What is the available guidance on using Sugammadex in patients with ESRD?

Comment by InpharmD Researcher

There is limited evidence to guide the use of sugammadex in patients with end-stage renal disease (ESRD). Available studies generally report administration of doses ranging from 2 to 4 mg/kg, and indicate that renal clearance of sugammadex is impaired; however, these pharmacokinetic differences compared with patients without renal impairment have not consistently translated into clinically meaningful outcomes. One recent prospective trial found that sugammadex at 2 mg/kg provided rapid and effective reversal of rocuronium-induced neuromuscular blockade in patients with severe renal failure undergoing kidney transplantation, though these findings may not be broadly generalizable to all patients with ESRD, as the study population was limited to transplant recipients.

Background

A 2023 narrative review meticulously evaluated the efficacy, pharmacokinetics, and safety of sugammadex in reversing rocuronium-induced neuromuscular blockade (NMB) in patients with end-stage renal disease (ESRD). Prospective trials demonstrated that sugammadex at 2 mg/kg effectively reversed moderate NMB in ESRD patients without significant adverse events, although with a modestly prolonged recovery time compared to healthy controls. Similarly, a 2015 clinical trial reported that sugammadex at 4 mg/kg successfully reversed deep NMB, with a recovery time of 5.6 minutes in ESRD patients, slower than the 2.7 minutes observed in controls, but with no indications of residual NMB or recurrence. Pharmacokinetic investigations, including a 2010 study that revealed markedly reduced clearance of sugammadex in ESRD patients, resulting in prolonged systemic exposure. Despite the stable sugammadex–rocuronium complex formation being theorized to minimize the risk of recurarization, the long-term safety of sustained high plasma concentrations remains unclear. Additional studies, such as a 2020 retrospective analysis and a propensity-score-matched assessment confirmed the safety of sugammadex in ESRD patients, showing no significant increase in 30-day or 1-year mortality. However, the absence of severe adverse events in controlled settings contrasts with the theoretical risks of prolonged clearance, anaphylaxis, or cardiovascular complications, emphasizing the need for quantitative neuromuscular monitoring and careful perioperative management. These findings collectively underline sugammadex's utility in ESRD patients while reinforcing the necessity for continuous safety evaluation and optimal dosing strategies. [1]

Another systematic review and meta-analysis, published in 2021, evaluated the efficacy, pharmacokinetics, and safety of sugammadex for reversing rocuronium-induced NMB in patients with ESRD compared to those with normal renal function. This comprehensive analysis included six prospective case-control studies with 179 participants and three retrospective observational studies comprising 476 ESRD patients; four studies used a 4 mg/kg dose, and the other two used 2 mg/kg. The pooled data revealed that recovery times to a train-of-four (TOF) ratio of ≥0.9, 0.8, and 0.7 were significantly prolonged in the ESRD cohort compared to the controls, although the differences were small and considered clinically manageable (mean difference: 1.14 min, 0.9 min, 0.89 min, respectively). The pharmacokinetic analysis showed substantially reduced plasma clearance of sugammadex in ESRD patients, while plasma concentrations of rocuronium were elevated post-administration due to the inability of the assay to distinguish between bound and unbound forms. Further, three retrospective studies provided supplementary safety information, reporting minimal post-anesthetic complications and no significant adverse events directly attributable to sugammadex. Hemodynamic instability and hypersensitivity were rarely observed, and no laboratory abnormalities were linked to sugammadex use. Despite the longer recovery times in ESRD patients, the data emphasized that the efficacy of sugammadex in achieving satisfactory NMB reversal remains uncompromised. The findings support the cautious use of sugammadex in ESRD patients, though the high variability in study designs and limited long-term safety data underscore the need for additional robust studies. [2]

A 2021 systematic review and meta-analysis evaluated the efficacy, pharmacokinetics, and safety of sugammadex in reversing rocuronium-induced NMB in patients with ESRD compared to those with normal renal function. This comprehensive analysis included six prospective case-control studies with 179 participants and three retrospective observational studies comprising 476 ESRD patients. The pooled data revealed that recovery times to a TOF ratio of ≥ 0.9, 0.8, and 0.7 were significantly prolonged in the ESRD cohort compared to the controls, although the differences were small and considered clinically manageable. The pharmacokinetic analysis showed substantially reduced plasma clearance of sugammadex in ESRD patients, while plasma concentrations of rocuronium were elevated post-administration due to the inability of the assay to distinguish between bound and unbound forms. Further, three retrospective studies provided supplementary safety information, reporting minimal post-anesthetic complications such as recurrence of NMB and no significant adverse events directly attributable to sugammadex. Hemodynamic instability and hypersensitivity were rarely observed, and no laboratory abnormalities were linked to sugammadex use. Despite the longer recovery times in ESRD patients, the data emphasized that the efficacy of sugammadex in achieving satisfactory NMB reversal remains uncompromised. The findings support the cautious use of sugammadex in ESRD patients, though the high variability in study designs and limited long-term safety data underscore the need for additional robust studies. [3]

