From Guideline to Practice :Before and After Surviving Sepsis Campaign in Taiwan - PowerPoint PPT Presentation

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From Guideline to Practice :Before and After Surviving Sepsis Campaign in Taiwan

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  1. From Guideline to Practice :Before and After Surviving Sepsis Campaign in Taiwan 余忠仁 臺大醫學院內科副教授 臺大醫院綜合內科部副主任

  2. Surviving Sepsis Campaign • Phase I: public awareness (2002) • Phase II: forming guidelines (2004) • Phase III: implementation of guidelines • Goal: To reduce the mortality of severe sepsis/septic shock by 25% within 5 years (2009)

  3. Surviving Sepsis CampaignGuidelines for Management of Severe Sepsis and Septic Shock Goal: To reduce the mortality of severe sepsis/septic shock by 25% in 2009 Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign Management Guidelines Committee.Crit Care Med 2004; 32:858-873

  4. Management of Sepsis • Infection control • Antibiotics, source control • Hemodynamic support • Ventilation, infusion, pump • Metabolic/endocrine support • Steroids, glucose control • New drug • Activated protein C

  5. Early Goal-Directed Therapy 28-day Mortality 60 49.2% P = 0.01* 50 40 33.3% 30 20 10 0 Standard Therapy n=133 EGDT n=130 *Key difference was in sudden CV collapse, not MODS River E. N Engl J Med 2001;345:1368.

  6. Central venous arterial catheterization CVP or FTc CVP < 8 mm Hg or FTc < 330 msec 500-ml bolus of NS or LR every 30 min prn CVP 8-12 mm Hg or FTc 330-360 msec < 65 mm Hg MAP Norepinephrine (adjustable dosage) ± vasopressin 0.04 U/min (fixed dosage) MAP >65 Cl < 2.0 and ScvO2 or SvO2 <70% Cl and ScvO2 or SvO2 Dobutamine 5 g/kg/min(adjustable dosage) Cl > 2.0 and ScvO2 or SvO2 >70% River E. N Engl J Med 2001;345:1368. Goals achieved

  7. Low-dose Steroids Placebo Low Dose Steroids and Septic Shock • Relative adrenal insufficiency: max < 9 mg/dL, 30-60 min after test Patients with Relative Adrenal Insufficiency (ACTH Test Non-responders)(77%) Patients Without Relative Adrenal Insufficiency (ACTH Test Responders)(23%) P=0.04 P=0.96 28-day Mortality N=115 N=114 N=36 N=34 (Annane et al. JAMA 2002;288:862)

  8. Intensive Glucose Control Initial Infusion Rate Blood Glucose Level (mg/dl) Insulin Infusion Rate(U/hr) 110-220 2 > 220 4 Blood Glucose Monitoring Guidelines Accuchecks every hour during insulin infusion until four consecutive values are within 80-110 mg/dl, then every 4 hours. If tube feedings or total parenteral nutrition is held or discontinued, hold infusion and monitor blood glucose levels every 2 hours. Insulin InfusionTitration Guidelines Blood Glucose Level (mg/dl) Insulin Bolus and Infusion Rate 41-60 Stop infusion 61-80 Reduce rate by 0.1-0.5 U/hr 81-111 No change unless decreased > 20% from previous result; if > 20%, decrease rate 20% 111-120 Increase rate by 0.1-0.5 U/hr 121-139 Increase rate by 0.5-1 U/hr > 140 Increase rate by 2 U/hr

  9. 100 96 Intensive treatment 92 P=0.01 Survival (%) 88 Conventional treatment 84 80 0 0 50 100 150 200 250 Days after admission The Role of IntensiveInsulin Therapy in the ICU Surgical ICU MICU3 days 100 80 Intensive treatment 60 Survival (%) P=0.02 40 Conventional treatment 20 0 0 100 200 400 300 500 Days after admission Berghe G, et al. N Engl J Med 2001;345:1359-67 Berghe G, et al. N Engl J Med 2006;354:449-61

  10. Fibrinolysis Inflammation Coagulation Neutrophil adhesion X Coagulation cascade PAI-1 X Monocyte adhesion VIIIa X Increased fibrinolysis X Va X Prothrombin PC Thrombin Thrombin P S aPC CD1/ MHC Tr Thrombomodulin

  11. Kaplan-Meier survival curves 100 90 Drotrecogin alfa (activated)(n = 850) Survival (%) 80 placebo(n = 840) 70 p = 0.006 (stratified log-rank test) 0 0 7 14 21 28 Days from start of infusion to death PROWESS. N Engl J Med 2001; 344:699-709

