1. Evidence and Medicine

2. Bradford Hill Strength of association Consistency of association SpecificityTemporality Biologic gradient PlausibilityCoherenceExperimentationAnalogy

3. Evidence and Medicine Objectives: Judicious skepticism Directed investigation Resist the urge to do something

4. Outcomes DeathDiseaseDisability Despair/ Dysphoria Debt

5. 21 5 101 12 8 7 8 12 4 3 1 1 2 8 7 2 1 1 1 2 8 1 5 15 6 Not Mentioned Routine Experimental Rare/Never Specific M M M M M M Textbook/Review Recommendations Odds Ratio (Log Scale) 0.51.02.0 Favours TreatmentFavours Control RCTsPts 1 23 2 65 3 149 4 316 7 1793 10 2544 11 2651 15 3311 17 3929 22 5452 P<.01 23 5767 27 6125 30 6346 33 6571 43 21 059 54 22 051 67 47 531 65 47 185 70 48 154 P<.001 P<.00001 Cumulative Year 1960 1965 1970 1980 1985 1990 Thrombolytic Therapy

6. Prophylactic Lidocaine in MI 1970 2 304 1974 91451 1976111686 1978121986 1985148412 1988158745 91 1 80 2 50 2 80 3 144 6 42 1 1989 - 1st meta-analysis published Recommendations YesNo Not mentioned Favors treatmentFavors placebo Outcome = death Relative risk (CI) 0.511.52 Cumulative Year # RCTs Subjects

7. Calcium Channel Blocker Post-MI 0.511.52 1988 - 1st meta-analysis published 1984 4 486 1985 7 587 1986115857 1987125879 1988166420 2 3 8 2 3 6 2 2 6 710 7 0 5 2 Relative risk (CI) Outcome = death Cumulative Year # RCTs Subjects Recommendations YesNo Not mentioned Favors treatmentFavors placebo

8. Growth Hormone strong physiological rationalestrong physiological rationale –high dose GH reverses -ve nitrogen balance in severe burns, trauma, sepsis, other critically ill –preserves muscle glutamine,  hand-grip strength, improves cough, increases MIPS randomized trial resultsrandomized trial results –two RCTs, one Finland, one other Europe –heterogeneous ICU pts, expected stay 10 days –Finland: 20% mortality control, 39% GH, p < 0.001 –Europe: 18% mortality control, 44% GH, p < 0.001

9. Failures of physiological rationale cardiology examplescardiology examples chronic heart failurechronic heart failure –milrinone, amrinone, ibopamine, epoprostonol –beta-blockers in heart failure rhythm disturbancesrhythm disturbances –encainide and flecainide and other Class I agents

10. Physiology failure in ICU penetrating chest traumapenetrating chest trauma –early volume replacement increased mortalityincreased mortality nitric oxidenitric oxide –impressive improved oxygenation –pooled results RR: 1.12 (0.90-1.40) prone positioningprone positioning –impressive improved oxygenation –three negative RCTs

11. Beta blockers airflow obstruction do you give beta blockers?do you give beta blockers? –COPD? –asthma? systematic review 17 blinded x-over trials cardioselective bb in 226 COPD pts systematic review 17 blinded x-over trials cardioselective bb in 226 COPD pts –no difference in FEV1 (short or long-term) or symptoms (short or long) systematic review 29 blinded RCTs, 381 mild to moderate asthmaticssystematic review 29 blinded RCTs, 381 mild to moderate asthmatics –8% drop in FEV1 in short term –no drop in FEV1 in longer studies, no change in symptoms, inhaler use

12. Critical Care Examples Historic practice The logic The results Your practice

13. Critical Care Examples The PAC trial Intensive Insulin Saline vs Albumin Less Intensive Insulin Renal Replacement Transfusion Triggers

14. Hierarchy of Evidence Meta-analysis of RCTs systematic review of RCTs Individual RCT Observational studies patient-important outcomes Basic research test tube, animal, human physiology Clinical experience

15. Model of evidence based clinical decisions clinical circumstances clinical circumstances patient preference research evidence Clinical expertise