brief outline of sepsis

1. Dr. Santosh Neupane
MDGP Resident 2nd year
Moderator
Dr. Sanjeeb Tiwari

2. SEPSIS: AN OVERVIEW
Topic Presentation
April 29, 2016
ση´ψις

3. Objectives of the presentation
• Have a brief overview of the problem
• To update on emerging concepts in sepsis
• To acknowledge few practice changing studies
• To focus on the role of Emergency physicians
in sepsis and
• How we can help

4. Outline of the presentation
• Understanding sepsis
• Third consensus definitions: Highlights
• Scale of the problem
• Landmark studies/trials
• Key role of early care in sepsis
• How we can help
• Comments/Queries

5. NEJM, 2013;369:840-51
Sepsis is one of the
oldest and most
elusive syndromes in
medicine.
ση´ψις

6. • HIPPOCRATES- the process by which flesh rots,
swamps generate foul airs, and wounds fester
• GALEN- a laudable event, necessary for wound
healing
• GERM THEORY- systemic infection “blood
poisoning”, assumed to be the result of host’s
invasion by pathogenic organisms that spread in
the bloodstream.
• ADVENT OF MODERN ANTIBIOTICS- it is the host,
not the germ that drives the pathogenesis of
sepsis.

7. 1992 Consensus Definitions
• Systemic inflammatory response to infection
• Can arise in response to multiple infectious
processes
• Septicemia neither a necessary condition nor a
helpful term
• “Severe sepsis”- instances of sepsis complicated
by organ dysfunction
• “Septic shock”- sepsis complicated by
hypotension refractory to fluid resuscitation or by
hyperlactemia.

8. 2003- Second Consensus Definitions
• Endorsed most of the concepts of the first
• CAVEAT: Signs of SIRS occur in many infectious
and non-infectious conditions and is not
helpful.
IMPLICATION: Sepsis and severe sepsis are often
used interchangeably to describe syndrome of
infection complicated by acute organ
dysfunction.

9. Third consensus definitions
(Sepsis-3)(JAMA 2016)
• Sepsis- Evidence of infection plus life
threatening organ dysfunction, clinically
characterized by an acute change of 2 points
or greater in the SOFA score.
• Septic shock: Sepsis with fluid-unresponsive
hypotension, serum lactate greater than
2mmol/l, and the need for vasopressors to
maintain MAP of 65mmHg or greater.
• Elimination of mention of SIRS

11. • Broad- Helpful in evaluation of epidemiology
and economics relating to sepsis,
• Does not help in segmenting patients into
subgroups based on underlying microbiology,
pathophysiology or cellular alterations.
• Limited utility to strengthen design of clinical
trials and to direct care for individual patients.

12. • Concerns with the information used to generate
the updated criteria (Retrospective databases
with substantial gaps in clinical information of
patients treated out of ICUs)
• Drawn almost exclusively from adults in high-
income countries.
• Ability to predict morbidity and mortality in low
and middle income countries, where levels of
patient monitoring and supportive care are often
not available, remains unanswered.

13. • Inclusion of serum lactate in the definition of
serum lactate is a concern especially in resource
limited setting.
• Introduction of qSOFA
– Proposed to help identify patients with suspected
infection who are being treated outside critical care
units and are likely to develop complications
– Require prospective, real time validation
– Further simplification of alteration of mental status
possible.

14. • Fundamental component of the new
definition is presence of infection
– Negative microbiological cultures from blood or
relevant anatomic sites are frequent in patients
clinically identified as being septic.
– Identification of patients whose organ dysfunction
is truly secondary to an underlying infection rather
than other causes continue to be a major
limitation. E.g. trauma or pancreatitis with
concomitant infection.

15. • Emphasizes the need to understand sepsis as a
syndrome and not a specific disease.
• Concluding remarks hope that the next consensus
process will take full advantage of the rapidly
advancing understanding of the molecular
processes that lead from infection to organ
failure and death so that sepsis and septic shock
will no longer need to be identified as a
syndrome but a group of identifiable disease,
each characterized by specific cellular alterations
and linked biomarkers.

