This document discusses updates in sepsis management and provides several case examples of patients presenting with sepsis. It reviews the new Sepsis-3 definitions which redefine sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. It discusses tools like QSOFA and SOFA for identifying sepsis and organ dysfunction. It also reviews the Surviving Sepsis Campaign guidelines for initial resuscitation of sepsis patients including fluid resuscitation of at least 30mL/kg within 1 hour, early antibiotics, and vasopressors for hypotension.

1. Updates in sepsis management
Kamal Osman Mergani
MD,FSCCM,FRCP
Internal Medicine & Critical Care Consultant
Clinical Director of ICU department
Omdurman military Hospital
kamalmergani@gmail.com

4. Sepsis is it serious!
Real cases

5. Quartz
MazenK
9
2
3
1
4
6
5
11
12
7
8
10
•E|R 16:15
•Female of 23 years
presented with high grade
fever +acute
confusion,postdelivery at
home 4days
•18.00 Refered to
psychiatric
department for
assessment and
mangement
• 20.40 Refered back to
medical emergancy for
reassessment and
management
21.15 O/E there is a burn on
back( caused by Bakhour of
Faki) Refered for plastic
surgery review
Event Clock
22.15 Seen by chance by
anesthesia &critical care
consultant,BP8040 HR120
septic shock( infected
episiotomy
1 L NS 23:05
23.15 Ceftriaxone1gm iv:
2.10 1 litre of N/S
added 02:05
4.30 1lit
NS: 04:30
5.00 Meropenam
1gm : 5:00 Dc
ceftriaxone
ICU: 6:30
Death

7. Quartz
MazenK
9
2
3
1
4
6
5
11
12
7
8
10
•E|R 16:15
•Diabetic pt with abscess
in neck B/P 80/40
•RR 26min ,febrile RBG
500,ABG M.acidosis
•1 L NS
•B/P 118/70
•Ceftriaxone 1gm for
driage when out of
DKA
•F/U 24 hrs
•ER: 20:40
•B/P 92/54
•RR: 41/m
•O2 sat 80% on 8L/m
Lasix: 21:15
Event Clock
Metronidazole added:
22:15
1 L NS added: 23:05
NA HCO3 iv: 23:15
Lasix 20 mg: 02:05
1lit NS:
04:30
Meropenam 1gm :
5:00 Dc ceftriaxone
ICU: 6:30
Death

9. Quartz
MazenK
9
2
3
1
4
6
5
11
12
7
8
10
•E|R 16:15
•Diabetic pt with abscess
in neck B/P 80/40
•RR 26min ,febrile RBG
500,ABG M.acidosis
•1 L NS
•B/P 118/70
•Ceftriaxone 1gm for
driage when out of
DKA
•F/U 24 hrs
•ER: 20:40
•B/P 92/54
•RR: 41/m
•O2 sat 80% on 8L/m
Lasix: 21:15
Event Clock
Metronidazole added:
22:15
1 L NS added: 23:05
NA HCO3 iv: 23:15
Lasix 20 mg: 02:05
1lit NS:
04:30
Meropenam 1gm :
5:00 Dc ceftriaxone
ICU: 6:30
Death

11. case
A50 years male EDRD on regular dialysis
twice per week for 2years with permecath
Presented to the ER with high grade fever
with shivering
RR 30 BP110/70 HR 120
Chest clear
Sc 12 urea 198 ABG PH 7.12 Pco2 30
Po2 98 Hco3 10

12. What is the best immediate
management

13. Severe Sepsis: Comparison
With
Other Major Diseases
†National Center for Health Statistics, 2001. §American Cancer Society, 2001. *American Heart Association.
2000. ‡Angus DC et al. Crit Care Med. 2001 .
0
50
100
150
200
250
300
AIDS* Colon Breast
Cancer§
CHF† Severe
Sepsis‡
Cases/100,000
Incidence of Severe Sepsis
1995
Mortality of Severe Sepsis
0
50,000
100,000
150,000
200,000
250,000
Deaths/Year
AIDS* Severe
Sepsis‡
AMI†
Breast
Cancer§

14. National age-specific number and
incidence of severe sepsis
0
10,000
20,000
30,000
40,000
50,000
60,000
70,000
80,000
90,000
100,000
Age (year)
Number
of
cases
0
5
10
15
20
25
30
Incidence
per
1000
Cases
Incidence
<1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 >85
Angus DC. Crit Care Med. 2001 .

