Outpatient treatment of symptomatic pulmonary embolism: A systematic review and meta-analysis

Background

Patients with acute deep vein thrombus (DVT) can safely be treated as outpatients. However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. We sought to determine the safety of outpatient management of patients with acute symptomatic PE.

Materials and Methods

A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled proportions for the different outcomes were calculated.

Results

A total of 1258 patients were included in the systematic review. The rate of recurrent venous thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95% CI: 0.47 to 3.0%; I²: 65.4%) during the 3 month follow-up period. The rate of fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I²: 0%). The rates of major bleeding and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I²: 0%) and 0.29% (95% CI: 0.06 to 0.68%; I²: 0%), respectively. The overall 3 month mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I²: 45%). The event rates were similar if employing risk stratification models versus using clinical gestalt to select appropriate patients for outpatient management.

Conclusions

Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate.     

Home treatment in pulmonary embolism

Background

Limited data exist on the feasibility of providing outpatient care to patients with acute pulmonary embolism (PE).

Methods

We conducted a multicenter randomized clinical trial in acute symptomatic PE to compare the efficacy and safety of early discharge versus standard hospitalization. A clinical prediction rule was used to identify low-risk patients. All patients were followed for three months. The primary outcomes were venous thromboembolic recurrences, major and minor bleeding, and overall mortality.

Results

One hundred and thirty two low-risk patients with acute symptomatic PE were randomized to early discharge (n = 72) or standard hospitalization (n = 60). Overall mortality was 4.2% (95% CI, 0.5-8.9) in the early discharge group and 8.3% (95% CI, 1.1-15) in the standard hospitalization group (Relative Risk (RR) 0.5; 95% confidence interval [CI], 0.12-2.01). Non-fatal recurrences were 2.8% (95% CI, 1.1-6.6) in the early discharge group and 3.3% (95% CI, 1.3-8%) in the standard hospitalization group (RR 0.8; 95% CI, 0.12-5.74). The rates of clinically relevant bleeding were 5.5% in the early discharge group and 5% in the standard hospitalization group (P = 0.60). Short-term mortality was 2.8% (95% CI, 0.8-9.6%) in the early discharge group as compared with 0% in the standard hospitalization group. Based on the rate of short-term death in a carefully selected population, the study was suspended.

Conclusions

In spite of the number of complications in patients with acute symptomatic PE randomized to standard hospitalization or early discharge did not differ significantly. The rate of short-term mortality was unexpectedly high in a (a priori) low-risk group of patients with acute PE. The accuracy of clinical prediction scores needs to be validated in well designed clinical trials. (ClinicalTrials.gov number, NCT00214929.)     

Unsolved issues in the treatment of pulmonary embolism

The three most controversial and unsolved issues in the treatment of pulmonary embolism (PE) are: (1) the role of thrombolysis, (2) the role of low molecular weight heparin and length of hospital stay, and (3) the optimal duration of anticoagulation. The trend is to use thrombolysis more frequently, to administer low molecular weight heparin and shorten the hospitalization duration in low-risk patients, and to give prolonged courses of anticoagulation with warfarin. PE thrombolysis appears most beneficial in patients at high risk of adverse clinical outcomes in whom the potential hazards of bleeding can be justified by the danger of conservative management with anticoagulation alone. With respect to utilizing low molecular weight heparin as a way of shortening the duration of hospitalization, there are no data to warrant this approach. The current FDA mandate for symptomatic PE patients is to administer intravenous unfractionated heparin administered as a bridge to therapeutic warfarin. Finally, the optimal duration of anticoagulation following acute PE remains mired in controversy. Despite the high rate of recurrent venous thrombosis after discontinuation of anticoagulation, there are currently insufficient data to recommend indefinite warfarin therapy.     

Managing pulmonary embolism from presentation to extended treatment

Pulmonary embolism (PE) remains a major healthcare problem. PE presents with a variety of non-specific symptoms, and confirmation of diagnosis involves the use of clinical risk scores, scanning techniques and laboratory tests. Treatment choice is informed by the risk of sudden death, with high-risk patients recommended to receive thrombolytic therapy or thrombectomy. Patients with less severe presentations are given anticoagulant therapy, traditionally with parenteral heparins in the acute phase of treatment, transitioning to oral vitamin K antagonists (VKAs). The limitations of these agents and the introduction of non-VKA oral anticoagulants challenge this paradigm. To date, clinical studies of four non-VKA oral anticoagulants to treat acute thrombosis have been published, and rivaroxaban is now approved for treatment and prevention of PE (and deep vein thrombosis). Rivaroxaban and apixaban alone, and dabigatran and edoxaban after parenteral anticoagulant induction, were non-inferior to enoxaparin/VKA for the prevention of recurrent venous thromboembolism; the risk of major bleeding was similar with dabigatran and edoxaban and significantly reduced with rivaroxaban and apixaban. Patients with an initial PE are recommended to receive continued anticoagulation for 3 months or longer, depending on individual risk factors, and studies of non-VKA oral anticoagulants have shown a continued benefit for up to 2 years, without a significantly increased risk of major bleeding. Given that the non-VKA oral anticoagulants are given at fixed doses without the need for routine coagulation monitoring, their adoption is likely to ease the burden on both PE patients and healthcare practitioners when longer-term or extended anticoagulation is warranted.     

