Skip Navigation


BJA Advance Access originally published online on February 7, 2006
British Journal of Anaesthesia 2006 96(4):473-479; doi:10.1093/bja/ael013
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
96/4/473    most recent
ael013v1
Right arrow E-Letters: Submit a response to the article
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (25)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by de Boer, H. D.
Right arrow Articles by Booij, L. H. D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Boer, H. D.
Right arrow Articles by Booij, L. H. D. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey{dagger}

H. D. de Boer1,*, J. van Egmond1, F. van de Pol1, A. Bom2 and L. H. D. J. Booij1

1Department of Anaesthesiology, Radboud University Medical Centre Nijmegen Nijmegen, The Netherlands
2Department of Pharmacology Organon Newhouse, ML1 5SH, Scotland, UK

*Corresponding author: Department of Anesthesiology, Radboud University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: HD.de.Boer{at}mzh.nl

Accepted for publication December 5, 2005.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Background. Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic {gamma}-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced by rocuronium or the non-steroidal neuromuscular blocking drugs, mivacurium or atracurium, in the anaesthetized Rhesus monkey.

Methods. After a bolus injection of rocuronium, mivacurium or atracurium, a continuous infusion of these drugs was started to maintain the first twitch contraction of the train-of-four at approximately 10% of its baseline value. After a steady state block of at least 10 min the infusion was stopped and the preparation was allowed to recover spontaneously. This process was repeated, but at the time the infusion was stopped, either sugammadex 0.5 or 1.0 mg kg–1 was given in the rocuronium-induced blockade and sugammadex 1.0 mg kg–1 was given in the mivacurium- and atracurium-induced blockade.

Results. Sugammadex caused a rapid and complete reversal of rocuronium-induced neuromuscular block. The recovery time to train of four ratio=0.9 after spontaneous recovery was 14.4 min (SD=3.4 min; n=14). This was reduced significantly (P<0.001) to 3.7 min (SD=3.3 min; n=4) with sugammadex 0.5 mg kg–1 and to 1.9 min (SD=1.0 min; n=4) with sugammadex 1.0 mg kg–1. Signs of residual blockade or re-curarization were not observed. Reversal of mivacurium- or atracurium-induced neuromuscular block (n=2 in each experiment) by sugammadex (1.0 mg kg–1) was not effective. In all experiments, injection of sugammadex had no effects on blood pressure or heart rate.

Conclusions. Sugammadex is effective in reversing rocuronium, but not mivacurium- or atracurium-induced neuromuscular block.

Keywords: neuromuscular block, atracurium; neuromuscular block, mivacurium; neuromuscular block, rocuronium; reversal agent, sugammadex (Org 25969)


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Binding of the rocuronium molecule by a cyclodextrin derivative is a novel approach to reversing rocuronium-induced neuromuscular block and prevention of the risk of postoperative residual blockade.1 2

This new method lacks the well-known side-effects associated with the use of cholinesterase inhibitors, as cyclodextrin derivatives do not interfere with other molecules or receptor systems, in particular the muscarinic system.1 Sugammadex (Org 25969) is a synthetic derivative of {gamma}-cyclodextrin designed to selectively bind the steroidal neuromuscular blocking drug rocuronium. Binding of the rocuronium molecule results in a rapid decrease in rocuronium concentration in plasma and subsequently at the motor endplate, which in turn results in reappearance of muscle activity.1 3 4 Calorimetry and X-ray crystallography have confirmed that sugammadex forms a complex with rocuronium, binding the rocuronium molecule within the cyclodextrin ring.1 Sugammadex has been shown to reverse neuromuscular block induced by steroidal neuromuscular blocking agents in an in vitro mouse hemi-diaphragm preparation and in vivo in cat, guinea pig and Rhesus monkey experiments and finally in human volunteers.1 3–8 Currently, limited data are available to demonstrate the reversibility of neuromuscular block induced by non-steroidal neuromuscular blocking agents by sugammadex.5 7

