approach to urosepsis/sepsis/septic shock. general approach to sepsis, severe sepsis, septic shock according to the latest guidelines. SCG2016/ EGDT2018/EUA2020

1. UROSEPSIS
Sushil Gyawali
MS resident
Urosurgery
IOM

2. Introduction
• Urosepsis is sepsis caused by an infection of the urinary tract
(UTI)
• Sepsis is the body’s inflammatory response to an infection that
can lead to multi-organ dysfunction, failure, and even death.

3. New definition of Sepsis
A life-threatening organ dysfunction caused by a dysregulated host
response to infection.
Singer M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA. 2016
qSOFA: quick 'Sequential (Sepsis
Related) Organ Failure Assessment'
score ≥2: mortality ≥10%
“systemic inflammatory response” ↔
“dysregulated host response
SIRS ↔ SOFA

4. mortality

5. Septic Shock
•“sepsis-induced hypotension persisting despite
adequate fluid resuscitation.”
1.Persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg
2.Blood lactate >2 mmol/L despite adequate volume resuscitation
•Underlying circulatory and cellular/metabolic abnormalities are profound enough to
substantially increase mortality.

6. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016

7. mc presentation in infants
and children
late, decompensated
early, compensated

9. Identifying Acute Organ Dysfunction as a
Marker of MODS
• Organ dysfunction: as an
acute alteration of SOFA
score by at least two
points higher than at the
onset of the infection

10. Urosepsis
• Urosepsis is defined as life threatening organ dysfunction caused by a
dysregulated host response to infection originating from the urinary
tract and/or male genital organs. (EUA 2020)
• These infections include both upper and lower urinary tracts.
• Systemic response to and potentially life-threatening sequelae of
urogenital tract infection.
• Classified as community acquired or hospital acquired,

11. Epidemiology
• Nearly 25% of sepsis cases originate from the urogenital tract.
• Estimated mortality rate from urosepsis is 30% to 40%.
• Among pts of noscomial UTI aquired in urology wards,
prevalence of Urosepsis is 12%. (Dtsch Arztebl Int 2015)

12. Etiology
The most common pathogen causing UTIs (and in turn urosepsis)
• Escherichia coli (50%)
• Proteus (15%),
• Enterobacter (15%),
• Klebsiella (15%),
• Pseudomonas aeruginosa (5%),
• and gram-positive bacteria (15%).
Dreger, Nici Markus et al. “Urosepsis--Etiology, Diagnosis, and Treatment.”(2015)

13. Risk factors for urosepsis
• Age (≥ 65 years): UTI
• Diabetes mellitus
• Immune suppression (organ transplantation, chemotherapy,
corticosteroid treatment, AIDS)
• Nosocomial UTI
• Local factors, such as urinary tract calculi, obstruction at any level in
the urinary tract, congenital uropathy, neurogenic bladder disorders, or
endoscopic manoeuvres
• Prior urological interventions

14. • Certain urologic conditions, specifically the obstruction of urinary flow
secondary to urolithiasis or BPH, can result in the rapid development of
urosepsis.
Bidnur S et al (2019) Urosepsis: Pathogenesis and Treatment. The Role of Bacteria in Urology. Springer

15. Pathophysiology
• Ascending infection: begins with
colonization of the urethral meatus or
vaginal introitus by either uropathogens or
fecal flora that ascends via the urethra to
the bladder up to kidney, causing
pyelonephritis.
• Lymphatics: Pyelonephritis also can be
caused by bacterial seeding of the kidneys
via the lymphatics.
• Hematogenous: the kidney is
occasionally secondarily infected in
patients with Staphylococcus aureus
bacteremia originating from oral sites or
with Candida fungemia.

16. • initial activation complement cascade, leading to a massive
initial pro-inflammatory response.
• Secondary mediators amplify : severe proinflammatory burst.
• anti-inflammatory response that leads to
immunosuppression :neutrophils become dysfunctional and
cause further damage to nearby cells.
• Increased severity - organ dysfunction : ARDS, AKI, and DIC

17. Evaluation
• The diagnosis of urosepsis requires both suspicion of sepsis as
well as evidence of a UTI
• SIRS signs and symptoms are indicators of sepsis but are no
longer required for the formal diagnosis.

