SBP2022

Kingsway Education Group (KEG) Clinically Useful Papers (CUP) April 2022 Background: the importance of early recognition -

A patient with SBP is walking around with a belly full of pus (no bueno) SBP almost always occurs in patients with cirrhosis + ascites Renal failure develops in 30-40% of SBP patients and is a major cause of death = hepatorenal syndrome Like sepsis, SBP is a time-sensitive presentation needing prompt diagnosis and treatment Inpatient mortality ranges from 20-40%1,2 (about 2x mortality of an untreated STEMI) SBP with concomitant renal impairment: mortality up to 60%1 (about 3x mortality of an untreated STEMI) Delays in diagnosis and treatment are associated with an hourly increase in mortality!

Pathophysiology6 -

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“spontaneous” descriptor was coined in 1964 as there was no obvious nidus for infection Cirrhosis → ascites → altered intestinal motility and increased permeability → bacterial translocation → rapid bacterial growth in ascites → peritonitis (SBP) SBP bacteria: E.coli > K. pneumoniae > Strep > other o So, ceftriaxone is a good choice empirically, but may not be the best option…

Clinical Presentation: SBP11 -

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Key: up to 13% of SBP patients may have no clinical signs or symptoms at the time of diagnosis “SBP can be silent and if a patient is sick enough to come to hospital then a paracentesis to rule out SBP should always be done as SBP can be the precipitant to a bleed, encephalopathy, renal failure and all things liver-related”12 There are no clinical signs or symptoms with high sensitivity or specificity, however:11 o Fever: 69% o Abdominal pain: 59% o Altered Mental Status: 54% o Abdominal tenderness: 49% o Diarrhea: 32% o Paralytic ileus: 30% o Hypotension: 21% o Hypothermia: 17

Diagnosis#1: Clinical Assessment -

Risk factors: Cirrhosis, +ascites, prior SBP or variceal bleed, on PPI, elevated bili >46 Clinical features: see box above

Diagnosis#2: Ascites Cell Count & Diff5,6 -

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Diagnosis: ascitic fluid absolute polymorphonuclear (PMN) leukocyte count >250cells/mm3 Are PMN’s the same thing as neutrophils? Yes3 o in Edmonton, PMN’s are reported as neutrophils Units: 1 mm3 = 1 µl In Edmonton, serum neutrophil units are cells x 109/L (how many billion/L) But peritoneal fluid neutrophils are cells x 106/L (how many million/L) SBP easy math: 250 PMN/mm3 = 250 PMN/µl = 250 x 106 PMN/L = 250 x 106 neutrophils/L o In other words, the units work out the same. Cool? Cool.

Diagnosis#3: Paracentesis? Who, me?

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Delayed paracentesis in patients with SBP leads to a 2.7-fold increased risk of death3 Each hour of delay in paracentesis is a/w a 3.3% increase in mortality3 At some institutions, routine ultrasonography is somewhat solar-powered* o *only available in the daylight ED physicians on evening or night shifts can and should perform U/S-guided paracentesis at the bedside when considering a diagnosis of SBP7 It’s 23:37, I’m tired. Why can’t I just give a dose of Ceftriaxone now and arrange for U/S paracentesis and fluid analysis by radiology in the morning?

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“Paracentesis should not be delayed in patients suspected of having SBP”3 o Hourly increase in mortality for delay “It is vital that patients suspected of having SBP undergo abdominal paracentesis before receiving any antibiotics (a single dose can lead to no growth in 86% of patients)”3 “In the vast majority of patients, a paracentesis can be safely carried out despite ↑INR”3 “70% of patients with ascites have abnormal prothrombin time, but the risk of bleeding following paracentesis is very low”8 Despite elevated INR and PTT, patients with liver disease can be hypercoagulable “There are no data to support coagulation testing prior to paracentesis”8 Can you walk me through it?

KEG: yes.

