Acute Abdominal Pain, Differential Diagnosis and Initial Pain Management

Introduction

Acute abdominal pain is one of the most common reasons to seek medical attention in clinical practice, in both the primary outpatient care and emergency settings.¹Abdominal Pain in Children. Available at: http://www.emedicinehealth. com/abdominal_pain_in_children/article_em.htm. [Accessed on 29.05.2017]   ²Cartwright SL, Knudson MP. Evaluation of acute abdominal pain in adults. Am Fam Physician. 2008;77(7):971-8.   ³Norton C, Czuber-Dochan W, Artom M, et al. Systematic review: interventions for abdominal pain management in inflammatory bowel disease. Aliment Pharmacol Ther. 2017;46(2):115-125.    It is commonly encountered in patients of all age groups, and is characterized by nociceptive pain arising in the abdominal region. Especially in younger children, it is the most common type of pain, and second most common type, after headache, in older children and adolescents.⁴Bufler P, Gross M, Uhlig HH. Recurrent Abdominal Pain in Childhood. Dtsch Arztebl Int 2011;108(17): 295–304.    The clinical significance of acute abdominal pain is wide ranging since it can be reflective of a wide array of underlying disorders that may range in severity from benign, self-limited conditions to life-threatening emergencies requiring specialist care.⁵ Murata A, Okamoto K, Mayumi T, et al. Age-related differences in outcomes and etiologies of acute abdominal pain based on a national administrative database. Tohoku J Exp Med. 2014;233(1):9-15.   ⁶Balachandran B, Singhi S, Lal S. Emergency management of acute abdomen in children. Indian J Pediatr. 2013;80(3):226- 34.   ⁷Ragsdale L, Southerland L. Acute abdominal pain in the older adult. Emerg Med Clin North Am. 2011;29(2):429-48, x.   ⁸Cartwright SL, Knudson MP. Diagnostic imaging of acute abdominal pain in adults. Am Fam Physician. 2015;91(7):452-9.   ⁹Ditkofsky NG, Singh A, Avery L, et al. The role of emergency MRI in the setting of acute abdominal pain. Emerg Radiol. 2014;21(6):615-24.   ¹⁰Falch C, Vicente D, Häberle H, et al. Treatment of acute abdominal pain in the emergency room: a systematic review of the literature. Eur J Pain. 2014;18(7):902-13.    Nonetheless, since general practitioners are often the first point of contact in many cases of acute abdominal pain, and face the challenge of meeting a wide and inhomogeneous spectre of complaints when dealing with the cohort of acute abdominal pain; it seems typically pertinent that the healthcare burden of acute abdominal pain would be particularly higher in primary care settings.¹¹Brekke M, Eilertsen RK. Acute abdominal pain in general practice: tentative diagnoses and handling. A descriptive study. Scand J Prim Health Care. 2009;27(3):137-40.    Together, the fact that many times it is hard to find the exact cause of abdominal pain in some cohorts complicates the scenario further. Regardless, it is imperative that each case of acute abdominal pain should be managed promptly to avoid prolonging the patients’ discomfort.

Causes of abdominal pain

In general, the origin of abdominal pain is quite complex, making it difficult to attribute it to a single model of causation.¹² Devanarayana NM, Rajindrajith S, de silva HJ. Recurrent Abdominal Pain in Children. Indian pediatrics 2009;46:389-99.    ¹³Shashidhar H, Omar HA. Recurrent lower abdominal pain in older children and adolescents: Revised Clinical Approach. The Scientific World journal 2005;5:64–70.    ¹⁴Kendall JL, Moreira ME. Evaluation of the adult with abdominal pain in the emergency department. Available at: https://www.uptodate. com/contents/evaluation-of-the-adult-with-abdominal-pain-in-theemergency- department [Accessed on 19/6/2017]    Nevertheless, considering the clinical pathogenesis, it is plausible to categorize the abdominal pain into following three categories: visceral (splanchnic) pain, parietal (somatic) pain, and referred pain (Table 1); and various possible causes ranging from trivial to lifethreatening etiologies (Figure 1), with little difference and an overlap in physical symptoms.¹Abdominal Pain in Children. Available at: http://www.emedicinehealth. com/abdominal_pain_in_children/article_em.htm. [Accessed on 29.05.2017]    ¹⁵Leung AKC. Acute abdominal pain in children. Am Fam Physician 2003; 67:2321-6.    Broadly, the etiological spectrum of acute abdominal pain can encompass

