Effective Use of Sugammadex for Incomplete Pyridostigmine Reversal of Muscle Relaxation by Rocuronium: A Case Report

doi:10.4236/ojanes.2013.39083

Paper Menu >>

Journal Menu >>

Open Journal of Anesthesiology, 2013, 3, 393-395

Published Online November 2013 (http://www.scirp.org/journal/ojanes)

http://dx.doi.org/10.4236/ojanes.2013.39083

Open Access OJAnes

393

Effective Use of Sugammadex for Incomplete

Pyridostigmine Reversal of Muscle Relaxation by

Rocuronium: A Case Report

Hee Jong Lee, Kyo Sang Kim*, Ji Seon Jeong, Sung Hwan Choi, Kyu Nam Kim

Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul, South Korea.

Email: *[email protected]

Received September 3rd, 2013; revised September 28th, 2013; accepted October 11th, 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Anticholinesterase does not allow adequate reversal of the deep neuromuscular blockade (NMB) achieved using high

doses of relaxants. A 71-year-old female patient (weight 70 kg, height 169 cm) was scheduled for a transurethral re-

section of a bladder tumor under general anesthesia. We administered rocuronium 30 mg (0.43 mg/kg) for tracheal in-

tubation due to an estimated short surgical time. During the operation, an additional rocuronium 10 mg was injected.

The surgical procedure ended abruptly 10 minutes after receiving the last dose of rocuronium. At the end of surgery, the

patient received pyridostigmine as a reversal. However, residual NMB persisted, and neuromuscular monitoring did not

show the expected degree of recovery. Sugammadex 2 mg/kg was used, and the patient experienced complete reversal

from NMB in just 2 min.

Keywords: Pyridostigmine; Residual Block; Rocuronium; Sugammadex

1. Introduction

Neostigmine is widely used in many countries, but a high

frequency (32%) of residual block (train-of-four (TOF)

ratios < 0.9) was noted after the use of intermediateac-

ting neuromuscular blockade (NMB) drugs in a post-

anesthesia care unit [1]. Pyridostigmine is frequently

used as reversal agent for rocuronium-induced NMB

only in Korea [2]. Pyridostigmine is preferred for its

longer duration of action compared with neostigmine or

edrophonium, although the onset of pyridostigmine is

slower [3]. However, there is a high risk of significant

residual neuromuscular block after rocuronium even with

reversal using a large dose of pyridostigmine in the re-

covery room [4]. Recent reports indicate that sugam-

madex, a modified γ-cyclodextrin, is highly effective for

reversal of deep or moderate NMB induced by steroidal

agents [5]. We report a case of successful reverse by su-

gammadex after previous administration of pyridostig-

mine that resulted in incomplete reversal of deep rocuro-

nium-induced NMB.

2. Case Report

A female patient, 71 years old, 70 kg, 169 cm, ASA II,

was scheduled for transurethral resection under general

anesthesia of a malignant bladder tumor located on the

dome of the bladder. She had a history of bladder cancer

five years before her presentation and which was treated

with subtotal bladder resection, and a cerebral hemor-

rhage 25 years ago for which surgery was performed.

She suffered from systemic hypertension and had been

receiving antihypertensive medication for 25 years. Preo-

perative laboratory investigations (normal range) showed

a hemoglobin level of 14.8 g/dL (11.3 - 16.1), alanine

aminotransferase (ALT) 65 U/L (5 - 45), aspartate ami-

notransferase (AST) 45 U/L (5 - 40), alkaline phospha-

tase 61 U/L (30 - 110), total bilirubin 0.68 mg/dL (0.2 -

1.2), high density lipoprotein (HDL) 46 mg/dL (32 - 71),

low density lipoprotein (LDL) 142 mg/dL (0 - 137), and

creatinine 0.92 mg/dL (0.6 - 1.4).

On the day of the surgery, the patient received atropine

0.5 mg and midazolam 1.5 mg as premedication. Moni-

tors included ECG, heart rate (HR), non-invasive blood

pressure (BP), blood oxygen saturation (SpO2), and end-

*Corresponding author.

Effective Use of Sugammadex for Incomplete Pyridostigmine Reversal

of Muscle Relaxation by Rocuronium: A Case Report

394

tidal CO2. Her pre-anesthetic vital signs were BP 130/82

mmHg, HR 73 bpm, and SpO2 96%. General anesthesia

was induced with remifentanil 0.5 μg/kg/min and propo-

fol 80 mg IV. After the loss of eyelash reflex was con-

firmed, neuromuscular monitoring began immediately.