  12. Kaplan-Meier survival curves 100 ENHANCEDrotAA (n = 2375) 90 Survival (%) 80 PROWESS DrotAA (n = 850) 70 Placebo (n = 840) 0 0 7 14 21 28 Days from start of infusion to death (NEJM 2001; 344:699, CCM 2005;33:2266)

  13. Therapeutic goals Absolute Mortality Rate  Low VT MV, Pplat 30 cmH2O 9% Appropriate antibiotic within 4 hrs 24% EGDT 16% Decreasing lactate to 2 mmol/L in 24hrs 25% Steroid when indicated 10% Insulin for glucose 80-110 mg/dL 3% (12 ms) DrotAA for APACHE II  25 13% Importance of Establishing Therapeutic Goals in Managing Sepsis

  14. Compliance to Guidelines • ED of Hospital general Universitario “Gregorio Maranon”, Spain • Determination of blood lactate 12.5% • Blood culture done: 85% • Antibiotic within 3 hrs: 32% • Aggressive fluid therapy: 46.6% • Vasoactive drugs when indicated: 43.3% • CVP monitor: 0% (de Miguel-Yanes JM. Am J Emerg Med 2006;24:553)

  15. The EGDT protocol utilized at Cooper University Hospital (an adaptation of the protocol by Rivers et al) (Trzeciak S et al. Chest 2006;129:225)

  16. Implementing EGDT in EDCooper University Hospital • 22 cases treated with EGDT, 20 completed • Median time to reach each end point was  6 hours • EGDT used more fluids, PRBC requirement in ED • EGDT reduced ICU PAC utilization (Trzeciak S et al. Chest 2006;129:225)

  17. Implementation of Sepsis Guideline • Bundle approach • Surviving sepsis bundle • STOP sepsis bundle • Multiple Urgent Sepsis Therapies (MUST) protocol

  18. Surviving Sepsis Bundles • Sepsis Resuscitation Bundle (to be accomplished ASAP and scored over first 6 hrs) • Serum lactate • Blood culture prior to antibiotic • Broad-spectrum antibiotics administered within 3 hrs for ED admissions and 1 h for non-ED ICU admission • If hypotension (SBP<90, or MAP <70) and/or lactate > 4 mmol/L • Deliver initial minimum of 20-40 ml/kg of crystalloid (or colloid equivalents) • Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain MAP  65 mmHg • If persistent hypotension despite fluid resuscitation or lactate > 4 mmol/L • Achieve CVP of  8 mmHg • Achieve ScvO2 of  70% or SvO2 of  65% (2005 surviving Sepsis Campaign and the Institute for Healthcare Improvement)

  19. Surviving Sepsis Bundles • Sepsis Management Bundle (to be accomplished ASAP and scored over 24 hrs) • Low-dose steroids administered for septic shock in accordance with a standardized ICU policy • Drotrecogin alfa (activated) administered in accordance with a standardized ICU policy • Glucose control maintained lower limit of normal, but < 150 mg/dL • Inspiratory plateau pressure maintained < 30 cmH2O for MV patients (2005 Surviving Sepsis Campaign and the Institute for Healthcare Improvement)

  20. Sepsis Bundles:Compliance vs. non-compliance (Gao F et al. Crit Care 2005;9:R764)

  21. Compliance to 24 h sepsis bundle (Gao F et al. Crit Care 2005;9:R764)

  22. ED patients First 3 months After 6 months Achieve EGDT in 6 hrs 8% 26% Lactate monitor at 6th hr 22% 52% Appropriate steroid therapy 49% 67% STOP Sepsis Bundle • In 208 sepsis patients treated, all components of the bundle were completed in 24 patients, the mortality rate was 12.5%, compared with a 34.2% mortality rate in whom the protocol was not completed, (P = .008), and the hospital length of stay averaged 8.1 days compared with 11.9 days for the 184 patients in whom the bundle was not completed (P = .06). Nguyen HB et al SCCM 34th Critical Care Congress: Abstract 44

  23. (Nguyen HB et al. Crit Care Med 2007;35:1105)

  24. STOP Sepsis Bundle • 2 years of intervention (Nguyen HB et al. Crit Care Med 2007;35:1105)

  25. STOP Sepsis Bundle (Nguyen HB et al. Crit Care Med 2007;35:1105)

  26. Before-after standardized hospital order set study (Scott M et al. Crit Care Med 2006;34:2707)

  27. (Scott M et al. Crit Care Med 2006;34: 2707)

