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Reference: Borgundvaag et al. Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department. AEM May 2024

Date: May 22, 2024

Dr. Bjug Borgundvaag

Guest Skeptic: Dr. Bjug Borgundvaag is the Founding Director of the Schwartz/Reisman Emergency Medicine Institute (SREMI), at Sinai Health System. He is a Professor of Emergency Medicine and a Clinician Scientist in the Department of Family and Community Medicine at U of T. Prior to his medical training, he completed a PhD in Pharmacology at U of T. He has been involved in ED-based clinical research examining ways to improve care for patients with alcohol use disorder in the ED for over two decades.

This is an SGEM HOP but with a twist. We are not going to do a structured critical appraisal of GRACE4 but rather turn it into an SGEM Xtra. When we combine SGEMHOP with an SGEM Xtra I hope we get some…AMAZING knowledge translation for GRACE4.

“The SAEM GRACE program addresses the best practices for the care of the most common chief complaints that can be seen on the tracking board of any emergency department in the country, based upon research and expert consensus. These guidelines are designed with de-implementation as a guiding principle to reasonably reduce wasteful testing, provide explicit criteria to reduce foreseeable risk, and define sensible and prudent medical care.”

  • GRACE1: Recurrent, Low-Risk Chest Pain
  • GRACE2: Recurrent, Low-Risk Abdominal Pain
  • GRACE3: Acute Dizziness & Vertigo

For this SGEMHOP Xtra combo episode on GRACE4, we are going to give a case scenario, a little background information, ask a clinical question, provide authors’ conclusions, go through the recommendations and a case resolution.

Case 1: A patient presents to the ED with nausea, vomiting and some abdominal pain complaining of alcohol withdrawal. He reports that his last drink was 9 hours ago, and he typically consumes 60 oz of spirits/day. He has had prior hospital admissions for the management of alcohol withdrawal, including seizures and one prior episode of delirium tremens.

Management: The patient is initiated on a Clinical Institute Withdrawal Assessment (CIWA) protocol and administered intravenous (IV) doses of diazepam hourly for the next 18 hours. There was a 6-hour delay until the first dose of diazepam was administered. Over those 18 hours, his CIWA stubbornly stays at around 18, and by the 15-hour mark, has increased to 21 despite receiving 20mg of diazepam hourly. By the 18-hour mark, he has had a total of 240 mg of diazepam and is getting worse.

Clinical Question 1: Is IV phenobarbital, in addition to diazepam, helpful in managing this case of severe alcohol withdrawal?

Authors’ Conclusions: There is limited direct high-quality evidence from clinical trials supporting the use of phenobarbital as an adjunct to benzodiazepines for managing moderate to severe AWS in the ED setting. Although the direct prospective evidence comparing these interventions in ED patient populations is limited, the balance between desirable and undesirable effects favours adjunctive phenobarbital over benzodiazepine alone. This is based, in large part, on indirect evidence illustrating the benefits of adjunctive phenobarbital including, but not limited to, reduction on the need for intubation, decreased hospital length of stay, decreased ICU admission and length of stay.

  • Recommendation 1: In adult ED patients (over the age of 18) with moderate to severe alcohol withdrawal, who are being admitted to the hospital we suggest using phenobarbital in addition to benzodiazepines as compared to using benzodiazepines alone. (Conditional recommendation, FOR) [Low to Very Low certainty of evidence]
    • Good practice statement: All patients treated for alcohol withdrawal should be offered follow-up treatment where such treatment is available.

Case 1 Resolution: After receiving 240 mg of diazepam over 18 hours with no improvement, the patient was given phenobarbital 5 mg/kg as an infusion. The patient’s symptoms showed significant improvement, and 1 hour later the patient was given an additional 5 mg/kg dose resulting in complete symptom resolution.

Case 2: A female patient presents to the ED with moderate alcohol withdrawal. She has consumed 26 oz of vodka a day, for the last four years. She has no history of being admitted to the hospital for the management of alcohol withdrawal syndrome (AWS).

Background 2: The patient is treated with diazepam using a symptom-driven approach including hourly CIWA assessments including long-acting benzodiazepines to manage symptoms according to severity. Her AWS resolves over the next 8 hours, and she is ready to be discharged home by the end of your shift. You make a referral to a local addiction medicine service for her to be seen a few days later.

Clinical Question 2: Should this patient be offered anti-craving medication upon discharge?

Authors’ Conclusions: There is limited high-quality direct evidence on the use of anti-craving medications in the ED for the treatment of AUD. Despite this limitation, the balance of desirable and undesirable effects favours prescribing anti-craving medications in the ED for people with AUD. This is based on indirect evidence demonstrating the effectiveness of naltrexone, acamprosate, and gabapentin in reducing heavy drinking days and increasing abstinence. In addition, these medications are well tolerated with mild side effects.