The first part of the present study evaluated the action of sugammadex at doses of 0.5 and 1.0 mg kg–1 in reversing constant 90% neuromuscular block, induced by continuous rocuronium infusion in the anaesthetized Rhesus monkey, using train-of-four (TOF) stimulation. The second part of this study used the same methods to evaluate the action of sugammadex at a dose of 1.0 mg kg–1 in reversing constant 90% neuromuscular block induced by continuous infusion of two non-steroidal neuromuscular blocking agents, mivacurium or atracurium.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
These in vivo experiments were performed in the experimental laboratories of the Department of Anaesthesiology at the University Medical Centre in Nijmegen, The Netherlands. The experiments were approved by the regional ethical committee on animal experiments.

Female Rhesus monkeys (CSIMS, Beijing, China) were sedated with ketamine 10 mg kg–1 (Nimatek Eurovet) administered by i.m. injection. Two i.v. lines were inserted; one for anaesthetic administration, including rocuronium, the other for test drug administration. Anaesthesia was induced by i.v. bolus injection of pentobarbital sodium (Ceva Sante Animale, 25 mg kg–1) and a subsequent continuous infusion of 5–10 mg kg–1 h –1. The monkeys were intubated endotracheally and the lungs ventilated with a mixture of oxygen and nitrous oxide at a ratio of 2:3. Heart rate (HR) and oxygen saturation were determined at the ear with a pulse oximeter (Ohmeda Biox). Blood pressure was determined with a cuff placed around the tail (Ohmeda, Finapres). Each time a TOF stimulus was triggered (every 15 s), all variables were requested by the measuring computer from both the pulse oximeter and the blood pressure device. Body temperature was kept at 37–38°C.

For monitoring purposes the median nerve of the right arm was stimulated supramaximally near the wrist using needle electrodes. Stimulation was performed with 2 ms square wave pulses in a TOF sequence of 2 Hz with an interval of 15 s delivered by a Grass S88 Stimulator (Grass Medical Instruments, Quincy, MA). The resulting contractions of the thumb muscles were quantified with a force displacement transducer, and recorded on a polygraph.

In the first part of this study, eight experiments were conducted in eight different Rhesus monkeys (body weight 4.2–6.6 kg). After a bolus injection of rocuronium bromide (100 µg kg–1), a continuous infusion (infusion rate varied between 285 and 606 µg kg–1 h–1) was started to maintain the first twitch contraction of the TOF at approximately 10% of its baseline value. After a steady state block had been maintained for ~10 min, the infusion was stopped and the preparation was allowed to recover spontaneously. This process was then repeated, but at the time the infusion was stopped, sugammadex either 0.5 or 1.0 mg kg–1 was given i.v. as a rapid bolus (n=4 for each dose). From the experimental traces TOF ratio recovery times were calculated at 50, 75 and 90% recovery. To verify that these data could be compared in a paired fashion, these experiments were preceded by six placebo experiments, in which the second recovery from 90% block was also spontaneous.

In the second part of the study, two experiments were performed using mivacurium and two using atracurium as neuromuscular blocking agents in four different Rhesus monkeys (body weight 5.2–6.6 kg). After a bolus injection of either mivacurium (100 µg kg–1), or atracurium (150 µg kg–1), a continuous infusion of mivacurium (infusion rate varied between 403 and 545 µg kg–1 h–1) or atracurium (infusion rate varied between 384 and 606 µg kg–1 h–1) was started to maintain the first twitch contraction of the TOF at approximately 10% of its base line value. After a steady state block had been maintained for 10 min, the infusion was stopped and the preparation was allowed to recover spontaneously. This process was repeated, but at the time the infusion was stopped, sugammadex 1.0 mg kg–1 was given i.v. as a rapid bolus. Again, from the experimental traces TOF ratio recovery times were calculated at 50, 75 and 90% recovery with and without sugammadex 1.0 mg kg–1.

At the end of the experiments, the animals were allowed to recover from anaesthesia.

