GRACE-4 – New Guidelines for Alcohol Withdrawal, Alcohol Use Disorder, and Cannabis Hyperemesis

July 9, 2024

Written by Jason Lesnick

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GRACE-4 is packed with practice-changing recommendations for patients with alcohol withdrawal syndrome (AWS), alcohol use disorder (AUD), and cannabinoid hyperemesis syndrome (CHS).

GRACE is back, this time slightly shorter than your favorite sci-fi novel
Folks, this was a massive tome. We are going to break it down, but this guideline summary is a bit longer than usual. It answers 3 PICO questions: 1) Does adding phenobarbital to benzodiazepines in AWS improve outcomes? 2) Does prescribing anti-craving medications improve outcomes in AUD? 3) Is there benefit to treating CHS with dopamine antagonists or capsaicin?

This document consists of 7 recommendations and is full of pearls and pitfalls, and I would highly recommend reading it yourself. Below are the recommendations, selectively quoted.

“Recommendation 1: In adult ED patients (over the age of 18) with moderate to severe alcohol withdrawal who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone. (Conditional recommendation, FOR; very low to low certainty of evidence).

Recommendation 2: In adult ED patients (over the age of 18) with AUD, we suggest a prescription for an anticraving medication for the management of AUD for patients who desire alcohol cessation. (Conditional recommendation, FOR; very low to low certainty of evidence)

Recommendation 2a: In adult ED patients (over the age of 18) with AUD who are not taking opioids, we suggest naltrexone (compared to no prescription) for the management of AUD to prevent return to heavy drinking and/or reduce heavy drinking. (Conditional recommendation, FOR; low certainty of evidence)

Recommendation 2b: In adult ED patients (over the age of 18) with AUD, with contraindications to naltrexone, we suggest acamprosate (compared to no prescription) for the management of AUD to prevent return to heavy drinking and/or reduce heavy drinking. (Conditional recommendation, FOR; low certainty of evidence)

Recommendation 2c: In adult ED patients (over the age of 18) with AUD, we suggest gabapentin (compared to no prescription) for the management of AUD to reduce heavy drinking days and improve alcohol withdrawal symptoms. (Conditional recommendation, FOR; very low certainty of evidence)

Recommendation 3a: In adult patients presenting to the ED with CHS, 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)

Recommendation 3b: In patients presenting to the ED with CHS, 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).”

Here are more highlights.

AWS:

• Multiple retrospective studies from non-ED settings found using phenobarbital with benzodiazepines resulted in a decreased need for intubation and ICU utilization.
• A small ED-based RCT found a single dose of 10 mg/kg of phenobarbital plus symptom-driven lorazepam led to significant decreases in patients admitted to an ICU from 25% to 8% (NNT = 6).
• The systematic review, done as part of these guidelines, didn’t show any evidence of increased adverse events associated with phenobarbital use (low quality evidence): hypotension, drug–drug interactions (cytochrome p450 inducer), or liver toxicity.
• Phenobarbital dosing varied widely across studies; overall, adjunctive phenobarbital with benzodiazepines resulted in decreased need for intubation, decreased hospital LOS, decreased ICU admission and LOS.

AUD:

• 7.8% of the U.S. population has AUD; 81.4% of these individuals used healthcare within the previous 12 months, only 11.6% received a brief intervention, 5.1% were referred to treatment, and only 5.8% received AUD treatment.
• 2021 U.S. National Survey on Drug Use and Health estimated that only 1.6% of individuals with AUD received pharmacotherapy for their condition.
• Naltrexone is associated with increased abstinence from alcohol, decreased binge drinking, decreased heavy drinking days, lower risk of hospitalization due to any alcohol related causes, and higher follow up rates in formal substance use disorder treatment.
• Acamprosate compared to placebo had an increased probability of abstinence at 12 months, OR 1.86 (95%CI 1.49-2.33), a risk difference of 38% (NNT = 3).
• The authors provided us with an incredible algorithm for prescribing these medications.

CHS:

• In a patient with cyclic vomiting, ask about relief of symptoms with hot showers.
• Haloperidol and droperidol have been found to provide symptom relief from nausea, vomiting, and abdominal pain, while decreasing need for rescue analgesics or antiemetics and opioids.

How will this change my practice?
AWS: Adding phenobarbital to benzodiazepines in moderate to severe patients is something I’ll advocate for at my institution.
AUD: I had no idea I was so bad at treating this! I’ll be prescribing naltrexone or acamprosate – rarely gabapentin – as outlined in the algorithm.
CHS: I’ll continue to use droperidol as my first line antiemetic in patients with suspected CHS and continue to prescribe capsaicin cream. I will try to order capsaicin and see if it’s feasible in my hospital system.

Source
Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department. Acad Emerg Med. 2024 May;31(5):425-455. doi: 10.1111/acem.14911. PMID: 38747203.