoulder surgery (SS), it is one of the most common reasons for readmission during the postoperative period, following surgical-site infection and other wound complications[4,5]. It is also the main cause of readmission after shoulder arthroscopy[6]. PE may occur primarily or secondarily to upper or lower-extremity DVT after SS[7]. The risk factors that increase the potential of PE after upper-extremity trauma or surgical treatment are similar to those for DVT. They include smoking, hypertension, diabetes mellitus, obesity, a history of cancer, and thrombophilia, among others[8-10]. If misdiagnosed or diagnosed late, PE may progress and become subsequently fatal[11]. Intensive care physicians must be aware of this dreadful condition following SS and keep a high index of suspicion to diagnose and manage it promptly and effectively.

EPIDEMIOLOGY

The overall incidence of PE after SS is 0.08% to 5.7%[12,13]. It has been reported in patients between 26 years and 83 years of age, with the highest occurrence in patients over 70 years of age[14-17]. Women are more prone to PE, with a reported prevalence of 67.5%[18]. The timing of a PE diagnosis ranges from day 1 to day 3 during inpatient care and from day 4 to day 90 after discharge from the hospital[11,15,19,20].

Regarding the primary diagnosis, patients have a two-fold increased risk of experiencing a PE compared with those with osteoarthritis[18]. Regarding the type of surgery, shoulder arthroscopy is associated with the lowest incidence of PE and fixation of proximal humerus fractures have the highest risk of occurrence[21]. The reported incidence of PE following shoulder arthroscopy ranges from 0.01% to 5.7%[12]. Arthroscopic procedures in ambulatory surgical centres are associated with a lower risk of PE than those performed in hospital-based outpatient departments[22,23]. The prevalence of PE following shoulder arthroplasty is reported to be 0.1% to 3%[24,25]. Hemiarthroplasty is associated with a lower incidence of PE than total shoulder arthroplasty (TSA), but anatomic TSA and reverse TSA have similar risk levels[24]. The frequencies of PE after TSA for proximal humerus fractures, osteoarthritis, or rotator cuff arthropathy are similar[26]. The percentage of PE after proximal humerus fracture fixation ranges from 0.3% to 3.3%[21,27]. Interestingly, both open reduction and internal fixation (referred to as ORIF) procedures have a higher prevalence of PE than closed reduction and internal fixation[28]. After readmission for other reasons during the postoperative period following SS, the rates of PE have been reported as 0.25% to 0.3%[29].

RISK FACTORS

While PE in the setting of SS is frequently reported secondary to DVTs in upper or lower extremities, it may occur without a concomitant DVT[15,30] (Table 1). Remarkably, PE seems to be more frequent than DVT after SS[31], and on some occasions, no pre-existing risk factors were identified[32,33]. In a large retrospective study, including 42237 patients, Young et al[18] correlated PE after TSA in patients with a history of proximal humerus fracture, deficiency anaemia, congestive heart failure, chronic lung disease, increased age, obesity, and fluid and electrolyte abnormalities. Longer surgical time and subsequent days of postoperative care have been also reported as significant risk factors[34]. The metabolic syndrome, which includes hypertension, diabetes mellitus, obesity and dyslipidaemia, has also been found to be significantly associated with an increased incidence of PE after SS[35]. In addition, Damodar et al[36] found that patients treated at an altitude over 4000 feet had nearly twice the risk of having postoperative PE than those treated at centres at sea level.

Table 1 Risk factors for development of pulmonary embolism after shoulder surgery.

General	Pulmonary embolism without deep vein thrombosis	Pulmonary embolism with deep vein thrombosis
Increased age; deficiency anaemia; congestive heart failure; chronic lung disease; metabolic syndrome; obesity; fluid and electrolyte abnormalities; proximal humerus fracture; TSA rather than HA; longer surgical time; longer hospitalization; higher altitude (over 4000 feet)	Older than 75 years of age; hypertension; diabetes mellitus; obesity; peripheral arterial disease; prolonged duration of surgery; history of cancer; congenital thrombophilia; prothrombin gene mutation; beta-thalassemia minor	Older than 40 years of age; hypertension; diabetes mellitus; obesity; smoking; personal or family history of thrombosis and thrombophilia; immobilization of the arm; pregnancy; oral contraceptive use; malignancy; central venous catheters; implantable cardiac rhythm devices

HA: Hemiarthroplasty; TSA: Total shoulder arthroplasty.

PE without DVT

The most common associated risk factors for primary PE after SS are an age of more than 75 years, peripheral arterial disease, hypertension, diabetes mellitus, obesity, prolonged duration of surgery, and a history of cancer[11,28,37,38]. Genetic conditions, such as congenital thrombophilia, prothrombin gene mutation, and beta-thalassemia minor have also been reported as predisposing factors[14,27]. Tranexamic acid, which is commonly used during shoulder arthroscopy and arthroplasty to limit blood loss and postoperative hematoma formation, does not seem to affect the risk of PE[39,40]. Similarly, the use of oral contraceptive pills has not been clearly related to an increased risk of PE after SS[41].

