Refeeding and Drug Therapy in Acute Diarrhea

In a child with acute gastroenteritis, rehydration restores volume and electrolytes, as described in Rehydration Management in Acute Diarrhea; feeding restores the gut’s absorptive workload; and drugs act only where a specific indication exists. In this topic the third layer is the smallest, and several of the interventions people reach for first are the ones the evidence most clearly withholds.

The main European guideline, from ESPGHAN and ESPID (the European paediatric gastroenterology and infectious diseases societies), grades each recommendation twice: by its strength, and by the quality of the evidence behind it. A strong recommendation can therefore rest on low-quality evidence.

Feeding during acute gastroenteritis

Early resumption of feeding is recommended — a strong recommendation, though on low-quality evidence — and an age-appropriate diet should be started during or after initial rehydration, conventionally at 4 to 6 hours. Fasting does not rest the gut in any useful way; it adds nutritional risk without shortening the illness.

Breastfeeding continues throughout rehydration and throughout any dietary change. Breast milk contains lactose, but the guideline recommends continuing regular feeding with no dietary change, including milk, and interrupting breastfeeding during diarrheal illness is itself one of the strongest risk factors for severe dehydration.

Other milk feeds are handled in the same spirit: formula does not need to be diluted, and a modified milk formula is usually unnecessary. The BRAT diet — bananas, rice, applesauce and toast — has not been studied and is not recommended, and beverages with high sugar content should not be used, because their sugar adds to the osmotic load.

Lactose-free feeds

The case for changing milk feeds rests on lactose. Viral enteritis damages the small-bowel mucosa, brush-border lactase (the enzyme on the intestinal surface that digests lactose) falls, undigested lactose stays in the lumen and holds water, and an osmotic diarrhea is layered on top of the original one. The mechanism is set out in Pathophysiology of Acute Diarrhea and Dehydration.

The trial evidence points to a benefit, drawn mainly from children in hospital. A Cochrane systematic review found that in young children given lactose-free rather than lactose-containing feeds, diarrhea lasted on average about 18 hours shorter — mean difference −17.77 hours, 95% CI (confidence interval) −25.32 to −10.21, 16 trials, 1467 participants, low-quality evidence — and treatment failure roughly halved, RR (risk ratio) 0.52, 95% CI 0.39 to 0.68, 18 trials, 1470 participants, moderate-quality evidence. Most trials were in inpatients; the two outpatient trials showed no significant effect on duration.

The recommendations are narrower than the mechanism might suggest, and they match that split between settings. Routine use of lactose-free feeds is not recommended in the outpatient setting — a strong recommendation on low-quality evidence — while in hospitalized children under 5 years lactose-free formulas can be considered, a weak recommendation on low-quality evidence. Diluted lactose-containing milk has insufficient evidence either way. A lactose-restricted diet for an older child means dropping cow’s milk and dairy, not dropping the breast.

Antibiotics

Anti-infective therapy should not be given to the vast majority of otherwise healthy children with acute gastroenteritis, and antibiotic therapy for acute bacterial gastroenteritis is not needed routinely but only for specific pathogens or in defined clinical settings. Most illness is self-limited regardless of the organism.

The exceptions are set by the organism and by the child. Treatment is recommended for Shigella and cholera; for Campylobacter it is recommended mainly in the dysenteric (bloody) form; for nontyphoidal Salmonella — the strains that do not cause typhoid fever — it depends on whether the child is at high risk of bacteremia, the spread of bacteria into the bloodstream; and for Shiga toxin-producing E. coli it is withheld.

The counterintuitive entry is the Shiga toxin-producing organism: bloody stool ordinarily suggests treatment, but here antibiotics are withheld. The guideline notes conflicting results about whether treating such gastroenteritis changes the risk of hemolytic uremic syndrome, and withholds the recommendation on that basis.

When an antibiotic is given, the route matters as well. Parenteral rather than oral antibiotics are recommended when the child cannot take oral medication, when an underlying immune deficiency comes with fever, in severe toxemia or suspected bacteremia, and in neonates and young infants under 3 months with fever.

Probiotics

Probiotics are live microorganisms given for a health benefit. Selected probiotics can be used in children with acute gastroenteritis as an adjunct to rehydration therapy — a strong recommendation on moderate-quality evidence — and the guideline groups whose use should be considered are Lactobacillus rhamnosus GG and Saccharomyces boulardii, both on strong recommendations with low-quality evidence. Lactobacillus reuteri DSM 17938 carries a weak recommendation on very low-quality evidence.

Probiotics as a group reduced the duration of diarrhea by approximately one day, but the effect is strain-specific: efficacy and safety cannot be extrapolated from one probiotic to another, and a product without one of the named strains has correspondingly weaker support. Effective strains may also reduce length of hospital stay in admitted children. None of this substitutes for rehydration.

Drugs aimed at the stools

Drugs that aim to reduce the stools themselves work in different ways, and the recommendations differ with them.

Racecadotril can be considered in the management of acute gastroenteritis — a weak recommendation on moderate-quality evidence. It is an antisecretory drug. It inhibits enkephalinases, the enzymes that break down endogenous enkephalins; enkephalins act on delta receptors and inhibit water and electrolyte secretion into the lumen, so prolonging their action reduces intestinal secretion. An individual patient data meta-analysis — a pooled analysis of each child’s data from the original trials — of 9 randomized trials in 1348 children found that racecadotril significantly shortened diarrhea compared with placebo, with almost twice as many children recovering at any given time, and no difference in adverse events.

Loperamide is not recommended in the management of acute gastroenteritis in children — a strong recommendation on very low-quality evidence. It acts as a mu-opioid receptor agonist rather than an enkephalinase inhibitor, and it is not the antisecretory drug this guideline endorses.

Diosmectite, an adsorbent (a substance that binds other material to its surface), can be considered — a weak recommendation on moderate-quality evidence — though combining it with Lactobacillus rhamnosus GG is no better than the probiotic alone. Other adsorbents, bismuth subsalicylate and antimotility agents are not recommended.

Zinc and antiemetics

Two further drugs depend on the setting, or on safety questions that remain open.

Zinc reduces diarrhea duration in children over 6 months in settings where zinc deficiency is common, but in regions where deficiency is rare no benefit is expected — the only European randomized trial found no difference. Routine zinc is therefore not a European recommendation.

Ondansetron, an antiemetic (a drug against vomiting), may be effective against vomiting related to acute gastroenteritis, but the guideline withholds a final recommendation pending safety clearance in children because of a warning about severe cardiac effects, and no other antiemetic has evidence to support it.

What not to do

Several of these recommendations run against common instinct, and they are easiest to remember side by side:

Even when fluids, feeding and drugs are handled well, a minority of children still develop complications — some from the fluid loss, some from the organism, and a few from the treatment itself.