Episode #142 PONV: Updated Guidelines and Medication Options

Hello and welcome back to the Anesthesia Patient Safety Podcast.  My name is Alli Bechtel, and I am your host. Thank you for joining us for another show. Last week, we talked about management options for post-operative nausea and vomiting. This is an important patient safety consideration that is related to a couple APSF priorities including perioperative brain health and medication safety and we are continuing the conversation today.

Before we dive into the episode today, we’d like to recognize Masimo, a major corporate supporter of APSF. Masimo has generously provided unrestricted support to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Masimo – we wouldn’t be able to do all that we do without you!”

Let’s return to our featured article from the February 2023 APSF Newsletter, “Dopamine-Antagonist Antiemetics in PONV Management: Entering a New Era?” by Connie Chung and Joseph W. Szokol. To follow along with us, head over to APSF.org and click on the Newsletter heading. First one down is the Current Issue. From here, scroll down until you get to our featured article today. I will include a link in the show notes as well.

Last week, we talked about the newest approved medication for PONV management. In 2020, the FDA approved Amisulpride for the prevention and treatment of PONV and it is the only approved agent for rescue treatment after failed prophylaxis. We also reviewed the three sub-classes of Dopamine D2-antagonits and the most common medications in the classes including:

1. Substituted Benzamides including amisulpride and metoclopromide
2. Butyrophenones including droperidol and haloperidol
3. Phenothiazines including prochlorperazine and promethezine

Check out Table1 in the article which includes the subclasses, the prototypical agent, key pharmacologic properties, important side effects, and noteworthy considerations. This is a good, quick reference of the D2 Subclass of Antiemetics. And if you haven’t listened to Episode #141 yet, make sure that you check it out for a review of adverse side effects and safety considerations related to D2-antagonists for PONV management.

Let’s take a step back from the treatment of PONV to talk about PONV in general. Postoperative nausea and vomiting or PONV is an important consideration for anesthesia patient safety that may have a big impact on prolonged post anesthesia care unit length of stay, unanticipated hospital administration, and increased health care costs. Recently, in 2020, the fourth consensus guidelines for the management of POMV was published which outlines identification of high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatments for PONV. The authors highlight two important considerations from the guidelines:

First, prevention of PONV must be a critical component of anesthesia care and patients with even just one or two risks factors for PONV should receive multimodal PONV prophylaxis.

Let’s take a quick commercial break to review the risk factors for PONV from the fourth consensus guidelines which include the following:

• Female sex
• History of PONV or motion sickness
• Nonsmoking
• Younger Age
• General versus Regional Anesthesia
• Use of Volatile Anesthetics and Nitrous Oxide
• Postoperative opioids
• Duration of anesthesia
• And type of surgery including cholecystectomy, laparoscopic, and gynecological procedures.

There is conflicting evidence for the following factors and the impact on PONV:

• ASA physical status
• Menstrual cycle
• Level of anesthesiologist’s experience
• And Perioperative fasting.

Here are some factors that have been either disproven or shown to be of little clinical relevance:

• BMI
• Anxiety
• Presence of a nasogastric tube
• History of migraines
• And Use of supplemental oxygen.

And now, back to the APSF article for the 2^nd point highlighted by the authors.

PONV treatment should include the use of an antiemetic medication from a different pharmacologic class than the initial prophylactic medication. That’s right, there is no benefit of re-dosing ondansetron even though this is a common practice.

Before we get to the exciting conclusion of the APSF article, let’s review the fourth consensus guidelines. I will include the citation in the show notes as well. Table 3 provides a plan to decrease the baseline risk for PONV which involves the following steps:

• Avoidance of GA by using regional anesthesia
• Use of propofol for induction and maintenance of anesthesia
• Avoidance of nitrous oxide in surgeries that are longer than 1 hour
• Avoidance of the use of volatile anesthetics
• Multimodal analgesia with a goal to minimize intraoperative and postoperative opioid administration
• Providing adequate hydration
• Use of Sugammadex rather than neostigmine for reversal of neuromuscular blockade.

Table 4 in the consensus statement provides a list of antiemetic medications with the dose and timing for adults. We are going to review a few of these.

• Amisulpride 5mg given at induction
• Dexamethasone 4-8mg IV given at induction
• Droperidol 0.625mg IV given at the end of surgery
• Haloperidol 0.5- less than 2mg IM or IV
• Metoclopromide 10mg
• Ondansetron 4mg IV given at the end of surgery
• Promethezine 6.25mg
• And Scopolamine transdermal patch given the evening prior or 2 hours preop

There is so much great information in the fourth consensus guidelines, let’s take a look at one more graphic. Figure 6 is an infographic that displays an algorithm for PONV management in adults. Step 1 is identifying risk factors. Step 2 is risk mitigation using some of the steps that we outlined earlier. Step 3 includes risk stratification and patients with 1-2 risk factors should receive 2 agents and patients with more than 2 risk factors should receive 3-4 agents. Step 4 is prophylaxis options, and step 5 involves rescue treatment using an antiemetic from a different drug class than the prophylactic class. As we work through the algorithm for the management of PONV in adults it is important to remember that the combination of non D2-antagonist antiemetic medications combined with older D2 antagonists like Droperidol, haloperidol, and promethazine are more effective than either agent alone. More recently, amisulpride has been evaluated in 6 clinical trials. In 5 of these trials, amisulpride was studied as the sole antiemetic drug and found to be superior to placebo for prevention and treatment of PONV. The 2018 study in Anesthesiology, “Amisulpride prevents postoperative nausea and vomiting in patients at high risk: a randomized, double-blind, placebo-controlled trial” reported that the combination of amisulpride with ondansetron or dexamethasone was more effective than ondansetron or dexamethasone along for preventing PONV or for rescue treatment. I will include this citation in the show notes as well.

