Emergency Department (ED) Critical Care   Emergency medicine critical care podcast

 

Liver and Biliary Tract

Liver

HAV-picoRNA virus, pt can not go to work until non-effective

HBV-DNA

HCV-

HDV-directly cytotoxic to hepatocytes, other secondary damage

Must have >2.5 billi to see jaundice

ETOH Liver Disease-

 

OCPs cause bleeds in the liver

NSAIDs cause renal failure

 

LIver fx pathway

 

Hepatic Encephalopathy

asterixis, fetor hepaticus, spider angioma, testicular atrophy, gynecomastia

Stage I-apathy, anxiety, decreased attention, mild flap, speech disruption

II-lethargy, flap, disorientation, loss of sphincter control

III-stupor c hyperreflexia, Babinski's

IV-coma

 

Etiology

·        Renal failure: Renal failure leads to decreased clearance of urea, ammonia, and other nitrogenous compounds.

·        Gastrointestinal bleeding: The presence of blood in the upper gastrointestinal tract results in increased ammonia and nitrogen absorption from the gut. Bleeding may predispose to kidney hypoperfusion and impaired renal function. Blood transfusions may result in mild hemolysis, with resulting elevated blood ammonia levels.

·        Infection: Infection may predispose to impaired renal function and to increased tissue catabolism, both of which increase blood ammonia levels.

·        Constipation: Constipation increases intestinal production and absorption of ammonia.

·        Medications: Drugs that act upon the central nervous system, such as opiates, benzodiazepines, antidepressants, and antipsychotic agents, may worsen hepatic encephalopathy.

·        Diuretic therapy: Decreased serum potassium levels and alkalosis may facilitate the conversion of NH4+ to NH3.

·        Dietary protein overload: This is an infrequent cause of hepatic encephalopathy

 

Lactulose (traps ammonia by acidifying the feces) 30 cc PO or PR (300 mL lactulose plus 700 mL water, given as a retention enema every 4 hours as needed)

 

Lactulose may be effective, but less so than abx (Als-Nielsen B, Gluud LL, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004)

 

Go-lytely also has very good effects

 

Flumazenil

2 mg IVP for severe encephalopathy, should have response in 6 hrs or it has poor prognostic associations

ACP Journal Club 2003, Jan-Feb 138:15.  (Ailment Pharm Ther. 2002; 16:361-72)  Meta-analysis of flumazenil vs. placebo showed clinical and EEG improvement. 

 

Neomycin 250 mg QID

protein restriction

Ammonia levels do not correlate c severity (very sensitive (90%), not specific)

Fulminant Hepatic Failure (FHF)

Encephalopathy in this setting is actually caused by increased permeability of the blood brain barrier with resultant brain edema.

Brain edema can be detected using transcranial doppler ultrasound.  It looks at mean flow velocity in the middle cerebral artery.

May need mannitol, CVVH, pentobarb coma, hypothermia.

 

Transaminase levels > 5000 U/L

Only 3 categories of hepatic insult commonly produce a transaminase level > 5000 U/L: (1) a toxic event, such as acetaminophen toxicity; (2) ischemic hepatopathy; and (3) infection by atypical viruses such as HSV (Mayo Clin Proc, Vol. 81, pg. 1097).

 

Myth--Interpretation of a single ammonia level in patients with chronic liver disease can confirm or rule out hepatic encephalopathy

Can J Emerg Med 2006;8(6):433-5

The degree of the correlation between ammonia levels and the severity of HE continues to be controversial. What is evident from the literature is that a single normal ammonia level does not rule out HE in a patient with CLD, and serial levels may not correlate with the evolving clinical picture. An ammonia level is merely a data point among the constellation of variables that may contribute to the development of HE and, for now, the final diagnosis remains a clinical one. Reliance on ammonia levels to make the diagnosis of HE is inappropriate and perhaps dangerous if it results in failure to seek other causes of altered mentation in ED patients with CLD.

 

Failure of liver within 8 weeks of development of disease

SBP

>250 PMNS=SBP

subtract 1 pmn for every 250 red cells in a traumatic tap

 

 

E. Coli, Klebsiella, Strep.  >250 WBCs or a difference of .1 between ABG and Ascites pH (or <7.34) 

RX c Amp and Gent

 

Hepatic Abcess-pyogenic or amebic

 

We studied the use of reagent strips for diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. A reagent strip for leukocyte esterase designed for the testing of urine with a colorimetric 5-grade scale (0 to 4) was used to evaluate ascitic fluid in 228 nonselected paracentesis performed in 128 cirrhotic patients. We diagnosed 52 SBP and 5 secondary bacterial peritonitis by means of polymorphonuclear cell count and classical criteria. When we considered positive a reagent strip result of 3 or 4, sensitivity was 89% (51 of 57), specificity was 99% (170 of 171), and positive predictive value was 98%. When we considered positive a reagent strip result of 2 or more, sensitivity was 96% (55 of 57), specificity was 89% (152 of 171), and negative predictive value was 99%. In conclusion, the use of reagent strips is a rapid, easy to use, and inexpensive tool for diagnosis of ascitic fluid infection. A positive result should be an indication for empirical antibiotic therapy, and a negative result may be useful as a screening test to exclude SBP. (HEPATOLOGY 2003;37:893-896.)
 

Precipitants of Acute Decompensation in Chronic Liver Disease

 

TIPS

TIPS Stenosis in the ED
A transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneously-placed shunt between the hepatic vein and the portal vein thereby creating a low-resistance channel between the portal and systemic circulations. A TIPS is placed to reduce portal pressure in patients with complications related to portal hypertension (ie, variceal hemorrhage and ascites).

For most patients, TIPS is successful initially, but over time shunts become stenotic or occluded. In two series of patients who underwent TIPS placement, by two years, virtually all surviving patients had developed TIPS stenosis (1,2). A patient who has undergone placement of a TIPS may present to the ED with an acute decompensation (e.g. worsening encephalopathy) which may be the result of TIPS stenosis. The Emergency Physician needs to be aware that the appropriate initial study to obtain is a RUQ ultrasound with doppler flow to evaluate the patency of the TIPS. It should be noted, however, that literature suggests that doppler sonography is relatively insensitive for detecting stent stenosis (3 - 5) - angiography is the gold standard - but it is a reasonable initial step in the ED. If TIPS stenosis is identified, the patient may be a candidate for a shunt revision.
 

