Description of Lactulose Administration by Balloon Rectal Tube in Severe Hepatic Encephalopathy (ALPACA)

Acute liver failure in cirrhotic patients is associated with a one-month mortality of 48%. Encephalopathy, largely related to hyperammonemia, is a frequent complication of liver failure and is a poor prognostic marker. Lactulose decreases ammonia by acidification of the colon, replacement of urease-producing bacteria and creation of a laxative effect. Thus, the administration of lactulose in patients with severe hepatic encephalopathy reduces mortality by more than 40%.

In intensive care patients, lactulose is often administered rectally. The use of simple rectal tubes is associated with frequent leakage of lactulose as well as faecal discharge and therefore risks of infection and skin lesions. Balloon rectal tubes with a drug delivery valve have recently been developed and used in this indication. The aim of this study is therefore to describe the use of these balloon rectal tubes to administer Lactulose in severe hepatic encephalopathy.

This suggests that ammonia reduction in these patients may prolong survival time.

No studies have described the administration of Lactulose via the rectal route with a balloon tube. The descriptive methodology is therefore appropriate. This is a preliminary study allowing data collection to establish the methodology for a subsequent clinical trial.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38000
    • Pr PIERRE BOUZAT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients with severe hepatic encephalopathy hospitalised in intensive care

Description

Inclusion Criteria:

• > 18 years
• Patients treated with Lactulose with balloon rectal probe

Exclusion Criteria:

• Patient(s) objecting to the use of their data for research purposes
• Rectal probe contraindication: damage to the rectal mucosa, rectal surgery, severe haemorrhoids, rectal stenosis, rectal tumour,
• Lactulose contraindication (person unable to absorb galactose)
• Patients deprived of liberty, under guardianship or curators
• Pregnant women
• Patient not affiliated to a social security scheme

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe ammonia during lactulose administration by balloon rectal tube	Variation of ammonia before treatment and after 48h of treatment	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the neurological course following administration of lactulose via a balloon rectal tube	Score Richmond Agitation-Sedation Scale from the minimum value -4 to maximum value + 4 Richmond Agitation and sedation scale , agitation	at 7 days
Patient outcomes	Duration of invasive ventilation, duration of resuscitation or intensive care, duration of hospital stay, mortality	at 28 days
Caregiver satisfaction	Anonymised use and maintenance satisfaction questionnaire into 0 is the worst score and 10 is the better score	at 7 days
Describe ammonia levels after lactulose administration via balloon rectal tube.	Change in ammonia over 1 week in µmol/l after administration	at 7 days
Describe balloon rectal probe retention	Frequency of leakage during and within one hour of lactulose administration when the rectal probe balloon is inflated	at 7 days
Describe the skin tolerance of patients during hospitalization.	Percentage of patients with at least one pressure sore or infection in the lumbar, pelvic, buttocks, or buttock area	at 7 days
Describe complications related to the balloon rectal tube	Percentage of patients with at least one of the following complications: leakage of faeces during or after use of the catheter; rectal bleeding; peri-anal skin damage (fissure, ulcer, infection); bowel obstruction; bowel perforation, rectal pain, abdominal distension.	at 7 days
Describe complications related to rectal lactulose administration	Percentage of patients with at least one of the following complications: hypernatremia > 150 mmol/L, dehydration, renal insufficiency urea creatinemia.	at 7 days

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Pierre BOUZAT, recruting, Centre Hospitalier Universitaire Grenoble Alpes

Publications and helpful links

General Publications

• Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut. 2006 Jan;55(1):98-104. doi: 10.1136/gut.2004.061754. Epub 2005 Jul 15.
• Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P. Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology. 1999 Mar;29(3):648-53. doi: 10.1002/hep.510290309.
• Shalimar, Sheikh MF, Mookerjee RP, Agarwal B, Acharya SK, Jalan R. Prognostic Role of Ammonia in Patients With Cirrhosis. Hepatology. 2019 Sep;70(3):982-994. doi: 10.1002/hep.30534. Epub 2019 Mar 21.
• Dasarathy S, Mookerjee RP, Rackayova V, Rangroo Thrane V, Vairappan B, Ott P, Rose CF. Ammonia toxicity: from head to toe? Metab Brain Dis. 2017 Apr;32(2):529-538. doi: 10.1007/s11011-016-9938-3. Epub 2016 Dec 24.
• Jalan R, De Chiara F, Balasubramaniyan V, Andreola F, Khetan V, Malago M, Pinzani M, Mookerjee RP, Rombouts K. Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension. J Hepatol. 2016 Apr;64(4):823-33. doi: 10.1016/j.jhep.2015.11.019. Epub 2015 Dec 2.
• Ravi S, Bade KS, Hasanin M, Singal AK. Ammonia level at admission predicts in-hospital mortality for patients with alcoholic hepatitis. Gastroenterol Rep (Oxf). 2017 Aug;5(3):232-236. doi: 10.1093/gastro/gow010. Epub 2016 May 1.
• Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology. 2007 Dec;46(6):1844-52. doi: 10.1002/hep.21838.

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): August 27, 2024
• Study Completion (Actual): August 27, 2024

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Brain Diseases; Hepatic Encephalopathy
• Other Study ID Numbers: CHU Grenoble/ ALPACA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No