The Effectiveness of Oral Lactulose Versus Lactulose Enema on the Time to Recovery from Overt Hepatic Encephalopathy

Abstract

Objectives: To compare efficacy of lactulose retention enema with oral lactulose therapy in terms of time to one grade improvement in hepatic encephalopathy (HE) and time to complete recovery from overt hepatic encephalopathy.

Methodology: This, open-label single blinded randomized controlled trial was conducted at Khyber Teaching Hospital, Peshawar from July to December 2024. The study protocol was registered with Clinicaltrials.gov with the ID: NCT05788627.  The trial enrolled 100 patients with Grade-III/IV hepatic encephalopathy precipitated by constipation. Patients were randomly assigned to oral or enema lactulose therapy - Clinical Arm 1 -CA1 and Clinical Arm 2 -CA2 respectively. Patients in CA1 received oral lactulose and placebo (plain water) enema, while patients in CA2 received oral lactulose alongside lactulose enema. The primary end points were time to one grade improvement and complete recovery. Data were analyzed using IBM SPSS 26.0. Qualitative variables were compared using Chi-square test and Intergroup comparison was done using independent samples T-test where needed. A p-value of < 0.05 was considered statistically significant.

Results: “Mean time for one grade improvement in hepatic encephalopathy” was 38.05 hours in CA1 while 30.13 hours in CA2 (p value 0.008). “Mean time to complete recovery from hepatic encephalopathy” in hours was 70.16 in CA1 and 54.86 in CA2 (p value 0.000). A statistically significant difference was noted in “Mean number of Doses required to bring about one grade improvement” (3.2 vs 4.9 in CA1 and CA2 respectively).

Conclusion: Lactulose enema in combination with oral lactulose shows faster improvement in the HE grades and quicker overall recovery in clinical status in overt HE patients as compared to oral lactulose alone.