CONTENTS
- Presenting clinical features
- Paracentesis
- Differentiating spontaneous versus secondary bacterial peritonitis
- Diagnosis of SBP
- Treatment
- Spontaneous bacterial empyema (SBE)
- Podcast
- Questions & discussion
- Pitfalls
presenting signs & symptoms
- SBP is often subtle (for example, 13% of patients are asymptomatic).(19266595)
- Fever or hypothermia.
- Nausea/vomiting, ileus, and/or diarrhea.
- Abdominal pain occurs in about half of patients. However, SBP usually doesn't cause frank peritoneal signs or focal pain (if these are present, then secondary bacterial peritonitis should be suspected 📖).
SBP can cause dysfunction of other organs
- SBP can trigger failure of other organs. In many cases, these other organ failures are more obvious than SBP itself. Consequently, presenting symptoms may center around the failure of other organs:
- Hepatorenal syndrome. 📖
- Hepatic encephalopathy. 📖
- Gastrointestinal hemorrhage or other foci of bleeding may also be the most obvious clinical finding. (SBP itself may lead to a coagulopathy, causing patients with smoldering underlying SBP to present with gastrointestinal hemorrhage).
- Septic shock can occur (although this may be difficult to sort out from the chronic hyperdynamic circulation often seen in cirrhosis).
- SBP can lead to full-blown acute-on-chronic liver failure (ACLF), a condition marked by multiple organ failures. ACLF has many parallels to septic shock and may be grossly conceptualized as a form of inflammation-induced multiorgan failure that occurs in the context of cirrhosis (more on ACLF: 📖).
indications for diagnostic paracentesis among inpatients
- Upon hospital admission: Any patient with cirrhosis and ascites.
- SBP is present in ~10% of patients admitted to the hospital with cirrhotic ascites, so it should be suspected in any cirrhotic patient who is admitted to the hospital even in the absence of symptoms.(29653741)
- This includes admission for GI bleed. (SBP may cause disseminated intravascular coagulation, which may precipitate a GI bleed. So there can actually be a causal relationship between infection and bleeding.)
- After hospital admission: For patients with cirrhosis and ascites who deteriorate in the hospital, with clinical features concerning for SBP, including:
- Fever, hypothermia, and/or septic shock (paracentesis should be included in an infection evaluation).
- Worsening gastrointestinal symptoms (e.g., nausea, emesis, ileus, abdominal pain).
- Worsening hepatorenal syndrome and/or hepatic encephalopathy.
- ⚠️ SBP usually occurs in the context of large-volume ascites which should be easily accessible via paracentesis. If the patient has a small volume of ascites which isn't easily sampled, then high-risk paracentesis is not beneficial. Serial ultrasonography may be performed to determine if the ascites expands over time, at which point paracentesis may be reconsidered.
tips on diagnostic paracentesis in the cirrhotic patient
- There is no need to correct the INR (in cirrhosis, the INR doesn't predict bleeding). 🌊
- Further discussion of pre-procedure hematology considerations for cirrhotic patients: 📖.
- Consider using a very thin lumbar puncture needle (e.g., a 22- or 24-gauge needle).
- Throw away the stylet and simply attach the needle to a 60-ml syringe.
- Using a smaller bore needle decreases the risk of ascites leakage and pain.
- Before needle insertion, look with ultrasonography:
- (a) Confirm that there is a sizable pocket of fluid.
- (b) Measure the thickness of the abdominal wall.
- (c) Use Doppler to exclude the presence of any arteries running through the abdominal wall.
- (You don't necessarily have to use real-time imaging while you insert the needle, especially if the pocket is sizable.)
ascitic fluid labs to obtain
- Cell count & differential.
- Gram stain.
- Bacterial cultures:
- ⚠️ Culture bottles should be inoculated at the bedside (10 ml each into an anaerobic bottle and an aerobic bottle). Bedside inoculation increases the sensitivity of culture to >90%.(33942342)
- Total protein, albumin.
- Glucose.
- Lactate dehydrogenase.
what is the difference between spontaneous bacterial peritonitis vs. secondary bacterial peritonitis?
- Spontaneous bacterial peritonitis involves a single bacterium translocating into the ascites and growing. It is more common and should generally respond to medical therapy.
