This document provides an overview and outline of topics related to septic shock management. It discusses key points including administering antibiotics within 1 hour, maintaining adequate preload with fluid resuscitation, and using appropriate vasopressors. The outline covers definitions, pathophysiology, early goal directed therapy involving fluid resuscitation, vasopressors, and achieving specific ScvO2 targets. Assessment of volume status and choices for fluid resuscitation are also reviewed.

1. Topic Review
Septic Shock Management
Piti Niyomsirivanich, MD.
10 Jan 2013

2. Take home message
• Adequate preload
• Appropriate Antibiotic within 1 hr
• Proper dose of vasopressors
• Consult

3. Outline
• Definition
• Pathophysiology
• Early Goal Directed Therapy
• Fluid Resuscitation
• Vasopressors
• Steroids
• Antibiotics
• Glucose control
• Blood product administration
• Bicarbonate therapy
• Stress ulcer prophylaxis

4. Definition
• Bacteremia : Bacteria in blood
• Septicemia : Bacteria + toxin in blood
• SIRS : 2/4 of following conditions
– 1)Temp > 38 C or < 36 C
– 2) Pulse rate > 90 /min
– 3) RR > 20 /min or PaCO2 < 32 mmHg
– 4) WBC > 12,000/ul or < 4000 /ul and/or Band form > 10%
• Sepsis = SIRS from infection
• Severe sepsis = Sepsis+ end organ damage
– CVS , Renal , pulmonary , Hematologic ,Metabolic acidosis
• Septic Shock = Sepsis + hypotension

5. Pathophysiology

6. Guideline
Surviving Sepsis Campaign: International guidelines for
management of severe sepsis and septic shock:2008

7. Since 2001 10+ years ago!!!

9. Result of EGDT
N Engl J Med 2001; 345:1368-
1377 November 8, 2001

10. Early goal directed therapy
SIRS
+
SBP < 90 mmHg or MAP < 65 mmHg ONE
-Or-
Lactate > 4 mmol/L Hour
After 20-30 ml/kg crystalloid IVF
Culture
Supplement oxygen Antibiotic within 1 hour Critical care consultation
or ET tube (if necessary) Volume accessment
< 8-12 mmHg
CVP ? IVF
8-12 mmHg
< 65 mmHg Five
MAP ? Vasopressor (NE/dopamine) Hours
>/= 65 mmHg
< 70% Blood transfusion to Hct > 30%
ScvO2 ?
> 70% Inotropic agent
Goals achieved
Sedatives & muscle relaxants
Resuscitation complete N Engl J Med 2001; 345:1368-1377November 8, 2001

12. Fluid Resusitation
• Fluid therapy
– crystalloids or colloids (1B)
– Target a CVP of 8-12 mmHg (1C)
– Give fluid challenges of 1000 mL of crystalloids
• or 300–500 mL of colloids over 30 mins.
Surviving Sepsis Campaign: International guidelines for
management of severe sepsis and septic shock:2008

13. Frank-Starling Law

14. Shock
• BP = CO X TVR
• CO = HR X SV
• SV = EDV – ESV
• BP = ( EDV- ESV ) X HR X TVR X EDV
EDV
• BP = EF X HR X TVR X EDV

15. Volume
N Engl J Med 2001; 345:1368-
1377November 8, 2001

17. Fluid
• Crystalloids
– NSS
– Ringer Lactate Solution
• Colloids
– albumin
– Dextrans
– Gelatins e.g. Haemaccel
– Hydroxyethylstarch e.g. Voluven

18. Fluid
• Crystalloids
– NSS
Low cost
– Ringer Lactate Solution
edema
• Colloids Hemodilution
Hyperchloremic metabolic acidosis
– albumin
– Dextrans
– Gelatins e.g. Haemaccel
– Hydroxyethylstarch e.g. Voluven

19. Fluid
• Crystalloids
– NSS Low cost
– Ringer Lactate Solution Lactate  liver
Acetate  peripheral tissue
• Colloids Potassium
– albumin edema
– Dextrans
– Gelatins e.g. Haemaccel
– Hydroxyethylstarch e.g. Voluven

20. Fluid
• Crystalloids
– NSS
SAFE Study *
– Ringer Lactate Solution not differrent VS NSS
• Colloids
hypocalcemia
– albumin expensive
– Dextrans
– Gelatins e.g. Haemaccel
– Hydroxyethylstarch e.g. Voluven
*A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit
N ENGL J MED 2004; 350:2247-2256 May 27, 2004