Statistics
To evaluate the effect of the reversal agent two methods were used, both taking advantage of the paired character of the data. First recovery times with and without the reversal agent were compared in a simple Student's t-test for paired observations. Also the ratios of recovery times of the TOF_ratio were calculated at 50, 75 and 90% recovery: R50=T50 with/T50 without, with similar equations for R75 and R90. Then the average ratio of these three variables was calculated: R=(R50+R75+R90)/3. The statistical significance of the reversal effect of the test drug was tested by comparing R50, R75 and R90 and this averaged ratio R with 1 in a Student t-test for paired observations. As can be concluded from the obtained P-values, using ratios eliminated inter-individual variability in spontaneous recovery times between monkeys. The effect of different doses of the test drug on rocuronium reversal was performed on the same variables with the Student t-test for unpaired data. P-values <0.05 were considered statistically significant. Measurements concerning the recovery times, calculated ratios and relative changes in haemodynamic variables are presented as mean (SD).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The difference in speed of the recovery of the TOF for sugammadex compared with spontaneous recovery is apparent in Figure 1.


Figure 1
View larger version (16K):
[in this window]
[in a new window]
  		Fig 1 (A) The combination of typical tracings of T1 and T4 (first and last twitch of TOF, left y-axis) and MAP (right y-axis) during an experiment. Spontaneous recovery of rocuronium neuromuscular block followed by reversal of the same block level with sugammadex at a dose of 1.0 mg kg–1. (B) Tracings of TOF ratio corresponding to ‘stop infusion’ and ‘stop infusion+sugammadex 1.0 mg kg–1’. Time of ‘stop infusion’ corresponds to t=0. (C) Two consecutive tracings of TOF ratios, both of spontaneous recovery from 10% constant blockade are superimposed. These placebo experiments, preceding the actual experiments, showed, that these spontaneous recoveries are very reproducible, and therefore evaluation of reversal effect can be best performed in this paired fashion, as demonstrated in (B).

 
Table 1 presents the data from placebo experiments, in which two spontaneous recoveries were measured in six experiments. From these data and Figure 1C it is clear that the two consecutive spontaneous recoveries for a single monkey in a single experiment are very reproducible, allowing evaluation of the effect of a reversal agent in a paired fashion as described.


View this table:
[in this window]
[in a new window]
  		Table 1 Recovery times (min) of neuromuscular block induced by rocuronium. Recovery ratios are provided. The table provides recovery times and ratios of placebo experiments (N=6)

 
In the first part of the study, in which rocuronium was the neuromuscular blocking agent, the body temperature of the eight Rhesus monkeys ranged from 37.1 to 37.7°C. Recovery from rocuronium-induced neuromuscular block was significantly faster after treatment with either sugammadex 0.5 mg kg–1 or 1.0 mg kg–1, compared with spontaneous recovery (Table 2 and Fig. 2).


View this table:
[in this window]
[in a new window]
  		Table 2 Recovery times (min) and recovery ratios of neuromuscular block induced by rocuronium. Recovery ratios are provided. The table provides data after spontaneous recovery and after sugammadex administration (0.5 or 1.0 mg kg–1). #P=0.07 comparing the two doses of sugammadex

 

Figure 2
View larger version (10K):
[in this window]
[in a new window]
  		Fig 2 Recovery, as measured by the TOF ratio, of neuromuscular block by rocuronium (N=4 at each dose of sugammadex), mivacurium (N=2) and atracurium (N=2). Spontaneous recoveries are depicted with filled symbols, recovery with sugammadex, 1 mg kg–1, with open symbols. For rocuronium block one extra curve is displayed, corresponding to recovery with sugammadex, 0.5 mg kg–1, as indicated in the figure (also open symbols). The spontaneous recovery curves are based on the recovery times of the related experiments (for rocuronium four experiments at each dose).

