肌松药的使用

Neuromuscular management and patient outcomes,by Glenn Murphy M.D.2014 ASA,Postoperative residual neuromuscular blockade is a common complication observed in the postanesthesia care unit(PACU) after general anesthesia. Recent large-scale clinical investigations have demonstrated that up to 24% to 42% of surgical patients arrive in the PACU with evidence of incomplete neuromuscular recovery.Although most clinicians are now using intermediate-acting muscle relaxants, the risk of residual neuromuscular block does not appear to be decreasing over time.,术后肌松阻滞残留是全麻后发生在PACU的一个常见并发症。最近的大型临床研究显示有24%到42%的外科患者在达到PACU时，肌松恢复不完全。虽然很多临床大夫现在应用的是中效肌松药，不过肌松阻滞残余的风险似乎并没有因此而降低。,Several large database studies have shown an association between neuromuscular blocking agent (NMBA)use and an increased risk of morbidity and mortality in the early period after surgery.Recent clinical trials have demonstrated that residual neuromuscular block in the PACU results in airway obstruction, hypoxemia, and pulmonary complications during recovery from general anesthesia.Patients with residual block are at risk for unpleasant symptoms of muscle weakness and prolonged PACU admission times.,很多大样本数据研究显示肌松药和术后早期并发症发生率和死亡率的增高有明显关系。最近的临床试验也显示全麻术后患者在PACU期间的肌松阻滞残留会导致气道梗阻、缺氧和呼吸系统并发症。有肌松阻滞残留的患者也面临肌肉乏力的不适感和PACU停留时间延长的问题,Careful management of neuromuscular blockade in the operating room may reduce the incidence of postoperative residual paralysis and the complications associated with residual block.Several principles related to NMBA dosing, monitoring, and reversal have been shown to reduce the risk of incomplete neuromuscular recovery in postoperative patients.The aim of this review is to provide a “best-available evidence” assessment of methods that can be used by clinicians to reduce the risk of complications due to residual neuromuscular blockade.,手术间内对肌松药使用的认真管理有可能降低术后肌无力的发生率和与肌松残留相关的并发症发生率。研究表明一些与NMBA剂量、监测和拮抗有关的管理原则可以降低术后肌松恢复不完全的风险。这篇综述的目的是提供一个“好的和可行”的评估方法，从而指导临床大夫降低与肌松残留相关的并发症发生的风险。,Q1: Does qualitative neuromuscular monitoring reduce the risk of residual block?A subjective (qualitative) visual or tactile assessment of a muscular response to peripheral nerve stimulation is the most common method of neuromuscular monitoring used in the OR.Pedersen et al. randomized 80 subjects to receive either TOF monitoring or no neuromuscular monitoring(clinical criteria such as breathing or moving). Median TOF ratios of 0.75 and 0.79 were observed in the two groups on arrival to the PACU(no difference).,Q1:定性肌松监测可以降低肌松残留的发生风险吗？客观上感知患者对外周神经刺激的反应是手术间里最常用的一种肌松监测方法。Pedersen等将80名患者随机分配接受TOF监测或非肌松监测（临床标准：呼吸或活动动度）。达到PACU时两组患者的TOF中位值分别是0.75和0.79，没有区别。,A similar study demonstrated that the proportion of patients with TOF ratios0.7 was significantly less in a monitored group(15%) compared to unmonitored patients(47%).Another randomized trial demonstrated that tactile evaluation of the response to double-burst stimulation(DBS) reduced, but did not eliminate, the occurrence of residual paralysis. Significantly fewer patients in the monitored group had TOF ratios0.7(24%) compared to the unmonitored group(57%).,一项相似的研究显示：肌松监测组患者到达PACU时TOF0.7的比例（15%）要明显低于没有监测组（47%）。