Sepsis in surgical patients, its biomarkers
and Surviving sepsis Campaign 2021
Presenter : Dr Samrat Shrestha

DAY 1
Sepsis in surgical patients
SOURCE CONTROL
Biomarkers
 DAY 2
Recent advances and recent biomarkers
Surviving sepsis Campain 2021
MANAGEMENT

SEPSIS
•Schottmuller,in 1914 defines sepsis as
“A state which is caused by microbial invasion from a local infectious
source into the blood stream which leads to sign of systemic illness in
remote organ.”
• Early diagnosis and treatment influence the morbidity and mortality
• Sepsis is life-threatening organ dysfunction caused by a dysregulated
host response to infection.

• SIRS was diagnosed clinically by the presence of at least two
features;
-Temp >38C or <36C
-HR > 90bpm
-RR>20 breaths/m or PaCO2 <32 mmHg
-WBC >12000/mm3 or <4000/mm3 or immature forms
(bandemia)>10%
• This definition was neither sensitive nor specific for sepsis.
• These features can be seen in postoperative patient , many non
infectious conditions like burns , pancreatitis , trauma ,
ischemia-reperfusion.

• Sepsis life threatening organ dysfunction caused by dysregulated
host response to infection.
• Focus has been shifted from inflammation to organ dysfunction in
presence of infection.

Septic Shock:
A subset of sepsis in which underlying circulatory and cellular/
metabolic abnormalities are profound enough to increase mortality.
Clinical criteria identifying such condition include:
• Persisting hypotension requiring vasopressors to maintain MAP≥65
mm Hg
• Blood lactate >2 mmol/L despite adequate volume resuscitation

EVOLUTION OF SEPSIS

• Organ dysfunction is defined in term of sequential organ failure
assessment (SOFA) score increase in two or more from baseline in
the presence of infections.
• For identification of pathogens such as blood culture take time and
are not helpful for rapid recognition.
• Early and rapid recognition could lead to early institution of therapy,
reduce morbidity and mortality and improve outcome.

SOFA Score

Pathophysiology

qSOFA score
Use three criteria;
• An alteration in mental status
• Systolic BP <100 mm Hg
• RR> 22 breaths/min
Significance
• Presence of at least 2 qSOFA criteria is predictor of both
increased mortality and ICU stays of >3 days for non ICU
patients.

“PqSOFA” score combined the qSOFA score with procalcitonin
Combining PCT and the qSOFA score can facilitate an early assessment
of acute sepsis severity and prognosis among adult patients, although its
predictive ability is less than ideal.
PqSOFA score can independently identify critically ill patients with
sepsis, predict their short-term adverse events, and their 28-day
prognosis.
PqSOFA score had superior predictive value than qSOFA score, although
its performance was comparable to SOFA or APACHE II scores.

• qSOFA score revealed sufficient prediction for mortality in the IMCU.
• SOFA score showed best results regarding mortality in IMCU/ICU
patients, its predictive quality depended on the severity of the
disease.
• Summarizing, it remains unclear whether qSOFA or SOFA score
should be used in surgical IMCU patients for risk stratification.

• Regarding hospital mortality, SIRS criteria and qSOFA score revealed
only poor predictive validity, whereas the SOFA score was predictive
for the patients’ death
• SIRS criteria and qSOFA score reached high sensitivity but low
specificity regarding mortality, whereas SOFA score performed
adequately.

SOURCE CONTROL OF SEPSIS

• Source control may include drainage of an abscess, debriding
infected necrotic tissue, removal of a potentially infected device, or
definitive control of a source of ongoing microbial contamination
Foci of infection readily amenable to source control include
• Intra-abdominal abscesses
• Gastrointestinal perforation,
• Ischemic bowel or volvulus
• Cholangitis
• Cholecystitis,
• Pyelonephritis associated with obstruction or abscess
• Necrotizing soft tissue infection
• Deep space infection (e.g., empyema or septic arthritis)
• Implanted device infections

• Source control should be achieved as soon as possible following
initial resuscitation
• Limited data to conclusively issue a recommendation regarding
timeframe in which source control should be obtained
• Smaller studies suggest that source control within 6 to 12 hours is
advantageous
• Studies generally show reduced survival beyond that point
• Clinical experience suggests that without adequate source control,
many severe presentations will not stabilize or improve despite rapid
resuscitation and provision of appropriate antimicrobials

• Selection of optimal source control methods must weigh benefits and
risks of specific intervention, patient’s preference, clinician’s
expertise, availability, risks of procedure, potential delays, and
probability of procedure’s success.
• Least invasive option that will effectively achieve source control
should be pursued.
• Open surgical intervention should be considered when other
interventional approaches are inadequate or cannot be provided in a
timely fashion.
• Surgical exploration may also be indicated when diagnostic
uncertainty persists despite radiologic evaluation, when probability
of success with a percutaneous procedure is uncertain, or when
undesirable effects of a failed procedure are high.