16. Scale of the problem
• The incidence of severe sepsis depends on how
acute organ dysfunction is defined and on
whether that dysfunction is attributed to an
underlying infection.
• Organ dysfunction is often defined by the
provision of supportive therapy (e.g. mechanical
ventilation), and epidemiological studies thus
count the “treated incidence” rather than the
actual incidence
• Extrapolated data from ICU- 19 million cases/yr
worldwide (Adhikari et. al- Lancet 2010)

17. • The clinical manifestations of sepsis are highly variable,
depending on
– the initial site of infection,
– the causative organism,
– the pattern of acute organ dysfunction,
– the underlying health status of the patient and
– the interval before initiation of treatment.
• The signs of both infection and organ dysfunction may
be subtle, and thus the recent international consensus
guidelines provide a long list of warning signs of
incipient sepsis. (Levy MM, Crit Care Med, 2003)

18. • Acute organ dysfunction-
– Respiratory compromise - acute respiratory distress syndrome
(ARDS), defined as hypoxemia with bilateral infiltrates of
noncardiac origin.
– Cardiovascular compromise-hypotension or an elevated serum
lactate levels, use of vasopressors, and myocardial dysfunction
– Central nervous system dysfunction -obtundation or delirium.
Critical illness polyneuropathy and myopathy
– Acute kidney injury
– Paralytic ileus, elevated aminotransferase levels, altered
glycemic control,
– Thrombocytopenia and disseminated intravascular coagulation,
– Adrenal dysfunction,
– Euthyroid sick syndrome

19. • Even with intensive care, rates of in-hospital death
from septic shock were often in excess of 80% as
recently as 30 years ago. (Crit Care Med 1998)
• With advances, mortality is now closer to 20 to 30% in
many series. (Crit Care Med 2001)
• Patients who survive to hospital discharge after sepsis
remain at increased risk of death in the following
month or years.
• Those who survive often have impaired physical or
neurocognitive functioning, mood disorders, and a low
quality of life.

20. LANDMARK STUDIES/TRIALS
• Rivers et al, 2001 (RCT, NEJM) EDGT (early goal
directed therapy)
– CVP guided approach of fluid therapy
– 16% absolute mortality benefit
• Kumar A. et al, 2006 (Crit Care 2006)
– Duration of hypotension before initiation of effective
antimicrobial therapy is the determinant of survival in
human septic shock.
– Delays in giving antibiotics can increase mortality by
up to 7.6% for each hour’s delay.

21. • Jones AE et al (Lactate clearance vs central
venous oxygen saturation as goals of early
sepsis therapy: a randomized clinical trial;
JAMA 2010)
– Early resuscitation in the first 6 hours after an
aggressive search for sepsis/septic shock using
bedside information and serial lactate
measurements was non-inferior to the more
regimented and resource intensive EDGT
approach suggested by Rivers et al.

22. • ProCESS trial(NEJM 2014):
– How fluids and vasoactive agents were provided
did not create a superior outcome as long as each
was done early, aggressively and in the backdrop
of early antibiotic use.
• ARISE trial(NEJM 2014):
– Compared EDGT compared to usual, unstructured
care
– Did not identify one as better than other.

23. • RECOMMENDATIONS
– Wider use of early and simple detection with the
goals of fluids that are adequate and directed by
bedside reassessment and appropriate antibiotic
therapy rather than a singular prescriptive form of
resuscitation.

24. Key role of early care in sepsis

25. • CHALLENGE:
– identify and recognize patients with sepsis and
impending organ dysfunction.
– Can be aided by a screening tool that combines
simple clinical characteristics with early lactate
measurements.

26. How can we help?
• ASSESS for SIGNS
• SUSPECT,
• REASSESS for history
• look for LACTATE and GLUCOSE
• Provide FLUIDS guided by clinical assessment and
APPROPRIATE ANTIBIOTICS early.
• TRACE INVESTIGATIONS # including culture of
appropriate sites.(#CBC, RFT, PLATELETS, PT,
BILIRUBIN, ABG)

27. Ongoing sepsis studies in our
Emergency
• Lactate levels in sepsis
• Robson Screening Tool for Identification of
sepsis in Emergency

28. Comments/Queries?

29. THANK YOU