Acute Gastroenteritis in Children: An overview

Introduction

Acute gastroenteritis, though often considered a benign disease, remains a major cause of childhood morbidity and mortality across the world, particularly in developing countries. The disease presents considerable burden on the community, being a major cause of visits to emergency departments, hospitalizations, investigations and prescription of drugs.^1-4Bruzzese E, Lo Vecchio A, Guarino A. Hospital management of children with acute gastroenteritis. Curr Opin Gastroenterol. 2013 Jan;29(1):23-30.
Leung AK, Robson WL. Acute gastroenteritis in children: role of anti-emetic medication for gastroenteritis-relatedvomiting. Paediatr Drugs. 2007;9(3):175-84.
Elliott EJ. Acute gastroenteritis in children. BMJ. 2007 Jan 6;334(7583):35-40.
Heyworth JS, Baghurst P, Mc caul KA. Prevalence of gastroenteritis among 4-year-old children in South Australia. Epidemiol. Infect. 2003;130:443-451.  

Importantly, gastroenteritis represents inflammation of the mucous membranes of the gastrointestinal tract, and the syndrome is characterized by vomiting and/or diarrhea, often accompanied by abdominal pain, fever, and anorexia.⁵Webb A, Starr M. Acute gastroenteritis in children. Aust Fam Physician. 2005 Apr;34(4):227-31.  

Etiology of gastroenteritis

A variety of viral, bacterial, and parasitic enteropathogens may be the cause of clinical syndrome of acute gastroenteritis.⁶Shek KC, Ng P, Hung CY. A review on the management of acute gastroenteritis in children. Hong Kong j.emerg.med. 2004;11:152-160.   Worldwide, most cases are because of viral infections (Table 1), with rotaviruses and noroviruses being most common.³Elliott EJ. Acute gastroenteritis in children. BMJ. 2007 Jan 6;334(7583):35-40.   Characteristically, viral infections damage small bowel enterocytes and cause low grade fever and watery diarrhea without blood. Peak age for rotavirus

infection, the most common viral enteropathogen in children, is between 6 months and 2 years, the mode of spread being fecal-oral or respiratory route.

Alternatively, bacterial pathogens invade the lining of the small and large intestine and trigger inflammation. Therefore, children with bacterial gastroenteritis are more likely to have fever, and may have blood and white blood cells in the stool. As such, infection with invasive bacteria, such as Campylobacter, Salmonella, and Shigella spp., and organisms that produce cytotoxins, such as Clostridium difficile (C. difficile) and enterohemorrhagic Escherichia coli (E. coli) (serotype O157:H7), often result in abdominal pain, and fever.⁷Lever DS, Soffer E. Acute Diarrhea. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/acute-diarrhea/ [Accessed on 15/6/13].  

Prevalence estimates

Acute gastroenteritis is widely prevalent worldwide-about 3-5 billion cases of acute gastroenteritis and nearly 2 million deaths occur every year in children under 5 years of age.³Elliott EJ. Acute gastroenteritis in children. BMJ. 2007 Jan 6;334(7583):35-40.   This epidemiologic impact may be more pronounced in developing nations like India, as reflected by common occurrence of the disease in general population.

In developing countries, where bacterial pathogens are more prevalent, rotavirus is still a major cause of gastroenteritis; 82% of worldwide deaths caused by rotavirus occur in these countries.⁸Dalby-Payne JR, Elliott EJ. Gastroenteritis in children. Available at: http://bestpractice.bmj.com/best-practice/evidence/background/0314.html [Accessed on 15/6/2013].   In India, one of every 250 children or about 100-150,000 children die of rotavirus diarrhea each year. Importantly, the diversity of rotavirus strains and the high prevalence of mixed infections are unique features of rotavirus epidemiology in India; prevalence of rotavirus diarrhea in India varies from 5-71% in hospitalized children less than 5 years of age with acute gastroenteritis. As such, distinctive features of rotavirus infection in India include occurrence of severe disease at an early age, and common neonatal rotavirus infections, which are often asymptomatic.⁹Broor S, Ghosh D, Mathur P. Molecular epidemiology of rotaviruses in India. Indian J Med Res. 2003 Aug;118:59-67.  

