Timing of thrombolytic in PE

Timing of thrombolytic in PE

In contrast to thrombolysis for myocardial infarction and stroke, thrombolysis for PE has a longer time window of opportunity. One group12 compared data for 308 patients from five PE thrombolysis trials and followed the improvement based on lung scans and angiograms up to 14 days after initial presentation with a PE. These data showed a persistent but attenuated benefit from thrombolysis when given up to 14 days later: 86 percent of patients improved an average of 16 percent when thrombolytics were given within the first 24 hours, whereas 69 percent of patients improved an average of 8 percent when treated seven to 14 days after a PE. Therefore, although benefit from thrombolysis for PE may be seen when given up to 14 days after the initial diagnosis of a PE, it is most beneficial when given as early as possible.

Although the principle in the treatment of venous and arterial
thrombosis is identical, the thrombolytic time window differs largely. Thrombolytic therapy is effective for arterial thrombo- sis within several hours after onset, but venous thrombosis can be delayed to several days, 2 weeks, or even longer. The mechanism underlying the difference in the thrombolytic time window between venous and arterial thrombosis still remains unclear.
Pulmonary artery catheter angiography was performed in a 31-year-old patient admitted with dyspnea, and pulmonary embolism (PE) diagnosis was confirmed. A catheter was inserted to the pulmonary artery, and the embolus was obtained for mass spectrographic analysis of thrombus proteins. Results showed that a majority of proteins were less than 130 kD in weight, with great differences in protein abundance. There are proteins found within the relative abundance of trace to 34.34% (Figure 1 and ,Table 1).
Mass spectrographic analyses showed that a large majority of proteins were fibrinogen; the remaining proteins included serum albumin and cytoskeletal proteins.
Early thrombolytic therapy may prove efficacious (1–3). Furthermore, some patients can benefit from thrombolytic therapy even 6 to 14 days after PE (4). In our experience, thrombolytic therapy was applied in patients more than 2 weeks after PE with favorable outcome, but the mechanism underlying the wide thrombolytic time window in patients with PE remains unclear. According to the phlebothrombosis theory, in veins the blood flow is slow and the thrombus is rich in fibrin and red cells, only with a small amount of platelets. Ten days after the onset of acute PE in the patient described above, the embolus was found to be red, flexible, elastic, and fragile. Our mass spectrographic analysis showed that the main component of thrombus in acute PE was fibrinogen, with some serum albumin and cytoskeletal proteins. Fibrinogen makes the embolus frag- ile, which explains the reason for the wide thrombolytic time window; it also explains why patients with PE with stable hemodynamics may benefit from anticoagulant therapy alone, and why interventional thromboclasis is still effective for patients with acute PE (5). The thrombus of venous thromboembolism (VTE) in pathology mainly includes red thrombus and mixed thrombus, with a small mount of white thrombus. The protein component of red thrombus in acute PE is mainly fibrinogen, which can convert to fibrin, but this needs some time, which may explain why patients with VTE may benefit from antico- agulant therapy alone.

Fever in PE

PE-related fever is usually low-grade, rarely exceeding 38.3°C, and short-lived, reaching its peak the same day on which the PE occurs and gradually disappearing within 1 week

The pathogenesis of PE-related fever has not yet been fully clarified. It has been suggested that 1 or a combination of a variety of potential pyrogenic mechanisms occurs: infarction and tissue necrosis, hemorrhage, local vascular irritation or inflammation, atelectasis, or self-limited occult superinfections.2,5 The presence of a slight inflammatory response is indirectly confirmed by the concomitant increase of serum markers of inflammation.4,6 The presence of a modest leucocytosis (rarely exceedingly 20 000/mm3) during the first hospital week is not uncommon, being described in up to 20% of patients with PE who have no other possible or defined cause of leucocytosis.2,7 The differential white blood cell count usually remains normal, only rarely showing a slight neutrophilia.7 Similarly, a slight increase in erythrocyte sedimentation rate and in C-reactive protein can also be observed.

PE risk

High risk PE
-Massive PE

Intermediate risk
-Hemodynamic stable with RV dysfunction and/or injury

Right ventricular hypokinesis and dilatation have been shown to be independent predictors of 30-day mortality among hemodynamically stable patients.

Right ventricular dysfunction, as assessed by means of multidetector CT, has been suggested to be an in- dependent predictor of 30-day mortality

a value of less than 1.0 for the ratio of the right ventricular diameter to the left ventricular diameter had a 100% negative predictive value for an uneventful outcome

elevated levels of troponin had an in- crease in the short-term risk of death by a factor of 5.2 (95% CI, 3.3 to 8.4) and an increase in the risk of death from pulmonary embolism by a factor of 9.4 (95% CI, 4.1 to 21.5).

Normal levels of BNP and pro- BNP were shown to have a nearly 100% negative predictive value for an adverse outcome in hemo- dynamically stable patients.

Massive Pulmonary embolism

Massive Pulmonary embolism definition

-1. arterial hypotension (sys- temic arterial pressure of <90 mmHg or a drop in systolic arterial pressure of at least 40 mmHg for at least 15 min) -2.cardiogenic shock (peripheral hypoperfusion, hypoxia including altered mental status, syncope, oliguria, and cool, clammy extremities)

Massive PE frequently results in acute right ventricular failure and death. within one to two hours of the event, although patients remain at risk for 24 to 72 hours [

All acute PE not meeting the definition of massive PE are considered submassive PE.

A saddle PE is a PE that lodges at the bifurcation of the main pulmonary artery into the right and left pulmonary arteries.

