신부전 환자에서 Vecuronium의 근이완작용에 대한 Neostigmine의 길항효과

Abstract

[한글]

항콜린에스테레이스제제들은 간에서 주로 대사되나, 그 배설에 있어서는 신장에 의존한다. Cronnelly등(1980년)과 Morris등(1981년)은 정상인에서는 pyridostigmine, edrophonium 및

neostigmine이 각각 75.70 및 50%가 신장을 통하여 배설된다고 하였다. 한편 신부전이 있으면 neostigmine과 pyridostigmine의 혈중 제거율이 감소되고 배설 반감기가 지연된다는 것은 약동학적으로 이미 밝혀진 사실이나 (Cronnelly등, 1979 및 1980) 이것이 약력학적으로 어느 정도 증감 효과를 가져오는지는 밝혀진 바 없다.

본 연구는 neostigmine의 길항효과를 규명하기 위하여, 신기능이 정상인 정형외과적 수술 혹은 신기능 부전이 있어 신장이식술을 받기 위해 전신마취가 요구되는 성인 남녀 환자 각각 18명씩을 Ⅰ 및 Ⅱ군으로 하여 vecuronium의 지속적 점적주입하에 척골신경 주행

표피에 supramximal (??)를 가하고 flexor carpi ulnaris electromyography를 얻음으로써 neostigmine의 용량 - 반응 곡선, 발현 시간, 작용 지속 시간 및 길항 효과 정도를 비교하여 다음과 같은 결론을 얻었다.

1. Neostigmine투여 전 15%내외의 연축(twitch height)을 유지하기 위한 vecuronium의 점적 주입 속도는 양군간에나 neostigmine 용량간에 유의한 차이가 없었다.

2. 세가지 서로 다른 neostigmine 용량을 투여하기 직전, 연축의 평균치는 11.7에서 13.7%이었다.

3. Neostigmine 정주후의 작용 발현 시간, 최대 연축 반응 및 최대 가역 효과는 양군간에 유의한 차이가 없었다.

4. Neostigmine의 작용 지속 시간은 ED^^20의 1/2용량에서만 Ⅰ군에 비해 Ⅱ군에서 의의있게 연장되었으며, 다른 용량에서는 유의한 차이를 보이지 않았다.

이상의 결과로 보아 vecuronium의 근이완 작용에 대한 neostigmine의 길항효과는 신부전 환자에서 연장될 가능성이 있으며, 이는 근이완제 배설에 제한을 갖고 있는 신부전 환자에서 vecuronium 사용후 가역시 이점이 될수가 있다고 사료된다.

The Antagonism Effects of Neostigmine on Vecuronium -induced Neuromuscular Blockade

in the Renal Failure Patients

Jeong Seon Han

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Professor Kwang Won Park, M.D.)

The elimination of most anticholinesterases depends on the kidney, even if the

main organ for their metabolism is the liver.

Renal excretion of pyridostigmine, edrophonium and neostigmine accounts for 75%,

70% and 50%, respectively. (Cronnelly et al, 1980: Morris et al. 1981)

In the absence of renal function, the serum half-life of neostigmine is

prolonged, its plasma clearance is decreased (Cronnelly et al, 1979 & 1980).

However, the pharmacodynamics of neostigmine have not been determined in renal

failure.

This study was designed to compare the neostigmine dynamics in 18 patients with

normal renal function to that in 18 patients with renal failure(Group Ⅰ & Ⅱ,

respectively).

Using the flexor carpi ulnaris EMG via ulnar nerve stimulation with

Train-Of-Four(TOF) under the constant infusion of vecuronium to produce about 85% -

twitch depression, the responses of neostigmine with three different doses were

obtained.

The results are follows;

1. The constant infusion rates of vecuronium to maintain about 15%-twitch height

prior to the administration of neostigmine showed no significant difference between

two groups.

2. Immediately prior to each dose of neostigmine, the mean values of twitch

heights were 11.7 to 13.7%.

3. There was no significant difference in the onset time, maximum twitch

responses and antagonism effects between trio groups in respect to each same dose

of neostigmine.

4. The duration of neostigmine with the half of ED^^20 only in Group Ⅱ was

significantly longer than that in Group Ⅰ, even if the durations with the other

doses in Group Ⅱ were not significantly longer than these in Group Ⅰ.

These results suggest that the reversal effect of neostigmine to

vecuronium-induced blockade may be outlasted in patients with renal failure and the

prolongation of neostigmine effect may render saute benefits to reverse the

relaxants which have the limitation of its elimination in this patients.

[영문]

The elimination of most anticholinesterases depends on the kidney, even if the main organ for their metabolism is the liver.

Renal excretion of pyridostigmine, edrophonium and neostigmine accounts for 75%, 70% and 50%, respectively. (Cronnelly et al, 1980: Morris et al. 1981)

In the absence of renal function, the serum half-life of neostigmine is prolonged, its plasma clearance is decreased (Cronnelly et al, 1979 & 1980).

However, the pharmacodynamics of neostigmine have not been determined in renal failure.

This study was designed to compare the neostigmine dynamics in 18 patients with normal renal function to that in 18 patients with renal failure(Group Ⅰ & Ⅱ, respectively).

Using the flexor carpi ulnaris EMG via ulnar nerve stimulation with Train-Of-Four(TOF) under the constant infusion of vecuronium to produce about 85% - twitch depression, the responses of neostigmine with three different doses were obtained.

The results are follows;

1. The constant infusion rates of vecuronium to maintain about 15%-twitch height prior to the administration of neostigmine showed no significant difference between two groups.

2. Immediately prior to each dose of neostigmine, the mean values of twitch heights were 11.7 to 13.7%.

3. There was no significant difference in the onset time, maximum twitch responses and antagonism effects between trio groups in respect to each same dose of neostigmine.

4. The duration of neostigmine with the half of ED^^20 only in Group Ⅱ was significantly longer than that in Group Ⅰ, even if the durations with the other doses in Group Ⅱ were not significantly longer than these in Group Ⅰ.

These results suggest that the reversal effect of neostigmine to vecuronium-induced blockade may be outlasted in patients with renal failure and the prolongation of neostigmine effect may render saute benefits to reverse the relaxants which have the limitation of its elimination in this patients.