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SGEM#196: Gastroparesis – I Feel Like Throwing Up

SGEM#196: Gastroparesis – I Feel Like Throwing Up

Podcast Link: SGEM196

Date: November 24th, 2017

Reference: Roldan et al. Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis. AEM November 2017

Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the Director of Simulation Education at Markham Stouffville Hospital in Ontario. He is the creator of the excellent #FOAMed project called First10EM.com

Case: You charge nurse approaches as you finish charting on the trauma patient who was just transferred out. “Mrs. G. is back again, vomiting and screaming in pain. This is the third time this month, and nothing ever seems to help. Is there anything we can do for her?”

Mrs. G is a 37-year-old female with gastroparesis secondary to diabetes. You know her well, and none of the usual anti-emetics seem to help her symptoms. While inwardly wishing you worked in a country where droperidol was available, you wonder whether there is any new research to guide your management.

Background: Gastroparesis is a challenging and frustrating condition for both patients and providers. Patients can present with abdominal pain, nausea, vomiting, early satiety and postprandial fullness. Gastroparesis has also been called delayed gastric emptying and it literally means paralysis of the stomach.

The most common cause of gastroparesis is idiopathic. However, when a cause is known it is often due to diabetes or surgery. Unfortunately, nothing really works well for this condition. The Food and Drug Administration has only approved metoclopramide for gastroparesis. It works by blocking dopamine receptors with antiemetic and prokinetic properties.

Multiple other drugs have been tried to treat gastroparesis. This includes serotonin 5-HT3 antagonists (ondansetron), histamine antagonists (meclizine and promethazine) prokinetic agents like serotonin 5-HT4 receptor agonists (cisipride) and motilin receptor agonists (erythromycin).

One drug that has been tried is haloperidol. It is an antipsychotic drug used for a number of psychiatric conditions including schizophrenia. Haloperidol blocks the dopamine receptors in the brain. It has been used for years to treat nausea and vomiting in post-operative patients and cancer patients.

A retrospective study was published earlier this year on haloperidol for the treatment of gastroparesis secondary to diabetes mellitus. It was called HUGS and showed lower hospital admissions and opioid use in patients receiving 5mg of haloperidol (Ramirez et al AJEM). You can find a good review on this paper on REBEL EM.

There has never been a randomized control trial looking at the efficacy of haloperidol on nausea and vomiting in any setting, until now.


Clinical Question: Does haloperidol, when added to conventional therapy, decrease abdominal pain and nausea at one hour in patients presenting to the emergency department with known gastroparesis?


Reference: Roldan et al. Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis. AEM November 2017.

  • Population: Adults 18 years and older presenting to the emergency department with abdominal pain due to their known gastroparesis.
    • Exclusions: Past history or current evidence of QT prolongation, hypotension (systolic blood pressure < 90 mm Hg), presence of other acute abdominal pathologic conditions, allergy to haloperidol, pregnancy, incarcerated status, or an inability to give informed consent.
  • Intervention: Haloperidol 5mg IV
  • Comparison: Placebo
  • Outcome:
    • Primary Outcomes: Abdominal pain measured on a validated 10-point visual analog scale (VAS) and nausea intensity scored on a 5-point VAS at one hour.
    • Secondary Outcomes: Disposition status, emergency department length of stay, adverse events and nausea resolution at one hour. Nausea resolution was defined as the patient not requesting additional antiemetic medication.

Dr. Carlos Roldan is an assistant professor of Pain Medicine and a Clinical Associate Professor of Emergency Medicine at the University of Texas MD Anderson Cancer Center

Authors’ Conclusions: Haloperidol as an adjunctive therapy is superior to placebo for acute gastroparesis symptoms.”

checklistQuality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the emergency department. Yes
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). Yes
  6. The patients in both groups were similar with respect to prognostic factors. Unsure
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
  8. All groups were treated equally except for the intervention. No
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Unsure
  11. The treatment effect was large enough and precise enough to be clinically significant. Yes

Key Results: 33 patients were included in the study s(15 in the haloperidol group and 18 in the placebo group). The mean age was in the mid 40’s with about 75% women.


