Clinical Question: What is the best treatment for acute dyspepsia?

In Clinical Questions, Medical Concepts by Colin Siu3 Comments

The Case: Tummy Ache? Piece of Cake!

A 26-year-old woman presents with epigastric pain after consuming a large piece of cake. She describes that she had previously been diagnosed with heartburn by her family doctor and was on a heartburn medication but stopped taking it when she went on vacation. She denies associated chest pain, shortness of breath, and changes in bowel habits. She describes the pain as a 7/10 sharp stabbing pain. She is otherwise well with no medical history or regular medications. Her vital signs are normal, she looks well and she has some mild tenderness in the epigastric area. The rest of her physical exam is unremarkable.

Your working diagnosis is acute dyspepsia but you suggest some other basic blood work including liver enzymes, bilirubin, and a lipase to rule out other abdominal causes. As the workup is pending your preceptor asks: “How would you like to manage this patient’s symptoms?”

The Clinical Question: What is the best treatment for acute dyspepsia?

Studies around the management of acute dyspepsia in an Emergency Department setting are scarce.

  • There has been controversy around the use of GI cocktails or “Pink Ladies” (a mixture of an antacid, viscous topical anesthetic, and an anti-spasmodic agent like donnatol).1,2 A double-blind randomized study from 2003 suggested that there is no significant difference in pain reduction at 30 minutes post-medication administration between groups in Emergency Departments treated with an antacid alone and groups treated with Pink Ladies.2
  • Some consider proton-pump inhibitors a go-to. However, in 2012 a single-centre RCT consisting of 87 patients presenting at the ED showed that the addition of IV pantoprazole 80mg to a regiment of oral antacid and IV antispasmodic agent did not show a significant difference in perceived pain score at the 60-minute mark when compared with a control group that received only an antacid and an antispasmodic agent.3 Most recently, a single-center RCT with 72 patients comparing IV ranitidine 50mg with IV pantoprazole 40mg found that both treatments reduced pain effectively and there was no significant difference between pain scores with both treatments at the 30 and 60-minute marks.4
  • Other studies conducted in the outpatient setting around the management of acute dyspepsia showed that treatment with oral antacid was superior to oral H2-receptor antagonists or placebo in decreasing dyspeptic symptoms at the 30 to 45 minute mark.5,6 Notably, antacid treatment yielded a faster onset of pain relief when compared with oral H2-receptor antagonist treatments though the latter had a superior overall response rate at 4 hours.5–7

A pharmacological perspective

The results showing a faster onset of action with antacids as compared with proton-pump inhibitors and  H2-receptor antagonists reflect the pharmacology of these medications. Antacids act as weak bases and neutralize acidic gastric contents providing rapid relief of dyspepsia. H2-receptor antagonists are slightly slower as they block H2-receptors and prevent ongoing acid secretion. Peak serum concentration of H2-receptor antagonists are established at 1 to 3 hours post-oral administration. It should be noted that there is no evidence that higher doses of H2-receptor antagonists (ie. 300mg of oral ranitidine) leads to improved symptoms. Finally, proton-pump inhibitors are the slowest acting as they are prodrugs that have to be converted into their active forms in the acidic environment of the stomach. After this, the activated form of the PPI binds to proton pumps to stop acid secretion and it is believed that this prodrug activation slows their onset of action. While it has been hypothesized that the concurrent administration of a PPI with an antacid may increase the gastric pH leading to decreased activation of the PPI prodrug, this has not been borne out in at least one clinical trial of healthy volunteers.8

The Bottom Line

Most of the evidence points towards initial management of acute dyspepsia with an oral antacid. There does not seem to be additional benefits to using a GI cocktail or Pink Lady over antacids alone. If symptom relief is not achieved with an antacid, a trial of intravenous or oral H2-receptor antagonists may be considered. In patients that have not responded to antacids or H2-receptor antagonists in previous dyspeptic episodes, a trial of IV proton-pump inhibitors may be considered. However, intravenous proton-pump inhibitors are not recommended for concurrent use with antacids, given the former is an acid-activated pro-drug.

