Prognostic Role Of Aa Do2 In Acute Pulmonary Embolism

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Prognostic Role Of Aa Do2 In Acute Pulmonary Embolism

  1. 1. Prognostic Role of Alveolar-arterial Oxygen Pressure Difference (AaDO2) in Acute Pulmonary Embolism Hsu Jen Te
  2. 2. Background <ul><li>This study investigated the utility of alveolar-arterial oxygen pressure difference (AaDO2) in predicting short-term prognosis of acute pulmonary embolism (PE). </li></ul>
  3. 3. Introduction <ul><li>Acute pulmonary embolism (PE) has high incidence and mortality rates </li></ul><ul><li>The International Cooperative Embolism Registry of 2454 patients reported a high 90-day all-cause mortality rate of 17.4% </li></ul>
  4. 4. ICOPER: Mortality 11.4% at 2week & 17.4 at 3 months
  5. 5. Acute Pulmonary Embolism <ul><li>Low PaO2 </li></ul><ul><li>Low PaCO2 </li></ul><ul><li>High AaDO2 </li></ul>
  6. 6. Four processes cause arterial hypoxaemia due to inefficient pulmonary gas exchange : <ul><li>ventilation–perfusion ( V / Q ) mismatch </li></ul><ul><li>Hypoventilation </li></ul><ul><li>diffusion limitation </li></ul><ul><li>true shunt. </li></ul>
  7. 7. ABG analysis have proved disappointing as diagnostic modalities <ul><li>normal values for alveolar-arterial oxygen gradient do not exclude acute PE </li></ul><ul><li>hypoxemia discriminates poorly between those with and without acute PE. </li></ul><ul><li>absence of such abnormal values of arterial blood gas analysis, alone or in combination, do not exclude PE. </li></ul>
  8. 8. Paper reviews <ul><li>AaDO2 has a linear correlation to actual perfusion defect </li></ul><ul><li>a sensitive indicator suggestive of resolved emboli </li></ul>
  9. 9. Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study <ul><li>a linear correlation existed between AaDO2 and PE severity </li></ul><ul><li>pulmonary artery mean pressure , </li></ul><ul><li>the number of mismatched perfusion defects </li></ul>
  10. 10. Our interests <ul><li>The possibility of different gradients of AaDO2 or other artery blood gas analyses can be utilized to predict prognosis of acute PE </li></ul>
  11. 11. Methods and Materials CMRGP 650031
  12. 12. Study Sample <ul><li>This study retrospectively identified 114 consecutive patients hospitalized at Chang Gung Memorial Hospital (CGMH), Taiwan, between May 2001 and July 2003 with acute PE. </li></ul>
  13. 13. Including criteria <ul><li>spiral computed tomography (CT) or </li></ul><ul><li>high probability ventilation and perfusion lung scan </li></ul><ul><li>first arterial blood gas analysis under room air(FIO2=0.21)<24 hours </li></ul>
  14. 14. Excluding criteria <ul><li>low probability ventilation and perfusion lung scan </li></ul><ul><li>Moderate probability ventilation and perfusion lung scan </li></ul><ul><li>Suspecting Septic emboli or tumor emboli </li></ul><ul><li>Chronic lung disease </li></ul>
  15. 15. Treatment <ul><li>unfractionated heparin or low molecular weight heparin for all pts </li></ul><ul><li>Selective thrombolysis with tPA 100mg IVF(2 hours) </li></ul><ul><li>Oral warfarin for all discharged pts, at least 6 months </li></ul>
  16. 16. Clinical features and biochemical data <ul><li>Characteristics of pts - gender, age, duration of symptoms, underlying disease, and possible risk factors </li></ul><ul><li>Baseline biochemical data - blood urea nitrogen, serum creatinine, troponin I, D-dimer, artery blood gas, platelet count </li></ul><ul><li>Electrocardiography, chest X-ray and echocardiography findings </li></ul>
  17. 17. Artery blood gas analysis <ul><li>AaDO2(mmHg)=150-1.25PaCO2-PaO2(FIO2=0.21) </li></ul><ul><li>a/APO2=1- AaDO2/PAO2 </li></ul><ul><li>[Arterial/alveolar oxygen tension ratio (a/APO2)] </li></ul><ul><li>All measurements were obtained within 24 hours prior to anticoagulant therapy </li></ul>
  18. 18. The arterial/Alveolar oxygen tension ratio(a/APO2 : an index of gas exchange applicable to varying inspired oxygen concentrations) Gilbert and Karetzky et al. American review of respiratory disease 1974
  19. 19. Stability of the arterial/alveolar oxygen partial pressure ratio: effects of low ventilation/perfusion regions. Gilbert el al. Critical care medicine 1979
  20. 20. Clinical Endpoints <ul><li>Primary endpoint: 30-day all-cause death </li></ul><ul><li>Secondary endpoint: composite endpoint of 30-day death and in-hospital complications, including cardiopulmonary resuscitation , mechanical ventilation and vasopressors for systemic arterial hypotension. </li></ul><ul><li>All enrolled patients were received follow-up for > 1 year. </li></ul>
  21. 21. Statistical analysis <ul><li>The student’s t-test for comparing continuous variables </li></ul><ul><li>the proportion test for categorical variables </li></ul><ul><li>Receiver operating characteristic(ROC) analyses were applied to determine the high-sensitivity AaDO2 and a/APO2 cutoff value </li></ul><ul><li>Multivariate Cox regression analyses were employed to estimate the cumulative probability of primary and composite endpoints </li></ul>
  22. 22. Results <ul><li>Total 114 patients </li></ul><ul><li>Only 1 patient had an AaDO2< 20 mmHg. </li></ul><ul><li>The other 113 patients had abnormal AaDO2 values (AaDO2> 20 mmHg). </li></ul>
  23. 23. Table 1. Clinical characteristics, echocardiographic parameters, and cardiac troponin I in PE survivors and patients who died at 30 days.
