【精华】Anesthesiology，A&A 摘要翻译

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【第360篇】泛caspase抑制剂可减轻慢性坐骨神经压迫损伤大鼠的肌细胞凋亡和神经病理性疼痛

Anesth Analg. 2013 Jan;116(1):216-23

A pan-caspase inhibitor reduces myocyte apoptosis and neuropathic pain in rats with chronic constriction injury of the sciatic nerve.

Gradl G, Herlyn P, Finke B, Gierer P, Wree A, Witt M, Mittlmeier T, Vollmar B.

Institute for Experimental Surgery, University of Rostock, Schillingallee 69a, 18057, Rostock, Germany. [email protected].

Abstract

BACKGROUND: Chronic constriction injury is a widely used model for neuropathic pain in rats. It presents with symptoms resembling human neuropathic pain, such as spontaneous pain, hyperalgesia, and allodynia. Recently, myocyte apoptosis was found in neuropathic rats as a possible promoter of pain and motor dysfunction. Our aim in this study was to demonstrate whether muscle cell apoptosis contributes to neuropathic pain in this animal model.

METHODS: To clarify this issue, we examined pain, nutritive perfusion, and inflammation in muscle tissue as well as myocyte apoptosis in rats with neuropathic pain established by chronic constriction injury of the sciatic nerve. Animals received either the pan-caspase inhibitor zVAD (OMe)-fmk (n = 5) or equivalent volumes of vehicle (n = 6). Sham-operated rats served as controls (n = 6).

RESULTS: At day 4 after nerve ligation, there were no signs of perfusion failure or muscle tissue inflammation in all experimental groups. However, animals treated with the vehicle had marked myocyte apoptosis, which was found almost completely blocked in zVA-Dtreated animals. The zVA-Dtreated animals presented with a significant reduction of pain upon heat, cold, and mechanical stimulation comparable with values found in sham controls.

CONCLUSIONS: Myocyte apoptosis possibly contributes to thermal and mechanical allodynia in this experimental model for neuropathic pain. The development of neuropathic pain symptoms did not depend on disturbances in microcirculation or muscle tissue inflammation.
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泛caspase抑制剂可减轻慢性坐骨神经压迫损伤大鼠的肌细胞凋亡和神经病理性疼痛

【摘要】

背景： 慢性压迫损伤是大鼠神经病理性痛常用的动物模型。它可以较好模拟人类的神经病理性疼痛，例如自发性疼痛、痛觉过敏和异常性疼痛。近来，在神经病理性痛大鼠中发现肌细胞凋亡可能促进疼痛和运动功能障碍。本实验旨在验证在该动物模型中肌细胞凋亡是否促进神经病理性疼痛。

方法： 为阐明该问题，我们建立慢性坐骨神经压迫的神经病理性疼痛大鼠模型，检测疼痛、微循环灌注、肌肉组织中的炎症反应以及肌细胞的凋亡情况。实验动物接受泛caspase抑制剂zVAD (OMe)-fmk (n = 5)或者相同剂量的安慰剂(n = 6)。假手术组作为对照组。

结果： 神经结扎后4天，在所有实验组中未出现灌注障碍和肌肉组织炎症的情况。然而，安慰剂处理组出现显著肌细胞凋亡，而在zVAD处理组几乎未出现。与假手术组对比，zVAD处理组对热、冷及机械刺激的疼痛明显减轻。

结论： 在该病理性疼痛动物模型中，肌细胞凋亡可能促进热能和机械痛觉过敏。痛觉过敏的症状与肌肉组织微循环灌注障碍或肌肉炎症反应无关。

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【第359篇】蛛网膜下腔和颅内出血患者复极化异常：危险因素及其预后相关性

Anesth Analg. 2013 Jan;116(1):190-7

Repolarization abnormalities in patients with subarachnoid and intracerebral hemorrhage: predisposing factors and association with outcome.

Junttila E, Vaara M, Koskenkari J, Ohtonen P, Karttunen A, Raatikainen P, Ala-Kokko T.

Department of Anesthesiology, Oulu University Hospital, PO Box 21, FIN-90029 OUH, Oulu, Finland. [email protected].

Abstract

BACKGROUND: Electrocardiographic (ECG) abnormalities are frequent in patients with intracranial insult. In this study, we evaluated the factors predisposing to the repolarization abnormalities, i.e., prolonged corrected QT (QTc) interval, ischemic-like ECG changes and morphologic end-repolarization abnormalities, and examined the prognostic value of these abnormalities in patients with subarachnoid and intracerebral hemorrhages requiring intensive care.

