We continue our discussion of the guidelines for the performance of neuraxial anesthesia and analgesia in anticoagulated patients. Today we will be discussing the risks involved in the performance of a regional anesthetic in patients with impaired coagulation.
1.  What is the big deal about neuraxial anesthesia and anticoagulation? If it is safe to perform the surgery, then it must be safe to perform a regional anesthetic!
2.  What is the typical presentation of a spinal hematoma?
3.  How do you diagnose a spinal hematoma?
4.  What is the treatment of choice for a spinal hematoma?
1.神经阻滞和抗凝药之间关系有多大？如果实施手术时安全的，是否意味着区域阻滞也必然是安全的？
2.椎管内血肿的典型表现是什么？
3.如何诊断椎管内血肿？
4.椎管内血肿的治疗措施有哪些？

[每周一问]NO.9参考答案
1.神经阻滞和抗凝药之间关系有多大？如果实施手术时安全的，是否意味着区域阻滞也必然是安全的？
并非必然如此！在没有停止使用抗凝药的情况下安全实施手术和外周神经阻滞只占极少部分。INR<1.5对于安全的手术是可行的[1]。外科出血时可见的，可以通过吸引，并在必要时给与输血。如果患者持续出血，可以通过给与新鲜冰冻血浆逆转抗凝药的作用。
硬膜外静脉破裂可能导致硬膜外血肿发生。血肿可能压迫脊髓产生占位性病变，虽然神经阻滞后出现椎管内血肿非常罕见（硬膜外麻醉1:150,000，蛛网膜下腔麻醉后1:220,000），但是很多病例（在一报道中为68%）出现凝血功能受损[2]。

2.椎管内血肿的典型表现是什么？
如果出现严重的背痛，同时伴有下肢肌张力减弱与感觉减退，应该怀疑椎管内血肿。其代表患者存在生命威胁，并应该立即得到救治。

3.如何诊断椎管内血肿？
磁共振成像通过对脊髓病变进行评估，是怀疑有椎管内血肿患者的诊断性选择之一。MRI对于该情况非常敏感，也是特有的可无创显示脊髓影像及周围结构如CSF、灰白质结构及邻近韧带的技术。马尾及腰区的神经根也可以得到评估[3]。

4.椎管内血肿的治疗措施有哪些？
椎管内血肿诊断明确后，必须立即进行椎板减压切除术，因为手术时间耽误可导致不可逆的神经损伤。如果在第一症状出现后8小时后未行椎板减压术，椎管内血肿可导致严重的破坏性结果，如下肢的弛缓性麻痹。

[每周一问]NO.9之英文参考答案
What is the big deal about neuraxial anesthesia and anticoagulation? If it is safe to perform the surgery, then it must be safe to perform a regional anesthetic!
Not necessarily! Relatively minor surgical and peripheral nerve procedures can be safely performed without discontinuing the anticoagulant regimen. An INR value of < 1.5 is acceptable for the safe performance of surgery (1). Surgical bleeding is visible, could be suctioned and the patient may be transfused if necessary. If the patient continues to bleed, reversal of the anticoagulation may be attempted with fresh frozen plasma.
The presence of blood from a ruptured epidural vein in the epidural space could lead to a spinal hematoma. This hematoma could produce a mass occupying lesion with cord compression. Although spinal hematoma after a neuraxial blockade is very unusual (1:150,000 after epidural anesthesia and 1:220,000 after spinal anesthesia), most cases (68% in one report) have resulted in patients with impaired coagulation (2).

What is the typical presentation of a spinal hematoma?
A spinal hematoma should be suspected if severe backache appears in combination with weakness and decreased sensation of the lower extremities. It represents a life threatening emergency and the patient should be evaluated immediately.

How do you diagnose a spinal hematoma?
Magnetic resonance imaging is the diagnostic test of choice in patients with a suspected spinal hematoma by allowing the evaluation of spinal cord processes. MRI is very sensitive in this regard and is also unique in its inherent noninvasive ability to image the spinal cord and surrounding structures such as CSF, dura, and adjacent ligaments. The cauda equina and existing nerve roots in the lumbar region can also be assessed (3).

What is the treatment of choice for a spinal hematoma?
Immediate decompression laminectomy is the treatment that must be used in the presence of a spinal hematoma because irreversible neurologic deficit can result from delaying surgery. A spinal hematoma could lead to severe devastating results, such as a lower extremity flaccid paralysis, if the laminectomy is not performed within 8 hours of the first symptom presentation.
Question Author: David Hepner, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
References:
1.  Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. NEJM 1997:1506-11.
2.  Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg 1994;79:1165-77.
3.  Goetz CG, Pappert EJ. Textbook of Clinical Neurology, 1st ed. 1999, W. B. Saunders Company.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School

[每周一问]NO.10-The Guidelines for the Performance of Neuraxial Anesthesia and Analgesia in Anticoagulated Patients
today we will be discussing Low Molecular Weight Heparin (LMWH) and regional anesthesia.
A 48 y/o white male presents to the pre-admission test center to get his workup prior to his anterior cruciate ligament repair. He takes warfarin for atrial fibrillation and was instructed to discontinue it 5 days prior to his procedure and to start lovenox (enoxaparin - the most common LMWH used in the United States) 30 mg twice a day. He is planning to inject his last dose the night prior to the surgery and desires an epidural anesthetic.
1.  Is it safe to provide a regional anesthetic on this setting?
2.  How about if this patient was receiving a higher dose of LMWH such as 70 mg twice a day?
3.  Is there any role in monitoring the Heptest (antifactor Xa level) prior to a regional anesthetic?
今天我们讨论低子量肝素（LMWH）与区域阻滞
一48岁白种男性在行前交叉韧带手术前到院前诊断中心行手术前评估。其因房颤一直在服用华法林，医生要求其在手术前5日停止服用华发林而改用依诺肝素（美国最常用的LMWH）30mg,2次/日。患者准备在术前晚注射最后一次剂量的肝素，并希望接受硬膜外麻醉方法。
1.在该情况下实施区域阻滞是否安全？
2.如果该患者接受更高剂量肝素（如70mg,2次/日），实施区域阻滞是否安全？
3.在实施区域阻滞前监测Heptest (抗因子Xa水平)是否有用？

[每周一问]NO.10-低子量肝素（LMWH）与区域阻滞[病例讨论] 参考答案
1.在该情况下实施区域阻滞是否安全？
如上周综述中所述，LMWH的血浆半衰期在皮下注射后为3-6小时。因此，在2个半衰期后大多数抗纤维蛋白酶活性降低而抗因子Xa保持在50%水平[1]。LMWH在最后一次预防剂量后24小时完全从循环中清除。ASRA指南推荐在实施区域阻滞前给予LMWH时至少要过10-12小时方可实施。指南进一步强调在该情况下应该首选单次腰麻作为区域阻滞[2]。在Brigham and Women's Hospital (BWH)，通常要求为停止使用24小时方可实施区域阻滞。

2.如果该患者接受更高剂量肝素（如70mg,2次/日），实施区域阻滞是否安全？
急性静脉血栓或急性冠状动脉综合征的患者经常接受高剂量的LMWH (1 mg/kg，2次/日)。为治疗活动性血栓，必须监测抗Xa因子(Heptest)的水平并维持在0.4-1.0 U/mL[3]。在接受更高剂量预防性的LMWH的患者在实施穿刺时必须推迟24小时以上[2] 。

3.在实施区域阻滞前监测Heptest (抗Xa因子水平)是否有用？
ASRA指南强调，因为抗Xa因子水平并非出血危险的预测因素，因此不推荐监测抗Xa因子水平。而麻醉届以外的部分权威人士则认为heptest可以预测出血，同时他们认为，在血浆肝素水平<0.2 U/mL时实施有创性操作是安全的[3]。在BWH医院我们的作法是：仅在患者接受比常规剂量(>1 mg/kg)还高剂量的LMWH治疗时，检测heptest。接受如此大剂量肝素治疗的患者一般不实施区域阻滞，除非最后一次LMWH治疗超过24小时，同时heptest i< 0.2 U/mL.

