Sepsis

Sepsis
Dr Pritish Chandra Patra
Associate Professor
Department of Hematology
IMS and SUM Hospital, Bhubaneswar

Outline
2
Sepsis
Definition
Screening
Epidemiology
Pathophysiology
Management goals
Resuscitation
Serum lactate
Blood culture
Antimicrobials
Procalcitonin
Vasopressors
Other supportive measures

Definition (Sepsis 3)
• Sepsis-
– Life-threatening organ dysfunction caused by a dysregulated host
response to infection
• Septic shock-
– a subset of sepsis with circulatory, cellular and metabolic dysfunction
associated with a higher risk of mortality
– clinically
• vasopressor requirement to maintain a MAP ≥ 65 mmHg
• serum lactate level >2mmol/L (>18mg/dL)
• no hypovolemia
– 40% mortality
3
Singer M etal, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), JAMA. 2016;315(8):801-810

The Spectrum
5
•Martin GS, Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes, Expert Rev Anti Infect Ther. 2012 Jun; 10(6): 701–706
•Bone RC et al, American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the
use of innovative therapies in sepsis. Crit Care Med. 1992;20(6):864-874.
Bacteremia
SIRS
SEPSIS
Infection
Parasitemia
Fungemia
Viremia
Others
Pancreatitis
Burns
Trauma
Others
SOFA score

Screening for sepsis: SOFA score
6
qSOFA
RR ≥ 22/min
SBP ≤ 100 mmHg
GCS < 15
Vincent JL et al; Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. The SOFA (Sepsis-related Organ Failure Assessment) score to
describe organ dysfunction/failure. Intensive Care Med. 1996;22(7):707-710.

Approach to suspected sepsis
7
Singer M, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), JAMA. 2016;315(8):801-810

The Burden
• Accounted for more than $20 billion (5.2%) of total US
hospital costs in 2011
• leading cause of mortality and critical illness worldwide
• long-term...
– physical
– psychological
– cognitive disabilities
– care and social issues
8
Singer M, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), JAMA. 2016;315(8):801-810

Epidemiology of adult-population sepsis in India
9
Severe
sepsis was
common in
Indian
intensive
therapy
units (ITUs)
The
median
APACHE II
score was
13 (IQR, 13
to 14) with
90.93%
medical
admission
16.45% of
hospital
admissions
were due
to severe
sepsis
59.26% of
patients
with sepsis
died
Mortality of
severe
sepsis was
~65%
Sharmila C, et al. Indian J Crit Care Med. 2017;21(9): 573–7

Epidemiology:
India
10
Chatterjee S etal, Epidemiology of adult-population sepsis in India: A single center 5 year experience. Indian J Crit Care Med 2017;21:573-7

11
15.4
16.9
21.2
15.4
3.3
0.4
0.4
0.4
8.7
1.4
1
0.66.2
Micro organisms
Klebsiella Pseudomonas Acinetobacter E. coli Enterobacte
Brucella Salmoella Proteus MRSA Staph others
Strept. Viridans Strept. Pneumoniae Fungal
Gram Neg
73.4%
Gram pos
12.6%

12
Sri Ramachandra University Reasearch Institute, India
T T S Paary etal, Clinical profile and outcome of patients with severe sepsis treated in an intensive care unit in India, Ceylon Medical Journal 2016; 61: 181-184
Epidemiology:
India

Pathophysiology
Hypotension with normal/raised CO
Systemic vasodilatation
& peripheral pooling of
blood
DIC: microvascular thrombosis
Endothelial activation &
cellular injury leading to
hypercoagulable state
Reduced cellular function
Changes in tissue
metabolism
Tissue
Hypo-
perfusion &
MODS
Robbins & Cotran , Pathologic Basis of Disease , 8th Ed 14

Management
• Goals
– Initial resuscitation
– Diagnosis & infection control
– Continuation of fluid and other supportive therapy
to maintain organ perfusion
15

Initial resuscitation
• Medical emergency
• IV fluid- crystalloid- at least 30 ml/kg- 1st 3 hrs
• MAP ≥ 65 mm Hg
• 4% albumin- if fluid requirement is more
16
Casserly B et al, Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med (2015) 43(3):567–
573
ProCESS ProMISe ARISE
Mar 2015 May 2014 Oct 2014
30 ml/kg 2 lit

Reassessment
• Additional fluid
• Dynamic measures of fluid
responsiveness
17
- Stroke Volume
- Systolic BP
- Pulse Pressure
↑Intrathoracic
pressure
Fluid
challenges
Passive leg
raising

