• Information
  1. Introduction
  2. Clinical Features
  3. Pathophysiology
  4. Laboratory and Definitions
  5. Differential Diagnosis
  6. Treatment
  7. Prophylaxis
  8. Epidemiology
  9. Symptoms
  10. Treatment

A. Introduction [1]

1. Common and severe complication of patients with cirrhosis and ascites
2. Ascites becomes spontaneously infected
3. Very low concentration of bacteria found in ascites fluid
4. Likely occurs from passage of bacteria from intestinal lumen to blood stream
   1. From blood stream, bacteria pass into ascites
   2. Most SBP occurs in setting of low protein concentration (<1gm/dL)
   3. Inability to locally opsonize bacteria
   4. Impaired immune responses in ill patients likely contribute
5. Characteristics of patients with SBP similar to those with sepsis (see below)

B. Clinical Features

1. Symptoms of neutrocytic ascites
   1. Acute onset of increased abdominal girth and pain
   2. Fever is also common
2. ~25% of patients present without any symptoms
   1. Often non-neutrocytic, bacterial ascites
   2. High risk for progression
3. 10-20% prevalance among inpatients with cirrhotic ascites

C. Pathophysiology

1. Bacteria traverse intestinal lumen and enter blood stream
   1. Very high endotoxin levels are found in bloodstream of SBP patients
   2. Impaired immunity likely aides escape of bacteria from intestine
   3. Increased portal pressures likely drives process
2. Bacteria enter ascites fluid in low concentrations
3. However, marked inflammatory response occurs (likely due to peritoneal inflammation)
   1. Levels of tumor necrosis factor alpha (TNFa) and interleukin 6 (IL6) are very high
   2. These high levels are found in both blood and ascites
4. High circulating endotoxin, IL6, and TNFa levels cause endothelial activation / dysfunction
   1. Endothelial nitric oxide synthetase (iNOS) is induced
   2. Nitric oxide, a very potent vasodilator, is released
5. Effect is arterial vasodilation and effective reduction in vascular volume
   1. Cardiac output increases in compensatory fashion
   2. Sympathetic nervous system is activated
   3. Arginine vasopressin (ADH) is released from hypothalamus/pituitary
   4. Endothelin is released by endothelium
   5. These physiologic responses are found in sepsis syndrome as well as SBP
6. Renal perfusion pressure is reduced and kidney senses this
   1. Kidney releases renin and prostaglandins
   2. Effect is increase in angiotensin I (AT-1), AT-II, and aldosterone
   3. Increased AT-II increase renal efferent arteriolar vasoconstriction to maintain renal perfusion pressure
   4. Prostaglandins are released by kidney to maintain afferent arteriolar vasodilation
   5. However, reduced blood volume, increased endothelin and vasopressin, and sympathetic nervous system activation leads to renal afferent arteriolar vasoconstriction
   6. Result is that renal failure occurs in ~30% of patients with SBP

D. Laboratory and Definitions

1. Ascites Cell Counts
   1. Most experts require >250 PMNs/µL with postive cultures for diagnosis of SBP
   2. If cultures negative, then >500 PMN/µL - usually treat as SBP (Neutrocytic ascites)
   3. Nonneutrocytic bacteriascites with culture positive and <250 PMN/µL occasionally seen
2. Ascites Cultures
   1. Culture by 10 ml. of ascitic fluid directly into blood Culture bottle
   2. Overall, 80-90% of persons with neutrocytic ascites will be Culture +
   3. Culture negative neutrocytic ascites must be treated as well (33% will progress)
3. Organisms
   1. Gram - enteric rods are major cause (>50%)
   2. Escherichia coli - 40-50% of culture positive cases
   3. Streptococcus fecaelis and faeceum (Enterococcus) - ~30%
   4. Klebsiella pneumoniae - ~10%
   5. Other GNRs - 8%
4. Usually monobacterial
   1. Rarely anaerobes; never fungi
   2. Presence of >1 organism is atypical and should prompt further evaluation
   3. This evaluation should include tests for performation, contamination, etc.
5. Blood cultures typically negative
6. Peripheral WBC rarely >10K/µL (if so, suggests secondary infection)

E. Differential Diagnosis

1. If >1 organism cultured, consider secondary bacterial peritonitis
   1. Direct invasion (eg. fistula)
   2. Gut perforation
   3. Abscess
   4. ~15% of patients with cirrhotic ascities and peritonitis have secondary source
2. Secondary versus Primary Peritonitis
   1. If high titer of organisms, consider primary peritonitis
   2. Multiple organisms strongly suggest secondary source
   3. Other factors suggest secondary: glucose <50mg/dL, Protein >1gm/dL, LDH > Serum
   4. WBC > 10,000 /µL usually associated with secondary peritonitis
   5. Secondary peritonitis usually requires surgical correction (high mortality)

