Management of chronic/recurrent abdominal pain in children

Introduction

Abdominal pain is amongst the most common medical problems in pediatric medicine.¹Kaminski A, Kamper A, Thaler K, et al. Cochrane Database Syst Rev. 2011;(7):CD008013.   Hence, in practice, the physician must be able to distinguish abdominal pain diagnoses requiring immediate attention from self-limiting processes. In fact, pediatric patients can be challenging, and, therefore, the clinician must rely on a detailed history from a parent or caregiver, in addition to a careful physical examination, in order to narrow the differential diagnosis.²Marin JR, Alpern ER. Emerg Med Clin North Am. 2011;29(2):401-28, ix-x.   Also, care providers should ask about parental gastrointestinal problems because this is a risk factor (moderate evidence) for persistence of chronic abdominal pain in children.³Gieteling MJ, Bierma-Zeinstra SM, van Leeuwen Y, et al. J Pediatr Gastroenterol Nutr. 2011;52(2):154-61.  

Chronic/recurrent abdominal pain in children: Functional cause more evident

Chronic/recurrent abdominal pain is common among children and adolescents, affects about 10% of schoolgoing children and adolescents, and continues to be a diagnostic and therapeutic challenge; it interferes with everyday life, causes absence from school, and leads to frequent medical consultations.⁴Bufler P, Gross M, Uhlig HH. Dtsch Arztebl Int. 2011;108(17):295-304.  

More than 50 years ago, Apley, working in Bristol, UK, gave initial definition of recurrent abdominal pain in children in 1958, and concluded that less than 10% of recurrent abdominal pain cases have organic origin.⁵Fishbone M, Bernard B, Ehrlich C. J Clin Gastroenterol. 2006;40(6):497-503.  ^,6El-Matary W, Spray C, Sandhu B. Eur J Pediatr. 2004;163(10):584-8.  ^,7Nygaard EA, Størdal K, Bentsen BS. Scand J Gastroenterol. 2004;39(10):938-40.   Nevertheless, few Indian studies have reported an organic cause in 30%-40% of children with recurrent abdominal pain⁸Ganesh R, Arvind Kumar R, Suresh N, et al. Natl Med J India. 2010;23(2):94-9.  , and, accordingly, the majority of cases might be suggested to be having a functional etiology. Indeed, Devanarayana et al also documented that the majority of the children affected with recurrent abdominal pain have functional gastrointestinal diseases; and the exact cause of pain remains obscure.⁹Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatr. 2009;46(5):389-99.   Table 1 gives recommended clinical definitions of long-lasting intermittent or constant abdominal pain in children.¹⁰Pediatrics 2005;115;812.  

Emerging evidence suggests that emotional stress, visceral hypersensitivity and gastrointestinal motility disorders may play a vital part in its origin – impaired gastric emptying and antral motility, and excessive vagal withdrawal may have a possible role for gastric motility disturbances in the pathogenesis of childhood functional recurrent abdominal pain.⁷Nygaard EA, Størdal K, Bentsen BS. Scand J Gastroenterol. 2004;39(10):938-40.  ^,9Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatr. 2009;46(5):389-99.  ^,11Devanarayana NM, de Silva DG, de Silva HJ. J Gastroenterol Hepatol. 2008;23(11):1672-7.  ^,12Sowder E, Gevirtz R, Shapiro W, et al. Appl Psychophysiol Biofeedback. 2010 Sep;35(3):199-206.  

A practical approach to chronic abdominal pain in children

Ganesh et al presented a practical approach to chronic abdominal pain in children.⁸Ganesh R, Arvind Kumar R, Suresh N, et al. Natl Med J India. 2010;23(2):94-9.  

• The first step is to elicit a detailed history, and do a thorough physical examination to categorize chronic abdominal pain in relation to the site of pain (epigastric, periumbilical or left lower quadrant), the predominant symptom associated with pain (dyspepsia, isolated pain or altered bowel habits), and to differentiate the pain – organic or functional – based on the characteristics of pain and presence or absence of alarm signs (Table 2).¹³Berger MY, Gieteling MJ, Benninga MA. BMJ 2007;334:997-1002.  