Serum Lactate
• Tissue hypoxia
• Excessive β-adrenergic stimulation
18
Regardless of source- Increased lactate→ poor outcome
• Lactate guided Vs lactate non-guided
– >2 mmol/L (>18 mg/dL)
– ↓mortality
– Objective marker of tissue perfusion
>> physical examination
>> urine output

19
Casserly B et al (2015) Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med 43(3):567–573

20
Casserly B et al (2015) Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med 43(3):567–573

21
Am J Respir Crit Care Med Vol 182. pp 752–761, 2010

Blood cultures
• Microbiologic cultures (including blood)-
– before starting antimicrobial therapy
– shouldn’t delay starting of antimicrobials
23
Kaasch AJ et al, Differential time to positivity is not predictive for central line related Staph. aureus blood stream infection in routine clinical care. J Infect (2014), 68(1):58–61
Timing
Within 45 mins
Numbers
aerobic anaerobic
Sites
blood, CSF, urine, wound,
respiratory secretion, abscess… Pan culture
• Cultures can become sterile shortly after Abx initiation
• CVAD for >48hrs- site of infection not proven- paired
samples for c/s
2 sets of
blood cultures
aerobic
anaerobic

Antimicrobials
• Start ≤ 1 hr
– Each hour delay- measurable increase in
mortality
• Choice of Abx-
– Anatomic site
– Prevalent organisms
– Local resistance patterns- if any
– Age and co-morbidities
• Empiric therapy- Broad Spectrum
• Adequate doses
• Adjusted for organ impairment
• Daily assessment- de-escalation
• Empirical antifungal
24
Kumar A,et al , Crit Care Med, 2006, 34(6):1589–1596
Ferrer R,et al, Crit Care Med, 2014, 42(8):1749–1755

Hour-1 bundle-of-care elements:
Surviving Sepsis Campaign
Measure lactate
levela
Blood cultures before
administering
antibiotics (at least 2
sets; aerobic and
anaerobic)
Administer broad-
spectrum antibiotics
Begin rapid
administration of 30
mL/kg crystalloid for
hypotension or
lactate level ≥4
mmol/L
Apply vasopressors
if hypotensive during
or after fluid
resuscitation to
maintain MAP ≥ 65
mmHg
aRemeasure lactate if initial lactate is elevated (>2 mmol/L)
Minasyan S. J Trauma Resusc Emerg Med. 2019;27:19.
25

Hour-1
bundle-of-care
elements:
Surviving
Sepsis
Campaign
26

Code Sepsis Protocol
ICU, intensive care unit, SBP, systolic blood
pressure.
1. Whitfield PL, et al. Am J Emerg Med.
27
Objectives
• To ensure rapid identification of sepsis and/or
septic shock
• To facilitate early initiation of clinical interventions
• To meet the expectations of the core measure,
including initiation of all 3- and 6-hour bundle
elements; and
• To build interdepartmental cooperation and
accountability

Initiation of Code sepsis and its benefits
ICU, intensive care unit; PSA, Perfect score attainment; SBP, systolic blood pressure.
1. Boter NR, et al. Med Clin (Barc). 2019;152(7):255–260. 2. CHA 2019, Available at: https://cha.com/wp-content/uploads/2019/04/6.10-
Screening-and-Code-Sepsis-Best-Practices.pdf. Accessed on: 05 JUN 2020. 3. García-López L, et al. Med Intensiva. 2017;41:12---20. 4. Whitfield
PL, et al. Am J Emerg Med. 2020 May;38(5):879-882. 5. Kim HI, et al. Tuberc Respir Dis (Seoul). 2019 Jan;82(1):6-14.
28
• Temperature >100.4 or <96.8 °F,
• heart rate >90 beats per minute,
• respiratory rate >22 breaths per minute,
• SBP <100 mmHg, or
• altered mental status
Triggering an alert
when following
occurs:1
• Mobilizing resources to the patient’s bedside, as available in the facility:
laboratory technologists, pharmacists, house managers, respiratory
therapists, or rapid response teams
• Roles of each person responding should be well defined
• As soon as possible, after the alert (before the end of shift), gather the
team to review/assess the case to identify exceptional care recognition
or opportunities for improvement
Code sepsis should
include:2
• Improved compliance with Surviving Sepsis Campaign recommendations
• Improved antibiotic use
• Significant increase in gradual therapeutic reduction
• Significant reduction in mortality
• Tendency towards a shorter ICU stay
Benefits of early
initiation of code
sepsis:3, 4, 5

Implementation of an adult code sepsis
protocol and its impact:
A retrospective cohort study
Population: Adults (≥18 years of age) patients met the
definition of severe sepsis or septic shock were
included.
A total of 450 patients were included in the final
analysis, (300 in the pre-protocol cohort and 150
patients in the post-protocol cohort)
• The primary outcome was PSA, which was abstracted in an all-or-
none fashion, increased from 30.7% to 71.3% (p <0.001; p <0.05
indicate significant difference).
• Inpatient mortality was reduced from 4% to 0% (p=0.011).
• Improved the time to initiation of effective antimicrobial therapy.
After protocol implementation:
Whitfield PL, et al. Am J Emerg Med. 2020 May;38(5):879-882.

