肌松藥的臨床應用學案

1、肌松藥的臨床應用學案Part 1 The Rational Use of Muscle Relaxants 第一節(jié) 肌松藥的合理應用 Muscle relaxants can lead to skeletal muscle relaxation. Their principal pharmacologic effect is to interrupt transmission of synaptic signaling at the neuromuscular junction (NMJ) by antagonism of the nicotinic acetylcholine recepto

2、r (AChR) .Main Goals of Use一.應用肌松藥的目的 1.As the very important adjuncts for general anesthesia,muscle relaxants can provide adequate paralysis needed tracheal intubation, or relaxation for surgery. 肌松藥是全麻的重要輔助用藥，用于全麻誘導時氣管插管或維持全麻時肌松，避免深麻醉帶來的危害。 2. To be used in the critical patients who are receiving

3、mechanical ventilation care. 危重病人機械通氣時用肌松藥來消除自主呼吸對呼吸機的拮抗。 3.To be used in the treatment of spasmodic diseases.用于治療痙攣性疾病。 4. To be used in the electric shock treatment.在電休克治療時用其控制肌張力和減少肌強烈收縮引起的并發(fā)癥。 Fundamental Principles of Use二. 應用肌松藥的基本原則 1. Muscle relaxants should be viewed as adjuncts,not as subs

4、titutes for anesthesia. Perfect general anesthesia should include:analgesia, amnesia and relaxation.肌松藥不能代替麻醉藥，應有完善的鎮(zhèn)痛。 2. Strict control of airway. 應有嚴密的呼吸管理。 Muscle relaxants can influence the respiration ability of patients to maintain adequate ventilation, so strict control measures of airway mu

5、st be given. 3. Proper muscle relaxants and appropriate doses (minimal doses). 選擇合適的肌松藥和最小有效劑量。 4. To avoid inappropriate combined administration. 避免不恰當?shù)穆?lián)合用藥。 5. To utilize the synergistic action between muscle relaxants and anesthetics properly. 合理利用麻醉藥與肌松藥的協(xié)同作用。 6. Proper monitoring of neuromuscul

6、ar function.最好能夠對肌松藥的作用進行監(jiān)測。 Part 2 Use of Muscle Relaxants During Anesthesia 第二節(jié)肌松藥在麻醉期間的應用 There are two important safety issues in practice with muscle relaxants: cardiovascular side effects and adequacy of recovery to normal neuromuscular function. Of the two, the latter is by far the more impor

7、tant. To avoid prolonged residual paralysis or inadequate antagonism of residual blockade or both, the main goal should be to use the lowest possible dose that will provide adequate relaxation for surgery.For Tracheal Intubation一用于氣管插管 To provide the very deep paralysis needed for tracheal intubatio

8、n, the initial dose in the range two to three times the ED95 is usually given to facilitate the maneuver within one to three minutes, depending on the choice and dose of muscle relaxant. Succinylcholine is still preferred for this critical maneuver. Now, however, there are suitable alternatives amon

9、g the nondepolarizing relaxants but as yet no replacement For Maintenance of relaxation 二. 肌松維持 Maintenance of relaxation by continuous infusion of intermediate and short-acting drugs can be performed and is useful to keep relaxation smooth and to rapidly adjust the depth of relaxation to surgical n

10、eeds.Dosage for Priming三. 預給量 A small subparalysis dose of nondepolarizer be given 2 to 4 minutes before giving a second large dose for tracheal intubation. This procedure, termed priming, has been shown to accelerate the onset of block of most nondepolarizing relaxants by about 30 to 60 seconds, wi

11、th the result that intubation can be performed within about 90 seconds following the second dose. Interaction of Succinylcholine with Nondepolarizing muscle relaxants 四. 琥珀膽堿與非去極化肌松藥的相互作用 This Interaction is very complex, depending on whether Succinylcholine is administered before or after the nonde