• The second step is to apply appropriate investigations, restricted to simple tests when functional pain is suspected, and more investigations if there are alarm signs and pain appears to be organic in nature. Invasive investigations, for example gastrointestinal endoscopy, may be reserved for those with possible organic pain. Investigations such as EEG, workup for food allergy and porphyria may be required in a small percentage of children.
• The third step includes management of organic pain according to the etiology; while for functional chronic abdominal pain the pharmacological, and, rarely, psychological intervention is more difficult but should be done discreetly and tailored to the childs’ needs.

Use of Rome III criteria in diagnosing pediatric functional abdominal pain

The updated Rome III criteria for pediatric functional gastrointestinal disorders include new categories and changes to the Rome II criteria for various functional gastrointestinal disorders (Table 3).⁹Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatr. 2009;46(5):389-99.  ^,14Rasquin A, Di Lorenzo C, Forbes D, et al. Gastroenterology 2006;130(5):1527-1537.   These changes to the Rome criteria make the Rome III criteria more inclusive, allowing classification of 86.6% of pediatric patients with medically unexplained chronic abdominal pain, compared with the Rome II criteria (68.0%). Nevertheless, IBS was the most common diagnosis according to both Rome II (44.0%) and Rome III (45.1%).¹⁵Baber KF, Anderson J, Puzanovova M, et al. J Pediatr Gastroenterol Nutr. 2008;47(3):299-302.  

In a different study, Helgeland et al aimed to determine the proportion of referred children with nonorganic abdominal pain who meet the criteria for ≥ 1 diagnoses of functional gastrointestinal disorders, explore the distribution of diagnoses according to the revised pediatric Rome III criteria (PRC-III), and to investigate reasons for failure to meet these criteria.¹⁶Helgeland H, Flagstad G, Grøtta J, et al. J Pediatr Gastroenterol Nutr. 2009;49(3):309-15.   The authors recruited children (4-15 years) consecutively referred by general practitioners to 4 general pediatric outpatient clinics for the evaluation of recurrent abdominal pain. The diagnoses of functional gastrointestinal disorders were based on the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III version, completed by parents of respective children. All patients underwent medical investigations to exclude organic disease, and were re-evaluated at follow-up after 6 to 9 months.

Results showed that, of the 152 patients included, 142 (93%) had functional abdominal pain. Of these, 124 (87%) met the criteria for ≥ 1 diagnoses according to the PRC-III: 66% met the criteria for 1, 29% for 2, and 5% for 3 diagnoses. IBS was the most common diagnosis (43%) and overlapped with aerophagia in 16 children (38% of the children with overlapping diagnoses), and with abdominal migraine in 14 (33%). In the 18 patients (13%) not fulfilling the PRC-III for any functional gastrointestinal disorder diagnosis, the main reason was insufficient pain frequency (83%). Thus, it showed that of the referred children with functional abdominal pain, 87% met the PRC-III for specific diagnoses, supporting the use of these criteria as a diagnostic tool. However, the significant overlap between different functional gastrointestinal disorders makes it unclear whether some of the diagnoses represent distinct disorders or artificial categories.

Rectal Sensory Threshold for Pain: A diagnostic marker of IBS and functional abdominal pain in children

Because markers for these disorders are lacking, diagnostic evaluations may vary.¹⁷Fishbein M, Bernard B, Ehrlich C. J Clin Gastroenterol. 2006 Jul;40(6):497-503.   Halac et al conducted a study to evaluate the diagnostic value of the Rectal Sensory Threshold for Pain (RSTP) in children and

adolescents with chronic abdominal pain. Dependent on the study protocol, 51 patients (25 girls; median age 14.2 years; range 8.4-17.6) with abdominal pain >2 months underwent a series of rectal distensions with an electronic barostat; and RSTP and viscerosomatic referrals were assessed. The final diagnosis was documented three months after the barostat.¹⁸Halac U, Noble A, Faure C. J Pediatr. 2010;156(1):60-65.e1.  

Results showed that 35 patients had a functional gastrointestinal disorder (IBS or functional abdominal pain), and 16 had an organic disease. RSTP was lower in the functional gastrointestinal disorder group than in the organic disease group (25.4mm Hg vs. 37.1mm Hg; P = 0.0002). At the cutoff of 30mm Hg, the RSTP measurement for the diagnosis of functional gastrointestinal disorder had a sensitivity of 94%, and a specificity of 77%. Both groups similarly reported aberrant viscerosomatic projections, showing that viscerosomatic referrals are similar in children with functional gastrointestinal disorder and organic diseases. In conclusion, in children, RSTP is a diagnostic marker of IBS and functional abdominal pain.