Is it safe to provide a regional anesthetic on this setting?
As mentioned in last week's review, the plasma half-life of LMWH is three to six hours after subcutaneous injection. Therefore after 2 half-lives, most of the anti-thrombin activity has diminished but anti-Xa levels remain at 50% of peak levels (1). LMWH is completely cleared from the circulation 24 hours after the last prophylactic dose. The American Society of Regional Anesthesia (ASRA) guidelines for LMWH and neuraxial block recommend to wait at least 10-12 hours after the LMWH prior to the administration of a regional anesthetic. The guidelines further state that a single-dose spinal anesthetic is the preferred regional technique in this setting (2). It is our practice at the Brigham and Women's Hospital (BWH) to discontinue the LMWH for at least 24 hours prior to the administration of a regional anesthetic.
How about if this patient was receiving a higher dose of LMWH such as 70 mg twice a day?
Patients with acute venous thrombosis or acute coronary syndromes receive a high weight-adjusted dose of LMWH (1 mg/kg) twice a day. For treatment of active thrombosis, the plasma antifactor Xa level (Heptest) should be monitored and targeted to the range of 0.4-1.0 U/mL (3). Needle placement should be delayed greater than 24 hours in patients receiving higher doses of thromboprophylaxis with LMWH (2).
Is there any role in monitoring the Heptest (antifactor Xa level) prior to a regional anesthetic?
The ASRA guidelines state that testing of antifactor Xa level is not recommended as it is not predictive of the risk of bleeding. There are some authorities outside of the field of anesthesia that believe that the heptest is predictive of bleeding and state that a plasma heparin level <0.2 U/mL is safe prior to the performance of an invasive procedure (3). It is our practice at BWH to only measure the heptest if the patient was taking a higher than usual dose (>1 mg/kg) of LMWH. Patients receiving such a high dose will not be administered a regional anesthetic unless the last dose of LMWH was greater than 24 hours prior to the anesthetic and the heptest is < 0.2 U/mL.
Question Author: David Hepner, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
References:
1.  Horlocker TT, Heit J. Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis regimens, and guidelines for regional anesthetic management. Anesth Analg 1997;85:874-85.
2.  Horlocker TT, Wedel DJ. Neuraxial block and low molecular weight heparin: balancing perioperative analgesia and thromboprophylaxis. Reg Anesth Pain Med 1998:23 Suppl. 7-8.
3.  Aguilar D, Goldhaber SZ. Clinical uses of low-molecular-weight-heparins. Chest 1999;115:1418-23.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
Founders and Editors-in-Chief: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School

Today we will finish our discussion with a very controversial topic: when to pull epidural catheters in patients receiving warfarin or Low Molecular Weight Heparin (LMWH) prophylaxis.
1.Does it really matter when you remove the epidural catheter in an anticoagulated patient?
2.Are there any guidelines for the removal of epidural catheters in anticoagulated patients?
今天我们通过一非常有争议的话题结束讨论：对于接受华发林或LMWH预防性治疗的患者什么时候拔除硬膜外导管。
1.对抗凝患者拔除硬膜外导管时真的重要吗?为什么？
2.抗凝患者拔除硬膜外导管遵循原则是什么？

1.时机很重要，因为不论是置管还是拔管都增加硬膜外血肿的机会。
2.接受华发林的患者拔管时INR<1.5,接受LMWH的导管要在最后一次剂量10~12h后拔除，并且随后要给的LMWH最少要在拔除后2小时给，拔管后要在24h内常规检查躯体感觉和运动，如果INR>1.5时拔管要在更长的时间内注意运动和感觉的检查。
3.在TEG中低凝状态和凝血因子未恢复可见到r和K值明显延长，Ma和Me变小

参考答案
1.对抗凝患者拔除硬膜外导管时真的重要吗?为什么？
拔除硬膜外导管如同放置导管一样具有创伤性。Vandermeulen及其同事回顾性分析了61例在硬膜外或蛛网膜下腔麻醉后发生椎管内血肿病历后发现，其中53例（或87%）因抗凝药物使用而导致凝血功能异常，或穿刺针置入及导管拔除时凝血功能障碍。此外硬膜外麻醉下发生率为75%（46/61），而其中47%发生在拔除导管时。作者通过这些结果得出结论：在凝血功能异常患者及导致椎管内血肿的风险上，拔除硬膜外导管与放置同样重要[1]。
2.抗凝患者拔除硬膜外导管遵循原则是什么？
ASRA关于轴索麻醉和抗凝状态一致强调，对于接受口服抗凝药治疗患者拔除硬膜外导管没有作出确定的建议。他们进一步强调当决定是否拔除硬膜外导管时，应该进行临床判断。指南建议在导管拔除后进行神经病学测验24小时，如果在导管拔除时INR>1.5，评估应该超过24小时[2]。
治疗剂量的非分化肝素（使PTT达到60-80）经常用于接收轴索麻醉患者。ASRA指南建议导管拔除前，肝素应停止使用2-4小时并评估PTT。拔除导管后1小时内不用肝素[3]。
正如我们上周所述，LMWH生物利用度好、半衰期长、剂量反应可以预测，是现在常用的的抗凝选择。在最后一次剂量LMWH后导管拔除至少推迟10-12小时，导管拔除后至少2小时后方可使用LMWH[4]。我们在Brigham and Women's Hospital的做法是：在最后一次LMWH后24小时拔除导管，此时凝血功能完全正常。
对于凝血链的完整理解及如何确定药物的影响对于我们实施局部麻醉与镇痛很重要。过去两周我们回顾了在外科手术前和局部操作技术前抗凝治疗的管理主题。我们也回顾了在通常使用抗凝治疗情况下连续轴索镇痛方法的使用。

Does it really matter when you remove the epidural catheter in an anticoagulated patient?
Removal of an epidural catheter could be as traumatic as the placement. Vandermeulen and colleagues reviewed 61 case reports of spinal hematoma after epidural or subarachnoid anesthesia and found that 53/61 cases or 87% had an abnormality in coagulation because of an anticoagulant drug or a clotting disorder at the time of needle placement or catheter removal. Furthermore 75% of cases (46/61) happened when an epidural anesthetic was used and of those 47% (15/32) occurred when the epidural catheter was removed. These results lead the authors to the conclusion that removal of an epidural catheter is just as critical as the placement in terms of coagulation abnormalities and the risk of a spinal hematoma (1).