For the calibration of acceleromyography (TOF-Watch

SX®, Organon Ltd., Dublin, Ireland), a 5-s 50-Hz supra-

maximal tetanic stimulus was administered over both

ulnar nerves [6]. A supramaximal current was obtained

after the initial single twitch calibration. After stabiliza-

tion of control responses, rocuronium 30 mg (0.43 mg/kg)

was administered due to an estimated short surgical time,

and tracheal intubation was performed at the disappear-

ance of the TOF response. Anesthesia was maintained

with desflurane 6% by volume in 50% oxygen-enriched

air and remifentanil 0.2 μg/kg/min, and this mixture was

titrated to maintain a bispectral index (BIS) of approxi-

mately 40. At 45 minutes after induction of anesthesia,

the patient bucked in response to surgical traction, so ro-

curonium 10 mg was injected. At that time, the TOF re-

sponse showed three twitches. The surgical procedure

ended 10 minutes after receiving the last dose of rocuro-

nium. The neuromuscular block was antagonized with

glycopyrrolate 0.4 mg and pyridostigmine 10 mg IV,

when one twitch was shown at TOF stimulation. Fifteen

minutes passed after the reversal with no indication that

the patient was recovering from the rocuronium-induced

NMB. Only one twitch was not changed at TOF stimula-

tion. At that point, a bolus of IV sugammadex 140 mg (2

mg/kg) was injected to remove the residual NMB. A TOF

ratio of 1.0 was confirmed by acceleromyography within

2 minutes. Tracheal extubation was performed unevent-

fully in the operating room. The patient’s postoperative

recovery course was unremarkable.

3. Discussion

The recovery time from rocuronium may be increased in

elderly and female patients [7]. Due to this fact and an

estimated short surgical time, low-dose rocuronium 30

mg (0.43 mg/kg) was injected initially for this patient.

However, an additional dose of rocuronium 10 mg was

required once the surgical time was prolonged, and the

patient began bucking in response to surgical traction.

The surgical procedure ended abruptly 10 minutes after

receiving the last dose of rocuronium. Initially, we de-

cided to use glycopyrrolate 0.4 mg and pyridostigmine

10 mg IV after the confirmation of one twitch at TOF

stimulation, which have an onset of 2 - 5 minutes, a peak

activity occurring at about 10 - 20 minutes, and a 2 - 4

hour duration [8]. After fifteen minutes from the reversal,

the TOF response of one twitch was not changed. Pyri-

dostigmine does not achieve complete reversal of muscle

blockade compared to neostigmine at 10% of initial first

twitch height during pancuronium-induced NMB [9].

The incidence of residual block (TOF ratio < 0.7) after

reversal using pyridostigmine 10 mg is 21.5% in the re-

covery room [4]. Moreover, the time to obtain a TOF

ratio of 0.9 is extended greatly [10]. Only in Korea

pyridostigmine is still used as a reversal agent in clinical

practice (more than 80%) [11]. We think that the stan-

dard of care for reversal of rocuronium-induced NMB in

Korea should be changed from pyridostigmine, with its

lower potency and slower onset, to neostigmine. The rea-

son of prolonged paralysis after reversal of neuromuscu-

lar blockade was not known, but we suspect that the con-

comitant drugs (local anesthetics, antibiotics, and cal-

cium channel blockers, etc) have also been affected.

Sugammadex is a modified γ-cyclodextrin that forms

tight one-to-one complexes with rocuronium and, to a

slightly lesser extent, vecuronium, resulting in rapid ter-

mination of NMB [12]. Sugammadex is a fast and predi-

ctable dose-dependent reversing agent of any degree of

block induced by rocuronium, a property that cannot be

replicated with neostigmine/glycopyrrolate [13]. In mod-

erate degrees of neuromuscular block (reappearance of

two twitches), significantly faster recovery (1.5 min) to a

TOF ratio of 0.9 occurred after administration of sugam-

madex 2 mg/kg compared to neostigmine 50 µg/kg (18.6

min) [14]. Sugammadex (4.0 and 8.0 mg/kg) reversed

profound NMB (post-tetanic count 1 or 2) induced by ro-

curonium in a mean time of 1.7 minutes [13]. Sugam-

madex has the potential to be cost-effective compared

with neostigmine/glycopyrrolate for the reversal of ro-

curonium-induced moderate or profound NMB and po-

tentially provides increased patient safety due to the in-

creased predictability of recovery from NMB [15]. In this

case, moderate rocuronium-induced NMB was success-

sfully reversed within 2 minutes with sugammadex at

doses of 2 mg/kg. Sugammadex made it possible that the

predictable effectiveness of a reversal agent, and which

fully prevents residual block, is therefore highly desir-

able.