15. Severe Sepsis:
A Significant Healthcare
Challenge
†Angus DC et al. Crit Care Med. 2001 .
‡Sands KE et al. JAMA. 1997;278:234-40.
§Zeni F et al. Crit Care Med. 1997;1095-100.
28%†
34%‡
50%§
0
20
40
60
Mortality
(%)
Angus Sands Zeni

19. The Sepsis Continuum
• A clinical response arising
from a nonspecific insult,
with 2 of the following:
 HR >90 beats/min
 RR >20/min
 WBC >12,000/mm3 or
<4,000/mm3 or >10%
bands
 T >38oC or <36oC
SIRS = systemic inflammatory
response syndrome
SIRS with a
presumed
or confirmed
infectious
process
Chest
Sepsis
SIRS
Severe
Sepsis
Septic
Shock
Sepsis with
organ failure
Refractory
Hypoperfusion
(hypotension)

20. Sepsis: What Happened in 2016?
JAMA, Feb. 23, 2016: Sepsis-3, New
criteria for defining sepsis
Sepsis is redefined as : “life-threatening
organ dysfunction caused by a
dysregulated host response to infection.”

21. Sepsis-3 Definitions
• Sepsis: Life-threatening organ dysfunction
caused by dysregulated host response to
infection
• Septic Shock: Subset of sepsis with
circulatory and cellular/metabolic
dysfunction associated with higher risk of
mortality
JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287

22. Sepsis-3 Definitions
• For clinical operationalization,organ
dysfunction can be represented by an
increase in the Sequential Sepsis-related
Organ Failure Assessment(SOFA) score of
2points or more, which is associated
with an in-hospital mortality greater
than10%.

23. Sequential[Sepsis-related]Organ Failure
Assessment(SOFA) score

24. QSOFA For ER and ward patients

25. Septic shock
Defined as a subset of sepsis in
which particularly profound
circulatory,cellular,and metabolic
abnormalities are associated with a
greater risk of mortality than with
sepsis alone.

26. Septic shock
• Patients with septic shock can be clinically
identified by a vasopressor requirement to
maintain a mean arterial pressure of
65mmHg or greater and serum lactate level
greater than 2mmol/L(>18mg/dL)in the
absence of hypovolemia.
• This combination is associated with hospital
mortality rates greater than 40%.

27. How Good is SOFA?

28. How Good is Q SOFA?

29. How Good is Q SOFA?

30. Its Good because Q SOFA has a highly
specificity for detecting clinical deterioration in
infected patients
How Good is Q SOFA?

31. SOFA is For ICU Patients

32. IDENTIFYING ACUTE ORGAN DYSFUNCTION
AS A MARKER OF SEPSIS and Septic shock
Tachycardia
Systolic BP 90, or
MAP 70 despite
fluids
Vasopressors
Urine Output <0.5
mL/kg/hr despite fluids
Creatinine >50% from
baseline
Acute dialysis
 Platelets <100,000/mm3
 PT/aPTT
 D-dimer
Liver Enzymes
>2x ULN
Altered
Consciousness
Reduced GCS
Tachypnea
PaO2/FiO2 250
Mechanical
Ventilation
PEEP >7.5
Balk RA. Crit Care Clin. 2000;16:179-192.
Low pH with high
lactate (eg, pH, 7.3 &
lactate>ULN)

33. QSOFA For ER and ward patients

34. Quick SOFA (qSOFA)
1)Respiratory rate of 22/minor
greater
2) Altered mentation
3)Systolic blood pressure of
100mmHg or less

35. Q SOFA
• How to use QSOFA in real practice
• Was it easy to apply
• Dose it need any requirements
• Any evidence

37. NOTE
RRT is needed in early
identification of sepsis

38. SEPSIS PATHOPHYSIOLOGY
Microvascular
dysfunction
 Inflammation
 Coagulation
 Fibrinolysis
Hypoperfusion/hypoxia
Microvascular thrombosis
Endothelial dysfunction
Organ dysfunction
Global tissue hypoxia
Direct tissue damage
 

39. Homeostasis Is Unbalanced in
Sepsis
Carvalho AC, Freeman NJ. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock. 1996;5:223-8;
Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44.