21. Fluid
• Crystalloids
Coagulopathy (inh. F VIII/ vWF)
– NSS
Renal damage
– Ringer Lactate Solution
Cross matching problem
• Colloids
Osmotic diuresis
– albumin
Anaphylaxis 0.27%
– Dextrans
– Gelatins e.g. Haemaccel
– Hydroxyethylstarch e.g. Voluven

22. Fluid
• Crystalloids Gelofundol
Haemaccel
– NSS
– Ringer Lactate Solution 30,000-35,000 kDa
• Colloids Renal Excretion
– albumin Short half life
– Dextrans Anaphylaxis 0.34%
– Gelatins e.g. Haemaccel
– Hydroxyethylstarch e.g. Voluven

23. Fluid
• Crystalloids • MW 450-480 kDa
Hetastarch Hespan
– NSS
•MW 200 kDa
– Ringer Lactate Solution •HAES-Steril 6%,10%
• Colloids •MW 70 kDa
•HES 70/0.5
– albumin
•Voluven
– Dextrans Anaphylaxis 0.058%
– Gelatins e.g. Haemaccel
– Hydroxyethylstarch e.g. Voluven

24. Cochrane Database Syst. Rev. CD 001319,2003

25. Volume Assessment
• Static VS dynamic
• Non-invasive
– U/S IVC
– Passive leg raising test
– Pulse oximetry plethysmographic waveform amplitude variation
• Invasive
– CVP
– Fluid challenge test
– CVP variation
– Pulse pressure variation

26. Volume Assessment
• Require Endotracheal tube
• No Endotracheal tube
• W/WO Endotracheal tube

27. CVP measurement
a= Atrial contraction
c= Ventricular Contraction
x= Atrial relaXation
v= Venous filling
y = Tr”Y”cuspids opening

28. CVP
• CVP : poor predictor of fluid volume
CHEST. July 2008;134(1):172-178.

29. Fluid Challenge Test for CVP
Load IV fluid 200-250 ml in 10 min
CVP + CVP + CVP +
</=2 2-5 >/=5
Continue fluid therapy Wait
Decrease rate of fluid therapy

30. Ultrasound IVC
Caval Index = 100 x (diam expiration - diam inspiration)/diam expiration
Caval Index > 50%  suggest low CVP
Ann Emerg Med 2010; 55:290-295.

31. Passive leg raising test
Esophageal doppler : in cardiac output > 8% predict fluid responsiveness
Critical Care 2006, 10:170

32. Pulse oximetry plethysmographic waveform amplitude variation

33. CASE A CASE B
CVP =15 cmH2O CVP =5 cmH2O

34. Pulse oximetry plethysmographic waveform amplitude variation
%POP variation POP max – POP min X 100
> 13%
POP mean

35. Arterial Line

36. Pulse Pressure Variation

37. Vasopressor therapy
• Dopamine VS Norepinephrine
Kaplan–Meier Curves for
28-Day Survival in the
Intention-to-Treat
Population.
N Engl J Med 2010; 362:779-789

38. Vasopressure therapy
Dopamine
Low dose
Moderate dose (beta adrenergic receptor )
5-10 ug/kg/min
High dose (alpha adrenergic receptor)
>10 ug/kg/min
Maximum dose 50 ug/kg/min
Norepinephrine
start 0.5 mcg/min
Harrison Int. Med edition 18 th

39. Vasopressor therapy
Example
ผู้หญิง 64 ปี หนัก 70 kg มาด้วย ไข้ หนาวสั่น ปัสสาวะแสบขัด
CBC : WBC 25000/ul N% 85 Band 2% Hb 12 g/dl Plt 200,000/ul
UA WBC 50-100
BP 80/40 mmHg PR 95/min Temp 37.8 C RR 18/min
จงคำานวณ dose ของ Dopamine ให้ start 5 ug/kg/min

40. Vasopressor therapy
Example
ผู้หญิง 64 ปี หนัก 70 kg มาด้วย ไข้ หนาวสัน ปัสสาวะแสบขัด
่
CBC : WBC 25000/ul N% 85 Band 2% Hb 12 g/dl Plt 200,000/ul
UA WBC 50-100
BP 80/40 mmHg PR 65/min Temp 37.8 C RR 18/min
จงคำานวณ dose ของ Dopamine ให้ start 5 ug/kg/min
60 X W (kg) X D (ug/kg/min)
Rate (ml/min)
C
Solute
C= 1,000
Volume

41. Vasopressor therapy
Example
ผู้หญิง 64 ปี หนัก 70 kg มาด้วย ไข้ หนาวสัน ปัสสาวะแสบขัด
่
CBC : WBC 25000/ul N% 85 Band 2% Hb 12 g/dl Plt 200,000/ul
UA WBC 50-100
BP 80/40 mmHg PR 65/min Temp 37.8 C RR 18/min
จงคำานวณ dose ของ Dopamine ให้ start 5 ug/kg/min
60 X 70 X 5
Rate (ml/min) = 10.5 ml/hr
2000
1000
C= 1,000 = 2000
500
(Dopamine 1000 mg ผสม 5%D/W 500 ml)