Treatment approaches

Managing abdominal pain in childhood is important since those children with functional abdominal pain who cannot adapt to the pain run the risk of developing a somatoform adjustment disorder.¹⁹Schulte IE, Petermann F, Noeker M. Psychother Psychosom. 2010;79(2):73-86.   Further, this might be important since chronic abdominal pain is a risk factor for functional gut disorders in adulthood.²⁰Bremner AR, Sandhu BK. Indian Pediatr. 2009;46(5):375-9.  ^,21Chitkara DK, Talley NJ, Schleck C, et al. Scand J Gastroenterol. 2009;44(3):301-7.   Nonetheless, the diluted presentation with indistinct symptoms often makes it difficult to decide whether a complaint needs emergency care or not.²²Available at: http://www.emedicinehealth.com/abdominal_pain_in_children/article_em.htm.  

Repeated physical examination by the same physician over an extended time is the key to diagnosis in many patients with recurrent abdominal pain.
In those with a functional gut disorder, the aim of therapy is:

• Reassurance
• A return to normal activity
• Symptom control.

Psychological interventions, such as cognitive behavioral and family therapy are effective, reducing symptoms and improving school attendance.²⁰Bremner AR, Sandhu BK. Indian Pediatr. 2009;46(5):375-9.   Some authors also support use of hypnosis as a part of the biobehavioral approach for this dilemma, and found directed hypnotherapy to be highly effective in the treatment of children with longstanding functional abdominal pain or IBS.²³Vlieger AM, Menko-Frankenhuis C, Wolfkamp SC, et al. Gastroenterology. 2007;133(5):1430-6.  ^,24Galili O, Shaoul R, Mogilner J. J Laparoendosc Adv Surg Tech A. 2009;19(1):93-6.  

Pharmacotherapy

Emerging understanding of the interactions of mechanisms leading to chronic abdominal pain forms the basis for identification of potential pharmacological treatments for functional abdominal pain and IBS.²⁵Lebel AA. J Pediatr Gastroenterol Nutr 2008;47(5):703-705.   A significant proportion of abdominal pain in functional disorders is believed to be associated with abnormal perception of visceral sensations or alterations in motility. Accordingly, targets for modulation might include smooth muscle cells of the gastrointestinal tract, together with other target mechanisms.

IBS is the most common single diagnosis in undifferentiated recurrent abdominal pain, and can be readily identified using the current Rome criteria; pharmacologically reducing bowel spasm, and attenuating neural-pain processing are commonly used and effective strategies.²⁶Kohli R, Li BU. Pediatr Ann. 2004;33(2):113-22.  

Anti-depressants

Anti-depressants are amongst the most studied pharmacologic agents for functional gastrointestinal disorders, which are thought to act through reduction of pain perception, improvement of mood and sleep patterns, as well as modulation of the gastrointestinal tract, often through anti-cholinergic effects. However, in the preceding few years, overall use of anti-depressant medications in children and adolescents has been somewhat tempered by concerns for increased behavioural problems.

Further, clinicians must be aware that for the majority of anti-depressant medications no evidence exist that supports their use for the treatment of abdominal pain-related functional gastrointestinal disorders in children and adolescents. Moreover, studies in children with depressive disorders have shown that antidepressants can lead to substantial, sometimes life-threatening, adverse effects. Therefore, until better evidence evolves, clinicians should weigh the potential benefits of antidepressant treatment against known risks of anti-depressants in pediatric patients.²⁷Kaminski A, Kamper A, Thaler K, et al. Cochrane Database Syst Rev. 2011;(7):CD008013.   Still, it is the major problem facing efforts to identify the possible ‘suicidal effects’ of anti-depressants.²⁸Möller HJ, Baldwin DS, Goodwin G, et al. Eur Arch Psychiatry Clin Neurosci. 2008;258 Suppl 3:3-23.  

Anti-cholinergics

Anti-cholinergic medications are thought to be helpful for functional abdominal pain and IBS through their effects on decreasing smooth muscle spasms in the gastrointestinal tract that may produce symptoms such as pain.

