Christopher Amling, MD, FACS
Nick Cowan, MD
BASICS
DESCRIPTION
• Sepsis is the systemic inflammatory response syndrome (SIRS) with associated infection, and urosepsis identifies the source of the infection as originating somewhere in the urinary tract.
• International Sepsis Definitions Conference definitions:
– SIRS: 2 or more of the following:
Temperature >38°C or <36°C
Heart rate >90 beats/min
RR >20 breaths/min or PaCO2 <32 mmHg
WBC >12,000 cells/mL or <4,000 cells/mL or >10% bands
– Sepsis:
SIRS in response to a suspected or proven infection
– Severe sepsis: Sepsis-induced tissue hypo-perfusion or organ dysfunction (any of the following thought to be due to infection):
Sepsis induced hypotension
UOP <0.5 mL/kg/hr for more than 2 hr despite adequate resuscitation
Lactate above upper limits normal
Acute mental status changes
Platelets <100,000 cells/mL
Acute lung injury/ARDS
– Septic shock: Sepsis-induced hypotension despite adequate fluid resuscitation, along with signs of hypoperfusion
• Differentiate SIRS and sepsis
– Noninfectious processes (such as acute pancreatitis) may also be complicated by tissue injury secondary to the inflammatory system.
– SIRS refers to the dysregulated host inflammatory response in the absence of infection.
– It is essential to distinguish an underlying disease (infection or non-infection) and the host response (sepsis or SIRS).
• It is estimated that UTIs account for 5% of severe sepsis cases.
EPIDEMIOLOGY
Incidence
• Sepsis occurs in >1.6 million patients in the United States annually, with an estimated incidence of 240 cases per 100,000 population.
• Patients aged ≥65 yr account for nearly 60% of all episodes of severe sepsis.
Prevalence
N/A
RISK FACTORS
• Advanced age (≥65 yr)
• Diabetes, malignancy, immunosuppression, cachexia, immunodeficiency, alcoholism
• Obstructive uropathy: BPH, prostate cancer, stricture, urolithiasis, neurogenic bladder disorders, retroperitoneal masses and fibrosis, sloughed papilla, endometriosis
• Abnormal/congenital anatomy: ureteropelvic junction obstruction, polycystic kidneys, ureterocele, vesicoureteral reflux, phimosis
• Inflammatory/infectious diseases:
– Pyelonephritis, acute bacterial prostatitis, renal abscess, perinephric abscess, epididymo-orchitis, Fournier gangrene
• Precipitating interventional/nosocomial events resulting in bacteremia and subsequent urosepsis:
– Indwelling catheters, urologic instrumentation/surgery such as prostate biopsy, transurethral surgery
Genetics
Genetic factors are known to be major determinants of susceptibility to death from infectious disease.
PATHOPHYSIOLOGY
• Sepsis is a systemic, deleterious host response to infection leading to severe sepsis and septic shock.
• The most common etiology of urosepsis is secondary to a bacterial infection with Escherichia coli, Proteus sp., Enterobacter and Klebsiella sp., and Pseudomonas aeruginosa
• Obstruction in an infected urinary tract further contributes to the development of sepsis.
• Primary initiator of gram-negative bacteria septic shock is endotoxin, a lipopolysaccharide component of the bacterial cell membrane.
• Exotoxins released by some bacteria can initiate septic shock:
– However, the bacteria themselves and cell wall components are primarily responsible for the development of septic shock.
• The intravascular activation of inflammatory systems results in overproduction of cytokines such as tumor necrosis factor (TNF) and IL-1.
ASSOCIATED CONDITIONS
• Acute pyelonephritis
• Lower UTI
• Urolithiasis
• Urologic procedure/instrumentation
GENERAL PREVENTION
• Urine culture and appropriate antibiotic coverage prior to urologic procedure
• To further reduce incidence of nosocomial UTI: remove Foley as soon as it is no longer needed, use aseptic insertion technique, maintain unobstructed flow, use closed urinary drainage systems (1)[B].
DIAGNOSIS
HISTORY
• A thorough history should be obtained, with emphasis on identifying the primary etiology:
– Classic presentation of fevers, chills, followed by hypotension seen in only ∼30% of patients.
