Sepsis

1. Approach to Management of
Fever & Sepsis
Arwindran

2. DEFINITION OF FEVER
• Body temperature > 38OC
• Low grade fever
• High grade temperature
Mackowiak et al, 1992

3. DURATION OF FEVER
• Continuous: above normal, doesn’t fluctuate >1 in 24hrs
• Intermittent: at certain period
• Remittent: above normal, fluctuate >1 in 24hrs

4. FEVER OF UNKNOWN ORIGIN
• Fever of unknown origin (FUO) in adults is
defined as a temperature higher than 38.3 C
(100.9 F) that lasts for more than three weeks
with no obvious source despite appropriate
investigation.

5. CAUSES OF FEVER
(Antoon et al, 2015).

6. Pathophysiology of fever

8. MANAGEMENT
• INVESTIGATIONS
✔ P/E
✔ BLOODS
✔ IMAGING
• SYMPTOMATIC TREATMENT

9. TREATMENT
• NSAIDS
• ACETAMINOPHEN
• Tepid sponging (reduce 1.4 in 20 mins)

10. SEPSIS

11. DEFINITION
• Systemic inflammatory response syndrome (SIRS) requires 2 or more of the following (the
definition differs for children):
1. T >38 C or <36 C
2. P >90/min
3. RR >20/min or PaCO2 <32 mmHg
4. WCC >12 or >10% immature band forms
• SEPSIS= SIRS + INFECTION
• SEVERE SEPSIS= SEPSIS WITH ORGAN DYSFUNCTION
• SEPTIC SHOCK= REFRACTORY HYPOTENSION

12. SEPSIS 3
(3rd International Consensus of Sepsis & Septic Shock
• life-threatening organ dysfunction due to a dysregulated host response to infection
• Increase 2 points in SOFA score
• Septic shock: subset of sepsis in which particularly profound circulatory, cellular, and
metabolic abnormalities are associated with a greater risk of mortality
• Septic shock clinical criteria: Sepsis and (despite adequate volume resuscitation) both of:
– Persistent hypotension requiring vasopressors to maintain MAP greater than or equal
to 65 mm Hg, and
– Lactate greater than or equal to 2 mmol/L
– With these criteria, hospital mortality is in excess of 40%

13. SOFA SCORES
Singer M, et al. 2016

14. qSOFA
• A validated ICU mortality prediction score, to help identify patients with suspected
infection that are at high risk for poor outcome
Singer M, et al. 2016

15. Clinical presentation sepsis & septic shock

17. Investigations
When faced with a patient with sepsis, initial investigations to identify end organ hypoperfusion and identify the
source of infection are important.
Investigations to assess for end organ hypoperfusion
● Full blood count
● Clotting profile, with prothrombin time and INR
● Urea and electrolytes
● Liver function tests
● Serum lactate
● Arterial blood gas measurement

18. 2018 update to SSC bundle of care
● Measure lactate level
● Obtain blood cultures prior administration of antibiotics
● Administer broad spectrum antibiotics
● Begin rapid administration of 30ml/kg crystalloid for hypotension or
lactate level >4mmol/L
● Apply vasopressor if patient is hypotensive during or after fluid
resuscitation to maintain MAP > 65mmHg

20. Initial Fluid Resuscitation
● Early effective fluid resuscitation is crucial for stabilization of sepsis-induced
tissue hypoperfusion or septic shock.
Type of fluid
● Initial fluid resuscitation should be with crystalloids. There is no convincing
evidence to suggest the superiority of any alternative.
○ Colloid solutions may be associated with increased risk of acute kidney injury and a marginal
benefit has been observed for resuscitation with albumin-containing solutions.
○ Crystalloids are cheaper and more readily available.

21. Intravenous fluids
● A minimum of 30 mL/kg of intravenous crystalloid fluid should be
administered as a fluid challenge within 3 hours.
● There is no evidence to suggest the optimum volume of fluid to administer.
The response to initial resuscitation should determine the total volume
administered.
● The SSC recommends a conservative fluid strategy for patients with sepsis-
induced acute lung injury (pulmonary oedema).
● It is therefore important to monitor response to fluids to prevent fluid overload
or worsening of sepsis-induced acute lung injury.

23. End point of fluid resuscitation
● Mean arterial pressure of 65 mm Hg
● Urine output of 0.5 mL/kg/hour
● Central venous pressure of 8–12 mm Hg
● Superior vena cava oxygen saturation of 70% or mixed venous oxygen
saturation of 65%

24. Vasopressor therapy
● When intravenous fluid administration fails to restore adequate mean arterial
pressure and organ perfusion.
● Norepinephrine is the first choice for patients who need vasopressors.
Dopamine: alternative to Norad only in selected patients
• Patients with low risk of tachycardia or absolute relative bradycardia

25. Cont (vasopressor therapy)
Phenylephrine:
• Not recommended except:
• NE is a/w serious arrythmias
• Cardiac output is known to be high as BP persistently low
• Salvage therapy when combined inotropes/vasopressor drugs have failed