- Secondary bacterial peritonitis is the presence of perforation or inflammation of an intra-abdominal organ (e.g., cholecystitis) in the presence of ascites. This is much less common than spontaneous bacterial peritonitis. Secondary bacterial peritonitis may often fail to respond to antibiotics alone, so it's essential to recognize this as a separate entity.
Right lower quadrant abdominal ultrasound showing features concerning for secondary bacterial peritonitis: (1) Septations (2) Debris visible within the fluid. This patient had a bowel perforation, not spontaneous bacterial peritonitis.
🚩 red flags for secondary bacterial peritonitis
- 🚩 Frank peritoneal signs on exam or localizing abdominal pain.
- 🚩 Complex, loculated fluid seen on ultrasonography (video above).
- 🚩 Multiple different organisms seen on gram stain or culture.
- 🚩 Failure of medical management for “spontaneous bacterial peritonitis.”
- 🚩 Laboratory criteria: At least two of the following criteria are present in ascitic fluid:(2293571)
- Total protein >1 g/dL.
- Glucose <50 mg/dL (2.8 mM).
- Lactate dehydrogenase above the upper limit of normal for serum (~225 U/ml).
evaluation for suspected secondary bacterial peritonitis
- The key test is a CT scan of the abdomen/pelvis, to exclude any focus of infection requiring source control.
- If biliary pathology is suspected, right upper quadrant ultrasonography may also be helpful.
diagnostic criteria for SBP
- Three criteria are required:
- (1) Chronic underlying cirrhosis.
- (2) Ascites neutrophil count >250/mm3.
- (3) Exclusion of secondary bacterial peritonitis (discussed in the section above).
- Ascitic fluid cultures are often negative, so SBP may be diagnosed without microbiological proof of infection.
monomicrobial non-neutrocytic bacterascites
- This is defined as an ascitic fluid culture positive for a single organism, yet the neutrophil count is <250/mm3.
- Guidelines recommend that patients should not receive antibiotics, since most cases are either due to contamination or may self-resolve over time. Repeat paracentesis should be performed to investigate for progression to SBP.(33942342)
prompt diagnosis is important ⏰
- SBP has the capacity to cause organ failures, with many parallels to septic shock.
- Diagnostic paracentesis should be performed promptly (e.g., <12 hours after admission to the hospital, for patients with cirrhosis and ascites).(34182617)
Spontaneous bacterial peritonitis may push patients into a state of decompensated cirrhosis (marked by hypotension, malperfusion, and hepatorenal syndrome). The following treatments should be implemented promptly, to avoid this.
#1/4: antibiotics
- Coverage is needed for gram-negative bacilli and also for selected gram-positive organisms. Most commonly isolated organisms include Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium.(33942342)
- Empiric antibiotics should be initiated as soon as ascitic fluid demonstrates spontaneous bacterial peritonitis.
- Community-acquired SBP:
- The usual therapy is a third-generation cephalosporin (ceftriaxone 💉 two grams IV daily).
- For patients with septic shock and/or multi-organ failure, broader empiric antibiotic coverage might be reasonable (e.g., piperacillin-tazobactam – noting that ceftriaxone lacks enterococcal coverage).(33942342)
- Nosocomial SBP (or healthcare-associated SBP):
- Broader coverage is appropriate (e.g., piperacillin-tazobactam or a carbapenem).
- Antibiotic selection will vary depending on the hospital's antibiogram and whether the patient has recently been colonized or infected with any drug-resistant organisms.
- Narrowing & weaning antibiotics:
- If ascitic fluid cultures are positive, antibiotics should be narrowed appropriately (SBP is a mono-microbial process, so you only need to cover a single organism).
- The recommended duration of antibiotic therapy is 5-7 days.(33942342)
#2/4: albumin
- Albumin has been proven to reduce the incidence of hepatorenal syndrome and mortality.(10432325) The treatment regimen is 1.5 gram/kg of 20% albumin at the time of diagnosis, followed by 1 gram/kg albumin 48 hours later.
- The seminal RCT that demonstrated the benefit of albumin utilized 20% albumin.(10432325)
- There is some debate regarding whether albumin may be omitted among patients at low risk for hepatorenal syndrome, based on retrospective subgroup analysis. However, omission of albumin hasn't been adequately validated in this subgroup. Furthermore, a meta-analysis concluded that albumin caused improvements, regardless of disease severity.(32533951)
#3/4: evaluate patient's antihypertensives & nephrotoxic medications
- Discontinue beta-blockers, as these may increase the risk of hypotension and hepatorenal syndrome.(24631577) If the blood pressure is robust (MAP >>65 mm) and there is no concern regarding renal dysfunction then beta blockers may be continued (but this situation would be somewhat unusual, since most patients with SBP have borderline hemodynamics).(33942342)
- Consider holding other antihypertensives or vasodilators as well (especially ACE inhibitors or ARBs).
