Advances in the Management of Gastroenteritis

Introduction

Gastroenteritis is one of the major public health concerns across the globe.¹Majowicz SE, Hall G, Scallan E, et al. A common, symptom-based case definition for gastroenteritis. Epidemiology and Infection. 2008;136(7):886-894.    The disease particularly acute gastroenteritis is common in children and associated with remarkable risk of morbidity and mortality. According to global statistics, 3 to 5 billion are affected annually with and 1.5 to 2.5 million deaths occur each year. Of note, 12% of mortality occurs among children less than 5 years of age. In addition, it imposes significant burden on the healthcare resources.²Malik OAA. Role of Chow CM, Leung AK, Hon KL. Acute gastroenteritis: from guidelines to real life. Clinical and experimental gastroenterology. 2010;3:97-112.    Individuals with gastroenteritis develop inflammation of the mucus membranes of the gastrointestinal tract. Bacterial, viral or parasitic infections are presumed to be some of the major causes as enlisted in box 1.²Malik OAA. Role of Chow CM, Leung AK, Hon KL. Acute gastroenteritis: from guidelines to real life. Clinical and experimental gastroenterology. 2010;3:97-112.    ³Elliott EJ. Acute gastroenteritis in children. BMJ : British Medical Journal. 2007;334(7583):35-40.

In relation to symptomatology, gastroenteritis is associated with diverse range of symptoms such as diarrhea, nausea, vomiting, and abdominal cramping. It is considered acute, when diarrhea or vomiting or both occur for more than 7 days and may or may not be associated with fever, abdominal pain and anorexia. From the management point of view, the aim is to prevent and treat dehydration, maintain nourishment and minimize damage. Therefore, it is necessary to assess the hydration status of the individual with gastroenteritis in order to determine the emergent management.³Elliott EJ. Acute gastroenteritis in children. BMJ : British Medical Journal. 2007;334(7583):35-40.    In addition, the role of preventive measures such as sanitation and hygiene cannot be neglected. Sanitation prevents the transmission of pathogens from an infected person. Additionally, hand washing practice and food hygiene interventions may help in mitigating the risk of diarrhea in young children.⁴Brown J, Cairncross S, Ensink JHJ. Water, sanitation, hygiene and enteric infections in children. Archives of Disease in Childhood. 2013;98(8):629-634.

Underused oral rehydration therapy

Oral rehydration therapy is the first-line treatment option for mild-to-moderate dehydration. World Health Organization (WHO) has vigorously promoted its use. It has been shown that use of oral rehydration therapy has contributed to decrease mortality attributable to diarrhea by almost 75% from 1980 to 2008. It is also important to appreciate that oral therapy is equieffective to intravenous rehydration therapy in mild-tomoderate dehydration. Oral rehydration therapy is advantageous as it circumvents the complications associated with intravenous therapy such as infections, seizures and mortality.⁵Nir V, Nadir E, Schechter Y, Kline-Kremer A. Parents ‘ attitudes toward oral rehydration therapy in children with mild-to-moderate dehydration. ScientificWorldJournal. 2013 Nov 4;2013:828157.    Further, intravenous therapy may only be administered by an expert or highly trained personnel thus imposing financial burden. Other important drawbacks of intravenous rehydration therapy include problems associated with rapid over-correction of electrolyte imbalance, inflammation and extravasation of infusion into the surrounding tissues.⁶Bellemare S, Hartling L, Wiebe N, et al. Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials. BMC Medicine. 2004;2:11.

Regardless of its potential benefits and promotion by various international agencies, mounting data has proved underutilization of oral rehydration therapy.5 The plausible reasons contribution to underuse of oral rehydration therapy include the fear of inducing hyponatremia, time requirements, parental preference and debatable efficacy in patients with moderate dehydration. Oral rehydration therapy is safe to use, less traumatic for the patients, less expensive, lowers hospital admission and length of stay and can be instituted at home. Moreover, oral rehydration therapy is also recognized to reduce mortality due to diarrheal diseases.⁶Bellemare S, Hartling L, Wiebe N, et al. Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials. BMC Medicine. 2004;2:11.    ⁷Doan Q, Chan M, Leung V, Lee E, Kissoon N. The impact of an oral rehydration clinical pathway in a paediatric emergency department. Paediatrics & Child Health. 2010;15(8):503-507.