Are there any guidelines for the removal of epidural catheters in anticoagulated patients?
The American Society of Regional Anesthesia (ASRA) consensus statements on neuraxial anesthesia and anticoagulation states that no definitive recommendation can be made for removal of epidural catheters in patients with therapeutic levels of oral anticoagulants. They further state that clinical judgment should be used when making decisions about removing epidural catheters. The guidelines recommend neurologic testing for 24 hours after catheter removal and longer than 24 hours if the INR >1.5 at the time of catheter removal (2).
Unfractionated heparin in therapeutic doses (to try to achieve a partial thromboplastin time (PTT) of 60-80) is occasionally used in patients receiving neuraxial analgesia. The ASRA guidelines recommend that prior to catheter removal the heparin be discontinued for 2-4 hours and that the PTT be evaluated. The heparin should be withheld for one additional hour after catheter removal (3).
As mentioned last week, low molecular weight heparin (LMWH) has a good bioavailability, long half-life, and predictable dose response and is now the anticoagulant of choice in many situations. Catheter removal should be delayed at least 10-12 hours after the last dose of LMWH and the next dose should not be given until two hours after catheter removal (4). Our practice at the Brigham and Women's Hospital is to remove epidural catheters 24 hours after the last dose of LMWH as a complete normalization of the coagulation is achieved at this time.
A complete understanding of the coagulation cascade and how certain medications affect it is essential for our practice of regional anesthesia and analgesia. During the last two weeks we have reviewed this topic as well as the management of anticoagulants prior to a surgical procedure and prior to a regional technique. We have also reviewed the use of continuous neuraxial analgesia in the presence of commonly used anticoagulants.
Question Author: David Hepner, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
References:
1.  Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg 1994;79:1165-77.
2.  Enneking KF, Benzon HT. Oral anticoagulants and regional anesthesia: A perspective. Reg Anesth Pain Med 1998:23 Suppl. 3.
3.  Liu SS, Mulroy MF. Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain Med 1998:23 Suppl. 6.
4.  Horlocker TT, Wedel DJ. Neuraxial block and low molecular weight heparin: balancing perioperative analgesia and thromboprophylaxis. Reg Anesth Pain Med 1998:23 Suppl. 7-8.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
Founders and Editors-in-Chief: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School


周中问之参考答案
记住ASRA关于轴索麻醉与抗凝指南很重要。指南不推荐监测抗Xa水平或同时的其他实验室检测[1]。
近期的前期研究与血栓弹性描记法（TEG）测定的抗Xa浓度相关[2]。TEG是一全血测量，其检测与凝血相关的所有血液成分的网状结构产物。TEG可以判断凝血强度、凝血块形成、加强及纤溶速度。此外，可以检测血小板功能、血浆因子活性以及凝血功能相关的激活和抑制因素。TEG可以对全身凝血功能状态进行快速、简单的测量，在创伤、心血管及肝脏手术中应用广泛[3-5]。晚近研究中，TEG已经用于研究高危产科病人特别是血小板减少症患者的凝血状况[6-8]。
Klein及其同事证实了在TEG在反应时间（R-time，可检测到血快形成的第一显著水平需要的时间）和K-时间（血块变硬时间）方面与血清抗-Xa因子水平的高峰具有相关性。他们进一步证实，R-time在给与LMWH3天内延长，血清抗-Xa因子呈相应趋势。他们假定了在R-time与抗-Xa因子水平在前2天的相关性，推导出第三天的对LMWH的反应结果有夸大。他们的结论为：TEG在检测LMWH活动是有帮助的，因为其可以测量全部凝血功能并与抗-Xa因子具有相关性。
虽然该项工作是有趣并在将来是有用的，但是其代表的是前期的信息并不能用于临床实践，直到得到进一步的验证。而且，如上所述，在实施局部麻醉前抗-Xa因子测量的有用性尚存在明显争议。

Yesterday we discussed the controversy behind the monitoring of anti-Xa level and the risk of bleeding in patients receiving LMWH. Is there any other test that may be helpful in monitoring the coagulation status in patients receiving LMWH?
It's important to remember that the American Society of Regional Anesthesia (ASRA) guidelines for neuraxial anesthesia and anticoagulation do not recommend monitoring the anti-Xa level or any other laboratory test at the present time (1).
Preliminary work done recently has correlated the anti-Xa concentration with the thromboelastography (2) (TEG-please refer to week of March 26). TEG is a whole blood test that measures the net product of all blood components involved in coagulation. TEG can determine the clot strength, the rate of clot formation/strengthening and fibrinolysis. In addition, it is a test of platelet function, plasma factor activity, and activators and inhibitors of coagulation. TEG is a rapid, simple, and global test of coagulation and has useful applications in trauma, cardiac, vascular and hepatic surgery (3-5). More recently, TEG has been extended to study the coagulation profile in high-risk obstetric patients particularly those with thrombocytopenia (6-8).
Klein and colleagues demonstrated a correlation between the reaction time (R-time or time until the first significant levels of detectable clot formation) and K-time (clot firmness) of the TEG and the peak and through serum anti-Xa levels. They further demonstrated that the R-time was prolonged at the time of the through serum anti-Xa level on day 3 of the administration of LMWH. These authors hypothesized that given the correlation of R-time and anti-Xa levels during the first two days, these results may indicate an exaggerated response to LMWH on day three. Their conclusion was that TEG might have a role in following LMWH activity because it measures the overall coagulation and also because of its correlation with anti-Xa levels.
Although this work is very interesting and may be useful in the future, it represents preliminary information and cannot be used in clinical practice until it is further validated. Furthermore, as mentioned above, there is significant controversy in the usefulness of measuring the anti-Xa level prior to the administration of a regional anesthetic.
Question Author: David Hepner, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
References:
1.  Horlocker TT, Wedel DJ. Neuraxial block and low molecular weight heparin: balancing perioperative analgesia and thromboprophylaxis. Reg Anesth Pain Med 1998:23 Suppl. 7-8.
2.  Klein SM, Slaughter TF, Vail PT, et al. Thromboelastography as a perioperative measure of anticoagulation resulting from low molecular weight heparin: a comparison with anti-Xa concentrations. Anesth Analg 2000;91:1091-5.
3.  Kaufmann CR, Dwyer KM, Crews JD, Dols SJ. The usefulness of thromboelastography in assessment of trauma patient coagulation. The Journal of Trauma 1987;42:716-22.
4.  Kang YG, Martin DJ, Marqueq J, Lewis JH, Bontempo FA, Shaw BW, Starzi TE, Winter PM. Intraoperative changes in blood coagulation and thromboelastographic monitoring in liver transplantation. Anesth Analg 1985;64:888-896.
5.  Tuman KJ, Spiess BD, McCarthy RJ, Ivankovich KD: Comparison of viscoelastic measurements of coagulation after cardiopulmonary bypass. Anesth Analg 1989;69:69-75.
6.  Sharma SK, Philip J, Wilen J. Thromboelastographic changes in healthy parturients and postpartum women. Anesth Analg 1997;85:94-8.
7.  Sharma SK, Vera RL, Stegall WC, Whitten CW. Management of a postpartum coagulopathy using thromboelastography. Journal of Clinical Anesthesia 1997;9:243-7.
8.  Irkujiwsju CEP, Rocke DA, Muray WB, Gouws E, Moodley J, Kenoyer DG, Byrne S. Thromboelastography changes in preeclampsia and eclampsia. Brit J Anaesth 1996;77:556-8.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
Founders and Editors-in-Chief: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School