Hepatopulmonary syndrome is from dilation of pulmonary capillaries in lower portions of the lung. when they stand up they desaturate=platypnea

 

Child's classification(liver cirrhosis)

 

The Child- Pugh classification is a means of assessing the severity of liver cirrhosis.

Score 1 2 3
bilirubin (micromol/l) <34 34-50 >50
albumin (g/l) >35 28-35 <28
PT (s prolonged) <4 4-6 >6
encephalopathy none mild marked
ascites none mild marked

If there is primary biliary cirrhosis or sclerosing cholangitis then bilirubin is classified as <68=1; 68-170=2; >170=3.

The individual scores are summed and then grouped as:

  • <7 = A
  • 7-9 = B
  • >9 = C

A C classification forecasts a survival of less than 12 months.

From: Pugh RNH, Murray-Lyon IM, Dawson JL et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:649-9.

 

Fulminant Hepatic Failure

 

high coags are not a contraindication to paracentesis (Grabau CM, et al. Performance standards for therapeutic abdominal paracentesis  Hepatology 2004;40:484-8.)

 

Hepatocellular Carcinoma

TI Hepatocellular carcinoma presenting with intractable diarrhea. A radiologic-pathologic correlation. 
AU Steiner E; Velt P; Gutierrez O; Schwartz S; Chey W 
SO Arch Surg 1986 Jul;121(7):849-51. 
 
  A 44-year-old woman with hepatocellular carcinoma presented with intractable watery diarrhea and her condition was evaluated angiographically. Surgical ablation of the tumor resulted in complete resolution of the diarrhea. The tumor cells of the hepatocellular carcinoma were found to contain vasoactive intestinal polypeptide, gastrin, and prostaglandinlike immunoactivity. To our knowledge, this is the first report of such an association. 
 
TI Diarrhea as a presenting symptom of hepatocellular carcinoma. 
AU Bruix J; Castells A; Calvet X; Feu F; Bru C; Sole M; Bruguera M; Rodes J 
SO Dig Dis Sci 1990 Jun;35(6):681-5. 
 
  The clinical manifestations of hepatocellular carcinoma (HCC) are highly nonspecific since they usually mimic those of hepatic cirrhosis, which frequently underlies this neoplasm. The fact that some HCC patients present with severe diarrhea, an unusual symptom in liver cirrhosis, prompted us to determine the prevalence of diarrhea in a series of 23 consecutive HCC patients and compare it with that of a control group formed by cirrhotic patients without HCC, matched by age, sex, and etiology of the liver disease. All the patients were interviewed about the existence of diarrhea (defined as the presence of three or more loose stools per day appearing over three or more days) in the three months prior to admission. Both groups of patients were similar in regards to the degree of liver failure and presence of diarrhea-favoring factors. By contrast, diarrhea was significantly more frequent among HCC cases than among cirrhotics without HCC (47.8% vs 8.7%, P less than 0.005). HCC
 patients with diarrhea exhibited higher alkaline phosphatase and bilirubin levels and worse liver function, assessed by the Child-Pugh's classification, than patients without diarrhea. However, neither tumor size, vascular invasion, or the degree of tumor differentiation were significantly different between these two groups of HCC patients. These results show that diarrhea is a frequent manifestation of HCC in patients with cirrhosis. Therefore, the development of HCC in these patients should be suspected upon the appearance of diarrhea. 
 
AD Department of Radiology, Hospital Clinic i Provincial, University of Barcelona, Spain. 

 

Bleeding into Tumor

need angio

Liver Dialysis

Liver Dialysis is on UpToDate HemoTherapies Unit for Liver Dialysis

 

More MARS (Crit Care 2006;10:118)

Biliary Tract Disorders

Antispasmodics

Bentyl 20 mg PO QID or 20 mg IM (not IV) Q4-6

Glycopyrrolate 1-2 mg PO Bid/Tid or 0.2 mg IV/IM Tid/Qid

Cholelithiasis

Pigmented stones vs. cholesterol stones (70% of stones) which are radiolucent

Symptomatic known as biliary colic should resolve in a few hours

Most sensitive test is HIDA or DISIDA scanning (morphine may increase specificity)

Choledocolithiasis

Common duct stones also are defined as retained, if discovered within two years of cholecystectomy, or recurrent if detected more than two years after cholecystectomy. Retained stones most likely were present at the time of cholecystectomy.

IF mild disease without ultrasound CBD dilation precede with op

otherwise consider ERCP or MRCP first

 

Combination of bilirubin level > 3.0 and alkaline phosphatase >250: >75% chance of common duct stone (Surg Gynecol Obstet. 1982 Mar;154(3):381-4)
 

Cholecystitis

Having a fever is highly predictive.  Murphy's Sign has sensitivity of 97.2%. (Annals 28:3, 1996. p. 267)

 

Acute cholecystitis – gangrene:
59% lack fever
27% lack leukocytosis
6% lack fever and leukocytosis

Acute cholecystitis – nongangrene:
71% lack fever
32% lack leukocytosis
28% lack fever and leukocytosis
Gruber PJ, et al. Ann Emerg Med. 1996 Sep;28(3):273-7

 

Does pt have cholecystitis? (JAMA 289(1):80, 2003)  Murphy's is pretty good (2.8 LR), Enzymes not useful.  Epigastric was just as common as RUQ pain.  Pain was constant more often than colicly. 

 

can see mild elevation in billi and amylase

Acalculous

occurs in 5-10% of patients with acute cholecystitis, tends to be more rapid and malignant. Patients frequently are elderly and have a history of diabetes mellitus. Other risk factors include multiple trauma, extensive burn injury, prolonged labor, major surgery, systemic vasculitic states, gallbladder torsion, and parasitic or bacterial infections of the biliary tract.