  • Recommendation 2: In adult ED patients (over the age of 18) with alcohol use disorder, we suggest a prescription for an anti-craving medication for the management of alcohol use disorder for patients who desire alcohol cessation (conditional recommendation, FOR) [Very Low to Low Certainty of Evidence].
    • Good practice statement: Please see the anti-craving medication algorithm (Figure 4) which was designed to help guide clinicians in the selection of anti-craving medication based upon patient-level factors and the strength of evidence for three medications. Dosage adjustments related to hepatic and renal function can be made at follow-up.
    • Good practice statement: As per the American Society of Addiction Medicine Guidelines clinicians should consider offering patients with AUD supplemental thiamine as part of their ED treatment plan, and should be offered follow-up treatment where such treatment is available.
  • Recommendation 2a: In adult ED patients (over the age of 18) with alcohol use disorder who are not taking opioids, we suggest naltrexone (as compared to no prescription) for the management of alcohol use disorder to prevent return to heavy drinking and/or to reduce heavy drinking (Conditional Recommendation, FOR) [Low Certainty of Evidence].
    • Good practice statement: A bridging prescription of up to four weeks until follow-up with an addiction medicine physician, primary care physician, or other appropriate health care provider can take place is preferred. Monitoring of liver enzymes should be at the discretion of the provider seeing the patient in follow-up. For patients not treated with long-acting benzodiazepines for AWS in the ED, patients should be advised that sudden cessation of alcohol consumption (as a result of anti-craving medication) may produce acute AWS. These patients should be counselled to slowly taper consumption and seek treatment for AWS management should symptoms occur.
  • Recommendation 2b: In adult ED patients (over the age of 18) with alcohol use disorder, with contraindications to naltrexone, we suggest acamprosate (as compared to no prescription) for the management of alcohol use disorder to prevent return to heavy drinking and/or to reduce heavy drinking (Conditional Recommendation, FOR) [Low Certainty of Evidence].
    • Good practice statement: A bridging prescription of up to four weeks until follow-up where renal function can be monitored with an addiction medicine physician, primary care physician, or other appropriate health care provider is preferred.
  • Recommendation 2c: In adult ED patients (over the age of 18) with alcohol use disorder, we suggest gabapentin (as compared to no prescription) for the management of alcohol use disorder to reduce heavy drinking days and improve alcohol withdrawal symptoms (Conditional Recommendation, FOR) [Very Low Certainty of Evidence].
    • Good practice statement: Given the known misuse potential of gabapentin, a bridging prescription, for example less than 2 weeks, is preferable to a long-term prescription. Patients should be cautioned about the sedative effects of gabapentin, and it should be prescribed with caution or avoided altogether in patients who use opioids. In patients with high self-reported withdrawal symptoms when they stop or reduce their alcohol intake, consider prescribing gabapentin in addition to naltrexone or acamprosate. Consider a weekly dispensing interval for gabapentin prescriptions longer than 2 weeks.

Case 2 Resolution: The fact that the patient’s AWS was well controlled, and they were comfortable created an environment in which an exploratory conversation about the effects that alcohol consumption at this level was having on the patient’s health was possible. She was interested in becoming abstinent but had tried and failed many times on their own. They had never been treated with anti-craving medications and had never had any specialized additional medicine support for their alcohol use disorder. The patient was offered and accepted 50 mg of naltrexone/day (10-day script), and a referral was made to an addiction medicine clinic for follow-up within a few days.

Case 3: A 28-year-old patient with no prior abdominal surgeries presents to the ED with 24 hours of uncontrollable nausea and vomiting. The patient is unable to get comfortable and is in some distress. They have had several ED visits to your hospital for similar presentations in the last two years. On each occasion, the patient has been treated with fluids, anti-emetics and pain medications and undergone abdominal imaging (CT scans and an ultrasound) which have never demonstrated a cause for the patient’s symptoms. On one previous occasion, the patient was admitted to the hospital for further treatment and observation.

Background 3: The patient is again treated with IV fluids and anti-emetics, which are not effective in bringing the patient’s nausea and vomiting under control. On further questioning the patient says the only thing that brings any relief is very hot showers, which he has been taking over the course of the day, but as soon as he gets out his symptoms get worse. During your physical examination, you become aware of the relatively strong smell of cannabis. You make the diagnosis of cannabis hyperemesis syndrome.

Clinical Question 3: Does the use of dopamine antagonists (haloperidol/droperidol) or capsaicin as compared to usual care (or no treatment) lead to improved outcomes?

Authors’ Conclusions: There is limited, low-quality evidence evaluating the use of either droperidol or haloperidol in the treatment of CHS in the ED. However, the balance between desirable and undesirable effects supports the recommendation of these agents, in comparison to the lack of effectiveness of standard therapies for symptoms related to CHS (e.g., abdominal pain, nausea and vomiting). Indirect evidence supports its use in nausea and vomiting for other non-CHS-related presentations with low rates of adverse effects.

Capsaicin also received a conditional recommendation. The evidence supportive of capsaicin was even more limited with the recommendation mainly based on the lack of significant adverse effects, the low cost of capsaicin, and the ability of the patient to apply the medication at home after discharge. Improvements in prompt access to capsaicin in the ED and support in removing the necessity of cardiac monitoring for haloperidol and droperidol in appropriate patients will ease concerns regarding the feasibility of implementation. In conjunction with treatment of acute symptoms in the ED, abstinence from cannabis is required for complete resolution of symptoms and prevention of recurrence, and referral for additional treatment is recommended for patients with a suspected cannabis use disorder.