 
In the second part of the study the effect of sugammadex 1.0 mg kg–1 on a constant neuromuscular block of about 90% induced by either mivacurium or atracurium was evaluated. The body temperature of the monkeys ranged from 37.0 to 37.6°C. As determined from the recovery ratios, sugammadex at a dose of 1.0 mg kg–1 had no significant effect on the speed of recovery from mivacurium- or atracurium-induced neuromuscular block, compared with spontaneous recovery (Table 3 and Fig. 2). These experiments showed that non-steroidal molecules such as atracurium and mivacurium do not bind to sugammadex. The lack of affinity of sugammadex for these neuromuscular blocking agents has already been clearly demonstrated in other species.5 7 For ethical reasons, the number of experiments was limited to two animals per non-steroidal drug.


View this table:
[in this window]
[in a new window]
  		Table 3 Recovery times (min) and recovery ratios of neuromuscular block induced by either mivacurium or atracurium, after either spontaneous recovery or sugammadex (1.0 mg kg–1)

 
The relative changes in HR and mean arterial pressure (MAP) are presented in Table 4. Injection of sugammadex had no significant effects on blood pressure or HR (Fig. 1A). Also in the experiments with either mivacurium or atracurium, sugammadex had no visible effect on HR or arterial blood pressure (Table 4).


View this table:
[in this window]
[in a new window]
  		Table 4 Cardiovascular changes attributable to sugammadex. Relative changes of HR and MAP are shown as group means with SD in parentheses. Minimum values (min) and maximum values are expressed as a percentage of the value at time of injection. The first row corresponds to the placebo experiments with saline. The high dose of sugammadex (third row) is an assembly of rocuronium, atracurium and mivacurium experiments. Means and dispersions, in the form of SD in parentheses, do not differ between placebo and sugammadex injections

 
All animals recovered completely without complication. Signs of residual blockade or re-curarization (up to 1 h after recovery) were not observed in the experiments with sugammadex.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Sugammadex (Org 25969), per-6-(2-carboxyethylthio)-per-6-deoxy-{gamma}-cyclodextrin sodium, belongs to the family of {gamma}-cyclodextrins. This group of oligosaccharides are cylindrical capsules with a lipophilic internal cavity and a hydrophilic exterior. With this lipophilic internal cavity, cyclodextrins are able to encapsulate lipophilic guest molecules such as steroids to form a host–guest inclusion complex. Nuclear magnetic resonance spectroscopy and X-ray crystallography of the host–guest inclusion complex between sugammadex and rocuronium showed a tight 1:1 complex with the rocuronium molecule intercalated in the cyclodextrin ring (Fig. 3).9 Cyclodextrins are highly water-soluble and do not possess intrinsic biological activity, and therefore it is unlikely that side-effects will occur.1 3 Sugammadex is excreted rapidly and dose-dependently in the urine of anaesthetized guinea pigs.10


Figure 3
View larger version (53K):
[in this window]
[in a new window]
  		Fig 3 Complex formation of sugammadex and rocuronium as obtained by X-ray diffraction. The rocuronium molecule (model with spheres) is completely encapsulated by sugammadex (model with sticks).1 (Reproduced with permission from Wiley–VCH.)

 
The present study showed that sugammadex (0.5 and 1.0 mg kg–1) caused a rapid and efficient reversal of rocuronium-induced neuromuscular block. In both dose groups the recovery from neuromuscular block was significantly faster than spontaneous recovery. This is most obvious from the recovery ratios that equal unity if there is lack of any effect, and approach to zero in the case of instantaneous 100% recovery. Comparing the recovery ratios for the two different dosages of sugammadex in the rocuronium experiments shows that the difference is close to significant, implying that a dose of 0.5 mg kg–1 does not provide the most efficient reversal. Signs of residual blockade or re-curarization were not seen up to 1 h after recovery. The level of block was selected because in clinical practice reversal of neuromuscular block with neostigmine is ineffective until 10% recovery of the first twitch or the recurrence of the second twitch of the TOF.11

The binding of the rocuronium molecule by sugammadex results in a rapid decrease of the concentration of rocuronium in plasma, in the biophase, and subsequently at the motor endplate. Rocuronium is then less available to block nicotinic receptors in the neuromuscular junction.12 13 This will promote the liberation of acetylcholine receptors, and in turn muscle activity will reappear.