18. History and Examination
• fever, dysuria, flank pain
• frequency,urgency,suprapubic pain
• malaise, hematuria, turbid urine
• Decreased output
• urinary retention, catheterization
• pertaining to risk factors/complicated UTI
• associated symptoms/signs

19. Clinical Examination
• full physical exam to identify the source of the infection.
(cystitis/ pyelonephritis/ perinephric abscess)
• costovertebral angle tenderness
• in men, scrotal pain or fluctuance or tenderness on the DRE
(suggesting prostatitis or abscess).

20. • Investigations: blood, urinalysis, blood and urine culture, r/o
other infective foci
• Radiological imaging: Ultrasound (calculi, hydronephrosis,
pyonephrosis, perirenal abscess, Scrotal abscess) , CXR, Xray
KUB, CT scan (diagnostic/therapeutic drainage)
• Additional workup: CRP, procalcitonin, ABG

21. Evidence of organ dysfunction
• hypotension,
• oliguria, or
• ileus and
• leukocytosis or
leukopenia,
hyperbilirubinemia,
• hyperlactatemia,
• hyperglycemia,
• coagulation
abnormalities, and
elevated CRP and
procalcitonin

22. Treatment
• Early diagnosis, early initiation of treatment such as
identification and control of the complicating factor in the
urinary tract and the specific sepsis therapy.
1. Resuscitation
2. Antimicrobial agents
3. Source control: drainage or elimination of infection
4. Adjunctive: supportive care and monitoring
ICU
admission

23. • A lot of research aimed at reducing mortality from sepsis via
aggressive treatment modalities, including the original Rivers
trial, has shown that early goal-directed therapy (EGDT) 2018
reduces mortality from sepsis. (by 15%)

24. Resuscitation
• Resuscitation : ABC
• Tissue perfusion: crystalloid and or colloid/blood
products,vasopressors
• Optimization of oxygen delivery
• Correction of coagulopathies
• Maintenance of blood glucose levels below 110 mg/dL with
intensive insulin therapy

25. Surviving sepsis guideline (2016/2018 update)
Resuscitation: ABC
•Fluid therapy: 30 mL/kg of IV crystalloid fluid be given within the
first 3 hours, (for hypotension or lactate>4)
•additional fluid after reassessment (Urine output, HR, BP, SaO2)
Vasopressors: norepinephrine primarily; dobutamine in myocardial
dysfunction; low dose dopamine as renal protector (MAP>65)
Hydrocortisone: should be given only if fluid and vasopressors do not
achieve MAP> 65 mmHg

26. • Add albumin, if crystalloids are not adequately increasing
blood pressure
• Normalise lactate
If initial lactate is elevated (> 2mmol/L), it should be remeasured
within 2−4 h to guide resuscitation to normalize lactate in
patients with elevated lactate levels as a marker of tissue
hypoperfusion

27. EGDT 2018
Goals:
CVP>8mmHg
MAP>65mmHg
ScVO2> 70%
If goals achieve:
observe every 30mins
for 6 hours

28. • Identification of the presumptive source of infection and
cultures (blood/urine/sputum) before the initiation of
antimicrobial therapy.
• At least 2 set of blood cultures (anaerobic and aerobic)

29. Antimicrobial
• Initial empiric antimicrobial therapy : broad spectrum
• Later as per culture report
• The dosage generally be high, with appropriate adjustment for
renal function .
• Surviving sepsis campaign suggests the initiation of broad-
spectrum antibiotics as soon as possible after recogniton and
within one hour for both sepsis and septic shock

30. • A broad-spectrum antimicrobial either alone or in combination with an
aminoglycoside (in case of septic shock) should be administered
• If the infection is hospital acquired, or has multiple infections or
immunocompromised or severely ill, : Aminoglycoside and anti-
Pseudomonas β-lactam or a third-generation cephalosporin

31. EUA
2020

32. • Duration of 7 to 10 days
• Until afebrile for 3 to 4 days and is clinically stable.
• Longer courses :if slow clinical response, undrainable foci of
infection
• Measurement of procalcitonin levels can be used to support
shortening the duration of antimicrobial therapy

33. Procalcitonin
PCT can be a better
biomarker in detecting
bacterial sepsis at initial
stages.
Act as a tool for antibiotic
therapy
Vijayan, Ashitha L et al. “Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy.” Journal of
intensive care ( 2017)

34. Source control
• Obstruction in the urinary tract is the most frequent urological
source of urosepsis.
• Drainage of obstruction and abscesses, and removal of foreign
bodies, such as urinary catheters or stones is therefore the
most important source control strategy.
• Eg: PCN, Pigtail drainage of abscess, SPC, Foleys Catheterization,
control of other non urological sources

