Paediatric Gastroenteritis Review

Acute Gastroenteritis (AGE) kills thousands of children each year and consequences are worse in the developing world as diarrhoeal diseases occur on top of pre-existing malnutrition. It remains one of the most common ED presentation among children. Fortunately, most cases of acute gastroenteritis require minimal intervention, but severe dehydration and hypoglycemia may develop in cases of prolonged vomiting and diarrhoea requiring prompt management. The mainstay of treatment for mild-to-moderately dehydrated patients with acute gastroenteritis is oral rehydration solution (ORS). Antiemetics such as Ondansetron can decrease the need for intravenous fluids and hospitalisations.

Viral pathogens are the most common cause of AGE, accounting for up to 80% of cases

Common Bugs

E coli and Shigella are the most common bacterial pathogens in developing countries whereas Campylobacter is the most common bug in the developed world. Since most cases are viral, antibiotics are not required and only a few bacterial infections require treatment with antibiotics to hasten recovery and decrease bacterial shedding. It is critical to remember that some bacterial causes of colitis (ie, E coli O157:H7) can cause HUS that may be exacerbated by antibiotic administration. Therefore, antibiotics should not be started in most cases of suspected bacterial AGE until the species has been identified. Exceptions are made for children who are critically ill. Antibiotics do not come without side effects. Also, each course of antibiotics alters gut biome and can lead to a myriad of GI distress manifesting as abdominal pain, nausea, vomiting, and diarrhoea and  C diff colitis. Thus it is imperative to check recent antibiotic use in all patients who present with vomiting and diarrhoea. 

Children aged < 12 months should always be approached with a very broad differential. The most serious diagnosis to consider is intestinal malrotation and volvulus 

Brief Pathophysiology
Infection leads to gut biome alteration and host’s own immune system leads to inflammation of the lining of the stomach and intestines causing abdominal pain, nausea, vomiting, diarrhea, and hematochezia.

Vomiting that has continued for more than 24 to 48 hours without diarrhea is not AGE, and, while it may represent merely gastritis, a broad differential should be considered.

Key Questions in history:

• Color of both the emesis and stool (bilious or bloody emesis and bloody stools) 
• Fever
• History of recent travel and sick contacts 
• Quantity of urine output
• Regular medications or recent Antibiotic intake 

Protein allergies should be in the differential diagnosis in young infants presenting with vomiting and diarrhoea. 

Physical Exam and determining the degree of dehydration

• Vital Signs including CRT
• Hypotension is a late finding in children
• Segregate as  mild dehydration (< 3% loss of body weight - Normal exam), moderate dehydration (3%-9% loss of body weight - may have slightly sunken eyes, decreased tears, dry mouth, and slightly increased heart rate) or severe dehydration (> 9% loss of body weight - lethargic and tachycardic, with no tears, very dry mouth, and prolonged capillary refill)
• Abdo exam - localised tenderness to palpation. AGE might cause mild diffuse abdominal pain but not focal tenderness. 

Bloods, Imaging and Cultures

• Bloods are not required in mild to moderate illness. Inflammatory markers such as CRP has not been shown to differentiate viral versus bacterial causes of AGE and is not recommended in obvious cases of AGE. 
• Stool cultures and other stool studies are not required in most cases of uncomplicated AGE. However, in children with prolonged (> 3 days) or bloody diarrhea, toxic-appearance, and those with h/o recently travel abroad, stool cultures may be appropriate. 
• Stool ova and parasite examinations (Giardiasis, Toxocariasis and Cysticercosis)  are low-yield tests and should only be sent with appropriate travel history or prolonged disease with negative prior stool cultures or if there is evidence of weight loss or failure to thrive.
• Fecal calprotectin is an inflammatory marker in the stool which may aid in differentiating viral from bacterial AGE. Children with bacterial infections had signicantly higher levels of fecal calprotectin in the stool than children with viral infections. In general, fecal calprotectin does not affect the acute management of vomiting and diarrhea in the ED but it may be helpful in the outpatient workup of other illnesses, and can be sent in consultation with pediatric gastroenterology. 

Laboratory studies should be obtained in

all neonates with any level of dehydration and in

patients with an altered mental status not explained

by their suspected level of dehydration.