In a randomized, controlled trial, outcomes related to oral rehydration therapy were compared with intravenous fluid therapy in a group of 470 children with severe gastroenteritis. The oral therapy was instituted in two phases; a rehydration phase consisting administration of high sodium isotonic fluid and a maintenance therapy consisting low sodium isotonic fluids. It was noted that oral rehydration therapy can be successfully used for treatment of severe diarrhea and dehydration. Further, it has significant advantages over intravenous therapy; reduced complications, rapid method for correcting hypokalemia and acidosis, decreased duration of diarrhea and weight gain in debilitated individuals.⁸Sharifi J, Ghavami F, Nowrouzi Z, Fouladvand B, Malek M, Rezaeian M, Emami M. Oral versus intravenous rehydration therapy in severe gastroenteritis. Arch Dis Child. 1985 Sep;60(9):856-60.    A study was conducted to assess the assumption that failure with oral rehydration therapy will not be greater than >5% compared to failure rate of intravenous rehydration therapy. It was also tested that patients administered oral rehydration therapy may receive prompt therapy, show more improvement after 2 hours of treatment, lower hospitalization rates and would prefer oral rehydration therapy in similar future episodes. Of the 73 patients recruited, 36 received oral rehydration therapy and 3 received intravenous rehydration therapy. Baseline values for dehydration score, and number of diarrhea or emesis episodes were similar both the groups. It was noted that oral rehydration therapy was non-inferior to intravenous therapy for primary outcome and favorable for secondary outcomes of the study. The time required to initiate oral therapy was 19.9 minutes compared to 41.2 minutes for intravenous therapy. The dehydration score at 2 hours was similar in both the groups. The need for hospitalization was less in patients receiving oral therapy (less than one-third required hospitalization; 30.6%) compared to intravenous therapy (nearly half required hospitalization; 48.7%).⁹Spandorfer PR, Alessandrini EA, Joffe MD, Localio R, Shaw KN. Oral versus intravenous rehydration of moderately dehydrated children: a randomized, controlled trial. Pediatrics. 2005 Feb;115(2):295-301.

Zinc and its proposed role in gastroenteritis

Zinc is a component of a variety of foods. Zinc supplementation has been proven to be beneficial in diarrhea and reduces disease related complications including death. Recently, there has been wide-spread promotion of zinc supplementation in diarrhea owing to its pleiotropic advantages. WHO recommends daily supplementation of zinc for 10 to 14 days for management of acute episodes in children.¹⁰Goldman RD. Zinc supplementation for acute gastroenteritis. Canadian Family Physician. 2013;59(4):363-364.    Zinc is required for cellular growth, differentiation and metabolism. It has been noted that deficiency of zinc restricts childhood growth and makes the patient vulnerable to infections. In gastroenteritis, zinc has been shown to reduce duration and severity of diarrhea and prevent recurrence.¹¹Zinc supplementation in the management of diarrhea. Available at: http://www.who.int/ elena/titles/zinc_diarrhoea/en/. Accessed on: 27-5-2017    In this regards, a study was performed to understand the impact of zinc supplementation with oral rehydration therapy on recuperation in acute or persistent diarrhea. In acute diarrhea trials, patients had 15% lower propensity of continuing diarrhea when zinc was supplemented. In persistent diarrhea trials, patients showed 24% lower probability of continuing diarrhea and 42% lower chances of treatment failure or death if zinc supplementation was given. Therefore, it can be appreciated that zinc supplementation is useful for reducing the duration and severity of acute and persistent diarrhea.¹²Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr. 2000 Dec;72(6):1516-22.

Lactose malabsorption /Intolerance in Gastroenteritis

In gastroenteritis, Secondary lactase deficiency can occur. This happens due to destruction of the cells in the lining of the upper gut (small intestine) which produce lactase. It is common and often occurs after viral or bacterial gastroenteritis. It can also be a complication of other bowel diseases or chemotherapy. This is a temporary condition which improves when the lining of the gut heals. It takes 6 to 8 weeks for Mucosa and Lactase to get restored. Post gastroenteritis, many patients do not tolerate milk and dairy, hence they are advised to avoid milk and dairy as the gut may not have sufficient lactase to digest lactose. These patients often complain of bloating/distention, flatulence, loose stools and other symptoms of lactose intolerance. Hydrogen breath test remains to be positive in patients post gastroenteritis, signifying that lactose is not digested.¹³Robb TA, Davidson GP. Hydrogen breath test in gastroenteritis. Archives of Disease in Childhood. 1982;57(7):561-562.

