Hepatic encephalopathy

Antibiotics With or Without Rifaximin for Acute Hepatic Encephalopathy in Critically Ill Patients With Cirrhosis

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INTRODUCTION: Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE).

METHODS: In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r). Resolution (or 2 grade reduction) of HE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the 2 groups. A subgroup analysis of patients with decompensated cirrhosis and acute-on-chronic liver failure was performed.

RESULTS: Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used ab. On Kaplan-Meier analysis, 44.6% (41/92; 95% confidence interval [CI], 32-70.5) in ab-only arm and 46.7% (43/92; 95% CI, 33.8-63) in ab + r arm achieved the primary objective ( P = 0.84).Time to achieve the primary objective (3.65 ± 1.82 days and 4.11 ± 2.01 days; P = 0.27) and in-hospital mortality were similar among both groups (62% vs 50%; P = 0.13). Seven percent and 13% in the ab and ab + r groups developed nosocomial infections ( P = 0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower in-hospital mortality (hazard ratio: 0.39 [95% CI, 0.2-0.76]) in patients with decompensated cirrhosis but not in patients with acute-on-chronic liver failure (hazard ratio: 0.99 [95% CI, 0.6-1.63]) because of reduced nosocomial infections.

DISCUSSION: Reversal of overt HE in those on ab was comparable with those on ab + r.

Polyethylene Glycol for Hepatic Encephalopathy:A New Solution to Purge

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Hepatic encephalopathy is a well-known neuropsychiatric complication of cirrhosis with symptoms ranging from mild confusion and sleep disturbance to obtundation. It is highly associated with increased mortality and health care costs.1 As the population of patients with cirrhosis grows, so do these burdens on the health care system. Lactulose treatment has long been the standard of care,2thought to be effective by acidifying stool and eradicating toxic metabolites created by gut flora that the cirrhotic liver is unable to clear. This therapy is widely available and inexpensive. However, with reported 20% to 30% nonresponse rate and refractory encephalopathy, additional therapies have been sought. Nonabsorbable antibiotics have been explored, with the goal of altering the gut microbiome and decreasing ammonia levels and other toxins implicated in hepatic encephalopathy. A randomized, double-blinded controlled trial from 20133 demonstrated the greater efficacy of lactulose with rifaximin compared with lactulose alone.

A Randomized, Double-Blind, Controlled Trial Comparing Rifaximin Plus Lactulose With Lactulose Alone in Treatment of Overt Hepatic Encephalopathy. .

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Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE.

METHODS:In this prospective double-blind randomized controlled trial, 120 patients with overt HE were randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay.
RESULTS:A total of 120 patients (mean age 39.4+/-9.6 years; male/female ratio 89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7+/-2.8 and the MELD (model for end-stage liver disease) score was 24.6+/-4.2. At the time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and 58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29 (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8+/-3.4 vs. 8.2+/-4.6 days, P=0.001).
CONCLUSION:Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.

Source: American  Journal  Gastroenterology

 

Nutritional Management of Patients with Cirrhosis and Hepatic Encephalopathy.

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Consensus recommendations are now available despite continued knowledge gaps in this area.
An expert panel commissioned by the International Society for Hepatic Encephalopathy and Nitrogen Metabolism has recommended that all patients with cirrhosis and hepatic encephalopathy should receive nutritional management similar to that for patients with cirrhosis but without hepatic encephalopathy. Specific recommendations from their consensus document are described below.

Strongest recommendations:

  • All patients should undergo baseline nutritional assessment as a part of management. (The authors acknowledged that no clinically practical, well-validated tools to assess nutrition are currently available.)
  • Optimal daily energy intake should be 35 to 40 kcal/kg ideal body weight.
  • Optimal daily protein intake should be 1.2 to 1.5 g/kg ideal body weight.
  • Small meals evenly distributed throughout the day and a late-night snack of complex carbohydrate are ideal.
  • Hyponatremia should always be corrected slowly.

Recommendations with less certainty, but with moderate evidence:

  • Encourage a diet rich in vegetable and daily protein.
  • Branched-chain amino acid supplementation might allow recommended nitrogen intake to be maintained in patients intolerant of dietary protein.
  • A 2-week course of a multivitamin could be justified in patients with decompensated cirrhosis.
  • Encourage a diet containing 25 to 45 g of fiber daily.
  • Avoid long-term treatment with manganese-containing nutritional formulations.

Source: NEJM