Nonetheless, conventionally, the use of anti-cholinergic analgesics is discouraged in patients with abdominal pain for fear of interfering with accurate evaluation and diagnosis since they often mask the physical symptoms of “acute abdomen” making it difficult to achieve a rapid diagnosis and accurate management in emergency situations.²⁹Leung AKC. Am Fam Physician 2003;67:2321-6.   Also, sedation, constipation, dryness of mouth and other bothersome side-effect caused by anti-cholinergic anti-spasmodic agents may interfere with diagnostic evaluation, and can be a hindrance for their long-term use (Table 4).³⁰Jones JD, Ramakrishnan K. The Internet Journal of Emergency Medicine 2005;2(2).   Consequently, there exists the need of an agent that does not mask the underlying etiology, and, thus, does not interfere with the diagnosis. Also, it should be free of side effects so that it can be safely given to children for the management of acute and recurrent abdominal pain, particularly long-term.

Drotaverine suspension: A safe and effective anti-spasmodic to manage the abdominal pain

Drotaverine, being a selective inhibitor of phosphodiesterase isoenzyme IV, possess a powerful spasmolytic action on smooth muscle cells, and has been found useful is spastic and motility disorders of the smooth muscle.³¹Misra SC, Pandey RM. The American Journal of Gastroenterology 2000;95:2544.   Drotaverine does not have any morphine or dextropropoxyphene like effect, and, thus, do not result in addiction. In humans the drug was quickly absorbed, with maximum plasma concentration appearing within 45 min.³²Blasko G. JAMA India; 4(12).  

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. In fact, it contributes very effectively in relieving painful spasms in a large variety of diseases, including those of gastroenterological origin. Drotaverine improves motility by relaxing distal muscles and sphincters participating in peristaltic reflex.³³Data on File. Walter-Bushnell.  

Essentially, Drotaverine would help in prolonging the pain-relief, and is efficacious for the maintenance of spasmolysis. The drug does not mask the symptoms of “acute abdomen”; a feature making it unique in the group, and may have relevant application in practice. Moreover, the drug is free of the side-effects associated with anti-cholinergic anti-spasmodics, such as dicyclomine etc, and may be given safely over long-term.³²Blasko G. JAMA India; 4(12).   Figure 1 shows some of the benefits of using Drotaverine suspension for pain abdomen.

Thus, Drotaverine could be given in cases without finalized diagnosis. Indeed, the recent 2010 report on the survey of all pediatric uses of medicinal products in Europe showed that Drotaverine is used commonly in preschool and school children.³⁴Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/01/WC500101006.pdf.  

Dosage of oral Drotaverine in children dependent on age group:

• 1-6 years age: Per kg body weight dose = 2 mg or 1 ml TID not to exceed 120 mg per day
• 6-12 years age: 40-60 mg or 20-30 ml TID or as required up to 200 mg or 1 tab (40 mg) TID

Acid suppressants

Acid suppression agents, such as H2 blockers and proton pump inhibitors, are among the common medications used in children with abdominal pain.

Prokinetics

Prokinetic agents, stimulating gastrointestinal motility, have been employed for patients with functional gastrointestinal disorders, especially for conditions involving constipation or delayed gastric emptying, such as IBS and functional dyspepsia.³⁵Gershon MD, Tack J. Gastroenterology 2007;132(1):397-414.  ^,36Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010; 4(3): 293-304.  

Conclusion

Chronic/recurrent abdominal pain is a common complaint evaluated by pediatricians, and a cause of concern for children and parents.³⁷Van Tilburg MA, Chitkara DK. Minerva Pediatr. 2010 Apr;62(2):179-87.   Studies have reported that a considerable proportion of school-going children and adolescents experience chronic abdominal pain. These children report reduced quality of life and interferences with school and play due to their pain. The large majority of these children will not have a readily identified cause for their symptoms, and chronic abdominal pain is frequently classified as a functional gastrointestinal disorder. A detailed history, examination, and basic stool, urine and hematological investigations are sufficient to exclude organic pathology in them, and pharmacological treatments are commonly used in an effort to manage symptoms. Besides, discussing parents’ fears and worries about their children’s chronic abdominal pain may facilitate discussions of social learning of gastrointestinal illness behavior.³⁸Van Tilburg MA, Chitkara DK, Palsson OS, et al. J Pediatr Gastroenterol Nutr. 2009;48(3):311-7.  

While administering pharmacotherapy, it is important to consider that the anti-spasmodic drug used does not mask the underlying pathology, to have prompt diagnosis. Drotaverine, an anti-spasmodic, serves this purpose quite well since it does not mask the symptoms of “acute abdomen”, and, thus, may be valuable both as initial drug used for pain-killing effect in a child presenting with abdominal pain, and for maintenance of spasmolysis. In fact, the drug can be given effectively in cases without a final diagnosis to decrease pain and spasm, without interfering the association of correct diagnosis. These characteristics of Drotaverine could make it an initial choice in children presenting with pain abdomen.