During this phase oral lactase supplement can be helpful for the patients, as they would neutralise the lactose content in milk and dairy. Oral lactase enzyme tablets are available in India and they can be taken with milk and dairy products.

Probiotics

In acute gastroenteritis, apart from early rehydration and avoiding dietary restrictions, probiotics have been suggested to have a remarkable role. It is recommended that Lactobacillus rhamnosus GG and Saccharomyces boulardii are among few of the commonly used probiotics.¹⁴Szajewska H, Guarino A, Hojsak I, Indrio F, Kolacek S, Shamir R, Vandenplas Y, Weizman Z; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014 Apr;58(4):531-9.    It is rational to use probiotics as perturbation of bacterial microflora of the gastrointestinal tract has a pathological role in the development of gastrointestinal tract. Probiotics per se help in restoring normal bacterial microflora and modulating the function of gastrointestinal tract by multiple mechanisms (Table 2).¹⁴Szajewska H, Guarino A, Hojsak I, Indrio F, Kolacek S, Shamir R, Vandenplas Y, Weizman Z; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014 Apr;58(4):531-9.    ¹⁵Guarino A, Vecchio AL, Canani RB. Probiotics as prevention and treatment for diarrhea. Current Opinion in Gastroenterology 2008, 25:18-23.    Probiotics are effective in several gastrointestinal disorders such as antibiotic-associated diarrhea, Clostridium difficile colitis, infectious diarrhea, ulcerative colitis, Crohn’s disease, pouchitis, and irritable bowel syndrome.¹⁶Verna EC, Lucak S. Use of probiotics in gastrointestinal disorders: what to recommend? Therapeutic Advances in Gastroenterology. 2010;3(5):307-319.

Fecal microbiota transplantation

Remarkable efforts have been invested in understanding the gut microbiota and its role in pathophysiology of gastrointestinal diseases. Recent advances in therapeutics for optimal management of gastrointestinal disorders have unveiled usefulness of fecal microbiota transplantation.¹⁷Barnes D, Park KT. Donor Considerations in Fecal Microbiota Transplantation. Curr Gastroenterol Rep. 2017 Mar;19(3):10.    FMT involves administration of a solution of donor fecal matter into the intestinal tract of a recipient to modulate the composition of receiver’s gut microbiota in order to attain health benefits.¹⁸Gupta S, Allen-Vercoe E, Petrof EO. Fecal microbiota transplantation: in perspective. Therapeutic Advances in Gastroenterology. 2016;9(2):229-239.    The FMT therapy may be administered through nasogastric or nasoduodenal tube, enema, colonoscope or capsules.¹⁹Choi HH, Cho Y-S. Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives. Clinical Endoscopy. 2016;49(3):257-265.

FMT is suggested to be useful in the management of Clostridium difficile infection, inflammatory bowel disease and gastrointestinal disorders. Gut microbiota alters in response to insults and has the ability to recover from continued perturbations.¹⁸Gupta S, Allen-Vercoe E, Petrof EO. Fecal microbiota transplantation: in perspective. Therapeutic Advances in Gastroenterology. 2016;9(2):229-239.    Of late, FMT is gaining popularity as a mainstream therapy instead of previously considered last resort alternative.²⁰Borody TJ, Paramsothy S, Agrawal G. Fecal Microbiota Transplantation: Indications, Methods, Evidence, and Future Directions. Current Gastroenterology Reports. 2013;15(8):337.   

Antibiotics in gastroenteritis

Although antimicrobial therapy is not required in all the patients with acute gastroenteritis, nevertheless, empirical antimicrobial therapy is mandatory in some situations, likewise in patients with febrile diarrheal illness, with fever and bloody diarrhea, symptoms persisting for more than 1 week, or in case the patient is immunocompromised.²¹Zollner-Schwetz I, Krause R. Therapy of acute gastroenteritis: role of antibiotics. Clin Microbiol Infect. 2015 Aug;21(8):744-9.    Considering this, rifaximin, a broad spectrum of antimicrobial drug, with good safety profile and efficacy profile can be used to shorten the duration of acute infectious diarrhea and travelers’ diarrhea. Furthermore, the overall efficacy of rifaximin is similar to that of ciprofloxacin.²²Hong KS, Kim JS. Rifaximin for the treatment of acute infectious diarrhea. Therapeutic Advances in Gastroenterology. 2011;4(4):227-235.

