Anesthesia Patient Safety Podcast

#250 Sugammadex in Special Populations: What Every Anesthesia Professional Needs to Know

• Anesthesia Patient Safety Foundation • Episode 250

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Sugammadex safety considerations span across patient populations with renal impairment, pediatric patients, and pregnant or breastfeeding individuals, requiring nuanced clinical decision-making based on current evidence and ongoing research.

• Sugammadex reversal of moderate blockade is safe and faster than using neostigmine/cisatracurium for patients with renal impairment
• Quantitative neuromuscular monitoring is essential to ensure adequate reversal (TOF >90%)
• FDA approval exists for children 2+ years with the same dosing parameters as adults
• Infants <2 years require special consideration due to immature neuromuscular systems and distinct physiology
• Recurarization cases exist but are rare, primarily in very young patients
• Pregnancy considerations include theoretical concerns about progesterone binding
• Breastfeeding compatibility varies based on lactation stage, with early postpartum period requiring more caution
• Continued research needed to establish definitive guidelines, especially for neonates, infants, and lactating patients

For show notes & transcript, visit our episode page at apsf.org: https://www.apsf.org/podcast/250-sugammadex-in-special-populations-what-every-anesthesia-professional-needs-to-know/

© 2025, The Anesthesia Patient Safety Foundation

Speaker 1:

You're listening to the Anesthesia Patient Safety Podcast, the official podcast of the Anesthesia Patient Safety Foundation. We're bringing you the very best from the APSF newsletter and website, as well as the latest information in perioperative patient safety. Thanks for joining us.

Speaker 2:

Hello and welcome back to the Anesthesia Patient Safety Podcast. My name is Allie Bechtel and I'm your host. Thank you for joining us for another show. Last week we started the conversation about safety considerations with Sugamidex administration for patients with renal impairment as well as pregnant and breastfeeding patients. We are continuing this important discussion today to talk about Sugamidex use for pediatric patients. Plus, we have a late-breaking letter to the APSF newsletter editors that was published on March 12th that we are going to talk about as well. Before we dive further into the episode today, we'd like to recognize GE Healthcare, a major corporate supporter of APSF. Ge Healthcare has generously provided unrestricted support to further our vision that no one shall be harmed by anesthesia care. Thank you, ge Healthcare. We wouldn't be able to do all that we do without you.

Speaker 2:

Our featured article again today is Safety of Sugaminex in Pregnancy, pediatrics and Renal Failure by Kevin Yang, christina Rado, joseph Skokul and Ashley Ozumi. To follow along with us, head over to apsforg and click on the newsletter heading First. One down is the current issue. Then scroll down until you get to our featured article today. I will include the link in the show notes as well To help kick off the show. Today we are going to hear from another one of the authors. I will let him introduce himself now and help highlight important considerations about the safe use of Sugaminex.

Speaker 3:

I am a professor of clinical anesthesiology at the Keck School of Medicine at the University of Southern California. I also served on the ASA task force that brought forth the 2023 guidelines for the monitoring and antagonism of a neuromuscular blockade. The guidelines had eight recommendations, which focused on quantitative over qualitative monitoring and reversal of the anti-block, except for shallow block with Sugamidex. The product information for Sugamidex does not recommend Sugamidex in patients with severe renal impairment, including those on dialysis At Keck USC.

Speaker 3:

We are one of the busiest solid organ plant centers in the United States, and the issue of which neuromuscular blockage to administer is a commonplace one. The concern is one of eukaryotization resulting in potential paralysis or residual weakness due to dissociation of the rocuronium-suganimax complex. In normal individuals, over 90% of the complex is excreted within 24 hours. This is delayed in those with renal impairment. However, the rocuronium-suganimax complex is a highly stable one due to van der Waal forces. For over 25 million rocuronium-suggammix complexes, only one dissociates. The complex is also grouped during dialysis with a high-flux filter. The other option for those concerned about the theoretical risk of recurarization is to utilize a benzyl isoquinolone such as sesachicurum. Reversal neostigmine Again, the ASA guidelines recommend neostigmine reversal for only shallow block, thus highlighting the need for quantamon to determine the depth of blockade.

