Pulmonary Embolus ER Management in a Rural Setting

1. Pulmonary Embolus ER Management in a Rural Setting Prepared by Shane Barclay MD

2. Outline and Objectives Review the pathophysiology of Pulmonary Embolus (PE) on the cardiopulmonary system. Define the clinical types of Pulmonary Embolus. Review possible indications, contraindications, adverse effects and outcomes of using thrombolytic therapy in acute hemodynamically compromised patients with known or suspected PE.

3. The Question for Rural Hospitals.. Given the lack of CT confirmed PE in the rural setting, is there any role for treating patients with a high clinical suspicion of PE who are hemodynamically unstable? We will come back to this question.

4. Overview of the Treatment 'dilemma' • The spectrum of treatment for 'uncomplicated' and massive 'unstable' PE seem well agreed upon. ie CT and anticoagulants for the former and attempted resuscitation for the later, including possible administration of thrombolytics. • The treatment of 'sub-massive PE' however is still much debated in the literature. This has been confused by differing clinical trials, using different protocols.

5. A quick word on diagnosing PE This presentation will not go into the clinical diagnosis of PE. Overall the 'clinical' signs and symptoms of PE are fraught with low sensitivity/specificity. One tool has been the Well’s criteria for diagnosing PE – click on this link: http://www.mdcalc.com/wells-criteria-for-pulmonary-embolism-pe/

6. Pathophysiology of pe on the cardiopulmonary system PE are usually multiple and preferentially in the lower lobes. As clot burden increases, hypoxia increases. Hypercapnia and acidosis are rare. With increased pulmonary vascular resistance secondary to obstruction, hypotension can develop. This in turn obstructs right ventricular outflow which then causes right ventricular dilation (often with flattening and even bulging of the septum into the left ventricle). Reduced flow from the right ventricle in turn decreases cardiac output from the left ventricle, all of which results in hypotension then cardiac arrest and death.

7. Pathophysiology of pe on the cardiopulmonary system Clot burden increases Increase pulmonary vascular resistance Hypotension Obstruction of the right ventricle Flattening/bulging of the septum Reduced Rt ventricular flow Reduced cardiac output. Hypotension/Shock Cardiac arrest (usually PEA)

8. Pathophysiology of pe on the cardiopulmonary system Clot burden increases Increase pulmonary vascular resistance Hypotension Obstruction of the right ventricle Flattening/bulging of the septum Reduced Rt ventricular flow Reduced cardiac output. Hypotension/Shock Cardiac arrest (usually PEA)

9. Pathophysiology of pe on the cardiopulmonary system Clot burden increases Increase pulmonary vascular resistance Hypotension Obstruction of the right ventricle Flattening/bulging of the septum Reduced Rt ventricular flow Reduced cardiac output. Hypotension/Shock Cardiac arrest (usually PEA)

10. Pathophysiology of pe on the cardiopulmonary system Clot burden increases Increase pulmonary vascular resistance Hypotension Obstruction of the right ventricle Flattening/bulging of the septum

11. Pathophysiology of pe on the cardiopulmonary system Clot burden increases Increase pulmonary vascular resistance Hypotension Obstruction of the right ventricle Flattening/bulging of the septum Reduced Rt ventricular flow

12. Pathophysiology of pe on the cardiopulmonary system Clot burden increases Increase pulmonary vascular resistance Hypotension Obstruction of the right ventricle Flattening/bulging of the septum Reduced Rt ventricular flow Reduced cardiac output.

13. Pathophysiology of pe on the cardiopulmonary system Clot burden increases Increase pulmonary vascular resistance Hypotension Obstruction of the right ventricle Flattening/bulging of the septum Reduced Rt ventricular flow Reduced cardiac output. Hypotension/Shock Cardiac arrest (usually PEA)

14. Categories of PE 1. Low Risk Stable. 2. Submassive Stable - Low Risk Bleeding. 3. Submassive Stable - High Risk Bleeding. 4. Massive Unstable.

15. Categories of PE Historically, the 'categories' of PE were defined by the 'amount' of clot burden in the pulmonary vasculature. Now, PE's are defined by hemodynamic status and more importantly whether there is right ventricular dysfunction. In addition elevated Troponin or BNP is often used to 'calculate' clot risk.