It should be noted that when interpreting these data that the Rhesus monkey is more sensitive to rocuronium compared with humans (ED90 in man is ~300 µg kg–1; in Rhesus monkey ED90 is ~100 µg kg–1). Given that sugammadex provides reversal of neuromuscular block by reducing the concentration of free rocuronium, the dose of reversal agent should be increased in humans because the ED90 for rocuronium in humans is greater than that in the Rhesus monkey. Moreover, there is another obvious difference between Rhesus monkey and man: spontaneous recovery from 90% blockade is much faster in Rhesus monkey than in man.

In vitro studies in the mouse hemi-diaphragm preparation and in vivo studies in guinea pigs showed that sugammadex is almost inactive against neuromuscular block induced by non-steroidal neuromuscular blocking drugs such as succinylcholine, D-tubocurarine, atracurium and mivacurium compared with rocuronium-induced blockade.5 7 This emphasizes the selectivity of sugammadex in binding rocuronium. The present study confirms and extends these earlier findings by showing that sugammadex at a dose of 1.0 mg kg–1 had no effect on neuromuscular block induced by atracurium or mivacurium. This confirms that the size of the cyclodextrin cavity is too small to accommodate the bulky molecules of mivacurium and atracurium.

Sugammadex has no direct or indirect action on components of cholinergic transmission (cholinesterase, nicotinic receptors or muscarinic receptors), and therefore it is unlikely that muscarinic side-effects will occur.1 4 In-vivo experiments in cat, guinea pig and Rhesus monkey have confirmed the ability of sugammadex to reverse neuromuscular block induced by rocuronium, without significant cardiovascular side-effects.6 7 13 In the present experiments significant cardiovascular changes were not observed with sugammadex, indicating that it appears to be free of the cardiovascular effects associated with cholinesterase inhibition, muscarinic antagonism, or both. This can be most easily interpreted from Figure 1A, which is typical of all other experiments, showing that any effect directly related to the injection of the drug is small compared with other variations within the experiment. Moreover, inter-individual variation for circulatory variables is substantial. Any observed change in HR or blood pressure was smaller than 10% and very small compared with inter-individual variation. These findings were in agreement with previous studies.6 13

Cholinesterase inhibitors are not able to reliably reverse the deeper level of neuromuscular block induced by rocuronium. Sugammadex may be able to reverse such a profound neuromuscular block, owing to its unique mechanism of action, but this remains to be determined. Studies on the reversal of profound neuromuscular block are in progress.

In conclusion, in the model sugammadex is a rapid-acting reversal agent for neuromuscular block induced by rocuronium, and is without cardiovascular side-effects. This study has shown that the reversal activity of sugammadex is specific to neuromuscular block induced by the steroidal agent rocuronium, and that sugammadex has no effect on neuromuscular block induced by the non-steroidal neuromuscular blocking agents mivacurium and atracurium.


   Footnotes
 
{dagger}Declaration of interest. This study was supported by a grant from Organon. A. Bom is employed by Organon and L.H.D.J. Booij is a member of their scientific advisory board. H.D. de Boer is currently working at the Department of Anaesthesiology at the Martini Hospital Groningen, Groningen, The Netherlands. Back


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Bom A, Bradley M, Cameron K, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin-based synthetic host. Angew Chem Int Ed 2002; 41:266–70

2 Hayes AH, Mirakur RK, Breslin DS, Reid JE, McCourt VC. Post operative residual block after intermediate acting neuromuscular blocking drugs. Anaesthesia 2001; 56:312–18[CrossRef][Web of Science][Medline]

3 Booij LHDJ, De Boer HD, Van Egmond J. Reversal agents for nondepolarizing neuromuscular blockade: reasons for and development of a new concept. Sem Anesth Periop Med Pain 2002; 21:92–8

4 Bom A, Cameron K, Clark JK, et al. Chemical chelation as a novel method of NMB reversal—discovery of Org 25969. Eur J Anaesthesiol 2001; 18:A99

5 Millar S and Bom A. Org 25969 causes selective reversal of neuromuscular blockade induced by steroidal NMBs in the mouse hemi-diaphragm preparation. Eur J Anaesthesiol 2001; 18:A100[CrossRef]

