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British Journal of Anaesthesia 97 (2): 1603 (2006)

doi:10.1093/bja/ael142 Advance Access publication June 17, 2006

Neostigmine-induced reversal of vecuronium in normal weight,overweight and obese female patients

T. Suzuki1*, G. Masaki

2and S. Ogawa

1

1Department of Anaesthesiology, Surugadai Nihon University Hospital, 1-8-13, Kanda-Surugadai,

Chiyoda-Ku, Tokyo, 101-8309, Japan. 2Department of Anaesthesia, Tokyo Rinkai Hospital, Tokyo, Japan

*Corresponding author: 3-24-3, Asagaya-Kita, Suginami-Ku, Tokyo 166-0001, Japan.

E-mail: [email protected]

Background. The purpose of this study was to compare neostigmine-induced reversal of

vecuronium in normal weight, overweight and obese female patients.

Methods. In total, 15 each of normal weight (18.5


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None of the patients had neuromuscular, hepatic and renal

disorders, or were taking any drug known to interact with

neuromuscular blocking agents.

Patients were grouped according to their BMI

[BMI=weight (kg)/height2 (m)]; the normal weight group

(18.5


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hydrophilic and is therefore distributed mainly in lean tis-

sues. In obese individuals, adipose tissue accounts for the

most part of the excess of body weight. Therefore, if vecuro-

nium based on the patients RBW is administered, it should

lead to a relative overdosing for the lean body mass1 2 and a

higher serum concentration in obese patients compared with

normal weight patients.2 Faster onset and prolonged dura-

tion of action of vecuronium-induced block observed in the

overweight and the obese groups are consistent with a rel-

ative excess of the dosing based on the patients RBW. The

explanation of relative overdosing is additionally supported

by the fact that duration of action of non-depolarizing neu-romuscular block in obese patients is similar to that in nor-

mal weight patients when the obese are dosed on the basis of

the IBW.9 10 The obese patients in our study received

1.5 times doses of the IBW-based vecuronium. Pharmacoki-

netic and pharmacodynamic studies by Fisher and

colleagues3 4 revealed that increasing the dose of vecuro-

nium significantly increased the spontaneous recovery from

neuromuscular block because of its cumulative effect. Fahey

and colleagues5 found that the average time at which twitch

tension recovered spontaneously from 25 to 75% of control

increased from 8 to 21 min as the vecuronium dose was

increased from 0.07 to 0.14 mg kg1. Reversal time is deter-

mined by two processes which include direct antagonism by

anticholinesterase and spontaneous recovery (elimination of

neuromuscular blocking agent from the plasma).11 Reversal

effect of neostigmine usually appears within about 12 min

and the maximum effect occurs in about 610 min.11 12 It is

therefore considered that the early facilitated recovery to a

TOF ratio of 0.5 or 0.7 observed in overweight and obese

patients may be attributable to competitive antagonism to

vecuronium at the neuromuscular junction because of

increased acetylcholine concentration. Following peak

antagonistic effect of neostigmine, the further recovery of

TOF ratios from 0.7 to 0.9 in obese patients is slow like a

plateau phase that may represent a balance between spon-taneous recovery from overdosed vecuronium-induced neu-

romuscular block and the waning reversal effect of

neostigmine. We did not evaluate the speed of spontaneous

recovery without reversal in this study. Based on our pre-

vious study,6 the average time for spontaneous recovery of a

TOF ratio from 0.7 to 0.9 was about 15 min (Suzuki T,

Fukano N, Kitajma O, Saeki S, Ogawa S; unpublished

data). It is therefore anticipated that overdosed vecuronium

should prolong more the spontaneous recovery time. It is

likely that total reversal time may also be increased when

spontaneous recovery time is considerably prolonged by an

excess dose of vecuronium in obese patients.

In contrast to vecuronium, it is reported that

atracurium-induced neuromuscular block is rapidly antag-

onized by neostigmine even if atracurium is administered in

obese patients based on RBW.13 As the dose of atracurium is

increased, the duration of action should also be increased.4

However, the spontaneous recovery time is similar follow-

ing doses that ranged from 0.2 to 0.6 mg kg1.14 Therefore,

the reversibility of atracurium with neostigmine may not be

influenced by obesity.

It is known that the depth of block influences itsreversibility.15 In general, neostigmine 0.04 mg kg1 should

be adequate for prompt reversal of vecuronium-induced

block if neostigmine is administered after 25% recovery

of twitch.15 16 Increasing the neostigmine dose from 0.04

to 0.08 mg kg1 could not accelerate the recovery of TOF

ratios.15 It is therefore likely that high-dose neostigmine

cannot facilitate the late recovery from vecuronium-induced

neuromuscular block in obese patients. The ceiling is sup-

ported by the fact that human acetylcholinesterase activities

following neostigmine 0.036 and 0.071 mg kg1 similarly

decrease to the lowest values, 11.3 and 11.4% of baseline,

respectively within 2 min.17 Whereas, it is also accepted that

high doses of neostigmine can antagonize neuromuscular

block more rapidly than smaller doses.18 Therefore, the

maximum dose of neostigmine (e.g. 0.070.08 mg kg1

11 15 19 20) may be recommended for reversal of overdosing

vecuronium in obese patients. Further investigations may be

warranted with regard to the dosereversal effect relation-

ship of neostigmine in obese patients.

In conclusion, total reversal time following neostigmine

0.04 mg kg1 is longer in overweight and obese female

patients compared with normal weight patients when

vecuronium 0.1 mg kg1 is administered on the basis of

their RBW.

AcknowledgementFinancial support: institutional funding.

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Table 3 Neostigmine-induced recovery in theTOF ratios.Dataare presentedas mean (SD) (range). Allthe times aremeasuredfrom anadministrationof neostigmine.

*P


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Effect of neostigmine in obese patients

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