Primary Outcomes: Haloperidol group works better than placebo for treating pain and nausea from gastroparesis.


  • Primary Outcomes:
    • Pain: Decreased from a mean of 8.5 to 3.1 with haloperidol (p<0.001). Decreased from a mean of 8.3 to 7.2 with placebo (p=0.11).
    • Nausea: Decreased from a mean of 4.5 to 1.8 with haloperidol (p<0.001). Decreased from a mean of 4.1 to 3.4 with placebo (p=0.05)
  • Secondary Outcomes:
    • Disposition: Fewer patients were admitted to hospital in the haloperidol group (27% vs 72%, p=0.009).
    • Length of Stay: Median length of stay was statistically unchanged, but the point estimate was shorter in the haloperidol group (5 vs 9 hours, p=0.77).
    • Resolution of Nausea: This was not listed in the results?
    • Adverse Events: No adverse events were reported.

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Dr. Carlos Roldan

Dr. Carlos Roldan

We see a lot of patients in the emergency department with cyclic vomiting syndromes. It is great to have the first ever randomized control trial to provide some additional evidence to help us better address this issue. Listen to the SGEM Podcast on iTunes to hear Carlos’ answers to our nerdy questions.

  1. Population and Sample Size: This study limited enrolment to patients with known gastroparesis. Given that the mechanism attributed to haloperidol is antagonism of dopamine receptors in the chemoreceptors trigger zone, why limit the study to only patients with gastroparesis rather than undifferentiated cyclic vomiting, which would have broader applicability in the emergency department? Your sample size calculation determined that 18 participants were needed in each group, but you only had 15 patients in the haloperidol group. Other researchers will add a buffer to increase the sample size in anticipation of losing a few patients. Did you consider doing this and how do you think the smaller sample size impacts the results/conclusions?
  2. ECG: You performed ECGs on all patients in order to exclude patients with a long QT. Is there any evidence that you are aware of the screening ECGs prevent adverse events with anti-psychotic use? Research protocols are much stricter than routine clinical practice. IF you were using haloperidol for these patients in your clinical practice would you get an ECG  every time before administering this medication?
  3. Statistical vs. Clinical Significance: Although they were not statistically different, there seem to be important differences between the two groups in terms of the treatments they received. For example, 40% of the haloperidol group received morphine as compared to 28% of the placebo group. Similarly, 53% of the haloperidol group received and ondansetron as compared to only 28% of the placebo group . Do you think these imbalances might have affected your results? In addition, there was no statistical difference in emergency department length of stay. However, the five hours in the haloperidol group vs. nine hours in the placebo group might be clinically significant to the patient and the physician.
  4. Outcomes: First of all, you had two primary outcomes. Did you know that there can only be one primary outcome (Highlander)? You chose pain and nausea at one hour as your primary outcome. In terms of patient oriented outcomes, do you think choosing a longer follow up period might have been better? Pain score VAS has been validated previously. Has the 5-point nausea VAS been validated?  One final thing under outcomes. Your secondary outcomes included nausea resolution at one hour defined as not requesting additional antiemetic medication. We could not find this reported in the result section?
  5. Adverse Events and Safety: Adverse events are typically under reported in studies. We really liked that you looked for adverse events and you did not claim safety. You recognized that the study was far too small to make such a positive claim. Instead, you stated that there were no adverse events reported. Would you consider doing a larger study on undifferentiated gastroparesis presentations to the emergency department and what size to you think it would take to claim safety of haloperidol?

Is there anything else you want the SGEMers to know about your study Carlos?

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions.


SGEM Bottom Line: Consider adding 5mg IV haloperidol as an adjunct treatment to patients presenting to the emergency department with abdominal pain and nausea from their known gastroparesis.  


Case Resolution: You discuss this new trial with your patient, and after a shared decision-making conversation, you decide to try haloperidol as part of their symptom control strategy.

