1. Major Pulmonary Embolism: Early Care & Cautions Ram E. Rajagopalan, MBBS, AB (Int. Med & Crit. Care) Consultant & Head, Dept. Critical Care Medicine SUNDARAM MEDICAL FOUNDATION, Chennai

2. Goals of this talk To discuss the acute management of Major Pulmonary Embolism with a focus on the patho- physiology of haemodynamic alterations

3. Is all PE the same? Clinical Syndromes: Dyspnea with or without pleuritic pain, haemoptysis Acute syncope, haemodynamic instability, shock, arrest ~ 90% ~ 10% Major PE / “Haemodynamically unstable” PE 7 x mortality Wood, KE. Chest 2002 No haemodynamic  RV dysfunction in 25-40% Goldhaber et al; Circ 1997

4. “Massive” PE; A Misnomer Clot size is not the only predictor RIP Mortality PE Size Good LV function Poor LV function

5. Factors influencing survival 399 patients in PIOPED followed for a year Mortality predicted by: Underlying CancerHazard Ratio 3.8 Prior LV FailureHazard Ratio 2.7 Underlying COPDHazard Ratio 2.2 (Carson et al; N Engl J Med 1992.)

6. Major (High-risk)* PE Defined as PE with: Hypotension - SBP 40 mm Hg) Cardiogenic shock (organ perfusion defects) Cardiac Arrest (PEA) Syncope is an underemphasized feature * ECS n=407 n=316 n=102 n=126 Mortality (%) (MAPPET Registry)

7. The Shock Index HR (beats/ min) SBP (mm Hg) >1 high risk / <1 low risk More sensitive & specific than SBP in predicting All Death Fatal PE & Recurrent fatal PE RIETE Registry Eur Respir J 2007; 30: 1111–1116 Shock Index =

8. Shock Index & Mortality Both the Shock index and SBP were independent predictors of mortality RIETE Registry Eur Respir J 2007; 30: 1111–1116

9. Diagnosis of Major PE Though Multi-slice CT Pulmonary Angiography may be the gold standard of diagnosis, patients may be too unstable for the test Alternative testing?

10. (From Wood, KE. Chest 2002) RV Pressure Load & Failure

11. RV Dimensions Absolute values irrelevant; error-prone Compare ratio of RVED to LVED area in apical 4-chamber view Normal: RV:LV area <0.5 Moderate dilation RV: LV >0.6 & <1.0 Severe dilation RV:LV >1.0

12. Change in Septal Kinetics ECG LV Pres. RV Pres.

13. Septal Kinetics: RVF RV LV Vent Septum RV LV

14. Septal Kinetics; B-mode Eccentricity Index

15. RV Dysfunction ECHO features include: - Mc Connell sign - RV dilatation (RV/LV >1) - Flattening of IV septum - No phasic collapse of IVC - Tricuspid regurgitation

16. Warning: Echo diagnosis No echocardiographic parameter has sufficient sensitivity to allow its use for diagnosis of PE in stable patients irrespective of severity of symptoms But, in shock, ……..

17. ECHO in Major PE Eur Heart J 2003; 24: 366-76 No patient with Shock Index >1 & No RVF on Echo had PE on CTPA

18. In Extremis? Haemodynamically Unstable PE Shock Index >1 Other causes: AMI, aortic dissection tamponade, valve 2-D Echo Emboli in PA; in transitNon Contributory No PE Treat: ’Lysis, embolectomy Yes

19. Major PE: ’Lysis? 1. Wan et al, Circulation 2004. 2. Kucher et al, Circulation 2006. Meta-analysis of studies that included major PE: “Real-world” registry data: ICOPER; 108 major PE (4.5%) 68% got only heparin; 46% mortality (vs. 55% with ’lysis, NS) & 12% recurrence (vs. 12% after ’lysis)

20. Long-term Effects of ’Lysis RV pressures at 6 months are less than if Rx with heparin alone ’Lysis Heparin Chest. 2009; 136: 1202-10.

21. Which Agent for ’Lysis? Alteplase infusions result in best clinical outcomes 100 mg over 2 hours is the recommendation Capstick & Henry; Eur Resp J 2005

22. Treatment of Major PE Risk of bleeding to be considered; recent surgery, stroke, haemorrhage Surgical embolectomy vs. Catheter embolectomy Circ 2011; 123: 1788-1830

23. Cardiac arrest in PE Patients will present with PEA identified easily by RV distension (Strongly presumptive) ECHO during arrest is a valuable tool Case studies identify improved survival if thrombolysis is done during CPR The only controlled trial of ’lysis in CPR showed no benefit But AHA/ ERC/ ILCOR recommends lysis (Alteplase 50 mg) during CPR & continued compression up to >1 hour

