Study of clinical profile and management of patients with pulmonary embolism – Single center study

Objective

To study the clinical profile, diagnostic methods and management in patients with symptomatic pulmonary embolism (PE).

Methods

Retrospective assessment of clinical features and management of patients presenting with symptomatic pulmonary embolism from January 2005 to March 2012.

Results

35 patients who were newly diagnosed to have pulmonary embolism with a mean age of 52.1 years were included in the study. Dyspnea (91.4%) and syncope (22.8%) were the predominant symptoms. Echocardiography was done in all patients. 30 patients (85.7%) had pulmonary arterial hypertension, 31 patients (88.5%) had evidence of RV dysfunction and 4 patients (16.7%) had evidence of thrombus in PA, RV. Out of 35 patients, 34 patients (97.14%) showed positive d-dimer reports. Among 35 patients, 24 (68.5%) had positive troponin values. V/Q scan was done in 14 patients (40%) and CT pulmonary angiogram (CTPA) was done in 24 patients (68.5%.). Thrombolysis was done is 24 patients (68.5%). All patients received low molecular weight heparin followed by warfarin. Of the 35 patients, 34 (97.1%) were discharged and were under regular follow up for 6 months and one patient died during the hospital stay.

Conclusion

Pulmonary embolism is a common problem and can be easily diagnosed provided it is clinically suspected. Early diagnosis and aggressive management is the key to successful outcome.     

Is there a place for inhaled nitric oxide in the therapy of acute pulmonary embolism?

Acute pulmonary embolism (PE) is a serious complication resulting from the migration of emboli to the lungs. Although deep venous thrombi are the most common source of emboli to the lungs, other important sources include air, amniotic fluid, fat and bone marrow. Regardless of the specific source of the emboli, very little progress has been made in the pharmacological management of this high mortality condition. Because the prognosis is linked to the degree of elevation of pulmonary vascular resistance, any therapeutic intervention to improve the hemodynamics would probably increase the low survival rate of this critical condition. Inhaled nitric oxide (iNO) has been widely tested and used in cases of pulmonary hypertension of different causes. In the last few years some authors have described beneficial effects of iNO in animal models of acute PE and in anecdotal cases of massive PE. The primary cause of death in massive PE that is caused by deep venous thrombi, gas or amniotic fluid, is acute right heart failure and circulatory shock. Increased pulmonary vascular resistance following acute PE is the cumulative result of mechanical obstruction of pulmonary vessels and pulmonary arteriolar constriction (attributable to a neurogenic reflex and to the release of vasoconstrictors). As such, the vasodilator effects of iNO could actively oppose the pulmonary hypertension following PE. This hypothesis is consistently supported by experimental studies in different animal models of PE, which demonstrated that iNO decreased (by 10 to 20%) the pulmonary artery pressure without improving pulmonary gas exchange. Although maximal vasodilatory effects are probably achieved by less than 5 parts per million iNO, which is a relatively low concentration, no dose-response study has been published so far. In addition to the animal studies, a few anecdotal reports in the literature suggest that iNO may improve the hemodynamics during acute PE. However, no prospective, controlled, randomized clinical trial addressing this issue has been conducted to date. Future investigations addressing the effects of iNO combined with other drugs such as vasoconstrictors and inhibitors of phosphodiesterase III or V, may increase the responsiveness to iNO in acute PE.     

Does saddle embolism influence short-term prognosis in patients with acute pulmonary embolism?