Treatment 

1. ABC (IV Cannula and fluid resus in critically ill, hypotensive, Consider Abx)

2. Antiemetics

PO/IV Ondansetron is safe and effective for AGE treatment in the ED. Vomiting children who are given ondansetron prior to an oral challenge are less likely to fail oral rehydration, require IV hydration, and be admitted to the hospital. Children treated with ondansetron also leave the ED sooner than those who are not given ondansetron prior to oral challenge. Most studies recommend the following oral pediatric dosing guidelines for ondansetron: children weighing < 15 kg: 2 mg; children weighing 15 kg to 30 kg: 4 mg; children weighing ≥ 30 kg: 8 mg. If the oral disintegrating tablets or oral solution are not available or tolerated, the IV preparation can be given orally. For children with severe dehydration in whom IV hydration will be started immediately, IV ondansetron can be given (0.15 mg/kg, max 8 mg).

3. Rehydration 

Liquids such as water, juices, sports drinks, soups, etc, are not traditionally recommended for mild-to- moderate dehydration because they do not contain the ideal ratio of sugars and salts to promote intestinal absorption, and they may serve as an osmotic diuretic. However, in a recent study from Canada, children with minimal dehydration due to AGE were treated with dilute apple juice had less treatment failure and less IV fluid administration. 

Oral challenge should be given as 5- 10 mL every 5 minutes for the first 30 minutes. If the child is tolerating, then the amount consumed can be increased by 5-mL increments over the next 30 minutes. Depending on the degree of dehydration, 50 to 100 mL/kg of ORS should be given over 3 to 4 hours to correct dehydration. Those who fail oral rehydration after antiemetics get IV (do Renal Function, Electrolutes, Glucose when inserting IV) or NG fluids. 

Majority agrees on starting with a 20 mL/kg NS bolus crystalloids. In children with stable blood pressure and normal capillary refill, infusion over 30 to 60 minutes is appropriate. In severely dehydrated patients appearing toxic, administer bolus IV fluids. Additionally, in if they are hypoglycaemic, then start with a 20 mL/kg bolus of D5NS followed by crystalloids. 

4. Anti-Diarrheal agents 
Loperamide is an opioid receptor agonist that acts as both an antisecretory and antimotility agents but has the potential of causing drowsiness and ileum. Thus it is strongly discouraged in children of all ages. Bismuth Salicylate is another option but it may cause salicylate toxicity if it is used incorrectly and therefore, it is also not recommended for use in children. 

Racecadotril is another antidiarrheal drug that has been shown in a few studies to reduce the duration and frequency of diarrhea in infants and children. It is an enkephalinase inhibitor and results in decreased secretion of water and electrolytes into the intestines. A recent meta-analysis of studies that examined the effectiveness of racecadotril in decreasing diarrhea found that it was well-tolerated and resulted in decreased duration of symptoms, as well as less stool frequency and volume. However, the included studies were of poor quality and subject to bias. 

  

5. Probiotics

• Probiotics are nonpathogenic organisms that work by regulating the gut biome and help to lessen in ammatory pathways. These agents help to decrease stool volume and frequency in AGE. Numerous studies have shown that Lactobacillus rhamnosus GG and Saccharomyces boulardii can reduce the length of diarrheal symptoms in children, with very few side effects but probiotics are probably most effective if started early. Also probiotics seem to have the greatest impact on diarrhea due to viral causes.
• Prebiotics are food products that promote the growth and activity of bacteria that reside in the gut and Synbiotics are a combination of probiotics and probiotics. 

6. Zinc

Zinc supplementation should be strongly considered when treating diarrhea in children residing in developing countries; supplementation significantly reduces diarrhea duration in children with underlying zinc deficiency. 


Safety Netting and discharge advise: Advise parents and carers of children:

• To continue usual feeds, including breast or other milk feeds and include ORS solution as supplemental fluid
• To discourage the drinking of fruit juices and carbonated drinks
• A rough calculation of the amount of ORS needed to replace emesis and diarrhea is 10 mL/kg for each episode of emesis or diarrhoea
• To seek advice if the child refuses to drink the ORS solution or vomits persistently
• Usual duration of diarrhoea is 5–7 days and in most children it stops within 2 weeks
• Usual duration of vomiting is 1 or 2 days and in most children it stops within 3 days
• Advise regarding hand Hygiene and inform that children should not go back to their school or other childcare facility until at least 48 hours after the last episode of diarrhoea or vomiting. 

