What’s new in Clinical Practice Guidelines (CPG) in Critical Care Kuwait, April 11, 2013 What is new in CPG in Critical Care Past, Present, Future 1. Process of CPG development (GRADE) 2. Examples of new and / or controversial recommendations 3. Future tasks 4. Allow you to use those guidelines with more satisfaction New developments in communism The evolution of power in medicine • Clinical Experience and pathophysiological knowledge • RCTs • Meta-analyses, decision analyses, economic analyses • Above with recommendation Practice guidelines In the beginning... • Early 2000 – CPG increasing in importance – Chaos all over the place, especially for ‘generalists’ – Need to create order out of chaos GRADE: Guideline development process – What is the question? • Step two – Find and summarize best evidence • Step three – Apply judgments (quality of evidence, strength of recommendations) rade • Step one G 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 Recommendations: Weak or strong? strong methods AND benefits clearly outweigh downsides weak recommendations weak methods OR balance of benefits and downsides unclear or close ecommendation strong recommendations R Formulate question Select outcomes Rate importance of outcomes Systematic Review (outcomes across studies) Evidence Profile (GRADEpro) 1 2 Pooled estimate of effect for each outcome Quality of evidence for each outcome PICO Critical Outcome2 Critical Outcome3 Important Outcome4 Not start RCT observational rate down action Outcome1 1. 2. 3. 4. 5. rate up High Moderate High | Moderate |Low Low| Very Very low low 1. large effect 2. dose-response 3. antagonistic bias risk of bias inconsistency indirectness imprecision publication bias systematic review of evidence 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) recommendation Guideline panel 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) high low Strength of recommendation degree of confidence that desirable effects of adhering to recommendation outweigh the undesirable effects. Desirable effects •health benefits •less burden •savings Undesirable effects •harms •more burden •costs Strong or Weak Recommendation? • Quality of the evidence • Balance between desirable and undesirable effects • Values and preferences • Costs (resource allocation, feasibility) Strenght of Recommendations • 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 Why Grade Recommendations? Implications • strong recommendation – one size fits all – expect uniform clinician behavior – use as performance indicator • weaker recommendation – expect action to vary Strenght of Recommendations • do it or don’t do it –strong recommendation • probably do it, or probably don’t –weaker recommendation 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 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 Surviving Sepsis Campaign • New or controversial recommendations • • • • • • 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 Formulate question Select outcomes Rate importance of outcomes Systematic Review (outcomes across studies) Evidence Profile (GRADEpro) 1 2 Pooled estimate of effect for each outcome Quality of evidence for each outcome PICO Critical Outcome2 Critical Outcome3 Important Outcome4 Not start RCT observational rate down action Outcome1 1. 2. 3. 4. 5. rate up High Moderate High | Moderate |Low Low| Very Very low low 1. large effect 2. dose-response 3. antagonistic bias risk of bias inconsistency indirectness imprecision publication bias systematic review of evidence 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) recommendation Guideline panel 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) high low Importance of team work! Controversies and changes – team work • Sepsis management requires a multidisciplinary team (physicians, nurses, pharmacy, respiratory, dieticians, and administration) and multispecialty collaboration (medicine, surgery, and emergency medicine) to maximize the chance for success. 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 Controversies and changes (plus some gossiping) • The administration of effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) should be the goal of therapy. • Remark: Although the weight of the evidence supports prompt administration of antibiotics following the recognition of severe sepsis and septic shock, the feasibility with which clinicians may achieve this ideal state has not been scientifically evaluated. Controversies and changes (plus some gossiping) • The administration of effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) should be the goal of therapy. • Remark: Although the weight of the evidence supports prompt administration of antibiotics following the recognition of severe sepsis and septic shock, the feasibility with which clinicians may achieve this ideal state has not been scientifically evaluated. surviving patients [%] time from onset of hypotension [hours] Importance of team work! Controversies and changes (plus some gossiping) • The administration of effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) should be the goal of therapy. • Remark: Although the weight of the evidence supports prompt administration of antibiotics following the recognition of severe sepsis and septic shock, the feasibility with which clinicians may achieve this ideal state has not been scientifically evaluated. 