F. Treatment [2]

1. Treatment of ascites greatly decreases risk of SBP development
2. Mainstay is broad antibiotic therapy with albumin infusions following paracentesis [3]
3. Empiric Antibiotic Therapy
   1. Should cover GNR and gram positive cocci
   2. Cefotaxime (3RD generation cephalosporin) 2gm q6-8° recommended in most cases
   3. This does not cover enterococci well, but appears effective, at least initially
   4. 5 day course appears as effective as 10 day course
   5. Consider: Ampicillin/sulbactam, ticarcillin/clavulanate, or piperacillin/tazobactam
   6. Norfloxacin 400mg po bid reduces endotoxin levels in cirrhotic patients [4]
   7. Antibiotic choice should be tailored to ascites' and blood culture results
4. Paracentesis must be performed [3]
   1. Initial paracentesis is for diagnostic use only and large volumes should not be removed
   2. Large volume paracentesis for therapeutic purposes is delayed until infection resolves
   3. Large volume paracentesis performed during active infection can precipitate hemodynamic compromise and death
   4. Without albumin infusions, ~30% of patients with SBP will develop renal failure
   5. Albumin infusions strongly recommended to reduce renal dysfunction and death
   6. Albumin dose is IV 1.5gm/kg initially and 1gm/kg on day 3 following paracentesis
5. Maintain Good nutritional status
6. Avoid all nephrotoxic medications
   1. Particularly aminoglycoside antibiotics
   2. NSAIDs and ACE inhibitors are relatively contraindicated
   3. High risk for development of hepatorenal syndrome
7. Repeat diagnostic paracentesis
   1. Should typically be carried out 48-72 hours after initiation of therapy
   2. Neutrophil counts and bacterial counts should decrease
   3. Bacteria should not grow from treated ascites fluid
8. Hepatorenal Syndrome (HRS) [5]
   1. Patients with SBP at increased risk for HRS
   2. Intranveous (IV) albumin infusions reduce HRS development
   3. Albumin is given 1.5gm/kg at diagnosis and 1gm/kg 48 hours later IV

G. Prophylaxis

1. Treatment of ascites
   1. Spironolactone (up to 450mg/d) + low dose furosemide often very effective
   2. Opsonin concentration increased by decreasing ascites and mainting nutrition
   3. Acutely, high volume paracentesis may be done with albumin replacement
2. Bowel decontamination with norfloxacin (Norflox®) 400mg/day
   1. Prevents recurrence of SBPs by ~70%
   2. No apparent effect on mortality or number / duration of hospitalizations
   3. Higher doses reduce endotoxin levels in cirrhotics without clear SBP [4]
3. TMP/SFX (Bactrim®) Prophylaxis [6]
   1. 1 double strength pill 5 days/week decreased risk of bacterial peritonitis by >80%
   2. Overall infection risk was decreased by 90%
   3. Death rate decreased from 20% to 7% with prophylaxis but was not significant
   4. The drug was extremely well tolerated with no dropouts
4. Overall Prognosis
   1. Probability of recurrance is >40% at 6 months, ~70% at 1 year, 75% at 2 years
   2. 1 year survival rate after first SBP episode is ~40%

1. About 9/1000 emergency hospital admissions in USA
2. Also develops in ~15% of patients undergoing elective abdominal surgery
3. Intestinal perforation is most common cause
4. Mortality ranges from 20% to 60% depending on population
5. Long hospital stays and relaparatomy often required
6. Typically due to mixed enteric flora, espeically gram negative enteric rods, anaerobes

B. Symptoms

1. Fever
2. Abomdinal Pain
3. Rigors
4. Hypotension progressing to shock
5. Multiorgan dysfunction, particularly renal failure

C. Treatment

1. Aggressive intravenous antibiotics with full spectrum coverage
2. Initial emergency laparatomy in all patients
   1. Repair underlying defect (usually perforation)
   2. Identify, irrigate and drain an abscesses
3. Relaparatomy electively is as safe and utilizes less resources than definite relaparatomy [7]

References

1. Bhuva M, Ganger D, Jensen D. 1994. Am J Med. 97(2):169
2. Runyon BA. 1994. NEJM. 330(5):337
3. Sort P, Navasa M, Arroyo V, et al. 1999. NEJM. 341(6):403
4. Chin-Dusting JP, Rasaratnam B, Jennings GLR, Dudly FJ. 1997. Ann Intern Med. 127(11):985
5. Gines P, Guevara M, Arroyo V, Rodes J. 2003. Lancet. 362(9398):1819
6. Singh N, Gayowski T, Yu VL, Wagener MM. 1995. Ann Intern Med. 122(8):595
7. Van Ruler O, Mahler CW, Boer KR, et al. 2007. JAMA. 298(8):865