16. Right ventricular Dysfunction Categorization of PE are now based on hemodynamic status and right ventricular dysfunction. As mentioned previously as clot burden increases, the right ventricle dilates and then flattens and shifts the septum into the left ventricle. The result is decreased cardiac output. How do you quickly assess RV Dysfunction in the ER? Cardiac EDE.

17. Normal Subcostal cardiac view Note large left ventricle with septum deviating into the right ventricle

18. Right Ventricular Dilation Note large right ventricle with septum bulging into the left ventricle.

19. Right Ventricular Dilation

20. Right Ventricular Dilation

21. Low risk - Stable These are the patients identified via spiral CT, V/Q scans to have a segmental PE and who are clinically and hemodynamically stable. (No indication of Right Ventricular Dysfunction) Treatment is with LMW Heparin and Warfarin or NOAC as per protocol.

22. Submassive stable Low risk Bleeding These are patients who have RVD but who are hemodynamically stable ‘at this time’. They are also the patients that if thrombolytics were given, their risk of bleeding (ICH) would be low – no bleeding risk factors, recent surgery etc.

23. Submassive stable High risk Bleeding These patients again have RVD but hemodynamically stable – ‘at this time’. But they are the patients with high risk of bleeding due to the same risk factors covered in TNK administration for acute MI.

24. Massive unstable These are patients with RVD who by definition have severe hemodynamic compromise – anywhere from hypotension to cardiac arrest. Definition: PE with sustained SBP < 90 for > 15 minutes. or requiring inotropic support not due to other causes or pulselessness or profound bradycardia < 40 bpm and in shock.

25. Who to treat? As PE size increases, Cardiopulmonary status worsens. Even in patients who are normotensive, (ie ‘stable submassive PE’) 30% still have Right Ventricular Dysfunction. Of these 10% progress to shock and 5% die in hospital

26. Risks versus outcomes Clinical trials have indicated that thrombolytic therapy for PE can lead to early hemodynamic improvement and reduced mortality, but at a possible cost of increased risk of serious bleeding. However what has not been addressed is whether this bleeding (predominately ICH) is related to the thrombolytics or to concomitant heparin.

27. Risks versus outcomes JAMA , 2014 June (meta-analysis of 16 trials, 2115 patients) Thrombolytic therapy, for patients who were hemodynamically stable but with right ventricular dysfunction [submassive PE], was associated with lower all cause mortality (NNT=59) but greater risks of major bleeding (NNT=18)(1.27% absolute risk increase). However major bleeding was not significantly increased in patients under 65 years of age.

28. Risks versus outcomes Journal of Thrombosis and Haemostasis, June 2014. (meta-analysis of 6 trials, 1510 patients) Concluded there was no statistically significant mortality benefit to thrombolysis for PE [in submassive PE]. However it showed an overall absolute risk reduction of 1.4%.

30. Risks versus outcomes The issue of bleeding may be related to patients who are on heparin at the time or who were given heparin immediately after the acute thrombolytic treatment. In the previous slide, the studies of half dose versus full dose Alteplase versus full dose Tenecteplase and the rates of ICH, did not tease out whether the compounding factor was heparin (both timing and dose).

31. Risks versus outcomes No one has done RCT looking at Massive PE mortality benefit, but the general consensus in the medical ‘commentaries’ is that it is probably of benefit in this group as non treatment is associated with such horrible outcomes.

32. Risks versus outcomes So currently, the general consensus seems to be that for patients under 65, with Submassive Low Risk, or massive PE, or with cardiac arrest PEA that is suspected of being due to PE, thrombolytics can be a viable option. As well the opinion seems to be to not give heparin concurrently or immediately after thrombolytics, but rather after 3 - 6 hours or so. Once heparin infusion is started, the goal should be to keep the PTT at 1.5 - 2 X the upper limit of normal.

33. One conclusion... by Dr. Josh Farkis – Pulmcrit.org • Our approach to treatment of submassive PE may be flawed based on a series of historical events. Heparin was introduced prior to the era of evidence-based medicine and universally adopted as first-line therapy despite no evidence of efficacy. Thrombolytics were introduced some decades later, by which time the use of heparin was so entrenched that it was inconceivable not to use heparin. Therefore, thrombolytics were tested in combination with heparin (heparin +/- thrombolytic) instead of being compared to heparin (heparin vs. thrombolytic). The combination of heparin and thrombolytics has at times led to hemorrhage which is invariably blamed on the thrombolytic (rather than the synergistic combination of thrombolytic plus heparin), causing clinicians to retreat back to the use of heparin monotherapy.

