Evidence-based critical care – Update

1. Evidence-based critical care – Update

2. Intensivist shortage • Experts predict that as the US population ages, the shortage of intensivists will become increasingly acute • By 2020, the supply of intensivists will meet only 22% of the demand for their services

3. The old way… • Intern/junior resident (Dr. X) was taught a concept by his/her: Senior resident Chief resident Fellow Attending • Dr. X practiced what he was taught…

4. The old way… • Dr. X went on to become: A senior resident A chief resident A fellow An attending • And taught the same concept to his/her junior resident, and so on and so on….

5. The old way…”Why do you do it that way??” • “Well, I learned this from Dr. X” • “We’ve always done it this way” • “We have good outcomes” • “I have an article to prove it” (more on this later…)

6. The old way… dopamine • Dopamine in low doses activates dopamine receptors in the kidney • Renal blood flow is increased • Urine output is increased (sometimes) • The assumption, and teaching, became…

7. The old way… dopamine • Dopamine is indicated for: Preventing renal failure Treating renal failure Reversing renal vasoconstriction when vasopressors are used Preventing renal failure during aortic and renal cross-clamping • Dopamine flowed like water (often better than urine) in ICUs worldwide

8. Evidence-based critical care • THERE NOW EXISTS A MORE “SCIENTIFIC” METHOD TO PROVIDE CARE…

9. The new way… • Try to adapt practice based on the quality of clinical studies that support the test or intervention – “Evidence-based” • A careful evaluation of existing studies • Type of trial • Number of centers • Number of patients • Quality of the study

10. Evidence-based concepts • The best study is: Prospective Randomized Double Blinded – not always possible Multicenter • Meta-analyses evaluate a number of similar studies

11. Evidence-based concepts • Surviving Sepsis Campaign Guidelines for the Management of Severe Sepsis and Septic Shock • 11 critical care societies - international • Initial document: CCM March, 2004 • Evidence-based review: CCM supplement November, 2004

12. Grading system • Grade A: At least 2 large, randomized trials with clearcut results • Grade B: At least 1 large, randomized trial with clearcut results • Grade C: Small, randomized trials, uncertain results

13. Grading system • Grade D: Nonrandomized, contemporaneous controls • Grade E: Nonrandomized, historical controls; case series; uncontrolled studies; expert opinion

14. Evidence-based critical care • VENTILATOR MANAGEMENT OF ARDS Vt settings Level of PEEP Use of steroids in “late” ARDS

15. Low tidal volume strategy • Barotrauma • High pressure generated with flow of air into lungs • Volume trauma (volutrauma) • Overdistention of alveoli can lead to further lung damage

16. Low tidal volume strategy • Classic practice: Vt 10-15 cc/kg • Hypothesis: lower Vt is protective of alveolar damage and outcome in ARDS • ARDS-net trial, NEJM, 2000 • Comparison of 6 ml/kg vs 12 ml/kg • 861/1000 patients • Mortality 31% vs 39.8% • Reduction in mortality of 22%

17. Low tidal volume strategy • When ARDS diagnosed, adjust Vt for ideal body weight • 60 kg x .6 cc/kg = 360 cc • pCO2 will likely increase – permissive hypercapnea • GRADE B

18. PEEP levels in ARDS • ARDS-net, NEJM, 2004 • Comparison of low and high PEEP in ARDS • 549 patients • Low versus high PEEP algorithm • All patients had low Vt • No difference in ventilator free days or mortality

19. Steroids for “late” ARDS • Fibroproliferation can occur after 5-7 days of ARDS • This inflammatory process may present with worsening oxygenation, fever and leukocytosis (infection may present with same signs) • Case series of steroids to minimize the late inflammatory fibroproliferation

20. Steroids for “late” ARDS • ARDS-net randomized placebo-controlled trial • Goal 200 patients over 6-8 years • No value in use of steroids in “late” ARDS

21. Other ARDS modalities • We no longer consider: Prone position Inhaled nitric oxide Surfactant Liquid ventilation

22. Evidence-based critical care • Glucose control in critically ill patients

23. Intensive insulin therapy • NEJM, 2001, single center study • 1,548 surgical patients • Randomized to tight vs non tight control • 80-120 mg/dl vs 150 mg/dl • ICU mortality 4.6% vs 8.0% • 43% risk reduction

24. Intensive insulin therapy • 50% decrease in BSI, ARF requiring RRT, critical illness polyneuropathy and transfusion requirement • Shorter duration of mechanical ventilation and ICU care • Less multiple organ failure

25. Intensive insulin therapy • Mayo Clin Proc, 2004 • 800 critically ill medical-surgical patients in a community ICU • Hospital mortality decreased • Decreased ICU LOS, ARF, transfusion requirement • Most benefit in septic patients

26. Intensive insulin therapy • GRADE D based on original study, (randomized but single center, mainly surgical patients), likely upgrade to C • German study (600 patients) – negative • Two large scale randomized trials underway • European study – 3500 medical/surgical patients • Australia/NZ – 4500 medical/surgical patients