Emphysematous Cholecystitis

1% of cholecystitis cases

diabetes is a risk factor

 

need operation within 24 hours

subtotal cholecystectomy it is better to remove 95% than 101%

leave a 1cm rim of hartmann's puch and sture buttress this over the cystic duct

leave any friable posterior waal, oversew and blast with diathermy until you smell fried liver

 

cholecystotomy

can be open or perc

use a large foley

 

Mirizzi

syndrome where an impacted cystic duct stone causes

gallbladder distension and leads to hepatic duct

compression

 

 

 

Gall Bladder
acalculous is a result of microcirculatory dysfunction.
gram negative bacteria, occ. anaerobic infections, though rarely sole source 10% of AC will have assoc. choledocolithiasis these patients rarely have the assoc. complications of choledoco such as pancreatitis, cholangitis, or severe jaundice
 

 

“Since the patient was in her third trimester, she

had an appointment with her obstetrician within

the week, so I thought she could follow up.”

Jaundice in the third trimester is especially

concerning. Conditions not to be missed are acute

fatty liver of pregnancy (which can lead to fulminant

liver failure) and intrahepatic cholestasis

(which can lead to preterm labor). The former

requires delivery, the latter monitoring, possibly

as an inpatient. All pregnant patients with

jaundice should be managed in conjunction with

their obstetrician.

 

Liver Abscesses

pyogenic abscess

from biliary tract disease, gi tract infection, hematogenous spread via hepatic art, direct extension from intar-abd pathology, trauma e. coli, klebsiella, and proteus are the most common organisms
 

Amebic

e. histolytica gains access by oral ingestion of contaminated food. cysts are digested and the trophozoites are released into the GI tract they then reach the liver via the portal system.
can get indirect hemagglutination and gel diffusion precipitation secondary infection is the msot common complication
treatment flagyl 750 mg tid for 7-10 days

 

hydatid disease

echinococcus granulosus and multilocularis first inactivate cysts and then remove them hypertonic saline can be used along with treatment with al or mebendazole

 

 

Cholangitis

Charcot's Triad:  RUQ pain, Fever, Jaundice.  AMP/Gent/Flagyl or Mezlocillin

the ruq pain is along the entire liver, not the murphy's sign pan of AC

 

ABX:  Cipro/Flagyl, amp/gent/Flagyl, zosyn, unasyn, imipenem, ceftaz/Flagyl, aztreonam/clinda

Gallstone Ileus

Radiographic triad of SBO, pneumobilia, and ectopic gallstone

25% of non-strangulated SBO in pts > 65

cholecystoenteric fistula

Pyelophlebitis

Clot with superimposed infection of the portal vein

 

Cirrhotics get pulmonary htypertension, they die during transplant operations

 

LFT Interpretation

 

Alanine transaminase and aspartate transaminase

Alanine transaminase and aspartate transaminase are found in clinically important concentrations in:

Their levels may be markedly elevated in hepatitic liver damage as well as in other disease, such as myocardial infarction.

Very high levels (greater than 1000) are generally found only with:

Alcoholic hepatitis, chronic viral hepatitis (for example, hepatitis B or C), and fatty liver typically result in levels less than 100.

The ratio of aspartate transaminase to alanine transaminase may be useful for distinguishing fatty liver due to alcoholic and non-alcoholic aetiologies.5

 

Alkaline phosphatase

Alkaline phosphatase largely originates from liver (mainly cells lining biliary ducts or membranes adjoining bile canniculae) and bone. Marked increases are typical of cholestasis (often with raised gamma glutamyl transferase - see below) or a variety of bone disorders (usually without raised gamma glutamyl transferase). Isoenzymes may be useful for distinguishing these sources.

Gamma glutamyl transferase

Gamma glutamyl transferase is found in hepatocytes and in biliary epithelial cells. Elevation typically indicates cholestasis or, when alkaline phosphatase is normal, induction of hepatic metabolic enzymes, often in response to long term exposure to excessive alcohol or drugs such as anticonvulsants or rifampicin.

Bilirubin

Bilirubin is produced by haemoglobin catabolism. Elevation may indicate:

High levels of unconjugated bilirubin, where other LFTs are normal, may identify haemolysis or Gilbert's syndrome.

Bilirubin is a powerful prognostic marker for chronic liver disease.6 It is useful for assessing a patient's need for liver transplantation.7

 

Albumin

Albumin is synthesised by the liver. Although low levels may indicate severe synthetic liver dysfunction, it is not a specific marker of liver disease and may fall acutely in severe illness, such as sepsis.

The serum half life of albumin is 20 days, so it is not a good marker for acute liver injury. However, it may be useful for predicting prognosis and is a good synthetic marker for chronic liver disease.6

Prothrombin time

Although prothrombin time is not usually included in LFT panels, it is a highly important marker of prognosis in acute and chronic liver disease, once vitamin K deficiency or malabsorbtion have been ruled out (often by giving intravenous vitamin K).6 8

 

ABNORMAL LIVER FUNCTION TESTS—G. Anton Decker, MD, Instructor

of Medicine, Division of Gastroenterology, Hepatology,

and Internal Medicine, Mayo Clinic College of Medicine, Scottsdale,

Arizona

Introduction: elevations in liver function tests (LFTs) often not

pathologic; few conditions (eg, acetaminophen [Tylenol] toxicity)

require immediate action; spontaneous resolution common

Case: man, 30 yr of age, asymptomatic with total bilirubin 2.5 mg/dL,

direct bilirubin 0.1 mg/dL, alanine aminotransferase (ALT), aspartate

aminotransferase (AST), and alkaline phosphatase (ALP)

within normal ranges; he drinks 1 glass of wine daily and takes no

medications; ultrasonography of liver reveals no abnormal findings;

diagnosis—Gilbert’s syndrome; isolated unconjugated hyperbilirubinemia

clue to diagnosis; syndrome occurs in 5% of

population; hemolysis ruled out in healthy patients

Liver function tests: ALT, AST, ALP, bilirubin, 􀁊-glutamyltransferase

(GGT), albumin, and prothrombin time (PT); measures

of hepatocyte integrity and cholestasis; albumin and PT

may reflect liver function, but not specific for liver disease;

extrahepatic sources of AST and ALP also exist

Investigation: clinical context (eg, history, medications) important;

pattern (cholestatic or hepatocellular) and degree of abnormality

(mild, moderate, or severe) give clues to diagnosis;

abnormalities in AST and ALT generally reflect hepatocellular

injury; abnormalities in ALP and (to lesser extent) bilirubin

generally reflect cholestatic injury; GGT sometimes useful to

determine source of ALP; general guidelines—immediately

evaluate patients with LFTs >5 times upper limit of normal

(ULN) and signs and symptoms of liver disease; retest LFTs in

3 to 6 mo in patients with levels <3 times ULN, in absence of

concerning signs and symptoms; retest LFTs in 1 to 3 mo in

patients with intermediate levels (3-5 times ULN)

