Sub-clinical hepatic encephalopathy in cirrhotic patients is not aggravated by sedation with propofol compared to midazolam: A randomized controlled study

Background & Aims

The risk of exacerbating sub-clinical hepatic encephalopathy (HE) by propofol has not been established. The aim of this study is to determine whether the use of propofol, for upper endoscopy in patients with cirrhosis, precipitates sub-clinical HE.

Methods

Sixty-one patients with compensated HCV and HBV cirrhosis (CP score 5–6) were randomly selected and divided into two groups (intent-to-treat population) matched for age, gender, and BMI. The first group received a single propofol sedation (N=31, age 57±12, dose range 70–100mg/procedure) and the second group (N=30, age 56±12, dose 3–6mg/procedure) received a single midazolam sedation, all done by an anesthesiologist. All patients completed number connection test (NCT), cognitive function score, time to recovery, time to discharge sheets, and hemodynamic parameters before sedation, and at discharge from the endoscopy unit, 1h post-procedure. Thirty control subjects without cirrhosis were matched to the cirrhotic patients who received sedation with regard to age, gender, BMI, and education level.

Results

A total of 58/61 cirrhotic patients (95%) had sub-clinical encephalopathy before the endoscopy (mean NCT 84.7±77s, normal <30s). No patient developed overt HE after sedation. There were no differences between groups in the incidence of adverse effects, cognitive function, MELD score, CP score, oxygen saturation, or respiratory and heart rates before and after sedation. Propofol did not exacerbate minimal HE when compared to midazolam (NCT changed from 87.5±62s prior to sedation to 74.2±58s after sedation in the propofol group versus 72.8±62s before to 85.6±72s after sedation in the midazolam group; p<0.01). Time to recovery (4.1±1.9min vs. 11.5±5.0min, p<0.001), and time to discharge (38.0±9min vs. 110±42min, p<0.001) were significantly shorter with propofol than midazolam. Pre- and post-procedure NCT (from 25±20s to 24±20s), cognitive function score (from 25 to 26), time to recovery (3.5±1.0min), and time to discharge (35±10min) did not change in the healthy controls.

Conclusions

Sedation with propofol has a shorter time recovery and a shorter time to discharge than midazolam and does not exacerbate sub-clinical hepatic encephalopathy in patients with compensated liver cirrhosis.

Abbreviations: HE, hepatic encephalopathy, CP, Child-Pugh’s score, NCT, number connection test, GI, gastro intestinal, GABA, γ-amino butyric acid, BMI, body mass index, ALT, alanine aminotransferases, AST, aspartate aminotransferases, GGT, gamma glutamyl tranferases, MELD, model of end stage liver disease, RR, respiratory rate, HR, heart rate, ANOVA, analysis of variance

Keywords: Sedation, Endoscopy, Midazolam, Propofol, Cirrhosis, Encephalopathy