  • Recommendation 3a: In adult patients presenting to the ED with cannabinoid hyperemesis syndrome we suggest the use of haloperidol or droperidol (in addition to usual care/serotonin antagonists e.g., ondansetron) to help with symptom management. [Conditional, FOR] (Very Low Certainty of Evidence)
    • Good practice statement: IV fluids and non-opioid analgesics could be administered/offered to help with symptom management.
  • Recommendation 3b: In patients presenting to the ED with cannabinoid hyperemesis syndrome we suggest offering the use of topical capsaicin (in addition to usual care/serotonin antagonists e.g., ondansetron) to help with symptom management.  [Conditional, FOR] (Very Low Certainty of Evidence)
    • Good practice statement: One member of the SAEM GRACE-4 Writing Team emphasized the importance of recognizing that not all patients experience relief with capsaicin, and clinicians should be prompt in escalating treatment for patients whose symptoms are not alleviated promptly.  This member also emphasized that capsaicin should not be used for patients for whom it had not been effective in the past. [Conditional, FOR] (Very Low level of Evidence)
    • Good practice statement: In patients presenting to the ED with CHS, benzodiazepines and opioids should not be used as first line treatment for CHS symptom management. In balance with the lack of evidence supporting the effectiveness of benzodiazepines and opioids in this setting, and considering prior SAEM GRACE recommendations for avoiding opioids in the management of chronic abdominal pain, we believe the potential risks associated with the administration of these medications outweigh any potential benefit.
    • Good practice statement: These interventions should be used in conjunction with anticipatory guidance on the necessity of cannabinoid abstinence for complete symptom resolution. We found no published evidence that reduction in use will prevent CHS, however anecdotal evidence from our representative with lived experience suggests that in some cases reducing use may reduce the frequency of episodes. If the healthcare team suspects concurrent cannabinoid use disorder based on screening with a validated tool such as the CUDIT-R consider referral to psychosocial interventions and/or addiction medicine specialists if available. Hydration and other supportive treatments should not be delayed by administering either haloperidol/droperidol or capsaicin (if the patient would like to try it). Clinicians should educate patients on the rationale for the use of these medications if questioned and caution them about the intensity of burning related to capsaicin application.

Case 3 Resolution: The patient was offered, and accepted treatment with 2mg haloperidol in addition to all the other usual treatments for unremitting nausea and vomiting. Their symptoms markedly improved over the following 30 minutes. With additional IV fluid replenishment, the patient was able to tolerate PO fluids and food. The patient was also offered capsaicin cream to be applied to their abdomen (15×15 cm patch of skin).

10 Takeaways from the Topic:

  1. ED visits related to alcohol-related conditions exceed the combined number of visits related to all other recreationally consumed substances.
  2. ED providers are the best-situated people in the healthcare system to recognize and offer help for alcohol-related problems.
  3. There is a lack of education in medical school or residency training on how to best manage alcohol-related conditions in the ED
  4. Even though anti-craving medications have been around and approved for decades, and are extremely safe and effective, these drugs are prescribed to fewer than 1% of patients with alcohol use disorder.
  5. Cannabis hyperemesis is a real thing. These patients are challenging to manage in the ED as usual treatments (anti-nauseants, IV fluids) are not very effective in helping with symptoms. The scientific evidence for dopamine antagonists and capsaicin is poor, but anecdotal evidence for their effectiveness, especially for dopamine antagonists, is growing.
  6. There is a strong need for additional evidence in all these areas, but the existing evidence supports the regular use of these treatments.
  7. Providing these clinical practice guidelines should encourage clinicians to use them. Additionally, giving clinicians advice on how to manage these conditions where there has never been any, will hopefully create an environment of patient collaboration and caring and reduce the stigma associated with substance use disorders.
  8. It is very challenging for patients to overcome alcohol substance use disorder on their own. With medications and support, there is a good chance they can achieve their objectives for alcohol consumption.
  9. The only cure for cannabis hyperemesis syndrome is cessation. There are anecdotal reports that significantly reducing consumption can reduce the frequency/severity of CHS, but it is unclear if this is 100% effective.
  10. We can help.

We’ve covered alcohol use disorder (AUD) and cannabis hyperemesis syndrome (CHS) on the SGEM:

  • SGEM#46: Don’t Pass the Dutchie (Cannabinoid Hyperemesis Syndrome)
  • SGEM#313: Here Comes A Regular to the ED
  • SGEM#318: Why Am I Throwing Up – Because You Got High
  • SGEM#434: It’s (Un) Happy Hour Again – Mortality in Younger Patients with Alcohol-Related ED Attendances

The SGEM will be back next episode doing a structured critical appraisal of a recent publication. Trying to cut the knowledge translation window down from over ten years to less than one year using the power of social media. So, patients get the best care, based on the best evidence.

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