42. Early goal directed therapy
SIRS
+
SBP < 90 mmHg or MAP < 65 mmHg ONE
-Or-
Lactate > 4 mmol/L Hour
After 20-30 ml/kg crystalloid IVF
Culture
Supplement oxygen Antibiotic within 1 hour Critical care consultation
or ET tube (if necessary) Volume accessment
< 8-12 mmHg
CVP ? IVF
8-12 mmHg
< 65 mmHg Five
MAP Vasopressor (NE/dopamine) Hours
>/= 65 mmHg
< 70% Blood transfusion to Hct > 30%
ScvO2
> 70% Inotropic agent
Goals achieved
Sedatives & muscle relaxants
Resuscitation complete N Engl J Med 2001; 345:1368-1377November 8, 2001

43. ScvO2
ให้เงินไป
โรงเรียน
ขากลับ
เหลือ 50
บาท
แปลว่าให้เงินไปโรงเรียนพอใช้

44. ScvO2
O2 content
O2 content
เหลือ 70%
แปลว่าให้ออกซิเจนไปเนือเยือพอใช้
้ ่

45. ScvO2

46. O2 delivery
• DO2 = [1.39 x Hb x SaO2 + (0.003 x PaO2)] x CO
• Depend on < 70%
Blood transfusion to Hct > 30
ScvO2
– Hemoglobin > 70% Inotropic agent
– O2 saturation Goals achieved
– Cardiac output
– ScvO2 < 70%
• target Hct > 30
• Inotropic drug  increase cardiac output
Contin Educ Anaesth Crit Care Pain (2004) 4 (4) 123-126

47. Alternative for ScvO2
• Lactate clearance
– lactate clearance >10% or higher
• 6% lower in-hospital mortality than those resuscitated
to an ScvO2 of at least 70%
– (95% CI, −3% to 15%)
– noninferiority trial.
JAMA. 2010 Feb 24;303(8):739-46.

48. Antimicrobial Therapy
• administration of broad-spectrum antibiotic therapy within 1
hr of diagnosis of septic shock (1B) and severe sepsis without
septic shock (1D);
• reassessment of antibiotic therapy with microbiology and
clinical data to narrow coverage, when appropriate (1C);
• a usual 7–10 days of antibiotic therapy guided by clinical
response (1D);
• source control with attention to the balance of risks and
benefits of the chosen method (1C);
Survival Sepsis Guideline .Crit Care Med 2008

49. Empirical Antibiotic
• Host
– Immunocompetent
– Neutropenia
– IVDU
– Post Splenectomy
– AIDS
• Risk factors & exposures
• Site of infection
• Antibiotics of choice ??
Antibiotic therapy in patients with septic shock
European Journal of Anaesthesiology (EJA). 28(5):318-324, May 2011

50. Tips
• every 10 min, survival is decreased by 1%.*
• First dose  Full dose
– Then renal adjustment
* Antibiotic therapy in patients with septic shock
European Journal of Anaesthesiology (EJA). 28(5):318-324, May 2011

51. De-escalate Therapy
• De-escalate  Empirical antimicrobial therapy
in life-threatening situations
– Start with Broad Spectrum
• ‘Broad-spectrum antibiotics’ refers to antibiotics with
activity against Pseudomonas aeruginosa, including
imipenem-cilastatin, piperacillin-tazobactam,
ceftazidime or ciprofloxacin.
• Limited-spectrum antibiotics will only refer to β-lactam
antibiotics without activity against P. aeruginosa
(essentially, ceftriaxone and amoxicillin-clavulanate).
Antibiotic therapy in patients with septic shock
European Journal of Anaesthesiology (EJA). 28(5):318-324, May 2011

52. De-escalate Therapy : Life Threatening
• "สันๆ แต่ aggressive" แล้วปรับลงมา
้
– Recurrent infections were more common in Group No
De-escalate (19% versus 5%, P = 0.01)
– An inadequate empiric antibiotic therapy was more
frequent in Group No De-escalate (27.5% versus 7.7% P =
0.02)
– Mortality between the two groups 18.3% (D) vs 24.6%
(ND)
Critical Care 2010, 14:R225

