Lactulose-induced Hypernatremia in Cirrhotic Patients With Hepatic Encephalopathy

Lactulose is an osmotic laxative used to treat hepatic encephalopathy (HE) in cirrhotic patients. However, lactulose may cause hypernatremia (HN).

We identified all patients admitted with cirrhosis and HE at our institution (January 1, 2018 to December 31, 2023). To compare HE patients with and without HN, we used propensity matching to control for the severity of HE and underlying liver disease. The primary endpoint was mortality, and secondary endpoints included total and rectal lactulose dose (g) and length of stay (LOS).

Among 6742 patients admitted with cirrhosis, 1651 (25%) had a primary diagnosis of HE; 347 patients had HN (21%), and 106 patients (6%) developed a sodium≥150 mEq/L (HN group) during hospitalization. Cirrhosis was most commonly caused by alcohol or MASH and the median MELD was 24. Admission sodium was 137 mEq/L and peak, 152 mEq/L (medians); all patients received lactulose. The average daily lactulose dose to peak sodium level was higher in the HN group than in matched HE controls (87 g vs. 38 g, P<0.001). 67 (63%) patients in the HN group received rectal lactulose (median sodium 154 mEq/L). Rectal lactulose was the strongest independent predictor of HN (OR=7.12, P<0.001), and doses ≥485 g (rectal ± oral lactulose) over 5 days were associated with increased HN risk (OR:7.89, P<0.001). Overall, 64 HE patients (60%) with HN died during hospitalization, compared with 37 (35%) without HN (P<0.001).

Lactulose-induced HN in patients with HE was associated with a remarkably high mortality rate. Rectal lactulose in HE patients may be unsafe.