acute surgical diseases, intra- and extra-abdominal disorders, systemic illnesses and, more commonly, functional abdominal pain.¹⁶Yang W-C, Chen C-Y, Wu H-P. Etiology of non-traumatic acute abdomen in pediatric emergency departments. World Journal of Clinical Cases : WJCC. 2013;1(9):276-284.    ¹⁷Boyd CA, Riall TS. Unexpected gynecological findings during abdominal surgery. Current Problems in Surgery. 2012;49(4):195-251.     A diverse range of specific causes have therefore been explored, but some among them, such as appendicitis, biliary colic, cholecystitis, diverticulitis, bowel obstruction, visceral perforation, pancreatitis, peritonitis, renal colic, and intestinal infection seem to rank among the most common.¹⁶Yang W-C, Chen C-Y, Wu H-P. Etiology of non-traumatic acute abdomen in pediatric emergency departments. World Journal of Clinical Cases : WJCC. 2013;1(9):276-284.    ¹⁸Abdullah M, Firmansyah MA. Diagnostic approach and management of acute abdominal pain. Acta Med Indones. 2012;44(4):344-50.   In a study evaluating age-related differences in outcomes and etiologies of acute abdominal pain in a hospital-based population, Murata et al5 demonstrated intestinal infection to be the most frequent etiology, followed by ileus, peritonitis, cholelithiasis and diverticulitis (Figure 2A). However, in general practice, the most common non-urgent causes are non‑specific abdominal pain, labeled in up to one-fifth of patients (Figure 2B).¹¹Brekke M, Eilertsen RK. Acute abdominal pain in general practice: tentative diagnoses and handling. A descriptive study. Scand J Prim Health Care. 2009;27(3):137-40.   

Diagnosis and differential diagnosis of abdominal pain

Clinical evaluation of patients with abdominal pain can be meticulous for the physician, and should encompass a thorough history to identify the most likely cause, followed by a physical examination and a reassessment of certain points of the history.¹⁵Leung AKC. Acute abdominal pain in children. Am Fam Physician 2003; 67:2321-6.    History taking should focus on description of symptoms that permit presumptive etiopathological diagnosis. Essentially, it is important that the assessment be performed in a stepwise manner because the precise etiology of abdominal pain may often be hard to assess due to multiple pathophysiological factors of the underlying disorder, and the variable intensity and nature of pain amongst patients. Herein, the character and site of pain may aid in predicting some causes of acute abdomen and narrowing the underlying cause across vast spectrum of differential diagnosis (Figure 3).¹⁸Abdullah M, Firmansyah MA. Diagnostic approach and management of acute abdominal pain. Acta Med Indones. 2012;44(4):344-50.   ¹⁹Mazzei MA, Guerrini S, Cioffi Squitieri N. The role of US examination in the management of acute abdomen. Critical Ultrasound Journal. 2013;5(Suppl 1):S6.    Together, age is an important factor while evaluating abdominal pain in relation to differential diagnosis,¹⁵Leung AKC. Acute abdominal pain in children. Am Fam Physician 2003; 67:2321-6.    and pain history. It is therefore important that inquiry into important points such as location, onset, character, severity, duration, and radiation of pain be viewed in context to patients’ age. In addition, the progress of pain and its modulation may also point towards the possible origin – pain aggravated by movement points a parietal origin, relief in pain following a bowel movement suggests a colonic source, whereas relief following a vomiting episode suggests a source in the more proximal bowel. Further, it is important to have a detailed past medical, surgical and drug history before establishing any association because a history of similar pain in the past may suggest a recurrent problem.

Physical examination and investigations

A thorough physical examination is important before proceeding to any specific investigation that is often backed by a positive finding on initial examination. While abdominal physical examination may provide key assistance in establishing the initial diagnosis, rectal and pelvic examination should be performed only when required and when significant information is sought or expected. Further, laboratory studies should be customized to the patient’s signs and symptoms and findings elicited on clinical examination. Usually, initial investigations include a complete blood cell count (CBC) and urinalysis, and specific investigations are required in only certain cases.