Clinical relevance of pulmonary infarction in patients with pulmonary embolism

Introduction

Data regarding the clinical relevance of pulmonary infarction (PI) in patients with pulmonary embolism (PE) are lacking. The aim of this study was to investigate the clinical features of PE patients with PI and the prognostic role of PI for PE patients.

Materials and Methods

Based on computed tomography scan, 509 patients with PE were divided into two groups, the infarction group (n = 45) and the non-infarction group (n = 464). A variety of clinical parameters were compared between the two groups.

Results

In the infarction group, the largest pulmonary arteries involved by emboli were central rather than peripheral and more proximal as compared to the non-infarction group (p = 0.01 and p < 0.03, respectively). Thrombolytic agents tended to be more frequently administered in the infarction group (13.3% [n = 6] versus 6.3% [n = 29], p = 0.07). In-hospital mortality, PE-related deaths, and the recurrence rate of PE did not differ between the two groups.

Conclusions

The present study did not demonstrate that PI is a prognostic indicator of recurrence and mortality in PE patients. We suggest the possibility that blood clot burden is greater in PE patients with PI, although PI by itself occurs in small pulmonary arteries.     

Catheter-directed ultrasound-accelerated thrombolysis for the treatment of acute pulmonary embolism

Background

Systemic thrombolysis rapidly improves right ventricular (RV) dysfunction in patients with acute pulmonary embolism (PE) but is associated with major bleeding complications in up to 20%. The efficacy of low-dose, catheter-directed ultrasound-accelerated thrombolysis (USAT) on the reversal of RV dysfunction is unknown.

Materials and methods

We performed a retrospective analysis of 24 PE patients (60 ± 16 years) at intermediate (n = 19) or high risk (n = 5) from the East Jefferson General Hospital who were treated with USAT (mean rt-PA dose 33.5 ± 15.5 mg over 19.7 hours) and received multiplanar contrast-enhanced chest computed tomography (CT) scans at baseline and after USAT at 38 ± 14 hours. All CT measurements were performed by an independent core laboratory.

Results

The right-to-left ventricular dimension ratio (RV/LV ratio) from reconstructed CT four-chamber views at baseline of 1.33 ± 0.24 was significantly reduced to 1.00 ± 0.13 at follow-up by repeated-measures analysis of variance (p < 0.001). The CT-angiographic pulmonary clot burden as assessed by the modified Miller score was significantly reduced from 17.8 ± 5.3 to 8.7 ± 5.1 (p < 0.001). All patients were discharged alive, and there were no systemic bleeding complications but four major access site bleeding complications requiring transfusion and one suspected recurrent massive PE event.

Conclusions

In patients with intermediate and high risk PE, low-dose USAT rapidly reverses right ventricular dilatation and pulmonary clot burden.     

Diagnosis of pulmonary embolism

Pulmonary embolism (PE) is a common, lethal yet treatable disease. The clinical diagnosis of PE remains to be a problem due to the nonspecific presenting signs, symptoms, electrocardiographic findings, arterial blood gas abnormalities and chest X-ray changes. Despite these nonspecific clinical findings, clinicians are adept at assigning pretest probability using overall clinical assessment. Clinical models have been developed to improve the accuracy of pretest probability assessment. D-dimers are becoming a widely available clinical tool useful in the diagnostic management of suspected PE. The limitations of the imaging modalities for PE [ventilation–perfusion (V/Q) scanning, spiral computerised tomography, pulmonary angiography and venous leg imaging] necessitate the use of these tests in series and in combination with clinical pretest probability assessment and D-dimer in diagnostic management algorithms. These algorithms permit safe diagnostic management of patients with suspected PE while limiting invasiveness, inaccessibility and expense.     

