5. Sepsis: Definition
• Life-threatening organ dysfunction caused by a dysregulated host response to
infection.
• Major health problem impacting millions of people around the world.
• Between 1 in 3 and 1 in 6 people die from sepsis.
• Early identification and appropriate management in initial hours after
development of sepsis improves outcomes.
6. Continuum of Severity
Infection Bacteremia Sepsis
Septic
Shock
MODS Death
SIRS and Severe Sepsis no longer included in this continuum.
7. Definitions
• Infection: Invasion of normally sterile tissue by organisms resulting in infectious
pathology.
• Bacteremia: Presence of viable bacteria in the blood.
• Septic Shock: Sepsis that has circulatory, cellular, and metabolic abnormalities that
are associated with a greater risk of mortality than sepsis alone..
• Clinically, a Patient with sepsis who despite adequate fluid resuscitation, require
vasopressors to maintain mean arterial pressure >65 mm Hg and have lactate level
> 2 mmol/lr.
8. Definitions
• MODS: Progressive organ dysfunction in an acutely ill patient such that
homeostasis cannot be maintained without intervention.
Primary: Result of a well-defined insult in which organ dysfunction occurs early
and is directly attributable to the insult itself.
Secondary: Organ failure that isn’t in direct response to insult itself but is
consequences of the host’s response.
10. Sepsis: Screening
• The sepsis performance improvement
program consists of sepsis screening,
education, patient outcomes and
actions for identified opportunities.
Sepsis screening tools
SIRS criteria
Sequential Organ Failure Assessment
Score (SOFA)
qSOFA Score
National Early Warning Score (NEWS)
Modified Early Warning Score (MEWS)
11. Studies have shown that qSOFA is more
specific but less sensitive that having two
of four SIRS criteria for early identification
of infection-induced organ dysfunction.
Neither SIRS nor qSOFA is ideal screening
tools for sepsis.
Recommendation: Don’t use qSOFA compared with SIRS, MEWS or NEWS as single screening tool
for sepsis or septic shock. (Strong, Moderate)
12. Suspected sepsis: Lactate level
• Association of lactate level with mortality in patients with suspected sepsis well
established.
• Studies have shown an association between the point of care lactate
measurement and reduced mortality, results are inconsistent.
• Lactate alone is neither sensitive nor specific.
Recommendation: For adults suspected of having sepsis, suggested to mesure blood lactate level.
(Weak, Low)
13. Admission to intensive care
• Outcome of critically ill patients depends on the timely application of critical care
interventions.
• Delayed admission to ICU a/w increased mortality, ventilator duration, and
hospital LOS.
Recommendation: For patients with sepsis or septic shock, patients should be admitted to ICU
within six hours.
14. Initial resuscitation
• Sepsis and septic shock are medical emergencies and treatment and
resuscitation should begin immediately.
• For sepsis induced hypoperfusion or septic shock, at least 30 ml/kg of IV
crystalloid fluid should be given within the first 3 hours of resuscitation.
(Weak, Low).
• Dynamic parameters are suggested over physical examination or static
parameters in guiding further fluid resuscitation. (Weak, very low).
15. Dynamic parameters Standard parameters
Response to passive leg raise Systolic blood pressure
Stroke volume variation Heart rate
Pulse pressure variation Central venous pressure
Use of echocardiography
16. Mean arterial pressure (MAP)
• MAP is a key determinant of mean systemic filling pressure; which in turn major
driver of venous return and CO.
• Increasing MAP results in increasing tissue blood flow and augments the supply
side of tissue perfusion.
Recommendation: For adults with septic shock on vasopressors, initial target of MAP should be
65 mm of Hg or higher. (Strong, Moderate).
17. Fluid management
• Crystalloids are inexpensive and easily available.
• For decades, NS has been the initial choice; potential adverse effects include
hyperchloremic metabolic acidosis, renal vasoconstriction and AKI.
• Increased interest in chloride restrictive solutions( balanced solution).
• Meta-analysis of 14 RCTs showed decreased mortality with balanced solutions
compared with NS.
18. …Fluid management
• Cochrane review found no difference in 30 or 90 day mortality comparing
albumin vs crystalloids in septic patients.