Acute abdominal pain is a common indication for imaging.²⁰Fung CI, Fishman EK. Nonmalignant gastric causes of acute abdominal pain on MDCT: a pictorial review. Abdom Radiol (NY). 2017 Jan;42(1):101- 108.    Imaging may have a positive effect on the accuracy of the clinical diagnosis, increase the degree of diagnostic certainty, and assist in decision making. Nonetheless, the choice of imaging study as an initial test generally depends on clinical presentation (Figure 4).¹³Shashidhar H, Omar HA. Recurrent lower abdominal pain in older children and adolescents: Revised Clinical Approach. The Scientific World journal 2005;5:64–70.    ²¹Cartwright SL, Knudson MP. Diagnostic imaging of acute abdominal pain in adults. Am Fam Physician. 2015;91(7):452-459.    ²²Kumar AS, Coralic J, Vegeler R, et al. Magnetic resonance enterography: The test of choice in diagnosing intestinal “Zebras”. Case Reports in Gastrointestinal Medicine 2015 (2015);Article ID 206469:8 pages.     Plain-film abdominal radiographs may be useful in cases of suspected intestinal obstruction or when perforation of a viscus in the abdomen is a concern. Similarly, chest radiographs may help to rule out pneumonia. Whether to use ultrasonography and/or computed tomography (CT) in patients with abdominal pain is however a contentious issue in emergency medicine; since both modalities have their intrinsic utilities in diverse situations. Regardless, both clinical patterns of presentation and disease process and operational issues in particular healthcare setting should govern the decision and choice to use any particular investigation and/or imaging. Often, if abdominal ultrasound is not conclusive, contrast-enhanced CT should be performed.²³Becker P, Böttcher KA, Schilling D. Acute abdominal pain. Dtsch Med Wochenschr. 2017;142(6):432-441.

Initial management of acute abdominal pain

In general, treatment of abdominal pain should be directed at the underlying cause. However, it is often seen that the indistinct presentation of acute abdomen with overlapping symptoms renders difficulty in deciding whether a complaint needs emergency care or not.1 Regardless, alleviation of pain and spasm is the main concern in almost all cases, and hence physicians frequently opt using a variety of analgesics available. Here it is important to note that the use of anticholinergics is typically discouraged in acute abdominal pain for fear of interfering with accurate evaluation and diagnosis, which could affect further definite work-up.¹⁵Leung AKC. Acute abdominal pain in children. Am Fam Physician 2003; 67:2321-6.    Anticholinergic agents often mask the physical “acute abdomen” making it difficult to achieve a rapid diagnosis on reaching the hospital. In addition, sedation caused by these agents may interfere with the diagnostic evaluation related to central nervous system (CNS) function;²⁴Jones JD, Ramakrishnan K. Analgesics In The Initial Management Of Acute Abdominal Pain. The Internet Journal of Emergency Medicine 2005;2(2).    box 1 depicts some side-effects, which may be encountered with the use of anticholinergic antispasmodics.²⁵Antispasmodic. Available at: http://www.drugs.com/mtm/antispasmodic. html [Accessed on 29.05.17].

This masking effect of anticholinergics pose an important real-life dilemma since many patients would cooperate for physical checkups only once pain has subsided. Accordingly, there is a need for more judicious selection of drugs; and an agent that provides prompt and effective analgesia without masking the underlying etiology of acute abdominal pain could be a significant strategy here. Antispasmodics can be used in emergency related with smooth muscle spasm, and thereafter prompt diagnosis may help in deciding the optimal treatment modality based on the underlying etiology.

Drotaverine: A suitable anti-spasmodic in managing abdominal pain

Members of the synthetic isoquinolines are known to possess a powerful spasmolytic action on smooth muscle cells, and drotaverine is an isoquinoline derivative that shares this beneficial application. This selective inhibitor of phosphodiesterase isoenzyme IV has been found useful in spastic and motility disorders of the smooth muscle, and hence widely employed in several indications of acute abdominal pain.²⁶Misra SC, Pandey RM. Efficacy of drotaverine in irritable bowel syndrome: a double blind, randomized, placebo-controlled clinical trial. The American Journal of Gastroenterology 2000;95:2544.    ²⁷Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent. JAMA India;4(12).   ²⁷Zhu J, Cao Y, Yu ML, et al. Efficacy and safety of combination therapy with drotaverine and ketorolac versus ketorolac monotherapy for acute renal colic: a retrospective study of 322 patients. Int J Clin Exp Med 2017;10(2):3454-3461.