Symptoms & signs of gastroenteritis

Acute gastroenteritis is consistently characterized by diarrhea, which is often accompanied by abdominal pain, nausea, vomiting, and fever.¹⁰Colletti JE, Brown KM, Sharieff GQ, Barata IA, Ishimine P; ACEP Pediatric Emergency Medicine Committee. The management of children with gastroenteritis and dehydration in the emergency department. J Emerg Med. 2010 Jun;38(5): 686-98.   Dehydration is an important complication; and signs that best suggest dehydration in children are an abnormal respiratory pattern, abnormal skin turgor, and prolonged capillary refill time (decreased peripheral perfusion), though parental report of the child’s history is also helpful in the assessment.⁵Webb A, Starr M. Acute gastroenteritis in children. Aust Fam Physician. 2005 Apr;34(4):227-31.  ^,11Churgay CA, Aftab Z. Gastroenteritis in children: Part 1. Diagnosis. Am Fam Physician. 2012 Jun 1;85(11):1059-62.  

While frequent, watery stools are more consistent with viral gastroenteritis, stools with blood or mucus are indicative of a bacterial pathogen. In addition, presence of fever, chills, myalgias, rash, rhinorrhea, sore throat, and cough may indicate evidence of systemic infection.¹²Levine A, Santucci KA. Pediatric Gastroenteritis. Available at: http://emedicine.medscape.com/article/801948-clinical. [Accessed on 15/6/2103].  

Abdominal spasm – an important manifestation in gastrointestinal diseases

Abdominal pain accompanied by gastrointestinal symptoms, such as vomiting or diarrhea, is common chief complaint in young children who present in emergency departments.¹³McCollough M, Sharieff GQ. Abdominal pain in children. Pediatr Clin North Am. 2006 Feb;53(1):107-37, vi.   Here, as diarrhea and vomiting are non-specific symptoms in young children¹⁴Blakelock RT, Beasley SW. Infection and the gut. Semin Pediatr Surg. 2003 Nov;12(4):265-74.  , the diagnosis of gastroenteritis needs to be questioned in children with high fever, prolonged symptoms, or signs such as severe abdominal pain, bilious vomiting, and abdominal mass³Elliott EJ. Acute gastroenteritis in children. BMJ. 2007 Jan 6;334(7583):35-40.  ; often, pain that precedes diarrhea and vomiting may be due to some underlying abdominal pathology. Therefore, the physician should assess location, quality, radiation, severity, and timing of pain, as per report of parents and/or child.¹²Levine A, Santucci KA. Pediatric Gastroenteritis. Available at: http://emedicine.medscape.com/article/801948-clinical. [Accessed on 15/6/2103].  

Management of gastroenteritis

Most children with gastroenteritis with minimal or no dehydration can be managed at home, and should be encouraged to continue usual diet and drink adequate fluids. Children with mildmoderate dehydration can be treated with oral rehydration using oral rehydration solution (ORS), which is invariably a treatment choice for such children with mild-to-moderate gastroenteritis. However, notwithstanding this definite approach, the complaint of abdominal pain and spasm may warrant treatment even before rehydration therapy is considered (see below). Anti-emetics and antidiarrheals are usually not indicated in children with acute gastroenteritis.<sup5Webb A, Starr M. Acute gastroenteritis in children. Aust Fam Physician. 2005 Apr;34(4):227-31.   However, severely dehydrated or shocked children generally require intravenous fluids and hospital admission.³Elliott EJ. Acute gastroenteritis in children. BMJ. 2007 Jan 6;334(7583):35-40.  ^,15Churgay CA, Aftab Z. Gastroenteritis in children: Part II. Prevention and management. Am Fam Physician. 2012 Jun 1;85(11):1066-70.  

Management of abdominal pain

Often, the challenges of childhood abdominal pain, a common complaint in most gastrointestinal diseases, are to treat the majority of children with self-limited conditions of obscure but benign causes, such as acute gastroenteritis, and to identify the child with a rare, life-threatening cause of pain.⁶Shek KC, Ng P, Hung CY. A review on the management of acute gastroenteritis in children. Hong Kong j.emerg.med. 2004;11:152-160.   As follows, the child that presents with abdominal pain must be evaluated with a careful history, physical examination, and selective laboratory studies, if required.¹⁷Mason JD. The evaluation of acute abdominal pain in children. Emerg Med Clin North Am. 1996 Aug;14(3):629-43.  