METHODS: This was a prospective, observational clinical study in a university-level intensive care unit. Clinical characteristics, the level of consciousness, and findings in primary head computed tomography were recorded on admission. The study period was divided into three 2-day sections. In each section, a 12-lead ECG, transthoracic echocardiography, the results of standard blood electrolytes and cardiac troponin I, as well as the rate of vasoactive and sedative drug infusions were recorded. Repolarization abnormalities such as prolongation of the QTc interval (millisecond), ischemic-like ECG changes, and morphologic end-repolarization abnormalities (present/absent) were evaluated and analyzed. The 1-year functional outcome was determined using the Glasgow Outcome Score.

RESULTS: During the 2-year study period, 108 patients were included in the study. Different repolarization abnormalities were frequent in both types of hemorrhage. Prolongation of the QTc interval was predisposed by female gender (β, 24.5; P = 0.010) and the use of propofol (β, 30.5; P = 0.001). The predisposing factor for ischemic-like ECG changes were male gender (odds ratio [OR], 5.9; P = 0.003) and for morphological end-repolarization abnormalities aneurysmatic bleeding (OR, 13.0; P = 0.002). Ischemic-like ECG changes were common, in 87/108 patients during the study period, and were associated with a poorer 1-year functional outcome (OR, 4.7; lower 95% confidence interval, 1.5; P = 0.010).

CONCLUSIONS: Each repolarization abnormality has characteristic predisposing factors. Ischemic-like ECG changes are common and are associated with a poorer 1-year functional outcome.
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蛛网膜下腔和颅内出血患者复极化异常：危险因素及其预后相关性

【摘要】

背景： 颅内病变患者常出现心电图异常。在本研究中，我们评估负极化异常（例如， QT间期延长、缺血样心电图改变和复极化晚期形态异常）相关的危险因素及其作为判断需要监护治疗的蛛网膜下腔及颅内出血患者预后的价值。

方法： 该研究是在大学级别医院ICU内进行的前瞻性观察性临床研究。记录入院时患者临床特点、意识水平及头颅CT检查的主要发现。研究分为3个为期两天的阶段。在每个阶段，记录12导联心电图、经胸壁超声心动图、电解质、心肌肌钙蛋白I及血管活性药物和镇静药物的输注速度。分析和评估负极化异常（例如， QT间期延长、缺血样心电图改变和复极化晚期形态异常）相关的危险因素。通过格拉斯评分评估1年期间患者运动功能恢复情况。

结果： 研究为期2年，共108位患者。在不同类型出血患者中均频繁出现不同程度负极化异常。女性和丙泊酚应用为QT间期延长的危险因素(β, 24.5; P = 0.010)(β, 30.5; P = 0.001) 。 男性是缺血样心电图改变(odds ratio [OR], 5.9; P = 0.003) 和复极化晚期形态异常(OR, 13.0; P = 0.002)的危险因素。缺血样心电图改变发生较为普遍，108位患者中有87位出现，并且与1年期患者功能恢复差有关(OR, 4.7; lower 95% 可信区间, 1.5; P = 0.010)。

结论： 每种不同的负极化障碍有不同的危险因素。缺血样心电图改变发生较为普遍，并且与1年期患者功能恢复差有关。

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【第358篇】 地塞米松预防术后恶心呕吐：一项更新的临床随机对照试验Meta分析 Anesth Analg.2013 Jan;116(1):58-74.

Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials.

De Oliveira GS Jr, Castro-Alves LJ, Ahmad S, Kendall MC, McCarthy RJ.

MSCI, Department of Anesthesiology, Northwestern Memorial Hospital, 251 E Huron St, F5-704, Chicago, IL 60611. [email protected].

BACKGROUND: Dexamethasone has an established role in decreasing postoperative nausea and vomiting (PONV); however, the optimal dexamethasone dose for reducing PONV when it is used as a single or combination prophylactic strategy has not been clearly defined. In this study, we evaluated the use of 4 mg to 5 mg and 8 mg to 10 mg IV doses of dexamethasone to prevent PONV when used as a single drug or as part of a combination preventive therapy.

