31．易使宁

出处：按学科分类—医药、卫生 军事医学科学出版社《临床常用进口药物手册》第166页（16114字）

【中文释文】：

(安氟醚)

〔概述〕

易使宁(安氟醚)是一种稳定的不燃烧的吸入麻醉药物。它是2-氯-1，1，2-三氟乙基二氟甲基醚。

化合物的一些物理常数是：

分子量 184．5

101．325kPa下沸点 55．5℃～57．5℃

屈光指数n 1．3028

25°／25℃比重 1．517

蒸气压(kPa)⁽¹⁾ 20℃ 23．20 25℃ 28．93 36℃ 46．00

37℃时的分配系数

水／气 0．82

血／气 1．91

油／气 98．5

25℃时对橡胶和塑料的分配系数

导电橡胶 74．0

丁基橡胶 90．0

聚氯乙烯 120．0

聚乙烯 ～2．0

气相色谱纯度 >99．9%

在空气中的可燃性 不可燃

在氧气中的可燃性 不可燃

(均在22～45℃及99．06 kPa压力下完全浓缩至饱和)

MAC(最低肺泡浓度)

人类，与纯氧 1．68

人类，与70%氧化亚氮 0．56(估算)

易使宁是一种不加化学稳定剂的无色稳定的液体。具令人愉快的醚嗅。在22～45℃气温及大气压下，在其完全麻醉的浓度范围内，它的蒸气与氧气、空气或氧-氧化亚氮混合均不燃烧不爆炸。它的样品贮于无色透明玻璃容器内，置于非直射的阳光下5年之久，以及暴露于2安培115伏60周的长波紫外光30h，以气相色谱分析其成分并无改变。易使宁置于强碱，一当量的甲氧基甲醇钠溶液6个月以上并无碱消耗，说明它在强碱中的稳定性。同样，易使宁和氧气，水蒸气混合在40℃持续循环通过碱石灰达19h之久，亦无分解。

易使宁不侵害铝、锡、黄铜、铁或青铜。

〔作用〕

易使宁是一种全身麻醉剂药。它能提供迅速平稳的诱导和复苏。使用易使宁时很少或没有刺激唾液及支气管的分泌。抑制咽喉反射使气管插管术易于施行。

像其他吸入麻醉剂一样，随着麻醉加深，潮气量减少。然而对比其他麻醉剂，呼吸率基本保持不变或轻度减慢。与其他卤化药物不同，易使宁引起叹息样反应。

麻醉诱导期间，血压有些下降，但因手术的刺激而恢复接近正常。随着麻醉深度的增加，血压相应也降低。心率保持不变，并无明显心动过缓。心电监护指示心律保持稳定。动脉二氧化碳张力提高不影响心律。易使宁能提高狗的心肌对肾上腺素及去甲肾上腺素的敏感性，易使宁与这两种药物伍用时可导致心律不齐。人的有效的数据显示，以等于或稀于1∶100000的肾上腺素皮下注射，10min内剂量为10ml，1h内不能多于30ml。

易使宁不影响血液凝固，也不改变血象和血容量，本品对血化学也无影响。

在麻醉维持期间，肌肉松弛能满足腹部手术的要求。若需更加松弛，可以使用少量的肌肉松弛剂。所有常用的肌肉松弛剂均与易使宁相容；然而，易使宁能明显增强非去极化肌肉松弛剂的作用，因此，其用量应该是接近常用剂量的一半。

新斯的明不能抵消易使宁的肌肉松弛作用。在人类，易使宁多少有些分解代谢，业已证明其代谢远低于其他卤化剂。尿氟测定显示，本品的分解代谢仅为其他常用的卤化剂的10%～25%。这是因为易使宁分子的化学稳定性，以及其血气分配系数低。

〔适应证〕

易使宁适用于成人和儿童作全身麻醉的诱导与维持。也适用于剖腹产，但未有足够数据支持本品在其他产科手术时应用。

〔禁忌证〕

以往用本品或其他卤素麻醉剂后发生过黄疸或不明原因发热的病人不宜使用本品，因有肝坏死的可能性。不能排除易使宁和其他卤素麻醉剂有交叉过敏。

〔注意事项〕

易使宁对脑电图的改变正如所有吸入麻醉剂一样。使用超过推荐剂量的易使宁的麻醉深度可以产生以电压增高，频率增快，尖穹形的复波，间隔有电静止期为特征的脑电图的改变。这种活跃的脑电活动往往在全身肌肉抽搐或不同的肌肉群“抽动”的发作期间出现，它能自行减轻，或通过减低麻醉浓度而抑制之。这种脑电图的改变与麻醉太深有关，并且可以被过度换气加重，并受动脉二氧化碳张力降低的影响。这种脑电图变化有助于警惕麻醉过深。