• A history of hydronephrosis, urolithiasis, flank pain, UTIs, immunocompromised status, urinary retention, and recent urologic instrumentation/procedure is common.
• Evaluate for mental status changes.
PHYSICAL EXAM
• Emphasis on identifying the primary source of the infection
• Most common findings: Hyper thermia, hypothermia, tachycardia, tachypnea, and hypotension
• Earliest signs of sepsis may be increased respiratory rate with respiratory alkalosis.
• Examine for all urologic and non-urologic sources of bacteremia:
– Purulent subcutaneous fluid collections; chest exam; costovertebral angle tenderness; abdominal or suprapubic tenderness; examine of the scrotum, testis, perineum; prostatic fluctuance; extremities for tenderness or swelling.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• CBC with differential: Usually shows elevated WBC count with elevated neutrophil count.
– Patients may also have neutropenia
• Basic metabolic panel (BMP), liver finction tests (LFT’s), lactate: May show evidence of end-organ dysfunction
• Blood, urine, and wound culture with a Gram stain for preliminary identification:
– If possible obtain 2 sets of blood cultures before starting empiric antibiotics
– Specific organisms causing sepsis are identified in about half of patients
Imaging
• Obtain based on presumptive initiating event and clinical symptoms
– US can quickly evaluate for hydronephrosis
– CT scan can evaluate for stones, fluid collections and gas within tissues
Diagnostic Procedures/Surgery
Diagnostic procedures should be tailored to identifying the initiating event.
Pathologic Findings
N/A
DIFFERENTIAL DIAGNOSIS
• Upper urinary tract source:
– Emphysematous pyelonephritis
– Pyelonephritis, pyonephrosis
– Renal and perirenal abscess
– Xanthogranulomatous pyelonephritis
• Lower urinary tract source:
– Acute bacterial prostatitis
• External genitalia:
– Epididymitis/orchitis
– Fournier gangrene
– Pyoderma gangrenosum
– Testicular abscess
• Common non-urologic causes of sepsis:
– Central lines
– Empyema, pneumonia
– Endocarditis, mediastinitis
– Prosthetic device infection
– Intra-abdominal processes: Pancreatic infection, cholecystitis, cholangitis, peritonitis, diverticular/appendiceal/tubo-ovarian abscess
– Septic arthritis
– Soft-tissue infection
• Noninfectious conditions that mimic sepsis:
– Acute adrenal insufficiency
– GI bleed
– Myocardial infarction
– Pancreatitis
– Pulmonary embolus
– Transfusion reactions
TREATMENT
GENERAL MEASURES
• Early goal-directed therapy, “Rivers protocol”:
– Goal MAP ≥65 mmHg, CVP 8–12 mmHg, UOP ≥0.5 mL/kg/hr
– Start empiric IV antibiotics (ABX) within 1 hr. of recognition of severe sepsis or septic shock
– Volume expansion with isotonic fluids
– Supplemental oxygen with or without intubation and assisted ventilation if indicated
– Vasoactive drugs to achieve hemodynamic goals (norepinephrine preferred to dopamine)
– Maintain glycemic control
Keep glucose <180 mg/dL as intensive glycemic control (80–110 mg/dL) has shown either no change or increased mortality, and increased rates of hypoglycemia (2)[A]
ALERT
Autopsy studies in persons who died in the ICU show that the failure to diagnose and treat infections with antibiotics or surgical drainage is the most common avoidable error.
MEDICATION
First Line (3)
• Broad-spectrum antibiotic coverage (against both gram-positive and gram-negative bacteria) should be instituted immediately.
• Nosocomial urosepsis monotherapy:
– Piperacillin/tazobactam, imipenem, or meropenem
– Add vancomycin if MRSA a concern
• Monotherapy for urosepsis due to aerobic gram-negative bacilli:
– Aztreonam: 2 g IV q6–8h; max 8 g/d
– Levofloxacin: 500 mg IV q24h
– 3rd-generation cephalosporins:
Ceftriaxone: 1–2 g IV q12–24h
Cefotaxime: 2 g IV q6–8h
Ceftazidime: 500 mg IV q8–12h
– 4th-generation cephalosporin:
Cefepime: 2 g IV q12h
• Monotherapy for suspected enterococci (E. faecalis) urosepsis: Ampicillin or vancomycin (penicillin-allergic).
