A recent randomized multicenter study (D Jarzebicka et al. JPGN 2019; 68: 318-24) compared polyethylene glycol 3350 (PEG, aka Miralax) and lactulose for functional constipation in a cohort of 102 patients (12 weeks of treatment and 4 weeks of follow-up).
- PEG 3350 dosing divided into 2 doses:
- <8 kg: 5 g/day
- 8-12 kg: 10 g/day
- 12-20 kg: 15 g/day
- >20 kg: 20 g/day
- Lactulose was given as 1 mL/kg twice a day
A “good clinical outcome” was considered if there were three or more stools per week and an improvement in stool consistency of at least 2 types in the Bristol scale.
- At week 12, a good clinical outcome was noted in 98% of PEG group compared with 90% in the lactulose group
- PEG group had increased defecations relative to lactulose: 7.9 vs. 5.7, less stool retention: 7% vs 10%, and fewer hard stools 7% vs 13%
- Side effects, mainly abdominal pain and bloating, were reported more frequently with lactulose than with PEG: 23 vs 15, P=0.02)
My take: This study showed that PEG 3350 was more effective and had fewer side effects than lactulose for constipation in children between 6 months of age and 6 years.
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From Civil and Human Rights Museum, Atlanta
A recent review (Clin Gastroenterol Hepatol 2014; 12: 1964-72) provides useful advice on testing for bacterial overgrowth and explains the limitations/obstacles in determining whether bacterial overgrowth is present.
- Preparation: avoid antibiotics for 4 weeks prior to testing, avoid bismuth for 2-4 weeks, avoid probiotics for 2-3 weeks before testing, avoid consumption of non absorbable carbohydrates (eg. pasta, bread, fiber cereal, beans) the night prior
- Glucose substrate for hydrogen breath testing is likely most suitable. 50 g in 250 mL. Check baseline and then every 15 minutes over 120 minute testing interval. Positive study: increase of 12 ppm (or more) over baseline and/or baseline >20 ppm (if proper test conditions)
- Glucose breath test (GBT): sensitivity 20-93%, specificity 30-86%. False-positive results can occur with rapid small-bowel transit. GBT may not detect distal small bowel bacterial overgrowth. Lactulose breath test (LBT) generally has lower specificity.
- If breath testing is not available, small-bowel aspiration for quantitative culture is a reasonable consideration (challenging methodology). Alternatively, a trial of empiric antibiotics may be considered if pretest probability is high.
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In a study (JAMA Intern Med. Published online September 22, 2014. doi:10.1001/jamainternmed.2014.4746) with 50 participants, PEG was more effective than standard therapy of lactulose for hepatic encephalopathy. PEG vs Lactulose (HELP study) Abstract.
Here’s an excerpt:
Design, Setting, and Participants The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE.
Interventions Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization…
Results Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01)… The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related.
Conclusions and Relevance PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE.
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Hepatology 2014; 60: 715-33. This publication is the AASLD Practice Guideline for Hepatic Encephalopathy in Chronic Liver Disease. The recommendations are too extensive to summarize. Here’s one: despite concerns about efficacy, “lactulose is the first choice for treatment of episodic” overt hepatic encephalopathy. Rifaximin is an effective add-on therapy to lactulose for prevention of OHE recurrence. AASLD Guidelines Website
Hepatology 2014; 60: 679-86. Using the Drug-Induced Liver Injury Network between 2004-2012, the authors identified 22 cases of hepatotoxicity attributed to statins. Median age was 60 years. The latency to onset of symptoms varied from 34 days to 10 years with a median of 155 days. Nine patients had a cholestatic hepatitis pattern and 12 had hepatocellular injury, including six with an autoimmune phenotype. Severity: nine required hospitalization, four had evidence of hepatic failure and one died.
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