MULTIDISCIPLINARY APPROACH FOR SOURCE
CONTROL
• Procedures for source control should be tailored to infection site and
extent, and degree of derangement of patient physiology
• Well-balanced decision as to the timing and methodology for source
control is mandatory.
• Multidisciplinary approach involving surgeons, infectious disease
physicians, interventional radiologists, interventional endoscopists,
anaesthesiologists, and intensivists to ensure selecting best source
control strategy for the individual patient.

• Conclusions:
• For patients of GI perforation with associated septic shock, time from
admission to initiation of surgery for source control is a critical
determinant, under condition of being supported by hemodynamic
stabilization.
• Target time for a favorable outcome may be within 6 hours from
admission.
• We should not delay in initiating early goal-directed therapy assisted
surgery if patients are complicated with septic shock.

Conclusions:
• Our data provide important clinically based evidence for the
beneficial effects of surgical treatment within 12 hours of admission
for V vulnificus-related NF.

Biomarkers Of SEPSIS
• Biomarkers are naturally occurring molecules , genes or other
characteristics by which physiological and pathological processes
can be identified.
• Characteristics of ideal biomarker:-
It should be an objective parameter
Easy to measure
Reproducible
Inexpensive
Fast kinetics
High sensitivity and specificity
Short turn around time
Show Appropriate response to therapy(Decline In response with
therapy)

• Differentiate local infection, disseminated infection and sepsis.
• Differentiate viral and fungal infection from bacterial infection.
• Determine response of antibiotics , response to therapy , prediction
of organ dysfunction and complications.

• Initial biomarkers investigated in sepsis were
WBC count
Lactate
ESR
C-reactive protein
Pro calcitonin .
• WBC : leucocytosis can be seen in both noninfectious and infectious
cause hence it is not specific.
• ESR is an indicator of inflammation and its utility in sepsis is limited as
it can be influenced in presence of anemia , immunoglobulins ,
change in erythrocyte size , shape and number ,malignancy , tissue
injury.

• Lactate: a byproduct of glycolysis is a marker of sepsis, hypoperfusion
leading to anaerobic glycolysis causes hyperlactatemia .
• Lactate level is high in hypovolemia and haemorrhage during trauma
and surgery.
• Lactate clearance is used as a marker of adequate resuscitation.
• Lactates are not a good marker of sepsis but a important indicators of
severity of shock , hypoperfusion and adequacy of resuscitation.
LACTATE

• Association of lactate level with mortality in patients with suspected
infection and sepsis is well established
• Currently recommended as part of the SSC Hour-1 sepsis bundle for
those patients with sepsis
• Lactate cutoffs determining an elevated level ranged from 1.6−2.5
mmol/L, although diagnostic characteristics were similar regardless
of the cutoff.
• Presence of an elevated or normal lactate level significantly increases
or decreases, respectively, likelihood of a final diagnosis of sepsis in
patients with suspected sepsis.
• Lactate alone is neither sensitive nor specific enough to rule-in or
ruleout the diagnosis on its own

• CONCLUSION
• The evidence reviewed suggested that whole blood, plasma or serum
lactate measurement could not provide specific prognostic information for
individual patients.
• There may be a role for monitoring for normalization of serum D- or L-
lactate concentrations during goal-directed therapy in ICU but further good-
quality studies are needed.
• Measurement of the D-lactate stereoisomer shows promise, such that
further studies are warranted.

• C-reactive protein is an acute phage reactant which is synthesized in
liver(hepatocytes) in response to inflammation or tissue injury and
upregulated by interleukin 6.
• Normal level: Less then 0.3 to 0.5 mg/dl.
• Level can rise upto 1000times in response to acute phase stimulus.
• Starts to rise after 6 hours and peak at about 48 hours with half life of
20 hours.
CRP

• Elevated in both infectious and noninfectious conditions
• Modest elevation can be seen in low grade inflammatory conditions
such as atherosclerosis, obesity , hypertension, diabetes and
obstructive sleep apnea.
• Marked elevation is associated with bacterial infections.
• It has good sensitivity but poor specificity.
• It is a good marker of inflammation rather then infection.

