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ACTEP2014: Sepsis management has anything change

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Sepsis management: Has anything changed? - อ.นพ.กลวิชย์ ครองตระกูล

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ACTEP2014: Sepsis management has anything change

  1. 1. Sepsis Management: Has anything changed ? นพ.กลวิชย์ ตรองตระกูล หน่วยเวชบำบัดวิกฤต ภาควิชาเวชศาสตร์ฉุกเฉิน คณะแพทยศาสตร์วชิรพยาบาล มหาวิทยาลัยนวมินทราธิราช ACTEP @ เขาใหญ่, ๒๘ พฤศจิกายน ๒๕๕๗, ๐๘:๓๐-๐๙:๐๕ น. 1 Introductions • Pathophysiology of sepsis, severe sepsis and septic shock • What is new in septic shock resuscitation? • Protocolized in resuscitation • EGDT, CVP, MAP target, ScvO2, and blood transfusion threshold • Type of fluid resuscitation • Chloride base, HES, and albumin 2 Pathophysiology of Sepsis Angus DC, et al. New Engl J Med 2013;369:840-51. 3 Sepsis: Disease of continuum Infection • T ≤ 36, ≥ 38 °C • HR ≥ 90 • RR ≥ 20, or PaCO2 < 32 mmHg • WBC ≥ 12,000 or ≤ 4,000 or > 10% immature WBC Angus DC, et al. New Engl J Med 2013;369:840-51. Shock despite adequate fluid resuscitation Peripheral vasodilatation Inotrope Presence of organ dysfunction SIRS with presume/ confirm infections Fluid Vasopressor Sepsis with ≥ 1 sign of organ failure (renal, respiratory, sepsis induce hypotension, confusion) MODs SIRS Sepsis Severe Sepsis Septic Shock Relative hypovolemia Myocardial suppression 4 Oxygen Delivery Oxygen in atm Cardiac Output (CO) Lung Heart Vascular RBC Oxygen delivery Tissue X Oxygen Content (CaO2) Preload Afterload Contractility Heart rate Hemoglobin Oxygen Fluid Vasopressor Inotrope RBC txf FiO2 } Oxygen Consumption BP = CO x SVR 5 การกู้ชีพเบื้องต้น (initial resuscitation) ในช่วง 6 ชั่วโมงแรกของภาวะภาวะติดเชื้อใน กระแสโลหิตแบบรุนแรง (severe sepsis) และภาวะช็อกจากการติดเชื้อในกระแสโลหิต (septic shock) จากข้อแนะนำของ SSC 2012 1. ผู้ป่วยที่มีภาวะติดเชื้อในกระแสโลหิตที่ทำให้ความดันโลหิตต่ำ (sepsis-induced hypotension) หรือ แลกเตทในเลือดมากกว่าหรือเท่ากับ 4 มิลลิโมลต่อลิตร ควรได้รับ การกู้ชีพตามข้อกำหนดซึ่งวัดเป็นเชิงปริมาณได้ (protocolized, quantitative resuscitation) ได้แก่ ก) Central venous pressure 8 - 12 มิลลิเมตรปรอท ข) Mean arterial pressure (MAP) มากกว่าหรือเท่ากับ 65 มิลลิเมตรปรอท ค) ปัสสาวะออกมากกว่าหรือเท่ากับ 0.5 มิลลิลิตรต่อกิโลกรัมต่อชั่วโมง ง) Central venous oxygen saturation (ScvO2) หรือ mixed venous oxygen saturation (SvO2) มากกว่าร้อยละ 70 หรือ 65 ตามลำดับ (grade 1C) 2. ในผู้ป่วยที่มีระดับแลกเตทในเลือดสูง ควรให้การกู้ชีพจนค่าแลกเตทเข้าสู่ค่าปกติ (grade 2C) 6
  2. 2. Protocolized resuscitation What is new ? 7 Early Goal Directed Therapy Rivers, NEJM 2001 fluid 500 ml q 30 min crystalloid to achieve CVP 8-12 mmHg Vasopressor if MAP <=65, vasodilator if MAP > 90 DBT 25 mcg/kg/min, increased by 2.5 q 30 min until ScvO2 > 70 or max 20, decrease or stop if HR > 120 or MAP < 65 - 263 SS&SSh pts at ED in US randomised to EGDT vs standard therapy - Primary outcome: In hospital mortality Fluid Vasopressor RBC Inotrope 8 Increasing in Oxygen Demand Normal condition Oxygen delivery SaO2 = 100% o2 o2 o2 o2 Venous Oxygen SvO2 = 75% o2 o2 co2 o2 Oxygen delivery SaO2 = co 100% o2 o2 o2 o2 Venous Oxygen SvO2 = 50% o2 o2 co2 Increase demand co2 co co2 9 Early Goal-Direct Therapy in The Treatment of Severe Sepsis and Septic Shock (EGDT) - 263 SS&SSh pts at ED in US randomised to EGDT vs standard therapy - Primary outcome: In hospital mortality Outcome EGDT collaborative group, New Engl J Med 2001,345:1368-77. 10 CVP is only 56% in predicting fluid responsiveness Osman et al. Crit Care Med 2007;35(1) Marik PE et al. Chest 2008;134:172-8. 11 Limitation of EGDT 12