Recommendations
a. Crystalloids are recommeded as first-line fluid for resuscitation. (Strong, Moderate)
b. Balanced crystalloids are recommended over normal saline. (Weak, Moderate)
c. Albumin is suggested in patients who receive a large volume of crystalloids. (Weak, Moderate)
19. Diagnosis of infection
• Signs and symptoms of sepsis are nonspecific and mimic multiple other diseases.
• HCW can’t have d/d of sepsis alone in a patient with organ dysfunction.
• Third or more patients initially diagnosed with sepsis turn out to have the non-
infectious condition.
• Best practice is to continually assess patients to determine if other diagnoses are
more or less likely.
Recommendation: In patients with suspected sepsis or septic shock(unconfirmed), continuously
reevaluate, search for alternate diagnoses, and discontinue antibiotics if an alternate cause is
demonstrated,(BPS)
20. Time to antibiotics
• Early administration of appropriate antimicrobials most effective intervention to
reduce mortality.
• Must be balanced against potential harms a/w administering unnecessary
antimicrobials without infection.
• Mortality reduction appears strongest in patients with septic shock compared
with sepsis alone.
22. Biomarkers to start antibiotics
• Procalcitonin rises rapidly in response to proinflammatory stimuli, especially bacterial
infections.
• In a meta-analysis of 30 RCTs, procalcitonin had a sensitivity of 77% and specificity of 79% for
sepsis in critically ill patients.
• Another meta-analysis of 3 RCTs found no difference in short-term mortality, length of ICU
stay or length of hospitalization when comparing procalcitonin guided protocols vs usual care
for antibiotic initiation.
Recommendation: Suggested against using Procal plus clinical evaluation to initiate antimicrobials
versus clinical evaluation alone. (Weak, very low)
23. Antimicrobial choice
• The decision to include MRSA covering antibiotic on empiric regimen depends on:
a. Likelihood that the patient’s infection is caused by MRSA.
b. Risk of harm a/w withholding t/t for MRSA in patients with MRSA.
c. Risk of harm a/w MRSA t/t in patients without MRSA.
24. MRSA
• Accounts for 5% of culture positive infections among critically ill.
• Risk factors:
a. Prior history of MRSA infection or colonization.
b. Recent IV antibiotics.
c. History of recurrent skin infections or chronic wounds.
d. Presence of invasive devices.
e. Hemodialysis
f. Recent hospital admission and severity of illness.
25. …MRSA
• Delay of >24-48 hours until antibiotic administration in documented MRSA
infected patients a/w increased mortality in some studies.
• Other studies show higher mortality among undifferentiated patients with
pneumonia or sepsis started on MRSA covering antibiotics.
Recommendation:
a. For patients with high risk of MRSA, empiric MRSA coverage is recommended. (BPS)
b. For patients with a low risk of MRSA, MRSA coverage is not suggested. (Weak, Low)
26. Multidrug therapy
• The use of multidrug therapy is often required to ensure at least one agent is
active against the offending pathogen.
• Optimal empiric therapy depends on:
a. Local prevalence of resistant organisms.
b. Patient risk factors for resistant organisms.
c. Severity of illness.
27. …Multidrug therapy
• Factors to guide double gra negative coverage:
a. Proven infection/ colonization by antibiotic resistant organisms within past
year.
b. Local prevalence of antibiotic-resistant organisms.
c. Hospital-acquired vs community-acquired infection.
d. Broad-spectrum antibiotic use within the past 90 days.
e. Travel to a highly endemic country within the past 90 days.
28. Recommendation
a. For patients with a high risk of MDR organisms, two antimicrobials with gram-
negative coverage as empiric therapy suggested. (Weak, very low)
b. For patients with low risk of MDR organisms, use of two gram-negative agents as
empiric therapy nor suggested. (Weak, very low)
c. For patients, once causative agent and susceptibilities are known, two gram-
negative agents are not suggested.
29. Delivery of antibiotics
• Beta lactams are subject to changes in pharmacokinetic properties in the setting of
sepsis resulting in sub-therapeutic concentrations.
• Continuous infusion results in sustained concentration, aligning with the
pharamcodynamics of these drugs.
• Reduction in short-term mortality is significant with a prolonged infusion with a
minimal cost implication or side effects.