Take Home:

• Start ondansetron early to children presenting with AGE. 
• Mainstay of treatment is oral rehydration with ORS and IV fluids are indicated only in severe dehydration or in children who are unable to take ORS orally.
• Laboratory studies are not indicated in mild-to-moderate dehydration due to AGE. In children with severe dehydration, start IV fluids and do renal function, blood glucose and electrolytes. 
• Probiotics can help decrease the duration of their diarrhea by approximately 24 hours but should be prescribed for children with AGE early in the course of their illness.Viral infections are the most common cause of AGE, so stool cultures are not needed. 

References and Further Reading:

1. http://pedemmorsels.com/diarrhea-and-dehydration/
2. http://pedemmorsels.com/probiotics-for-age/
3. Roslund G, Hepps TS, McQuillen KK. The role of oral ondansetron in children with vomiting as a result of acute gastritis/gastroenteritis who have failed oral rehydration therapy: a randomized controlled trial. Ann Emerg Med. 2008;52(1):22-29. 
4. O’Ryan M, Lucero Y, O’Ryan-Soriano MA, et al. An update on management of severe acute infectious gastroenteritis in children. Expert Rev Anti Infect Ther. 2010;8(6):671-682. 
5. Bonadio WA. Acute infectious enteritis in children. Emer- gency department diagnosis and management. Emerg Med Clin North Am. 1995;13(2):457-472.
6. Bruzzese E, Lo Vecchio A, Guarino A. Hospital management of children with acute gastroenteritis. Curr Opin Gastroen- terol. 2013;29(1):23-30. 
7. Sýkora J, Siala K, Huml M, et al. Evaluation of faecal calpro- tectin as a valuable non-invasive marker in distinguishing gut pathogens in young children with acute gastroenteritis. Acta Paediatr. 2010;99(9):1389-1395. 
8. Duman M, Gencpinar P, Biçmen M, et al. Fecal calprotectin: can be used to distinguish between bacterial and viral gas- troenteritis in children? Am J Emerg Med. 2015;33(10):1436- 1439. 
9. Leung AK, Robson WL. Acute gastroenteritis in children: role of anti-emetic medication for gastroenteritis-related vomiting. Paediatr Drugs. 2007;9(3):175-184. 
10. Freedman SB. Acute infectious pediatric gastroenteritis: beyond oral rehydration therapy. Expert Opin Pharmacother. 2007;8(11):1651-1665. 
11. Levine DA. Antiemetics for acute gastroenteritis in children. Curr Opin Pediatr. 2009;21(3):294-298.
12. Marchetti F, Bonati M, Maestro A, et al. Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: multicenter double blind ran- domized controlled trial. PLoS One. 2016;11(11):e0165441. 
13. Freedman SB, Tung C, Cho D, et al. Time-series analysis of ondansetron use in pediatric gastroenteritis. J Pediatr Gastroenterol Nutr. 2012;54(3):381-386. 
14. Magrone T, Jirillo E. The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis. Curr Pharm Des. 2013;19(7):1329-1342. 
15. Vandenplas Y, De Greef E, Hauser B, et al. Probiotics and prebiotics in pediatric diarrheal disorders. Expert Opin Phar- macother. 2013;14(4):397-409. 
16. Caffarelli C, Cardinale F, Povesi-Dascola C, et al. Use of pro- biotics in pediatric infectious diseases. Expert Rev Anti Infect Ther. 2015;13(12):1517-1535. 
17. Thomas DW, Greer FR, Committee on Nutrition; Section on Gastroenterology, Hepatology, and Nutrition. Probiotics and prebiotics in pediatrics. Pediatrics. 2010;126(6):1217-1231. 
18. Colletti JE, Brown KM, Sharieff GQ, et al. The management of children with gastroenteritis and dehydration in the emer- gency department. J Emerg Med. 2010;38(5):686-698. 
19. Freedman SB, Willan AR, Boutis K, et al. Effect of dilute apple juice and preferred uids vs electrolyte mainte- nance solution on treatment failure among children with mild gastroenteritis: a randomized clinical trial. JAMA. 2016;315(18):1966-1974. 
20. Granado-Villar D, Cunill-De Sautu B, Granados A. Acute gastroenteritis. Pediatr Rev. 2012;33(11):487-494.
21. Gordon M, Akobeng A. Racecadotril for acute diarrhoea in children: systematic review and meta-analyses. Arch Dis Child. 2016;101(3):234-240. 
22. https://www.nice.org.uk/guidance/cg84/chapter/1-Guidance#antibiotic-therapy