27. Evidence-based critical care • Activated protein-C in sepsis (Xigris)

30. RH Activated Protein C • Prowess Study • Recombinant human activated protein C worldwide evaluation in severe sepsis • Randomized, double blinded, placebo controlled • 96 hour infusion of activated protein C (APC) • Endpoint: death at 28 days

31. RH Activated Protein C • Prowess study • 1690 patients (840 placebo; 850 APC) • Mortality 30% vs 24.7%, p=0.005 • 6.1% reduction of death • Serious bleeding 2% vs 3.5%, p=0.06 • Similar number of blood transfusions

32. RH Activated Protein C • Prowess study • The difference in outcome was greatest in patients with an APACHE score >25 • Address study • PRCT of RHAPC in patients with APACHE <25 • No improvement in outcome • May be worse outcome in SURGICAL patients with single organ dysfunction

33. RH Activated Protein C • Contraindications • Internal bleeding, hemorrhagic CVA, CHI, neurosurgical procedures, surgery within 12 hours • Many patients with abdominal sepsis require repeat explorations • The drug is expensive ($100/kg)

34. RH Activated Protein C • GRADE B for patients with severe sepsis, multiple organ dysfunction, with APACHE >25 • “Dear doctor” letter from Eli Lilly re: surgical patients with single organ dysfunction

35. Evidence-based critical care • CORTICOSTEROIDS AND SEPTIC SHOCK

36. Corticosteroids and sepsis • Old teaching: don’t give septic patients high dose steroids • New thought: patients with septic shock who are unresponsive to pressor agents may have adrenal insufficiency

37. Corticosteroids and sepsis • Incidence of adrenal insufficiency • 30-50% in critically ill patients • 50-60% in patients with septic shock • Clinical presentation • resistant hypotension • hyponatremia, hyperkalemia • Low or “normal” serum cortisol level

38. Corticosteroids and sepsis • JAMA, 2002; multicenter, RCT, 300 patients • Septic shock, vasopressor therapy • A baseline cortisol level of <25 mcg/dl • Corticotropin stimulation test (cortrosyn) • An increase in serum cortisol of 9 mcg/dl after corticotropin – “responders” • Unable to increase serum cortisol 9 mcg/dl – “nonresponders”

39. Corticosteroids and sepsis • Nonresponders randomized to placebo vs hydrocortisone 50 mg IV every 6 hours + fludrocortisone • Mortality improved in patients with adrenal insufficiency • Faster time to vasopressor withdrawal • No difference in patients with adequate corticotropin response

40. Corticosteroids and sepsis • Should low doses of corticosteroids be used in the treatment of septic shock? • GRADE C • SSC guidelines suggest steroids in pressor-dependent patients with low serum cortisol (don’t even bother with the cortrosyn stimulation)

41. Evidence-based critical care • PULMONARY ARTERY CATHETER USE IN THE ICU

42. PA catheter use in the ICU • Old practice: any unstable patient who didn’t respond to fluids or who had possible cardiac dysfunction; “we didn’t know where we were…” • Preoperative “optimization” of high risk patients • Old practices questioned: Connors, et al, JAMA, 1996 • Editorial: “abandon PACs until PRCT”

43. PA catheter use in the ICU • JAMA, 2005 • Meta-analysis, 13 RCTs, 5051 patients • Use of PA catheter neither increased overall mortality or hospital days, nor conferred benefit • Use of the PA catheter was associated with a higher use of inotropes and vasodilators

44. PA catheter use in the ICU • RCT in progress • ARDS-net, 1000 patient goal • FACTT Study: PRMCT of PAC vs CVP for management of ALI and ARDS • and • PRMCT of “fluid conservative” vs “fluid liberal” management of ALI and ARDS

45. Evidence-based critical care • EARLY GOAL-DIRECTED THERAPY IN SEPSIS

46. Early goal-directed therapy • “Standard” goals for sepsis (resuscitation) • MAP >65 • CVP 8-12 • Urine output >0.5 cc/hr

47. Early goal-directed therapy • DO2 = Hgb (SaO2) x 1.34 x CI x 10 • “Supranormal” goals for PAC (1980s) • CI > 4.5 L/min/m2 • DO2I > 600 ml O2/min/m2 • VO2I > 170 ml 02/min/m2 • Fluids, blood, inotropes, pressors… • We could measure our progress with a calculator!!

48. Early goal-directed therapy • Supranormal goals disproven in established sepsis (NEJM x2) • Will this theory work if we get to the patient earlier?

49. Early goal-directed therapy • NEJM, 2001, Henry Ford Hospital • 263 ED patients • Control group: MAP, CVP, UO • Protocol group: MAP, CVP, UO, SCVO2 >70 • Mortality 46.5 vs 30.5%, p=.009

50. Early goal-directed therapy • There IS value to optimizing cardiac output, oxygen delivery and SVO2 if you intervene early enough • (Is it really the SVO2 that makes the difference, or is it resuscitation??)