Nonalcoholic fatty liver disease (NAFLD): most common cause

of mild elevations in LFTs in western world (prevalence 􀁤23%);

most patients asymptomatic, with elevated transaminases;

NAFLD includes simple steatosis and nonalcoholic steatohepatitis

(NASH; inflammatory component); 60% of obese patients

have simple steatosis, 20% to 25% haveNASH; over 5 yr, 􀁼15%

of NASH cases progress to cirrhosis, and small percentage of

these progress to hepatocellular carcinoma (HCC); NASH

may also progress directly to HCC; predictors of advanced

liver disease—age >45 yr; body mass index (BMI; weight

(kg)/[height (m)]2) >30; AST to ALT ratio >1; presence of type

2 diabetes; liver biopsy recommended in these patients to look

for fibrosis and evidence of cirrhosis; management of

NAFLD—weight loss important, although losing weight too

quickly may exacerbate NAFLD; tightening glucose control

helpful (medications not proven effective); patients with advanced

liver disease require referral and close follow-up

Medications and LFTs: many medications cause mild elevations

in LFTs; persistent mild elevations unlikely to require

action; statins—1% to 3% of patients develop abnormalities

in ALT >3 times ULN (indication for stopping statin); usually

occurs in first 3 mo of therapy; threshold arbitrarily established

for clinical trials; no evidence that liver damage occurs

at this level; preexisting abnormalities in LFTs or chronic liver

disease does not increase risk for hepatotoxicity on statins

(check LFTs 12 wk after starting statin; discontinue statin if

LFTs >3-5 times ULN); general approach for medication-induced

elevations in LFTs—stop medication if LFTs >5 times

ULN; retest in 3 mo if LFTs <3 times ULN; retest in 1 mo if

LFTs 3 to 5 times ULN

Viral hepatitis: LFTs often fluctuate, especially in patients with

hepatitis C; level of aminotransferase poor indicator of severity

of disease; screening—hepatitis B surface antigen (HBsAg),

antibodies to hepatitis C virus (HCV), and hepatitis A virus

(HAV) IgM

Other sources of mild elevations in LFTs: hemochromatosis—

look for transferrin saturation >45%; autoimmune hepatitis—

hypergammaglobulinemia common; clues to diagnosis include

high total protein and low albumin; celiac disease—up to 10%

of patients with unexplained abnormalities in LFTs have celiac

disease; 􀄮1-antitrypsin deficiency—screen for phenotype, because

level of 􀄮1-antitrypsin fluctuates; Wilson’s disease—

younger patient presents with hemolysis and psychiatric abnormalities;

risk for fulminant liver disease

Moderate to severe increases in LFTs: ischemic hepatitis—clinical

setting (eg, recent surgery) important; AST peaks before

ALT, then bilirubin (bilirubin last to recover); most patients improve

spontaneously with only supportive measures; viral

hepatitis—transaminases peak before jaundice appears; elevation

generally less severe with HCV; symptoms more common

with HAV and hepatitis B virus (HBV); screening serologies important;

acetaminophen toxicity—careful drug history required

(overdose not always intentional); 7.8 g causes hepatotoxicity in

adults (less in alcoholic patients); ALT begins increasing 48 to

72 hr after ingestion; suspicion of acetaminophen toxicity warrants

administration of N-acetylcysteine (Mucomyst); acetaminophen

levels unreliable within 4 hr of ingestion; acute biliary

obstruction—acute obstruction of common bile duct (eg, by

gallstone) may cause massive elevations in AST and ALT, followed

by ALP and bilirubin; alcoholic hepatitis—moderate elevation

in transaminases (200-400 U/L); AST to ALT ratio >1 or

>2 important clue for diagnosis; may be acute on chronic alcoholic

hepatitis; biopsy may appear identical to NAFLD

Cholestatic pattern: less common than hepatocellular pattern;

usually associated with elevated ALP (but remember extrahepatic

origin of ALP) and bilirubin (less specific to cholestasis);

drug-induced hepatotoxicity—normalization of LFTs may require

several months (8 mo in case of toxicity from amoxicillinclavulanic

acid [Augmentin]); medications causing cholestasis

include anabolic steroids, erythromycin, total parenteral nutrition

(TPN), gold, imipramine, and estrogen; primary biliary

cirrhosis—uncommon condition, typically occurring in middle-

aged women; presentation includes fatigue, pruritus, and

isolated elevated ALP; antimitochondrial antibodies present in

95% of patients; total IgM often elevated; hypercholesterolemia

caused by elevation in high-density lipoprotein (HDL); patients

at risk for osteoporosis; treatment ursodeoxycholic acid; primary

sclerosing cholangitis—70% of cases associated with inflammatory

bowel disease ([IBD]; sometimes asymptomatic);

condition involves sclerosis of intrahepatic and extrahepatic bile

ducts; magnetic resonance cholangiopancreatography (MRCP)

recommended for diagnosis; patients at high risk for cholangiocarcinoma

and colon cancer (independent of IBD); chronic biliary

obstruction—intrahepatic or extrahepatic obstruction; bile

ducts appear dilated on ultrasonography; painless jaundice in

older patient with dilated common bile duct suggests malignancy;

sources of obstruction include stones and liver masses

(primary lesions or metastases)

 

abnormal LFTs
pts under 30, viral hepatitis will be the cause of jaundice in 90% of cases
40-60 y/o etoh is th major cause

Pressors

Vasopressor hyporeactivity may be due to antioxidant deficiency. It can be reversed by giving vitamin C (Crit Care Med 2005;33(9):2028)

 