Speaker 2:

Thank you so much to Skokul for contributing to the show today and this article. The big takeaway when it comes to the use of Sugaminex for patients with renal impairment may be the following use of Sugaminex for patients with renal impairment may be the following Using Sugaminex to reverse moderate blockade is safe and faster than the combination of neostigmine and cisatricurium, and it is important to use a quantitative neuromuscular monitor to ensure adequate reversal to a train of four of greater than 90%. We are going to save our review for the safety considerations for patients who are pregnant or breastfeeding until the end when we talk about the letter to the editor article, and this means that it is time to dive back into the article to talk about the safety considerations for the use of Sugaminex for pediatric patients. You may remember that when Sugaminex was first introduced in the United States, the FDA approval was for the use in adults. The Bridian package insert stated that the safety and effectiveness of the drug had yet to be established in patients under 17 years old. This is a complex undertaking, since there is a high age-dependent variability for pediatric patients following administration of muscle relaxants and neuromuscular blockade reversal agents. Following a lot of research in this area by 2021,. Sugamidex received FDA approval for use in patients two years and older, with an updated package insert for dosing recommendations.

Speaker 2:

Let's take a closer look at the use of Sugaminex in different pediatric age groups, starting with children between the ages of 2 and 17. Here are important considerations Sugaminex has received FDA approval for the use in children 2 years and older. The dosing parameters in this age group are the same as adults for moderate and deep blockade. Administration of 16 mg per kg Sugamidex for the immediate reversal in pediatric patients has not been studied and this does not have FDA approval. A literature review for studies in this age group reveals the following Compared with neostigmine, reversal of moderate blockade with 2 mg per kg Sugaminix occurred significantly faster Within 3 minutes. Over 90% of pediatric patients had a train-of-four ratio greater than 90%. Have you seen this in your clinical practice? In addition, the time-to-reversal of deep neuromuscular blockade with the 4 mg per kg dose was the same as with adults. The use of Sugamidex decreases the time from reversal administration to train of four ratio greater than 90% and likely the time to extubation as well. It appears that the use of Sugaminex is superior for reversal of neuromuscular blockade compared to acetylcholinesterase inhibitors.

Speaker 2:

What about the use of Sugaminex for infants less than two years old. This is an off-label use right now, since the safety and effectiveness data has not been clearly established. Infants have very different reactions to neuromuscular blocking agents due to immature neuromuscular junctions, larger extracellular volume during development and distinct body composition, anatomy, respiratory physiology and muscle mass. Infants are not just very small adults. Their morphology of acetylcholine receptors is different than adult receptors and neuromuscular transmission is immature in neonates and infants until they are about two months old. Another consideration is that fetal post-junctional receptors are more sensitive to neuromuscular blockers with prolonged opening times. The pharmacokinetic differences are due to underdeveloped hepatic and renal function, leading to decreased neuromuscular blocking drug clearance.

Speaker 2:

Let's look at a prospective pilot trial of Sugamidex administration in children aged 1 to 12 months old who received a 2 mg per kg dose. There was a similar time to recovery of the train of four ratio for all age groups and no subsequent train of four ratio decrease after the initial train of four ratio recovery to greater than 0.9. A single center retrospective cohort study of patients less than 24 months old reported that redosing of Sugamidex occurred in 4.2% of cases after an initial dose of 3.45 milligrams per kg. A limitation of this study was the limited use of train-of-form monitoring in only 43.7% of patients. Additional research is needed in this area to determine dosing guidelines for neonates and infants under 2 years of age.

Speaker 2:

We worry about residual weakness and recurarization in pediatric patients because this can lead to impaired respiratory function and compromised ventilation, especially since pediatric patients are at high risk for hypoxemia due to smaller lung volumes, decreased functional residual capacity, immature respiratory control and high oxygen demand. Keep in mind that children have anatomical airway differences that may lead to postoperative respiratory complications when there are residual effects from neuromuscular blocking agents. Did you know that the overall incidence of residual postoperative weakness is reported as high as 28.1% in children? This is quite high and may be due to inappropriate neostigmine use for patients with deep neuromuscular block. This is where there is an advantage for the use of Sugaminex, which can reverse moderate and profound block, with a decreased risk of residual neuromuscular blockade.

Speaker 2:

Multiple large-scale retrospective and prospective studies on Sugamonex administration to pediatric patients has not shown events of recurarization or additional doses of reversal agent. There are case reports and case series. There was a four-patient case series of pediatric patients with residual weakness or recurarization. Three of the patients were less than two years old. After adequate reversal and extubation. The patients were noted to have decreased respiratory effort, minimal limb movement weakness and cyanosis. Repeat Sugamonex administration led to immediate improvement in respiratory effort and strength. A similar effect was seen in an 11-year-old patient who required an additional dose of Sugamidex 50 minutes after the first dose. Another case report of an 8-month-old who was adequately reversed with train of form monitoring at the adductor pollicis muscle required repeat Sugaminix dose administration 20 minutes after extubation.