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

  

Diarrhea, “Answers” from EM Lyceum

by emlyceum

Acute gastrointestinal disorders are some of the most frequent problems evaluated by ED physicians.  Complaints of diarrhea account for almost 5% of visits to the emergency departments (Bitterman, 1988).  Although the disease entity is extremely prevalent and current evidence on the subject is nothing short of “voluminous,” practice differences among ED physicians in its evaluation and management are as varied and inconsistent as the stools themselves.

1. When do you send stool cultures, stool ovum and parasites, and/or fecal WBC? How do you use the results in diagnosis and management?

Stool evaluation of fecal leukocytes (WBC) and occult blood is sent in many ED’s as a positive result has traditionally been thought to be predictive of either an inflammatory or infectious etiology of the diarrhea. Fecal WBC’s and RBC’s are generally found in stool infected with invasive bacterial pathogens such as Salmonella, Shigella, Campylobacter, Enteroinvasive E-coli, Enterohemorrhagic E-coli ( E-coli 0157-H7), but also in stools of patients with inflammatory disorders such as Crohn’s disease, Ulcerative Colitis, and pseudomembranous colitis. Studies show a sensitivity for predicting bacterial infection for fecal WBC ranging from 40% (Chitkara, 1996) to 73% (Thielman, 2004). Fecal WBC testing also appears to have a specificity of approximately 85% (Thielman, 2004) for bacterial pathogens.

Many studies have demonstrated that fecal occult blood testing (FOBT) is nearly equivalent in sensitivity to fecal WBC in predicting the presence of an invasive bacterial pathogen. One large, well-designed study of 1040 patients with acute diarrhea found that a negative FOBT had a negative predictive value of 87% for invasive bacterial pathogens (McNeely, 1996). Another large study of 446 children demonstrated an 88% sensitivity for the combination of bloody diarrhea by history, positive fecal WBC and positive FOBT for predicting a bacterial pathogen  (Huicho, 1993).

Underpinning the problems inherent in many of these studies is that the gold standard for determining sensitivities, specificities and predictive values was often stool cultures, which themselves have not been shown to be the greatest of tests (as we will discuss). What do we do with these results then, you ask? Well, there is no consensus on when to order fecal WBC or occult RBC’s, however, guidelines by the Infectious Disease Society of America (IDSA) and the American Association of Gastroenterology (AAG) recommend a selective approach since most run-of-the-mill cases of infectious diarrhea are viral in etiology, self-limiting and do not require any testing. They recommend testing patients at high risk for invasive bacterial pathogens (fever > 101.3, severe, or persistent diarrhea (> 7 days), severe abdominal pain, bloody diarrhea, the immunocompromised, elderly or systemically ill patients) (Guerrant, 2001).

Stool cultures, though frequently ordered in the ED, are notoriously poor at identifying bacterial pathogens as a result of their relatively low yield. In six studies conducted between 1980 and 1997 only 1.5%-5.6% of cases grew positive stool cultures. This results in a cost of about $1000 for each positive culture (Guerrant, 2001). Similar low yields have been duplicated by other studies as well. Most people are also unaware that routine stool cultures in most laboratories don’t test for ALL possible pathogens, but primarily identify Shigella, Campylobacter, and Salmonella only.  All other bacteria, including E-coli O157-H7 usually require special requests. As a result, most guidelines also recommend only sending stool cultures in high-risk patients (as denoted above), plus those with positive fecal WBC/occult blood, or those patients being admitted for their diarrhea. The vast majority of patients will not require stool cultures (Dupont, 2014).