41. Failure of compensatory mechanism
• Decreased blood flow to the tissues causes
cellular hypoxia
• Anaerobic metabolism begins
• Cell swelling, mitochondrial disruption, and
eventual cell death
• If Low Perfusion States persists:
IRREVERSIBLE DEATH IMMINENT!!

42. SEPTIC SHOCH-ASSOCIATED
MORTALITY INCREASES WITH THE
NUMBER OF ORGAN DYSFUNCTIONS
Angus DC, et al. Crit Care Med. 2001;29:1303-1310.
Vincent JL, et al. Crit Care Med. 1998;21:1793-1800.
%
Mortality
Organ
Dysfunctions
21% 22%
44%
38%
65%
69%
69%
83%

45. STANDARD of Care for Sepsis
• Resuscitation
• Control the focus of infection
• Early appropriate Antibiotics
• Corticosteroids
• Glycaemic control using insulin
• Mechanical ventilation
• Renal replacement therapy

46. SSC update 2018
• The most important change in the
revision of the SSC 2018 bundles is that
the 3-h and 6-h bundles have been
combined into a single “hour-1 bundle”

47. Hour-1 bundle
• Fluid
• Antiboitics
• Intropes
• Lactate and cultures

48. SCC 2018
• More than 1 h may be required for resuscitation
to be completed, but initiation of resuscitation
and treatment, such as obtaining blood for
measuring lactate and blood cultures,
administration of fluids and antibiotics, and in
the case of life-threatening hypotension,
initiation of vasopressor therapy, are all begun
immediately

49. Surviving Sepsis Campaign: International Guidelines
for Management of Sepsis and Septic Shock: 2018
• We recommend that, in the resuscitation
from sepsis-induced hypoperfusion, at least
30 mL/kg of IV crystalloid fluid be given
within the first hour (strong
recommendation, low quality of evidence).

50. Resuscitation

51. Volume resuscitation
• Optimizing volume
–Early resuscitation
– which fluid is the best???
–How much ???
–WITHIN ??? TIME???

52. What fluid and How much,
within ??time ??

53. Saline versus Albumin Fluid
versus

54. Albumin administration in
critically ill patients: SAFE study
• Prospective, controlled, randomized study
• Total 7000 Patients
– Albumin N= 3497
– Saline N= 3500
• Mortality:
– Albumin 20.9%
– Saline 21%

56. Ringers Lactate

57. Ringers Lactate
• In many institutions around the globe
Ringers Lactate is used in sepsis patients,
whether it is superior to saline is unclear,
however, there is data that suggest, that
there are more adverse effects with
physiologic saline.

58. 18/August/2015

59. HETASTARCH
• HETASTARCH with Mw more than
200 dalton is not recommended for
fluids Resuscitation in sepsis
• Associated with AKI

60. Fluid resuscitation 2016
• We recommend that, in the
resuscitation from sepsis-induced
hypoperfusion, at least 30 mL/kg of
IV crystalloid fluid be given within
the first 3 h
• (strong recommendation, low quality of evidence).

61. Adequate Faster fluids

62. Central venous catheter vs peripheral lines
Which is better in fluid Resuscitation???

63. PLEASE NOTE
• Multiple wide bore cannulae(14 or16
gauge) is more effective than a
central line in fluid resuscitation in
case of shock.

64. GIVE fluids to achieve the targets

65. Targets in resuscitation
• Map  65 mmHg (SBP  90 mmHg)
• Urine output  0.5 ml/kg /hr
• SVO2  70%
• CVP 8-12 mmHg
• LACTATE ≤ 2.0

66. O2
SvO2 O2 Content
O2 Consumption
ScvO2
O2 Return O2 Delivery
Capillary Beds
Venous Arterial
Cardiac
Output
 Central venous oxygen saturation (ScvO2)
 Mixed venous oxygen saturation (SvO2)


67. Don’t set it and Forget it!
Data Source: A Users Guide to the 2016 Surviving Sepsis Guidelines. Society of Critical care Medicine. March 2017 Volume 45 Number 3.

