Sepsis update

Dr. Harshil Mehta

Associate Consultant

Accident and Emergency

Kokilaben Dhirubhai Ambani Hospital, Mumbai

Definitions

• Infection

• Bacteremia

• SIRS

• Sepsis

• Severe sepsis

• Septic shock

• MODS / p- MODS

•Emergency physician at Henry ford Hospital, Detroit•Study was conducted in 2001•Aim was to evaluate efficacy of EGDT before ICU admission

Supportive EvidenceQuality / Grade A B C D E FOutstanding • Rivers,NEJM,

2001Good Nguyen,CCM,2007;

Ferrer, JAMA 2008Adequate Micek, CCM, 2006; Kortgen,

El Sohl, J Am Ger CCM,Soc, 2008 2006

Surviving sepsis campaign

SSC partners

SSC 3 hour bundle

1. Measure lactate level

2. Obtain blood culture prior to administration of antibiotics

3. Administer broad spectrum antibiotic

4. Administer 30 ml/kg crystalloids for hypotension and lactate > 4 mmol/l

SSC 6 hour bundle

1. Apply vasopressors to maintain MAP > 65 mmHg

2. In persistent hypotension despite volume resuscitation or initial lactate > 4 mmol/l• Measure CVP

• Measure ScvO2

3. Remeasure lactate if initial lactate was elevated

3 hour bundle

1. Measure lactate level:– Essential to identify tissue hypoperfusion

– Limiatation:• Raised in cellular metabolic failure

• Elevated in hepatic clearance failure

– Implication:• Mortality is high in hypotension, raised lactate level or in

both

• Lactate > 4 mmol/L – 6 hour bundle patient

– Turnaround time:

– Arterial v/s venous??

0

5

10

15

20

25

Intent to treat Per protocol

Lactate group

ScvO2 group

2. Obtaining blood cultures before administering antibiotics:

– Collection strategy:

• Two or more culture from percut and veach vascular access device

• Wound, urine, sputum, CSF, ascitic fluid, pleural fluid

– Indications:

• Fever, chills, hypothermia, leukocytosis, renal failure, hemodynamic compromise, other unexplained organ dysfunction

3. Administer broad spectrum antibiotics:– Timing of antibiotic:

• Once sepsis is identified, antimicrobial agent should be administered as soon as possible.

• Adequate antibiotic therapy is required.

– Choice of antibiotic:• Use broad spectrum antibiotics until specific pathogen is

identified

• Use combination of antibiotics initially

– Re-evaluation after 24-48 hours:• Once organism is identified, restrict antibiotic to specific

pathogen narrow the spectrum

4. Administer 30 ml/kg crystalloid for hypotension and lactate > 4 mmol/L:

• Initial fluid resuscitation

– 30 ml/kg, as early as possible after diagnosis

– Requirement is not easy calculate, so repeated boluses should be given

– Target : CVP > 8 mmHg

Lactate clearance

ScvO2 > 70%

t

• SSC recommends MAP of at least 65 mmHg.•Whether this is effective or not in unknown•Aim of this trial was to study significant difference between high target blood pressure and low target blood pressure group

Lower v/s higher hemoglobin threshold for blood transfusion in septic shock

• Multicenter, RCT

• To establish harms and benefits of blood transfusion in patients with high and low threshold level

• High threshold <9 g/dl

• Low threshold < 7 g/dl

• Primary outcome – 90 days mortality

Published in NEJM.org on October 1, 2014

•Total 1545 blood transfusion were given to low threshold group v/s 3040 to high threshold group (p<0.001)

•176 patients (36.1%) in low threshold group didn’t undergo transfusion as compared to only 6 patients (1.2%) in high threshold.

International trials on sepsis

• Aim : whether River’s findings were generalized and whether all aspects of protocol were necessary.

• Patients were divided in three groups:

– Protocol based EGDT

– Protocol based standard therapy

– Usual care

•No benefit of CV line and central monitoring in all patients

•Two protocol based management lead to initial transient improvement in blood pressure, but a higher requirement of intensive care and renal replacement therapy.

•No significant difference in mortality

• Question: Does EGDT compared with standard care decrease mortality at 90 days?

• Design:

– Multi centered, RCT

– 51 hospitals from 2008-2014

– Around 1600 patients

• Strength of the study:– Clinical relevance

– Large multi center study

– Use of original EGDT algorithm

– No confounding effect of antibiotic administration

– Statistical analysis

• Bottom line:– Contradictory to EGDT, continuous central venous

oximetry, liberal blood transfusion policy and dobutamine

– Early recognition, source control, early antimicrobial therapy, fluid resuscitation and escalation remain fundamental goals

• ARISE and PROCESS have not demonstrated any adverse outcome in groups using CVP and ScvO2 monitoring. So no harm in continuing SSC bundle

• SSC will review their bundle and treatment plan and update accordingly

• For now, no change in 3 hour bundle pattern

• Objective:

– Determine the association between compliance with SSC bundle and mortality

• Design:

– Based on 2004 SSC guidelines

– Data collection from 2005 to 2012

– 218 hospitals from US, South America and Europe

• Results:

– Hospital mortality rate dropped 0.7% per site for every 3 months of participation (p<0.001)

– Hospital and ICU LOS decreased 4% (p-0.012) for every 10% increase in site compliance with resuscitation bundle.

Compliance High Low P value

Resuscitation bundle 29.0% 38.6% <0.001

Management bundle 33.4% 32.3% 0.039

• Purpose:

– To describe and compare the design of three multi centered independent trials on EGDT for severe sepsis and septic shock

• Conclusion:

– Harmonization is feasible

– Facilitate pooling of data on completion of trials

Duration for first bolus

Duration of third bolus

Duration of first dose of antibiotic