  3. 3. Pace of Goal directed study 2001 2014 2014 2015 EGDT by Rivers US 263 SS/SSh EGDT 6 hr vs usual Rx In Hos MR ProCESS US 1351 SS/SSh EGDT 6 hr vs standard usual Rx 60-MR ARISE ANZICs 1600 SS/SSh EGDT 6 hr vs usual Rx 90-MR ProMISe UK 1260 SS/SSh EGDT 6 hr vs usual Rx 90-MR 13 A Randomized Trial of Protocol-Based Care for Early Septic Shock (ProCESS study) Protocol-based standard therapy SI (HR/SBP) ≤ 0.8 Early goal directed therapy Usual care therapy 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care ProCESS Study. N Engl J Med 2014;370:1683-93. No central line SBP ≥ 100 mmHg HB ≥ 7.5 gm/dL CVP ≥ 8-12 mmHg MAP ≥ 65 mmHg SCVO2 ≥ 70 mmHg Hct ≥ 30 % vs vs Usual Care 14 SI = HR/SBP *Time Sensitive target Time allowed7 Corrective action Fluid bolus (500-1000 ml) 20 minutes 3rd IV or central line Initial fluid bolus (2L) 1 hour 3rd IV or central line SBP ≥ 100 mmHg 1 hour Vasopressors -Fluid overload by clinical Dx: JVD, rales, drop in SpO2 -Definition of hypoperfusion: MAP < 65 despite SBP > 100, arterial lactate 4, mottled skin, oliguria and altered sensorium 15 A Randomized Trial of Protocol-Based Care for Early Septic Shock (ProCESS study) ProCESS Study. N Engl J Med 2014;370:1683-93. 16 Goal-Directed Resuscitation for Patients with Early Septic Shock (ARISE trial) • 1,600 enrolled pts, 796 were assigned to EGDT and 804 to usual care • Conducted at 51 enters (mostly in Australia or New Zealand, 3#care and not 3# care centre) ARISE trial. N Engl J Med 2014;371:1496-506. 17 Goal-Directed Resuscitation for Patients with Early Septic Shock (ARISE trial) ARISE trial. N Engl J Med 2014;371:1496-506. 18
  4. 4. Outcome of 3 protocolized studies EGDT ProCESS ARISE ProMISe Location US US ANZICs UK Publications 2001 2014 2014 ~2015 Population 263 1351 1600 1260 Fluid before randomisatio n 20-30 mL/kg 20 > 30 mL/kg 1000 ml 1000 ml Hos MR 30.5 vs 46.5, p = 0.009 - - 90-day MR 28 day MR 33.3 vs 49.2, p = 0.01 - 14.8 vs 15.9, p = 0.53 (3°) n/a 60 day MR 44.3 vs 56.9, p = 0.03 21.0 vs 18.0 vs & 18.9, p = 0.83 - n/a 90 day MR - 31.9 vs 30.8 vs 33.7, p =0.06 18.6 vs 18.8, p = 0.90 (1°) n/a 19 Baseline characteristic EGDT ProCESS ARISE Location US US ANZICs Age 67.1±17.4 vs 64.4±17.1 60±16.4 vs 62±16.0 62.7±16.4 vs 63.1±16.5 APACHE II 21.4±6.9 vs 20.4±7.4 20.8±8.1 vs 20.7±7.5 15.4±6.5 vs 15.8±6.5 Lactate 7.7±4.7 vs 6.9±4.5 4.8±3.1 vs 4.9±3.1 4.4±3.3 (6.7±3.3) vs 4.2±2.8 (6.6±2.8) SBP 106±36 vs 109±34 100.2±28.1 vs 99.9±29.5 78.8±9.3 vs 79.6±8.4 Septic shock 54.7% vs 51.3% 55.6% vs 53.3 70% vs 69.8% ScvO2 48.6±11.2 vs 49.2±13.3 71.±13 vs n/a 75.9±8.4 vs n/a 20 High versus Low Blood-Pressure Target in Patients with Septic Shock (SEPSISPAM) Outcome Low target (N=388) High target (N=388) P value Death at day 28-no.(%) 132 (34.0) 142 (36.6) 0.57 Death at day 90-no.