Back to the Case

Your staff agrees with your plan to give the patient a trial of an antacid. You check on the patient after 45 minutes and she reports that her pain is currently a 5/10, down from 7/10. She asks if there is anything else that can help with her pain. After discussing with your staff, you decide to give the patient 150mg of oral ranitidine. You check in with the patient after another 45 minutes and she describes that she feels much better now and that her pain is only a 1/10. Her labs come back negative. You talk with your staff and decide to discharge the patient with a prescription for ranitidine and ask her to follow up with her GP for management of her GERD symptoms. The next day, you find a cake in the staff room – a thank you gift from your patient.

References

1.
Welling LR, Watson WA. The emergency department of treatment of dyspepsia with antacids and oral lidocaine. Annals of Emergency Medicine. 1990;19(7):785-788. doi: 10.1016/s0196-0644(05)81704-4 [Source]
2.
Berman DA, Porter RS, Graber M. The GI Cocktail is no more effective than plain liquid antacid: a randomized, double blind clinical trial. The Journal of Emergency Medicine. 2003;25(3):239-244. doi: 10.1016/s0736-4679(03)00196-3 [Source]
3.
Musikatavorn K, Tansangngam P, Lumlertgul S, Komindr A. A randomized controlled trial of adding intravenous pantoprazole to conventional treatment for the immediate relief of dyspeptic pain. The American Journal of Emergency Medicine. 2012;30(9):1737-1742. doi: 10.1016/j.ajem.2012.02.001
4.
Senay E. Comparison of intravenous pantoprazole and ranitidine in patients with dyspepsia presented to the emergency department: a randomized, double blind, controlled trial. World J Emerg Med. 2016;7(1):30. doi: 10.5847/wjem.j.1920-8642.2016.01.005
5.
Konturek J, Beneke M, Koppermann R, Petersen-Braun M, Weingärtner U. The efficacy of hydrotalcite compared with OTC famotidine in the on-demand treatment of gastroesophageal reflux disease: a non-inferiority trial. Med Sci Monit. 2007;13(1):CR44-9. [PubMed]
6.
Holtmeier W, Holtmann G, Caspary WF, Weing??rtner U. On-demand Treatment of Acute Heartburn With the Antacid Hydrotalcite Compared With Famotidine and Placebo. Journal of Clinical Gastroenterology. 2007;41(6):564-570. doi: 10.1097/mcg.0b013e31802e7efb
7.
Faaij, Van Gerven, Jolivet-Landreau, et al. Onset of action during on-demand treatment with Maalox suspension or low-dose ranitidine for heartburn. Aliment Pharmacol Ther. 1999;13(12):1605-1610. doi: 10.1046/j.1365-2036.1999.00654.x
8.
Yasuda S, Higashi S, Murakami M, Tomono Y, Kawaguchi M. Antacids have no influence on the pharmacokinetics of rabeprazole, a new proton pump inhibitor, in healthy volunteers. Int J Clin Pharmacol Ther. 1999;37(5):249-253. [PubMed]

Reviewing with the Staff

While not the sexiest of topics, this post underscores the importance of looking up the literature on the basics. Patients with dyspepsia are not uncommon and, while we must always diligently rule out more dangerous causes (depending on the patient\'s age and the particulars of their presentation, things like Acute Coronary Syndrome, Pulmonary Embolism, Pneumothorax, Pericarditis, Pancreatitis, Cholecystitis, and more may be on your list of things to \'rule out\'!), sometimes it is the diagnosis that is most likely at the end (and beginning!) of the work-up. You would think that we have a great evidence-based approach to its management, but as this post shows the treatments that we provide are more often steeped in dogma and tradition than they are evidence. The \"Pink Lady\" is still alive and well in my ED - and I suspect the same is true for many others - despite its unproven efficacy. Finally, I appreciate the pharmacological details of this post. Although have not seen evidence that antacids will truly decrease the efficacy of PPI\'s, it does make pharmacological sense that their efficacy might be delayed or reduced in a less acidic environment. Overall, I found that this post provide an excellent overview of the options for treating dyspepsia and their efficacy.

Dr. Brent Thoma
Interim Program Director of the Emergency Medicine Residency Program at the University of Saskatchewan and one of the founders of CanadiEM

Colin Siu

Colin is a medical student at the University of Alberta. His interests include emergency medicine, medical education, and social determinants of health. Outside of work, he can be found catching up on his Netflix shows, perusing Yelp for new restaurants to try and planning his next travel destination.