Lecture องค์กรแพทย์ เรื่องติดเชื้อในกระแสเลือด Septic Shock

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