Incidence of chronic pulmonary hypertension in patients with previous pulmonary embolism

IntroductionThe true incidence of chronic thromboembolic pulmonary hypertension (CTPH) remains a matter of debate. Symptomatic CTPH is probably more common than previously reported, whereas the occurrence of asymptomatic CTPH has not been defined since very limited evidence on the incidence of asymptomatic CTPH diagnosed with echocardiography Doppler are currently available. We therefore carried out a prospective cohort study to assess the incidence of CTPH diagnosed with echocardiography Doppler in consecutive patients with a first episode of PE.MethodsConsecutive patients with a first episode of PE were evaluated with Doppler transthoracic echocardiography within 6 to 12 months after the index event. Pulmonary hypertension was defined as a systolic pulmonary artery pressure ≥ 40 mmHg at rest in the presence of residual perfusion defects at perfusion scintigraphy. Presence of symptoms related to pulmonary hypertension was evaluated with a standardized questionnaire.ResultsNinety-one patients (mean age 61.9 ± 15.7 years; range 22-89; 39 men) were enrolled. Eight patients (8.8%; 95% CI 4.5,16.4) had CTPH: of these, 4 (4.4%; 95% CI 2.0, 9.3) were symptomatic.ConclusionsAsymptomatic CTPH is not an uncommon finding after PE. Larger prospective trials with a longer follow up should assess the prognostic significance of asymptomatic CPTH.     

Stroke associated with pulmonary embolism after air travel

Prolonged air travel is associated with an increased incidence of thromboembolic events. The occurrence of stroke was studied in patients with pulmonary embolism after air travel in a review of all flights arriving at Charles de Gaulle Airport in Paris during an 8-year period. Thromboembolic stroke and patent foramen ovale were diagnosed in four patients with pulmonary embolus.     

颅咽管瘤术后肺动脉栓塞的研究

目的研究颅咽管瘤术后肺动脉栓塞的发生情况及可能原因。方法回顾性分析185例颅咽管瘤病人的临床资料,其中发生肺动脉栓塞5例(2.7%),经CT肺动脉造影证实4例。对5例病人的血电解质水平、去氨加压素及地塞米松的使用进行研究。结果随访5例,时间6~30个月,死亡3例,痊愈2例。3例病人血钠持续高于正常值(145~170 mmol/L)。5例病人均至少使用1个月的去氨加压素及7 d的地塞米松。结论高钠血症、长期使用去氨加压素和地塞米松可能诱发血液高凝状态而增加病人术后发生肺动脉栓塞的风险。     

Prognostic value of D-dimer in patients with pulmonary embolism

D-dimer levels appear to be associated with the extent of the thromboembolic burden in patients with pulmonary embolism (PE). We therefore hypothesized that D-dimer levels at admission would be associated with prospective risk of mortality in patients with PE. We used data from 366 patients diagnosed with PE at four hospital emergency departments. A highly sensitive D-dimer test was prospectively performed at admission. The outcome was overall mortality within three months. We divided patients into quartiles on the basis of their D-dimer levels and compared mortality rates by quartile. We estimated sensitivity, specificity, and predictive values for mortality in the first and fourth quartile. Overall mortality was 5.2%. Patients who died had higher median D-dimer levels than patients who survived (4578 versus 2946 microg/l; p = 0.005). Mortality increased with increasing D-dimer levels, rising from 1.1% in the first quartile (<1500 microg/l) to 9.1% in the fourth quartile (>5500 microg/l) (P = 0.049). Sensitivity, specificity, and positive and negative predictive values of D-dimer levels <1500 microg/l to predict mortality were 95%, 26%, 7%, and 99%, respectively. Patients with PE who have D-dimer levels below 1500 microg/l have a very low mortality. Further studies must assess whether D-dimer, alone or combined with other prognostic instruments for PE, can be used to identify low-risk patients with PE who are potential candidates for outpatient treatment or an abbreviated hospital stay.     

Outpatient treatment for patients with eating disorders

In the treatment of eating disorders, patients in either the acute or chronic stage are generally treated on outpatient basis as much as possible in the living condition of daily life. This paper describes the flow of diagnosis and treatment, first examination and introduction into treatment, way of parents treating their child, parental counseling, criteria for admission (immediate hospitalization or not), and outpatient therapy.     

Acute pulmonary embolism in childhood

Pulmonary embolism is an uncommon, but potentially fatal disease in children. Most children with pulmonary embolism have underlying clinical conditions, of which the presence of a central venous catheter is the most frequent. The clinical presentation is often subtle, or masked by the underlying clinical condition. Diagnostic as well as therapeutic strategies for pulmonary embolism in children are mostly extrapolated from studies in adults. Pulmonary angiography is still the gold standard in diagnosing pulmonary embolism, but several other radiographic tests can be used to diagnose pulmonary embolism, including ventilation-perfusion lung scanning, helical computed tomography, magnetic resonance imaging and echocardiography. The choice of treatment depends on the clinical presentation of the patient. Anticoagulation is the mainstay of therapy for children with pulmonary embolism. However, thrombolytic therapy can be considered for patients with hemodynamic instability. The outcome of pediatric pulmonary embolism is uncertain and needs to be studied.