- Discontinue or avoid any nephrotoxins (listed here: 📖).
#4/4: repeat paracentesis after 48 hours
- Guidelines recommend usually repeating a paracentesis after >48 hours.(33942342)
- Paracentesis may be unnecessary if a single organism is isolated from the original paracentesis, the organism is susceptible to the antibiotic therapy, and the patient is improving clinically.(33942342)
- Re-culturing may be useful to exclude the possibility of bacterial resistance.
- (As discussed above, ascitic fluid should be inoculated into blood culture bottles at the bedside.)
- If the neutrophil count doesn't decrease by at least 25%, this carries a substantial likelihood of treatment failure.(29653741)
definitions & terminology
hepatic hydrothorax
- In some patients with cirrhosis, ascitic fluid tracks into the pleural space, leading to a pleural effusion (commonly termed “hepatic hydrothorax”). This may result from tiny holes in the diaphragm and the negative pressure of the thorax, causing ascitic fluid to be drawn into the chest.
- The overall pathophysiology of hepatic hydrothorax is largely identical to that of ascites (e.g., treatment may involve diuretics and TIPS to reduce the portal pressure).
spontaneous bacterial empyema (aka, spontaneous bacterial pleuritis)
- Spontaneous bacterial empyema is a superinfection of hepatic hydrothorax in the absence of pneumonia.
- This may occur in various different ways:(Light 2016)
- Roughly half occur as a primary infection of the pleural space (without concomitant spontaneous bacterial peritonitis).
- Roughly half occur simultaneously with spontaneous bacterial peritonitis (perhaps representing spread of infection from the abdomen into the pleura).
- 💡 Spontaneous bacterial empyema is essentially a thoracic version of spontaneous bacterial peritonitis.
epidemiology & clinical features
epidemiology
- Spontaneous bacterial empyema is reported in ~14% of hospitalized patients with cirrhosis and a significant pleural effusion.(35978675)
clinical features of spontaneous bacterial empyema may include:
- Clinical manifestations are similar to spontaneous bacterial peritonitis. Like SBP, inflammation may be muted in the context of cirrhosis – so symptoms may be unimpressive.
- (1) Localizing symptoms, such as chest discomfort or respiratory failure.
- (2) Systemic manifestations of infection:
- Fever, chills.
- Organ dysfunction (e.g., encephalopathy, hypotension, hepatorenal syndrome).
diagnosis
when is a thoracentesis indicated?
- Precise indications for thoracentesis are unclear.
- Indications to perform thoracentesis might include:
- Clinical suspicion of infection.
- New development of a pleural effusion.
- Rapid enlargement of a pre-existing pleural effusion.
- Therapeutic relief from respiratory failure.
- 💡 Whenever a patient with cirrhosis receives a thoracentesis for any reason, pleural fluid should be analyzed for cell count and microbiology to exclude spontaneous bacterial empyema.
- 💡 If you're thinking about the possibility of SBP, you should also be thinking about the possibility of spontaneous bacterial empyema.
pleural fluid analysis in spontaneous bacterial empyema
- The overall pattern of pleural fluid labs doesn't usually resemble a typical empyema:(Murray 2022)
- Glucose can be normal.
- LDH is usually elevated, but fluid can be transudative.
- pH is occasionally <7.30.
- Pleural fluid culture is positive in most patients (yield may be improved substantially by inoculation of blood culture bottles at the bedside).
diagnostic criteria for spontaneous bacterial empyema:
- Three criteria are required:
- (1) Chronic underlying cirrhosis.
- (2) Pleural effusion with neutrophil count >250/mm3.
- (3) Exclusion of an alternative diagnosis (e.g., underlying pneumonia).
- Any alternative infectious focus must be excluded (e.g., intra-abdominal pathology, or pneumonia). If pleural fluid studies are unusually inflammatory, consider CT scan of the chest, abdomen, and pelvis to exclude a focus of infection (“secondary bacterial empyema”).