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 Another protocol JAMA Feb 24, 2010 (Jan 2007-Jan 2009) 17% mortality 23% mortality Controversies and changes – new protocol • We suggest targeting resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion (grade 2C) • Text: If Scvo2 is not available, lactate normalization may be a feasible option in the patient with severe sepsis-induced tissue hypoperfusion. Scvo2 and lactate normalization may also be used as a combined endpoint when both are available. Controversies and changes – new diagnostic possibilities (plus gossiping) • We suggest the use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who appeared septic, but have no subsequent evidence of infection (grade 2C). Vasopressors and inotrops – positive thinking Controversies and changes - vasopressors • We recommend norepinephrine as the first-choice vasopressor (grade 1B). • We suggest epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B). • We suggest dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia) (grade 2C). • A trial of dobutamine infusion up to 20 mcg/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP (grade 1C) Low dose long term glucocorticosteroids for severe sepsis and septic shock Outcomes Illustrative comparative risks (95% CI) Assumed risk Corresponding risk Placebo Low dose long term glucocorticost eroids Mortality 432 per 1000 394 per 1000 Follow-up: mean 28 (329 to 467) days Mortality in higher 612 per 1000 baseline mortality studies Follow-up: mean 28 days Mortality in lower 317 per 1000 baseline mortality studies Follow-up: mean 28 days 471 per 1000 (343 to 642) 336 per 1000 (270 to 425) Relativ No of Quality of Comments e effect Participa the (95% nts evidence CI) (studies) (GRADE) RR 0.91 (0.76 to 1.08) RR 0.77 (0.56 to 1.05) 968 ⊕⊕⊝⊝ (6 low1,2 studies) 381 ⊕⊕⊕⊝ (3 moderate3, studies) 4 RR 587 ⊕⊕⊕⊝ 1.06 (3 moderate5 (0.85 to studies) 1.34) Controversies and changes 2008: We suggest that intravenous hydrocortisone be given only to adult septic shock patients after it has been confirmed that their blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy (grade 2C) 2012: We suggest not using intravenous hydrocortisone as a treatment of adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. If this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day (grade 2C) ARDS 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 levels of PEEP for patients with sepsis-induced moderate to severe ARDS (grade 2C). • We suggest recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (grade 2C). • We suggest a short 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 have experience with such practices (grade 2B). Sedation Controversies and changes – less sedation • We recommend that either continuous or intermittent sedation be minimized in mechanically ventilated sepsis patients, targeting specific titration endpoints (grade 1B). Stress ulcer prophylaxis Controversies and changes • 2008: We recommend that stress ulcer prophylaxis using H2 blocker (grade 1A) or proton pump inhibitor (grade 1B) be given to patients with severe sepsis to prevent upper gastrointestinal (GI) bleed. • 2012: We recommend that stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to patients with severe sepsis/septic shock who have bleeding risk factors (grade 1B). • When stress ulcer prophylaxis is used, we suggest the use of proton pump inhibitors rather than H2 receptor antagonists (H2RA) (grade 2C). • We suggest that patients without risk factors should not receive prophylaxis (grade 2B). 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. difficile infections. Controversies and changes – DVT 2008: • We recommend that patients with severe sepsis receive DVT prophylaxis with either a) low dose UFH administered twice or three times per day; or b) daily LMWH unless there are contraindications (grade 1A). • We suggest that in patients at very high risk, LMWH be used rather than UFH as LMWH is proven superior in other highrisk patients (grade 2C). • We recommend that patients with severe sepsis receive daily pharmacoprophylaxis against VTE (grade 1B). • We recommend that this be accomplished with daily subcutaneous LMWH (grade 1B versus UFH twice daily and grade 2C versus UFH given thrice daily). Sweet is good! Controversies and changes – sweet is good! • 2008 We suggest use of a validated protocol for insulin dose adjustments and targeting glucose levels to the 150 mg/dL range (grade 2C). • A protocolized approach to blood glucose management in ICU patients with severe sepsis commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL. • This protocolized approach should target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL (grade 1A). Controversies and changes - platelets • 2012: In patients with severe sepsis, we suggest that platelets be administered prophylactically when counts are ≤ 10,000/ mm3 (10 × 109/L) in the absence of apparent bleeding, as well when counts are ≤ 20,000/mm3 (20 × 109/L) if the patient has a significant risk of bleeding. Higher