Comprehensive Management of Gastroenteritis

Gastroenteritis: A Common Cause of Morbidity and Mortality

Infective gastroenteritis by far becomes the most common explanation when young children experience sudden onset of diarrhea, with or without vomiting.¹Diarrhoea and Vomiting Caused by Gastroenteritis, Diagnosis, Assessment and Management in Children Younger than 5 Years. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0016589/. Accessed on: 4.5.16.   It is a very common childhood disease and its frequency amongst is generally more than one episode in a year.Nearly 3-5 billion children are affected worldwide with gastroenteritis each year, accounting for 1.5-2.5 million deaths per year or 12% of total global mortality in the age group between 1-4 years.²Chow CM, Leung AK, Hon KL. Acute gastroenteritis: from guidelines to real life. Clinical and experimental gastroenterology. 2010;3:97-112.   Even in the developing nations, children with gastroenteritis are particularly at risk of both morbidity and mortality.²Chow CM, Leung AK, Hon KL. Acute gastroenteritis: from guidelines to real life. Clinical and experimental gastroenterology. 2010;3:97-112.   ³Glass RI, Bresee J, Jiang B, Gentsch J, Ando T, Fankhauser R, Noel J, Parashar U, Rosen B, Monroe SS. Gastroenteritis viruses: an overview. Novartis Found Symp. 2001;238:5-19;discussion 19-25.   For instance, in India, diarrhea is the third leading cause of mortality among children less than 5 years, attributing to 13% deaths in this age-group, equivalent to over 3,00,000 deaths each year.⁴Lakshminarayanan S, Jayalakshmy R. Diarrheal diseases among children in India: Current scenario and future perspectives. Journal of Natural Science, Biology, and Medicine. 2015;6(1):24-28.   A wide variety of pathogens or poor nutrition status of children may be responsible for some of the apparent increase in the prevalence and associated poor prognosis of gastroenteritis.³Glass RI, Bresee J, Jiang B, Gentsch J, Ando T, Fankhauser R, Noel J, Parashar U, Rosen B, Monroe SS. Gastroenteritis viruses: an overview. Novartis Found Symp. 2001;238:5-19;discussion 19-25.   ⁵Elliott EJ. Acute gastroenteritis in children. BMJ: British Medical Journal. 2007;334(7583):35-40.  

Etiological Basis of Gastroenteritis

Gastroenteritis is characterized by the inflammation of mucous membranes of the gastrointestinal tract. Although the underlying pathology may be multifactorial, different classes of microorganisms and parasites, which include viruses, bacteria, protozoa, and helminths, constitute the most common cause (box 1).⁶Webb A, Starr M. Acute gastroenteritis in children. Aust Fam Physician. 2005 Apr;34(4):227-31.   Of these, majority of the cases are due to viral infection, such as rotaviruses and noroviruses that are most commonly implicated. Rotavirus that prevails throughout the year in the tropics, manifests as a seasonal infection in the temperate climates with a peak in the late winters.⁵Elliott EJ. Acute gastroenteritis in children. BMJ: British Medical Journal. 2007;334(7583):35-40.   Overall, the viruses are often transmitted by fecal contamination of food or water and may affect individuals belonging to all age groups.³Glass RI, Bresee J, Jiang B, Gentsch J, Ando T, Fankhauser R, Noel J, Parashar U, Rosen B, Monroe SS. Gastroenteritis viruses: an overview. Novartis Found Symp. 2001;238:5-19;discussion 19-25.   Once infected, viral infections may injure the small bowel enterocytes, thereby causing low-grade fever and watery diarrhea without blood.⁵Elliott EJ. Acute gastroenteritis in children. BMJ: British Medical Journal. 2007;334(7583):35-40.   Similarly,clinical presentation may vary according to the infective pathogens.⁷National Collaborating Centre for Women’s and Children’s Health (UK). Diarrhoea and Vomiting Caused by Gastroenteritis: Diagnosis, Assessment and Management in Children Younger than 5 Years.London: RCOG Press; 2009 Apr. (NICE Clinical Guidelines, No. 84.)3, Diagnosis.  

Clinical Picture of Gastroenteritis

As previously stated, gastroenteritis clinically presents as sudden onset of diarrhea with or without vomiting in a child who otherwise was healthy. Besides, a sudden change in the stool consistency to loose or watery stools is also suggestive of gastroenteritis. However,since these are common symptoms, these may be misinterpreted as other non-enteric infections or non-infective gastrointestinal disorders, such as ulcerative colitis, Crohn’s disease or coeliac disease. Therefore, it is important to note the duration of diarrhea and vomiting in children with gastroenteritis, which is generally as follows:

• Diarrhea: Lasts for 5-7 days, and ceases within 2 weeks in most cases
• Vomiting: Lasts for 1-2 days, and ceases within 3 days in most cases