69. Note
• FIRST 24 HRS KEEP YOUR
PATIENT WET
• KEEEP YOUR PATIENT DRY
AFTERWARD

70. What Is the Best best vasopressors/inotropes
for Septic Shock?
The New England Journal of
Medicine
2012

74. REMMBER

75. • Do not use low-dose dopamine for renal
protection in the treatment of severe sepsis
or septic shock (1A)
NO RENAL DOSE DOPAMINE

76. Inotropes in septic shock
(After adequate FLUIDS)
• Noradrenaline
• Adrenaline
• Vosopressin
• Dpoamine( selected cases)
• Dobutamine added when there is low
cardiac output (insure adequate BP)

77. Timing of Vasopressor Initiation and
Mortality in Septic Shock
Vance Beck, Dan Chateau, Gregory L Bryson, Amarnath Pisipati, Sergio
Zanotti, Joseph E Parrillo, Anand Kumar
Disclosures
Crit Care. 2014;18(R97)

78. Conclusion
• Markedly delayed initiation of vasopressor
medications in patients with septic shock is
modestly associated with increased organ failure
risk and decreased survival.
• Substantial delays of vasopressor initiation (>14
hours after hypotension documentation) is
associated with mortality more than 70%

80. EARLY Antibiotics
–Early within (1) HR
–Appropriate spectrum
–Duration

81. Appropriate antibiotics
reduce mortality by
10%-15%; mortality
remains 28%-50%
Sepsis Septic shock
Death
Antibiotics and Sepsis:
Outcome: Stopping Progression of Disease
Appropriate antibiotics
decrease evolution to
septic shock by ~50%
Infection
Inflammation/Coagulation Activation

82. Please Note
• use of an early appropriate antibiotic
regimen can reduce the evolution to
sepsis by approximately 50%.
• Appropriate antibiotic therapy is best
used to stop the evolution to severe
sepsis, not when severe sepsis has
already set in.

83. Antibiotics
• We recommend that administration of IV
antimicrobials be initiated as soon as possible
after recognition and within 1 h for both sepsis
and septic shock.
(strong recommendation, moderate quality of
evidence).
• We recommend empiric broad-spectrum therapy
with one or more antimicrobials to cover all likely
pathogens.
(strong recommendation, moderate quality of
evidence).

84. New Guideline:
Surviving Sepsis Campaign 2016
• 7-10 days of antimicrobial therapy for most serious
infections, but shorter duration for some (rapid
clinical resolution after intraabdominal source
control, urinary sepsis, uncomplicated
pyelonephritis)
• Suggest use of procalcitonin to support shortening
duration of antimicrobial therapy

85. Critical Influence of the Time to 1st Antibiotic
Dose on Mortality in Septic Shock
Patient survival with delayed
antibiotic administration in septic shock
5%
39%
48%
50%
58%
71%
33%
10%
0%
20%
40%
60%
80%
100%
0 5 10 15 20 25 30 35 40
Time to first appropriate antibiotic dose (hour)
Percent
Survival
Kumar et al. HSC and St. Boniface General Hospital. August 2003
N = 1004 patients
Every one-hour delay…
you drop survival by 7.5%

86. Appropriate antibiotics in septic shock
• ‘Hit hard Hit fast’ with a high dose
of broad-spectrum antibiotic
– Take pharmacodynamics into
account
–Adjust antibiotics according to
microbiological results

87. ‘Hit hard Hit fast’

88. Antibiotic selection
• When the potential pathogen or infection
source is not immediately obvious, broad-
spectrum antibiotic coverage directed against
both gram-positive and gram-negative
bacteria is indicated.

89. Which is the most beneficial
management in sepsis

90. In this study , the most
beneficial management was
• 3-hours bundle of care for patients with sepsis
– (i.e., blood cultures),
– broad-spectrum antibiotic agents,
– and lactate measurement

91. Among 49,331 patients at 149
hospitals, 40,696 (82.5%) had the 3-
hour bundle completed within 3 hours

92. Timing
THE Message
Time is life

93. Initial Resuscitation, Diagnosis, and
Antibiotic Therapy
Recommend early goal-directed therapy
Give early appropriate antibiotics
Give early appropriate fluids
Give appropriate inotropic support
Take early cultures
Take early lactate level
Take early central venous oxygen saturation(SVO2)