Cardiopulmonary resuscitation (CPR) is a skill that has significant impact on asystolic patient survival. This week, we'll discuss some recent changes in the performance of this skill. Today we'll discuss some basic facts regarding CPR.
1.What is the primary determinant of CPR effectiveness?
2.How much time may elapse following cardiac arrest for patient survival to occur?
3.Is CPR with only chest compressions effective?
心肺复苏（CPR）
CPR对心搏停止病人的存活影响显著。本周，我们将讨论在这方面的一些新变化，今天我们讨论关于CPR的基本情况。
1.评价CPR效果的基本决定因素是什么？
2.对病人存活影响的心跳停止时间为多长？
3.仅仅实施胸部按压CPR是否有效？
一.CPR效果的基本决定因素是:
1.进行CPR的时间。
2.病人的导致心肺停止病因
3.进行CPR的操作是否正确。
二.对病人存活影响的心跳停止时间4~6分钟
.三仅仅实施胸部按压CPR无效，因行CPR的原则为ABCDE。
a.保持呼吸道通畅b行人工通气c. 行胸部按压。
ABCDE应同时进行

提示：
第一题可以重点从对心肺复苏的生理效果来评价
第三题如果是简单的否定或肯定未免显得本题意义不大，但是其结果真的是值得所有从事复苏工作的医务人员思考的。
xyft9707提供的连接很重要，大家可以对该内容进行较深入的阅读相信会发现令人惊讶的内容
其中文中有一段这样的话：In any case, an editorialist -- a CPR researcher -- states that this report is "of immense importance and will have worldwide implications."

[每周一问]NO.12-Cardiopulmonary resuscitation (CPR)

1.评价CPR效果的基本决定因素是什么？
最近研究的室颤病人，心肌和脑灌注是CPR效果的基本决定因素[1]。而脑和纤颤心脏继续消耗ATP和其他能源，这是确定的。如果心肌缺血时间过长，心肌细胞死亡，此时的电除颤只会产生无脉性电活动或心搏停止。
同样，发生于医院之外的由于室颤导致的心跳停止的总的生存率的重要影响因素包括是否有目击者发现并开始CPR，以及心脏除颤多久完成。

2.对病人存活影响的心跳停止时间为多长？
Eisenberg等[2]的一经典研究发现，院外发现病人因室颤发生心跳停止时，如果CPR能在4分钟内进行并8分钟内开始实施确定性治疗，43%可以存活出院。相比之下，如果CPR在8和16分钟开始，只有7%和0%的病人存活。

3. 仅仅实施胸部按压CPR是否有效？
过去十年，人们试图通过实验室研究评估单纯胸外按压行CPR的价值。在室颤导致的心跳停止的猪的模型中，发现24小时存活率在单纯胸外按压组与合并呼吸辅助组相近[3]。最近，Hallstrom等[4]通过一城市急救医学服务机构开展的研究，随机化通过电话指导目击者实施带或不带有呼吸辅助的CPR，存活出院作为研究的基本终结点，单独胸外按压CPR者241名，呼吸辅助CPR者279名病人，存活率分别为14.6%和10.4%（P = 0.18，无显著意义）。同样，landmark研究也支持单独胸外按压CPR可以应用于目击者实施CPR的情况，并与告知的CPR的方法有关。这个研究证明对于目击者实际实施CPR的意愿有重要影响。在对975名告知其假定知道如何实施CPR调查发现，如果仅仅要求对陌生人进行胸外按压，68%调查者确定会实施CPR；而如果需要口对口辅助呼吸时，只有15%愿意这样做[5]。

What is the primary determinant of CPR effectiveness?
In patients with ventricular fibrillation of recent onset, myocardial and cerebral perfusion are the primary determinants of CPR effectiveness (1). This is true as the brain and the fibrillating heart continue to consume ATP and other energy sources. Should myocardial ischemia continue too long, myocyte death occurs, and electrical shock after this will only result in pulseless electrical activity or asystole.
As such, the major determinant of overall survival after witnessed out of hospital cardiac arrests due to ventricular fibrillation include whether a bystander initiates CPR, and how quickly defibrillation is accomplished.
How much time may elapse following cardiac arrest for patient survival to occur?
In a classic study by Eisenberg et al. (2) observing patients with out-of-hospital cardiac arrest due to ventricular fibrillation, 43% survived to hospital discharge if CPR was initiated and definitive therapy was delivered in four and eight minutes, respectively. By contrast, if CPR was initiated in 8 or 16 minutes, 7% and 0% of patients survived.
Is CPR with only chest compressions effective?
In the past decade, laboratory studies have attempted to evaluate the value of CPR with chest compressions only. In the swine model of cardiac arrest induced by ventricular fibrillation, survival at 24 hr. was noted to be similar to when CPR included only chest compression as when it involved assisted breathing and chest compressions (3). Recently, and of immense importance, Hallstrom et al. (4) in a trial conducted through an urban emergency medical services system, randomized telephone dispatchers to inform bystanders to perform CPR using chest compressions with or without assisted breathing. Using as their primary endpoint survival to hospital discharge, of the 241 and 279 patients in the CPR alone and with assisted breathing, respectively, the rate of survival was 14.6 versus 10.4% (P = 0.18 i.e. a non-significant difference). As such, this landmark study supports the idea that CPR with chest compressions alone may be applicable to the setting of the bystander-initiated CPR, and may have implications to the way CPR is taught. This demonstration may also have an important impact on bystanders willingness to actually perform CPR. In a survey of 975 laypersons instructed to assume that they knew how to perform CPR, 68% reported that they would definitely perform CPR on a stranger if only chest compressions were required, whereas only 15% would do so if mouth-to-mouth assisted ventilation was also necessary (5).
References:
1.  Ewy GA. Cardiopulmonary resuscitation-strengthening the links in the chain of survival. N Engl J Med 2000;342:1599-601.
2.  Eisenberg MS, Bergner L, Hallstrom A. Cardiac resuscitation in the community. Importance of rapid provision and implications for program planning. JAMA. 1979;241(18):1905-7.
3.  Berg RA, Kern KB, Hilwig RW, Ewy GA. Assisted ventilation during 'bystander' CPR in a swine acute myocardial infarction model does not improve outcome. Circulation. 1997;96(12):4364-71.
4.  Hallstrom A, Cobb L, Johnson E, Copass M. Cardiopulmonary resuscitation by chest compression alone or with mouth-to-mouth ventilation. N Engl J Med. 2000;342(21):1546-53.
5.  Locke CJ, Berg RA, Sanders AB, et al. Bystander cardiopulmonary resuscitation. Concerns about mouth-to-mouth contact. Arch Intern Med. 1995;155(9):938-43.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
Founders and Editors-in-Chief: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School

Cardiopulmonary resuscitation (CPR)
Cardiopulmonary resuscitation (CPR) is a skill that has significant impact on asystolic patient survival. This week, we'll discuss some recent changes in the performance of this skill. Today we'll discuss ventilation changes with CPR.
1.  What is an important change to the Guidelines 2000 for CPR in regards to ventilation?
2.  How do esophageal detector devices work?
3.  What are CO2 confirmation devices sometimes misleading?
4.  Any new recommendations in regards to ventilation tidal volume?
5.  Are there recommendations regarding endotracheal tube holders/securing devices?
CPR是对心搏停止患者的存活有显著影响的一种方法。本周，我们讨论关于该方法的一些近期变化。今天我们讨论CPR的机械通气变化。
1.  CPR2000年指南中关于机械通气的重要变化是什么？
2.  食道探测设备是如何工作的？
3.  CO2确认设备（注：如PETCO2）在什么情况下可出现误导？
4.  关于机械通气潮气量的新建议是什么？
5.  关于气管导管支架或安全设备有没有什么建议？

