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)
• 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
• 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.
• 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.
 CRP
• 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.
• 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
• 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.
• 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
• 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