36. Adjunctive therapy
• Fluid therapy maintenance with crystalloids
 passive leg raising-induced changes in cardiac output and in arterial
pulse pressure are predictors of fluid responsiveness in adults
• Blood products Packed red cells/WB: haemoglobin level of 7-9 g/dL
FFP , PRP when needed (keep >50000/mm3)
• Mechanical ventilation should be applied with a tidal volume 6 mL/kg
and plateau pressure < 30 cm H2O and a high positive end-expiratory
pressure;
SCCM 2016

37. • Sedation : given minimally, neuromuscular blocking agents should be
avoided; continuous or intermittent sedation be minimized in
mechanically ventilated sepsis patient
• Glucose levels : target at < 180 mg/dL
• DVT prevention : LMWH subcutaneously;
• Stress ulcer prophylaxis should be applied in patients at risk, using
PPI/H2 blockers ;if risk of GI bleeding
• Enteral nutrition should be started early (< 48 hours).

39. Kurt Naber et al. Urosepsis: Overview of the Diagnostic and Treatment Challenges 2015

40. Renal Replacement therapy (SCG 2016)
• Suggest either continuous or intermittent renal replacement
therapy (RRT) be used in patients with sepsis and acute kidney
injury
• But suggest against the use of RRT in patients with sepsis and
acute kidney injury for increase in creatinine or oliguria
without other definitive indications for dialysis

41. (EUA 2020)
• Nosocomial urosepsis may be reduced by measures used to
prevent nosocomial infection,
e.g. reduction of hospital stay,
early removal of indwelling urinary catheters,
avoidance of unnecessary urethral catheterisation,
correct use of closed catheter systems, and
attention to simple daily aseptic techniques to avoid cross-
infection.

42. • Multidisciplinary : that include a nephrologist, infectious
disease expert, urologist, intensivist, microbiologist, a nurse
and a pharmacist.
• The key to preventing high morbidity is to prevent the
condition that promotes infection.

43. Outcomes
• Depend on the cause and severity of the infection.
• Prognosis depends on the type of bacteria, antimicrobial
resistance, and patient comorbidity.
• If left untreated, the condition has a very high mortality. Even
those who survive have a prolonged recovery period.
• Residual disturbance in renal function is not uncommon.

44. Preventive measures (EUA 2020)
• Isolation of patients with multi-resistant organisms
• Prudent use of antimicrobial agents for prophylaxis and treatment of
established infections, to avoid selection of resistant strains
• Reduction in hospital stay
• Early removal of indwelling urethral catheters
• Use of least-invasive methods to release urinary tract obstruction until the
patient is stabilised.
• Attention to simple everyday techniques to assure asepsis, including the
routine use of protective disposable gloves, frequent hand disinfection, and
using infectious disease control measures to prevent cross-infections.

45. Conclusion
• Early recognition of symptoms followed by appropriate investigations,
accurate diagnosis and early goal directed therapy is essential to
improve outcomes
• Comprehensive management requires team approach with timely
inputs from microbiologists, radiologists, surgeons and intensive care
physicians
• ‘Surviving Sepsis Guidelines’, aims to reduce mortality by 25% in the
next years
• The surviving sepsis campaign and early goal-directed therapy have
been shown to improve outcomes in critically ill patients

46. References
• Surviving Sepsis Campaign Guidelines (2016/2018 update)
• EUA Guidelines (2020)
• EGDT 2018 guideline
• Campbell and Walsh Textbook of Urology,12e, 2020
• Wagenlehner FM et al. An update on classification and
management of urosepsis. Curr Opin Urol ( 2017)

47. THANK YOU

48. SSC 2018 revision of the SSC bundles is that the 3-h and 6-h bundles have been combined
into a single “hour-1 bundle” with the explicit intention of beginning resuscitation and
management immediately.

49. Covid 19 and Urology
• urinary symptom is not a clinical manifestation of COVID-19.
• Acute kidney injury could occur in COVID-19 patients, and its occurrence
was associated with high mortality rate.
• As viral RNA positivity was detected in both urine and stool samples,
precautions are needed when urologists perform transurethral or
transrectal procedures.
• Special considerations in managing specific urological conditions are
also needed in the pandemic of COVID-19.
Chan, Vinson Wai-Shun et al. “A systematic review on COVID-19: urological manifestations, viral RNA detection
and special considerations in urological conditions.” World journal of urology, 1–12. 27 May. 2020,
doi:10.1007/s00345-020-03246-4