1,4:CPR中机械通气要用容量控制模式，不能用压力控制模式。并为院前抢救设计患者转运通气装置（ATVs)。G2000建议潮气量潮气量控制在10～15 ml/kg；呼吸频率在12～15次/min; 呼吸间隔在2秒以上并提供纯氧。
2：食道探测设备在气管导管末端产生吸引力，如果气管插管在食道中这种引力推压食道黏膜阻碍检测仪的末端，阻止检测仪活塞的运动或使吸引囊再次彭起。
3：患者在心搏停止前进使用过碳酸盐，或复苏中用NaHCO3会出现误导。

本期问题可能因为翻译的准确性较差参与人很少，看来要好好提高翻译水平了，也欢迎大家对翻译中存在的问题给予批评指正，也正是处于考虑翻译可能有误解，每次中英文不同进行，大家参考。
本期答案：
1.CPR2000年指南中关于机械通气的重要变化是什么？
虽然在上周的问题中我们讨论了CPR仅仅进行胸外心脏按压的作用，但是该技术需要进一步成功的确认。然而根据指南，众多学者[1]推荐的新建议中最重要的一条是，正确的气管导管位置必须由CPR实施者予以确定。包含在其中的是大多数麻醉学家非常熟悉的设备，如食道探测设备，呼吸末CO2定量检测设备，CO2图及capnometric设备（详细信息见1998年11月10 问题）

2.食道探测设备是如何工作的？
通过一大注射器或可压缩的弹性容器在气管导管末端产生一吸引力的设备，可帮助鉴别气管内插管术。在食道，靠近气管导管远端的粘膜溃烂，因此限制了注射器回抽的能力或弹性可压缩容器的膨胀性。相比之下，气管软骨环允许注射器或压缩容器的完全膨胀。

3.CO2确认设备（注：如PETCO2）在什么情况下可出现误导？
在低肺血流状态如完全心搏停止，呼吸末CO2不足将可能导致CO2确认设备错误地认为进行了食道插管。相比之下，对于摄入含CO2液体患者，食道插管可事实的产生CO2读数，因此延缓不正确气管内插管的纠正时机。因此，临床征象如胸廓移位、肺部和上腹部听诊，直接喉镜检查应该如同CO2确认设备一样重要的使用。
有趣的是，在非CPR情况下研究者发现CO2确认设备对于经鼻胃管位置的正确判断有帮助[2]。
4.关于机械通气潮气量的新建议是什么？
关于潮气量在新指南中有精细的差别。当对不安全气道使用囊-阀门设备（如呼吸囊辅助呼吸）时，指南建议使用低流量温和通气，潮气量为2S以上6-7 mL/kg。这个比气管内插管后建议的10-12 mL/kg低，期望胃膨胀降低，但是随后发现有反流误吸。
5.关于气管导管支架或安全设备有没有什么建议？
不同组织的复苏指南[1，4]认识到了大量发生在成功插管后的气管内导管移动现象。像这样，安全稳妥的固定导管位置应该被强调。并且，CO2检测设备和氧饱和度监测在长时间转运过程中被推荐使用。没有特别的气管内导管固定产品被推荐。
What is an important change to the Guidelines 2000 for CPR in regards to ventilation?
Although in yesterday's Question of the Day we discussed the use of chest compression only CPR, the promotion of these technique awaits further confirmation of its success. In terms of the guidelines, however, and considered one of the most important new recommendations by many experts (1) is that confirmation of proper tracheal tube position must be made by CPR responders. Included in these are devices which most anesthesiologists are very familiar, i.e. esophageal detector devices, qualitative end-tidal CO2 indicators, and capnographic and capnometric devices (for further details, see the Question of the Day for November 10, 1998).
How do esophageal detector devices work?
Devices that create a suction force at the tracheal end of an endotracheal tube, either through a large syringe or a compressible flexible bulb, may assist in identifying an endotracheal intubation. In the esophagus, the mucosa collapses against the distal end of the endotracheal tube, thereby limiting the ability to fully pull back on a syringe or for a flexible compressed bulb to reexpand. By contrast, the cartilaginous rings of the trachea allow for full expansion of a syringe or a compressed bulb.
What are CO2 confirmation devices sometimes misleading?
In low pulmonary blood flow states such as with a full cardiac arrest, an insufficient amount of expired CO2 would allow a CO2 confirmation device to falsely indicate an esophageal intubation. By contrast, in patients who have ingested carbonated liquids, an esophageal intubation may actually produce CO2 readings and delay the removal of an improperly sited endotracheal tube. Thus, clinical signs, such as chest excursion, auscultation of lungs and over the epigastrium, and direct laryngoscopy should be used as important confirmatory adjuncts.
Interestingly, in non-CPR situations, some investigators have found these CO2 confirmatory devices useful to confirm proper nasogastric tube placements (2).
Any new recommendations in regards to ventilation tidal volume?
There is a subtle distinction in the new guidelines in regards to tidal volume. When using bag-valve devices with an unsecured airway, the guidelines recommend a slow and gentle delivery of a tidal volume of 6-7 mL/kg over 2 seconds. This is lower than the 10-12 mL/kg recommended following the placement of an endotracheal tube, and conceivably a reduction in gastric inflation, subsequent regurgitation and aspiration may be seen.
Are there recommendations regarding endotracheal tube holders/securing devices?
A number of resuscitation guidelines by different organizations (1,4 ) recognize the significant number of endotracheal tube dislodgments that occur following a successful placement. As such, continued attention to securely tying or taping the tube in place has been emphasized. Moreover, the use of CO2 detectors and oxygen saturation monitors have been recommended for long transport efforts. No specific commercial endotracheal tube securing devices have been recommended.
References:
1.  Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: advanced cardiovascular life support: 7C: a guide to the International ACLS algorithms. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation. 2000;102(8 Suppl)142-57.
2.  Menegazzi JJ, Heller MB. Endotracheal tube confirmation with colorimetric CO2 detectors. Anesth Analg. 1990;71(4):441-2.
3.  Thomas BW, Falcone RE. Confirmation of nasogastric tube placement by colorimetric indicator detection of carbon dioxide: a preliminary report. J Am Coll Nutr. 1998;17(2):195-7.
4.  Cummins RO, Hazinski MF. Guidelines based on the principle 'First, do no harm'. New guidelines on tracheal tube confirmation and prevention of dislodgment. Resuscitation. 2000;46(1-3):443-7.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
Founders and Editors-in-Chief: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School