platelet counts (≥ 50,000/mm3 [50 × 109/L]) are advised for active bleeding, surgery, or invasive procedures (grade 2D). • 2008: In patients with severe sepsis, we suggest that platelets be administered when counts are 5000/mm3 (5x109/L) regardless of apparent bleeding. • Platelet transfusion may be considered when counts are 5000–30,000/mm3 (5–30 109/L) and there is a significant risk of bleeding. Higher platelet counts (50,000/mm3 [50 109/L]) are typically required for surgery or invasive procedures (grade 2D). Nutrition Controversies and changes – don’t push calories... • 1. We suggest administering oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (grade 2C). • 2. We suggest avoiding mandatory full caloric feeding in the first week, but rather suggest low-dose feeding (eg, up to 500 kcal per day), advancing only as tolerated (grade 2B). • 3. We suggest using intravenous glucose and enteral nutrition rather than total parenteral nutrition (TPN) alone or parenteral nutrition in conjunction with enteral feeding in the first 7 days after a diagnosis of severe sepsis/septic shock (grade 2B). • 4. We suggest using nutrition with no specific immunomodulating supplementation in patients with severe sepsis (grade 2C). • Translation: Atempt feeding as patient tolerates, don’t push full caloric intake for its own sake, underfeeding (2/3) / trophic feeding (up to 500 kcal) is OK/even better (but may increase it if fast recovery), don’t use TPN early, do not use supplements (all 2C) Controversies and changes - Communication 2008 Consideration for Limitation of Support 2012 Setting Goals of Care • 1. We recommend that advance care planning, including the communication of likely outcomes and realistic goals of treatment, be discussed with patients and families (grade 1D). • 1. We recommend that goals of care and prognosis be discussed with patients and families (grade 1B). • 2. We recommend that the goals of care be incorporated into treatment and end-of-life care planning, utilizing palliative care principles where appropriate (grade 1B). • 3. We suggest that goals of care be addressed as early as feasible, but no later than within 72 hrs of ICU admission (grade 2C). Sepsis bundles: Converting guidelines into meaningful change in behavior Controversies and changes - Fluids 2008 We recommend fluid resuscitation with either natural/artificial colloids or crystalloids (1B) 2011 We recommend not using ‘200 starch’ (Grade 1A) and suggest not using 130 starches (2B) Albumin versus other fluids for sepsis Patient or population: Patients with sepsis Settings: Intensive care unit Intervention: Albumin versus other fluids. Outcomes Illustrative comparative risks (95% CI) Assumed risk Corresponding risk Other fluids (may be crystalloid or colloid) Albumin Relative effect (95% CI) No of Participants (studies) Quality of the evidence (GRADE) Short term mortality Study population 342 per 1000 287 per 1000 (249 to 332) RR 0.84 (0.73 to 0.97) 1683 (11 studies) ⊕⊕⊕⊝ moderate Short term mortality (albumin vs crystalloids) 444 per 1000 377 per 1000 (324 t o440) RR 0.85 (0.73 to 0.98) 1402 (4 studies) ⊕⊕⊕⊝ moderate1 342 per 1000 Short term mortality (albumin vs other colloids) 195 per 1000 (249 to 396) RR 0.81 (0.57 to 1.16) 281 (7 studies) ⊕⊕⊕⊝ moderate1 Comments *The assumed risk is the control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio Grade reduced for imprecision. Controversies and changes fluids 2011 We suggest to include some albumin over crystalloids alone in the initial fluid resuscitation regimen(2B) and recommend albumin be combined with crystalloids in the initial fluid resuscitation regimen when serum albumin concentration is known to be low (1B) In the initial volume management of septic patients we suggest crystalloids with supplemental discretionary use of albumin over other management strategies (2B) Controversies and changes - fluids 2012 We recommend crystalloids be used as the initial fluid of choice in the resuscitation (1B) 2012 We recommend against the use of hydroxyethyl starches (HES) for fluid resuscitation (grade 1B). 2012 We suggest the use of albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C) Controversies and changes - fluids 2013 administration of saline should be limited in septic shock (2C) (proposal) PAD guideliens PAD guidelines PAD guideliness • Process – 20 people – 6 year long work – Developing questions, review/evaluate/sumarize evidence – Develop descriptive statements and actionable recomendation – Evaluated and compared pain, agitation/sedation and delirium measurement tools PAD guideliness • Differences from previous 2002 guidelines: – Use of GRADE (connecting evidence with recommendations) – Use of professional librarian (19,000 papers, 472 references) – Scope (Pain, Agitation, Sedation, Delirium) – Anonymous pooling of opinions and assessments – Multidisciplinary approach (MD (9), RN (6), pharmacy (2), geriatrics) PAD guidelines Descriptive statement Actionable recommendation • Adult medical, surgical, and trauma ICU patients routinely experience pain, both at rest and with routine ICU care (B) • We recommend that pain be routinely monitored in all adult ICU patients (+1B) • Pre-procedural analgesia