另一项随机试验显示感觉患者对双爆发刺激（DBS）的反应可以降低，但不能消除残留肌松的发生。有肌松监测组的患者TOF0.7的概率（24%）要低于没有肌松监测组的患者（57%）。,Q2:Does quantitative neuromuscular monitoring reduce the risk of residual block?A study showed during 40 patients, there are 50% patients in the no monitoring had TOF ratios0.7 in the PACU, compared to only 5.3% in the AMG(acceleromyograph) group.A another study showed that 17% of patients in the no monitoring group had residual block( defined as a TOF0.8) compared to only 3% in the AMG group.,Q2:定量肌松监测降低肌松残留的发生风险吗？一项研究显示在40例患者中，在PACU期间在非监测组有50%的患者TOF0.7，而在加速度仪监测组只有5.3%的患者TOF0.7. 另一项研究显示非监测组有17%的患者有肌松残留（定义为TOF0.8），而加速度仪组只有3%的患者有肌松残留,In the largest study, 185 patients were randomized to receive either standard qualitative monitoring(peripheral nerve stimulator) or AMG monitoring(TOF-Watch). 30% of patients in the former group had a TOF ratio0.9 in the PACU, versus only 4.5% in the AMG group.在一项大样本研究中，185例患者被随机分配为标准定性监测（外周神经刺激）或者AMG监测（TOF-Watch）。前一组中有30%的患者在PACU期间TOF0.9，而AMG组只有4.5%的患者TOF0.9,Q3:Can neuromuscular monitoring impact postoperative recovery?Although there is evidence that qualitative monitoring can reduce the risk of postoperative residual block, at the present time there is no data demonstration that this type of monitoring improves clinical outcomes. In contrast, there is emerging evidence that intraoperative quantitative monitoring can beneficially impact postoperative recovery in surgical patients.Mortensen et al noted that patients randomized to receive AMG monitoring had fewer clinical signs of muscle weakness in the PACU.,Q3:神经肌肉监测可以反应术后的恢复情况吗？虽然有证据表明定性的监测可以降低术后肌松残留的风险，不过目前，还是没有数据说明这种监测可以改善临床愈后。与此相反，有证据提示术中的肌松定量监测对手术患者的术后恢复有一定好处。Mortensen等发现接受AMG监测的患者在PACU期间很少表现出肌肉乏力的临床征象。,A study showed that a significantly higher incidence of hypoxemia events(oxygen saturation90%) and airway obstruction was observed in the peripheral nerve stimulator group(21.1% and 11.1%) compared to the AMG group(0% and 0%) in PACU.Patients randomized to receive AMG monitoring had significantly fewer symptoms of muscle weakness in the PACU during the first 60 minutes, and overall quality of recovery at the time PACU discharge was significantly improved in these patients.,一项研究显示与AMG组（0%和0%）相比，仅接受外周神经刺激监测的患者在PACU期间发生低氧血症（SPO20.9 four hours after the intubation dose of vecuronium.,Q4:在手术结束时应该给大多数患者使用抗胆碱酯酶药吗？一些研究提示如果不用抗胆碱酯酶药，那么肌力恢复不完全的风险会比较高。Caldwell等观察了给予单次插管剂量的维库溴铵后1-4小时的肌松残留发生率，在4小时后约一半的患者达不到TOF0.9的水平。,Q5:At what TOF count will neostigmine produce a rapid and reliable reversal?Several investigations have examined the time required to achieve a TOF ratio of 0.9 or greater when neostigmine is administered at various levels of neuromuscular block(TOF count of 1-4 with TOF stimulation).Neostigmine should not be administered until there is some evidence of spontaneous neuromuscular recovery(should not be given at a TOF count of 0-the concentration of NMBA at the neuromuscular junction it too high to competitively antagonize).,Q5：在TOF计数多少时新斯的明可以产生比较迅速和可靠的肌松拮抗效果？