Other than these two primary symptoms, gastroenteritis is also accompanied by fever and abdominal pain. Extraintestinal features of infection may also be seen, which include toxic look, poor feeding, hepatosplenomegaly,and pneumonia. As mentioned earlier, the extent and severity of these symptoms are majorly influenced by the type of infectious agent. Rotavirus infection may cause sudden onset of vomiting, high incidence of fever, and dehydration, with a mean diarrhea duration of 5.9 days.Longer lasting diarrhea with an average duration of 10.8 days is more commonly seen in infection with enteric adenovirus. On the other hand, bacterial infections have been found to be associated with abdominal pain, bloody and prolonged diarrhea (mean 14.1 days), leukocytosis,and an increased erythrocyte sedimentation rate (ESR). Similarly, infection of protozoal or mixed origin demonstrates higher incidence of stool containing blood and/or mucus, in comparison to rotavirus. Abdominal pain, although more common in bacterial infection, can also be observed in infections with Shigella, Salmonella, and Campylobacter.⁷National Collaborating Centre for Women’s and Children’s Health (UK). Diarrhoea and Vomiting Caused by Gastroenteritis: Diagnosis, Assessment and Management in Children Younger than 5 Years.London: RCOG Press; 2009 Apr. (NICE Clinical Guidelines, No. 84.)3, Diagnosis.  

Pain in Abdomen

Pain in abdomen is one of the leading pediatric complaints for physician visits.⁸Shakya KN, Dongol UM, Khadka SB. A study of abdominal pain in children. JNMA J Nepal Med Assoc. 2008 Oct-Dec;47(172):193-6.   Gastroenteritis represents the most common non-surgical condition implicated in acute abdominal pain. Its pathophysiologic mechanism can be directly related to visceral pain receptors, which are located on the serosal surface, in the mesentery, within the intestinal muscle, and the mucosa of hollow organs.These pain receptors are triggered in the presence of mechanical and chemical stimuli, such as stretching,tension, and ischemia. As a result, diffuse abdominal tenderness before diarrhea and severe cramping abdominal pain develops.⁹Kim JS. Acute Abdominal Pain in Children. Pediatric Gastroenterology, Hepatology & Nutrition. 2013;16(4):219-224.   Besides, the intensity of accompanying dehydration indicated by certain clinical signs, such weight loss, prolonged capillary refill, poor turgor, reduced urinary output and abnormal respiration warrant immediate medical care in order to avoid any untoward complications.¹⁰Turner D, Ashkenazi S, Mimouni F, Shamir R. [Recommendations for the diagnosis and management of pediatric acute gastroenteritis in Israel]. Harefuah. 2010 Jan;149(1):53-8, 61, 60.  

Management of Gastroenteritis

Gastroenteritis is managed by combining various therapeutic agents, targeting either the etiology or the pathophysiologic mechanism. Oral rehydration solutions (ORS) are considered the mainstay for treating rehydration. Subsequent to at least 4 hours of rehydration, it is advisable to resume full diet, including lactose. The self-limited conditions may not require any further therapeutic interventions. Probiotics are the food supplements that are also prescribed in the therapeutic regimen of gastroenteritis, as these shorten the diarrheal episodes and reduce its severity. Antimicrobial therapy is selected based on the pathogenic organism responsible,such as in cases with shigellosis and campylobacter infections. Moreover, as per the European, American and Israeli guidelines, vaccination against rotavirus is also recommended.¹⁰Turner D, Ashkenazi S, Mimouni F, Shamir R. [Recommendations for the diagnosis and management of pediatric acute gastroenteritis in Israel]. Harefuah. 2010 Jan;149(1):53-8, 61, 60.   ¹¹Ciccarelli S, Stolfi I, Caramia G. Management strategies in the treatment of neonatal and pediatric gastroenteritis. Infection and Drug Resistance. 2013;6:133-161.   Besides, symptomatic therapy is also advised in cases with abdominal pain. Drotaverine hydrochloride is an antispasmodic agent, which is considered effective and tolerable for the management of recurrent abdominal pain in children (table 1).¹²Narang 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.  

Drotaverine, being a selective inhibitor of phosphodiesterase isoenzyme IV, possess a powerful spasmolytic action on smooth muscle cells, and has been found useful in spastic and motility disorders of the smooth muscle.¹³Misra SC, Pandey RM. Efficacy of drotaverine in irritable bowel syndrome: a double blind, randomized, placebo-controlled clinical trial. The American Journal of Gastroenterology. 2000;95(9):2544.   Drotaverine does not exert any morphine or dextropropoxyphene like effect; thereby,risk of addiction is minimized. It has been observed in human studies that the drug gets quickly absorbed, with half-life and maximum plasma concentration appearing within 12 and 45 minutes, respectively. Moreover, nearly 65% of the dose reaches unchanged in the systemic circulation¹⁴Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent. JAMA India. 2001;4(12):55-6.  