Cardiopulmonary resuscitation (CPR) is a skill that has significant impact on asystolic patient survival. This week, we'll discuss some recent changes in the performance of this skill. Today we'll discuss some new antiarrhythmic drug recommendations.
1.  How are recommendations for drug treatments classified?
2.  What is the status of bretylium for the treatment of ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT)?
3.  What is the status of lidocaine for the treatment of ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT)?
4.  What is the role of amiodarone in the treatment of ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT)?
今天我们讨论新的抗心律失常药物。
1.  治疗心律失常药物循证医学如何分类？
2.  溴苄胺在室颤（VF）或无脉性室性心动过速（VT）治疗中处于何种地位？
3.  利多卡因在室颤（VF）或无脉性室性心动过速（VT）治疗中处于何种地位？
4.  胺碘酮在室颤（VF）或无脉性室性心动过速（VT）治疗中的作用是什么?
1: 指南2000对抗心律失常药物可能是致心律失常药物的循证评价，药物致心律失常的可能对受到损害的心脏变得尤为重要，在受到损害的心脏正常的心肌间以疤痕和受损的组织，这些区域成为折返性心律失常、异位起搏点和传导阻滞的根源。不考虑抗心律失常药物的Vaughn-Williams分级，所有抗心律失常药物都有致心律失常作用，当应用第二种抗心律失常药物时，负面作用是呈指数级增长。因此，指南建议每个病人用1种，且只用1种抗心律失常药物，这将显著减少1种以上抗心律失常药物导致病人状况明显恶化的事件的发生。

3: 由于β阻滞剂的应用，使得室颤的发生率已降到较低的水平。ISIS-Ⅲ的一项数据分析显示，利多卡因虽能降低室颤率却同时有增加死亡率的倾向，这可能与心脏收缩力减弱有关。一项荟萃分析和新的临床数据支持这一假设，这使它能降低室颤治疗作用有所抵销。目前不提倡利多卡因做预防性应用和治疗无症状的恶性心律失常。
呵呵！其他的要听各位老大的建议了。

1Vaughn Williams分类法
2溴苄胺可用于对电除颤和肾上腺素治疗无效的VT和VF，但其副作用大，来源受限，而且已有同样有效又更为安全的药物。
3利多卡因只用于电除颤和给予肾上腺素后仍表现为VF或无脉性VT的病人；利多卡因也可作为其他药物无效时的第二选择。
4心脏停搏患者，如持续性VT或VF，在电除颤和使用肾上腺素后，使用胺碘酮。对严重心功能不全患者静注胺碘酮比其他抗房或室性心律失常的药物更适宜。

参考答案：
1.治疗心律失常药物循证医学如何分类？
2000年国际指南会议在决定对心律失常药物的使用问题上使用了循证医学原则。这些药物被分为以下几种：
如下图。
2.溴苄胺在室颤（VF）或无脉性室性心动过速（VT）治疗中处于何种地位？
一旦在VF或无脉性VT电除颤后推荐使用Ⅱb类药物治疗，溴苄胺现已被排除在该系统外[2]。部分是因为世界上生产溴苄胺的自然资源近乎耗尽、有限的优点以及高副作用，特别是在复苏后出现低血压。溴苄胺是Ⅱb类药物，乙胺碘呋酮（另一Ⅱb类药物）可以代替溴苄胺使用。
3.利多卡因在室颤（VF）或无脉性室性心动过速（VT）治疗中处于何种地位？
利多卡因被乙胺碘呋酮替代，并被归于不确定的分类中，因为其在在VF或无脉性VT中作用能够很弱且支持其的文献都已经过时。此外，在MI>8年以上情况时，利多卡因已不被推荐常规用于预防性室性心律失常的治疗[2]。然而对急性心梗，利多卡因似乎可减低VF的发生，但是不会降低死亡率。结果是，利多卡因不被推荐预防性使用。利多卡因仍旧用于顽固性VF和无脉性VT、室早导致的血流动力学损害，以及血流动力学稳定性VT[1]。
4.胺碘酮在室颤（VF）或无脉性室性心动过速（VT）治疗中的作用是什么?
虽然关于乙胺碘呋酮的抗心律失常作用只有一些证据支持，但是用于VF或无脉性VT的的药物中，乙胺碘呋酮比其他药物（包括利多卡因、镁（如果低镁）、和普鲁卡因酰胺）有更多的文献支持[1]。此外，对于稳定的单一型和多样型VT，乙胺碘呋酮推荐作为Ⅱb类药物。最后，对于血流动力学稳定范围较大的复杂心动过速，特别是对于心功能不全的病人，乙胺碘呋酮作为优于利多卡因和腺苷的Ⅱb类药物而被推荐[2]

How are recommendations for drug treatments classified?
The "International Guidelines 2000" conference used the principles of evidence-based medicine in determining their final recommendations on drugs. These drugs were divided into the following classes (1):
What is the status of bretylium for the treatment of ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT)?
Once a recommended IIb therapy following defibrillation for VF/ pulseless VT, bretylium has now been omitted from this algorithm (2). In part, this stems from the world's natural sources for bretylium being almost exhausted, the limited information confirming its benefit, and the high incidence of side effects, in particular hypotension, in the postresuscitation setting. Bretylium was and remains a Class IIb drug. In lieu of bretylium, amiodarone (another Class IIb drug) can be used.
What is the status of lidocaine for the treatment of ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT)?
Lidocaine was supplanted by amiodarone and placed in the "indeterminate" classification due to the weak and dated references supporting its use for VF/pulseless VT. Moreover, lidocaine is no longer recommended for routine prophylaxis of ventricular arrhythmias in the setting of an MI > 8 years ago (2). For acute MI, however, lidocaine appears to reduce the incidence of VF, but does not lower mortality. Consequently, lidocaine is not recommended as a routine prophylaxis. Lidocaine does remain in use for persistent VF/pulseless VT, hemodynamically compromising PVC's, and hemodynamically stable VT (1).
What is the role of amiodarone in the treatment of ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT)?
Although only fair evidence exists on its antiarrhythmic properties, amiodarone has greater literature support than other agents used in the VF/pulseless VT algorithm (which include lidocaine, magnesium (if hypomagnesemic), and procainamide) (1). Moreover, for stable monomorphic and polymorphic VT, amiodarone has been recommended as a Class IIa agent. Finally, for hemodynamically stable wide complex tachycardia, especially in patients with compromised cardiac function, amiodarone has been promoted as a class IIb drug ahead of lidocaine and adenosine (2).
References:
1.  2000 Handbook of Emergency Cardiovascular Care for Healthcare Providers. American Heart Association. 2000.
2.  Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: advanced cardiovascular life support: 7C: a guide to the International ACLS algorithms. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation. 2000;102(8 Suppl)142-57.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
Founders and Editors-in-Chief: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical Scho

Cardiopulmonary resuscitation (CPR) is a skill that has significant impact on asystolic patient survival. We'll discuss some recent changes in the performance of this skill. Today we'll discuss some special challenges in resuscitation.
1.  What should be the response to cocaine toxicity?
2.  What should be the response to tricyclic overdose?
3.  What should the response be to acute opiate overdose?
今天我们讨论关于急救复苏中的一些特殊问题：
1.  可卡因中毒如何处理？
2.  三环类抗抑郁药过量如何处理？
3.  急性阿片剂过量如何处理？

1. 可卡因中毒如何处理？
可卡因的作用时间很短,急性中毒一般不需要治疗,如果超量必需处理可给予巴比妥或安定,同时给予密切观察和支持性处理.对于可卡因引起的高热和血压升高对症处理.
2. 三环类抗抑郁药过量如何处理？
三环类抗忧郁药中毒确诊后应快速静滴碳酸氢钠直到ＰＨ值接近正常，在６小时内洗胃，并通过胃管注入活性碳达到吸附作用，２４小时后导泻．药物方面应用毒扁豆碱，首次静注２mg,必要时２０分钟后重复，对毒扁豆碱引起的副作用可以用阿托品拮抗．
3. 急性阿片剂过量如何处理？
急性阿片中毒的主要表现：瞳孔针尖样大小，呼吸抑制，昏迷．首先给予全身支持疗法，昏迷病人要保持气道通畅必要是气管插管．口服的病人用高锰酸钾洗胃，硫酸镁导泻．用阿片类的特异性拮抗剂naloxone,可首次0.4mg静注，因其作用时间为６０～～９０分钟要注意再次呼吸抑制的可能性，必要时持续静滴，同时要注意在拮抗的同时引起的血压升高，心率加快等不良反应，对高血压，冠心病，心率失常的病人要慎用．