REFERENCES

[1] G. S. Murphy, J. W. Szokol, J. M. Marymont, et al., “Re-

sidual Paralysis at the Time of Tracheal Extubation,” An-

esthesia & Analgesia, Vol. 100, No. 6, 2005, pp. 1840-

1845.

http://dx.doi.org/10.1213/01.ANE.0000151159.55655.CB

[2] S.-J. Jeong, J.-I. Han, H.-J. Baik, H. Lee, et al., “The

Effect of Pyridostigmine on Bispectral Index during Re-

covery from Sevoflurane Anesthesia,” Korean Journal of

Anesthesiology, Vol. 61, No. 6, 2011, pp. 460-464.

http://dx.doi.org/10.4097/kjae.2011.61.6.460

[3] R. D. Miller, L. S. Van Nyhuis, E. I. Eger 2nd, et al.,

“Comparative Times to Peak Effect and Durations of Ac-

tion of Neostigmine and Pyridostigmine,” Anesthesiol-

Open Access OJAnes

Effective Use of Sugammadex for Incomplete Pyridostigmine Reversal

of Muscle Relaxation by Rocuronium: A Case Report

Open Access OJAnes

395

ogy, Vol. 41, No. 1, 1974, pp. 27-33.

[4] K. S. Kim, S. H. Lew, H. Y. Cho, et al., “Residual Pa-

ralysis Induced by Either Vecuronium or Rocuronium af-

ter Reversal with Pyridostigmine,” Anesthesia & Anal-

gesia, Vol. 95, No. 6, 2002, pp. 1656-1660.

[5] R. K. Mirakhur. “Sugammadex in Clinical Practice,” Anaes-

thesia, Vol. 64, Suppl. 1, 2009, pp. 45-54.

http://dx.doi.org/10.1111/j.1365-2044.2008.05870.x

[6] A. F. Kopman, S. Kumar, M. M. Klewicka, et al., “The

Staircase Phenomenon. Implications for Monitoring of

Neuromuscular Transmission,” Anesthesiology, Vol. 95, No.

2, 2001, pp. 403-407.

[7] R. S. Matteo, E. Ornstein, A. E. Schwartz, et al., “Phar-

macokinetics and Pharmacodynamics of Rocuronium

(Org 9426) in Elderly Surgical Patients,” Anesthesia &

Analgesia, Vol. 77, No. 6, 1993, pp. 1193-1197.

[8] A. Ferguson, P. Egerszegi, D. R. Bevan, et al., “Neo-

stigmine, Pyridostigmine, and Edrophonium as Antago-

nists of Pancuronium,” Anesthesiology, Vol. 53. No. 5,

1980, pp. 390-394.

[9] F. Donati, J. Lahoud, D. McCready, et al., “Neostigmine,

Pyridostigmine and Edrophonium and Neostigmine as

Antagonists of Deep Pancuronium Blockade,” Canadian

Journal of Anaesthesia, Vol. 34, No. 6, 1987, pp. 589-

593.

[10] A. Y. Oh, S. D. Kim and C. S. Kim, “Early and Late Re-

versal of Rocuronium with Pyridostigmine during Se-

voflurane Anaesthesia in Children,” Anaesthesia and In-

tensive Care, Vol. 32, No. 5, 2004, pp. 649-652.

[11] S. J. Jeong, J. I. Han, H. J. Baik, et al., “The Effect of Py-

ridostigmine on Bispectral Index during Recovery from

Sevoflurane Anesthesia,” Korean Journal of Anesthesio-

logy, Vol. 61, No. 6, 2011, pp. 460-464.

http://dx.doi.org/10.4097/kjae.2011.61.6.460

[12] A. Abrishami, J. Ho, J. Wong, et al., “Cochrane Corner:

Sugammadex, a Selective Reversal Medication for Pre-

venting Postoperative Residual Neuromuscular Block-

ade,” Anesthesia & Analgesia, Vol. 110, No. 4, 2010, p.

1239.

[13] S. B. Groudine, R. Soto, C. Lien, et al., “A Randomized,

Dose-Finding, Phase II Study of the Selective Relaxant

Binding Drug, Sugammadex, Capable of Safely Rever-

sing Profound Rocuronium-Induced Neuromuscular Blo-

ck,” Anesthesia & Analgesia, Vol. 104, No. 3, 2007, pp.

555-562.

http://dx.doi.org/10.1213/01.ane.0000260135.46070.c3

[14] M. Blobner, L. I. Eriksson, J. Scholz, et al., “Reversal of

Rocuronium-Induced Neuromuscular Blockade with Su-

gammadex Compared with Neostigmine during Sevoflu-

rane Anaesthesia: Results of a Randomised, Controlled

Trial,” European Journal of Anaesthesiology, Vol. 27. No.

10, 2010, pp. 874-881.

http://dx.doi.org/10.1097/EJA.0b013e32833d56b7

[15] F. Paton, M. Paulden, D. Chambers, et al., “Sugammadex

Compared with Neostigmine/Glycopyrrolate for Routine

Reversal of Neuromuscular Block: A Systematic Review

and Economic Evaluation,” British Journal of Anaesthe-

sia, Vol. 105, No. 5, 2010, pp. 558-567.

http://dx.doi.org/10.1093/bja/aeq269