(%) 164 (42.3) 170 (43.8) 0.74 Doubling S cr 161 (41.5) 150 (38.5) 0.32 No HTN 71/215 (33.0) 85/221 (38.5) 0.32 HTN 90/173 (52.0) 65/167 (38.9) 0.02 RRT day 1- 7 139 (35.8) 130 (33.5) 0.50 No HTN 66/215 (30.7) 77/221 (34.8) 0.36 HTN 73/173 (42.2) 53/167 (31.7) 0.046 SEPSISPAM. N Engl J Med 2014; 370:1583-93. 776 pts with SSh in France Target: High 80-85 mmHg vs Low 65-70 mmHg x for 5 day/wean off P=0.57 at 28 days P=0.74 at 90 days 21 Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock (TRISS study) TRISS study. N Engl J Med 2014; 371:1381-91. 998 pts with SSh assigned to receive Leukoreduced PRC for different Hb threshold in ICU ( 7 vs 9 g/dL) Primary outcome: death by 90 days Exclusion: ischemic heart disease, severe hypoxia, life-threatening bleeding, ischemia developed in the ICU, and ECMO 22 Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock (TRISS study) TRISS study. N Engl J Med 2014; 371:1381-91. 23 Which vasopressors? Which inotropes? 24
  5. 5. Comparison of Dopamine and Norepinephrine in the Treatment of Shock • Which one agent is superior to the other? • Multicenter RCT in 1679 patients (MAP<70 or SBP<100) • 858 were assigned to dopamine (20 mcg/kg/min) • 821 were assigned to norepinephrine (0.19 mcg/kg/min) Mortality Rates Backer DD. N Engl J Med 2010;362:779-89. 25 Comparison of Dopamine and Norepinephrine in the Treatment of Shock Backer DD. N Engl J Med 2010;362:779-89. 26 “Fluid Strategy in Sepsis” 1. Early resuscitation 2. Maintenance fluid 27 Fluid resuscitation why? • Relative hypovolemia • Arterial and venous dilatation and leakage of plasma to extravascular space • Low SVR, increase CO2 production, tachycardia, and elevated oxygen concentration in PA = hyper-dynamic shock syndrome 28 “Type of fluid using in Sepsis” Colloid vs Crystalloid 29 Starling’s Law Qf = Kf [(Pcap - Pif) - ơ (¶cap-¶if)] Qf = net fluid filtration between compartment Kf = Capillary filtration coefficient Pcap = Capillary hydrostatic pressure In Sepsis • ↑ Pcap, ↓¶ cap = ↑ edema formation Pif = Interstitial hydrostatic pressure ơ = reflection coefficient ¶cap = Colloid osmotic pressure ¶if = Interstitial oncotic pressure 30
  6. 6. A) Normal endothelial glycocalyx (EG) layer B) Damaged EG in sepsis etc. C) Transvascular exchange by Starling’s Law Resuscitation fluid. New Engl J Med 2013,369:1243-51. c Qf = Kf [(Pc - Pi) - ơ (¶c-¶i)] 31 Basic fluid therapy Intracellular 40% of BW Intra vascu lar 5 % of BW Interstitial 15 % of Extra cellular 20% of BW BW BP,HR,UOP,CVP Thirst skin tugor, mucosa Osmotic (oncotic) and hydrostatic pressure 32 33 Stages of volume status Volume status Time Resuscitation Optimization Stabilization Deescalation 34 Ideal of fluid resuscitation • Predictable and sustained increase in intravascular volume • Chemical composition as close as possible to ECF • Metabolized and completely excreted without accumulation in tissue • Does not produce adverse metabolic or systemic effects • Cost-effective in terms of improving outcomes Resuscitation fluid. New Engl J Med 2013,369:1243-51. 35 Normal saline: toxic to kidney? Chloride solutions may cause renal failure • Chloride rich fluid (0.9% NSS, 4% gelatine, 4% albumin) vs Chloride restrictive fluids (chloride poor 20% albumin, Hartmann solution, Plasma-lyte 148) • Serum Creatinine was higher in chloride rich fluid than chloride restriction • 22.6 (17.5-27.7) vs 14.8 (9.8-19.9) umol/L; p=0.03 • Severity stage of AKI and RRT was lower in chloride restriction group than chloride rich fluid JAMA 2012;308:1566-72. 36