Results:
• CRP had a sensitivity and specificity of 84.3% and 46.15%,
respectively. Area under the receiver operating characteristics curve
was calculated to be 0.683 (±0.153, P < 0.05). The cutoff value with
the best diagnostic accuracy was found to be 61 mg/L.
Conclusion:
• CRP is a sensitive marker of sepsis, but it is not specific.

Conclusion
• An admission CRP level >100 mg/L is associated with an increased
risk of ICU and 30-day mortality as well as prolonged Length Of Stay
in survivors, irrespective of morbidity.
• Thus, CRP may be a simple, early marker for prognosis in ICU
admissions for sepsis.

• Procalcitonin a precursor of calcitonin , produced by C –cells of
thyroid under the control of calcitonin gene related peptides (CALC-1)
gene.
• During infection there is increase of CALC-1 gene expression in
various extrathyroid tissue like parenchymal tissue such as lungs ,
liver , kidney which is mediated by proinflammatory cytokines such as
TNF-a and IL-6.
PROCALCITONIN

• Both microbial toxins and host response by humoral or cell mediated
can lead to release of PCT.
• PCT starts rising by 2 hours after stimulus , peaks at 6 hours , plateau
at 8-24 hours and decrease to base line by 2 days.
• Half life is around 20 hours.
• Low or negligible amount is seen in healthy individuals however it can
be increased to 1000 folds during active infection and sepsis.

• Interferon gamma released during the viral infections suppress PCT.
• High level of PCT is seen in systemic infections therefore local
bacterial colonization , encapsulated abscess , localised and limited
infections may shows normal level of PCT.
• Some condition where PCT can be elevated are :
Neonate less then 48 hours of age
First day after major surgery
Trauma, Burns
Pancreatitis
Invasive fungal infections
Malaria
Severe cardiogenic shock
Malignancies eg . Medullary carcinoma of thyroid ,small cell
carcinoma of lungs.

Interpretation of procalcitonin level
Procalcitonin values(ng/ml) interpretation
Less then 0.05 normal
0.05-0.5 Localized infection possible.
Retest after 6-24 hours.
0.5 -2.0 Systemic bacterial infection possible. Retest after 6-24
hours.
2.0-10 Systemic bacterial infection highly likely. High risk of severe
sepsis
Greater then 10 Severe sepsis

• An early diagnosis and the initiation of an appropriate antibiotic treatment are still the
cornerstones of effective sepsis care.
• In this respect, PCT has shown promising results for the treatment of patients with sepsis.
• However, it should be noted that PCT values are not intended to replace good clinical
practice, but should be used as a complementary tool combined with available clinical and
diagnostic parameters.
• The prognostic information derived from PCT kinetics can influence further procedure with
regard to diagnostic testing, but also therapeutic decisions and timing of patients discharge
• In high risk situation the use of PCT should not delay or inhibit the start of empirical
treatments, but should rather be used for treatment termination in case PCT is <0.5 µg/L or
decreased by 80–90% of the peak level.
• To date, integration of the host-response marker PCT into a comprehensive clinical
assessment seems to be a promising approach to reduce diagnostic uncertainties and
antibiotic overuse.
• Still, further research is needed to understand optimal use of PCT, also in combination with
other remerging diagnostic tests for most efficient sepsis care.

• Objective: To evaluate the prognostic value of C-reactive protein (CRP),
procalcitonin (PCT), and their combination for mortality in patients with septic
shock.
• Combination matrix of CRP and PCT was compared to determine the 28-day
mortality.
• OR of both CRP and PCT elevated was 1.552 (95% CI 1.184–2.035), mortality rate
was 26.9%.
• 28-day mortality of both CRP and PCT elevated was signifcantly higher than that
of only PCT elevated (17.8%) and both CRP and PCT not elevated (18.1%).
• However, the 28-day mortality of patients with only CRP elevated was 21.5%
which was not signifcantly different from those with both CRP and PCT elevated.
• Nevertheless, in the multivariate logistic regression analysis, both CRP and PCT
elevated was not an independent predictor of 28-day mortality.

• Sabiston textbook of surgery -20th edition
• Bailey & Love’s short practice of surgery- 27th edition
• Roshan Lall Gupta’s Recent Advances in SURGERY, Volume
17.
• Surviving Sepsis Campaign: International Guidelines
for Management of Sepsis and Septic Shock: 2021
• Pubmed recent articles
• Source Control: A Guide to the Management of Surgical
Infections

To be continued……………………………..
THANK YOU