Gastroenteritis is always an important differential diagnosis of acute abdominal pain in children – it is commonly thought that dehydration and depletion of electrolytes will lead to muscle spasm and cramping. As such, diarrhea can be associated with colicky pain, whereby the muscles within the colon wall spasm just before a watery bowel movement.¹⁸Wedro B, Shiel WC Jr. Muscle Spasms. Available at: http://www.medicinenet.com/muscle_spasms/page2.htm. [Accessed on 14/6/2013].   Per se, pain from smooth muscle spasm may be severe enough to present to an emergency department, whereby pain control is initiated simultaneously with efforts to make the diagnosis. It is here that anti-spasmodic treatment is considered, with different objectives: symptomatic treatment of spasm without being involved in disease pathogenesis; and spasmolytic drug may be a part of causal therapy if the spasm is a leading symptom or cause of the underlying disease.

Anti-cholinergics as anti-spasmodics

Anti-cholinergic medications may be helpful in spasmodic conditions, which may produce symptoms such as pain, through their effects on decreasing smooth muscle spasms in the gastrointestinal tract. However, their use is generally discouraged in subjects with abdominal pain for fear of interfering with accurate evaluation and diagnosis given that they often mask the physical symptoms of “acute abdomen”, making it difficult to achieve a rapid diagnosis and accurate management in emergency situations. In addition, the associated bothersome side effects of anti-cholinergic agents, such as sedation, constipation, dryness of mouth, may interfere with diagnostic evaluation, and can be a hindrance for their consistent use.

Drotaverine – drug of choice for smooth muscle spasm in acute gastroenteritis

The above-mentioned shortcomings of anticholinergics invariably depict the need of having a safe and effective agent that does not mask the symptoms of underlying etiology, and does not interfere with the diagnosis. Drotaverine is one such drug that may be considered a drug of choice in treatment of acute and chronic smooth muscle spasms, and different pathological conditions accompanied by spastic pain. Being an isoquinoline derivative, it possess a powerful spasmolytic action on smooth muscle cells; evaluation of the prescription profile of drotaverine usage and its efficacy in different gastrointestinal indications provided evidence of pain relief in most patients.

Drotaverine has significant inhibitory effect on phosphodiesterase (PDE) enzyme; it inhibits PDE IV enzyme in vitro without inhibiting PDE III and PDE V. This selective inhibition may be important since PDE IV appears, functionally, to be very important in reducing contractile activity of the smooth muscles, suggesting that selective PDE IV inhibitors may be useful in the treatment of hypermotility disorders and various diseases associated with spastic conditions of the gastrointestinal tract. Thus, widely attributable to this characteristic pharmacological profile, drotaverine is a potential spamolytic in a large number of indications, of gastrointestinal origin, with smooth muscle spasm (Table 2).

Drotaverine is well-absorbed (90%) from all parts of the small intestine through linear absorption. As well, in contrast to the general concept that spasmolytics inhibit intestinal passage, preclinical evidence revealed that drotaverine, at therapeutic concentrations, had no inhibitory effect on gastrointestinal motility.

Importantly, the anti-spasmodic and painrelieving effect of drotaverine does not mask the symptoms of “acute abdomen”, and this may have relevant application in practice to achieve a rapid diagnosis (Box 1). Drotaverine, thus, may be given in cases without finalized diagnosis; pre-treatment in the emergency results in decrease of pain and spasm, without interfering the association of correct diagnosis.¹⁹Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent- drotaverine. JAMA India-The physician update;vol 4(12).   Such prompt alleviation of abdominal pain may be beneficial for both the child and parents, as most of the discomfort to children is due to colic pain of unknown cause. Therefore, pain in child has to be controlled without delaying given that besides directly affecting the child, abdominal pain in children is often frightening and frustrating for parents. Again, this may be an important real-life scenario requiring judicious use of drugs since the child would cooperate for physical checkups, and other treatment measures, only once pain has subsided. Thus, definite treatments, such as oral rehydration therapy for diarrhea and dehydration in acute gastroenteritis, may follow subsequently, or can be instituted simultaneously along with drotaverine.

Dosage of oral drotaverine in children:

• Children of 1-6 years age: 2 mg per Kg body weight TID not to exceed 120 mg per day
• Children of 6-12 years age: 40-60 mg TID or as required up to 200 mg.