Lastly, in developed countries, routine use of stool ova and parasite testing is rarely indicated (Siegel, 1990). Primarily it is used to help identify diarrhea caused by parasites including Giardia, Entamoeba, Cyclospora and Cryptosporidium. As these pathogens are relatively rare in the US, only consider sending these tests in travelers recently returning from Russia (Giardia and Cryptosporidium) or the mountainous regions of North America (Giardia), in AIDS-associated diarrhea (Cryptosporidium), those exposed to infants at a daycare center (Giardia and Cryptosporidium), or longstanding diarrhea not responsive to antibiotic therapy. If you clinically suspect any of these pathogens be sure to send multiple samples for stool ova and parasites to improve the yield, as parasite excretion may be intermittent.

Bottom line: It is prudent to order fecal WBCs as a screening test in high risk patients (denoted above), as it may help you determine the presence of an invasive bacterial pathogen, but in these patients an FOBT may be easier, cheaper, and just as good.  Stool cultures should be sent if fecal WBC/RBC testing is positive, or if patients are being admitted for their diarrhea. Stool O&P is rarely indicated or cost-effective in the US except for very few special circumstances (denoted above).  

2. When do you get bloodwork? When do you pursue imaging?

Most patients who present to the ED with acute diarrhea will have a self-limited disease course. However, many physicians often reflexively order a set of basic labs in these patients to check for any “electrolyte disturbances” from the presumed water loss. Many studies have shown that routine blood work in these patients is unnecessary. In a study by Olshaker, et al., 281 adult patients with acute gastroenteritis were retrospectively reviewed and only 1% of patients were found to have a clinically significant electrolyte abnormality that required treatment or affected disposition. None of the patients with acute gastroenteritis alone had electrolyte abnormalities. They also found that the time spent in the ED was 3-4 times longer for those patients who had electrolytes ordered (Olshaker, 1989).

Routine CBC is also unnecessary in most patients with acute diarrhea as an elevated WBC is non-specific. A hemoglobin level may be appropriate in cases of large amounts of bloody diarrhea. A platelet count may be helpful in children with bloody diarrhea in which you are concerned about Hemolytic Uremic Syndrome (HUS) as a further complication, but otherwise these tests are largely unhelpful.

So does this mean we should never order routine lab work on anyone with acute diarrhea? Not necessarily. The above description and evidence is primarily true for cases with a self-limited diarrhea that is likely due to a viral or non-invasive bacterial pathogen (the majority of patients seen in the ED). In the smaller subgroup of patients with risk-factors for invasive bacteria (i.e., high fever, severe or persistent diarrhea (> 7 days), severe abdominal pain, bloody diarrhea, positive fecal WBC or fecal occult blood, the immunocompromised, elderly, or systemically ill/toxic appearing patients), obtain at least a CBC and BMP to assist with your evaluation and treat any electrolyte abnormalities that may be present (Dupont, 2014).

Similarly, most patients seen in the ED with acute diarrhea do not need any imaging to be performed.  It is important, however, to expand your differential diagnosis outside of infectious etiologies of diarrhea to identify the subset of patients at risk for other pathologies for whom further imaging may be warranted.

For example, patients with appendicitis may also present with diarrhea.  Usually vomiting and diarrhea precede abdominal pain in infectious diarrhea, whereas vomiting often follows abdominal pain in patients with appendicitis.  In a study of 181 children < 13yrs old who were eventually discovered to have appendicitis, 27% were initially misdiagnosed, and many of those children presented with diarrhea as an initial symptom (Rothrock, 1991).  Ischemic bowel disease should also be on the differential diagnosis in elderly patients with severe abdominal pain and a history of vascular disease as these patients may also present with occasional diarrhea and bloating (Tabrez, 2001).  If ischemic bowel disease is being considered, a contrasted CT of the abdomen and pelvis should be ordered.  Furthermore, small bowel obstruction and diverticulitis can often present with diarrhea, but may not be diagnosed unless formal imaging is obtained.

Be extra cautious in evaluating elderly patients with diarrhea and abdominal pain as these patients tend to have more serious, often surgical, illnesses that present atypically or go unrecognized longer (Hendrickson, 2003).

Bottom line: most patients seen in the ED with acute diarrhea require no “routine” blood work unless the patient has high-risk features. Imaging is also usually not necessary unless you are considering other diagnoses including appendicitis, mesenteric ischemia, small bowel obstruction, and diverticulitis.  