一些研究观察了在不同肌松阻滞程度时（TOF刺激仪上TOF计数从1-4）给予新斯的明到达到TOF0.9或更高值所需的时间。只有当自主呼吸开始恢复时，才可以给新斯的明（TOF计数是0时不能给新斯的明，这表明神经肌肉接头的非去极化肌松药浓度很高，很难被竞争性拮抗）,Kim reversed patients with neostigmine (70ug/kg) at a TOF count of either 1,2,3,or 4. At a TOF count of 1, the median time to achieve a TOF ratio of 0.9 was 28.6 minutes (range 8.8 to 75.8 minutes)At a TOF count of 4, the median time to achieve a TOF ratio of 0.9 was 9.5 minutes (range 5.1 to 26.4 minutes).It also showed that beginning with a TOF count 4, only 55% of patients had achieved a TOF ratio of 0.9 with 10 minutes.,Kim分别在TOF计数为1，2，3，4时用新斯的明(70ug/kg)给患者进行拮抗。TOF是1时，TOF达到0.9的平均时间是28.6分钟(8.8-75.8min)TOF是4时，TOF达到0.9的平均时间是9.5分组(5.1-26.4min)如果在TOF是4时开始拮抗，仅有55%的患者可以在10min内TOF值达到0.9,Kirkegaard et al showed that the times from reversal until achieving a TOF ratio of 0.9 were 20.0(6.5 to 70.5)minutes at a TOF count of 2 and 16.5(6.5-143.3) minutes at a TOF count of 4.These studies demonstrate that reversal of neuromuscular blockade is not rapid with neostigmine (requires approximately 15 minutes at a TOF count of 4 at the end of surgery). In addition, there is large variability in reversal times, even at a TOF count of 4.,Kirkegaard等的研究显示在TOF值是2和4时，给予拮抗药到TOF达到0.9，分别需要20min(6.5-70.5)和16.5（6.5-143.3）。这些研究显示新斯的明的拮抗作用并不快（在手术结束TOF是4时，一般需要约15min）。另外，即使TOF计数为4时才开始拮抗，拮抗肌松作用所需的时间差异也很大。,Q6:Are clinical signs reliable indicators of neuromuscular recovery?Studies in awake volunteers and postoperative surgical patients have examined the predictive value of these tests in determining whether full recovery of muscle strength(TOF ratio 0.9) has occurred.The ability to maintain a 5-second head-lift is a commonly-used test of muscle recovery in the OR.In a study in which 12 awake volunteers were given an infusion of rocuronium, 11 of 12 volunteers were able to maintain a 5-second head-lift at a TOF ratio of 0.5.,Q6：临床征象是肌松恢复的可靠指标吗？在清醒志愿者和术后患者的一些研究调查了这些试验对肌松完全恢复（TOF0.9）的预测价值。OR内常用的一个检测肌松恢复的试验是5-秒抬头试验在一项对12名清醒志愿者的研究中，给与静注罗库溴铵，在12名志愿者中有11名可以在TOF是0.5时完成5-秒抬头试验。,In another investigation, 12 awake volunteers were given an infusion of mivicurium. At a TOF ration of 0.5, all of the volunteers could speak, open eyes and protrude tongues, and 8 of the 12 could maintain a 5-second head-lift and swallow.In a cohort study 640 surgical patients were examined the residual block(TOF ratio0.9), none of the eight clinical signs tests or combinations of test, were able to reliable detect the presence of residual block.These studies demonstrate that clinical signs of muscle strength are insensitive in determining the presence or absence of incomplete neuromuscular recovery.,在另一项调查研究中，12名清醒志愿者被静注了美维松，在TOF为0.5时，所有的志愿者都可以讲话，睁眼和伸舌。12个志愿者里有8名可以完成5-秒抬头试验和吞咽。在一项640例手术患者参与的队列研究中，对这些患者TOF0.9的肌松残留情况的研究发现，8项临床征象没有一个或者几个联合起来可以可靠的发现肌松的残留作用。这些研究表明用于判断肌力的临床体征并不是神经肌肉是否完全恢复的敏感指标。