Thread by @dolan_russell

1: What causes WBC/PMN elevation (neutrophilic-predominant pleocytic) ascites? The differential is broad and extends beyond Spontaneous Bacterial Peritonitis (SBP).

(A #MedTwitter and #Tweetorials contribution). Appreciate edits by @ebtapper.

2: 26yoW w/ cirrhosis 2/2 congestive hepatopathy 2/2 hypoplastic L heart syndrome s/p Fontan presented to OSH with fevers, abdominal pain. Prev tx by PCP for ?PID w/ IM CTX, doxycycline. Dx para shows WBC 2480, PMN 74%, total protein 4.3, SAAG >1.1. What is cause of ascites here?

3. Portal Hypertension (PH) due to liver dz causes albumin- and protein-poor ascites. This is due to sinusoidal scarring causing reduced albumin and protein translocation into ascites [Serum-Ascites Albumin Gradient (SAAG) >1.1]. But this case is not due to cirrhosis...

4. In CARDIAC ascites, total protein (TP) continues to traverse hepatic sinusoids, therefore the TP is >2.5g/dL, as in our pt.

Looking again at our para studies (WBC 2480, PMN 74%, total protein 4.3, SAAG >1.1), what is the diagnosis?

Culture-Negative Neutrocytic Ascites = CNNA

5. This patient was diagnosed with SBP and treatment initiated.

By the way, which of the following systems fail in cirrhosis, increasing susceptibility to SBP?

Macrophage = MØ

6. All contribute to SBP pathogenesis: increased portal hypertension (PH) ➡️ microthombotic hepatocyte ischemia ➡️ increased bacterial translocation ➡️ failed innate host defenses (ascitic MØ, complement) ➡️ recruitment of PMN’s to ascites ➡️ PMN function impaired in cirrhosis

7. Gut barrier function decline as consequence of increased PH causing hepatocyte ischemia through microthrombus development is supported by Villa et al (Gastro 2012), where enoxaparin appeared to actually DECREASE translocation (and therefore SBP):

gastrojournal.org/article/S0016-…

8. Cirrhosis is a long-known common cause of acquired immune deficiency. A few reasons:
- Serum complement levels become deficient
- Ascites is 5 to 10-fold more dilute than serum = reduced complement/opsonization
- PMN/Kupffer cell functional impairment
gastrojournal.org/article/0016-5…

9. In fact, total protein (TP) >1.5g/dL substantially reduces risk of developing SBP as increased ascitic protein is correlated with increased complement activation and opsonization. As shown previously, TP >2.5g/dL (SAAG <1.1) is associated with cardiac ascites.

10: Our case: for dx of SBP, started on Zosyn x2 days before transition to Augmentin/doxycycline for discharge. Ascites cultures from admission were negative. Following successful treatment, does she warrant SBP antibacterial prophylaxis?

11: Indications for SBP abx ppx:
- Cirrhosis with GI bleeding
- Recurrent SBP

Standard abx for ppx include the following:
- ciprofloxacin 500mg qdaily
- norfloxacin 400mg qdaily
- Bactrim DS qdaily

Note ➡️ important to consider tendon rupture risk w/ FQ's in this young adult.

12: Pt returns 3 days later with progression of fevers, abdominal pain. Repeat dx para: WBC 2616, PMN 71%, protein 4.6, SAAG >1.1, RBC 12,000, glucose 67, LDH 47. For diagnosis of recurrent SBP, she was initiated on CTX and doxycycline. At this point, what would be next step(s)?

13: This fluid is NOT consistent with secondary BP. There is c/f secondary BP when Protein >1, Glucose <50, LDH > serum LDH ULN (sens 67%, spec 89%). Etiologies of secondary BP include cholecystitis, carcinomatosis, etc. Great review can be found here: sciencedirect.com/science/articl…

14: Albumin was given at 1.5 g/Kg day 1, 1g/Kg day 3 for concern for recurrent SBP with goal to repeat para on day 3. Why is albumin given to cirrhotics in setting of SBP?

HRS = hepatorenal syndrome

15: Albumin is typically provided in attempt to prevent AKI and worse, specifically HRS (as well as reduce large-volume fluid shifts). A mortality reduction from 29% to 10% was shown when given IV albumin in addition to abx in setting of cirrhosis w/ SBP.
nejm.org/doi/pdf/10.105…

16: Indications for albumin include:
- Cr>1.0, BUN>30, or T bili>4.0
- Recurrent SBP given increased risk for renal failure

17: Cultures from our patient’s most recent dx para were negative. How often are ascites cx’s positive in setting of SBP?

The short answer is culture positivity varies widely, but yield increases when immediate bedside inoculation occurs.

ncbi.nlm.nih.gov/pmc/articles/P…

18: Repeat para on day 3: protein 4.8, SAAG >1.1, RBC 4,000, Leukocytes 2420, Neutrophils 82%. Bedside cx again negative. Pt switched to Zosyn and diagnosis refined to Culture Negative Neutrocytic Ascites (CNNA) due to recurrent neutrophilic pleocytosis w/ neg cultures.

19: If SBP and secondary BP are ruled out, which of the following can cause CNNA?

20: All of the above can cause neutrophil elevation in ascitic fluid and should be considered in a differential, particularly when bacterial etiology is ruled out. Beyond ascitic fluid evaluation, peritoneal bx can be pursued to improve yield for TB, malignancy.

21: Following second dx para and no improvement on Zosyn, pt requested discharge. Ppx abx were held given impression for non-bacterial etiology. She subsequently initiated cardiac and liver transplant evaluations. Etiology of CNNA remains unknown.

22. In summary, this 26yoW presented with signs/symptoms and initial ascitic fluid studies c/w SBP and subsequently found to have CNNA of unknown cause. The ddx for neutrophilic pleocytic ascites extends well-beyond SBP.

23. Some learning points:
1/ SBP diagnosis: ascitic WBC >500, PMN >250
2/ Consider repeat dx para on day 3 if sx’s persist (fever, abd pain)
3/ Rule out secondary BP w/ Protein >1, Glucose <50, LDH > serum LDH ULN
4/ Ascitic fluid cx yield improves w/ bedside inoculation

@CPSolvers ➡️ can add SBP to outstanding Abdominal Pain schemas, which I highly encourage all to review:
clinicalproblemsolving.com/wp-content/upl…
clinicalproblemsolving.com/wp-content/upl…

Thanks for reading! #FOAMed #MedEd

Upmost respect for @tony_breu for his rate of #Tweetorial development!