Drotaverine is a highly potent and tolerable spasmolytic agent, suited for oral administration, and capable of relieving or preventing smooth muscle spasms, including those of gastroenterological origin..¹⁵Report on the survey of all paediatric uses of medicinal products in Europe.Available from: http://www.ema.europa.eu/docs/en_GB/document_ library/Report/2011/01/WC500101006.pdf. Accessed on: 5.5.16.   Essentially, as it also maintains the spasmolysis, this way it may help in prolonging the pain-relief. A study was conducted by Narang and coworkers¹²Narang 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.   to evaluate the efficacy and tolerability of drotaverine hydrochloride in children with recurrent abdominal pain. Of the total 132 children recruited, those between 4-6 years of age were administered 10 mL syrup orally (20 mg drotaverine hydrochloride or placebo) thrice daily for 4 weeks. Children older than 6 years of age were supplemented with one tablet orally (40 mg drotaverine hydrochloride or placebo) thrice daily for 4 weeks. It was observed that number of episodes of abdominal pain and school absence significantly reduced in the drotaverine group in contrast to placebo. All the children well tolerated the drug. Moreover, drotaverine does not mask the symptoms of “acute abdomen”; a feature making it unique in the group. In comparison to its counterparts, such as dicyclomine, it is also devoid of anticholinergic sideeffects,including drowsiness, nausea, vomiting, bloating, decreased sweating or urination, constipation, decreased taste sensation, dry mouth, headache, dizziness, weakness, blurred vision, and painful or difficult urination (box 2).¹⁴Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent. JAMA India. 2001;4(12):55-6.   These adverse effects make anticholinergics unsuitable for patients with glaucoma and benign prostatic hyperplasia (BPH). In addition, a report on the survey of use of pediatric medicinal products in Europe revealed that drotaverine has been a commonly used therapeutic agent in preschool and school children.¹⁵Report on the survey of all paediatric uses of medicinal products in Europe.Available from: http://www.ema.europa.eu/docs/en_GB/document_ library/Report/2011/01/WC500101006.pdf. Accessed on: 5.5.16.  

Smooth muscle spasm is often associated with colicky abdominal pain. In such cases, combining a spasmolytic agent with an analgesic may result in prompt and adequate relief, improving both spasm and pain. Such ombinations have been well accepted for a long time. In light of this, therapy comprising acetaminophen and drotaverine may be beneficial. Acetaminophen, other than being an effective antipyretic, also inhibits prostaglandin synthesis, thereby exerting rapid analgesic action. It produces the analgesic effect as fast as within 7 minutes, complementing the fast antispasmodic action of drotaverine. Moreover, no adverse interactions have been reported between drotaverine and acetaminophen.By virtue of their different mechanisms of action, the combination of drotaverine and acetaminophen proves to be a potential therapeutic alternative that provides rapid pain relief (box 3).

References

1. Diarrhoea and Vomiting Caused by Gastroenteritis, Diagnosis, Assessment and Management in Children Younger than 5 Years. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0016589/. Accessed on: 4.5.16.
2. Chow CM, Leung AK, Hon KL. Acute gastroenteritis: from guidelines to real life. Clinical and experimental gastroenterology. 2010;3:97-112.
3. Glass RI, Bresee J, Jiang B, Gentsch J, Ando T, Fankhauser R, Noel J, Parashar U, Rosen B, Monroe SS. Gastroenteritis viruses: an overview. Novartis Found Symp. 2001;238:5-19;discussion 19-25.
4. Lakshminarayanan S, Jayalakshmy R. Diarrheal diseases among children in India: Current scenario and future perspectives. Journal of Natural Science, Biology, and Medicine. 2015;6(1):24-28.
5. Elliott EJ. Acute gastroenteritis in children. BMJ: British Medical Journal. 2007;334(7583):35-40.
6. Webb A, Starr M. Acute gastroenteritis in children. Aust Fam Physician. 2005 Apr;34(4):227-31.
7. National Collaborating Centre for Women’s and Children’s Health (UK). Diarrhoea and Vomiting Caused by Gastroenteritis: Diagnosis, Assessment and Management in Children Younger than 5 Years.London: RCOG Press; 2009 Apr. (NICE Clinical Guidelines, No. 84.)3, Diagnosis.
8. Shakya KN, Dongol UM, Khadka SB. A study of abdominal pain in children. JNMA J Nepal Med Assoc. 2008 Oct-Dec;47(172):193-6.
9. Kim JS. Acute Abdominal Pain in Children. Pediatric Gastroenterology, Hepatology & Nutrition. 2013;16(4):219-224.
10. Turner D, Ashkenazi S, Mimouni F, Shamir R. [Recommendations for the diagnosis and management of pediatric acute gastroenteritis in Israel]. Harefuah. 2010 Jan;149(1):53-8, 61, 60.
11. Ciccarelli S, Stolfi I, Caramia G. Management strategies in the treatment of neonatal and pediatric gastroenteritis. Infection and Drug Resistance. 2013;6:133-161.
12. 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.
13. Misra SC, Pandey RM. Efficacy of drotaverine in irritable bowel syndrome: a double blind, randomized, placebo-controlled clinical trial. The American Journal of Gastroenterology. 2000;95(9):2544.
14. Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent. JAMA India. 2001;4(12):55-6.
15. Report on the survey of all paediatric uses of medicinal products in Europe.Available from: http://www.ema.europa.eu/docs/en_GB/document_ library/Report/2011/01/WC500101006.pdf. Accessed on: 5.5.16.