Metocurine iodide의 근육이완 효과와 심혈관계에 미치는 영향

Abstract

[한글]

비탈분극성 근육이완제중 d-tubocurarine은 자율신경절을 차단하고 histamine을 유리시켜 혈압 하강을 일으키는 단점이 있으며 pancuronium, gallamine 등은 미주신경 차단 효과가 있어 빈맥과 혈압 상승을 유발한다. Metocurine은 1935년 King에 의해 처음 합성된d-tubocurarine의 trimethyl 유도체로서 d-tubocurarine에 비하여 심혈관계에 미치는 영향이 적으며 비교적 긴 작용지속시간을 갖고있다고 알려져있으나(Hushes등, 1976) 이에대한 신경근 약리학적 연구는 빈약한 형편이다.

이에 본 연구에서는 metocurine의 혈역학적 영향과 근육 이완에 대한 효과를 알아보기위하여 장시간의 전신 흡입마취가 요구되는 건강한 성인 남녀 환자 109명을 선택하여 thiopental sodium과 succinylcholine 정주후 기관내삽관하여 50% 아산화질소와 enflurane으로 마취 유지하면서 metocurine을 체중 kg당 0.1, 0.2, 0.3mg 투여한 후 근육이완 효과를 ABM Datex를 사용하여 분석하고 혈역학적 변동을 측정하였으며 또한 이를 d-tubocurarine 및 pancuronium등과 비교함으로써 다음과 같은 결과를 얻었다.

1. Enflurane으로 마취유지되어 안정된 상태에서 4회연속자극(train-of-four)중 제1 반응(T1)이 대조치의 80.0±10.64%로 감소하였다.

2. Metocurine 0.1, 0.2, 0.3mg/kg을 투여하였을 때의 근육이완효과의 발현시간은 각각 119.5±40.0, 120.9±61.1, 84.0±61.1 초였으며, 작용지속 시간은 각각 75.1±37.6, 104.9±42.1, 131.0±42.5 분이었다.

3. Metocurine 0.1, 0.2, 0.3mg/kg을 투여한 후 혈역학적 변동을 관찰한결과, 수측기 혈압, 이완기 혈압, 맥박수 모두 대조치와 비교하여 의의있는 차이를 보이지 않았으나, d-tubocurarine 0.3mg/kg 투여로는 수측기 혈압이 대조치 116.6±15.7mmHg에서 2분후 99.0±10.9mmHg로 의의있게 하강하였으며 pancuronium 0.O6mg/kg을 투여하였을 때는 수축기 혈압이 증가하는 경향을 보였으나 대조치와 의의있는 차이는 없었다.

4. Metocurine과 기타 비탈분극성 근육이완제들을 비교하였을 때 약물투여 1분 및 2분후에 수측기 혈압이 pancuronium 0.06mg/kg(127.8±16.0 및 125.3±13.1mmHg)에서 metocurine 0.2mg/kg(107.2±11.7 및 110.2±14.3mmHg)보다 높았다(p<0.05).

이상의 결과로 보아 metocurine은 작용발현시간이 빠르며 작용지속시간은 긴 비탈분극성 근육이완제로서 d-tubocurarine이나 pancuronium 등과 같은 다른 비탈분극성 근육이완제들에 비하여 혈역학적 변동을 적게 일으키므로 심혈관계 질환을 가진 환자의 장시간 마취시 유용하게 사용될 수 있을 것으로 사료된다.

[영문]

Among nondepolarizing neuromuscular blocking agents, d-tubocurarine may cause blood pressure reduction due to ganglionic blockade and histamine release, while pancuronium and gallamine are associated with vagal blockade and heart rate acceleration.

Metocurine, as a trimethylated derivative of d-tubocurarine synthesized by King in 1935, is known to have relatively long duration of action and produces little change in cardiovascular system. Despite its relative lack of cardiovascular effects, the accumulation of data with regard to human neuromuscular pharmacology and the clinical use has been scant, and the drug is probably not frequently used by anesthesiologists at present. Therefore this study was performed to observe the effect of metocurine on neuromuscular blocking action and cardiovascular response.

One hundred and nine adult patients of either sex were anesthetized with thiopental sodium and 50% nitrous oxide with 1.5-2.5% enflurane. For evaluation of neuromuscular blocking effect of metocurine, train-of-four stimulation(2.0 Hz for 2

seconds) was applied at the wrist along the ulnar nerve distribution and the response was measured via ABM Datex. Systolic, diastolic blood pressure and heart rate were recorded continuously after administration of metocurine, d-tubocurarine

or pancuronium. All date were analized by ANOVA, Scheffe test.

The results are follows;

1. The mean onset times of metocurine 0.1, 0.2, 0.3mg/kg groups were 119.5± 40.0, 120.9초±61.1, 84.0±61.1 seconds and the mean durations were 75.1±37.6, 104.9±42.1, 131.0±42.5 minutes respectively.

2. Single-bolus dose of metocurine 0.1, 0.2, and 0.3mg/kg did not causes significant cardiovascular changes from the control values, but d-tubocurarine 0.3mg/kg decreased mean systolie blood pressure significant from 116.6±15.7 to 99.0±10.9mmHg 2 minutes after injection.

3. Systolic blood pressures of metocurine 0.2mg/kg(107.2±11.7mmHg) and d-tubocurarine 0.3mg/kg(100.4±12.9mmHg) were significantly different from that of pancuronium 0.06mg/kg(127.8±16.OmmHg) after 1 minute, and 2 minutes metocurine after injection, systolic blond pressure of metocurine 0.2mg/kg(110.2±14.3mmHg) and d-tubocurarine 0.3mg/kg(99.0±10.9mmHg) were different from that of pancuronium

0.06mg/kg(125.3±13.1mmHg). Five minutes after injection, systolic pressure of d-tubocurarine 0.3mg/kg group(101.1±10.2mmHg) was significantly different from that of pancuronium 0.06mg/kg group(118.7±11.OmmHg).

4. Diastolic blood pressure of d-tubocurarine 0.3mg/kg(63.4±12.9 mmHg) was significantly different from that of pancuronium 0.06mg/kg(84.2±13.3mmHg) after 1 minute, and 2 minutes after injection, diastolic blood pressure of d-tubocurarine 0.3mg/kg(65.4±11.3mmHg) was different from that of pancuronium 0.06mg/kg(83.1±11.6mmHg). There was no significant difference among the groups with respect to heart rate.

In summary, metocurine has relatively rapid onset and long duration of action, and used in a dose sufficient to provide surgical relaxation, it produces little change in cardiovascular system in contrast to d-tubocurarine or pancuronium. It is

therefore suggested that metocurine may be recommended as a muscle relaxant for patients having cardiovascular disease.