通过减少麻醉药剂量和／或辅助呼吸率来重新调整麻醉过程能终止上述脑电活动。一次少量的肌肉松弛剂能立刻控制这种活动。对健康的志愿者作脑血流和代谢研究，在出现这种脑电活动期间没有脑缺氧征象，复苏以后亦无合并症。非去极化肌肉松弛剂与易使宁有协同作用，故此应该把肌肉松弛剂的用量减至常用量的一半左右。对某些药品有依赖的病人，应小心使用易使宁，病人皮层兴奋性增高，对该药品更为敏感。

在大鼠和兔作过生殖研究，并无影响动物胎儿。尚不知道这些研究与人的相关性。因对妊娠妇女使用本品尚乏足够经验，本品对妊娠妇女的安全性尚未明确。

由于麻醉深度极易迅速变化，应该使用具有一定精确度的能控制输出浓度的蒸发器。

已知某些病人使用易使宁时血糖浓度中度增加，此点在糖尿病病人应该加以考虑。

有报告使用卤素类麻醉剂后发生肝功能障碍、黄疸或严重的肝坏死。对本品过敏的病人亦可出现这些反应。肝硬化或其他涉及肝功能障碍的疾病，包括有过病毒性肝炎的历史者均应选用其他非卤化类药物。

〔副作用〕

过深的麻醉可以导致局限性肌肉颤搐(见注意事项)。低血压和呼吸抑制可发生于诱导期间，而经手术的刺激回复正常。

已知复苏期发生恶心与呕吐，但少于大部分其他卤素化的麻醉剂。偶然发生寒颤或呃逆。罕见暂时性心律不齐。

〔药物配伍〕

易使宁能与所有常用的辅助麻醉药物配伍。

〔用法与剂量〕

通过专为易使宁制造及标定刻定的穿流型蒸发器给药，亦可使用其他蒸发器，但应重新按易使宁的特性重新标定刻度(使用附表所述的列线图)

〔术前用药〕

根据具体病人需要来选择，同时应考虑到易使宁轻度刺激分泌要保持心率衡定。选用抗胆碱类药物亦为合理。

〔诱导〕

诱导可用易使宁为主配合氧气或氧与氧化亚氮的混合物。亦可使用催眠剂量的短效巴比妥类药物诱导至意识丧失，然后用易使宁的混合气体。

建议在诱导时，易使宁的吸入浓度由0．5%开始逐步升高，每数次呼吸后增加0．5%，直至到达外科麻醉期为止。这时的吸入浓度应该不超过4．0%

〔维持〕

用0．5%～2．0%的易使宁浓度能维持外科手术要求的麻醉深度。用这种剂量已经使肌肉松弛程度可达到腹部手术的要求。如需进一步松弛，可用补充剂量的肌肉松弛剂。防止换气不足或换气过度，通气应保持动脉血中二氧化碳张力在4．67～6．00kPa范围内，以免发生中枢神经系统兴奋。在没有其他合并症时，维持期间血压与易使宁的浓度相反。血压过度降低(排除了低血容量的关系)可能与麻醉过深有关，此时应该用减轻麻醉来矫正。

〔复苏〕

外科手术接近完成时，应该把易使宁的浓度减至0．5%，开始关合皮肤时停止吸入。

停止所有麻醉药物以后，应该用100%氧气吹洗病人的呼吸系统几次，直到病人完全复苏为止。

〔过量〕

一旦发生过量，应该采取下列步骤：

停止给药，清理气道，采用辅助呼吸或控制呼吸，必要时使用纯氧。

〔包装〕

易使宁(安氟醚)以125ml、250ml及280ml琥珀色瓶装。

无添加剂或稳定剂

〔生产厂家〕

意大利ABBOTT

(附本品别名：恩氟烷，Enflurane，氟醚麻醉剂，Enthrene lnheltran)

【外文释文】：

Enflurane

Description

Ethrane(enflurane)is a stable，nonflammable inhalation anesthetic agent．It is 2-chloro-1，1，2-trifluoroethyl difluoromethyl ether．