References

1. Kaminski A, Kamper A, Thaler K, et al. Cochrane Database Syst Rev. 2011;(7):CD008013.
2. Marin JR, Alpern ER. Emerg Med Clin North Am. 2011;29(2):401-28, ix-x.
3. Gieteling MJ, Bierma-Zeinstra SM, van Leeuwen Y, et al. J Pediatr Gastroenterol Nutr. 2011;52(2):154-61.
4. Bufler P, Gross M, Uhlig HH. Dtsch Arztebl Int. 2011;108(17):295-304.
5. Fishbone M, Bernard B, Ehrlich C. J Clin Gastroenterol. 2006;40(6):497-503.
6. El-Matary W, Spray C, Sandhu B. Eur J Pediatr. 2004;163(10):584-8.
7. Nygaard EA, Størdal K, Bentsen BS. Scand J Gastroenterol. 2004;39(10):938-40.
8. Ganesh R, Arvind Kumar R, Suresh N, et al. Natl Med J India. 2010;23(2):94-9.
9. Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatr. 2009;46(5):389-99.
10. Pediatrics 2005;115;812.
11. Devanarayana NM, de Silva DG, de Silva HJ. J Gastroenterol Hepatol. 2008;23(11):1672-7.
12. Sowder E, Gevirtz R, Shapiro W, et al. Appl Psychophysiol Biofeedback. 2010 Sep;35(3):199-206.
13. Berger MY, Gieteling MJ, Benninga MA. BMJ 2007;334:997-1002.
14. Rasquin A, Di Lorenzo C, Forbes D, et al. Gastroenterology 2006;130(5):1527-1537.
15. Baber KF, Anderson J, Puzanovova M, et al. J Pediatr Gastroenterol Nutr. 2008;47(3):299-302.
16. Helgeland H, Flagstad G, Grøtta J, et al. J Pediatr Gastroenterol Nutr. 2009;49(3):309-15.
17. Fishbein M, Bernard B, Ehrlich C. J Clin Gastroenterol. 2006 Jul;40(6):497-503.
18. Halac U, Noble A, Faure C. J Pediatr. 2010;156(1):60-65.e1.
19. Schulte IE, Petermann F, Noeker M. Psychother Psychosom. 2010;79(2):73-86.
20. Bremner AR, Sandhu BK. Indian Pediatr. 2009;46(5):375-9.
21. Chitkara DK, Talley NJ, Schleck C, et al. Scand J Gastroenterol. 2009;44(3):301-7.
22. Available at: http://www.emedicinehealth.com/abdominal_pain_in_children/article_em.htm.
23. Vlieger AM, Menko-Frankenhuis C, Wolfkamp SC, et al. Gastroenterology. 2007;133(5):1430-6.
24. Galili O, Shaoul R, Mogilner J. J Laparoendosc Adv Surg Tech A. 2009;19(1):93-6.
25. Lebel AA. J Pediatr Gastroenterol Nutr 2008;47(5):703-705.
26. Kohli R, Li BU. Pediatr Ann. 2004;33(2):113-22.
27. Kaminski A, Kamper A, Thaler K, et al. Cochrane Database Syst Rev. 2011;(7):CD008013.
28. Möller HJ, Baldwin DS, Goodwin G, et al. Eur Arch Psychiatry Clin Neurosci. 2008;258 Suppl 3:3-23.
29. Leung AKC. Am Fam Physician 2003;67:2321-6.
30. Jones JD, Ramakrishnan K. The Internet Journal of Emergency Medicine 2005;2(2).
31. Misra SC, Pandey RM. The American Journal of Gastroenterology 2000;95:2544.
32. Blasko G. JAMA India; 4(12).
33. Data on File. Walter-Bushnell.
34. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/01/WC500101006.pdf.
35. Gershon MD, Tack J. Gastroenterology 2007;132(1):397-414.
36. Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010; 4(3): 293-304.
37. Van Tilburg MA, Chitkara DK. Minerva Pediatr. 2010 Apr;62(2):179-87.
38. Van Tilburg MA, Chitkara DK, Palsson OS, et al. J Pediatr Gastroenterol Nutr. 2009;48(3):311-7.