Evidence and Medicine

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

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

Outcomes DeathDiseaseDisability Despair/ Dysphoria Debt

Not Mentioned Routine Experimental Rare/Never Specific M M M M M M Textbook/Review Recommendations Odds Ratio (Log Scale) Favours TreatmentFavours Control RCTsPts P< P<.001 P< Cumulative Year Thrombolytic Therapy

Prophylactic Lidocaine in MI st meta-analysis published Recommendations YesNo Not mentioned Favors treatmentFavors placebo Outcome = death Relative risk (CI) Cumulative Year # RCTs Subjects

Calcium Channel Blocker Post-MI st meta-analysis published Relative risk (CI) Outcome = death Cumulative Year # RCTs Subjects Recommendations YesNo Not mentioned Favors treatmentFavors placebo

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 < –Europe: 18% mortality control, 44% GH, p < 0.001

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

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 ( ) prone positioningprone positioning –impressive improved oxygenation –three negative RCTs

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

Critical Care Examples Historic practice The logic The results Your practice

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

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

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