Speaker 2:

Reversal of neuromuscular blockade is a time to remain vigilant, with very close monitoring. We also need to remain vigilant for adverse events following Sugaminix administration, which may include recurrizization, anaphylaxis and dose-dependent bradycardia leading to decreased cardiac output and hypotension. The good news is that studies have revealed no significant difference in bradycardia incidence with doses of 2 mg per kg, 4 mg per kg and neostigmine administration. A meta-analysis with trial sequential analysis reported a significantly lower incidence of bradycardia for patients receiving Sugamidex compared to acetylcholinesterase inhibitors or placebo in the operating room. We made it to the end of the article. This was an excellent review of the safety and efficacy of Sugamidex for patients with renal impairment during pregnancy and during pediatric anesthesia care. We are looking forward to more clinical evidence going forward to help keep patients who require neuromuscular blockade and reversal safe during anesthesia care.

Speaker 2:

Before we wrap up for today, we have another featured article. It is the article between issues that was published on March 12th 2025. Concerns regarding Sugamonex use during pregnancy and lactation by Sarah Dodd and colleagues. To follow along with us, head over to APSForg and click on the newsletter heading. The second one down is articles between issues. Then scroll down until you get to our next featured article today and I will include a link in the show notes as well.

Speaker 2:

This is a letter to the editors in response to our featured newsletter article with concerns about inaccurate information related to Sugaminix use for pregnant and lactating patients. Here are their three areas of concern. Number one Sugaminix use in pregnancy. Looking at the available evidence, which includes teratogenicity in one rabbit study but not in rat or human studies, the superiority over neostigmine and the lack of evidence for harm, the authors do not think a blanket recommendation to avoid Sugamidex in pregnancy is best for patients. Number two Sugamidex compatibility with uninterrupted breastfeeding.

Speaker 2:

The authors report on some of the benefits of breastfeeding, which include nutrition to support infant growth and development, protect against infection, reduce the risk of sudden infant death syndrome and lower the risk of heart disease and breast and ovarian cancer in moms. It is important to provide accurate and consistent information to help support initiation and maintenance of lactation. Multiple expert bodies support continued breastfeeding after a patient receives Sugaminex, based on its low transfer to milk, low oral bioavailability and minimal risk of harm to the infant. The authors state that the APSF recommendation that Sugaminex is incompatible with lactation is not consistent with current expert opinion and available data. Number three breast milk production and composition change over time. The authors highlight that lactating patients may present for surgery and anesthesia care after the postpartum period. There is a difference between early lactation, when the junctions between the lactocytes are leaky and Sugamidex molecules may pass into breast milk, and late lactation after the first few days up to two weeks, when Sugamidex is extremely unlikely to pass into mature breast milk. The authors recommend the following changes the use of the phrase potential interaction with progesterone. Remove the phrase potential teratogenicity and use the phrase safe in established lactation, with consideration for judicious use in early postpartum period, or remove any summary recommendations for lactation to avoid inaccurate information. Thank you to Dodd and colleagues for your insights and these important considerations. Now let's see what the newsletter authors have to say in response For Sugaminex use in pregnancy, the authors highlight the potential for Sugaminex to bind progesterone as an area of concern and the lack of large-scale human studies leading to a cautious approach.

Speaker 2:

The use of Sugaminex for rescue reversal in cannot-intubate, cannot-ventilate scenarios is appropriate to avoid severe hypoxia that would be more detrimental than Sugamin-X exposure. However, the current recommendations from the Society for Obstetric Anesthesia and Perinatology and the Merck prescribing information advise against routine use of Sugamin-X in pregnancy and this position is consistent with the current best available data and clinical evidence. Consistent with the current best available data and clinical evidence. For Sugaminix compatibility with breastfeeding, the authors highlight the physiologic considerations of increased permeability of lactocyte junctions, leading to greater drug transfer during early lactation. There is limited human data and this is an area that needs further research. The authors acknowledge that this is an important area for individual risk-benefit assessment when considering Sugaminix use in lactating patients. Finally, for the differentiation between pregnant and lactating patients, the authors recognize that later stage breast milk may have reduced permeability to medications and that anesthesia professionals need to be aware of the changing physiologic process to help with decision making.

Speaker 2:

Considerations for medication administration and lactating patients requires understanding of the drug pharmacokinetics, infant physiology and the precautionary principle that, while no reported cases of harm exist. The absence of data does not equal proof of safety. What a great discussion and continued review of the guidelines and current clinical evidence. This is a cautious approach to the use of Sugamonex, taking into consideration perinatal pharmacology and patient safety. Going forward more research in this area is essential to help further our understanding on the safe use of Sugaminex during pregnancy and lactation. If you have any questions or comments from today's show, please email us at podcast at apsforg. 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 apsforg for detailed information and check out the show notes for links to all the topics we discussed today. Until next time, stay vigilant so that no one shall be harmed by anesthesia care.