3. Which patients do you treat with antibiotics?

Whether or not to prescribe antibiotics and to which patients is one of the most controversial and most discussed aspects of the management of diarrhea. Analyzing all the evidence currently available is enough to cause one to have diarrhea in and of itself, but fear not. Let’s break it down in pieces . . .

Why give antibiotics in the first place, you ask, if many of these disease processes are self-limited?  In various studies, antibiotics appear to decrease the length of the diarrhea symptoms by about 24-48 hrs regardless of whether the diarrhea was guiac positive, fecal WBC positive, or had positive stool cultures  (Guerrant, 2001; Dryden, 1996; Wistrom 1992).  The moderately to severely ill seem to benefit more from antibiotics.  Why would antibiotics decrease symptoms in culture negative stools? Some believe the antibiotics are eradicating bacterial pathogens that stool cultures were unable to detect. Traditionally it was thought that antibiotics may not be beneficial in mild-moderate diarrhea, due to their tendency to prolong the carrier state, especially amongst those infected with Salmonella.  However, newer studies show and that carrier rates are approximately equivalent in those treated with or without antibiotics (Dryden, 1996).

So now that we understand why we may give antibiotics, the question becomes who we should give them to? Many experts argue that most patients, regardless of symptoms and lab test results, don’t need antibiotics since most acute diarrheal illnesses are self-limited.  Additionally, further prescription of antibiotics will lead to increased drug resistance and side-effects. Other guidelines, including those from the IDSA and AAG, provide a more conservative approach. They state patients should receive antibiotics if they are presenting with symptoms of traveler’s diarrhea, as immediate treatment can reduce symptom duration by 2-3 days (Guerrant, 2001).  They further recommend antibiotic therapy in those patients with high fever (>101.3), history suspicious of a moderate-severe bacterial infection, guiac positive stools or positive fecal WBC (Guerrant, 2001).  Some criticize the IDSA guidelines for relying too heavily on stool testing to decide whether or not to give antibiotics.

Just as important as knowing which patient to give antibiotics to is knowing which patients to be cautious about giving antibiotics. In general, antibiotics are not advised for the treatment of diarrhea in most pediatric patients.  The cornerstone of treatment in pediatric patients is fluid replacement. Inadequate fluid replacement leads to the 9% of hospitalizations in children < 5 yrs of age caused by diarrhea (Cicirello, 1994).  Caution is also advised in prescribing antibiotics in patients with grossly bloody diarrhea.  This is because one of the common causes of grossly bloody diarrhea is Enterohemorrhagic E-coli (AKA E-coli 0157-H7).  Various studies (including one published in the New England Journal of Medicine in 2000) demonstrated higher risk of HUS in pediatric patients with EHEC who were treated with antibiotics (Wong, 2000).  There is also concern that elderly patients with EHEC may develop TTP if treated with antibiotics.

If you decide to give antibiotics to a patient with an acute diarrheal illness, which antibiotics should you give? Most studies and current guidelines recommend ciprofloxacin to help eradicate acute bacterial pathogens. Two basic regimens exist, either a one-time dose of ciprofloxacin 1gm or a regimen of ciprofloxacin 500mg twice/day x 3 days.  Some regimens use macrolides, as fluoroquinolones will not be effective in cases of Campylobacter (Dupont, 2014).

Bottom line: In most cases of watery diarrhea, no antibiotics are needed as the disease is usually self-limiting. When there is concern for invasive disease (positive fecal WBCs or RBCs, or young, adult, healthy patients with grossly bloody stools), it may be reasonable to prescribe ciprofloxacin 500mg BID x 3 days to help reduce symptoms by 24-48 hours (although many sources argue that this is unnecessary). Also, be cautious in giving antibiotics to pediatric and elderly patients with grossly bloody diarrhea as HUS and TTP are concerns.       

4. What other medications do you use? Loperamide, Lomotil, Pepto? What about probiotics?

Loperamide (Imodium) is a peripheral opioid receptor agonist that acts on the mu-opioid receptors in the myenteric plexus of the large intestine without affecting the mu-receptors in the CNS. It works by slowing gastrointestinal motility, thereby allowing more time for fluid and electrolytes to be absorbed from the fecal material. Loperamide is generally considered to be safe in most acute infectious diarrhea in patients who are afebrile and have non-bloody diarrhea and those individuals with chronic diarrhea from inflammatory bowel disease (Gore, 2003).

