What’s new in Clinical Practice Guidelines (CPG) in Critical Care Kuwait , April 11, 2013

1. What’s new in Clinical Practice Guidelines (CPG) in Critical CareKuwait, April 11, 2013

2. What is new in CPG in Critical CarePast, Present, Future • Process of CPG development (GRADE) • Examples of new and / or controversial recommendations • Future tasks • Allow you to use those guidelines with more satisfaction

3. New developments in communism

4. The evolution of power in medicine • Clinical Experience and pathophysiological knowledge • RCTs • Meta-analyses, decision analyses, economic analyses • Above with recommendation  Practice guidelines

5. In the beginning... • Early 2000 • CPG increasing in importance • Chaos all over the place, especially for ‘generalists’ • Need to create order out of chaos

7. GRADE: Guideline development process • Step one • What is the question? • Step two • Find and summarize best evidence • Step three • Apply judgments (quality of evidence, strength of recommendations) G rade

8. GRADE defining feature • Evidence: high or low quality? • quality of evidence: the likelihood that our estimates of effects are true and adequate to support given recommendation • Recommendation: weak or strong? • confidence that following the recommendation will cause more good than harm

9. Recommendations: Weak or strong? strong recommendations strong methods AND benefits clearly outweigh downsides weak recommendations weak methods OR balance of benefits and downsides unclear or close R ecommendation

10. Formulate question Select outcomes Rate importance of outcomes Systematic Review (outcomes across studies) Evidence Profile (GRADEpro) Pooled estimate of effect for each outcome 1 Quality of evidence for each outcome 2 High  Moderate  Low  Very low High | Moderate | Low | Very low Critical Outcome1 action PICO start RCT observational high low Critical Outcome2 risk of bias inconsistency indirectness imprecision publication bias Important Outcome3 rate down Not Outcome4 important large effect dose-response antagonistic bias rate up Guideline panel systematic review of evidence recommendation • Formulate recommendations • For or against an action • Strong or weak (strength) • Strong or weak: • Quality of evidence • Balance benefits/downsides • Values and preferences • Resource use (cost) Rate overall quality of evidence across outcomes • Wording • “We recommend…” | “Clinicians should…” • “We suggest…” | “Clinicians might…” • unambiguous • clear implications for action • transparent (values & preferences statement)

12. Strength of recommendation degree of confidence that desirable effects of adhering to recommendation outweigh the undesirable effects. • Undesirable effects • harms • more burden • costs • Desirable effects • health benefits • less burden • savings

13. Strong or Weak Recommendation? • Quality of the evidence • Balance between desirable and undesirable effects • Values and preferences • Costs (resource allocation, feasibility)

14. Strenght ofRecommendations • strong recommendation • authors confident that following the recommendation will cause more good than harm • weak recommendation (suggestion) • authors believe that following the recommendation will cause more good than harm, but are less confident

15. Why Grade Recommendations? Implications • strong recommendation • one size fits all • expect uniform clinician behavior • use as performance indicator • weaker recommendation • expect action to vary

16. Strenght ofRecommendations • do it or don’t do it • strong recommendation • probably do it, or probably don’t • weaker recommendation

17. How to present grades? • words only • recommendations versus suggestions • quality high, moderate, low, very low • numbers and letters • recommendation 1 and 2 • quality A, B, C, D

19. GRADE pragmatic approach • If question appropriate, look for meta-analysis (MA) • If no published MA, identify main studies • If possible, do your own MA • If no MA, describe main studies and their results • Be explicit about the way you identified and summarized the evidence • Make sure there is explicit link between recommendation and evidence

20. Surviving Sepsis Campaign • New or controversial recommendations

21. 68 international authors • 30 international organizations • 19 reviewers • Attention to COI • GRADE system • Emphasis on meta-analyses (636 references) • If you can't dazzle them with brilliance, baffle them with bs

22. Formulate question Select outcomes Rate importance of outcomes Systematic Review (outcomes across studies) Evidence Profile (GRADEpro) Pooled estimate of effect for each outcome 1 Quality of evidence for each outcome 2 High  Moderate  Low  Very low High | Moderate | Low | Very low Critical Outcome1 action PICO start RCT observational high low Critical Outcome2 risk of bias inconsistency indirectness imprecision publication bias Important Outcome3 rate down Not Outcome4 important large effect dose-response antagonistic bias rate up Guideline panel systematic review of evidence recommendation • Formulate recommendations • For or against an action • Strong or weak (strength) • Strong or weak: • Quality of evidence • Balance benefits/downsides • Values and preferences • Resource use (cost) Rate overall quality of evidence across outcomes • Wording • “We recommend…” | “Clinicians should…” • “We suggest…” | “Clinicians might…” • unambiguous • clear implications for action • transparent (values & preferences statement)

23. Importance of team work!

24. Controversies and changes – team work • Sepsis management requires a multidisciplinaryteam (physicians, nurses, pharmacy, respiratory,dieticians, and administration) and multispecialty collaboration(medicine, surgery, and emergency medicine) to maximize thechance for success.

25. Calibrating the level of your enthusiasm • There will be one week of extra paid vacation for all attending this conference • Kuwait and UAE meet in the opening match of the World Cup in Qatar 2022 • New personal income tax is introduced to pay the football team players for winning more games

26. Controversies and changes (plus some gossiping) • The administration of effective intravenous antimicrobialswithin the first hour of recognition of septic shock (grade1B) and severe sepsis without septic shock (grade 1C)should be the goal of therapy. • Remark: Although the weightof the evidence supports prompt administration of antibioticsfollowing the recognition of severe sepsis and septicshock, the feasibility with which clinicians may achieve thisideal state has not been scientifically evaluated.