Role of antispasmodics in gastroenteritis

Acute abdominal pain is a common complaint in patients with gastroenteritis. Abdominal pain can occur due to bacterial, parasitic and viral infections. The management of such condition should aim at controlling the underlying cause of pain.

The following aspects must be taken into account:²³Kim JS. Acute Abdominal Pain in Children. Pediatric Gastroenterology, Hepatology & Nutrition. 2013;16(4):219-224.

• Initial resuscitation- correction of hypoxemia, replacement of volume loss and correction of metabolic cause
• Gastric decompression if bowel obstruction is the cause
• Empirical antibiotic therapy
• Adequate analgesia to decrease pain severity

Dietary and pharmacological therapies are two components of comprehensive management. Generally, it is advised to remove dietary triggers, increase fiber intake and subsequently prescribe anticholinergics, antispasmodics, antimotility (in some cases) and antidiarrheal agents.²⁴Dellon ES, Ringel Y. Treatment of functional diarrhea. Curr Treat Options Gastroenterol. 2006 Jul;9(4):331-42.    Antispasmodic agents help in alleviating abdominal pain through their action on decreasing smooth muscle spasms in the gastrointestinal tract that may produce symptoms such as pain.²⁵Chiou E, Nurko S. Management of functional abdominal pain and irritable bowel syndrome in children and adolescents. Expert review of gastroenterology & hepatology. 2010;4(3):293-304.    Drotaverine is an antispasmodic medication with selective inhibitory phosphodiesterase 4 activity. It has no anticholinergic activity. It has dose-dependent analgesic activity.²⁶Drotaverine. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/drotaverine. Accessed on: 29-5-2017.    The analgesic potential of drotaverine was evaluated in a group of children with recurrent abdominal pain. A total of 132 children were recruited and randomized to receive drotaverine or placebo. The following parameters were assessed: number of pain episodes and number of pain free days. Number of school days missed, parental satisfaction and adverse events were estimated as secondary outcomes of the study. There was remarkable reduction in number of abdominal pain episodes with drotaverine compared to placebo (10.3 episodes versus 21.6 episodes). The number of pain free days was comparable in both the groups. Parental satisfaction was favorable for drotaverine group and determined using Likert scale (evaluation of mood, activity, alertness, comfort and fluid intake). Frequency of side effects was equivalent in drotaverine and placebo group. It was thus suggested that drotaverine is effective in the management of abdominal pain and a well-tolerated agent.²⁷Narang M, Shah D, Akhtar H. Efficacy and Safety of Drotaverine Hydrochloride in Children with Recurrent Abdominal Pain: A Randomized Placebo Controlled Trial. Indian Pediatr. 2015 Oct;52(10):847-51.

Conclusion

Gastroenteritis is a problem of significant concerns across the globe, especially among children. The management of gastroenteritis primarily aims at prevention and treatment of dehydration, maintenance of nourishment and minimizing damage. Recently, there have been remarkable advances in the therapy of gastroenteritis. Various international agencies have promoted zinc supplementation along with rehydration therapy to facilitate recovery. Of late, fecal microbial transplantation has been recognized as an important step forward to alter the constitution of gut microbiota to achieve health benefits. In addition, it is important to note that abdominal pain is a problem in several patients with gastroenteritis. It is noted that abdominal pain may be reduced with use of drotaverine, an antispasmodic agent. Lactase supplements may be beneficial in post gastroenteritis as it helps to digest milk and dairy.