  24. 24. Table 2. Clinical characteristics, echocardiographic parameters, and cardiac troponin I in the 30-day composite-event free group vs. the 30-day composite event group
  25. 25. 30-day mortality & composite event rate <ul><li>All-cause 30-day mortality was 17.5%. </li></ul><ul><li>The 30-day composite event rate was 26.3%. </li></ul>
  26. 26. Parameters influences primary end point <ul><li>Cancer </li></ul><ul><li>Hypotension </li></ul><ul><li>Thrombocytopenia </li></ul><ul><li>low PaCO2 level </li></ul><ul><li>elevated Troponin I level. </li></ul>
  27. 27. Additive parameters influences secondary end point <ul><li>diabetes mellitus (DM) </li></ul><ul><li>AaDO2 level </li></ul><ul><li>a/APO2 level </li></ul><ul><li>renal insufficiency </li></ul><ul><li>right ventricular dilatation (RVD). </li></ul>
  28. 28. The analytical findings have not been published <ul><li>Statistical analysis demonstrated that incidence of thrombocytopenia and renal insufficiency were significantly different between 30-day composite endpoint group and 30-day composite event-free group; this analytical finding has not been published. </li></ul>
  29. 29. Incidence of thrombocytopenia <ul><li>The odds ratio for 30-day mortality was 4.49 (95% CI=1.86–10.87). </li></ul><ul><li>The odds ratio for 30-day composite endpoint was 2.96 (95% CI=1.44–6.11). </li></ul>
  30. 30. Figure 1. ROC curves for variable artery blood gas analysis.
  31. 31. Figure 2. ROC curves for AaDO2 and a/APO2-R <ul><li>The area for a/A PO2 =0.650 </li></ul><ul><li>The area for AaDO2 </li></ul><ul><li>=0.657 </li></ul>
  32. 32. The optimal cut-off value for AaDO2 was 53mmHg. <ul><li>The incidence of AaDO2≥53mmHg also showed a significant difference between those two groups(primary end points) </li></ul><ul><li>the positive predictive value for 30-day death was 25%; the negative predictive value was as high as 92% </li></ul><ul><li>for the secondary endpoint, the positive predictive value of a/APO2 was 39%, and negative predictive value was 83%. </li></ul>
  33. 33. A prognostic cut-off value of a/APO2 ratio was 0.49 <ul><li>the positive predictive value for primary end-point was 26.5%, and negative predictive value was 89%. </li></ul>
  34. 34. Figure 3. Survival curves at 1 year, based on a cut-off values of AaDO2≥53mmHg vs. AaDO2<53mmHg <ul><li>HR=3.55 </li></ul><ul><li>(95% CI=1.19–10.62) </li></ul>
  35. 35. Figure 4. Composite event-free survival curves at 1 year, based on cut-off values of AaDO2≥53mmHg vs. AaDO2<53mmHg <ul><li>HR=2.55 </li></ul><ul><li>(95% CI=1.14–5.74) </li></ul>
  36. 36. Discussion
  37. 37. What is the role of AaDO2 analysis in patients with documented pulmonary embolism? <ul><li>The AaDO2 is typically used as an index of gas exchange. </li></ul><ul><li>The factors influencing AaDO2 are diffusion gradient, ventilation-perfusion imbalance and true shunt. </li></ul><ul><li>The combination of AaDO2 and pulmonary artery pressure have been used for classifying PE. </li></ul>
  38. 38. AaDO2≧53mmHg <ul><li>high negative predictive rate </li></ul><ul><li>moderate positive predictive rate. </li></ul><ul><li>Aggressive thrombolytic strategy should be considered for patients with an AaDO2 ≥53mmHg. </li></ul>
  39. 39. Future investigation plan <ul><li>AaDO2 can be used in combination with other parameters, such as hypotension, high troponin I, RVD to improve the accuracy of prognosis evaluation. </li></ul>
  40. 40. The role of a/APO2 analysis in patients with documented pulmonary embolism. <ul><li>Gilbert et al. (7) investigated the impact of fractional inspired oxygen concentration (FIO2) on the AaDO2 gradient and a/APO2 ratio in normal subjects. </li></ul><ul><li>They demonstrated that a/APO2 provides a uniform guide to gas exchange function over the range of FIO2 used in clinical practice. </li></ul><ul><li>Gilbert et al. defined the lower limit of normal for the ratio as approximately 0.75 </li></ul>