used in about 20% (B) • All available IV opioids, when titrated to similar pain intensity endpoints, are equally effective (C). • We recommend that IV opioids be considered as the first-line drug class of choice to treat nonneuropathic pain in critically ill patients (+1C) • We suggest that analgesia-first sedation be used in mechanically ventilated adult ICU patients (+2B) Pain PAD guidelines - Pain • Pain frequent (especially in cardiac surgery, especially in women) (B) • All opioids, when titrated, are equally effective (C) • Preemptive analgesis prior to chest tube removal (1C) • Opioids first class of drugs (1C) • The Behavioral Pain Scale (BPS) and the Critical-Care Pain Observation Tool (CPOT) are the most valid and reliable behavioral pain scales (B). PAD guidelines - Pain Goal – 5 or less; 6 or more not acceptable PAD guidelines – Agitation and Sedation • Maintaining light levels of sedation : – is associated with shorter duration of MV and a shorter ICU LOS [B) – increases the physiologic stress response, but not myocardial ischemia (B) – its association with psychological stress remains unclear (C). • We recommend that sedative medications be titrated to maintain a light rather than a deep level of sedation in adult ICU patients, unless clinically contraindicated (+1B). – RASS and SAS (Richmond Sedation Agitation Scale and Reiker SAS) are valid sedation assesment tools (B) PAD guidelines – Agitation and Sedation PAD guidelines – Agitation and sedation • Prompt identification and treatment of possible underlying causes of agitation, such as pain, delirium, hypoxemia, hypoglycemia, hypotension, or withdrawal from alcohol and other drugs, are important • Maintenance of patient comfort, provision of adequate analgesia, frequent reorientation, and optimization of the environment to maintain normal sleep patterns, should be attempted before administering sedatives PAD guidelines – Agitation and Sedation • We suggest that sedation strategies using nonbenzodiazepine sedatives (either propofol or dexmedetomidine) may be preferred over sedation with benzodiazepines (either midazolam or lorazepam) to improve clinical outcomes in mechanically ventilated adult ICU patients (+2B). PAD guidelines – Agitation and Sedation Delirium PAD guidelines – Delirium • Delirium: – syndrome of acute onset of cerebral dysfunction with change or fluctuation in baseline mental status – disorganized thinking or an altered level of consciousness – inattention, inability to sustain or shift attention – reduced awareness of the environment – perceptual disturbance (i.e., hallucinations, delusions) are frequent but neither required for diagnosis – Other symptoms : sleep disturbances, emotional disturbances (i.e., fear, anxiety, anger, depression, apathy, euphoria) – may be agitated (hyperactive delirium), calm or lethargic (hypoactive delirium), or may fluctuate between the two subtypes. PAD guidelines – Delirium Delirium is associated with: – increased mortality (A) – prolonged LOS (A) – development of post-ICU cognitive impairment (B) – Risk factors (baseline): dementia, hypertension, alkoholism, severity of ilness (B) – Risk factors (later): coma, benzodiazepine use (in comparison to dex) (B) – Confusion Assesment Method (CAM-ICU) and Intensive Care Delirium Screening Checklist most valid for monitoring (A) – We recommend routine monitoring for delirium in adult ICU patients (+1B) PAD guidelines – Delirium • Delirium prevention: – early mobilization (1B) • Delirium treatment: – No evidence to support haloperidol (0) – Atypical may reduce duration (in comparison to placebo (all patients on haloperidol) (C) – Against ryvastigmine (1B) – Early mobilization (+1B) – If sedation required (and no benzos or alkohol withdrawal), suggest dexmedetomidine vs. benzos (2B) – No magic bullet drug, more in way of delivering care PAD guidelines – Management Strategies • Strategies for management: – Measure PAD – Analgesia first sedation (2B) – Daily sedation interruption OR light target sedation (with sedation only if required and goal to allow responsiveness and awarness) (1B) – Promoting and protecting sleep cycles (1C) – We recommend using an interdisciplinary ICU team approach that includes provider education, preprinted and/or computerized protocols and order forms, and quality ICU rounds checklists to facilitate the use of pain, agitation, and delirium management guidelines or protocols in adult ICUs (+1B) Future challenges for method center • training of GRADE resource individuals; • training of content area experts in GRADE methodology (rise and usefulness of webinars); • planning for the future updates and reiterations (succession plans); • continuous struggle to link the recommendation to evidence; Proton Pump Inhibitors Versus Histamine 2 Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients: A Systematic Review and Meta-Analysis. Waleed Alhazzani, Farhan Alenezi, et al Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and metaanalysis of randomized controlled trials. Alhazzani W, Alshahrani M, et al The Effect of Selenium Therapy on Mortality in Patients With Sepsis Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Waleed Alhazzani, et al النهاية. شكرا لك.