  7. 7. Abnormal saline !! AKI stage 2-3 by KDIGO definition Renal replacement therapy in ICU JAMA 2012;308:1566-72. 37 Chloride and Kidney KI 2014, doi:10.1038/ki.2014.105 38 Intensive Insulin therapy and Pentastarch Resuscitation in Severe Sepsis (VISEP study) -537 pts with SS in Germany, 18 ICU (Stopped early due to safety reason) -10% HES 200/0.5 vs Ringer lactate solution in pts with SS&SSh -Primary outcome: Death 28 days, Secondary outcome: AKI VISEP study, NJEM 2008,385:125-39. 39 Intensive Insulin therapy and Pentastarch Resuscitation in Severe Sepsis (VISEP study) VISEP study, NJEM 2008,385:125-39. Outcome HES (N=262) RLS (N=275) P value Death at 28 days - no./total (%) 70/262 (26.7) 66/274 (24.1) 0.48 Death at 90 days - no./total (%) 107/261 (41.0) 93/274 (33.9) 0.09 Acute renal failure - no./total (%) 91/261(34.9) 62/272 (22.8) 0.002 RRT - no./total (%) 81/261 (31.0) 51/272 (18.8) 0.001 RBC transfusion - no./total (%) 199/262 (76.0) 189/275(68.7) 0.06 No. of RBC transfusion (unit) 6 (4-12) 4 (2-8) < 0.001 40 Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis (6S trials) -798 pts with severe sepsis in Denmark Norway Finland and Iceland, 26 ICUs -6% HES 130/0.4 vs Ringer’s acetate throughout their illness -Primary outcome: Dead or need for dialysis at 90 days after randomization 6S trials, NJEM 2012. 41 Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis (6S trials) 6S trials, NJEM 2012. Outcome HES (N=398) RA (N=400) Relative risk (95%CI) P value Dead or dependent on dialysis at day 90 - no. (%) 202 (51) 173 (43) 1.17 (1.01-1.36) 0.03 Dead at day 90 - no. (%) 201 (51) 172 (43) 1.17 (1.01-1.36) 0.03 Dependent on dialysis at day 90 - no.(%) 1 (0.25) 1 (0.25) - 1.00 Use RRT - no. (%) 87 (22) 65 (16) 1.35 (1.01-1.80) 0.004 Doubling creatinine level - no. (%) 148 (41) 127 (35) 1.18 (0.98-1.43) 0.08 42
  8. 8. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care (CHEST trials) -7000 pts admitted to ICU in Australia & New Zealand -6% HES 130/0.4 vs 0.9% NaCl for fluid resuscitation until D/C -Primary outcome: Death, secondary outcome: AKI-I & F and RRT CHEST Trail, NJEM 2012,367:1901-11. 43 Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care (CHEST trials) -7000 pts admitted to ICU in Australia & New Zealand -6% HES 130/0.4 vs 0.9% NaCl for fluid resuscitation until D/C -Primary outcome: Death, secondary outcome: AKI-I & F and RRT Outcome HES Saline RR (95%CI) P value Death at day 90 - no.total no. (%) 597/3315 (18.0) 566/3336 (17.0) 1.06 (0.96-1.18) 0.26 Renal outcome RIFLE-R 1788/3309 (54.0) 1912/3335 (57.3) 0.94 (0.90-0.98) 0.007 RIFLE-I 1130/3265 (34.6) 1253/3300 (38.0) 0.91 (0.85-0.97) 0.005 RIFLE-F 336/3243 (10.4) 301/3263 (9.2) 1.12 (0.97-1.3) 0.12 Use RRT 235/3352 (7.0) 196/3375 (5.8) 1.21 (1.00-1.45) 0.04 CHEST Trail, NJEM 2012,367:1901-11. 