References

1. Majowicz SE, Hall G, Scallan E, et al. A common, symptom-based case definition for gastroenteritis. Epidemiology and Infection. 2008;136(7):886-894.
2. Chow CM, Leung AK, Hon KL. Acute gastroenteritis: from guidelines to real life. Clinical and experimental gastroenterology. 2010;3:97-112.
3. Elliott EJ. Acute gastroenteritis in children. BMJ : British Medical Journal. 2007;334(7583):35-40.
4. Brown J, Cairncross S, Ensink JHJ. Water, sanitation, hygiene and enteric infections in children. Archives of Disease in Childhood. 2013;98(8):629-634.
5. Nir V, Nadir E, Schechter Y, Kline-Kremer A. Parents’ attitudes toward oral rehydration therapy in children with mild-to-moderate dehydration. ScientificWorldJournal. 2013 Nov 4;2013:828157.
6. Bellemare S, Hartling L, Wiebe N, et al. Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials. BMC Medicine. 2004;2:11.
7. Doan Q, Chan M, Leung V, Lee E, Kissoon N. The impact of an oral rehydration clinical pathway in a paediatric emergency department. Paediatrics & Child Health. 2010;15(8):503-507.
8. Sharifi J, Ghavami F, Nowrouzi Z, Fouladvand B, Malek M, Rezaeian M, Emami M. Oral versus intravenous rehydration therapy in severe gastroenteritis. Arch Dis Child. 1985 Sep;60(9):856-60.
9. Spandorfer PR, Alessandrini EA, Joffe MD, Localio R, Shaw KN. Oral versus intravenous rehydration of moderately dehydrated children: a randomized, controlled trial. Pediatrics. 2005 Feb;115(2):295-301.
10. Goldman RD. Zinc supplementation for acute gastroenteritis. Canadian Family Physician. 2013;59(4):363-364.
11. Zinc supplementation in the management of diarrhea. Available at: http://www.who.int/ elena/titles/zinc_diarrhoea/en/. Accessed on: 27-5-2017
12. Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr. 2000 Dec;72(6):1516-22.
13. Robb TA, Davidson GP. Hydrogen breath test in gastroenteritis. Archives of Disease in Childhood. 1982;57(7):561-562.
14. Szajewska H, Guarino A, Hojsak I, Indrio F, Kolacek S, Shamir R, Vandenplas Y, Weizman Z; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014 Apr;58(4):531-9.
15. Guarino A, Vecchio AL, Canani RB. Probiotics as prevention and treatment for diarrhea. Current Opinion in Gastroenterology 2008, 25:18–23.
16. Verna EC, Lucak S. Use of probiotics in gastrointestinal disorders: what to recommend? Therapeutic Advances in Gastroenterology. 2010;3(5):307-319.
17. Barnes D, Park KT. Donor Considerations in Fecal Microbiota Transplantation. Curr Gastroenterol Rep. 2017 Mar;19(3):10.
18. Gupta S, Allen-Vercoe E, Petrof EO. Fecal microbiota transplantation: in perspective. Therapeutic Advances in Gastroenterology. 2016;9(2):229-239.
19. Choi HH, Cho Y-S. Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives. Clinical Endoscopy. 2016;49(3):257-265.
20. Borody TJ, Paramsothy S, Agrawal G. Fecal Microbiota Transplantation: Indications, Methods, Evidence, and Future Directions. Current Gastroenterology Reports. 2013;15(8):337.
21. Zollner-Schwetz I, Krause R. Therapy of acute gastroenteritis: role of antibiotics. Clin Microbiol Infect. 2015 Aug;21(8):744-9.
22. Hong KS, Kim JS. Rifaximin for the treatment of acute infectious diarrhea. Therapeutic Advances in Gastroenterology. 2011;4(4):227-235.
23. Kim JS. Acute Abdominal Pain in Children. Pediatric Gastroenterology, Hepatology & Nutrition. 2013;16(4):219-224.
24. Dellon ES, Ringel Y. Treatment of functional diarrhea. Curr Treat Options Gastroenterol. 2006 Jul;9(4):331-42.
25. Chiou E, Nurko S. Management of functional abdominal pain and irritable bowel syndrome in children and adolescents. Expert review of gastroenterology & hepatology. 2010;4(3):293-304.
26. Drotaverine. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/drotaverine. Accessed on: 29-5-2017.
27. Narang M, Shah D, Akhtar H. Efficacy and Safety of Drotaverine Hydrochloride in Children with Recurrent Abdominal Pain: A Randomized Placebo Controlled Trial. Indian Pediatr. 2015 Oct;52(10):847-51.