Diagnosis#4: Performing ED bedside Paracentesis7,8,9 -

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When? – promptly, anytime you are concerned about a diagnosis of SBP Ensure patient consent or double doctor consent if patient is altered Consider asking a nurse to assist for a sterile procedure Equipment: o Sterile suture tray o Chlorhexidine, 2x2 gauze, 2x empty 20cc syringe, 18G needle o Sterile gloves (cap and sterile gown not necessary)8 o Surgical marker o Lidocaine + syringe + needle Needle: o Generally, use the narrowest needle available (lower risk) o Diagnostic tap (small volume) = needed in the ED overnight  Pull off 2x20cc syringes for the nurses to send  Lean patient: can use a simple 1.5-inch 22G or 18G  Big patient: 22G spinal needle o KEG notes:  Up to date prefers to avoid plastic-sheathed needles in case plastic breaks off8  EM:RAP uses the plastic sheath and slips it off the needle once fluid aspirated7 o Therapeutic tap (larger volume) – typically not needed in the ED overnight  14G needle, tubing, negative pressure bottles, or serial 60cc aspirations Patient positioning: o supine, lying flat or slightly elevated o roll patient slightly towards side of entry so the bowel floats away from you Landmark for entry site: o Up To Date: LLQ site is typically used (thinner abdo wall + deep fluid pocket) o EM:RAP recommends RLQ or LLQ – whichever has better fluid pocket o See diagram for landmark from the ASIS8 o Use U/S to confirm this location has:  Good fluid pocket  No spleen or bowel  Turn on Doppler + high frequency probe to look for wall blood vessels

Diagnosis#4: Performing ED bedside Paracentesis7,8,9 -

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Sterile prep with 3x chlorhexidine passes (then wait for skin to dry) Drape with fenestrated drape or huck towels Lidocaine local anesthetic Note: on EM:RAP video, U/S is used in the landmarking process. Then, once landmark looks good, the area is marked and U/S not used again during the tap itself7 Advance your chosen paracentesis needle using the Z-track technique (minimize leaks)8

Slowly advance while aspirating until ascites is aspirated Diagnostic Tap: Fill two 20cc syringes with fluid for analysis Therapeutic tap: if the patient is quite distended and uncomfortable you may want to take off 1-2L to help them. This should be done with a bigger needle (14G) and multiple aspirations with a 60cc syringe. Vacuum bottles and connecting tubing are not always available in our ED

Complications: 1. Fluid leak: try some gauze, tegaderm, or place an ostomy bag over the site and let ‘er drip 2. Bleeding: a. Superficial bleed: figure of eight stitch b. Deep bleed: call for help, change your pants 3. Bowel perforation: rate 6/1000 taps, generally well tolerated, monitor Fluid Analysis: -

Cultures (blood culture bottles) & Gram stain Cell count & differential Albumin, protein, glucose

Management #1: Antibiotics

Empiric antibiotics? – suspicion of SBP, ascites, and ANY of: -

Temp >37.8oC Abdominal pain or tenderness on exam Altered mental status Ascites analysis shows PMN >250 (see above)

When? – ASAP after ascitic fluid + cultures, blood cultures, are sent Type?14 1. No Risk factors: Ceftriaxone 2g IV q24h (cephalosporin allergy? – cipro 400mg IV q12h) 2. Risk factors for healthcare associated infection (hospitalization or abx in past 3/12, from LTC, or on hemodialysis): Piperacillin-tazobactam 4.5g IV q8h 3. Hospital acquired infection (within 72h discharge) OR prior ESBL infection: Meropenem 500mg q6h 4. Septic Shock: Meropenem + Vancomycin

Management #2: Albumin -

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“Albumin administration within 6h of diagnosis has been shown to decrease the risk of both renal impairment and mortality in patients with SBP”1,2 Who? Patients with SBP (ascites >250 PMN) and renal impairment or hyperbilirubinemia: “albumin infusion should be given if creatinine >88 umol/L, urea >10.7 mmol/L, or total bilirubin >68umol/L”4 Why?1

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Dose: albumin 25% IV 1.5g/kg (max 100g), repeat dose on day 3 as inpatient

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Timing: within 6 hours of SBP diagnosis

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Increase intravascular volume (fix pre-renal issues) Binds of bacterial endotoxins, blocks neutrophils, modulates nitric oxide2

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Note: 25% is 25g/100ml (and it typically administered in a 100ml minibag) So, an 80kg patient, at 1.5g/kg, needs 120g (but max dose is 100g=4 vials)

Ok, what if they’ve gone to U/S, had 5L of ascites taken off, but the PMN count is normal? Do I still give albumin?