Clinical Application: Adding this first, small randomized control trial to the large clinical experience, we think it is reasonable to consider trying haloperidol as an adjunct to treat gastroparesis.

Dr. Justin Morgenstern

Dr. Justin Morgenstern

What Do I Tell My Patient? As you know, the symptoms from gastroparesis can be very difficult to manage. There is new research paper saying a medication called haloperidol could help. This medicine has been successfully used for years to treat post-operative patients and cancer patients with nausea and vomiting. I am not saying you have cancer. What I am saying is you have tried all these other medications that have not worked. This recent small study on haloperidol suggests it could work for you. I can see you are suffering and want to try something to help.

Keener Kontest: Last weeks’ winner was David Bowden and EMT from Texas. David knew honey bees are able to behaviorally induce fever in a whole-of-colony response to a fungal parasite?

I made a mistake last week with the keener winner. It was basically a tie with Julien Ginsberg-Peltz a PedEM from Baystate Medical Center in Springfield, MA and Mateusz Szmidt from Liverpool, England. I think the problem was due to the time zone difference. Regardless, they are both getting a cool skeptical prize.

Listen to the SGEM podcast on iTunes to hear this weeks’ question. If you know the answer send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

SGEM-HOP-SAEM-logo-227x300SGEMHOP: Now it is your turn SGEMers. What do you think of this episode? Tweet your comments using #SGEMHOP. What questions do you have for Dr. Roldan and his team? Ask them on the SGEM blog. Share your experience using haloperidol for gastroparesis. The best social media feedback will be published in AEM.

Also, don’t forget those of you who are subscribers to Academic Emergency Medicine can head over to the AEM home page to get CME credit for this podcast and article.

  • Go to the Wiley Health Learning website
  • Register and create a log in
  • Search for “Academic Emergency Medicine – November”
  • Complete the five questions and submit your answers
  • Please email Corey (coreyheitzmd@gmail.com) with any questions or difficulties.

FOAM logoOther FOAMed:

  • REBEL EM – Diabetic Gastroparesis Needs HUGS
  • EM in Focus – Haloperidol- one anti-emetic to rule them all.
  • First10EM – Articles of the Month November 2017
  • FOAMCast – Episode 73 – Gastroparesis & Biliary Pathology

 


Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.


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  • Kirsty Challen

    Too small a study to draw great conclusions, but definitely something to think about – and maybe offer in discussion with patients who are struggling.
    #paperinapic https://uploads.disquscdn.com/images/977ef3d1b2896b349758679abcba46bad9b732d5656bdbf0edb60dc45dd1d3d5.png

    • Carlos Roldan

      You are right,
      the sample size is small but I am not sure what would be the expected population of gastroparesis patients that follow in a single hospital. for a larger sample, a multicenter study would be the next step.
      It took us 2 years to collect 41 different patients with gastroparesis in two large urban hospitals.

      • Kirsty Challen

        I agree. Gastroparesis (like cyclic vomiting) is an uncommon presentation but very distressing for those who have it. Being a pragmatist, until the multicentre trial happens I am happy to use haloperidol based on your results!

      • SAEM EBM IG

        As opposed to a multi-center study (unlikely to be funded) I wonder if a more pragmatic approach to this relatively uncommon scenario would be a registry to monitor the epidemiology of gastroparesis, frequency of ED presentations, and adverse events from interventions like Haldol?

  • Pingback: Diabetic Gastroparesis Needs HUGS - R.E.B.E.L. EM - Emergency Medicine Blog()