Implementation of an adult code sepsis
protocol and its impact:
A comparative observational study
• Population: Patients admitted to the ICU with severe
sepsis or septic shock.
• A total of 92 patients with severe sepsis or septic
shock were enrolled (42 in the POST-SC group and
50 in the PRE-SC group)
Post-SC, post implementation of sepsis protocol; Pre-SC, pre implementation of sepsis protocol.
García-López L, et al. 2016. Med Intensiva. 2017;41(1):12---20.
30
P < 0.05 indicate significant difference
• The implementation of a Sepsis Code Protocol
– a significant reduction in mortality
• In addition, it will also:
– improve antibiotic use
– with a significant increase in gradual therapeutic
reduction
– a lower use of restricted use antibiotics
– a tendency towards a shorter ICU stay

• Initial empirical antibiotics
– Carbapenem
– Extended spectrum penicillin/β-lactamase inhibitors comb.
– Third/fourth generation cephalosporins
• Risk factors
– MDR- (Pseudomonas, Acinetobacter)
• supplemental gram -ve
– MRSA
• Vancomycin
• Teicoplanin
– Atypical
• Macrolide
• Fluoroquinolone
Antimicrobials
31
• β-lactam + aminoglycoside / fluoroquinolone
• Carbapenem + aminoglycoside
• Cefepime + aminoglycoside
Micek ST,et al, Empiric combination antibiotic therapy is associated with improved outcome in gram-negative sepsis: a retrospective analysis. Antimicrob Agents Chemother
(Bethesda). 2010; 54(5):1742–1748

Use of teicoplanin in sepsis
Teicoplanin has several advantages over vancomycin in the treatment of serious infections:
• Long half-life: allow longer dosing intervals
• Tolerability and safety: lower nephrotoxicity
• Penetrates tissue easily and reaches high concentrations in the kidney, trachea, lungs, and adrenals
• Home administered once daily or alternate daily dose
• Cost effective and improved quality of life
Teicoplanin regimen: three loading doses of 6 mg/kg (400 mg) q12h, and then 6 mg/kg (400
mg) q24h
No significant difference in efficacy between teicoplanin and vancomycin when at least 6
mg/kg teicoplanin is used
Teicoplanin is effective and safe in:
• Adults as well as pediatric patients
• Staphylococcal infections including endocarditis, osteomyelitis,
• Staphylococcus aureus infections, including methicillin-resistant strains and enterococci,
• Septic arthritis, and given in combination with another antimicrobial
Schaison G, et al. J Chemother. 2000;12(Sup5):26–33.
32

Dosing strategies
• Full, high end loading dose
– Rapid achievement of therapeutic drug level
– Increased volume of distribution
• Peak plasma concentration
 Comparable efficacy + less renal toxicity
– Fluoroquinolones
– Aminoglycosides
• Loading dose
 Low volume of distribution
– Teicoplanin
– Colistin
• Extended infusion
– β-lactams
 more effective than intermittent rapid infusion
 Initial doses- bolus/rapid infusion
 Further doses- extended infusion of drug over several hours
33

De-escalation
• longer courses-
– slow clinical response
– undrainable foci of infection
– bacteremia with S. Aureus
– Immunocompromised (neutropenia)
• shorter courses-
– rapid clinical resolution following effective source control
35
Initial combination therapy
clinical improvement and/or
evidence of infection resolution
7–10 days- adequate for most
serious infections
Daily assessment for de-escalation of antimicrobial therapy
Andrew Rhodes et al, Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med (2017) 43:304–377

De-escalation
36

Procalcitonin
• Differentiating infectious and non-infectious
• Duration shortening of antibiotics
• Discontinuation of empiric antibiotics
• (≤0.05ng/ml: Normal)
37

Vasopressors
38
1st choice
Norepinephrine
Vasopressin/
epinephrine
to raise MAP to
target
Vasopressin
to decrease
norepinephrine
dosage