References:

[1] Oh SK, Lim BG. Sugammadex administration in patients with end-stage renal disease: a narrative review with recommendations. Anesth Pain Med (Seoul). 2023;18(1):11-20. doi:10.17085/apm.22259
[2] Kim YS, Lim BG, Won YJ, Oh SK, Oh JS, Cho SA. Efficacy and Safety of Sugammadex for the Reversal of Rocuronium-Induced Neuromuscular Blockade in Patients with End-Stage Renal Disease: A Systematic Review and Meta-Analysis. Medicina (Kaunas). 2021;57(11):1259. Published 2021 Nov 17. doi:10.3390/medicina57111259
[3] de Souza CM, Tardelli MA, Tedesco H, et al. Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: A comparative prospective clinical trial. Eur J Anaesthesiol. 2015;32(10):681-686. doi:10.1097/EJA.0000000000000312
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

what is the available guidance on using Sugammadex in patients with ESRD?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-2 for your response.

 

Reversal of rocuronium-induced neuromuscular blockade by sugammadex in patients undergoing kidney transplantation: Pharmacokinetics, efficacy, and safety analyses
Design

Open-label, comparative, prospective clinical study

N= 34
Objective

To investigate the pharmacokinetics of sugammadex in patients with end-stage renal disease undergoing kidney transplantation and to evaluate its efficacy and safety
Study Groups

Renal failure (n= 17)

Control (n= 17)
Inclusion Criteria

Ethnic Han Chinese aged 18–65 years with American Society of Anesthesiologists (ASA) class I-III; kidney transplantation group with creatinine clearance (CrCl) < 30 mL/min and control group with CrCl ≥80 mL/min undergoing elective abdominal or neurosurgical procedures
Exclusion Criteria

Neuromuscular disorders, hepatic dysfunction, history of malignant hyperthermia, allergy to narcotics, neuromuscular blocking agents (NMBAs), or any medication used during general anesthesia, current use of anticonvulsants, magnesium, or aminoglycosides
Methods

Sugammadex 2 mg/kg administered at reappearance of the second twitch of the train-of-four for reversal of rocuronium-induced neuromuscular blockade. Plasma concentration was measured at regular intervals. Pharmacokinetics were determined using non-compartmental analysis.
Duration

December 2021 to July 2022
Outcome Measures

Pharmacokinetics of sugammadex and efficacy and safety of sugammadex in kidney transplantation
Baseline Characteristics  

Renal failure  (n= 17)

 Control  (n= 17)
Age, years

46.8 ± 10.9

 51.1 ± 9.9
Weight, kg 

62.8 ± 8.3

 60.5 ± 9.1
Height, m

1.66 ± 0.06

 1.62 ± 0.07
Female

13 (76%)

 10 (59%)

ASA Class

I

II

III

 

0 (0%)

0 (0%)

17 (100%)

 

5 (29%)

12 (71%)

0 (0%)
CrCl, mL/min (IQR)

6.4 (5.7-8.3)

 95.3 (88.2-108.9)
Results  

Renal failure (n= 17)

 Control (n= 17) p-value
Geometric mean recovery time, min (95% CI)*

2.04 (1.61 to 2.58)

 1.99 (1.67 to 2.38) 0.866
Mean recovery time, min*

2.28 (1.34)

 2.11 (0.84) 0.676
Median recovery time, min (IQR)* 2 (1.5-2.6)

1.75 (1.5- 2.5)

 0.931

Abbreviations: IQR= interquartile range; CI= confidence interval

*Time (min) from the start of administration of sugammadex to recovery of the train-of-four-ratio (TOFR) ≥ 0.9 

Pharmacokinetic data from 30 patients showed that the geometric mean elimination half-life of sugammadex was prolonged in renal failure (10 hours vs, 2 hours in controls; p< 0.001), with reduced plasma clearance (15.2 vs. 82.5 mL/min; p< 0.001). However, recovery of train-of-four ratio ≥ 0.9 was similar between the groups (see above).
Adverse Events

Serious Adverse Events: Pneumonia (12% in control group only), pulmonary congestion (6% in renal failure group only), acute myocardial infarction (6% in renal failure group only), wound hemorrhage (6% vs. 6%), increased blood creatinine levels (12% in renal failure group only)
Study Author Conclusions