Sepsis can induce cholestasis, typically with Billis of 5-10

 

vitamin K can worsen liver dysfunction in sepsis

insulin admin in excess of glycogen favors steatosis

 

Pneumobilia

Pneumobilia is defined as the presence of gas in the biliary tree of the liver. Its presence suggests an abnormal communication between the biliary tract and adjacent organs, commonly the gastrointestinal tract. Pneumobilia may reflect a benign incidental finding or herald a life-threatening disease state. The most common conditions associated with pneumobilia include: 1) a biliary-enteric surgical anastamosis, 2) an incompetent sphincter of Oddi, or 3) a spontaneous biliary-enteric fistula

 

When air is identified in the liver on CT scan, ultrasound or less commonly, plain abdominal radiographs, the first distinction that must be made is between biliary air and portal venous air (4). Both entities can be due to benign or life-threatening conditions, but the list of potential causes is different for each. For example, mesenteric ischemia accounts for approximately 50% of cases of portal venous air, but is not associated with pneumobilia (5). Although portal venous air is a late and ominous finding of mesenteric ischemia, distinguishing air in the portal venous system from pneumobilia may alert the clinician to the diagnosis of mesenteric ischemia and encourage prompt therapeutic intervention.

Fortunately, in most cases, these two entities can be distinguished from one another on CT scan. Pneumobilia, or air in the biliary tree, is found in a more central location within the liver than portal venous gas, as the flow of bile is directed toward the liver hilum (6). Pneumobilia usually appears as isolated bubbles in various sizes from 2–5 mm. Air noted in the gall bladder lumen may be much larger and indicates that any additional air noted within the liver is very likely to be biliary in origin as well.

In addition to mesenteric ischemia, portal venous gas can be seen secondary to a gastric ulcer, diverticulitis, small bowel obstruction, septicemia, or post-operatively (5). In 15% of cases the cause is idiopathic (7). On CT scan, portal venous air has a branching pattern that is more extensive than pneumobilia (Figure 6). Air bubbles are typically less than 2 mm in width. Portal venous air may extend to within 2 cm of the liver capsule, whereas pneumobilia usually does not (6). The presence of pneumotosis intestinalis in the same patient suggests that the location of air within the liver is most likely portal venous in origin.


Enlarge Image (91K)

Figure 6. Portal venous air. This patient was found to have mesenteric ischemia at laparotomy. Reprinted with permission (5).

Ultrasonography will detect pneumobilia and portal venous air in the hands of an experienced operator as multiple highly reflective areas in the liver with prominent shadowing. The liver is described as having an almost “striped” appearance. In one study of 25 patients with pneumobilia, both CT scan and ultrasound detected it in all cases (4). Differentiating pneumobilia from portal venous air, however, is much easier on CT scan. In addition, CT scan is more sensitive than ultrasonography in detecting biliary air in patients with emphysematous cholecystitis (8). Whenever this diagnosis is suspected, either clinically or after ultrasound of the gall bladder, a CT scan is recommended (9).

Plain abdominal radiography is infrequently recommended for evaluating biliary tract disease, but if performed may demonstrate a “saber” sign as air preferentially migrates to the common and left hepatic ducts in the supine patient. The saber sign is often present, but easily overlooked if not specifically searched for in the right paraspinal region. As the name implies, a sword-shaped lucency is present representing the air-filled branch of the common and left hepatic duct contrasted by the more radiodense liver (2 and 10).

Once it has been determined that pneumobilia, and not portal venous air, is present, the clinician should consider the conditions—both benign and life-threatening—that cause it (Table 1). The presence of air in the biliary tree suggests an abnormal communication between the biliary system and the surrounding organs. The incidence of pneumobilia is much higher after surgical intervention within or around the biliary tree and gall bladder. The three most common conditions in which pneumobilia occurs are a biliary-enteric surgical anastamosis, an incompetent sphincter of Oddi, or a spontaneous biliary-enteric fistula. An example of each of these three scenarios is provided in the cases presented above.

Table 1.

Causes of Pneumobilia

Most common causes
 Biliary-enteric surgical anastamosis
 Incompetent sphincter of Oddi
  Iatrogenic
  Non-iatrogenic
 Spontaneous biliary-enteric fistulae
  Gallstones (common)
  Peptic ulcer disease (rare)
Less common causes
 Infectious
  Emphysematous cholecystitis
  Acute cholangitis
  Liver abscess
 Bronchopleurobiliary fistulae
 Congenital anomalies
 Iatrogenic manipulation
  Whipple procedure
  Percutaneous transhepatic
 cholangiography

In Case 1, the patient developed pneumobilia secondary to a surgically created anastamosis—a choledochoduodenostomy. The indications for a choledochoduodenostomy include sphincter of Oddi dysfunction, a dilatated common bile duct secondary to choledocholithiasis, or a non-malignant stricture of the common bile duct. The procedure involves side-to-side anastomosis between the duodenum and the common bile duct that allows the enhancement of biliary drainage. Pneumobilia in patients with a choledochoduodenostomy is considered incidental and in the absence of clinical symptoms is inconsequential. Pneumobilia found on imaging of a patient with a history of an unspecified right upper quadrant surgery, as in our case, may suggest the origins of the air.

Previous studies have suggested that a choledochoduodenostomy is a safe alternative treatment for biliary tract disease, with low morbidity and mortality (11, 12 and 13). Despite that fact, it is less commonly used today in favor of laparoscopic and endoscopic techniques. The operation, however, creates a potential reservoir between the distal anastomosis and the ampulla of Vater. If stones or debris obstruct the outflow of bile at the ampulla of Vater, this potential reservoir acts as a “sump” or, literally, cesspool that is a nidus of infection (Figure 7).


Enlarge Image (108K)

Figure 7. Schematic drawing of choledochoduodenostomy with stones and debris within the sump. Reprinted with permission from the American Journal of Roentgenology (15).