In those with more severe illnesses (immunocompromised, bloody diarrhea, fever > 101.3), some experts believe the use of Loperamide will allow the invasive bacteria to remain in the gut for a longer period of time and potentially worsen the acute diarrheal illness. However, there is evidence that supports the use of Loperamide in sicker patients in combination with antibiotics. In two studies, one in Thailand on patients with dysentery and another amongst US soldiers with traveler’s diarrhea, the use of Loperamide effectively reduced the number of loose bowel movements compared to placebo when given in adjunct with ciprofloxacin (Petrucelli, 1992; Murphy 1993).

Loperamide may increase the risk of HUS in pediatric patients (Guerrant, 2001; Cimolai, 1990) and many guidelines advise against the use of anti-motility agents in pediatric patients.

Lomotil (diphenoxylate/atropine) is a combined opiate-agonist (diphenoxylate) and anticholinergic (atropine) agent that is also available as an adjunct for symptomatic treatment of diarrhea. The diphenoxylate component acts on the mu-receptors of the gut wall in a similar fashion to Loperamide, however, its mu effects are not restricted to the periphery and may cross into the CNS. As a result, atropine is combined in the medication to discourage overdose. From the drug description alone, it can be seen that this medication may be more dangerous and habit-forming than Loperamide in treating the acute symptoms of diarrhea. Diphenoxylate has not been studied in any randomized clinical trials and is not recommended by many experts for symptomatic treatment of acute diarrhea.

Bismuth subsalicylate, sold most commonly under the brand name Pepto-Bismol functions as an anti-secretory, anti motility agent with some weak but present bactericidal properties. As it is a salicylate, its toxicologic considerations, especially in pediatric patients, require extreme caution and likely avoidance in small children out of concern for at home dosing misadventures. Very little rigorous study of Pepto exists, with some volunteer reports of its use in traveler’s diarrhea in military personnel decreasing symptoms subjectively (Putnam, 2006). One double-blinded randomized study of Bangladeshi children aged 4-36 months found a modest improvement in acute diarrheal illness (Chowdhury, 2001). AN open label study in volunteers found loperamide to be faster and more effective than Pepto in adults (Dupont, 1990). Pepto, though, may be particularly useful in cases of norovirus, a common cause of acute diarrhea (Pitz, 2015). If toxicity is avoided in dosing, there is little downside in including this in a patient’s antidiarrheal armamentarium.

Probiotics are live organisms found in a variety of foodstuffs that have been used to help colonize the intestine with “good bacteria” to prevent or treat both infectious and antibiotic associated diarrhea. Lactobacillus is one of the most widely available and studied of these probiotics. In the Cochrane Review of over 23 studies involving over 1900 adults and children, probiotics were found to reduce the overall risk of having diarrhea at 3 days by approximately 35% and reduced the duration of the diarrhea by approximately 30 hours (Allen, 2004). Multiple other studies show similar results while also demonstrating a good safety profile.

In regards to the use of probiotics in the prevention of antibiotic-associated diarrhea, the largest meta-analyses was conducted in 2012 (62 studies, 11,000 patients). A majority of the included studies used Lactobacillus as the probiotic and found a 42% lower risk of developing antibiotic associated diarrhea than control groups (RR 0.58, 95% CI 0.5-0.68) with a number needed to treat (NNT) of 13 to prevent one case of antibiotic associated diarrhea (Hempel, 2012).

Bottom line: Loperamide (Imodium) may be useful and safe in most cases of acute diarrhea, however, some caution should be advised in the severely ill and in and those with bloody diarrhea unless an antibiotic is concurrently prescribed. Loperamide should be avoided in pediatric patients. Lomotil is not recommended for symptomatic relief. Probiotics (specifically Lactobacillus) are showing promising evidence for their use in the prevention and treatment of both infectious and antibiotic associated diarrhea.    

Author: Bhandari  Editors: Swaminathan, Bryant

Check out EM Lyceum page for more such reviews. 

Originally posted by EM Lyceum on 2/11/2015. Re-Posted with Permission.