Sugammadex at a dose of 2 mg/kg provided rapid and effective reversal of rocuronium-induced moderate NMB in patients with severe renal failure undergoing kidney transplantation, with a safety profile similar to that observed in patients with normal renal function. The donor kidney can excrete sugammadex within approximately 48 h.
Critique The study provides valuable insights into the pharmacokinetics and safety of sugammadex in renal transplant patients, highlighting its efficacy and safety. However, the study is limited by its single-center design and small sample size, which may affect the generalizability of the findings. Additionally, all donor kidneys were from deceased donors, leaving the PK profile following living donor transplantation unknown. Larger multicenter studies are needed to confirm these findings and assess long-term safety.
References:

Tang Y, Feng Y, Jia B, et al. Reversal of rocuronium-induced neuromuscular blockade by sugammadex in patients undergoing kidney transplantation: Pharmacokinetics, efficacy, and safety analyses. J Clin Anesth. 2025;105:111900. doi:10.1016/j.jclinane.2025.111900

 

Sugammadex for Reversal of Neuromuscular Blockade in a Patient With Renal Failure

Design

 Case report

Case presentation

A 19-year-old, 82.2-kg female with end-stage chronic kidney disease (glomerular filtration rate <15 mL/min) presented via ambulance for emergent ventriculoperitoneal shunt revision. Past medical history included myelomeningocele, hydrocephalus, neurogenic bowel and bladder, lower extremity paralysis, anemia, and secondary hyperparathyroidism. She was listed for cadaveric kidney transplant but had not yet received dialysis. Past surgical history included myelomeningocele repair, left ventriculoperitoneal shunt insertion, left clubfoot repair, debridement of a foot wound with skin grafting, and adenotonsillectomy.

Home medications included ergocalciferol 4000 units PO daily, ferrous fumarate 325 mg PO BID, sodium bicarbonate PO BID, sevelamer 800 mg PO TID, docusate sodium 100 mg PO QD, calcitriol 0.25 mcg PO BID, oxybutynin 10 mg × 2 PO daily, and amlodipine 10 mg PO daily. In the emergency department, she additionally received morphine 2 mg and ondansetron 4 mg.

On arrival, she reported severe frontal headache, nausea, emesis, photophobia, blurred vision, and declining mental status. Physical exam revealed altered mental status and nystagmus on upward lateral gaze. Her pulse was 113 beats/min; other vital signs, airway, cardiovascular, and respiratory exams were unremarkable. CT imaging revealed shunt dysfunction with enlargement of the lateral and third ventricles and a Chiari 2 malformation. Laboratory studies showed normal PT, PTT, INR, and cerebrospinal fluid analysis. Basic metabolic panel demonstrated blood urea nitrogen 37 mg/dL (reference 5–18 mg/dL) and creatinine 4.83 mg/dL (reference 0.5–1.20 mg/dL).

In the operating room, routine American Society of Anesthesiologists’ monitors were applied. Induction and rapid sequence intubation were performed with propofol 200 mg, fentanyl 200 mcg, lidocaine 80 mg, and rocuronium 80 mg. Anesthesia was maintained with isoflurane in air and oxygen. Intraoperative medications included cefazolin 2000 mg, dexamethasone 4 mg, and ondansetron 4 mg. Mild hypotension after induction was treated with phenylephrine (total intraoperative dose 400 mcg). Blood loss was minimal, and fluids included 500 mL of lactated Ringer’s.

Two hours and 10 minutes after rocuronium administration, no twitches were observed on train of four (TOF), but 4 posttetanic twitches were present. After 2 hours and 30 minutes, one twitch returned on TOF. At that time, sugammadex 4 mg/kg (total 328.8 mg) was administered. Within 10 minutes, there was full reversal of neuromuscular blockade, with return of protective airway reflexes, TOF response, adequate spontaneous ventilation, and purposeful movements.

The patient was extubated uneventfully and transferred to the postanesthesia care unit with supplemental oxygen until awake, alert, and oriented. She was subsequently transferred to the inpatient ward at baseline mental status. The postoperative course was unremarkable, and she was discharged home later that evening.

Study Author Conclusions

We describe a 19-year-old patient with renal failure who received sugammadex for reversal of rocuronium-induced neuromuscular blockade. Much of the concern for sugammadex use in renal failure patients stems from the delayed clearance of the sugammadex-rocuronium complex. Despite these concerns, our anecdotal experience and that from the literature demonstrate the safety and efficacy of sugammadex in this clinical setting.
References:

Pfaff K, Tumin D, Tobias JD. Sugammadex for Reversal of Neuromuscular Blockade in a Patient With Renal Failure. J Pediatr Pharmacol Ther. 2019;24(3):238-241. doi:10.5863/1551-6776-24.3.238