Prophylaxis of hepatic encephalopathy in acute variceal bleed: a randomized controlled trial of lactulose versus no lactulose.
OBJECTIVE
Acute variceal bleed (AVB) is an important precipitating factor for development of hepatic encephalopathy (HE). However, there is paucity of data on the role of lactulose for prevention of HE after AVB. We evaluated the role of lactulose for prophylaxis of HE after AVB.


METHODS
Consecutive patients of cirrhosis with AVB enrolled. Patients included if >18 years old and had no HE at the time of presentation. Patients were randomized to receive lactulose (Group-L) or no lactulose (Group-P) along with standard treatment of AVB as per Baveno 4 guidelines. Primary endpoint was development of overt HE as per West Haven criteria within 120 h of randomization.


RESULTS
Seventy patients were randomized into group-L (Gp-L, n = 35) and group-P (Gp-P, n = 35). There was no significant difference in baseline characteristics between the two groups. Characteristics of variceal bleed were also similar (Gp-L vs Gp-P [mean arterial pressure 81.0 ± 10.5 vs 79.5 ± 9.9 mmHg], Hb [8.4 ± 1.5 vs 9.3 ± 2.3 g/dL], blood transfusion requirement [1.6 ± 1.1 vs 1.3 ± 0.9 units], time to endoscopy [6.3 ± 2.8 vs 7.0 ± 3.1 h], and esophageal source of bleed [92% vs 88%]). Nineteen (27%) patients developed HE; five patients (14%) in Gp-L and 14 patients (40%) in Gp-P, P = 0.03. The median grade of HE was 2 (range 2-4) and median time interval of development of HE after randomization was 2 days (range 1-4). Nine patients (13%) died; three (8.5%) patients in Gp-L and six (17%) patients in Gp-P, P = 0.23. Patients who developed HE had significantly higher baseline Child-Turcotte-Pugh score score (10.2 ± 1.2 vs 9.4 ± 1.4 P = 0.04), model for end stage liver disease score (18.2 ± 3.9 vs 15.4 ± 4.5 P = 0.02), arterial ammonia level (112.2 ± 22.7 vs 94.8 ± 17.6 umol/L, P = 0.001), baseline total leukocyte count (10,505.2 ± 8911.9 vs 5784.3 ± 3387.0 P = 0.002), total bilirubin (3.4 ± 1.3 vs 2.1 ± 1.8 mg%, P = 0.008) as compared to patients who did not develop HE. On multivariate analysis only baseline arterial ammonia, blood requirement during hospital stay and lactulose therapy were predictors of development of HE.


CONCLUSIONS
Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed.
Department of Gastroenterology, G. B. Pant Hospital, New Delhi, India.
Praveen
P
Sharma
Amit
A
Agrawal
Barjesh C
BC
Sharma
Shiv K
SK
Sarin
D000208:Acute Disease; D000328:Adult; D001803:Blood Transfusion; D016009:Chi-Square Distribution; D004932:Esophageal and Gastric Varices / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007194:India; D007792:Lactulose / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D005765:Gastrointestinal Agents; D007792:Lactulose