12. 9 g/dL, and the platelet count is 120 × 103/µL.
The sodium is 123 mEq/L, potassium is 5. 2 mEq/L,
and creatinine is 2. 4 mg/dL, which is increased
from 1. 3 mg/dL at the most recent outpatient visit.
The bilirubin is 1. 1 mg/dL, and the INR is 1. 4. A
chest x-ray shows no focal infiltrates, and a urinalysis is unremarkable. Blood cultures are obtained. A
diagnostic paracentesis shows 460 nucleated cells
(88% polymorphonuclear leukocytes), and ascites
culture is obtained. The patient is placed on appropriate antibiotics and albumin for SBP treatment,
and lactulose is administered.
Patients with low-grade hepatic encephalopathy
can often be managed as outpatients, with ammonia-lowering therapy. For those with gross disorientation (grades 2–4), admission to the hospital is
often needed to provide appropriate therapy and
to investigate potential precipitating causes. This
is particularly the case for those with grades 3 and
4 hepatic encephalopathy, who may need admission to intensive care, and in some cases intubation for airway protection. Identification and treatment of precipitating causes is a vital component
of management, as untreated infections or other
conditions can progress to sepsis or death. One
other precipitating factor deserves special mention.
Hypokalemia is accompanied by a metabolic alkalosis which favors the conversion of charged ammonium (NH4+) to neutral ammonia (NH3), which
more readily crosses the blood-brain barrier and
contributes to hepatic encephalopathy. Therefore,
providers should carefully assess for hypokalemia
and correct it.
Because of its central role in the pathogenesis of
hepatic encephalopathy, ammonia is the primary
target of most therapies specific for hepatic encephalopathy. The synthetic disaccharides lactulose
and lactitol are the most commonly used ammonia-lowering therapies. Lactitol is not available in the
United States. These agents are catabolized by colonic bacterial flora into short chain fatty acids, which
acidifies the colonic lumen, converting ammonia
to ammonium, which is trapped in the lumen and
excreted in the stool. They are effective in improving hepatic encephalopathy, although many of the
studies are of poor quality.114 Lactulose is typically
given in doses of 20 to 30 g, and should be titrated
to achieve 2 to 3 soft bowel movements per day. For
inpatients who are unable to take oral medications,
lactulose can be administered via nasogastric tube
or as an enema.115
Oral antibiotics are also frequently used for the
treatment of hepatic encephalopathy, most often
as an adjunctive therapy with lactulose. They purportedly work by altering the gut microbiota, thereby reducing ammonia production and absorption.
Rifaximin, a poorly absorbed antibiotic, is the best
studied agent. In a randomized trial, rifaximin twice
daily reduced the risk of recurrent overt hepatic
encephalopathy and reduced the risk of hepatic
encephalopathy–related hospitalizations compared
to placebo.116 Rifaximin also improves health-related quality of life in these patients.117 Other antibiotics have also been used, including neomycin,
metronidazole, and oral vancomycin. None has
been as rigorously tested as rifaximin, and potential safety concerns have limited enthusiasm for
their use (eg, ototoxicity and nephrotoxicity with
neomycin, and neurotoxicity with metronidazole).
Probiotics have also been used, although their
clinical efficacy is not well established.118