Recommendation: Prolonged infusion of beta lactams for maintainence (after initial bolus) over
conventional bolus infusion. (Weak, moderate)
30. De-escalation of antibiotics
• Particularly relevant in emperic broad spectrum therapy.
Recommendation: Daily assessment for deescalation fo antimicrobials over a fixed duration of
therapy. (Weak, Low)
32. …Duration of antibiotics
• The optimal duration of antimicrobial therapy depends on many factors like host,
microbe, and anatomical site.
• In many trials, a shorter course of antibiotics was found just as effective with
fewer adverse effects as well.
Recommendation: Suggested using shorter over a longer duration of antimicrobial therapy.
(Weak, Very low)
33. Biomarkers to discontinue antibiotics
• While typically clinical evaluation alone is used to decide the duration, biomarkers could
offer additional information.
• Metanalysis(14 RCT) suggested improved mortality in patients managed with
procalcitonin versus control; while there was no effect on length of stay in the ICU.
• Algorithms for antimicrobial therapy, frequency of procalcitonin monitoring, and
threshold for discontinuation differed widely.
Recommendation: Using Procalcitonin and clinical evaluation is suggested to decide when to
discontinue antimicrobials. (Weak, Low)
34. Antifungal therapy
• Risk factors for fungal infection:
a. Neutropenia
b. Immunosuppression
c. Longer ICU length of stay
d. Central venous catheter and other IV devices
e. Total parenteral nutrition
f. IV drug users
g. Broad spectrum antibiotics
h. Prior surgery
36. Antiviral therapy
• Apart from endemics/pandemics, viruses are rarely the primary cause of sepsis.
• Immunocompromised patients are vulnerable to viral infection.
• The desirable effects of empiric antiviral therapy are unknown, plus the risk of
undesirable effects.
Recommendation: No recommendation on the use of anti viral agents.
37. Source control
• Appropriate source control is a key principle in the management of sepsis and
septic shock.
• May include drainage of abscess, debriding necrotic tissue, and removal of
potentially infected devices.
• Source control immediately after resuscitation; preferably within 6-12 hours.
• A least invasive option that effectively achieves source control should be pursued.
38. • 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 infection..
Deep space infection (Empyema or septic arthritis).
Implanted device infections.
Recommendation: Rapidly identify or exclude specific anatomical diagnosis of infection that
requires emergent source control and implement source control intervention as soon as possible.
(BPS)
39. Intravascular devices: Recommendation
• Intravascular device suspected to be a source should be removed after initial
resuscitation and another site is established.
• Some implanted catheter infections may be treated effectively with prolonged
antimicrobial therapy if removal is not practical.
40. Vasoactive agents
• Norepinephrine is potent alpha 1 and B1 agonist: increased MAP with minimal effect on
heart rate.
• Dopamine acts on D1, a1 and b1 receptors.
• At a lower dose, causes vasodilation via d1 receptors in renal, splanchnic, cerebral, and
coronary beds.
• At a higher dose, causes vasoconstriction and increased SVR via a1.
• Vasopressin causes vasoconstriction by binding to vascular smooth muscle cells.
• Unlike most vasopressors, vasopressin is not titrated and is given at a fixed dose of 0.03
units/min.
41. …Vasoactive agents
• In systemic review and meta-analysis (11 RCT), NE resulted in lower mortality and
lower risk of arrhythmia compared to dopamine.
• RCTs consistently have shown no difference in mortality while comparing
epinephrine and norepinephrine.
• Early use (NE dose of 0.25-0.5 mcg/kg/min) of vasopressin in combination with
NE may help reduce adrenergic burden; demonstrated to reduce mortality.
43. In next class..
• Oxygen targets
• Oxygen delivery methods.
• Prone vs supine ventilation
• Corticosteroid therapy.
• Blood transfusion strategy.
• Role of IV immunoglobulins.
• Stress ulcer prophylaxis.
• VTE prophylaxis.
• Renal replacement therapy.
• Glycemic control.
• Nutritional routes.
• Sodium bicarbonate therapy.
• Role of vitamin C.
• Palliative care.
• Golden hours of sepsis and summary.
44. References
• Bailey and Love textbook of surgery, 27th edition.
• Sabiston text book of surgery.
• Surviving Sepsis Campaign taskforce international guidelines 2021.
