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

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 started the conversation about safety considerations with Sugammadex administration for patients with renal impairment as well as pregnant and breastfeeding patients. We are continuing this important discussion today to talk about sugammadex use for pediatric patients. Plus, we have a late-breaking letter to the APSF Newsletter editors that was published on March 12^th that we are going to talk about.

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!”

Our featured article again today is “Safety of Sugammadex in Pregnancy, Pediatrics, and Renal Failure” by Kevin Yang, Christina Ratto, Joseph Szokol, and Ashley O-sumi. To follow along with us, head over to APSF.org 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 sugammadex.

[Joseph Szokol] “ 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 focus on quantitative over qualitative monitoring and reverse of any block except for shallow block with Sugammadex. The product information for Sugammadex does not recommend Sugammadex patients with severe renal impairment including those on dialysis. At CAC USC, we are one of the busiest solid organ transplant centers in the United States, and the issue of which neuromuscular blockage to administer is a commonplace one.

The concern is one of recurarization resulting in potential paralysis or residual weakness due to dissociation of the rocuronium sugan mix. In normal individuals, over 90 percent of the complex is excreted within 24 hours. This is delayed in those with renal impairment. However, the rocuronium sugammadex complex is a highly stable one due to van der Waals forces.

For every 25 million rocuronium sugammadex complexes, only one dissociates.  The complex is also removed during dialysis with a high flux filter. Their option, other option for those concerned about the theoretical risk of recurarization is to utilize a benzylquinolone such as cisatricurium reversal with neostigmine.

Again, the ASA guidelines recommend Neostigmine Reversal for only shallow block, thus highlighting the need for quantitative monitoring to determine, to determine the depth of blockade.”

[Bechtel] Thank you so much to Szokol for contributing to the show today and this article. The big takeaway when it comes to the use of Sugammadex for patients with renal impairment may be the following:

Using Sugammadex to reverse moderate blockade is safe and faster than the combination of neostigmine and cisatracurium and it is important to use a quantitative neuromuscular monitor to ensure adequate reversal to a TOF >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. This means that it is time to dive back into the article to talk about the safety considerations for the use of sugammadex for pediatric patients.

You may remember that when Sugammadex was first introduced in the United States, the FDA approval was for the use in adults. The Bridion 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 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, Sugammadex received FDA approval for use in patients 2 years and older with an updated package insert for dosing recommendations. Let’s take a closer look at the use of sugammadex in different pediatric age groups starting with children between the ages of 2-17. Here are the important considerations:

• Sugammadex 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 16mg/kg Sugammadex 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 2mg/kg Sugammadex 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 4mg/kg dose was the same as with adults.
• The use of Sugammadex 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 sugammadex is superior for reversal of neuromuscular blockade compared to acetylcholinesterase inhibitors.

What about the use of Sugammadex for infants less than 2 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 2 months old. Another consideration is that fetal postjunctional receptors are more sensitive to neuromuscular blockers with prolonged opening times. The pharmacokinetic different are due to underdeveloped hepatic and renal function leading to decreased neuromuscular blocking drug clearance.

Let’s look at a prospective pilot trial of sugammadex administration in children aged 1-12 months old who received a 2mg/kg dose. There was a similar time to recovery of the TOFR for all age groups and no subsequent TOFR decrease after the initial TOFR recovery to greater than 0.9. A single-centre retrospective cohort study of patients less than 24 months old reported that re-dosing of Sugammadex occurred in 4.2% of cases after an initial dose of 3.45mg/kg. A limitation of this study was the limited use of train of four 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.

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 difference 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 sugammadex which can reverse moderate and profound block with a decreased risk of residual neuromuscular blockade. Multiple large scale retrospective and prospective studies on sugammadex 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. Thress of the patients were less than 2 years old. After adequate reversal and extubation, the patients were noted to have decreased respiratory effort, minimal limb movement, weakness, and cyanosis. Repeat sugammadex 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 sugammadex 50 minutes after the first dose. Another case report of an 8month old who was adequately reversed with TOF monitoring at the adductor pollicis muscle required repeat sugammadex dose administration 20 minutes after extubation. Reversal of neuromuscular blockade is a time to remain vigilant with close monitoring.

We also need to remain vigilant for adverse events following sugammadex administration which may include recurarization, 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 2mg/kg, 4mg/kg, and neostigmine. A meta-analysis with trial sequential analysis reported a significantly lower incidence of bradycardia for patients receiving sugammadex 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 Sugammadex for patients with renal impairment, during pregnancy, and during pediatric anaesthesia care. We are looking forward to more clinical evidence going forward to help keep patients who require neuromuscular blockade and reversal safe during anaesthesia care.

Before we wrap up for today, we have another featured article. It is the article between issues that was published on March 12^th, 2025, “Concerns regarding Sugammadex Use During Pregnancy and Lactation” by Sarah Dodd and colleagues. To follow along with us, head over to APSF.org and click on the Newsletter Heading. Second one down is Articles Between Issues. Then, scroll down until you get to our featured article today. I will include a link in the show notes as well.

This is a letter to the editors in response to our featured Newsletter article with concerns about inaccurate information related to Sugammadex use for pregnant and lactating patients. Here are their three areas of concern:

1. Sugammadex 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 sugammadex in pregnancy is best for patients.
2. Sugammadex compatibility with uninterrupted breastfeeding. 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 months. 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 sugammadex 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 sugammadex is incompatible with lactation is not consistent with current expert opinion and available data.
3. Breast milk production and composition change over time. The authors highlight that lactating patients may present for surgery and anaesthesia care after the post-partum period. There is a difference between early lactation when the junctions between lactocytes are leaky and sugammadex molecules may pass into breastmilk and late lactation after the first few days up to 2 weeks when sugammadex is extremely unlikely to pass into mature breastmilk.

The authors recommend the following changes:

Use of the phrase Potential interaction with progesterone

Remove phrase Potential teratogenicity

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 Sugammadex use in pregnancy, the authors highlight the potential for sugammadex to bind progesterone as an area of concern and the lack of large-scale human studies leading to a cautious approach. The use of sugammadex for rescue reversal in cannot intubate/cannot ventilate scenarios is appropriate to avoid severe hypoxia that would be more detrimental than sugammadex exposure. However, the current recommendations from the Society for Obstetric Anesthesia and Perinatology and the Merck prescribing information advise against routine use of sugammadex in pregnancy and this position is consistent with the current best available data and clinical guidance.

For sugammadex 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 sugammadex 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 anaesthesia professionals need to be aware of the changing physiologic process to help with decision making. 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 Sugammadex 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 sugammadex during pregnancy and lactation.

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.

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

© 2025, The Anesthesia Patient Safety Foundation