27. Controversies and changes (plus some gossiping) • The administration of effective intravenous antimicrobialswithin the first hour of recognition of septic shock (grade1B) and severe sepsis without septic shock (grade 1C)should be the goal of therapy. • Remark: Although the weightof the evidence supports prompt administration of antibioticsfollowing the recognition of severe sepsis and septicshock, the feasibility with which clinicians may achieve thisideal state has not been scientifically evaluated.

28. surviving patients [%] time from onset of hypotension [hours]

29. Importance of team work!

30. Controversies and changes (plus some gossiping) • The administration of effective intravenous antimicrobialswithin the first hour of recognition of septic shock (grade1B) and severe sepsis without septic shock (grade 1C)should be the goal of therapy. • Remark: Although the weightof the evidence supports prompt administration of antibioticsfollowing the recognition of severe sepsis and septicshock, the feasibility with which clinicians may achieve thisideal state has not been scientifically evaluated.

31. Controversies and changes – protocolized care • EGDT (targets BP, CVP, UO, Scvo2) with the use of fluids, pressors, transfusion, dobutamine (1C) • CVP too low (high PEEP) • one protocol versus another • Transfusion and dobutamine

32. Another protocol

33. JAMA Feb 24, 2010 (Jan 2007-Jan 2009) 23% mortality 17% mortality

34. Controversies and changes – new protocol • We suggest targeting resuscitation to normalize lactate inpatients with elevated lactate levels as a marker of tissuehypoperfusion (grade 2C) • Text: If Scvo2 is not available, lactate normalization maybe a feasible option in the patient with severe sepsis-inducedtissue hypoperfusion. Scvo2 and lactate normalization may alsobe used as a combinedendpoint when both are available.

35. Controversies and changes – new diagnostic possibilities (plus gossiping) • We suggest the use of low procalcitonin levels or similarbiomarkers to assist the clinician in the discontinuationof empiric antibiotics in patients who appeared septic, buthave no subsequent evidence of infection (grade 2C).

37. Vasopressors and inotrops – positive thinking

38. Controversies and changes - vasopressors • We recommend norepinephrine as the first-choice vasopressor(grade 1B). • We suggest epinephrine (added to and potentially substitutedfor norepinephrine) when an additional agent isneeded to maintain adequate blood pressure (grade 2B). • We suggest dopamine as an alternative vasopressor agent tonorepinephrine only in highly selected patients (eg, patientswith low risk of tachyarrhythmias and absolute or relativebradycardia) (grade 2C). • A trial of dobutamine infusion up to 20mcg/kg/min be administered or added to vasopressor (if in use) in the presenceof (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs ofhypoperfusion, despite achieving adequate intravascular volume and adequate MAP (grade 1C)

41. Controversies and changes 2008: We suggest that intravenous hydrocortisonebe givenonly to adult septicshock patients after it has been confirmedthat their blood pressure ispoorly responsive to fluid resuscitationand vasopressor therapy (grade2C) 2012: We suggest not using intravenoushydrocortisone as a treatmentof adult septic shock patients if adequate fluidresuscitationand vasopressor therapy are able to restore hemodynamicstability. If thisis not achievable, we suggest intravenous hydrocortisonealone at a dose of 200 mg per day (grade 2C)

42. ARDS

43. Controversies and changes - ARDS • We recommend target a tidal volume of 6 mL/kg predicted body weight in patients with sepsis-induced ARDS (grade 1A vs. 12 mL/kg). • We suggest strategies based on higher rather than lower levelsof PEEP for patients with sepsis-induced moderate tosevere ARDS (grade 2C). • We suggest recruitment maneuvers in sepsis patients withsevere refractory hypoxemia due to ARDS (grade 2C). • We suggest ashort course of NMBA of not greater than 48 hours for patients with early sepsis-induced ARDS and a Pao2/Fio2< 150 mm Hg (grade 2C). • We suggest prone positioning be used in sepsis-induced ARDS patients with a Pao2/Fio2 ratio ≤ 100 mm Hg in facilities that haveexperience with such practices (grade 2B).

44. Sedation

45. Controversies and changes – less sedation • We recommend that either continuous or intermittentsedation be minimized in mechanically ventilated sepsispatients, targeting specific titration endpoints (grade 1B).

46. Stress ulcer prophylaxis

49. Controversies and changes • 2008:We recommend that stress ulcer prophylaxisusing H2 blocker (grade 1A)or proton pump inhibitor (grade 1B)be given to patients with severe sepsisto prevent upper gastrointestinal (GI)bleed. • 2012:We recommend that stress ulcer prophylaxis using H2 blockeror proton pump inhibitor be given to patients with severesepsis/septic shock who have bleeding risk factors (grade 1B). • When stress ulcer prophylaxis is used, we suggest the use ofproton pump inhibitors rather than H2 receptor antagonists(H2RA) (grade 2C). • We suggest that patients without risk factors should notreceive prophylaxis (grade 2B).

50. Stress ulcer prophylaxis • The balance of benefits and risks may thus depend on the individual patient’s characteristics (including the presence of enteral feeding) as well as on the local epidemiology of VAP and C. difficileinfections.