METHODS: A wide search was performed to identify randomized clinical trials that evaluated systemic dexamethasone as a prophylactic drug to reduce postoperative nausea and/or vomiting. The effects of dexamethasone dose were evaluated by pooling studies into 2 groups: 4 mg to 5 mg and 8 mg to 10 mg. The first group represents the suggested dexamethasone dose to prevent PONV by the Society for Ambulatory Anesthesia (SAMBA) guidelines, and the second group represents twice the dose range recommended by the guidelines. The SAMBA guidelines were developed in response to studies, which have been performed to examine different dosages of dexamethasone.

RESULTS: Sixty randomized clinical trials with 6696 subjects were included. The 4-mg to 5-mg dose dexamethasone group experienced reduced 24-hour PONV compared with control, odds ratio (OR, 0.31; 95% confidence interval [CI], 0.23-0.41), and number needed to treat (NNT, 3.7; 95% CI, 3.0-4.7). When used together with a second antiemetic, the 4-mg to 5-mg dexamethasone group also experienced reduced 24-hour PONV compared with control (OR, 0.50; 95% CI, 0.35-0.72; NNT, 6.6; 95% CI, 4.3-12.8). The 8-mg to 10-mg dose dexamethasone group experienced decreased 24-hour PONV compared with control (OR, 0.26; 95% CI, 0.20-0.32; NNT, 3.8; 95% CI, 3.0-4.3). Asymmetric funnel plots were observed in the 8-mg to 10-mg dose analysis, suggesting the possibility of publication bias. When used together with a second antiemetic, the 8-mg to 10-mg dose group also experienced reduced incidence of 24-hour PONV (OR, 0.35; 95% CI, 0.22-0.53; NNT, 6.2; 95% CI, 4.5-10). In studies that provided a direct comparison between groups, there was no clinical advantage of the 8-mg to 10-mg dexamethasone dose compared with the 4-mg to 5-mg dose on the incidence of postoperative nausea and/or vomiting.

CONCLUSIONS: Our results showed that a 4-mg to 5-mg dose of dexamethasone seems to have similar clinical effects in the reduction of PONV as the 8-mg to 10-mg dose when dexamethasone was used as a single drug or as a combination therapy. These findings support the current recommendation of the SAMBA guidelines for PONV, which favors the 4-mg to 5-mg dose regimen of systemic dexamethasone.
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地塞米松预防术后恶心呕吐：一项更新的临床随机对照试验Meta分析

背景： 地塞米松已经被证实能够降低术后恶心呕吐发生率；然而，其作为单独用药或者联合用药用于预防术后恶心呕吐的最佳剂量仍不明确。在本研究中，我们评估4-5mg和8-10mg地塞米松静脉注射作为单独或者联合用药用于预防术后恶心呕吐的作用。

方法：全面检索有关地塞米松全身应用作为预防用药预防术后恶心和/或呕吐的临床随机试验。按照地塞米松的用量，将研究分为两大组：4-5mg组和8-10mg组。第1组是门诊麻醉协会（SAMBA）推荐用于预防PONV的地塞米松剂量，第2组代表该推荐值两倍的剂量。SAMBA指南是根据既往不同剂量地塞米松的研究而制定的。

结果：共纳入6个随机临床试验，6696个患者。4-5mg地塞米松组与对照组相比可降低术后24小时恶心呕吐发生 (OR, 0.31; 95% 可信区间 [CI], 0.23-0.41)及需要治疗的人数(NNT, 3.7; 95% CI, 3.0-4.7)。与其它止吐药物联合使用时，4-5mg地塞米松同样能够降低术后24小时恶心呕吐发生 (OR, 0.50; 95% CI, 0.35-0.72; NNT, 6.6; 95% CI, 4.3-12.8)。8-10mg地塞米松组与对照组相比可降低术后24小时恶心呕吐发生(OR, 0.26; 95% CI, 0.20-0.32; NNT, 3.8; 95% CI, 3.0-4.3)。8-10mg组漏斗图呈不对称型，提示可能存在发表偏倚。与其它止吐药物联合使用时，8-10mg地塞米松同样能够降低术后24小时恶心呕吐发生(OR, 0.35; 95% CI, 0.22-0.53; NNT, 6.2; 95% CI, 4.5-10)。该研究直接比较两组不同剂量地塞米松的作用，结果表明8-10mg组与4-5mg组相比，在降低术后恶心呕吐发生率上没有优势。

结论： 我们的研究结果表明，地塞米松无论是作为单独用药还是与其它止吐药联合应用，4-5mg地塞米松与8-10mg地塞米松具有相同的临床作用。该结论支持SAMBA推荐的地塞米松作为预防术后恶心呕吐的剂量（4-5mg）。

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【第357篇 】布比卡因和罗布卡因在心肌细胞蓄积与可逆性线粒体功能异常和心功能减退相 Anesth Analg.2013 Jan;116(1):83-92.