  28. Before-after standardized hospital order set study (Scott M et al. Crit Care Med 2006;34:2707)

  29. Multiple Urgent Sepsis Therapies (MUST) Protocol (Shapiro et al. Crit Care Med 2006;34:1025-32)

  30. MUST Protocol • Nov, 2003- Jan, 2004, 116 protocol patients and Feb, 2000- Jan, 2001, 51 historical control • Mortality rate 20.3% vs 29.4% (p=0.3) • More fluid (4.0L vs. 2.5L, p<0.001) • Earlier antibiotics (90 vs. 120 mins, p<0.013) • More appropriate coverage (97% vs. 88%, p<0.05) • More vasopressor in the first 6 hrs (80% vs. 45%, p<0.001) • Tighter glucose control (123 vs. 140, p<0.001) • Frequent assessment of adrenal function (82% vs. 10%, p<0.001) (Shapiro et al. Crit Care Med 2006;34:1025-32)

  31. Economic implications of sepsis protocol (Shorr AF et al. Crit Care Med 2007;35:1257)

  32. Implementing Sepsis Guideline in Taiwan • Education • Practice module • “Bundled” approach • Quality improvement indicator • Information technology • Research • Taiwan Guideline

  33. EDGT Taiwan • 資料來源:台大醫院急診部李建彰醫師

  34. No 懷疑感染 Yes 至少符合下列兩點 1.體溫高於38.3℃ 或低於 36℃ 2.心率大於90 3.呼吸速率大於20 或PaCO2小於 32 4.白血球大於12k 小於4k 或 band > 10% 重新評估 • 本流程參考性治療準則,若病患合併有 UGI bleeding, CHF, ESRD等狀況 應以臨床情況決定輸液治療的量及速度 • 抽血間隔: Lactate Q2h , DM病患sugar Q2H, • Cirrhosis病患應檢查albumin 檢查lactate 做兩套血液培養 區分敗血症嚴重程度 敗血性休克 定義:半小時內輸注0.9NS 500 cc依舊休克 嚴重敗血症 超過一個以上器功能障礙 或lactate大於4 敗血症 給予適當廣效性抗生素住 一小時內建立上腔中心靜脈導管 一小時內給予適當廣效性抗生素 視情形給予插管及機械換氣 血糖以連續insulin控制在 90~150 考慮給予 H2 blocker for stress ulcer prophylaxis 進入早期目標導向治療 (early goal directed therapy) 六小時內完成下列目標 CVP 12-15 SBP 90-140 MAP 65-90 SvO2 >= 70 目標一:CVP 12-15* 未達目標0.9NS 繼續全速輸注直到CVP 8-12 然後維持100cc/hr, 輸液超過2000cc 0.9NS,未達目標, 考慮進入目標二 CVP < 4可考慮給予HAES (肝硬化患者考慮給予 Albumin ), 使用正壓換氣或有腹壓上升情形, 應維持CVP >=15 目標二:SBP 90-140 MAP 65-90 考慮給予昇壓劑 Dopamine, Norepinehrine 若一小時仍SBP<90 考慮給予Vasopressin (0.04u/min)及dexamethasone 2mg IV Q6h (如臨床懷疑adrenal insufficiency雖無敗血性休克亦應給予) 目標三:SvO2 >= 70 未達目標三, 若Hb<10 輸PRBC, 若Hb>10給予Dobutamine Q2h檢查lactate 直到lactate < 2 達成目標 ICU 住院 台大醫院急診部敗血症病患標準治療流程

  35. Preliminary Results • Period • 2006 Jan ~ 2006 May • Setting • NTUH ED Critical Area • Staffed by Visiting Staff / Chief Resident/ Physician assistant • 9 Rooms with Monitor Devices • 1 SCVO2 monitor • Patients • Randomly Selected patients with septic shock • Patients with severe sepsis not included in this preliminary trial

  36. Characteristics between Case and Control Groups

  37. Primary Outcome Survival Curve EGDT group Traditional group Log-Rank test: P=0.109 Days Mortality: 9.1% vs. 45%

  38. Secondary Outcome • Length of hospital stay ( alive ) • EGDT group: 20.1 +/- 25.9 • Traditional therapy: 27.4 +/- 22.9 (Non parametric test: P=0.22)

  39. STOP Sepsis Bundle, Taiwan 資料來源:奇美醫學中心柳營院區加護醫學部侯清正主任 Pre-intervention period: yr 2005 Post-intervention period: yr 2006

  40. 過程面指標

  41. 輸液及藥物的給予

  42. 結果面指標

  43. 敗血性休克6小時目標達成時間與其死亡率

  44. Glycemic control protocol, KMUH • 資料來源:高雄醫學大學附設中和紀念醫院胸腔內科許超群醫師 Sugar Control Protocol, 三次大改版 ICU專責主治醫師制