SGEM#302: We Didn’t Start the Fire but Can Antacid Monotherapy Stop the Fire?

Date: September 22nd, 2020 Guest Skeptic: Dr. Chris Bond is an emergency medicine physician in Calgary. He is also an avid FOAM supporter/producer through various online outlets including TheSGEM. Reference: Warren et al. Antacid monotherapy is more effective in relieving epigastric pain than in combination with lidocaine. A randomized double-blind clinical trial. AEM Sept 2020. Case: A 34-year-old male presents to the emergency department with burning epigastric pain after eating two hours ago. He says he gets this from time to time but this is the worst it has ever been. He denies chest pain, shortness of breath, fever and vomiting. His vital signs are within normal limits and his abdominal exam reveals mild epigastric and left upper quadrant tenderness with no peritonitis. Pink Lady Cocktail Background: Patients presenting to emergency departments (EDs) with epigastric pain are typically treated with an antacid, either alone or combined with other medications. Such medications include viscous lidocaine, an antihistamine, a proton pump inhibitor, or an anticholinergic (1,2). In Canada we often use an antacid plus viscous lidocaine referred to as a “Pink Lady”. This is different than the alcoholic cocktail called a Pink Lady. In the US, combination treatment is often called a “GI Cocktail”. There are mixed results from studies with varying methodological quality looking at acute dyspepsia management in the ED. One single-blind study comparing 30 mL of antacid with or without 15 mL of viscous lidocaine found the addition of lidocaine significantly increased pain relief, decreasing patient pain score by 40 mm compared to 9 mm with antacid monotherapy (3). Another single-blind RCT comparing antacid plus either benzocaine solution or viscous lidocaine found no statistical difference between the two interventions, however, there was no antacid monotherapy group (4). A larger, double-blind RCT of 113 patients compared 30 mL of antacid monotherapy, antacid with 10 mL of an anticholinergic, and antacid with anticholinergic and 10 mL of 2% viscous lidocaine. This study found all treatments had clinical efficacy and there was no statistical difference in pain relief between the three treatment groups. The conclusion from Berman et al was to recommend antacid monotherapy (5). Clinical Question: Is antacid monotherapy more effective in relieving epigastric pain than in combination with lidocaine? Reference: Warren et al. Antacid monotherapy is more effective in relieving epigastric pain than in combination with lidocaine. A randomized double-blind clinical trial. AEM Sept 2020. Population: Adult patients with epigastric pain or dyspepsia presenting to the emergency department. Excluded: Patients unable to consent or under 18 years of age. Intervention:  Arm 1 (Viscous): Received 10 mL oral lidocaine 2% viscous gel plus 10 mL antacid (traditional antacid/lidocaine mixture) Comparison: Arm 2 (Solution): Received 10 mL lidocaine 2% solution plus 10 mL antacid Arm 3 (Antacid): Received 20 mL antacid alone Outcome: Primary Outcome: Change in pain scores on 100mm visual analog scale (VAS) at 30 minutes after treatment. Secondary Outcomes: Medication palatability (taste, bitterness, texture, and overall acceptability) using a VAS, change in pain score 60 minutes post administration and adverse events. Dr. Jamie Warren This is an SGEMHOP episode which means we have the lead author on the show, Dr. Jaimee Warren. She is a first-year doctor at the Royal Melbourne Hospital and an aspiring emergency and retrieval physician. She hopes to one day work in rural and extreme environments. Authors’ Conclusions: “A 20 mL dose of antacid alone is no different in analgesic efficacy than a 20 mL mixture of antacid and lidocaine (viscous or solution). Antacid monotherapy was more palatable and acceptable to patients. A change in practice is therefore recommended to cease adding lidocaine to antacid for management of dyspepsia and epigastric pain in the ED.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The study participants were adequately randomized. Yes The randomization process was concealed. Yes The participants were analyzed in the groups to which they were randomized. Yes The study participants were recruited consecutively (i.e. no selection bias). No The participants in both groups were similar with respect to prognostic factors. Unsure All participants were unaware of group allocation. No All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Yes Key Results: The trial enrolled 94 patients and 89 could be analyzed (30 viscous, 31 solution and 28 antacid group). The mean age was in the early 40’s, with around 2/3 female and 80% of patients were discharged with a gastrointestinal diagnosis.  