Some physical constants of the compound are：

Molecular weight 184．5

Boiling point 760mm Hg 55．5-57．5℃

Refractive index n 1．3028

Specific gravity 25°／25℃ 1．517

Vapor pressure in mm Hg⁽²⁾ 20℃ 174．5 25℃ 217．7 36℃ 345．2

Partition coefficients at 37℃

water／gas 0．82

blood／gas 1．91

oil／gas 98．5

Partition coefficients at 25℃-rubber and plastic

conductive rubber 74．0

butyl rubber 90．0

polyvinyl chloride 1 20．0

polyethylene -2．0

Purity by gas chromatography >99．9%

Flammability in air None

Flammability in oxygen None

(Entire concentration range to saturation

between 22-45℃ and 743mm Hg pressure)

M．A．C．(minimum alveolar concentration) -

man with pure oxygen 1．68

man with 70%nitrous oxide 0．56(est．)

Ethrane is a colorless，stable liquid without added chemical stabilizers．Ethrane has a pleasant and ethereal odor．Its vapors，mixed with oxygen，air or oxygen-nitrous oxide mixtures，are nonexplosive and nonflammable over the entire anesthetic concentration range at atmospheric pressure and temperatures between 22-45℃．Storage of samples in indirect sunlight，in clear，colorless glass for a five-year period，as well as direct exposure for 30 hours to a 2 amp，115 V，60 cycle long-wave U．V．light produced no changes in composition detectable by gas chromatography．Ethrane in one normal sodium methoxide-methanol solution，a strong base，for over six months consumed none of the alkali，indicative of strong base stability．Similarly，ethrane does not decompose when circulated with oxygen and water vapor for 19 hours through soda lime maintained at 40℃．

Ethrane does not attack aluminum，tin，brass，iron or copper．

Actions

Ethrane is a general anesthetic．It provides rapid and smooth induction and recovery．Minimal or no stimulation of salivary or bronchial secretion is related to the use of ethrane．The pharyngeal and laryngeal reflexes are readily obtunded，simplifying tracheal intubation．

As with other inhalation agents，the tidal volume diminishes with increasing depth of anesthesia．However，in contrast to other agents，respiratory rate remains essentially constant or decreases only slightly．

Ethrane，unlike other halogenated agents，produces a sigh response．

There is a decrease in blood pressure during induction of anesthesia，but it returns to near normal values with surgical stimulation．Progressive increases in depth of anesthesia produce corresponding decreases in blood pressure．Heart rate remains constant without significant evidence of bradycardia．Electrocardiographic monitoring indicates that cardiac rhythm remains stable．Elevation of arterial carbon dioxide tension does not affect cardiac rhythm．In dogs ethrane sensitizes the myocardium to adrenalin(epinephrine)and noradrenalin(nor-epinephrine)，and the use of these two substances concomitant with ethrane may induce arrhythmias．Available data in humans indicate that subcutaneous injections of adrenalin(epinephrine)may be safely administered in concentrations of 1∶100 000 or less at a dose of 10 ml in any given 10 minutes period and not more than 30 ml per hour．

Ethrane does not affect blood coagulation or alter the hemogram．Blood volume is not altered by ethrane and there have been no significant effects on blood chemistry attributable to this agent．

Muscle relaxation is adequate for intra-abdominal operations，with maintenance levels of anesthesia．Should greater relaxation be desired，minimal doses of muscle relaxants may be used．All commonly used muscle relaxants are compatible with ethrane；however，non-depolarizing muscle relaxants are markedly potentiated by ethrane and should be given in approximately one-half their usual dosage．

Neostigmine does not reverse the muscle-relaxing effect of ethrane．The extent to which ethrane is metabolized in humans has been demonstrated to be significantly lower than that of other halogenated agents．Measurement of urinary fluorides indicates a degree of metabolic degradation only 10%-25%that of other currently used halogenated anesthetics．This has been attributed to the chemical stability of the ethrane molecule and to its relatively low blood／gas partition coefficient．

Indications

Ethrane is indicated for induction and maintenance of general anesthesia in adults as well as in children．It is also indicated for use in Caesarean section although available data do not support its use in other obstetrical procedures．

Contraindications

Ethrane should not be used when previous exposure to this agent or to other halogenated anesthetics has been followed by jaundice and／or unexplained fever because of the possibility of hepatic necrosis．Cross sensitivity between ethrane and other halogenated anesthetics cannot be excluded．