6 Hope F and Bom A. Org 25969 reverses rocuronium-induced neuromuscular blockade in the cat without important hemodynamic effects. Eur J Anaesthesiol 2001; 18:A99

7 Mason R and Bom A. Org 25969 causes selective reversal of neuromuscular block induced by steroidal NMBs in anaesthetized guinea pigs. Eur J Anaesthesiol 2001; 18:A100

8 Gijsenberg F, Ramael S, De Bruyn S, Rietbergen H, van Iersel T. Preliminary assessment of Org 25969 as a reversal agent for rocuronium in healthy male volunteers. Anesthesiology 2002; 96:A1008

9 Cameron KS, Fletcher D, Fielding L, Clark JK, Zhang MQ, Orbons LPM. Chemical chelation as a novel method of NMB reversal characterization of the Org 25969 NMB complex. Eur J Anaesthesiol 2001; 18:A99

10 Epemolu O, Mayer I, Hope F, Scullion P, Desmonm P. Liquid chromatography/mass spectrometric bioanalysis of a modified {gamma}-cyclodextrin (Org 25969) and rocuronium bromide (Org 9426) in guinea pig plasma and urine: its application to determine the plasma pharmacokinetics of Org 25969. Rapid Commun Mass Spectrom 2002; 16:1946–52[CrossRef][Web of Science][Medline]

11 Berg H, Roed J, Viby-Mogensen J, et al. Residual neuromuscular block is a risk factor for postoperative pulmonary complications: a post operative, randomized and blinded study of postoperative pulmonary complications after atracurium, vecuronium, pancuronium. Acta Anaesthesiol Scand 1997; 41:1095–103[Web of Science][Medline]

12 Epemolu O, Bom A, Hope F, Mason R, Cert HN. Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969. Anesthesiology 2003; 99:632–7[CrossRef][Web of Science][Medline]

13 Van Egmond J, van de Pol F, Booij L, Bom A. Neuromuscular blockade induced by steroidal NMBs can be rapidly reversed by Org 25969 in the anaesthetized monkey. Eur J Anaesthesiol 2001; 18:A100


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Br J AnaesthHome page
A. Srivastava and J. M. Hunter
Reversal of neuromuscular block
Br. J. Anaesth., July 1, 2009; 103(1): 115 - 129.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
M. Eikermann, S. Zaremba, A. Malhotra, A. S. Jordan, C. Rosow, and N. L. Chamberlin
Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing
Br. J. Anaesth., September 1, 2008; 101(3): 344 - 349.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
D. G. Lambert
Volume 100: basic sciences in the British Journal of Anaesthesia
Br. J. Anaesth., May 1, 2008; 100(5): 595 - 596.
[Full Text] [PDF]

Home page
 Br J AnaesthHome page
A. L. Molina, H. D. de Boer, M. Klimek, M. Heeringa, and J. Klein
Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1)
Br. J. Anaesth., May 1, 2007; 98(5): 624 - 627.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
M. Naguib
Sugammadex: Another Milestone in Clinical Neuromuscular Pharmacology
Anesth. Analg., March 1, 2007; 104(3): 575 - 581.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
H. D. de Boer, J. van Egmond, F. van de Pol, A. Bom, J. J. Driessen, and L. H. D. J. Booij
Time course of action of sugammadex (Org 25969) on rocuronium-induced block in the Rhesus monkey, using a simple model of equilibration of complex formation
Br. J. Anaesth., November 1, 2006; 97(5): 681 - 686.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
J. M. Hunter and E. A. Flockton
The doughnut and the hole: a new pharmacological concept for anaesthetists.
Br. J. Anaesth., August 1, 2006; 97(2): 123 - 126.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
96/4/473    most recent
ael013v1
Right arrow E-Letters: Submit a response to the article
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (25)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by de Boer, H. D.
Right arrow Articles by Booij, L. H. D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Boer, H. D.
Right arrow Articles by Booij, L. H. D. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?