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

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.
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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
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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)
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2. Protocolized resuscitation
What is new ?
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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
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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
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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
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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
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A Randomized Trial of Protocol-Based Care
for Early Septic Shock (ProCESS study)
ProCESS Study. N Engl J Med 2014;370:1683-93.
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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.
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Goal-Directed Resuscitation for Patients
with Early Septic Shock (ARISE trial)
ARISE trial. N Engl J Med 2014;371:1496-506.
18

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
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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
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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
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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
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Lower versus Higher Hemoglobin Threshold
for Transfusion in Septic Shock (TRISS study)
TRISS study. N Engl J Med 2014; 371:1381-91.
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Which vasopressors? Which inotropes?
24

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. 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. 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. 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. 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. 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. 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
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