Conclusion

Further to the classical manifestation of diarrhea, acute abdominal pain is a common occurrence in children with acute gastroenteritis. Therefore, each case of acute gastroenteritis should be managed promptly to avoid prolonging the child’s discomfort. In essence, to have prompt managed care in such a setting, or any other gastrointestinal condition characterized by smooth muscle spasms, it is important that the analgesic used does not mask the underlying pathology, a need well consistent with drotaverine application.

Drotaverine is a highly potent and safe spasmolytic agent, suited for oral administration, and capable of relieving or preventing smooth muscle spasm of various organs, including gastrointestinal tract. The drug does not mask the symptoms of “acute abdomen”, and, thus, may be valuable both as initial drug used for pain-relieving effect associated with spasmodic pain, and for maintenance of spasmolysis. In fact, drotaverine can be given effectively in cases without a final diagnosis to decrease pain and spasm, and without interfering the association of correct diagnosis. These characteristics make drotaverine an initial treatment choice in children presenting with pain abdomen. Further clinical management may follow dependent on the extent of diarrhea and presence of other symptoms. As such, ORS is invariably indicated to alleviate the impact of dehydration.

References

1. Bruzzese E, Lo Vecchio A, Guarino A. Hospital management of children with acute gastroenteritis. Curr Opin Gastroenterol. 2013 Jan;29(1):23-30.
2. Leung AK, Robson WL. Acute gastroenteritis in children: role of anti-emetic medication for gastroenteritis-relatedvomiting. Paediatr Drugs. 2007;9(3):175-84.
3. Elliott EJ. Acute gastroenteritis in children. BMJ. 2007 Jan 6;334(7583):35-40.
4. Heyworth JS, Baghurst P, Mc caul KA. Prevalence of gastroenteritis among 4-year-old children in South Australia. Epidemiol. Infect. 2003;130:443-451.
5. Webb A, Starr M. Acute gastroenteritis in children. Aust Fam Physician. 2005 Apr;34(4):227-31.
6. Shek KC, Ng P, Hung CY. A review on the management of acute gastroenteritis in children. Hong Kong j.emerg.med. 2004;11:152-160.
7. Lever DS, Soffer E. Acute Diarrhea. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/acute-diarrhea/ [Accessed on 15/6/13].]
8. Dalby-Payne JR, Elliott EJ. Gastroenteritis in children. Available at: http://bestpractice.bmj.com/best-practice/evidence/background/0314.html [Accessed on 15/6/2013].
9. Broor S, Ghosh D, Mathur P. Molecular epidemiology of rotaviruses in India. Indian J Med Res. 2003 Aug;118:59-67.
10. Colletti JE, Brown KM, Sharieff GQ, Barata IA, Ishimine P; ACEP Pediatric Emergency Medicine Committee. The management of children with gastroenteritis and dehydration in the emergency department. J Emerg Med. 2010 Jun;38(5): 686-98.
11. Churgay CA, Aftab Z. Gastroenteritis in children: Part 1. Diagnosis. Am Fam Physician. 2012 Jun 1;85(11):1059-62.
12. Levine A, Santucci KA. Pediatric Gastroenteritis. Available at: http://emedicine.medscape.com/article/801948-clinical. [Accessed on 15/6/2103].
13. McCollough M, Sharieff GQ. Abdominal pain in children. Pediatr Clin North Am. 2006 Feb;53(1):107-37, vi.
14. Blakelock RT, Beasley SW. Infection and the gut. Semin Pediatr Surg. 2003 Nov;12(4):265-74.
15. Churgay CA, Aftab Z. Gastroenteritis in children: Part II. Prevention and management. Am Fam Physician. 2012 Jun 1;85(11):1066-70.
16. Moir CR. Abdominal pain in infants and children. Mayo Clin Proc. 1996 Oct;71(10):984-9, quiz 989.
17. Mason JD. The evaluation of acute abdominal pain in children. Emerg Med Clin North Am. 1996 Aug;14(3):629-43.
18. Wedro B, Shiel WC Jr. Muscle Spasms. Available at: http://www.medicinenet.com/muscle_spasms/page2.htm. [Accessed on 14/6/2013].
19. Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent- drotaverine. JAMA India-The physician update;vol 4(12).