The patient in Case 1 demonstrates one of the rare infectious complications that can occur after a choledochoduodenostomy—biliary sump syndrome. Biliary sump syndrome is characterized by upper abdominal discomfort or pain, fevers, chills, and occasionally jaundice. As long as the anastomosis and the ampulla of Vater remain patent, biliary drainage is not compromised. Biliary sump syndrome occurs when stones, gastrointestinal contents, or other debris accumulate in the potential reservoir and impair biliary drainage and allow overgrowth of bacteria. If the clinical presentation suggests this diagnosis, broad-spectrum antibiotics should be administered, and the patient should be admitted with a gastroenterology consultation. The treatment of choice is endoscopic sphincterotomy. Other endoscopic procedures include dilatation of the anastomosis, removal of stones or debris with a wire basket, and stent placement (14, 15, 16 and 17).

A second method by which air can accumulate in the biliary system involves reflux through the biliary sphincter. Reflux occurs due to incompetence of the sphincter, seen in both iatrogenic and non-iatrogenic situations. The most common cause is iatrogenic—after manipulation with a biliary stent, sphinterotomy, or balloon dilatation of the sphincter. In Case 2, the patient improved after treatment of diabetic ketoacidosis alone, and the pneumobilia was thought to be incidental and secondary to sphincterotomy performed during an ERCP.

Sphincterotomy is the standard method for enlarging the bile duct opening for the endoscopic removal of stones and has a success rate of 90%. It involves electrocoagulation and transection of the biliary sphincter, which results in long-term incompetence with duodenobiliary reflux, bacterial contamination, and chronic inflammatory changes. As a result, air may reflux into the biliary system, causing pneumobilia at a rate of 40–50% at one-year follow-up. An alternative procedure, balloon dilatation of the sphincter, has been reported to have success rates similar to sphincterotomy. If balloon dilatation of the sphincter is performed without sphincterotomy, the incidence of pneumobilia decreases to 8% at 1-year follow-up (18, 19, 20, 21 and 22).

Incompetence of the sphincter also has been reported due to non-iatrogenic causes. Under normal conditions, the sphincter of Oddi can produce up to 60 cm H2O pressure to prevent retrograde flow (23). Non-iatrogenic clinical scenarios that can disrupt normal sphincter functioning include passage of common bile duct calculi, adhesions that produce traction on the sphincter, ampullary tumors, migration of an ascaris worm, fibrosis from chronic pancreatitis, or drugs such as atropine that cause relaxation of the sphincter musculature (23, 24 and 25). In addition, increased duodenal lumen pressure greater than 60 cm H2O may allow transient reflux of air through the biliary sphincter. Reported cases include increased distention from tube feedings, small bowel obstruction, and blunt abdominal trauma (1, 26 and 27).

A spontaneously forming biliary-enteric fistula, as determined to be the cause of pneumobilia in Case 3, is the most common non-iatrogenic etiology, accounting for greater than 90% of cases (23 and 25). In most cases, the fistula forms in patients with biliary tract disease and is frequently associated with gallstones (25). The most common cause is repetitive obstruction of the cystic duct by stones, which creates ischemic necrosis of the gall bladder wall and eventual fistula formation. In Asian countries where the incidence of common bile duct stones is much higher, fistulae forming between the common bile duct and intestine occur with greater frequency. Rarely, a chronic peptic ulcer will erode through the posterior portion of the duodenum and communicate with the common bile duct (26). A final mechanism involves a neoplastic lesion that causes necrosis of tissue and the formation of a fistula between the biliary system and an adjacent organ. The location and frequency of fistulae formation are: cholecystoduodenal (70%), cholecystocolic (14%), cholecystogastric (6%), choledochoduodenal (4%), and other (6%) (25).

Less common, but equally important causes of pneumobilia are listed in Table 1. These causes can be further categorized as infectious (emphysematous cholecytitis, acute cholangitis, and liver abscess), congenital, and iatrogenic.

Emphysematous cholecystitis is an uncommon variant of acute cholecystitis with a higher mortality rate. The incidence is higher in men and diabetics. The inciting event is different than acute cholecystitis and seems to be vascular compromise of the cystic artery, which creates an anaerobic environment favoring the proliferation of gas-forming bacteria. Gallstones are absent in up to one-third of patients (9). Characteristic features include symptoms similar to acute cholecystitis with the additional findings of gas within the gall bladder wall and lumen. Air has been reported in the common bile duct and the biliary tree in up to 20% of patients, as this form of cholecystitis is less frequently associated with cystic duct obstruction (28).

Emphysematous cholecystitis is distinguished from other causes of pneumobilia based on the appearance of gas in the gall bladder lumen, wall and pericholecystic soft tissue. Isolated pneumobilia without gall bladder wall/lumen air is a very rare finding in this disease, but has been reported in patients evaluated by plain radiography only (3 and 29).

Other infections due to gas-forming bacteria, such as Clostridium perfringens or Klebsiella pneumoniae, may cause pneumoblia (23). Pneumobilia is present on abdominal CT scan in 22% of patients diagnosed with acute cholangitis, according to one study. Biliary ductal dilatation is seen in over three-quarters of the patients, however, and may aid in differentiating pneumobilia secondary to cholangitis from its other causes (30). Gas formation is a frequent finding in the presence of a liver abscess, seen in almost one-third of patients evaluated by CT scan and ultrasound. It is more common in diabetic patients (55%) compared to non-diabetic patients (9%) (31).

Pneumobilia can also occur in patients with a bronchopleurobiliary fistula. Symptoms of this condition may be as insidious as a chronic cough (32). Bronchopleurobiliary fistulae have been described after thoracoabdominal trauma, inflammatory lesions of the lower lobe of the lung (i.e. tuberculosis), and with migration of an intrahepatic biliary stent. They also may be congenital in origin (25).

Pneumobilia is an expected finding after manipulation of the biliary tree or gall bladder by surgery, gastroenterology, or interventional radiology. Pneumobilia is a benign finding after a Whipple procedure and is present in 80–90% of patients postoperatively (33, 34 and 35). An additional iatrogenic cause is percutaneous transhepatic cholangiography (25). Pneumobilia may be secondary to any instrumental manipulation of the biliary tract.