BACKGROUND: In some patients with acute pulmonary embolism (APE) thrombi may lodge at the levels of the bifurcation of pulmonary trunk and extend into both main pulmonary arteries, forming so-called saddle embolism (SE). AIM: To assess the incidence of SE and whether it is associated with an increased risk of complicated clinical course. METHODS: We studied 150 consecutive patients (94 females, 56 males) aged 63.6+/-16.7 years with APE confirmed with contrast enhanced spiral computed tomography or transesophageal echocardiography. RESULTS: SE was detected in 22 (14.7%) patients. Mean age (SE vs N-SE) was 64.3+/-17.4 vs 63.5+/-16.6 years, heart rate 100.8+/-14.1 beats/min vs 97.8+/-21.1 beats/min, systolic blood pressure 126.2+/-20.1 vs 127.1+/-23.3 mmHg and blood pulsoximetry 92 (68-98) vs 91 (30-98) % (all differences NS). In patients with SE, echocardiographic signs of the right ventricular overload, defined as right to left ventricular end - diastolic ratio >0.6 with right ventricular hypokinesia and/or maximal tricuspid peak systolic gradient >30 mmHg with shortened acceleration time of pulmonary ejection <80 ms, were more frequent (77.3% vs 51.6%, p=0.04), as was the mid-systolic deceleration of pulmonary ejection velocity (77.3% vs 49.2%, p=0.04). Mortality and complicated clinical course rates were similar in patients with SE or N-SE (mortality: 4.5% vs 13.3%, NS, and complicated clinical course: 34.4% vs 25.0%, NS). CONCLUSIONS: Saddle pulmonary embolism is frequent, especially in patients with echocardiographic signs of impaired pulmonary ejection pattern. Saddle embolism does not indicate unfavourable clinical outcome and probably should not influence treatment selection.     

ACR Appropriateness Criteria® acute chest pain--suspected pulmonary embolism

Pulmonary embolism (PE) remains a common and important clinical condition that cannot be accurately diagnosed on the basis of signs, symptoms, and history alone. In the absence of high pretest probability and with a negative high-sensitivity D-dimer test, PE can be effectively excluded; in other situations, diagnostic imaging is necessary. The diagnosis of PE has been facilitated by technical advancements and multidetector computed tomography pulmonary angiography, which is the major diagnostic modality currently used. Ventilation and perfusion (V/Q) scans remain largely accurate and useful in certain settings. Lower-extremity ultrasound can substitute by demonstrating deep vein thrombosis; however, if negative, further studies to exclude PE are indicated. In all cases, correlation with the clinical status, particularly with risk factors, improves not only the accuracy of diagnostic imaging but also overall utilization. Other diagnostic tests have limited roles. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The development and review of the guidelines include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.     

Contribution of pulmonary vasoconstriction to haemodynamic instability after acute pulmonary embolism. Implications for treatment?

Acute pulmonary embolism with haemodynamic instability has a high mortality rate. Death results from an acute increase in right ventricular afterload, and the commonly held view is that mechanical obstruction of the pulmonary vascular bed is largely responsible for this increase. In accordance, recent treatment guidelines for severe pulmonary embolism focus exclusively on interventions aimed at relieving this mechanical obstruction, either by thrombolysis or (catheter) embolectomy. However, there is evidence to indicate that vasoconstriction is a very important contributor to the initial increase in pulmonary vascular resistance after pulmonary embolism. This is consistent with the observation that the degree of mechanical obstruction correlates at best poorly with haemodynamic manifestations. Thromboxane A(2) and serotonin are probably mainly responsible for pulmonary vasoconstriction. Cyclooxygenase inhibitors and serotonin antagonists have been shown in animal experiments to attenuate the haemodynamic response to acute pulmonary embolism and to reduce mortality. In addition, reports of a favourable response to pulmonary vasodilators in animals and in humans with acute severe pulmonary embolism have been published. In this paper, it is argued that we may need to reconsider our current therapeutic approach to patients with acute severe pulmonary embolism. Antagonising pulmonary vasoconstrictive mediators or administering pulmonary vasodilators may prove to be life-saving interventions in these patients.     

Should the cut-off value of D-dimer be elevated to exclude pulmonary embolism in acute exacerbation of COPD?

Objective

The aim of this study was to evaluate the D-dimer levels in patients with chronic obstructive pulmonary disease (COPD) exacerbation with and without pulmonary embolism (PE) and to attempt to define a new cut-off value for D-dimer to exclude the diagnosis of PE in patients with COPD exacerbation.

Methods

This cross-sectional study was performed between the June 2012 and January 2013. The COPD patients who were admitted to the emergency department with acute exacerbation were consecutively included. D-dimer levels were measured upon admission. All patients underwent computed tomography angiography (CTA) and Doppler ultrasonography (US) of the lower extremities.

Results

A total of 148 patients were enrolled. Fifty-three patients (36%) who did not have PE had higher than normal (>0.5 pg/mL) D-dimer levels. The D-dimer levels of the COPD patients with PE were significantly higher than those of the patients without PE (2.38±2.80 vs. 1.06±1.51 pg/mL) (P<0.001). The cut-off value for D-dimer in diagnosing PE in the COPD patients was 0.95 pg/mL. The area under the receiver operating characteristic (ROC) curve was 0.752±0.040 (95% CI: 0.672-0.831) (P<0.001).