53. Antibiotic therapy in patients with septic shock
European Journal of Anaesthesiology (EJA). 28(5):318-324, May 2011

55. Steroids in CIRCI
(critical illness related corticosteroid insufficiency)
•stress-dose steroid therapy given only
in septic shock after blood pressure is
identified to be poorly responsive to
fluid and vasopressor therapy (2C)
•Survival Sepsis Guideline 2008
Serum cortisol
•< 15 ug/dl  definite adrenal insufficiency
•13-35 ug/dl  Suspected
•>35 ug/dl  no benefit
•สมาคมเวชบำาบัดวิกฤติแห่งประเทศไทย

56. Steroids in CIRCI
Surge in cortisol (> 9 ug/dl) response to ACTH
250 ug stimulation
Benefit from steroids
JAMA. 2002 Aug 21;288(7):862-71

57. CIRCI
Baseline cortisol level < or = 35 microg/dl is a useful diagnostic threshold for
diagnosis of steroid responsiveness in Thai patients with septic shock
ACTH stimulation test should not be used
sensitivity was 85%, the specificity was 62%
J Med Assoc Thai 2010 Jan;93 Suppl 1:S187-95

58. CIRCI
• Hydrocortisone 100 mg bolus then 200 mg V
drip in 24 hr
• OR
• Hydrocortisone bolus q 4-6 hr NOT q 8 hr
– e.g. Hydrocortisone 50 mg V q 6 hr
• Then taper off

59. Blood Sugar control

60. Blood Sugar control
• NICE-SUGAR study
– 3050 patients
– Medicine & Surgery Ward
– Multicenter randomized open label study
– ICU & non ICU
– Intensive control 81-108 mg%
– Conventional control 144-180 mg%
The NICE-SUGAR Study Investigators
N Engl J Med 2009; 360:1283-1297March 26, 2009

61. NICE-SUGAR Study
The NICE-SUGAR Study Investigators
N Engl J Med 2009; 360:1283-1297March 26, 2009

64. Sliding Scale Insulin

65. Basal Insulin with Scheduled Insulin (prandial insulin) with
Correctional dose

67. • CBG (ก่อนอาหาร) เช้า กลางวัน เย็น
ก่อนนอน

68. Somchai Pathanaangkul ,Royal Thai Army Medica
Vol 57 No.4 Oct.-Dec. 2004

69. Blood Transfusion
● Give red blood cells when hemoglobin decreases to 7.0 g/dL (70 g/L) to
target a hemoglobin of 7.0–9.0 g/dL in adults (1B). A higher hemoglobin lev
el may be required in special circumstances (e.g., myocardial ischaemia, se
vere hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosi
s)
● Do not use erythropoietin to treat sepsis-related anemia. Erythropoietin may
be used for other accepted reasons (1B) Do not use fresh frozen plasma to
correct laboratory clotting abnormalities unless there is bleeding or planned i
nvasive procedures (2D)
● Do not use antithrombin therapy (1B)
Administer platelets when (2D) Counts are 5000/mm3 (5 109/L) regardless
of bleeding
Counts are 5000–30,000/mm3 (5–30 109/L) and there is significant
bleeding risk
Higher platelet counts (50,000/mm3 [50 109/L]) are required for surgery or
invasive procedures

70. Blood Transfusion
• TRICC Study
– Study design: Multicenter RCT
– Setting: 25 ICUs across Canada
– Hb
• 7-9 g/dl (Restrictive Strategy)
• 10-12 g/dl (Liberal Strategy)
– Primary Outcome : mortality rate 30 days
– Results
• Hb 7-9 g/dl group mortality rate 22.2%
• Hb 10-12 g/dl mortality rate 28.1%
• (P=0.05)

71. TRICC Study
Hb 7-9 g/dl
Hb 10-12 g/dl

72. Bicarbonate Therapy
• We recommend against the use of sodium
bicarbonate therapy for the purpost of
improving hemodynamics or reducing
vasopressure requirement with
hypoperfusion-induced lactic acidemia with
pH > 7.15 (1B)
Surviving Sepsis Campaign: International guidelines for
management of severe sepsis and septic shock:2008

73. Hb O2 Dissociation curve

74. Stress Ulcer Prophylaxis
• We recommend that stress ulcer prophylaxis
using H2 blocker (1A)
• Or PPI (1B) be given to patients with severe
sepsis to prevent upper GI bleed.
• Weighted aginst the potential effect of an
increased stomach pH on development of VAP
Surviving Sepsis Campaign: International guidelines for
management of severe sepsis and septic shock:2008

75. Other
• Sucralfate*
– Not associated with an increase in stress
ulceration.
– Less impact gastric colonization  Less VAP
– Increase aspiration
• Enteral Feeding
*EAST Practice Management Guidelines Committee

76. Take home message
• Adequate preload
• Antibiotic within 1 hr
• Proper dose of vasopressors.
• Consult

77. Thank you