Conclusion

The presence of air in the biliary system may indicate either a benign or potentially life-threatening condition. The presence of pneumobilia requires a prompt search to rule out serious infectious etiologies. This is especially true in ill-appearing patients without an alternative iatrogenic explanation for their pneumobilia. Surgical and gastrointestinal consultation may be necessary and early antibiotics are appropriate in patients with fever or signs of sepsis. If pneumobilia seems to be an incidental finding, especially after a medical or surgical procedure, a search for an alternative cause of the patient’s symptoms may be warranted. (JEM 2006;30(2):147)
 

 

 

Spontaneous Bacterial Peritonitis

Emergency Physicians frequently evaluate and manage patients with ascites.  Often, these patients present with a myriad of complaints.  Regardless of the chief complaint, the Emergency Physician must always consider the diagnosis of spontaneous bacterial peritonitis (SBP).  Frequently, symptoms of SBP are subtle and can easily be overlooked by even the seasoned clinician.  If the diagnosis is missed, or even delayed, patients incur substantially higher morbidity and mortality.  For patients with their first episode of SBP, mortality is reported to range from 20% to 40% (38). Furthermore, long-term survival after an episode of SBP is just 30% at the end of 2 years (39).

SBP is defined as the bacterial infection of ascitic fluid without an identifiable intra-abdominal source (40). In hospitalized patients with ascites, the prevalence of SBP ranges from 10% to 30% (39-41).  Over 90% of cases are monomicrobial (39). Although enteric gram-negative organisms still account for the majority of isolates, the incidence of gram-positive organisms is increasing.  Gram positive-cocci, namely streptococcal species, now account for approximately 25% of cases (40). Isolation of anaerobes, fungi, or multiple bacterial species should prompt consideration of secondary bacterial peritonitis.

The clinical manifestations of SBP can be subtle.  Fever and abdominal pain are traditionally considered the hallmarks of SBP.  Fever, however, is not universally present.  In fact, many patients with SBP will either be normothermic or have only modest degrees of temperature elevation (42). Abdominal pain in patients with SBP tends to be diffuse.  Physical exam findings, however, can be surprisingly mild due to the effect of ascites.  Moreover, peritoneal signs are frequently absent.  Additional manifestations of SBP that are can often be overlooked include mental status changes, paralytic ileus, unexplained metabolic acidosis, and altered renal function (42). Patients exhibiting any of these findings must undergo paracentesis to evaluate for SBP.  SBP should also be suspected in the patient with ascites presenting with GI bleeding.  These patients have a high incidence of SBP due to bacterial translocation with subsequent seeding of ascitic fluid.  On occasion, some patients are asymptomatic.  Depending on the study, as many as 13% of patients with SBP will not have signs or symptoms of infection (43). As a result, many hepatologists recommend routine paracentesis for any patient being admitted to the hospital.

A diagnosis of SBP cannot be made upon clinical findings alone.  Patients must undergo paracentesis.  Ascitic fluid should be sent for gram stain, culture, and cell count with differential.  A neutrophil count greater than 250 cells/mm 3 is suggestive of the diagnosis and warrants antibiotic administration.  Definitive diagnosis is made by ascitic fluid culture.  To ensure greater accuracy, blood culture bottles should be used and inoculated with at least 10 ml of fluid.  Inoculating at least 10 mL of fluid into blood culture bottles increases the sensitivity of cultures to almost 80% (44).

As stated, the diagnosis of SBP requires that a paracentesis be performed.  Many Emergency Physicians are hesitant to perform a paracentesis due to the presence of thrombocytopenia and/or coagulopathy.  Not surprisingly, up to 70% of patients with ascites have abnormal coagulation parameters (45). Nonetheless, paracentesis is a safe procedure in these patients.  In a recent study of over 1100 paracenteses, Grabou at al. found the procedure to be safe even in patients with international normalized ratio's as high as 8.7 or platelets as low as 19,000 (46).  Furthermore, the routine transfusion of blood products to correct abnormalities prior to the procedure is not supported by current literature.

Treatment of the patient with SBP centers on the early administration of antibiotics.  Antibiotic therapy should cover both enteric gram negative organisms and gram positive cocci.  Third generation cephalosporins are the agents of first choice (40). Up to 90% of patients will respond to a third generation cephalosporin (39) . Although cefotaxime is the traditional agent of choice, a recent analysis found no significant evidence when cefotaxime was compared with other third generation cephalosporins (38) . Aztreonam, amoxicillin plus clavulanic acid, and fluoroquinolones have also been used in the treatment of SBP.  Although oral fluoroquinolones are an option for the stable, well appearing patient, SBP caused by quinolone resistant bacteria is emerging (39).
 

(Emedhome)

 

 

Hyperammonemia

For both types of patients, initial treatment must focus on the management of ICH, which is a condition that is associated with increased morbidity and mortality.18 Usually, hyperammonemia in adults is associated with cerebral edema, decreased cerebral metabolism, and increases in cerebral blood flow. The management of these patients entails the reduction of cerebral edema and cerebral blood flow.18 However, in some patients cerebral blood flow may be reduced; in these patients, drugs that lower cerebral blood flow and cerebral perfusion pressure must be avoided.18 Unfortunately, placement of intracranial pressure monitoring is associated with complications,19 and management may need to be performed empirically. Given the dynamic changes in cerebral blood flow, there is controversy about which management strategy is most appropriate.

 Hypothermia121820 abrogates many of the metabolic effects of ammonia, as follows: decreasing free radical production,13 astrocyte swelling, and inflammation; while improving cerebral blood flow and autoregulation. Hypothermia also slows protein catabolism and the production of ammonia by bacteria and the kidney.20 Hypothermia is the least controversial of treatments. N-acetylcysteine may reduce cerebral edema and cerebral metabolism; as a result, N-acetylcysteine may be beneficial even in the absence of acetaminophen toxicity.18 Although mannitol may increase the influx of ammonia across the blood-brain barrier in canines,21 mannitol administration in humans has been shown to reduce cerebral edema and improve mortality.1822 Two additional controversial treatments include the following: the use of indomethacin, which reduces inflammation and decreases cerebral blood flow but which may cause renal failure121823; and propofol, which successfully sedates patients and decreases cerebral blood flow24 but which may be harmful in patients without adequate cerebral perfusion pressures.