Myocardial accumulation of bupivacaine and ropivacaine is associated with reversible effects on mitochondria and reduced myocardial function.

Hiller N, Mirtschink P, Merkel C, Knels L, Oertel R, Christ T, Deussen A, Koch T, Stehr SN.

DESA, Center for Sepsis Control and Care, University Hospital Jena, Erlanger Allee 101, 07747 Jena, Germany. [email protected].

Abstract

BACKGROUND: Mechanisms of local anesthetic cardiac toxicity are still not completely understood. In this study, we analyzed whether concentrations of local anesthetics found in clinical toxicity affect myocardial mitochondrial structure and oxygen consumption.

METHODS: Guinea pig isolated heart Langendorff preparations were exposed to bupivacaine (3.0 and 7.5 μg/mL) and ropivacaine (3.6 and 9.0 μg/mL) for 10 minutes. Heart rate, systolic blood pressure, the first derivative of left ventricular pressure (+dP/dt), electrocardiogram, and coronary flow were recorded. The local anesthetic tissue concentration was measured either immediately after local anesthetic exposure, or after 20- and 60-minute washout periods. In addition, electron microscopy of myocardial mitochondria was performed using a scoring system for structural damage of mitochondria. Cardiomyocyte cell culture was incubated with bupivacaine, and oxygen consumption ratio, extracellular acidification, and relative amounts of PGC-1α mRNA, a regulator of cellular energy metabolism, were determined.

RESULTS: Bupivacaine and ropivacaine induced reversible PR interval and QRS prolongation, and left ventricular pressure and +dP/dt reduction. Myocardial tissue concentration of local anesthetics was 3-fold the arterial concentration. Mitochondria showed a significant concentration-dependent morphological swelling after local anesthetic application. These changes were reversed by a 20-minute washout period for ropivacaine and by a 60-minute washout for bupivacaine. Bupivacaine reduced mitochondrial oxygen consumption and increased PGC-1α expression in neonatal cardiomyocyte cell cultures, whereas fatty acid metabolism remained unaffected.

CONCLUSIONS: Bupivacaine and ropivacaine accumulate in the myocardium. Reversible local anesthetic-induced mitochondrial swelling occurs at concentrations that induce a negative inotropic effect. Bupivacaine reduces cellular metabolism, whereas this reduction is reversible by fatty acids. Interaction with mitochondria may contribute to the negative inotropic effect of local anesthetics.
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布比卡因和罗布卡因在心肌细胞蓄积与可逆性线粒体功能异常和心功能减退相关

【摘要】

背景： 局麻药心脏毒性的机制仍未完全阐明。在本研究中，我们分析临床上可导致心脏毒性作用的局麻药是否影响心肌细胞线粒体结构和耗氧量。

方法： 用Langendorff法行豚鼠离体心脏灌流，记录布比卡因(3.0 and 7.5 μg/mL)和 罗哌卡因(3.6 and 9.0 μg/mL)作用10分钟后，心率、收缩压、左心室压力(+dP/dt)、心电图和冠脉血流量变化。测定局麻药暴露后即刻、洗脱后20分钟和60分钟组织内局麻药浓度。此外，电子显微镜观察心肌细胞线粒体结构的破坏，并进行评分。体外培养的心肌细胞暴露于布比卡因，检测耗氧量比例、细胞外酸化和细胞能量代谢调节物PGC-1α mRNA的浓度。

结果： 布比卡因和罗哌卡因导致可逆性RP间期和QRS间期延长，左心室压力(+dP/dt)降低。局部组织内局麻药浓度是动脉内的3倍。局麻药导致浓度依赖性线粒体肿胀。这些作用在罗哌卡因洗脱后20分钟，布比卡因洗脱后60分钟可恢复正常。布比卡因导致体外培养心肌细胞线粒体耗氧量降低，PGC-1α mRNA表达增加，对脂肪酸代谢无影响。

结论： 布比卡因和罗哌卡因可在心肌细胞内聚集。导致负性肌力作用浓度的局麻药可导致线粒体肿胀。布比卡因降低细胞代谢，然而，该作用可被脂肪酸逆转。通过对线粒体的作用，局麻药可导致负性肌力作用。

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【第356篇 】30mg和45mg利多卡因试验剂量在产科麻醉中预测鞘内注射的前瞻随机临床试验

Anesth Analg.2013 Jan;116(1):125-32.