PE secondary to DVT

PE following SS may be secondary to DVT of upper or lower extremities[37,42]. Thrombosis of the cephalic and subclavian veins subsequent to blood clot formation in the arm have also been described[43,44]. In such cases, the predisposing factors for PE are similar to those associated with DVT of the upper extremities and include central venous catheters, implantable cardiac rhythm devices, a personal or family history of thrombosis and thrombophilia, immobilization of the arm, pregnancy, use of oral contraceptives, and malignancy[45].

Lower-extremity thrombosis and PE may also be encountered after SS[46]. A personal or family history of VTE, congenital prothrombotic disorders, smoking, obesity, recent surgery or immobility, a history of cancer, pregnancy, combined hormonal contraceptives or hormone replacement therapy have been associated with an increased likelihood of developing lower-extremity DVTs[47]. Other patient characteristics include an age of more than 40 years, hypertension, diabetes mellitus, inflammatory bowel disease, rheumatic diseases, heart failure, spinal cord injury, and a Glasgow Coma Scale score of less than 8[37,48].

PATHOPHYSIOLOGY

PE after SS usually occurs following DVT of the upper or lower extremities[37,49-51]. The subclavian, axillary, brachial, and cephalic veins have been reported as sources of emboli from the upper limb[42,50,52]. The Virchow triad includes three factors that may lead to development of vascular thrombosis, namely hypercoagulability of the blood, alteration of blood flow, and endothelial damage[53].

Except for coagulopathy and anatomical factors, compression from the shaver or oedema from serum infusion during the operation, the beach-chair position, and elevated traction have been proposed as possible causes of regional DVT during shoulder arthroscopy[44,54]. In patients undergoing shoulder arthroplasty, the axillary vein may be damaged secondary to extreme traction, repeated rotation, position in extension, or by direct pressure from the retractors[55,56]. In some circumstances, the source of the PE remains unclear[30,38,57]. A DVT at the elbow or wrist after SS might be missed because the thrombus causing the PE had already been shed at the time of investigation, leaving only small residual thrombi to detect[54,58]. A right atrial thrombus secondary to atrial fibrillation has previously been implicated as a potential source of PE[58].

PROPHYLAXIS

Prophylaxis for VTE following SS remains a topic of debate. To date, the standard of care after SS does not routinely require prophylactic medication[59,60]. It is generally believed that early ambulation and rehabilitation beginning on the same day or the first day after the operation protects patients from VTE events[61]. The National Institute for Health and Care Excellence (commonly known as NICE) guidelines for VTE prevention recommend pharmacological thromboprophylaxis in high-risk patients with one or more of the proposed risk factors (Table 2).

Table 2 National Institute for Health and Care Excellence patient-related risk factors for venous thromboembolism[62].

Over 60 years of age

Obesity (BMI > 30 kg/m2)

Known thrombophilia

Dehydration

Active cancer or cancer treatment

One or more significant medical comorbidity

Personal history or first degree relative with a history of VTE

Varicose veins with phlebitis

Hormone replacement therapy

Oestrogen-containing contraceptive therapy

Pregnancy or delivery in the previous 6 weeks

BMI: Body mass index; VTE: Venous thromboembolism.

Regarding upper-extremity surgery, VTE prophylaxis is recommended in shoulder operations performed under general anaesthesia that lasts more than 90 min or when the patient’s condition does not allow early postoperative mobilization[62]. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease has been considered an additional risk factor for appearance of thromboembolic events[63].

Early ambulation, elastic stockings, foot impulse devices, and sequential compression devices on the lower extremities are widely used in the perioperative period after SS[64,65]. Medical agents used for prophylaxis in high-risk patients include aspirin, low-molecular-weight heparin, vitamin K antagonists, fondaparinux, and newer oral anticoagulants[66]. Daily administration of aspirin at 325 mg has been suggested in patients who are SARS-CoV-2-positive, in the immediate postoperative period after SS[67].

The repair of proximal humerus fractures may also require VTE chemoprophylaxis. Hoxie et al[33] reported that 7 of 137 patients treated with ORIF or hemiarthroplasty after isolated proximal humerus fractures developed a PE following procedures in which no pharmacological agents were used for VTE prevention. Only thromboembolic deterrent stockings and sequential compression devices were used. Widmer et al[68] reported that oral aspirin, pneumatic compression pumps, and early ambulation were effective for the prevention of VTE after ORIF of proximal humerus fractures. None of the 50 patients included in the study developed DVT or PE.

Shoulder arthroscopy is considered a safe procedure with a low incidence of VTE[46]. Mechanical prophylaxis alone seems to be enough for the prevention of VTE. Only 1 of 175 patients was diagnosed with asymptomatic PE following shoulder arthroscopy in a study of Takahashi et al[57], where only foot pumps or elastic stockings were used for VTE prophylaxis. Alyea et al[69] compared the effectiveness of mechanical prophylaxis alone or with concomitant aspirin administration and found no additional benefit of aspirin in cases undergoing arthroscopic rotator cuff repair.