• Community-acquired urosepsis infection:
– Levofloxacin, aztreonam, or an aminoglycoside plus ampicillin
• Fournier gangrene:
– Piperacillin/tazobactam 3.375 IV q6h, add vancomycin 1 g IV q12h if MRSA suspected
– Imipenem: 500–1,000 mg IV q6h for polymicrobial coverage.
– Clindamycin: 600–900mg IV q8hr for anaerobic coverage if Clostridia are suspected (to block toxin production)
Second Line
• Reassess antimicrobial regimen daily and deescalate when sensitivity results are available.
• Switch to PO ABX when clinically stable for at least 48 hr and usually complete a 7–10 day course based on the cause of the infection.
SURGERY/OTHER PROCEDURES
• Patients should undergo surgical drainage of purulent collections, debridement of necrotic tissue, and relief of urinary tract obstruction.
• Retrograde ureteral catheterization and percutaneous nephrostomy effectively relieve obstruction and infection due to ureteral calculi
– Neither modality has demonstrated superiority in promoting a more rapid recovery
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Definitive correction of any correctible factors when patient stabilized
• Corticosteroid use in sepsis is complex and current data do not show improved survival in severe sepsis
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Mortality rates associated with severe sepsis and septic shock are 25–30% and 40–70%, respectively.
• Factors associated with a higher risk of mortality from sepsis: Fever, WBC count, serum creatinine, diabetes mellitus, lactate, and albumin.
ALERT
Mortality rate decreased by 42% when early goal-directed therapy achieved within the first six hours for severe sepsis and septic shock.
COMPLICATIONS
Renal insufficiency, hepatic dysfunction, end organ failure, cardiac events, death
FOLLOW-UP
Patient Monitoring
• Patient should be continued on appropriate ABX coverage for 7–10 days, longer if needed.
• Repeat cultures can be obtained to ensure treatment is adequate.
Patient Resources
International Sepsis Forum: Understanding Sepsis. http://internationalsepsisforum.com/sepsis-booklet
REFERENCES
1. Russell J. Management of sepsis. N Engl J Med. 2006;355(16):1699–1713.
2. Dellinger R, Levy MM, Rhodes A, et al. ; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580.
3. Grabe M, Bjerklund-Johansen TE, Botto H. Guidelines on Urological Infections. Arnhem, The Netherlands: European Association of Urology (EAU); 2011:33–39.
ADDITIONAL READING
• Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet. 2005;365:63.
• Bugano DD, Camargo LF, Bastos JF, et al. Antibiotic management of sepsis: Current concepts. Expert Opin Pharmacother. 2008;9(16):2817–2288.
• Hotchkiss R, Karl I. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138–150.
• Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377.
• Wagenlehner FM, Weidner W, Naber KG, et al. Optimal management of urosepsis from the urological perspective. Int J Antimicrob Agents. 2007;30(5):390–397.
See Also (Topic, Algorithm, Media)
• Epididymitis
• Fournier Gangrene
• Prostatitis, Acute, Bacterial (NIH I)
• Pyelonephritis, Acute
• Pyelonephritis, Emphysematous
• Pyelonephritis, Xanthogranulomatous
• Renal and Perirenal Abscess
CODES
ICD9
• 599.0 Urinary tract infection, site not specified
• 785.52 Septic shock
• 995.92 Severe sepsis
ICD10
• N39.0 Urinary tract infection, site not specified
• R65.20 Severe sepsis without septic shock
• R65.21 Severe sepsis with septic shock
CLINICAL/SURGICAL PEARLS
• Early goal-directed therapy guided by invasive monitoring (mean arterial pressure [MAP], central venous pressure [CVP] and urine output [UOP]) within the first 6 hours after recognition or sepsis.
• Blood culture x2 prior to antibiotics if possible.
• Start empiric ABX within 1 hour of recognition of severe sepsis or shock.
• Initial fluid resuscitation with crystalloid.