Treating Hepatic Encephalopathy With Lactulose and Rifaximin

Arun Jesudian, MD: If we take those 2 medicines 1 at a time, lactulose is a type of laxative. It’s a syrup and patients can either take it orally or we give it rectally via an enema if the patient is not able to swallow properly, or sometimes we give it via an NG [nasogastric] tube in that situation as well. Early on when you administer it, do you write that order in any specific way? Are you saying until the patient has X amount of bowel movements, or are you just giving them a large amount to flush them out?

James Williams, MS, DO, FACEP: Typically, I’ll give 1 dose. It will be an ongoing therapy and I hope that I don’t have to give ongoing therapy because that means that the patient is still in the emergency department for that period. At least when I start it there, it lets everybody know—whether it’s the nurses, the pharmacy, the admitting service—that yes, this patient does have HE [hepatic encephalopathy], plus or minus any of their other primary diagnosis. One thing that’s interesting is that whenever we pull up rifaximin [Xifaxan], it pulls it up as it would any other antibiotic, and so sometimes that can be misconstrued as I’m treating some infection. So they may have an infection, but they may not have. It’s important to be explicit to say this is being used for hepatic encephalopathy and why, because that’s going to key people in on the other treatments that are going to be required for HE.

Arun Jesudian, MD: Yes, absolutely. That combination should set off red flags about this patient being an HE patient who has cirrhosis and has all the other potential complications of cirrhosis. I think you are absolutely fair in saying that you’d rather not being administering a bunch of lactulose, meaning that patient is still with you and not admitted to a hospital service or the floor. When we are managing these patients early on, do you like to give a lot of lactulose? Promoting a lot of bowel movements can sometimes clear up this altered mental status, particularly if the major reason they’re altered is that they were constipated or not taking their medications at home. Just as a reminder for the viewers that both of these medications, lactulose and rifaximin, work to decrease the bacterial burden in the colon, because it’s bacteria that are breaking down proteins and generating this ammonia that cannot be cleared in the setting of cirrhosis and portal hypertension. Lactulose promotes bowel movements and can sometimes decrease that ammonia load significantly. Then maintenance lactulose, which is definitely beyond the time when you’re seeing these patients, but as they are being stabilized during their hospitalization or on track to go home, the maintenance dosing, usually we look for 2 to 4 soft bowel movements a day where they’re clearing enough bacteria but they’re not dehydrated by having diarrhea, and adding that rifaximin, that nonabsorbable antibiotic, which is dosed twice daily can really add to lactulose in terms of efficacy. You mentioned length of stay which there are several studies that have shown that length of stay can be significantly decreased if patients are given that combination, lactulose plus rifaximin for treatment of HE. We know from well-designed trials that the risk of recurrent episodes of HE can be impacted by the addition of rifaximin to lactulose. You and I have spoken about this previously, but in terms of the audience, we know from a randomized trial where rifaximin was compared to placebo in patients who had had 2 or more episodes of overt hepatic encephalopathy, but were in remission at the start of the trial, that their 6-month risk of having a recurrent episode of hepatic encephalopathy was 58% less if they were on rifaximin plus lactulose compared to lactulose alone, or lactulose plus placebo. The risk of being hospitalized for HE was actually 50% less in that 6-month period, and that’s why it’s such an important medication to start in hospitalized patients with overt HE, whether that’s their first episode or, certainly, if it’s a recurrent episode. You mentioned that it is an oral medicine that the patients need to be able to swallow, so sometimes early on it can be a challenge. It sounds like you try to start it even in the emergency department when you can. Is that true?

James Williams, MS, DO, FACEP: I find that it’s helpful, not just in the long-term chronic, but also in the acute phase when you’re looking considering the fluid shifts that these patients have. If you’re giving lactulose it may be functional for the gut biome, but you’re messing up the fluid shifts dramatically. So now suddenly, what’s their potassium? What’s their sodium? What’s their overall total volume body balance? That’s really complicated. One of the other features that is beneficial for rifaximin is to minimize that. So not just because society guidelines recommend it and show that there is decrease in readmission and progression of disease, but that in the acute phase I’m not going to have those big fluid shifts and I’m going to minimize some of the electrolyte derangements by doing that. Another analogy would be within a hypertensives, that, typically, instead of increasing a dose of 1 into hypertensive, I’ll add a second agent, both at lower doses, and by doing that the concept is the same. That I optimize what my efficiency is of that treatment, and I minimize the side effects of it.The dual therapy with lactulose and rifaximin is beneficial both in the short- and long-term setting.

Arun Jesudian, MD: Such a key point about the fluid shift that you bring up. These patients are often hypovolemic when they present because they’re on diuretics, their PO [by mouth] intake is often poor, and they might be on lactulose at home. For those reasons, giving them more lactulose causing diarrhea could potentially cause more problems initially, unless you’re volume resuscitating them, and the rifaximin being a nonabsorbable antibiotic, doesn’t cause that same issue. It’s definitely important to keep in mind.

Transcript Edited for Clarity