• Dopamine-
– alternative to norepinephrine
– only in highly selected patients
(patients with low risk of
tachyarrhythmias and absolute
or relative bradycardia)
• Low-dose dopamine- renal
protection
– to be avoided
39
Vasopressors
Norepinephrine Dopamine
Increases MAP Increases MAP
More potent Less potent
Vaso-constrictive ↑ CO
x HR x SV ↑HR ↑SV
Less
arrythmogenic
More
arrythmogenic
Lower mortality

Inotropes
• Dobutamine
– in persistent hypoperfusion- despite IVF and vasopressor
agents
– myocardial dysfunction (↑cardiac filling pressures and
↓CO)
• Trial of dobutamine infusion up to 20 μg/kg/min be
administered or added to vasopressor
40

Steroids
• If fluid resuscitation and vasopressor- failed
• IV hydrocortisone @ 200 mg per day
• Tapered when vasopressors are no longer required
– ? fixed duration
– ? tapering
– ? abrupt cessation
• Shouldn’t be used to prevent septic shock
42

Blood products
• RBC transfusion- if Hb <7.0 g/dL
• Prophylactic platelet transfusion
– If <10,000/mm3 - in the absence of bleeding
– If <20,000/mm3 - if significant risk of bleeding
– ≥50,000/mm3 - if active bleeding, surgery or invasive procedures
• FFP to correct clotting abnormalities in the absence of
bleeding or planned invasive procedures- avoided
• EPO- not recommended
43

• Insulin-
– 2 consecutive blood glucose levels >180 mg/dL
– target an upper blood glucose ≤180 mg/dL
• Blood glucose monitored every 1–2 hrs until glucose values
and insulin infusion rates are stable and then every 4 hr
thereafter
• Glucose levels of capillary blood
– may not accurately estimate plasma glucose values
44
Blood glucose control

• Sedation (continuous or intermittent)
– minimized in sepsis patient on MV
• Renal Replacement Therapy
– CRRT facilitates management of fluid balance in hemodynamically
unstable septic patients
• Bicarbonate therapy
– Not recommended
• Venous thromboembolism prophylaxis
– LMWH > UFH- in the absence of contraindications
• Stress ulcer prophylaxis
– PPIs or H2RAs
45
Other supportive therapy

• higher PEEP
• prone > supine position- sepsis induced ARDS
• No NIV
• conservative fluid strategy
• β2agonists- avoid in sepsis-induced ARDS without
bronchospasm
46
Mechanical ventilation: ARDS

Limitations
• Both qSOFA & SOFA score cannot be used without restrictions in neutropenic patients:
– Mental status may change independently from the onset of sepsis and assessment
is therefore sometimes limited.
– Tumor-associated symptoms or complications can lead to neurological deficits.
– Platelet count cannot be used due to chemotherapy-associated or tumor-related
thrombocytopenia, and
– Chemotherapy-induced elevation of bilirubin and creatinine may influence the sofa
score calculation.
– Negative qSOFA score (< 2) should not cause any delays in starting treatment for
sepsis if there is clinical suspicion in high-risk population
Ann Intern Med 168:266–211
Crit Care Lond Engl 22:28.

Prevalence
Proportion of sepsis or septic shock in patients with neutropenia ranges from 7% to 45%

Diagnosis
Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the
German Society of Hematology and Medical Oncology (DGHO)

• Decreasing harmful capillary leak and edema formation by
protecting or restoring endothelial cell function
– Selepressin
– INF-β
– Thrombomodulin
• Reversing sepsis-induced immunosuppression by
immunostimulation
– GM-CSF
– INF-γ
– Anti PD-1 Ab
• Removal of harmful mediators from the blood using extracorporeal
techniques
– Hemofiteration-cytosorb/polymyxin B
52
Crit Care Clin (2017)

Types of sepsis by machine learning
53
Seymour CW et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA. 2019 May 28;321(20):2003-
2017.

Types of sepsis by machine learning
Most common type (33% of patients)
Normal lab test results
Lowest death rate
27% of patients
Elderly and had chronic illness with kidney problems
27% of patients
More inflammation, high fever, and breathing problems
13% of patients
Most likely to die
Associated with liver problems and dangerously low blood pressure
Seymour CW et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA. 2019 May 28;321(20):2003-
2017.
55

• Early recognition
– SOFA/qSOFA
• Early resuscitation
– IVF @ 30ml/kg-3hrs
• Blood cultures
– At least 2 sites
– Areobic + anerobic
• IV Abx
– Broad spectrum
– De escalation
• Serum lactate
• Procalcitonin
• Proper supportive treatment
56
Take home message

Sepsis

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Sepsis

Similar to Sepsis (20)

More from Pritish Chandra Patra

More from Pritish Chandra Patra (13)

Recently uploaded

Recently uploaded (20)

Sepsis

Editor's Notes