Why Would I Want To Monitor The Regional Circulation?

1. Why Would I Want To Monitor The Regional Circulation? Stephen O. Heard, M.D. University of Massachusetts Medical School Worcester, MA, USA

3. Outline • Available monitors • Reasons to monitor regional circulation • Regional circulation is perturbed during shock – organ and cellular injury • Intestine is particularly susceptible to shock • Predict outcome • Detect shock earlier • Guide resuscitation

4. The regional circulation and microcirculation in shock are altered

5. Cardiogenic shock and congestive heart failure • Forearm reactive hyperemia is reduced • Erythrocyte deformability is attenuated • Reduced conjunctival microvascular density • Fraction of perfused vessels in sublingual mucosa is reduced • Elevated regional (gastric) mucosal PCO2 and Pm-aCO2 gap

6. Kirschenbaum, et al. CCM 2000 • Critically ill patients • Eight with cardiogenic shock • Six critically ill controls • Six with septic shock • Forearm blood flow measured by venous air plethysmography • Red blood cell deformability

7. Kirschenbaum, et al. CCM 2000 FBF: Forearm Blood Flow; RH: Reactive Hyperremia

8. De Backer, et al. AHJ 2003 • Orthogonal polarization spectral (OPS) imaging • Forty patients with severe heart failure (31 with cardiogenic shock) • Controls – 15 preop cardiac patients

9. DeBacker, et al. AHJ 2004 Percent of small vessels perfused in cardiogenic shock

10. Hemorrhagic Shock • Attenuated functional capillary perfusion (number of capillaries actively moving blood) in skeletal muscle and intestine villi • Average red blood cell velocity is reduced by ~50% in the intestinal villi and ~70% in skeletal muscle

11. Septic Shock • Forearm reactive hyperemia and erythrocyte deformability are reduced • Microvascular compliance and skeletal muscle oxygen consumption are reduced • Postischemic reperfusion time is prolonged • Lack of normal cyclic blood flow variation • Reduction in perfused small vessels • Microcirculatory shunting (microcirc PO2 below venous PO2)

12. Astiz, et al. CCM 1995 • FBF measured at rest and during reactive hyperemia air plethysmography • RBC deformability • Nine normal controls • Eight patients with severe sepsis

13. Astiz, et al. CCM 1995

14. De Backer, et al. AJRCCM 2002 • OPS imaging in septic patients • Fifty patients with severe sepsis • Ten healthy volunteers • Sixteen preop cardiac patients • Ten critically ill patients without sepsis

15. DeBacker, et al. AJRCCM 2002

16. De Blasi, et al. ICM 2005 • Skeletal muscle oxygenation by phase-modulation NIRS • Septic patients (13) • Postop patients with sepsis (13) • Healthy controls • Venous and arterial occlusions

17. Brachioradialis Microvasc Compl

18. Muscle VO2 (µMO2 min-1 100 ml-1)

19. Why is this information important?

20. The Intestine • Susceptible to shock • Disruption of gut barrier function as a consequence of shock may contribute to morbidity and mortality of patients

21. Intestine andIschemia • Tips of intestinal villi are susceptible to ischemia (counter-current arrangement) – PO2 is low at apex of villi

22. Intestine and Ischemia • Plasma skimming • Abnormalities in microcirculation observed in shock may increase risk of ischemia • Ischemia may disrupt gut barrier function • Impair gut derived immune function • Translocation of bacteria/bacterial products • Generation of inflammatory mediators

23. Ischemia-induced Disruption of Gut Barrier Function (I)? • Patients resuscitated from hemorrhagic shock often have positive blood cultures with enteric organisms • Intestinal permeability is increased in endotoxemia • Following IR, intestinal epithelial cells prime PMNs that can lead to organ dysfunction

24. Ischemia-induced Disruption of Gut Barrier Function (II)? • Intestinal epithelial cells exposed to hypoxic conditions generate: • TNF • Reactive O2 species • Peroxynitrite • Can increase intestinal permeability and cause lipid peroxidation