An increase in the use of drugs for VTE prevention, especially aspirin and direct Factor Xa inhibitors, after shoulder arthroplasty has been reported recently[70]. However, the routine use of thromboprophylaxis in shoulder arthroplasty remains debatable[71]. Kirsch et al[72] found that a low dose of aspirin (81 mg) once daily for 6 weeks was associated with a low risk of VTE after primary shoulder arthroplasty. The authors recommended preoperative medical-risk stratification, but Kolz et al[15] reported that 5 of 10 patients with PE after elective shoulder arthroplasty had been taking aspirin (81 mg) daily, which makes the effectiveness of aspirin alone for VTE prophylaxis questionable.

CLINICAL FEATURES AND DIAGNOSIS

In general, chest pain and shortness of breath are the two most frequent symptoms of PE[73]. These symptoms also present in patients experiencing PE after SS[19,25]. Hypoxia, hypocapnia, tachypnoea, palpitations, tachycardia, and signs of right-side cardiac stress on electrocardiography are other possible clinical signs[73]. When PE occurs following DVT, swelling and a new onset of pain in the extremities are common[58]. Congestion of superficial veins, cyanosis of the hands, finger paraesthesia, and functional impairment may also be present[32]. PE after SS is rarely asymptomatic[58,64]. This is explained by an intrinsic tolerance in hypoxia, which may be related to living at a high altitude for a long time or presence of chronic obstructive pulmonary disease[74].

In asymptomatic cases, low arterial oxygen saturation and elevated D-dimers may raise suspicion of this condition. However, as they may be transiently elevated because of the operation, they cannot confirm the diagnosis[58]. Computed tomography pulmonary angiography is the current gold standard for the diagnosis of PE, and it has replaced ventilation-perfusion lung scintigraphy and pulmonary angiography[75]. In fatal cases, PE after SS has been diagnosed only during post-mortem examinations[51,56].

TREATMENT

Anticoagulant therapy is the mainstay for the treatment of PE and is classically divided into three phases. In the acute phase (i.e. the first 5 days to 10 days after diagnosis) the treatment options include subcutaneous injection of low-molecular-weight heparin or fondaparinux, intravenous unfractionated heparin, or the oral Factor Xa inhibitors rivaroxaban and apixaban[76]. In the second phase (i.e. the next 3 months to 6 months) direct oral anticoagulants or vitamin K antagonists are usually administered[77,78]. An overlap period of administering oral agents with heparins or fondaparinux is required until the former reach effective levels[75]. Oral anticoagulants include the thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitors rivaroxaban, apixaban, and edoxaban[73]. These agents have been proven equivalent to vitamin K antagonists but with lower risk of clinically relevant bleeding and no need to monitor the international normalized ratio[75]. In the event of PE after SS, warfarin is commonly used for up to 6 months during this period[11,15,19,33]. In the last phase, medical treatment is continued in high-risk patients for preventing PE recurrence. The optimal duration of this phase is estimated by weighting the risk of recurrence and bleeding[79].

Patients with PE who are hemodynamically stable are at low risk of death and can usually be discharged within the first 2 days after diagnosis[80]. However, PE may be associated with hemodynamic instability and a high risk of early mortality[73]. In such cases, immediate intravenous administration of thrombolytic agents is needed to promptly restore pulmonary perfusion. Extended hospitalization may be required[79].

PROGNOSIS

Most patients with PE after SS are properly treated[14,15,20,37]. Extended hospitalization or transfer to an intensive care unit are often needed until the patient is considered sufficiently stable for discharge[25]. PE secondary to cardiopulmonary arrest is rarely fatal[43,49]. The PE Severity Index uses 11 clinical criteria to predict the 30-day outcome of patients with PE[81]. An algorithm for the management of PE after SS is shown in Figure 1.

Figure 1 Management algorithm of pulmonary embolism after shoulder surgery. DVT: Deep vein thrombosis; ICU: Intensive care unit; PE: Pulmonary embolism.

In most patients, the functional outcome of the surgical procedure is not affected but a delay in rehabilitation should be expected[11,67]. Although strenuous exercise and squeezing of the arm are contraindicated, the evidence that physiotherapy of the shoulder should be avoided or modified is not sufficient[58]. The shoulder pathology and postoperative recommendations indicate that early passive or gentle active range-of-motion exercises can be commenced and continue until joint function is restored. However, data regarding the frequency, intensity, and duration of exercises are not available, and no specific rehabilitation protocol exists[42,67].

Stiffness is the most common complication and may take up to 6 months to resolve[32]. Aggressive physiotherapy and interventions, such as intra-articular injections or manipulation under aesthesia, may be needed if the joint range-of-motion does not improve postoperatively[37]. In rare cases, PE may lead to delayed recovery, persisting pain, and inability to reach former levels of strength, performance, and sports activity[50].

CONCLUSION

PE is a rare but potentially fatal complication after SS. Clinicians should have a high degree of suspicion for PE if respiratory difficulty develops in the postoperative period. While thromboprophylaxis following SS remains a topic of debate, the number of risk factors predisposing to the development of PE continues to increase. Prevention and early diagnosis and treatment are of utmost importance to limit the associated morbidity and mortality. As early physiotherapy and range-of-motion exercises do not adversely affect the prognosis of PE, they are highly recommended to preserve shoulder mobility and function.