Preclinical pharmacokinetic and metabolism data have shown an excellent absorption of drotaverine from the small intestine – in humans, the drug is quickly absorbed, with 12 min half-life of absorption after oral dosing, and maximum plasma concentration appearing within 45 min.²⁷Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent. JAMA India;4(12).   In accordance with this data, the beneficial effect of oral drotaverine has been emphasized in therapy of spastic pain; in fact, it is proposed that oral administration of drotaverine is efficacious in the maintenance of spasmolysis, and thus would help in prolonging the pain-relief. For instance, in cases of spastic pain due to gastrointestinal ulcer, disappearance of pain was found to begin in 5-6 minutes; effect was completed within 12 minutes, and patients did not report abdominal pain. In all, studies evaluating the prescription profile of usage of drotaverine and its efficacy in different gastrointestinal indications have found pain-relief in 72% – 86% of patients.

The experience has thus shown that drotaverine is a highly potent and well-tolerated spasmolytic agent, suited for oral administration, and capable of relieving or preventing smooth muscle spasm of various organs. The drug effectively contributes in relieving painful spasms in several etiologies of acute abdominal pain, not limited to those of gastroenterological origin. Incidentally, at therapeutic concentrations, drotaverine does not have inhibitory effect on gastrointestinal motility, unlike other spasmolytics that may potentially inhibit intestinal passage. Another important characteristic of drotaverine, relevant to the need of suitable analgesic in acute abdominal pain, is that the anti-spasmodic and pain-killing effect of drotaverine does not mask the symptoms of “acute abdomen”. This is a unique feature that seems to have application in real-world clinical practice to achieve a rapid diagnosis, without obscuring the underlying pathology.27 Besides, the drug is free of the side-effects associated with anticholinergic antispasmodics such as dicyclomine etc. Furthermore, it does not has any morphine or dextropropoxyphene like effect, and thus does not result in addiction. Box 2 depicts some of the benefits of using drotaverine in patients with acute abdominal pain.²⁹Data on File. Walter-Bushnell.

Overall, rapid absorption and onset of efficacy, wide therapeutic window, and possible coadministration with other analgesics possibly makes drotaverine an optimal choice in emergency situations. The drug could be given in cases without finalized diagnosis; pre-treatment in emergency would result in decrease of pain and spasm, without interfering the association of correct diagnosis.

Conclusion

Acute abdominal pain is a common presentation seen in both primary and emergency care settings. The work-up of acute abdomen is often challenging owing to wide ranging and often confusing differential diagnoses. In primary care, however, the most common presentation is often nonspecific. In such cases, it is important that the analgesic used does not mask the underlying pathology, to have prompt diagnosis. Drotaverine, an isoquinoline derivative, appears fit to this desired criteria since it does not mask the symptoms of “acute abdomen”. The drug may thus be of use both for initial pain-killing effect in patients presenting with abdominal pain, and for the maintenance of spasmolysis. Drotaverine exhibits rapid absorption and onset of efficacy, a wide therapeutic window, and can effectively be given in cases of acute abdominal pain without a final diagnosis as it would decrease the pain and spasm without interfering the association of correct diagnosis. Besides, the drug is free of the side-effects associated with anticholinergic agents.