44 HES increased AKI in Sepsis/septic shock Trial VISEP study 6S Trial CHEST Trial CRYSTMAS study Intervention 10%HES 200/0.5 vs RLS 6%HES 130/0.42 vs RA 6%HES 130/0.4 vs 0.9%NSS 0.6%HES130/0.4 vs 0.9%NSS Population 537 pts with Severe sepsis 798 pts with Severe sepsis in ICUs 7000 pts within ICU (fluid ressus) 196 pts with Severe sepsis Outcome Death at 28 days Death or ESKD at 90 days Death within 90 days Volume and time to reach HDS Results 81/261 (31%) vs 51/272 (18%), p 0.001 201/398 (51%) vs 172/400 (43%), p = 0.03 Death Not significant, RRT 235/3352 (7%) vs 196/3375 (5.8%), p = 0.04 Less HES volume was used to reach HDS vs NSS AKI 24.5% vs 20%, p = 0.454 Conclusion HES was harmful, increased risk of AKI HES increased risk of death and RRT HES increased RRT Less volume to reach HDS by HES vs NSS Journal NEJM2008;358:125-39. NEJM2012;367:124-34. NEJM2012;367:1901-11. Crit Care2012;16:R94. 45 A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit (SAFE study) : There were 726 deaths in the albumin group as compared with 729 deaths in the saline group at 28 days Outcome Albumin Saline RR (95%CI) P value Status at 28 days - no./total (%) Dead 726/3473 (20.9) 729/3460 (21.1) 0.99 (0.91-1.09) 0.87 SAFE study. N Engl J Med 2004;350:2247-56. Alive in ICU 111/3473 (3.2) 87/3460 (2.5) 1.27 (0.96-1.68) 0.09 Alive in hosital 793/3473 (22.8) 848/3460 (24.5) 0.93 (0.86-1.01) 0.10 46 A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit (SAFE study) : There were 726 deaths in the albumin group as compared with 729 deaths in the saline group at 28 days SAFE study. N Engl J Med 2004;350:2247-56. 47 Albumin Replacement in Patients with Severe Sepsis or Septic Shock (ALBIOS study) -1818 pts with SS admitted to 100 ICU in Italy -20% Albumin and crystalloid vs crystalloid alone (keep Alb>3g/dL until D/C) -Primary outcome: Death from any cause at 28 days In albumin group • Greater proportion reached the targeted MAP within 6 hours • During the first 7 days, higher MAP, whereas lower HR and net fluid balance 1121 patients with septic shock showed significantly lower mortality at 90 days in the albumin group than in the crystalloid group. ALBIOS study. N Engl J Med 2014;370:1412-21. 48
  9. 9. Saline or Albumin for Fluid Resuscitation in Patients with Traumatic Brain Injury (SAFE TBI) -460 pts with traumatic brain injury (Hx of HI, CT +ve, GCS ≤ 13) -4% Albumin and crystalloid vs crystalloid alone (keep Alb>3g/dL until D/C) -Outcome: Death from any cause at 28 days and 2 years SAFE TBI study. N Engl J Med 2007;357:874-84. 49 Fluid summary Table 1 Benefits Risks Saline Less expensive Hypercholemic metabolic acidosis Albumin Colloids of choice Expensive Increase mortality in TBI Gelatins Less expensive Hypersensitivity Hydroxyethyl strach Less expensive Acute kidney injury Coagulopathy Balance salt solution ?? ??? 50 Fluid therapy of Severe Sepsis 1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B). 2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (grade 1B) 3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients required substantial amounts of crystalloids (grade 2C) 4. Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients (grade1C) Hemodynamic support and adjunctive therapy,Surviving Sepsis Campaign 2012 51 Amount of fluid comparison from 3 studies Total fluid EGDT ProCESS ARISE Pre hosp n/a 2,254±1,472 vs 2,083±1,405 2,515±1,244 vs 2,591±1,331 0-6 hr 4,981±2,984 vs 3,349±2,438 2,805±1,957 vs 2,279±1,881 1,964±1,415 vs 1,713±1,401 6-72 hr 8,625±5,162 vs 10,602±6,216 4,458±3,878 vs 4,354±3,882 4,274±3,071 vs 4,382±3,136 0 - 72 hr 13,443±6,390 vs 13,358±7,729 7,253±4,605 vs 6,633±4,560 n/a vs n/a 52 Maintenance fluid 53 Comparison of Two Fluid Management Strategies in Acute Lung Injury (ARDS Clinical Trails Network) Data from 1000 patients with ALI with seven days fluid protocol Fluid accumulation in 7 days 6992±502 ml vs -136±491ml (P<0.001) CONCLUSIONS No significant difference in 60-day mortality. However CONSERVATIVE strategy of fluid improved lung function and shortened duration of mechanical ventilation and ICU without increasing non-pulmonary organ failure. ARDS Clinical Trial Network. New Engl J Med 2006;354:2564-75. 54
  10. 10. Fluid management in ALI Acute inflammatory insult Ebb phase Organ dysfunction Established Acute lung injury Coexisting condition Recovery Flow phase Identify and treatment Conservative fluid Mx Impaired fluid mobilization Rivers EP. N Engl J Med 2006;354:2598-600. Goal in resuscitation in first 6 hr Diuretic Ultrafiltration Hemofiltration Measure Fluid responsiveness Cerda J et al. Blood Purif 2010:29:331-8. 55 ยังต้องทำ EGDT ตาม protocol ของ Rivers ใน SS/SSh หรือไม่ ? 56 Lactate clearance vs central venous oxygen saturation as Goals of Early Sepsis Therapy ScvO2 > 70% vs lactate clearance at least 10% within 6 hr JAMA 2010;303:739-46. % Death 30 20 10 0 17 23 ScvO2 Lactate Observed difference between mortality rates did not reach the predefined -10% threshold 57 -Surviving Sepsis Campaign 2012- “Initial protocolized, quantitative fluid resuscitation during the first 6 hours” “Conservative fluid management and keep adequate tissue perfusion” 58 Key concepts in shock resuscitation • Early recognition of sepsis syndrome • Control source of infection • Appropriate antibiotic and timing of antimicrobial administration • Early resuscitation with intravenous fluids and vasoactive drugs 59 Effective antimicrobial initiation and survival association each hour of delay in initiation of effective antimicrobial was associated with mean decrease in survival of 7.6% 60
  11. 11. Sepsis supportive therapy Fluid restriction Nutritional support DVT prophylaxis Mechanical ventilation support Stress ulcer prophylaxis Sedation, analgesia, NMBA Renal replacement therapy Source of Infectious control De-escalate antibiotic Glucose control Restricted blood transfusion 61 Conclusion • Continuous ScvO2 monitoring • +/- Central venous pressure • Target in mean arterial pressure over 65 mmHg, and keep higher in chronic hypertension • Hb less than 7 g/dL is the trigger threshold • Noradrenaline is the vasopressor of choice • Crystalloid is the fluid of choice • Early effective antibiotic (within 1 hour) 62 SI = HR/SBP *Time Sensitive target Time allowed7 Corrective action Fluid bolus (500-1000 ml) 20 minutes 3rd IV or central line Initial fluid bolus (2L) 1 hour 3rd IV or central line SBP ≥ 100 mmHg 1 hour Vasopressors -Fluid overload by clinical Dx: JVD, rales, drop in SpO2 -Definition of hypoperfusion: MAP < 65 despite SBP > 100, arterial lactate 4, mottled skin, oliguria and altered sensorium 63

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