Conclusions

This study showed that the D-dimer concentrations of COPD patients who are in the exacerbation period may be higher than normal, even without PE. The cut-off level for D-dimer was 0.95 pg/mL (sensitivity 70%, spesificity 71%) for the exclusion of PE in the patients with COPD exacerbation. The D-dimer cut-off value that is used to exclude PE in patients with acute exacerbation of COPD should be reevaluated to prevent the excessive use of further diagnostic procedures.KEY WORDS : Chronic obstructive pulmonary disease (COPD), D-dimer, pulmonary embolism (PE)     

Platelet glycoprotein Ibα gene polymorphism and massive or submassive pulmonary embolism

Objective The −5T/C polymorphism in the Kozak sequence of glycoprotein Ibα, a component of the platelet glycoprotein Ib-IX-V receptor complex, is associated with an increase in this receptor density on the surface of the platelet. This study was designed to investigate the effect of platelet glycoprotein Ibα Kozak polymorphism on the clinical presentation of the patients with acute pulmonary embolism. Methods Forty-two patients with pulmonary embolism were genotyped for Kozak polymorphism of the glycoprotein Ibα by polymerase chain reaction/restriction fragment length polymorphism. Results Carriers of the −5T/C polymorphism of glycoprotein Ibα were significantly over-represented in the patient group with clinically massive or submassive pulmonary embolism (odds ratio 5.5, 95% confidence interval 1.4 to 22.2, P = 0.023). Also the association between this polymorphism and massive or submassive pulmonary embolism still existed even after being adjusted for conventional risk factors. Conclusion The −5T/C polymorphism in the Kozak sequence of glycoprotein Ibα may present as a risk factor for clinical manifestation of pulmonary embolism in which clot burden plays an important role.     

Clinical presentation and in-hospital death in acute pulmonary embolism: does cancer matter?

Cancer is one of the most common risk factors for acute pulmonary embolism (PE), but only few studies report on the short-term outcome of patients with PE and a history of cancer. The aim of the study was to assess whether a cancer diagnosis affects the clinical presentation and short-term outcome in patients hospitalized for PE who were included in the Italian Pulmonary Embolism Registry. All-cause and PE-related in-hospital deaths were also analyzed. Out of 1702 patients, 451 (26.5 %) of patients had a diagnosis of cancer: cancer was known at presentation in 365, or diagnosed during the hospital stay for PE in 86 (19 % of cancer patients). Patients with and without cancer were similar concerning clinical status at presentation. Patients with cancer less commonly received thrombolytic therapy, and more often had an inferior vena cava filter inserted. Major or intracranial bleeding was not different between groups. In-hospital all-cause death occurred in 8.4 and 5.9 % of patients with and without cancer, respectively. At multivariate analysis, cancer (OR 2.24, 95 % CI 1.27–3.98; P = 0.006) was an independent predictor of in-hospital death. Clinical instability, PE recurrence, age ≥75 years, recent bed rest ≥3 days, but not cancer, were independent predictors of in-hospital death due to PE. Cancer seems a weaker predictor of all-cause in-hospital death compared to other factors; the mere presence of cancer, without other risk factors, leads to a probability of early death of 2 %. In patients with acute PE, cancer increases the probability of in-hospital all-cause death, but does not seem to affect the clinical presentation or the risk of in-hospital PE-related death.     

Is pulmonary embolism a common cause of chronic pulmonary hypertension? Limitations of the embolic hypothesis.