1. 可卡因中毒如何处理？

可卡因类药物中毒中毒的表现

　　（1）中枢神经系统症状：开始多兴奋、言语增多或淡漠，思睡、瞳孔散大，重时甚至意识不清。也可出现震颤，强直性及阵挛性惊厥，如不及时抢救，可引起呼吸衰竭。

　　（2）循环系统症状：表现面色苍白或紫绀、出冷汗、脉搏细弱而快、血压下降，最后可致循环衰竭。

　　（3）消化系统症状：口干、吞咽困难、恶心、呕吐等。

治疗

急性可卡因中毒无特殊解毒治疗方法，主要为对症支持措施，其处置要点主要是防治癫痫样发作、维持呼吸、保护各重要脏器功能，并注意降温。

　　（1）可卡因类药物中毒，多发生于麻醉过程中。如发现中毒症状，应立即停止用药误服中毒时，应立即催吐，洗胃。洗胃后可在胃在投入鞣酸5克。

　　（2）对症治疗。
对付其中枢神经兴奋作用的特效办法乃静脉注射短效巴比妥类药物，如阿米妥钠（amytal）0.4~0.8g或硫喷妥钠（pentothal sodium0.1~0.2g，注射时需缓慢，并注意患者呼吸情况，必要时可重复使用；反复惊獗者还可静注安定（apozepam）10~20mg；高热时可给物理降温；明显烦躁者还可加用少量氟哌啶醇。

　　（3）一般忌用兴奋药，如咖啡因，可拉明等，因这类药物可过度剌激神经细胞的活动，从而增加氧的消耗，可使中枢抑制的时间反而延长。肾上腺素及吗啡也应忌用。

1.可卡因药理：1.主要是抑制外周去甲肾上腺素的重摄取。2.促去甲肾上腺素显著释放。3.对血清素和多巴胺的释放和重摄取中等程度的抑制。4.阻滞细胞膜Na+通道，使膜静息电位和动作电位振幅减小，并同时延长动作电位时间。5.可阻滞K+通道，并阻滞某些细胞的Na+ -Ca2+交换。6.其脂溶性可以通过血脑屏障，兴奋CNS，尤其是边缘系统的腹侧多巴胺能核群，从而产生欣快感。

病理生理学：快速型心律失常是可卡因中毒的主要死因。其它的死因还有休克、心梗、急性冠脉综合征、蛛网膜下腔出血、高热、精神谵妄、酸中毒、外伤等。

治疗：建立ABC，给氧，静脉通道的建立，心电和血氧的监护，监测血糖、避免低糖血症，苯二氮卓类药物和纳络酮的应用，G2000推荐CPR使用药物为Class IIb 包括肾上腺素、I型抗心律失常药、钙离子通道阻滞剂、β受体阻滞剂、拉贝络尔、纳络酮、氟马西尼，然而以上的这些药物还有相悖的地方。
肾上腺素：与可卡因在心血管方面有类似的效应，而且可卡因抑制其在外周的重摄取，故而G2000和AHA认为应当避免大剂量的使用，并使用的间隔时间应延长。如果室颤和心动过速重新出现或难以控制，或是怀疑肾上腺素or内源性的儿茶酚胺过量，应当考虑停止进一步使用肾上腺素。
利多卡因：使用存在争议，一些动物试验显示其能逆转可卡因对ECG的影响并降低死亡率。一些则认为会降低室颤阈值并增强可卡因的毒性。G2000认为在理论上利多卡因可增加可卡因的毒性；但在临床试验上利多卡因是安全有效的。G2001指出利多卡因的抗心律失常的作用可用于药物所至的VF和单一性的VT。
β受体阻滞剂：有强力的证据支持避免用非选择性的β受体阻滞剂来治疗可卡因所至的心肌缺血。Echocardiographic的研究认为心得安可降低心排和冠脉血流，而且可卡因毒性所致死前通常都是低血压，这会与β受体阻滞剂的效应相叠加。Malbrain et al 认为艾丝络尔可安全用于可卡因中毒，而其合用硝普钠可用于其它治疗无效的恶性高血压。G2000认为拉贝络尔的精细使用（carefully titrated doses ）可做为三线药用于药物所致的急性高血压，然而现在的动物试验发现拉贝络尔可以降低室颤阈值，使动物死亡率增加，故趋向于不用拉贝络尔。
Toxicity, Cocaine
2.TCAs过量主要影响副交感神经系统，CNS，心血管系统。
心血管系统：主要表现为心律失常和低血压。可由TCA的抗胆碱能作用；抑制肾上腺素能突触前去甲肾上腺素的重摄取；奎尼丁效应或胞膜稳定作用，不仅影响心传导功能，可致QRS延长、易出现室速或室颤，也可降低心收缩力。低血压取决于TCA的血药浓度和QRS间期的延长，以及对心肌的直接抑制作用，吩噻嗪类还有α受体阻滞作用。
神经系统：中枢的抗胆碱能作用可致谵妄和幻象，然而TCA过量的患者有50%处于昏睡状态，可有锥系和锥体外系症状，约有20%的患者出现低温、另20%出现体温上升。
还可影响到胃肠道（口干、胃肠蠕动下降、胃排空延迟），沁尿系统（尿潴留），肌肉骨胳系统（肌颤和DTRs下降），肺脏（肺水肿和吸入性肺炎）、眼（瞳孔扩大和对光无反应）

3. 急性阿片剂过量如何处理
明确一点，就是常见的阿片类毒品是吗啡和海洛因，阿片类毒品过量常出现特征性“三联征”，即昏迷、针尖样瞳孔、呼吸抑制（2~4次/分钟）；此外，还可见肺水肿、紫绀、颅压增高等表现，发生横纹肌溶解、肌红蛋白尿及急性肾功能衰竭者亦不少见。 及时留取尿液（24小时内）检测其有无阿片类化合物有助于明确诊断。

中毒的治疗：尽早建立输液通路或／和人工气道，及时人工辅助通气，充分给氧，迅速纠正低氧血症，维持水、电解质和酸碱平衡等，是抢救阿片类中毒病人，维持患者生命体征是最重要的治疗措施

解毒：关键是应用阿片类的拮抗剂，一旦疑为阿片类中毒，可尽早投用小剂量纳洛酮（0.4mg）缓慢静脉注射，必要时可于2~3小时后重复使用，直至病情稳定。注意勿过量应用，因会诱发戒断症状。如无纳洛酮，丙烯吗啡（nalorphine）3~5mg静注或丙烯左吗南（levallophan）1mg静注亦有效，因此二药也是阿片类的拮抗剂。

其他治疗
1。对口服中毒者，可先让其大量饮水，然后灌服1:2000高锰酸钾溶液洗胃，或诱导催吐；同时，还应服用利尿剂和泻药，促进毒物的排泄，减少人体对毒素的吸收。