 In addition to therapies that treat ICH, additional supportive therapy is recommended. Because up to 40% of patients with hyperammonemia and elevated intracranial pressure have subclinical seizures,1225 therapy with dilantin or phenobarbital should be considered.1825 Lactulose, a main stay of treatment in patients with chronic hyperammonemia,26 has not been shown to affect mortality in patients with acute hyperammonemia, but it is unlikely to be harmful.18 Antibiotics and antifungal agents can treat underlying infection and may prevent superinfection in these immunocompromised patients.2728 Nutritional support must be provided to prevent protein catabolism. Protein intake must be stopped; normal or supranormal caloric intake may be provided with dextrose and lipids. Once the patient is sufficiently stable to be fed enterally, a protein-free enteral formula (eg, Pro-Phree; Abbott Nutrition; Columbus, OH; or PFD 1 or 2 [formerly known as 80056]; Mead Johnson; Evansville, IN) should be provided.

 If ammonia levels remain at > 100 µmol/L and/or the etiology of hyperammonemia remains elusive, an IEM may be present. For these patients, additional therapies are useful to reduce ammonia levels, by actively removing ammonia, facilitating its metabolism, and by decreasing its production (Fig 3 ). A multifaceted approach can have a dramatic effect on serum ammonia levels (Fig 4 ). (chest 2007;

October 2007; Vol. 132, No. 4
 

 

Causes of Hyperammonemia in Adults*

 

Increased Ammonia Production Decreased Ammonia Elimination
Infection Liver failure
 Urease producing bacteria (Proteus, Klebsiella)  Fulminant hepatic failure
 Trans-hepatic, intrajugular
 Herpes infection Shunt
Protein load and increased catabolism  Portosystemic shunt (TIPSS)
 Severe exercise Drugs (see Table 2)
 Seizures  Glycine
 Trauma or burns  Valproate
 Steroid administration  Carbamazepine
 Chemotherapy  Rifabutin
 Starvation IEM
 Gastric bypass  Ornithine transcarbamylase deficiency
 GI hemorrhage
  Increased renal ammonia production  Carbamyl synthetase deficiency
  Increased splanchnic ammonia production  NAGS deficiency
 Arginosuccinate lyase deficiency
  Increased peripheral catabolism due to deficiency of essential amino acids
 Hyperomithinemia, hyperammonemia, homocitrillinuria
 TPN  Lysinuric protein intolerance
Other
 Cancers (multiple myeloma)  Organic acidurias
 Fatty acid oxidation defects
  Other:
   IHA

 * TIPSS = transjugular intrahepatic portosystemic shunt.

 

 

 

group recommendations on the crit care of acute liver failure (Crit Care Med 2007;35(11):2498)

 

 

 

Hypokalemia and Encephalopathy

Hypokalemia and metabolic alkalosis are considered precipitating factors for hepatic encephalopathy, as hypokalemia stimulates ammoniagenesis in the proximal tubule.

Although, the mechanism is not entirely clear, the likely hypothesis is as follows:

*Hypokalemia causes the movement of potassium out of the cells.
*To maintain electric neutrality, H+ ions move into the cells leading to intracellular acidosis (cellular ph decreases).
*This triggers the conversion of glutamine in the proximal tubule, to NH4+ and bicarbonate.
*Ammonia (NH3+ and NH4+) is selectively, either excreted in the urine or returned to the renal venous circulation (~25-45%).
*Ammonia, that subsequently enters portal circulation, is not metabolized by the cirrhotic liver, therefore likely to precipitate encephalopathy.

Potassium sparing diuretics such as spironolactone and epleronone are used to prevent hypokalemia and metabolic alkalosis for this reason. See Conall's post about diuretic choice in decompensated liver disease. Yet, frequently, hyperkalemia, and not hypokalemia, is a cause of concern among physicians, and frequently leads to discontinuation of spironolactone, administration of loop diuretics, dietary potassium restrictions, all of which further add to the risk of encephalopathy.

Conversely, high potassium levels may be protective by reducing the risk of hepatic encephalopathy. Although, somewhat speculative, this may happen in two ways
  1. Hyperkalemia may decrease total ammonia production in the proximal tubule by increasing intracellular ph and thereby impairing ammoniagenesis.
  2. Potassium competes with NH4+ for absorption by the NKCC2 transporter at the thick ascending limb of loop of henle, thereby reducing ammonia accumulation (read ammonia trapping) in the medullary interstitium and hence less ammonia available for absorption in the systemic circulation.
In an interesting study done by Zavagli et al, patients with higher potassium levels (5.4-5.5 meq/l) had a much better survival and less hepatic encephalopathy episodes as compared to patients with lower potassium levels (3.4-3.5meq/l).

While I certainly do not recommend ignoring severe or symptomatic hyperkalemia in liver cirrhosis patients, educating physicians about aggressive correction of hypokalemia, rather than mild hyperkalemia, may serve these patients best.

Viresh Mohanlal, MD

From Renal Fellow Network

 

Acute Liver Failure

(Great Article from Curr Opin Crit Care 2009)

1. absence of chronic liver disease
2. acute hepatitis (elevation in AST/ALT) accompanied by elevation in INR >1.5
3. any degree of mental alteration (encephalopathy)
4. illness less than 26 weeks duration

Wilsons

Wilson disease requires special consideration. Although this condition is quite rare, its identification in ALF has important management ramifications. Wilson disease may be difficult to diagnose because the low ceruloplasmin levels (characteristic of the disease) are present in most patients with ALF, as noted below, regardless of etiology. In addition, Kaiser–Fleischer rings are not uniformly present and serum copper levels require several days to obtain at most centers. However, patterns of common laboratory abnormalities may be more strongly associated with Wilson disease than these specialized tests. Very low alkaline phosphatase level (including ‘undetectable’ levels) associated with marked hyperbilirubinemia (bilirubin >20 mg/dl) due to profound hemolytic anemia is relatively specific for Wilson disease. A recent analysis concluded that the alkaline phosphatase:bilirubin ratio (less than four) may be the most efficient and rapid means of identifying Wilson's patients with ALF [4•]. The rapid diagnosis of Wilson disease in an ALF patient is critical. Once the disease is confirmed (or considered highly suspicious) in the setting of ALF, the patient should proceed to liver transplantation as rapidly as possible, as spontaneous recovery is estimated at 0% [5].

 

See Fulminant Hepatic Failure

 

 

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