To the Editor We read with interest the article by Rahimi et al,1 which we believe has potential to change existing clinical practice. We do, however, have a few thoughts we would like to share.
First, though the role of the intestine and gut flora in hepatic encephalopathy (HE) is complex, blood ammonia is still thought to play a major part.2 Presumably, both lactulose and polyethylene glycol (PEG) decrease the amount of ammonia generated in and/or absorbed from the intestine. Therefore, the finding that more rapid improvement in HE in the PEG group was accompanied by a relatively less robust decrease in blood ammonia requires explanation. The measured blood ammonia is in fact “total ammonia,” a combination of NH3 and NH4+ species, with only NH3 freely diffusing through the blood-brain barrier and hence having greater toxicity. In fact, the poor correlation between the degree of HE and total blood ammonia is much improved when NH3 is considered separately.3 Furthermore, the equilibrium between NH3 and NH4+ is determined by blood pH, with alkalemia increasing the blood NH3 concentration. It is attractive to speculate that excess diarrhea in the PEG group may have also induced a transient metabolic acidosis, causing a relative decrease in the blood NH3/NH4+ concentration ratio. Resolution of this transient acidosis may account for the rapid recurrence of HE seen in 2 patients in the study—an observation consistent with our anecdotal experience. Additional patient data on acid-base status before and after the treatment would be illuminating in this regard.
Cutler T, Mints G. Lactulose vs Polyethylene Glycol for Treatment of Hepatic Encephalopathy. JAMA Intern Med. 2015;175(5):867-869. doi:10.1001/jamainternmed.2015.0321