12、polarizer. 1.Succinylcholine is commonly given to facilitate intubation, and then a nondepolarizing relaxant is administered. Succinylcholine given first enhance the depth of block induced by a subsequent dose of nondepolarizing relaxant.用 Succinylcholine 誘導，用非去極化肌松藥維持，后者肌松作用被增強。 2. A small dose of

13、nondepolarizing relaxant is commonly given before administration of Succinylcholine to prevent some of the adverse effects of the later. The depth of block induced by Succinylcholine can be reduced. 為減少Succinylcholine的副作用，用Succinylcholine誘導前靜注小劑量非去極化肌松藥，此時琥珀膽堿作用被削弱，必須增加劑量。 3. A nondepolarizing relax

14、ant can be injected for prolonged relaxation, and then the short-acting Succinylcholine can be given to facilitate closure of the peritoneum. It maybe lead to severe residual paralysis. 術中長時間用非去極化肌松藥維持，手術后期如為了關閉腹膜再加用短效的Succinylcholine，此時琥珀膽堿即拮抗非去極化肌松藥又產(chǎn)生去極化阻滯，還有相阻滯，?？蓪е庐惓５募∷裳娱L。 Interaction among non

15、depolarizing relaxants非去極化肌松藥的相互作用 The changeover from one drug to another, when the duration are dissimilar, is a matter of simple kinetics.Three half-lives will be required for a clinical changeover and for the block duration to begin to take on the characteristics of the second drug. Part 3 Side

16、Effects of Muscle Relaxants第三節(jié) 肌松藥的不良反應 Autonomic Nerve System Effects一. 植物神經(jīng)系統(tǒng)作用: 肌松藥對植物神經(jīng)系統(tǒng)的興奮或抑制，常可以引起心血管副反應。 Histamine Release二. 組胺釋放 快速靜注相當量的肌松藥均可以引起組織漿細胞和嗜堿性細胞釋放組胺，使血漿組胺濃度升高可引起血壓下降和心動過速。 組胺釋放還可能引起支氣管痙攣。 TABLE 1. Clinical Autonomic Effects of Neuromuscular Blocking DrugsAUTONOMIC GANGLIA CARDIA

17、C MUSCARINIC RECEPTORS HISTAMINE RELEASE d-Tubocurarine Blocks NoneModerate Metocurine Blocks weakly NoneSlight Gallamine NoneBlocks stronglyNonePancuronium NoneBlocks moderately NoneAlcuronium Blocks weakly Blocks weakly NoneCisatracurium NoneNoneNoneAtracurium NoneNoneSlight Vecuronium NoneNoneNon

18、eRocuronium NoneNoneNoneMivacurium NoneNoneSlight Doxacurium NoneNoneNonePipecuronium NoneNoneNoneSuccinylcholine StimulatesStimulates Slight Part 4 PHARMACOLOGY OF MUSCLE RELAXANTS 第四節(jié) 影響肌松藥的因素 Pharmacokinetics一. 影響肌松藥的藥代動力學 Renal failure influences the pharmacology of nondepolarizing muscle relaxa

19、nts by producing either decreased elimination of the drug, or its metabolites via the kidney, or decreased activity of enzymes that metabolize the drug. Consequently, the duration of action of muscle relaxants may be prolonged in patients with renal failure. Patients with hepatobiliary disease may e

20、xhibit prolonged block with many muscle relaxants .表2 肌松藥經(jīng)腎清除 藥 名 清除占注藥量的百分比（%） 氯筒箭毒堿 40-60 氯二甲箭毒 80-100 加拉碘胺 100 泮庫溴胺 60-80 阿庫氯胺 0-90 法扎溴胺 70-90 阿曲庫胺 5 維庫溴胺 10-20 羅庫溴胺 10-20 美維松 0.7，BS2/BS1為0.5-0.6 2.Residual neuromuscular blockade 殘余肌松作用 乙酰膽堿結合的受體量增加低于25-30%時出現(xiàn)，表現(xiàn)為清醒病人面無表情、上瞼下垂、咬肌張力弱、不能伸舌、發(fā)音不清、頭不能