  • Ken Milne
  • Meghan Groth

    Hey guys, I really enjoyed this episode, thanks for cutting down the KT window! I’ve had providers asking me about using haloperidol for nausea and vomiting for a few years now, and it’s nice to be able to have some evidence to serve as a starting point on this topic.
    I really appreciate the discussion surrounding the concern with QTc prolongation with haloperidol. This is one of those warnings that comes up with a number of drugs, but my level of concern (as a pharmacist) isn’t always the same. For example, the QTc prolongation risk with 4 mg of IV ondansetron isn’t the same as 32 mg of ondansetron. And that risk isn’t necessarily equivalent to the risk with other medications like methadone, ziprasidone, levofloxacin, or azithromycin. The problem is, there isn’t a lot of literature out there detailing the magnitude of risk for each of these medications (or at different doses), but the drug interaction/warning software may make it appear as though the level of concern should be similar.
    The other point I would bring up that was briefly mentioned is the feasibility of ECG monitoring in a patient who is nauseous versus the “typical” patient who is receiving haloperidol in the ED (e.g. the acutely agitated, potentially violent patient). As the author mentioned, we may not be used to getting ECGs for a patient who needs emergency administration of an antipsychotic, but perhaps it’s more “doable” for the patient with gastroparesis or nausea/vomiting. As a pharmacist, if I were asked about the QTc prolongation in a patient where the provider wanted to use haloperidol, I’d probably look to see if we had any ECG data on file for the patient to evaluate whether or not they had a prolonged QTc at baseline, then check to see if there were any other drugs in their medication regimen which could prolong the QTc, and then come to a determination about whether or not I felt strongly that they should get another ECG before giving the haloperidol.
    Thanks again for being awesome!

    • Ken Milne

      Thanks for the comments Meghan. It reminds me why it would be great to work with an EMPharm person on every shift.

      I am glad you like the discussion around ECGs and QTc prolongation. It demonstrates how the same literature can be interpreted by different EM physicians depending on other factors besides just what the paper says. EBM is more than just the literature.

      I will look forward to seeing how the lead author and Justin respond.

    • Carlos Roldan

      Meghan,
      The concern about QT prolongation is always valid when the patient is taking other additional medications that can synergistically prolonged it. the concern is more significant if given IV push as described in our study.
      you don’t want to be the one putting the patient in torsade’s with the medication that everyone was questioning you about.

    • Justin Morgenstern

      Thanks for the comment Meghan. You make some very important points.
      I agree that patients with nausea and vomiting are different than patients with agitation. Practically speaking, it is not very difficult to get an ECG done in these patients before giving haloperidol. My only problem with that approach is that I am not sure of what to do with that information once I have it. What cutoffs would I use to stop me from using haloperidol?
      From my read of the literature, cardiovascular adverse events are incredibly rare after a single dose of either haloperidol or droperidol, especially at the low doses we would be using here. For example, Macht (2014 PMID 24460451) looked at 314 prehospital patients getting haloperidol and 218 getting droperidol, and there were only 5 patients with QTs over 500 and none had an adverse event. Calver (2015 PMID 25890395) looked at 1009 agitated patient given droperidol, and although 13 developed a prolonged QT, there were no adverse outcomes.
      We are left comparing a largely theoretical, and at most very rare adverse event to the 50% decrease in hospitalization (with all the known adverse event that come with being in hospital) that was seen in this study. When comparing those numbers, I am not sure that the theoretical QT effects of a single dose of haloperidol will outweigh the benefit. That being said, ECGs are cheap and easy to get, and I would probably not use haloperidol if the patient already had a QT over 500. However, the QT over 500 is so rare, I am not sure screening everyone is an effective use of time.

  • SAEM EBM IG

    My #SGEMHOP
    questions 1) Small sample size – how likely is Type II error and how
    large would a more convincing study need to be? 2) Sustainability –
    primary outcome at 1-hour can/does haldol prevent ED return in 2 hours (or 2
    days) with recurrent gastroparesis symptoms?

    • Justin Morgenstern

      Thanks for the comment Chris
      I was also originally concerned about the 1 hour cutoff as well – but I think the 50% decrease in admission, and large (not statistically significant) decrease in ED length of stay probably hint at longer beneficial outcomes from haloperidol. (Within the confines of a very small study)

  • Ken Milne
  • Ken Milne

    Just a reminder that we did do an episode with Meghan Groth (@EMPharmGirl) on smelling isopropyl alcohol for nausea.

    http://thesgem.com/2016/01/sgem144-that-smell-of-isopropyl-alcohol-for-nausea-in-the-emergency-department/