A Prospective Randomized Trial of Lidocaine 30 mg Versus 45 mg for Epidural Test Dose for Intrathecal Injection in the Obstetric Population.

Pratt S, Hess P, Vasudevan A.

Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. [email protected].

Abstract

BACKGROUND: The epidural test dose, used to identify unintended intrathecal placement, should reliably produce a spinal block without posing a threat to the patient. Most anesthesiologists administer a dose of local anesthetic, commonly lidocaine 45 mg. Pregnant patients are more sensitive to local anesthetics; high and total spinal anesthesia have been reported in the pregnant population with this dose. We hypothesized that lidocaine 30 mg was as effective as lidocaine 45 mg in creating rapid objective evidence of a sensory or motor block.

METHODS: In this prospective, randomized, double-blind trial, patients scheduled for cesarean delivery were assigned to 1 of 4 groups: lidocaine 30 mg in the spinal or epidural space, or lidocaine 45 mg by the same routes. A blinded observer assessed the degree of sensory and motor block. The ability to identify intrathecal injection of each dose was compared. Sensory block above T6 dermatome and hypotension were recorded as side effects.

RESULTS: Intrathecal administration of lidocaine 30 mg produced rapid subjective and objective signs of neuroblockade within 3 minutes (100%, 95% confidence interval CI, 85%-100% for each). Lidocaine 45 mg produced similar results. All patients in both groups described their legs as warm or heavy after 3 minutes and had a motor block by 5 minutes. On the basis of an intrathecal catheter rate of 1:380, the observed negative predictive value for intrathecal placement if the patient described no sensory changes at 3 minutes was 100% (95% CI, 99.95%-100%) for 30 mg and 100% (95% CI, 99.93%-100%) for 45 mg. We did not identify a decrease in the rate of side effects with the lower dose.

CONCLUSIONS: Our results suggest that there is unlikely to be a large difference in the ability of these doses to detect unintentional intrathecal catheter placement. While the negative predictive value for intrathecal injection is very high for both doses, the 95% CI for the sensitivity of either dose is too wide to demonstrate clinical safety to identify all intrathecal catheters. A much larger study is warranted to assess whether there is a lower sensitivity with the 30-mg dose, or a propensity toward high cephalad motor block levels with the 45-mg dose.

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【摘要】

背景： 硬膜外试验剂量旨在确保硬膜外置管未误入鞘内，其能够产生一定程度的脊髓麻醉，但不会对患者造成伤害。绝大多数麻醉医生注射45mg利多卡因进行试验。怀孕的患者较普通患者对局麻药的敏感性高；既往有报道该剂量可导致怀孕患者高位脊髓麻醉和全脊麻。我们假设30mg利多卡因与45mg利多卡因相比同样能够快速导致感觉或运动阻滞。

方法： 该研究为临床随机对照双盲试验，拟行剖宫产的患者随机分配在1-4组：利多卡因30mg蛛网膜下腔或硬膜外注射，或者利多卡因45mg蛛网膜下腔或硬膜外注射。另一观察人员评价感觉和运动阻滞程度。比较每种剂量预测鞘内注射的能力。达到T6水平皮肤感觉阻滞和低血压作为副作用而被记录。

结果： 30mg利多卡因蛛网膜下腔注射可在3min内导致主观和客观的神经阻滞(100%， 95% CI，85%-100%)。45mg利多卡因产生相似结果。不同组别的所有患者描述3min后他们的腿出现发热或发沉现象，5min后出现运动阻滞。根据鞘内置管的比例为1:380，30mg 和45mg 利多卡因注射后，如果患者3min内未出现感觉改变，其鞘内置管的阴性预测值分别为100% (95% CI，99.95%-100%)和100% (95% CI，99.93%-100%)。我们没有发现较低剂量可减少副作用发生率。

结论： 我们的结果表明，我们对比的两种剂量预测误行鞘内置管的作用没有大的区别。而所有剂量鞘内注射的阴性预测值都很高，所有剂量敏感度的95%可信区间太广，很难保证每个鞘内置管的安全性。因此，需要更多的研究来评价是否30mg利多卡因的敏感性较低，或者45mg利多卡因可导致更高平面的运动阻滞。