2009 AASLD guidelines recommend albumin replacement after Large Volume Paracentesis (LVP; >5L)5 -

Why? Paracentesis-induced circulatory dysfunction (PICD): vasodilation, hypotension, renal impairment, and faster ascites reaccumulation PICD occurs in up to 80% of patients who undergo LVP without albumin Dose: ideal dose is unclear. Most common recommendation (AASLD) is: o o o

6 to 8g albumin for every liter removed in LVP (>5L), some local docs use >3L12 Albumin is not recommended for paracentesis <5L So, if 8L were removed, give 48-64g of albumin (about 2x100ml of 25%)

Holy shit dude.

No one said there would be math involved. Is there an easier way to remember this?

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Yes, standardized albumin dosing seems to be the way to go5 o o o

5-6L removed: give 25g albumin (1 vial, or 100ml 25%) 7-9L removed: give 50g albumin (2 vials, or 200ml 25%) >10L removed: give 75g albumin (3 vials, or 300ml 25%)

Management #3: “throwing the kitchen sink”: Hepatorenal Syndrome (HRS)

“You cannot [typically] diagnose HRS in the ER [because] the patient must be volume repleted first [then once repleted] other causes of renal failure are ruled out. Clinical diagnosis of HRS made if elevated JVP but urine Na <10 so the patient looks overloaded, but the kidneys think the patient is dry”12 -

Albumin: “a GI Bleed or someone in shock needs whatever fluid you can get, just [consider] that NS will not help as much as albumin (or blood)”12

“Once renal failure has developed, treatment with a combination of octreotide and midodrine may be helpful”4 (in addition to the albumin and antibiotics) -

Octreotide: local dosing in Edmonton = 100-200µg sc TID13 Midodrine 5-10mg po TID o Midodrine forms an active metabolite, desglymidodrine, which is an alpha-1 agonist

Liver transplant for SBP survivors

Acknowledgements

KEG would like to thank Dr. Lana Bistritz (RAH gastroenterology) and Dr. Marilyn Zeman (RAH gastroenterology and “RAH liver person”)

References 1)

Jamtgaard L, et al. Does Albumin Infusion Reduce Renal Impairment and Mortality in Patients with Spontaneous Bacterial Peritonitis? Ann Emerg Med. 2015 2) EM:RAP. Albumin in Spontaneous Bacterial Peritonitis. November 2017 3) Runyon B, et al. Spontaneous Bacterial Peritonitis in adults: Diagnosis. UpToDate. April 8, 2022 4) Runyon B, et al. Spontaneous Bacterial Peritonitis in adults: Treatment and Prophylaxis. Up to Date. February 2022.

5) Anderson SS, et al. Standardizing the use of albumin in large volume paracentesis. Journal of Pharmacy Practice. 2020.

Vol 33(4), 420-424 6) Runyon B, et al. Pathogenesis of SBP. Up To Date. February 2022 7) Mason J, Anaya, A. Paracentesis. EM:RAP Videos.

8) Runyon B, et al. Diagnostic and therapeutic abdominal paracentesis. Up To Date. February 2022 9) Socransky et al. Essentials of Point-of-Care Ultrasound; The EDE Book. Copyright 2015.

10) Bugs & Drugs: Spontaneous Bacterial Peritonitis 11) Runyon B, et al. Spontaneous Bacterial Peritonitis in adults: Clinical Manifestations. April 8, 2022.

12) Email correspondence, Dr. Marilyn Zeman, local Gastroenterologist and “RAH liver person”.

13) Email correspondence, Dr. Lana Bistritz, local Gastroenterologist 14) Cirrhosiscare.ca – a brilliant, easy to use, local website for presentations related to cirrhosis (ascites, SPB, hepatic encephalopathy, varices, etc.)

CME Credits -

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Kingsway Education Group (KEG) content is a self-approved group learning activity (Section 1) as defined by the Maintenance of Certification Program of the Royal College of Physicians and Surgeons of Canada Due to COVID-19, the required 25% allotment of interactive time cannot be done in a group setting.

Please contact KEG Chair, Dennis Lefebvre at dclefebvre@gmail.com or 780-906-8054 with any questions or feedback to fulfill this interactive component This “event” is accredited for 1 hour