  41. 41. The arterial/Alveolar oxygen tension ratio(a/APO2 : an index of gas exchange applicable to varying inspired oxygen concentrations) Gilbert and Karetzky et al. American review of respiratory disease 1974
  42. 42. Stability of the arterial/alveolar oxygen partial pressure ratio: effects of low ventilation/perfusion regions. Gilbert el al. Critical care medicine 1979
  43. 43. In the real word, blood gas analysis could be checked under variable FIO2 <ul><li>Notably, high FIO2 can increase the magnitude of a true shunt and, as FIO2 is increased in normal subjects, thereby increasing the AaDO2. </li></ul><ul><li>Retrospective analysis of patient data in this study showed that many patients underwent their first blood gas analysis under varying concentrations of oxygen support in the ER. </li></ul>
  44. 44. a prognostic cut-off value of a/APO2 ratio was 0.49 <ul><li>Notably, a/APO2 has similar but less predictive power than AaDO2 for the short-term composite endpoint. </li></ul><ul><li>The cut-off value of a/APO2 may provide another method for adjusting the impact of different FIO2 in clinical practice. </li></ul><ul><li>future study will require an increased number of patients who were administered different oxygen ratios. </li></ul>
  45. 45. There was conflicting result about hypoxemia. <ul><li>In Geneva score, hypoxemia is an important predictor of death. </li></ul><ul><li>In our study, hypoxemia was not significantly different in 1st end point and 2nd end point </li></ul><ul><li>The major cause was different selection methods-high risk patients </li></ul><ul><li>In the landmark PIOPED study, only 41% of patients with PE had a high-probability lung scan. Most patients with PE (57%) had an intermediate-probability or low-probability scan. (5) </li></ul>
  46. 46. The mechanism for widening AaDO2 and hypoxemia . <ul><li>D’Alonzo et al. concluded that hypoxemia and increased AaDO2 was explained by large shunts </li></ul><ul><ul><li>lung regions with low ventilation/perfusion ratios and shunting due to perfusion of atelectatic areas </li></ul></ul><ul><li>Manier et al. had another rationale for the mechanism of hypoxemia and increased AaDO2. - decreased mixed venous O2 </li></ul><ul><li>Diffusion impairment plays only a minor role in the mechanism. </li></ul>
  47. 47. Thrombocytopenia has a significant role in acute pulmonary embolism . <ul><li>This phenomenon can be explained by increased platelet consumption in cases with severe PE </li></ul><ul><li>platelet-mediated release of humoral substances, including serotonin, adenosine diphosphate, prostaglandins, and thromboxane </li></ul><ul><li>Several physiological responses to platelet activation, such as pulmonary hypertension, bronchoconstriction, and RV failure, have been identified. </li></ul>
  48. 48. Study limitation <ul><li>sample size </li></ul><ul><li>uncontrolled retrospective study had a selection bias. </li></ul><ul><li>According to inclusion criteria, the study group had severe PE. </li></ul>
  49. 49. Conclusion <ul><li>Measurement of AaDO2 is a highly useful and simple measurement for predicting short-term mortality and composite events. </li></ul><ul><li>It has high negative predictive value and moderate positive predictive value for 30-day death and 30-day composite events. </li></ul><ul><li>Aggressive thrombolytic treatment strategies can be considered for patients with initial poor prognostic parameter-AaDO2≥53mmHg . </li></ul>
  50. 50. Conclusion 2 <ul><li>This value of a/APO2 requires further study to make a clear conclusion. </li></ul><ul><li>Thrombocytopenia was also an indicator of poor prognosis for patients with acute PE </li></ul>
  51. 52. 一個不經意的小發現,卻帶給我們喜悅的心情

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