26. Cont (vasopressor therapy)
Dobutamine:
• Upto 20 mcg/kg/min in presence of:
• Myocardial dysfunction as suggested by elevated cardiac filling pressures and
low cardiac output
• Ongoing signs of hypoperfusion, despite achieving adequate intravascular
volume and adequate MA
•Dobutamine in patients who show evidence of persistent hypoperfusion despite
adequate fluid loading and the use of vasopressor agents

27. Antimicrobial therapy
The initiation of appropriate antimicrobial therapy is one of the most important
facets of effective management of life-threatening infections causing sepsis and
septic shock.
● Should be started within 1hr recognition of sepsis and septic shock
● Empiric broad-spectrum therapy with one or more antimicrobials for patients
presenting with sepsis or septic shock to cover all likely pathogens (including
bacterial and potentially fungal or viral coverage)

28. ● The initial selection of antimicrobial therapy must be broad enough to cover
all likely pathogens.
● The choice of empiric antimicrobial therapy depends on complex issues
related to the
○ Nature of the clinical syndrome/site of infection,
○ Concomitant underlying diseases
○ Presence of immunosuppression or immunocompromised
○ Recent known infection or colonization with specific pathogens
○ Receipt of antimicrobials within the previous three months
○ Patient’s location at the time of infection acquisition (i.e., community, acute care hospital)
○ Local pathogen prevalence
○ Potential drug intolerances and toxicity

29. Source control
● Source control involves measures undertaken to eliminate a focus of
infection, to control ongoing contamination, and to restore premorbid anatomy
and function.
● SSC guidelines recommend that this should take place within the first
12 hours after diagnosis, and the least invasive procedure should be used.
This may include drainage of infected fluid collections, debridement of
infected solid tissue, and removal of devices and foreign bodies including
intravascular access devices or surgery.

30. Steroid therapy
● NOT recommended to treat septic shock if fluids or vasopressors can
maintain MAP (Hemodynamic stability)
● If this is not achievable, Inj. Hydrocortisone 200 mg/day

31. Transfusion of blood products
● Patients with sepsis should receive red cell transfusion when haemoglobin
falls below <7 g/dL.
● Patients with active bleeding, myocardial ischaemia or severe hypoxia are
exceptions and should be transfused at higher haemoglobin thresholds.
● The threshold for transfusion of platelets should be
○ <10×109/L in cases where there is no bleeding risk
○ <20×109/L if there is bleeding risk or the patient is receiving chemotherapy
○ <50×109/L if invasive procedures are planned
● Fresh frozen plasma should not be used to correct documentable
coagulopathy unless there is intercurrent bleeding or invasive procedures

32. Glucose control
● SSC therefore recommends intervention (with an insulin protocol) to maintain
glucose at a cut-off value of 10 mmol/L in sepsis and to avoid
hypoglycaemia and rapid glucose fluctuations.
● Serum glucose should be monitored every 1 to 2 hours until it is stable, and
every 4 hours thereafter

33. Additional care
● In sepsis particular care should be taken to ensure a patient receives:
○ venous thromboembolism (VTE) prophylaxis
○ stress ulcer prophylaxis with a proton pump inhibitor in those with bleeding risk (ie,
coagulopathy, prolonged hypotension, mechanical ventilation)
○ prevention of pressure ulcers

34. Prognosis
● Patients who survive sepsis, regardless of severity, have higher mortality
rates after discharge. One-year mortality rates from severe after hospital
discharge range from 7% to 43%.
● Survivors of sepsis also have an increased incidence of posttraumatic stress
disorder, cognitive dysfunction, physical disability, and persistent pulmonary
dysfunction

35. In Summary
● Rapid recognition and resuscitation of patients with sepsis is key to the
effective management of sepsis.
● The quick Sequential (sepsis-related) Organ Failure Assessment Score
(qSOFA) can be used by clinicians as a bedside tool to identify patients with
infection who may have sepsis. qSOFA is positive if the patient has at least
two of the following clinical criteria:
○ Respiratory rate of 22/min or greater,
○ Altered mentation (Glasgow Coma Scale of <15)
○ Systolic blood pressure of 100 mm Hg or less.

36. ● The clinical diagnosis of sepsis should trigger appropriate management
bundles, such as the Sepsis Six bundle, to be completed within 1 hour of
diagnosing sepsis:
○ Administer oxygen to maintain SpO2 at >94%.
○ Take blood cultures and consider infective source.
○ Administer intravenous antibiotics.
○ Consider intravenous fluid resuscitation.
○ Check serial lactates.
○ Commence hourly urine output measurement.

37. REFERENCES
• Mackowiak PA, Wasserman SS, Levine MM. A critical appraisal of 98.6 degrees F, the upper limit
of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA
1992; 268:1578.
• Antoon JW, Potisek NM, Lohr JA. Pediatric fever of unknown origin. Pediatr Rev. 2015
Sep;36(9):380-90;
• Arnow PM and Flaherty JP. 1997. Fever of unknown origin. Lancet. 350(9077):575-80.
• Feret BM. Fever. In: Krinsky DL, Ferreri SP, Hemstreet B, et al, eds. Handbook of Nonprescription
Drugs. 18th ed. Washington, DC: American Pharmacists Association; 2015.
• Kozier B. Fundamental of Nursing. 7th Ed. Vol.2. Jakarta: EGC; 2008.
• Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for
Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810. doi:10.1001/jama.2016.0287