- ⚠️ If multiple species are cultured or seen on gram stain, this suggests secondary empyema (e.g., due to bronchopleural fistula or mediastinitis).
- These diagnostic criteria are essentially the same as for spontaneous bacterial peritonitis. Some sources disagree about the neutrophil cutoff to use for spontaneous bacterial empyema (either >250/mm3 versus >500/mm3). The 250/mm3 cutoff is recommended by the most recent AASLD guidelines.(33942342)
treatment
treatment is largely identical to the treatment of SBP
- (1) All of the treatments for SBP described above should be utilized. 📖
- (2) The only difference in treatment is the issue of whether to place a chest tube (discussed below).
chest tube drainage is typically not indicated
- Unlike other empyemas, chest tube drainage is usually not helpful.
- Chest tubes are relatively contraindicated in cirrhosis, due to concerns regarding excessive fluid shifts.
- Indications for tube drainage might include:
- (1) Frankly purulent pleural fluid (but this is uncommon for spontaneous bacterial empyema, and would suggest another type of empyema).
- (2) pH <7.1
- (3) Failure to respond to medical management (e.g., serial thoracentesis showing worsening of pleural fluid chemistries over time).
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- Failure to consider and test for spontaneous bacterial peritonitis among patients admitted to the hospital with cirrhosis and ascites.
- Misdiagnosing a surgical abdominal emergency as spontaneous bacterial peritonitis.
- Failure to take adequate interventions to prevent hepatorenal syndrome (e.g., albumin administration, avoidance of nephrotoxins, and avoidance of beta-blockers).
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References
- 02293571 Akriviadis EA, Runyon BA. Utility of an algorithm in differentiating spontaneous from secondary bacterial peritonitis. Gastroenterology. 1990 Jan;98(1):127-33. doi: 10.1016/0016-5085(90)91300-u [PubMed]
- 10432325 Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999 Aug 5;341(6):403-9. doi: 10.1056/NEJM199908053410603 [PubMed]
- 16048569 Choi CH, Ahn SH, Kim DY, et al. Long-term clinical outcome of large volume paracentesis with intravenous albumin in patients with spontaneous bacterial peritonitis: a randomized prospective study. J Gastroenterol Hepatol. 2005 Aug;20(8):1215-22. doi: 10.1111/j.1440-1746.2005.03861.x [PubMed]
- 19266595 Koulaouzidis A, Bhat S, Saeed AA. Spontaneous bacterial peritonitis. World J Gastroenterol. 2009 Mar 7;15(9):1042-9. doi: 10.3748/wjg.15.1042 [PubMed]
- 24631577 Mandorfer M, Bota S, Schwabl P, et al. Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014 Jun;146(7):1680-90.e1. doi: 10.1053/j.gastro.2014.03.005 [PubMed]
- 29653741 European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69(2):406-460. doi: 10.1016/j.jhep.2018.03.024 [PubMed]
- 30158261 Soin S, Sher N, Saleem N. Spontaneous bacterial empyema: an elusive diagnosis in a patient with cirrhosis. BMJ Case Rep. 2018 Aug 29;2018:bcr2018224810. doi: 10.1136/bcr-2018-224810 [PubMed]
- 32533951 Mattos AA, Wiltgen D, Jotz RF, et al. Spontaneous bacterial peritonitis and extraperitoneal infections in patients with cirrhosis. Ann Hepatol. 2020 Sep-Oct;19(5):451-457. doi: 10.1016/j.aohep.2020.04.010 [PubMed]
- 33942342 Biggins SW, Angeli P, Garcia-Tsao G, Ginès P, Ling SC, Nadim MK, Wong F, Kim WR. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Aug;74(2):1014-1048. doi: 10.1002/hep.31884 [PubMed]
- 34182617 Popoiag RE, Fierbințeanu-Braticevici C. Spontaneous bacterial peritonitis: update on diagnosis and treatment. Rom J Intern Med. 2021 Nov 20;59(4):345-350. doi: 10.2478/rjim-2021-0024 [PubMed]
- 35978675 Reiche W, Deliwala S, Chandan S, Mohan BP, Dhindsa B, Ramai D, Perisetti A, Rangray R, Mukherjee S. Spontaneous bacterial empyema in cirrhosis: A systematic review and meta-analysis. World J Hepatol. 2022 Jun 27;14(6):1258-1268. doi: 10.4254/wjh.v14.i6.1258 [PubMed]