Management of PONV is multifactorial including prevention as well as management and this is a vital component of the anesthetic plan especially as part of the enhanced recovery after surgery pathways, for patients undergoing ambulatory surgery, and for high risk patients with high acuity and fragility levels. As we have talked about for the past two episodes D2-antagonists are effective medications for PONV management, but understanding the side effects, effective doses, and route of administration is critical. The future of PONV management is bright with a new option, Amisulpride, which is a D2 antagonists with less side effects and excellent efficacy for prevention and rescue treatment.

Before we wrap up for today, we are going to hear from one of the authors of the APSF Newsletter article, Connie Chung again. I asked her, “What do you hope to see going forward?” Let’s take a listen to what she had to say.

[Chung] “I really take to heart what is stated in the fourth consensus guidelines for the management of PONV published in anesthesia and analgesia in 2020. The prevention of PONV should be considered an integral aspect of anesthesia. However, sometimes despite our best efforts to identify high risk patients and administer prophylaxis, patients still develop PONV, and now there’s an FDA-approved treatment option for PONV with a favorable safety profile. My hope is that more patients can benefit from the use of Amisulpride.”

[Bechtel] Thank you so much for Chung for contributing to the show today. We hope more patients can benefit from treatment with Amisulpride when it comes to managing PONV going forward. We will be on the look out for future studies and a cost-benefit analysis related to this newer medication. Do you have Amisulpride at your institution? Have you used it for PONV management? Let us know by tagging up on twitter @APSForg using the hashtag, #apsfpodcast.

We made it to the end of the article, but we also need to address a threat to anesthesia patient safety for our pediatric patients. That’s right the management of PONV in children is so important. If we look at the fourth consensus statement, there are several considerations. First, reducing baseline PONV risk may include the use of TIVA, liberal fluid therapy, and opioid-sparing techniques. There is some evidence that IV lidocaine, IV acetaminophen, and alpha-2 agonists as part of a multi-modal anesthetic plan may help to decrease rates of PONV. PONV prophylaxis in children may include administration of the following medications:

• Aprepitant 3mg/kg up to 125mg
• Dexamethasone 150mcg/kg up to 5 mg
• Droperidol 10-15 mcg/kg up to 1.25mg
• And Ondansetron 50-100mcg/kg up to 4 mg

Looking a little closer at the fourth consensus guidelines, the authors report that when the risk for PONV is very low and the surgery is less than 30 minutes long, PONV prophylaxis may not need to be administered. For longer surgeries or patients at high risk, prophylaxis with a combination of medications is recommended. What is your preferred PONV prophylaxis combo for pediatric patients? The strongest evidence supports administration of dexamethasone plus ondansetron for prophylaxis.

If you have any questions or comments from today’s show, please email us at [email protected]. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today.

We’ll be back next week with more from the February 2023 APSF Newsletter. Until then, we have some exciting news from Ariadne Labs. Do you use checklists during OR crisis management? Have you modified an original OR Crisis Checklist or developed your own for specific emergencies? Well, Ariadne lab is making updates to the Operating Room Crisis Checklists and they want to hear from you. The goals for their newest update include the following:

• Review and update the existing twelve critical event checklists to reflect best practice
• Expand the compendium with checklists for five additional, often requested, events:
  • Myocardial ischemia
  • Obstetric hemorrhage
  • Local anesthetic systemic toxicity
  • Delayed emergence
  • Transfusion Reaction
• Produce a mobile device-friendly version of the checklists, preserving the key design features of the original documents in both digital and print versions
• And provide editing tools for local customization

This is so exciting. Healthcare professionals who are passionate about anesthesia patient safety may be able to contribute to this project in several ways. Here are the asks:

• If you have modified an original Crisis Checklist or Emergency Manual in a significant way, please send us a copy and tell us what you’ve changed and why– to guide the design of the customization tools
• If you have already created your own checklists for any of the five new topics, please share them with us– your choices about their content and design are valuable!
• If you feel you’re able to join Ariadne’s Editorial Review Panel for this project as an expert reviewer of one or more of the existing or new checklists, please let us know. Feel free to pass along this invitation to any colleagues that you think might be interested and have the expertise.  We anticipate circulating draft checklists with associated background folders during March and April.

They want to hear from you. The project lead is Alexander Hannenberg. I will include the contact information and details in the show notes as well.

Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

© 2023, The Anesthesia Patient Safety Foundation