94. So In our situation
where is the best area
to put our maximum
effort in mangement
of sepsis????

95. SIRS
Sepsis Septic Shock
Golden hours
EARLY directed therapy in
sepsis & septic shock
ER
Ward
ICU

96. The Golden Hours
•The systemic inflammatory response syndrome
can be self-limited or can progress to sepsis
and septic shock.
•The transition to serious illness occurs during
the critical “golden hours,” when definitive
recognition and treatment provide maximal
benefit in terms of outcome.
•These golden hours elapse in the emergency
department, hospital ward, or the intensive care
unit

97. Control focus of infection
•EARLY Adequate surgery
•Drainage of infection focus

98. Source Control
•Drainage
-Intra-abdominal abscess, cholangitis
•Device Removal
-Infected vascular catheter
-Urinary catheter
. Dellinger, et. al. Crit Care Med
2004, 32: 858-873

99. Source Control
•Definitive Control
-Sigmoid resection for
diverticulitis
-Amputation for diabetic
gangrenous septic foot
-Cholecystectomy for gangrenous
cholecystitis

100. Combination therapy for sepsis

101. Source Control
• We recommend that a specific anatomic
diagnosis of infection requiring emergent
source control be identified or excluded as
rapidly as possible in patients with sepsis
or septic shock, and that any required
source control intervention be
implemented as soon as medically and
logistically practical after the diagnosis is
made.
(Best Practice Statement).

102. Source Control
• We recommend prompt removal of
intravascular access devices that are a
possible source of sepsis or septic
shock
and other vascular access has been
established (BPS).

103. Bad Example
• Let us book the abscess drainage at the end
of the list because it contaminate the
operative room
• Diabetic septic foot let the medical team
get the patient out of DKA because the
Anesthesia team can do his Job
• This Central line is the responsibility of the
Nephrology team call them to do their Job

107. Use of corticosteroids in sepsis
• when fluids and vasopressors has
failed to restore patients hemodynamic
• Hydrocortisone 200mg /day iv
infusion OR
• 50 mg every six hours for seven days

109. CONCLUSIONS
• Among patients with septic shock
undergoing mechanical ventilation, a
continuous infusion of hydrocortisone did
not result in lower 90-day mortality than
placebo. (Funded by the National Health
and Medical Research Council of Australia
and others; ADRENAL ClinicalTrials.gov
number, NCT01448109.)

110. •!!!????

111. Glycaemic control with intensive
insulin therapy in critically ill
patients

112. 9.6
12.2
15.1
18.8
28.4
29.4
37.5
32.9
42.5
0
5
10
15
20
25
30
35
40
45
%
Mortality
80-99 100-119 120-139 140-159 160-179 180-199 200-249 250-299 >300
Glucose (mg/dL)
Hospital Mortality Rate (%) & Mean Blood Glucose

114. Glycemic control in sepsis 2016
• 1. We recommend a protocolized approach to
blood glucose management in ICU patients with
sepsis,
commencing insulin dosing when two consecutive
blood glucose levels are >180 mg/dL. This
approach should target an upper blood glucose
level ≤180 mg/dL rather than an upper target
blood glucose level ≤110 mg/dL (strong
recommendation, high quality of evidence)

115. Glycemic control in sepsis 2016
• Target blood glucose ≥110mg and ≤180 mg
• Improved survival
• Decreased infections
• Decreased organ failure

116. Nutrition
• Early enteral nutrition
• TPN when indicated
• Metabolic needs
25 - 35 kcal/kg/day

117. Mechanical ventilation/ARDS
• Low tidal volume ventilation
• Use of PEEP
• Permissive hypercapnia
• Prone positioning
• Nitric oxide (NO)

118. Renal replacement therapy
• Improving survival
• Hemodialysis vs. hemofiltration

119. Cornerstone of therapy for patients with
sepsis
• Early recognition of sepsis
syndrome
• Early administration of fluids and
appropriate broad-spectrum
antibiotics
• Early surgery where needed

121. TAKE HOME MEASSAGE
• More fluids
• Faster fluids
• Faster antibiotics
• Early inotropes
• Be GOAL directed:
MAP
Urine output
Lactate level
CVP
Svo2

122. TAKE HOME MEASSAGE

124. Team work in needed to mange
SPSIS properly

125. Thanks for your
attention