References

1. Abdominal Pain in Children. Available at: http://www.emedicinehealth. com/abdominal_pain_in_children/article_em.htm. [Accessed on 29.05.2017]
2. Cartwright SL, Knudson MP. Evaluation of acute abdominal pain in adults. Am Fam Physician. 2008;77(7):971-8.
3. Norton C, Czuber-Dochan W, Artom M, et al. Systematic review: interventions for abdominal pain management in inflammatory bowel disease. Aliment Pharmacol Ther. 2017;46(2):115-125.
4. Bufler P, Gross M, Uhlig HH. Recurrent Abdominal Pain in Childhood. Dtsch Arztebl Int 2011;108(17): 295–304.
5. Murata A, Okamoto K, Mayumi T, et al. Age-related differences in outcomes and etiologies of acute abdominal pain based on a national administrative database. Tohoku J Exp Med. 2014;233(1):9-15.
6. Balachandran B, Singhi S, Lal S. Emergency management of acute abdomen in children. Indian J Pediatr. 2013;80(3):226- 34.
7. Ragsdale L, Southerland L. Acute abdominal pain in the older adult. Emerg Med Clin North Am. 2011;29(2):429-48, x.
8. Cartwright SL, Knudson MP. Diagnostic imaging of acute abdominal pain in adults. Am Fam Physician. 2015;91(7):452-9.
9. Ditkofsky NG, Singh A, Avery L, et al. The role of emergency MRI in the setting of acute abdominal pain. Emerg Radiol. 2014;21(6):615-24.
10. Falch C, Vicente D, Häberle H, et al. Treatment of acute abdominal pain in the emergency room: a systematic review of the literature. Eur J Pain. 2014;18(7):902-13.
11. Brekke M, Eilertsen RK. Acute abdominal pain in general practice: tentative diagnoses and handling. A descriptive study. Scand J Prim Health Care. 2009;27(3):137-40.
12. Devanarayana NM, Rajindrajith S, de silva HJ. Recurrent Abdominal Pain in Children. Indian pediatrics 2009;46:389-99.
13. Shashidhar H, Omar HA. Recurrent lower abdominal pain in older children and adolescents: Revised Clinical Approach. The Scientific World journal 2005;5:64–70.
14. Kendall JL, Moreira ME. Evaluation of the adult with abdominal pain in the emergency department. Available at: https://www.uptodate. com/contents/evaluation-of-the-adult-with-abdominal-pain-in-theemergency- department [Accessed on 19/6/2017]
15. Leung AKC. Acute abdominal pain in children. Am Fam Physician 2003; 67:2321-6.
16. Yang W-C, Chen C-Y, Wu H-P. Etiology of non-traumatic acute abdomen in pediatric emergency departments. World Journal of Clinical Cases : WJCC. 2013;1(9):276-284.
17. Boyd CA, Riall TS. Unexpected gynecological findings during abdominal surgery. Current Problems in Surgery. 2012;49(4):195-251.
18. Abdullah M, Firmansyah MA. Diagnostic approach and management of acute abdominal pain. Acta Med Indones. 2012;44(4):344-50.
19. Mazzei MA, Guerrini S, Cioffi Squitieri N. The role of US examination in the management of acute abdomen. Critical Ultrasound Journal. 2013;5(Suppl 1):S6.
20. Fung CI, Fishman EK. Nonmalignant gastric causes of acute abdominal pain on MDCT: a pictorial review. Abdom Radiol (NY). 2017 Jan;42(1):101- 108.
21. Cartwright SL, Knudson MP. Diagnostic imaging of acute abdominal pain in adults. Am Fam Physician. 2015;91(7):452-459.
22. Kumar AS, Coralic J, Vegeler R, et al. Magnetic resonance enterography: The test of choice in diagnosing intestinal “Zebras”. Case Reports in Gastrointestinal Medicine 2015 (2015);Article ID 206469:8 pages.
23. Becker P, Böttcher KA, Schilling D. Acute abdominal pain. Dtsch Med Wochenschr. 2017;142(6):432-441.
24. Jones JD, Ramakrishnan K. Analgesics In The Initial Management Of Acute Abdominal Pain. The Internet Journal of Emergency Medicine 2005;2(2).
25. Antispasmodic. Available at: http://www.drugs.com/mtm/antispasmodic. html [Accessed on 29.05.17].
26. 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;95:2544.
27. Blasko G. Pharmacology, mechanism of action and clinical significance of a convenient antispasmodic agent. JAMA India;4(12).
28. Zhu J, Cao Y, Yu ML, et al. Efficacy and safety of combination therapy with drotaverine and ketorolac versus ketorolac monotherapy for acute renal colic: a retrospective study of 322 patients. Int J Clin Exp Med 2017;10(2):3454-3461.
29. Data on File. Walter-Bushnell.