All three treatments (viscous, solution or antacid monotherapy) worked and there was no statistical difference between groups. Primary Outcome: The lidocaine solution with antacid and antacid monotherapy provided clinically important (>13 mm) analgesia at 30 minutes (17mm and 20mm), viscous lidocaine with antacid did not (9mm). However, this still did not result in a statistically significant difference between treatments. Secondary Outcomes: At 60 minutes, all treatment groups (viscous, solution and antacid monotherapy) experienced additional pain relief. The change in median pain scores was clinically significant (>13 mm) for all three arms (21mm, 26mm, and 32mm). The most frequent adverse effect was oral numbness (lidocaine viscous 20% and lidocaine solution 26%). Two patients in the viscous arm reported dizziness and tiredness (7%), and four patients in the solution arm reported cough, nausea, and dizziness (13%). One patient in the antacid arm reported a dry mouth (4%). Participants found antacid monotherapy to be the most palatable solution, with statistically significant differences in taste, bitterness, and overall acceptability. Listen to the podcast on iTunes to hear Jaimee's responses to our ten nerdy questions. 1. Inclusion Criteria: Patients were enrolled prospectively based on the clinician providing an antacid therapy. This resulted in a large group of patients having non-GI causes of pain. Why not enroll patients for whom the final diagnosis was dyspepsia or epigastric pain after ED workup? 2. Selection Bias: Why were patients that presented overnight excluded from enrolment (funding for research staff 24/7)? Are these patients potentially different (eg. more severe presentations of alcohol related gastritis, large meals for dinner followed by lying down or other reasons)? 3. Unbalanced Groups: In Table 1, it appears that more patients in the lidocaine arms had prior proton pump inhibitor (PPI) use and more prior upper GI related diagnoses (eg. Peptic ulcer disease/gastritis/gastroesophageal reflux disease). It also appears the viscous group received more rescue analgesics in the ED. Can you confirm these are all non-statistically significant differences between groups as the p-values are not documented? 4. Blinding of Staff: The solutions were not made to look identical. This could have unblinded the trial to the nursing staff. Do you think that could have impacted the results and did you consider asking the nurses which group they felt the participant was randomized? 5. Placebo Effect: The patients may also have been unblinded and susceptible to a placebo effect. Lidocaine has a bitter taste and can cause oral numbness. It has been demonstrated that bitter tasting treatments can increase the placebo effect. Wright et al. If it Tastes Bad it Must Be Good: Consumer Naïve Theories and the Marketing Placebo Effect. Intern. J. of Research in Marketing 2013 Kihlstrom. Placebo: Feeling Better, Getting Better, and the Problems of Mind and Body. Mcgill J Med. 2008 Evans FJ. The placebo response in pain reduction. In: Bonica JJ, editor. Advances in Neurology. New York: Raven; 1974 6. Diagnosis: Do you think that the effectiveness of antacid monotherapy is the same whether the diagnosis is dyspepsia vs. GERD vs. gastritis vs. PUD? 7. Primary Outcome: Your primary outcome was a change in 100mm VAS at 30 min. While that is an important patient-oriented outcome (POO) what about length of relief? Your secondary outcome was 60min. What about a longer time frame or return to ED within 24hrs? 8. Other Comparisons: Can you comment on how use of these medications compares with H2 receptor antagonists and PPIs in terms of efficacy for treating dyspepsia and epigastric pain in the ED? 9. Down Under: This was a single centre study conducted in Melbourne, Australia. Patient expectations can be different depending on the country. What are your thoughts to the external validity to other countries (UK, USA, Canada, Europe, etc)? Do you think you would find similar results? 10. Anything Else: Is there anything else you’d like to comment on about your paper that we have not asked, or you think is important for the SGEMers to know? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions but would say that a change in practice should be “considered” rather than “recommended”. SGEM Bottom Line: Consider using antacid monotherapy in place of lidocaine/antacid combination therapy for patients with dyspepsia. Case Resolution: You give your patient 20 mL of antacid and his epigastric pain improves.