24. Major PE: Titrating Fluid Should hypotension in Major PE be resuscitated with fluid boluses?

25. (From Wood, KE. Chest 2002) “RV Failure”

26. Ventricular Interdependence With rising RV pressure: the shared IV septum & pericardial restraint influence LV function as well Septum “flattens” LV Dimensions  LV output declines After Greyson CR; Crit Care Med 2008; 36: S57–65

27. Volume Loading? Volume Loading? Physio-illogical! – RV has poor Starling response; Ventricular interdependence worsens LV function Mercat et al; Patients with acute PE and CI <2.5 L/min No hypotension 1 bolus; 500 ml dextran Cardiac index better RVEDI increases Crit Care Med 1999; 27: 540-44 Best response with small RV ; use RV size as goal? Not acceptable in RV shock

28. Pulse Pressure Variation Pulse pressure variation during MV is increasingly used to judge “volume responsiveness” Arterial Pressure Airway Pressure PPmax PPmin 45 0 120 70

29. Pulse Pressure variation + + + + + + B - - - - - - ++ A Positive pressure ventilation  venous return to right heart

30. Pulse Pressure Variation “In Series” effect on LV function RV output Determines LV preload & LV output  of RV load has a delayed (out-of-phase) effect on LV

31. In-phase variation in RV Failure From: Vieillard-Baron. Curr Opin Crit Care 2009; 15: 254-60 Pulse pressure variation in RV failure is a marker of interdependence; not fluid responsiveness

32. Classical Observation Circ Res 1954; 2:326–332 AC Guyton

33. (From Wood, KE. Chest 2002) “Auto-aggravation” Coronary ischemia is presumed to be the final arbiter of the lethal decline

34. Haemodynamic Support Avoid excessive fluid loading Consider inotropes Dobutamine (with care) Noradrenaline Raise systemic vascular pr. Noradrenaline ____________________________________________________________ Avoid BP drop at intubation Etomidate for sedation

35. Inotropes? Dobutamine: Aim; Improving RV contractility Doses: <5  g / Kg / min  PVR and CO 5-10  g / Kg / min HR, no  on PVR Better than noradrenaline in RVD Hypotension in RV shock patients Crit Care Med 2007; 35: 2037-50

36. Systolic Interdependence: Isolated heart preparations: Change in load (pr./ vol.) in one ventricle alters diastolic & systolic pr. in the other Acute fluid removal via VAD  Instantaneous change in both LV & RV pressures Not a result of in-series HD change

37. Systolic Interdependence: Magnitude? RV pressure has a biphasic peak; one of which coincides with LV pressure RV/LV separation in a paced, electrically- isolated model allows mathematical estimation of LV contribution to RV systolic function Santamore W; Chest 1995; 107:1134-45

38. Systolic Interdependence: Magnitude? LV contribution to LV syst pr.: 95% RV contribution to LV syst pr.: 5% LV contribution to RV syst pr.: 65% RV contribution to RV syst pr.: 35% Santamore W; Chest 1995; 107:1134-45 Since LV significantly contributes to RV output  LV function affects the RV output 15mm Hg 125mm Hg 75mm Hg 0 00 0

39. Vasoconstriction A strategy to improve systolic function Circulation 1995; 92: 546-554 Control PHT PHT + Aortic Cons Canine model of pulmonary constriction Coronary blood-flow controlled by roller-pump Aortic constriction  septal shift & LV output Allows better right heart pressure generation via systolic interdependence While  coronary flow coincides with the deterioration, the cycle of auto- aggravation may proceed independent of coronary ischemia

40. Impaired systolic interdependence Haemodynamic Support Avoid excessive fluid loading Rx Thrombus ’lysis, thrombectomy Raise systemic vascular pr. Noradrenaline ____________________________________________________________ Avoid BP drop at intubation Etomidate for sedation ________________________________ Consider inotropes Dobutamine (with care)

41. Thank you for your attention……

42. Summary HD strategy  Avoid volume loading  Initiate Vasopressors  Dobutamine <5  g/ kg/ min  ?Pulmonary vasodilation  Inhaled NO, Sildenafil, Levosimendan Crit Care Med 2006;34:2287-93

43. (From Wood, KE. Chest 2002) “Auto-aggravation” While  coronary flow coincides with the deterioration, the cycle of auto- aggravation may proceed independent of coronary ischemia

44. Haemodynamic Support Avoid excessive fluid loading Consider inotropes Dobutamine (with care) Noradrenaline Raise systemic vascular pr. Noradrenaline ____________________________________________________________ Avoid BP drop at intubation Etomidate for sedation

45. Definition for massive PE: Acute PE with sustained hypotension (SBP <90 mm Hg for at least 15 minutes or requiring inotropic support)), pulselessness, persistent profound bradycardia (heart rate <40 bpm with signs or symptoms of shock).