21、抬和握拳無力。 Antagonism of nondepolarizing muscle relaxants二.非去極化肌松藥的拮抗1. Antagonist拮抗藥The drugs used to antagonize residualneuromuscular blockade, neostigmine,edrophonium, and pyridostigmine areanticholinesterases. They antagonize anondepolarizing neuromuscular blockadeprimarily by increasing the concen

22、tration of acetylcholine at the muscle end plate mainly be inhibition of acetylcholinesterase.In addition, they may also increase release of acetylcholine from the motor nerve terminals, block neural potassium channels, and have a direct agonist effect. 1. 拮抗藥的選擇 對于非去極化肌松藥應用拮抗藥時，一般要待肌顫搐恢復到25%或四個成串刺激

23、已出現(xiàn)2個以上肌顫搐反應 膽堿酯酶抑制藥：新斯的明(Neostigmine)，吡啶斯的明(Pyridostigmine)和依酚氯胺(騰喜龍Edrophonium)。2.Factors that may interfere with antagonism Dose of antagonist Larger doses of anticholinesterases should antagonize neuromuscular blockade more rapidly and more completely than smaller doses. However, further amounts

24、 of anticholinesterases will not produce any greater antagonism.2. 影響抗膽堿酯酶藥的因素 拮抗殘余肌松的用量取決于肌松深度。新斯的明，吡啶斯的明和依酚氯胺的最大用量一般不超過0.07mg/kg，0.28mg/kg，1mg/kg。It is not advisable to administer further antagonist if maximal doses fail to antagonize residual block. The most likely cause of the inadequate antagon

25、ism should be sought. Rate of recovery of the relaxationFollowing administration of an anticholinesterase, two processes contribute to recovery of neuromuscular function. The first is antagonism induced by the effect of the anticholinesterase at the neuromuscular junction,the second is the natural p

26、rocess of decrease in plasma concentration of the relaxant consequent on its elimination. 拮抗時肌張力恢復的時間由殘余肌松的深度和肌松藥自然恢復快慢兩者決定。Acid-base state and electrolyte imbalance酸堿和電解質失衡 Acid-base state and electrolyte imbalance can prevent adequate antagonism. The probability of achieving adequate antagonism in

27、 the presence of significant respiratory acidosis (PaCO2 greater than 50 mm Hg) is low. metabolic alkalosis, Hypopotassaemia, and hypermagnesemia do diminish the antagonism of the residual blockade. Hypothermia低溫 Warning of use of antagonist3.拮抗藥使用注意事項 合用抗膽堿藥如阿托品和格隆溴銨新斯的明，吡啶斯的明主張合用格隆溴銨依酚氯胺與阿托品合用較好老年

28、人慎用抗膽堿酯酶藥使用拮抗藥時應進行心電圖監(jiān)測 CASE病 例患者，男性，48歲，因梗阻性黃疸入院，行肝內外膽管切開取石手術，于1PM入PACU。入室后接呼吸機行SIMV?；颊呙黠@呈現(xiàn)呼吸恢復延遲，不能脫機，6PM查血氣分析，PH：7.06,PCO2:48,HCO3:19.8，患者呈現(xiàn)呼吸恢復延遲的原因？如何處理？ 用拮抗劑有效嗎？Recovery of succinylcholine4. 琥珀膽堿的肌松消退 其引起的去極化阻滯，不需用拮抗藥，待其自行消退。相阻滯，拮抗藥有效， T4/T1比值愈小則效果愈肯定。肌張力恢復延遲時應用人工通氣維持讓其自然恢復。 Part 6 Neuromuscular Monitoring第六節(jié) 肌松藥作用的監(jiān)測 Introduction一. 概述 Goal of monitoring 1. 監(jiān)測目的用藥劑量個體化，合理使用肌松藥，減少不良反應。根據(jù)手術需要控制肌松深度。鑒別術后呼吸抑制的原因。鑒別殘留的神經(jīng)肌肉興奮傳導阻滯的性質。指導拮抗藥的應用和評定拮抗藥的效果。 Way to monitoring2.監(jiān)測方法