,Q7:Can residual neuromuscular block be reliably exclude with conventional peripheral nerve stimulators(qualitative neuromuscular monitoring)?Peripheral nerve stimulators are often used to determined whether recovery of neuromuscular function has occurred at the end of surgery. If no fade is detected with TOF, DBS, or tetanic stimulation, then recovery of muscle strength is assumed to be complete.Studies showed that clinicians are unable to use tactile assessment to identify fade in 55% of cases when TOF ratios were between 0.4-0.7,Q7：用传统的外周神经刺激器（定性肌松监测）是否可以有效的排除肌松阻滞残余？外周神经刺激器通常用来监测在手术结束时神经肌肉功能是否恢复功能。如果用TOF，DBS或强直刺激没有发现肌颤搐衰减，那么认为肌力恢复完全。研究显示当TOF在0.4-0.7时，临床大夫用触觉的方法难以发现55%的患者还有肌颤搐的衰减现象。,Relative surveysSurveys have consistently demonstrated that most clinicians do not routinely monitor patients with peripheral nerve stimulators in the OR. A survey showed that 24.3% of european respondents indicated that qualitative monitoring was not available in their department, and if such monitoring was available, it was often shared between 2-3 room.Despite high quality studies demonstrating a beneficial effect of quantitative monitoring on the incidence of residual neuromuscular blockade, few clinicians routinely use this type of monitoring.,相关调查：很多调查都发现多数临床大夫在OR并不常规用外周神经刺激器监测患者。一项调查显示有24.3%的欧洲麻醉医师指出他们的科室没有定性肌松监测仪，而且，即使有这种仪器，一般也是2-3个手术间配备一个。虽然研究显示定量的肌松监测对于术后肌松阻滞残留的发现有好处，不过很少有临床大夫常规使用这项监测。,Surveys suggest that anticholinesterase reversal agents are not routinely used by anesthesiologists. In the survey by Naguib, only 18% of European respondents and 34% of united states respondents noted that they always used an anticholinesterase agent at the end of surgery.More that one-half of the respondents from the US stated that rapid and reliable reversal could be achieved at a TOF count of 2 or less. Furthermore, more than one-half of the european respondents stated that they typically allow 5 minutes or less between the time of neostigmine administration and tracheal extubation.,调查发现麻醉医师并没有常规用抗胆碱酯酶药拮抗肌松作用。在Naguib的调查中，仅18%的欧洲麻醉大夫和34%的美国麻醉大夫提出他们在手术结束的时候会常规用抗胆碱酯酶药。超过一半的美国麻醉医师认为在TOF是2或更低时进行肌松拮抗是可以很快起效，并且拮抗效果满意。而且超过一般的欧洲麻醉医师指出从他们给拮抗药到拔管的时间通常是5分钟或者更短。,On the basis of surveys that have been published from around the world, there appears to be a significant difference between published “best-evidence”practices and the neuromuscular management strategies used by clinicians in daily practice.基于目前已发表的调查，临床大夫在日常工作中所做的肌松管理和已公布的“最佳证据”临床指南之间还有明显的差别。,Conclusions and recommendations 1. tactile evaluation of TOF and DBS fade reduces (but not eliminate) the incidence and degree of postoperative residual paralysis compared with the use of clinical criteria to assess readiness for tracheal extubation2.To exclude with certainty the possibility of residual paralysis in patients at risk, clinicians should use objective(quantitative) neuromuscular monitoring tests.3.Ideally, neuromuscular function should be monitored objectively (quantitatively) in all patients receiving NMBAs.,结论和推荐1. 与用临床征象来判断拔管的时间相比，通过对TOF和DBS导致的肌颤搐衰减的触觉评估可以判断降低术后肌松残留的发生率。2.为了排除肌松残留可能的风险，临床医师应该进行客观（定量