The hypothesis that chronic thromboembolic pulmonary hypertension results from unresolved pulmonary embolism has strongly influenced the diagnosis and management of this disease since the 1960s. However, it is nearly impossible to induce chronic pulmonary hypertension in any animal species by means of repeated embolization of thrombotic material. The haemodynamic effects of thrombotic pulmonary embolism of different degrees of magnitude have also been studied in humans and there is little to suggest that chronic pulmonary hypertension is a likely long term outcome. Furthermore many conditions which predispose to venous thromboembolism do not appear to cause thromboembolic pulmonary hypertension. Other arteriopathic and atherosclerotic risk factors, are found in patients with chronic thromboembolic pulmonary hypertension, but not in those with venous thrombosis, suggesting that these may be unrelated conditions. Thrombosis in situ of the pulmonary arteries is common in severe pulmonary hypertension of any cause. Such thrombosis cannot usually be distinguished from pulmonary embolism. It is hypothesized that in situ thrombosis and pulmonary arteriopathy are common causes of vascular occlusion which is usually diagnosed as "chronic thromboembolic pulmonary hypertension" and that venous thromboembolism is unlikely to be a common cause of chronic pulmonary hypertension. It is further hypothesized that pulmonary embolism is seldom the sole cause of "chronic thromboembolic pulmonary hypertension".     

Thiazides in the management of hypertension in older adults – a systematic review

Background

Thiazides are commonly prescribed to older people for the management of hypertension. The objective of this study was to identify the evidence on the risks and benefits of their use among adults aged ≥65 years and to develop recommendations to reduce potentially inappropriate use.

Methods

Systematic review (SR) of the literature covering six databases. We applied a staged search approach, where each search was undertaken only if the previous one did not yield high quality results. Searches 1 and 2 identified relevant SRs and meta-analyses published up to December 2015 from all databases. Search 3 identified additional individual interventional studies (IS) and observational studies (OS) not identified by the preceding searches. We included all studies evaluating the effect of thiazides on patient-relevant outcomes in the management of hypertension with a sufficient number of participants aged ≥65 years or a subgroup analysis based on age. Two independent reviewers extracted data and carried out quality appraisal. Recommendations were developed using the GRADE methodology.

Results

Searches 1 to 3 were performed. We included 34 articles reporting on 12 IS and 4 OS. Mean ages ranged from 59 to 83.8 years. Four studies had performed a subgroup analysis by age. Information on comorbidity, polypharmacy and frailty of the participants was scarce or not available. The IS compared thiazides to placebo or other antihypertensive drugs and evaluated cardiovascular endpoints or all-cause-mortality as primary outcomes. The OS investigated the association between thiazide use and the risk of gout, fractures and adverse effects. Our results suggest that thiazides are efficacious in preventing cardiovascular events for this population group. Low-dose regimens of thiazides may be safer than high-dose (low quality of evidence), and a history of gout may increase the risk of adverse events (low quality of evidence). Three recommendations were developed.

Conclusions

The use of low dose treatment with thiazides for the management of hypertension in adults aged 65 and older seems justified, unless a history of gout is present. The quality of the evidence is low and studies rarely describe characteristics of the participants such as polypharmacy and frailty. Further good quality studies are needed.

     

Changing management of gallstone-related disease in pregnancy – a retrospective cohort analysis

Objectives: Gallstone-related disease is the second most common non-obstetric cause, following appendicitis, for acute abdomen in pregnancy. This study aimed to investigate treatment strategies, changes over time and outcome.

Materials and methods: All consecutive patients with symptomatic gallstone-related disease during pregnancy admitted to Skane University hospital in Lund and Malmö 2001–2015 were analysed retrospectively. Information regarding the patient, pregnancy and fetus/child was recorded. The material was analysed by dividing it into two equal time periods and by comparing conservative management and surgical intervention.

Results: We included 96 patients with 97 pregnancies. The age was 30 (26–34) years and BMI 28 (24–31). Median length of pregnancy at first admission was 23 (13–31) weeks. The three most common diagnoses were biliary colic (n?=?63), cholecystitis (n?=?22) and acute pancreatitis (n?=?16). Conservative treatment was practiced in 62 (64%) patients and intervention in 35 (36%). Conservatively treated patients were admitted later during pregnancy (week 26 (20–33) versus 17 (10–22), p?<?.001). Surgically treated patients had a longer total length of stay (all admissions) than conservatively treated patients (p?=?.001), less readmissions (p?=?.001) and equal birth outcome. Surgical intervention was more common in the later time period (48% versus 22%, p?=?.011). Of the conservatively treated patients, 56% were subjected to surgical intervention within 2 years after delivery.

Conclusions: We found that intervention was more common in the later time period, with good results concerning safety, and less readmissions. A majority of the conservatively treated patients had surgical intervention within two years after delivery. Our results support surgical intervention in pregnancy.