Anticoagulant in PE

Anticoagulant in PE

-recommend subcutaneous low molecular weight (SC LMWH) for most hemodynamically stable patients with PE.
-Compared to intravenous unfractionated heparin (IV UFH), SC LMWH results in lower mortality, fewer recurrent thrombotic events, and less major bleeding

In 18 trials (8054 patients), SC LMWH decreased mortality (odds ratio 0.76, 95% CI 0.62-0.92).
In 22 trials (8867 patients), SC LMWH decreased recurrent thrombosis (odds ratio 0.68, 95% CI 0.55-0.84).
In 12 trials, thrombus size reduction was more common with LMWH (odds ratio 0.69, 95% CI 0.59-0.81).

-Additional advantages of SC LMWH over IV UFH include greater bioavailability, more predictable pharmacokinetics, once or twice daily administration, fixed dosing that does not require adjustment, and a decreased likelihood of thrombocytopenia
-แต่จริงๆ HIT ก็เกิดทั้ง heparin and enoxaparin นะ

-prefer SC LMWH > fondaparinux or SC UFH for the treatment of hemodynamically stable PE:
-SC LMWH and fondaparinux have not been directly compared, but each has been compared to IV UFH
-While SC LMWH may be superior to IV UFH as discussed above,
-fondaparinux and IV UFH appear to be equivalent [29].

-Randomized trials indicate that SC LMWH and SC UFH have similar outcomes and risks, regardless of whether or not such therapy was titrated to goal aPTT. One trial randomly assigned 720 patients with PE or DVT to receive SC LMWH, or SC UFH titrated to a goal aPTT [30]. The groups had similar rates of recurrent events (3.9 versus 4.2 percent for SC UFH) and major bleeding (0.8 versus 1.1 percent for SC UFH). In a similar trial, 708 patients with PE or DVT were randomly assigned to receive SC LMWH, or an initial weight-based dose of SC UFH followed by a fixed dose [31]. The groups had similar rates of recurrent events (3.4 versus 3.8 percent for SC UFH) and major bleeding (1.4 versus 1.1 percent for SC UFH).

-Different formulations of SC LMWH have been infrequently compared. In one trial, 505 patients with PE or DVT were randomly assigned to receive tinzaparin or dalteparin for at least five days [32]. There was no difference in the frequency of major bleeding, recurrent PE, or recurrent DVT, suggesting that tinzaparin and dalteparin are equally safe and effective in the management of acute PE. Similar trials comparing other types of LMWH are lacking

***แต่ถ้าจาก ESC
high risk recommend UFH (IA)
non high risk recommend LMWH or Fonda (IA)

Effect of position on IAP

Effect of position on IAP

-HOB (head of bed increase IAP) significant when > 20-30 degree
หัวยิ่งสูงยิ่ง increase
-Trendelenberg decrease IAP
-ถ้าต้องการหัวสูง ก็ reverse trendelenberg ก็จะลด IAP ได้
-Prone significant increase ยกเว้น ใช้เตียงแบบ เปิดพุง
-Knee chest position increase abdominal pressure (เอาไว้เบ่งอึ)

Hypoxia and Hypoxemia

Hypoxemia
1.low FiO2
2.Hypoventilation
3.Shunt
4.V/Q
5.Diffusion defect
6. Low mixed venous

Hypoxia
1.Low oxygen delivery
-Anemic hypoxia
-Hypoxic hypoxia
-Stagnic hypoxia
2.Cytotoxic or Histotoxic

SLE and Pleural effusion

pleural effusions in SLE usually small. Pleuritic chest pain is the most common symptom

bilateral 50%
left sided only 17%,
right sided only 17%,
alternate from one side to another in 17%

LE cell tests on the pleural fluid always correlated with the LE test results on the serum, the same test on the pleural fluid provided no additional information (40). There have been false-positive reports with the LE cell test on the pleural fluid

The pleural fluid ANA level should not be measured as it mirrors serum levels and is therefore unhelpful. [C]

Up to 50% of patients with systemic lupus erythematosus (SLE) will have pleural disease at some time in the course of their disease.107 The presence of LE cells in pleural fluid is diagnostic of SLE.107,112 Khare et al111 measured ANA levels in 82 consecutive pleural effusions. Six of the eight samples collected from patients with SLE were ANA positive with a homogenous staining pattern; the two effusions that were negative for ANA had other reasons for their effusions (pulmonary embolism and left ventricular failure). However, eight (10%) of the effusions where the patients had no clinical evidence of SLE were ANA positive. In five of these eight patients the underlying cause of the effusion was malignancy. Other studies have shown similar results and, as the pleural ANA levels often mirror serum levels, the test is of limited diagnostic value.108,112,113

Interferon gamma in pleral fluid

Unstimulated interferon g levels in pleural fluid have also been shown to have similar diagnostic accuracy as ADA in a meta- analysis.
more expensive.

Interferon g release assays (IGRAs) have been studied. Applied to blood in areas with a low incidence of TB, sensitivities as high as 90% have been reported but speci␣city is limited by an inability of the tests to distinguish latent from active TB.

Sensitivity of pleural fluid cytology and biopsy

Sensitivity of pleural fluid cytology
1st time 65%
a further 27% from the second specimen รวมแล้ว 90 %
only 5% from the third
การทำ Pleural Biopsy increase yield in Dx malignancy add on cytology 7%

pleural biopsy is high yield in TB plera
Pleural fluid AFB พบ 0-9 %
Culture 13-65%
Pleural biopsy positive result 50-80%
second time Bx add on 10-40%