2．系皮下注射中毒者，应迅速用止血带或布带扎紧注射部位上方，同时冷敷注射部位，以延缓毒物的吸收。必须注意的是，注射部位的结扎处，应每隔15-0分钟放松l-分钟，以免肢体坏死。对于吸收人血的毒物，必要时采取强化利尿、血液透析等加速毒物排除的措施。

3．维持心脏及循环功能，因海洛因对心脏及循环功能的抑制。抢救开始就应积极维持循环功能，适量使用肾上腺素或西地兰，增加心肌收缩力或心输出量。

本期参考答案：
1.可卡因中毒如何处理？
药物导致的高血压急症常作用短暂，常不需要有创治疗。可卡因特别被强调与高血压、室性心律失常和冠状动脉综合征相关。治疗其中毒的关键是避免β受体阻滞剂（Ⅲ级）的使用，特别是非选择性阻滞剂如心得安，因为其导致无法对抗的α肾上腺素能兴奋，加重高血压[1]。地西泮（Ⅱa级）除了作用短暂、titrateable（可滴定？）抗高血压药如硝酸盐类（Ⅰ级）应该作为治疗的首选。如果是难治性高血压，可以考虑使用α肾上腺素能阻滞剂（Ⅱb级），此时需注意心动过速和低血压的出现[2]。
2.三环类药物过量如何处理？
三环抗抑郁药（TCA）为钠通道阻滞剂，可导致心室传导的延长（增加PR和QT间期）与最终单一型VT[3]。最常见临床特征是口干、视力模糊、瞳孔散大、窦性心动过速、锥体束征和嗜睡。重度中毒时，可出现昏迷、子痫、呼吸抑制、低血压和心律失常。
对于TCAs中度的治疗主要是支持，然而，很多人推荐进行洗胃[4]。因为这些病人常处于低氧血症和酸中毒，作为一种姑息性治疗可能导致呼吸性碱中毒，直到碳酸氢钠（Ⅱa级）使用。
子痫应该使用安定或氯乙甲噻唑[镇静催眠、抗惊厥药]治疗。低血压应该给于补液，必要时给于拟交感神经药（多巴胺或多巴酚丁胺）。仅在低血压纠正失败情况下的循环衰竭时，使用抗心律失常药，如利多卡因和普鲁卡因酰胺（不确定级），因为其副作用未能充分研究。虽然毒扁豆碱[拟胆碱药]可逆转TCA中毒的大多数体征，但是是通过其严重的毒性作用而起效的，可产生明显副作用。即使如此，毒扁豆碱液应该被保留用于那些有昏迷或顽固性心脏毒性或子痫并发症的患者。最后，药物筛选和TCA血清浓度的定量测定在少数存在严重的、罕见或持续时间长的症状的病人中可能是有用的。
3.急性阿片剂过量如何处理？
如果呼吸功能不全的病人怀疑有阿片剂过量而脉搏存在，应该给于肌肉（IM）、皮下（SC）或静脉注射纳洛酮。IM和SC途径对于静脉吸毒者可减少严重脱瘾性脑综合征的发生率。纳洛酮的初次剂量为0.4-0.8mg静注或0.8mg肌注或SC，并应达到预期的呼吸反射和充分的通气[2]。不推荐达到完全唤醒的程度，因为突然对阿片剂的阻断可增加一些并发症的发生，如肺水肿、室性心律失常以及严重的躁动[5]。


What should be the response to cocaine toxicity?
Drug induced hypertensive emergencies are often short lived, and often aggressive therapy is not needed. Cocaine in particular is noted to be associated with hypertension, ventricular arryhthmias, and acute coronary syndromes. The important key to the treatment of this toxicity is avoiding the use of beta blockers (Class III), especially nonselective agents such as propranolol, as this allows for unopposed alpha adrenergic stimulation and worsening of the hypertension (1). Benzodiazepines (Class IIa) in addition to a short acting, titrateable antihypertensive such as nitrates (Class I) should be the first line of therapy. Should the hypertension be refractory, the use of alpha adrenergic blocking agents (Class IIb) may be considered, keeping in mind that tachycardia and hypotension may result (2).
What should be the response to tricyclic overdose?
Tricyclic antidepressants (TCA) are sodium channel blockers that may result in prolongation of ventricular conduction (increases the PR and QT intervals) and ultimately monomorphic VT (3). The most common clinical features are dry mouth, blurred vision, dilated pupils, sinus tachycardia, pyramidal neurological signs, and drowsiness. In severe poisoning, there may be coma, convulsions, respiratory depression, hypotension, and arrythmias.
Treatment of poisoning due to the TCAs is mainly supportive, however, gastric aspiration and lavage has been recommened by some (4). As these patient are often hypoxemic and acidotic, respiratory alkalosis can be induced as a temporizing measure, until the drug of choice sodium bicarbonate (Class IIa) can be used. Convulsions should be treated with diazepam or chlormethiazole. Hypotension should be treated by fluid replacement and sympathomimetic agents (dopamine or dobutamine) if necessary. Antiarrhythmic drugs, e.g., lidocaine and procainamide (Class indeterminate), should be employed only if there is evidence of circulatory failure which fails to respond to correction of hypotension, as their effects have not been adequately studied. Although physostigmine salicylate can reverse most of the features of TCA poisoning, its effects are short-lived in serious toxicity and it can produce significant side effects. As such, physostigmine should be reserved for those patients who have complications of coma or who have resistant cardiotoxicity or convulsions. Finally, drug screening and quantitative determination of tricyclic antidepressant serum concentrations can be useful in a minority of patients who have severe, unusual or prolonged symptoms.
What should the response be to acute opiate overdose?
If a pulse exists in patients with respiratory insufficiency suspected of an opiate overdose, naloxone should be administered, either intramuscularly, subcutaneously, or intravenously. IM and SC routes may provide less risk of severe withdrawal in patients addicted to IV narcotics. The initial dose of naloxone in 0.4-0.8 mg IV or 0.8 mg IM or SC and should be given to the desired endpoint of adequte airway reflexes and ventilation (2). The goal of complete arousal is not recommended, as the abrupt withdrawal from opiates may increase such complications as pulmonary edema, ventricular arrhythmias, and severe agitation (5).
References:
1.  Ramoska E, Sacchetti AD. Propranolol-induced hypertension in treatment of cocaine intoxication. Ann Emerg Med. 1985;14(11):1112-3.
2.  Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: advanced cardiovascular life support: 7C: a guide to the International ACLS algorithms. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation. 2000;102(8 Suppl)142-57.
3.  Kresse-Hermsdorf M, Muller-Oerlinghausen B. Tricyclic neuroleptic and antidepressant overdose: epidemiological, electrocardiographic, and clinical features--a survey of 92 cases. Pharmacopsychiatry. 1990;23 Suppl 1:17-22.
4.  Crome P. Poisoning due to tricyclic antidepressant overdosage. Clinical presentation and treatment. Med Toxicol. 1986;1(4):261-85.
5.  Brown TC. Tricyclic antidepressant overdosage: experimental studies on the management of circulatory complications. Clin Toxicol. 1976;9(2):255-72.
6.  Evans LE, Swainson CP, Roscoe P, Prescott LF. Treatment of drug overdosage with naloxone, a specific narcotic antagonist. Lancet. 1973;1(7801):452-5.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
Founders and Editors-in-Chief: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical Scho