34. management of hemodynamically unstable PE. So what do you do when the suspected or known PE patient starts to crash in front of you? General statements: Remember the underlying pathology that causes death is hemodynamic collapse, not hypoxia, due to RV dilation and impaired LV and RV function.

35. management of hemodynamically unstable PE. These patients can decompensate very rapidly – “die before your eyes”. Fluid resuscitation is likely of more harm than good. By adding more ‘preload’ the RV dilates more and increases the RV filling pressure, septal bulge, LV failure etc. – the ‘death spiral'

40. management of hemodynamically unstable PE. • Be very judicious in fluid administration. Small boluses and assess BP. If not improving or worsening BP – stop. • Start pressors early.

41. b1b1b1Drug a1InotrChronDromob2 V/C V/D Phenylephrine +++ Epinephrine ++ +++ ++ ++ ++ Norepinephrine +++ ++ ++ ++ +

42. management of hemodynamically unstable PE. • Be very judicious in fluid administration. Small boluses and assess BP. If not improving or worsening BP – stop. • Start pressors early. Norepinephrine 0.1 mcg/kg/min, titrate up as needed. NE is a positive inotrope and causes venoconstriction and therefore may increase preload, which can help increase MAP. Another choice could be Epinephrine as it has stronger inotropic activity than NE and causes bronchial vasodilation.

43. management of hemodynamically unstable PE. 3. Avoid intubation if at all possible. In crashing PE patients, intubation can result in hypoxemia, hypercapnia, positive pressure ventilation and sedation, all of which can worsen PE hemodynamics. If necessary use an LMA. Remember, these patients die of hemodynamic collapse, not respiratory failure.

44. management of hemodynamically unstable PE. 4. Determine contraindications to thrombolysis. - Hemorrhagic/Ischemic CVA within 3 months, AVM, CNS tumor, recent CNS surgery = absolute contraindication. - Recent head trauma with fracture or brain injury = absolute - Active bleeding (excluding menses) = absolute. - Major non-CNS surgery within 3 wks = relative. - Recent internal bleeding within 4 wks = relative. - Platelets less than 100 = relative - On oral anticoagulants = relative - Severe HTN, BP on presentation > 180/110 = relative - > 75 y/o = relative for STEMI, > 65 y/o for PE.

45. management of hemodynamically unstable PE. 5. If on heparin, stop it? or reverse it? No one has clearlyanswered this. Protamine sulfate: Best with UFH. Only partially neutralizes or reverses LMWH. Dosage: if LMWH dose > 8 hrs. ago: 0.5 mg/100 mg LMWH IV if LMWH dose < 8 hrs. ago: 1 mg/100 mg LMWH IV Maximum 50mg/dose. Infusion rate 5 mg/min

46. management of hemodynamically unstable PE. 6. Consider.. then give? Thrombolytics. (likely full dose TNK). Most studies have looked at half dose alteplase (TPA) as less ICH than full dose. The few studies available seem to indicate full dose TNK is fine but not in conjunction with heparin.

47. management of hemodynamically unstable PE. 7. Plan for failure. Even when you are doing everything right, these patients often code. With aggressive CPR and thrombolytics, many patients can do well. (J Am Coll Cardiol 1997 – 35% pts receiving CPR and thrombolytics survived) If you do give a thrombolytic during CPR, continue the resuscitation for some time as the drug takes time to work.

48. So.. Back to the question for Rural Hospitals.. Given the lack of CT confirmed PE in the rural setting, is there any role for treating patients with a high clinical suspicion of PE who are hemodynamically unstable?

49. For the Rural Doctor Use of thrombolytics for PE would/will be based on the comfort level of the physician. That same comfort level that many (older) rural doctors ‘grew into’ with the introduction of thrombolytics for acute STEMI.

50. For the Rural Doctor However consideration for PE Thrombolytics might include: If under 65: • Patient with known large DVT or actual PE presenting in hemodynamic crisis and/or.. • Patient in cardiac arrest where the rhythm is PEA. Although the most common cause of PEA is hypovolemia (5 H’s, 5 T’s) without an obvious cause of hypovolemia, PE should be a consideration (if you do nothing these patients die) and/or • If you do cardiac ultrasound and can determine RV dilation in the context of CV collapse and likely PE.