Precautions

Ethrane produces changes in the EEG patterns like all inhalation anesthetic agents．Depth of anesthesia with ethrane beyond the recommended dosage may produce a change in the electroencephalogram characterized by high voltage，fast frequency，progressing through spike-dome complexes，interspaced with periods of electrical silence．This pattern has on occasion been associated with motor activity which，when encountered，generally consists of twitching or“jerks”of various muscle groups；it is self-limiting and can be terminated by lowering the anesthetic concentration．This electroencephalographic pattern associated with deep anesthesia is exacerbated by hyperventilation and consequent low arterial carbon dioxide tension．The pattern ser ves as a warning that depth of anesthesia is excessive．

Re-adjustment of the anesthesia procedure，consisting of a reduction of dose and／or assisted-respiration rate，produces a cessation of the motor activity．Immediate control may be effected by the administration of a single small dose of muscle relaxant．Cerebral blood flow and metabolism studies in normal volunteers during the changes in the EEG patterns show no evidence of cerebral hypoxia，and recovery appears to be uncomplicated．The action of nondepolarizing relaxants is augmented by ethrane，so approximately one half the usual dose of those drugs should be used．Ethrane should be used with caution in patients who by virtue ofmedical or drug history may be considered more susceptible to cortical stimulation produced by this drug．

Reproduction studies have been performed in rats and rabbits，and there is no evidence of harm to the animal fetus．The relevance of these studies to the human is not known．Since there is no adequate experience in pregnant women who have received the drug，safety in pregnancy has not been established．

Since levels of anesthesia may be altered easily and rapidly，only vaporizers which deliver predictable output with reasonable accuracy should be used．

A mild increase in serum glucose concentration has been observed in some cases and this should be considered when ethrane is administered to diabetic patients．

Hepatic dysfunction，jaundice and fatal hepatic necrosis have been reported following anesthesia with halogenated anesthetics．Such reactions appear to represent a sensitivity reaction to the anesthetics．Cirrhosis or other abnormalities involving liver dysfunction including a history of viral hepatitis，may be a basis for selecting an anesthetic other than a halogenated agent．

Adverse reactions

Excessive depth of anesthesia may produce localized muscle twitching(see Precautions)．Hypotension and respiratory depression have been observed during induction，with a return to normal levels under surgical stimulation．

Incidence of nausea and vomiting in the recovery period have been reported to be less than with most other inhalation agents．Shivering or hiccups may occur occasionally．

Transient arrhythmias have also been observed in rare instances．

Drug compatibility

Ethrane is compatible with all ancillary drugs normally used in anesthesia．

Dosage and administration

Ethrane may be administered from a flow-through type vaporizer manufactured and specifically calibrated for ethrane．If calibration of other vaporizers is made(by use of attched nomograph)，their use for ethrane administration is acceptable．

Premedication

Premedication should be selected according to the need of the individual patient，taking into account that secretions are mildly stimulated by ethrane and the heart rate remains constant．The use of anticholinergic drugs is a matter of choice．

Induction

Induction may be achieved using ethrane and oxygen alone or in combination with oxygen-nitrous oxide mixtures．Alternately，a hypnotic dose of a shortacting barbiturate could be used to induce unconsciousness，followed by the ethrane mixture．

It is recommended that ethrane induction be initiated at a concentration of 0．5%and gradually increased by 0．5%increments every few breaths until surgical anesthesia is achieved．This level should be less than 4．0%．

Maintenance

Surgical levels of anesthesia may be maintained with 0．5%-2．0%concentrations of ethrane．With this dosage muscle relaxation is adequate for intra-abdominal surgery．If added relaxation is required，supplemental doses of muscle relaxants may be used．Ventilation to maintain the tension of carbon dioxide in arterial blood in the 35-45 mm Hg range is preferred to hyper or hypoventilation in order to minimize possible CNS excitation．The level of blood pressure during maintenance is an inverse function of etharane concentration in the absence of other complicating problems．Excessive blood pressure decreases(unless related to hypovolemia)may be due to depth of anesthesia and in such instances should be corrected by lightening the level of anesthesia．

Recovery

The concentration of ethrane may be reduced to 0．5%near the end of the surgical procedure or discontinued at the beginning of skin closure．

When all anesthetic agents are discontinued，the patient’s respiratory system should be flushed several times with 100%oxygen until recovery is complete．

Overdosage

In the event of overdosage，the following action should be taken：

Stop drug administration，establish that the airway is clear and initiate assisted or controlled ventilation with pure oxygen as circumstances dictate．

How supplied

Ethrane(enflurane)is supplied in 125 ml，250 ml and 280 ml amber bottles．

No additives or stabilizers are present．

Manufacturer

ABBOTT S．P．A．Italy