25. Ischemia-induced Disruption of Gut Barrier Function (III)? • Intraoperative splanchnic hypoperfusion during esophageal surgery (assessed by gastric tonometry): • Exaggerated acute phase response • Increased risk of postop septic complications

26. Measuring Regional Circulation Can Be Used For Outcome Prediction

27. Prognostication • Low gastric pHi better predictor of outcome than conventional hemodynamic or metabolic variables in critically ill patients • Low pHi associated with MODS, LOS and death in trauma patients • High Pg-aCO2 gap seen nonsurvivors of septic patients despite normalization of traditional endpoints. • Septic nonsurvivors have persistence of OPS imaging abnormalities • Higher gastric – end-tidal CO2 gradient associated with greater delays in postop recovery

28. Maynard, et al. JAMA 1993 • 83 critically ill patients • Instrumented with PA catheters and gastric tonometers • Gastric pHi measured at 12 and 24 hours • Gastric pHi • 88% sensitivity for predicting death (likelihood ratio of 2.32) • 24 hour pHi only independent predictor of death

29. Maynard, et al. JAMA 1993

30. Poeze, et al. CCM 2005 Risk of Death

31. Earlier Detection Of Shock

32. Detecting shock and impaired perfusion early is prerequisite to providing effective resuscitation: Rivers, et al. NEJM 2001 Detection of “cryptic” shock Experienced clinicians overestimate visceral perfusion in critically ill patients: Santoso, et al. Eur J Surg 1998 Early Detection Of Shock

33. Santoso, et al. Eur J Surgery 1998

34. Hamilton-Davies, et al. ICM 1997 25% of blood volume shed in 6 volunteers

35. Hamilton-Davies, et al. ICM 1997

36. Hamilton-Davies, et al. ICM 1997

37. NIRS-monitor Monitor showing trends in pHM, PO2M and Hct Fiber optic cable with stabilizer & light shield Dimensions: 8” W x 9” H x 6” D Weight: 8 lbs

38. Lower Body Negative Pressure Chamber NIRS muscle O2 sensor

39. Lower Body Negative Pressure To Simulate Progressive Hemorrhagic Shock NIRS-measured PO2 earlier indicator of cardiovascular collapse than BP

40. Lower Body Negative Pressure To Simulate Progressive Hemorrhagic Shock

41. Guide to Resuscitation

42. Resuscitation To Traditional End-points Will Not Normalize Regional Circulation • Oud and Haupt (CHEST 1999): resuscitation to BP > 100 mm Hg and normal lactate and u/o in septic patients did not reverse signs of mesenteric malperfusion • Venkatesh, et al. (J Trauma 2001): abnormal mesenteric perfusion despite normalization of BP, lactate and u/o

43. Efforts At Normalizing Regional Circulation • Monitor effects of resuscitation • Tonometry • Dobutamine and norepinephrine: + • Dopamine and epinephrine: - • Vasopressin: +/- • OPS • Vasopressin: 0/- • Nitroglycerin: + • Dobutamine: +

44. ScvO2 and SmO2 during 6 hours in ED with EGDT

45. Gutierrez, et al. Lancet 1992

46. Other regional circulation resuscitation studies • Ivatury, et al. J Am Coll Surg 1996 • Gomersall, et al. Crit Care Med 2000 • Miami Trials Group Am Surg 2005

47. Reasons For Clinical Trials Failure • Resuscitation is too late (Rivers, et al.) • Inadequate resuscitation modalities • Should we be using vasodilators? • Use different resuscitation fluids? • The impaired regional circulation and microcirculation are not the proximate cause of the patient demise – cytopathic hypoxia, e.g. • Monitors are not good enough

48. Conclusions: Why Would I Want To Monitor? • Detect regional and microcirculatory abnormalities (early): YES • Prognosticate: YES • Titrate therapy: currently NO – promising recent data

49. Thank You