【疼痛】骨科病人的疼痛管理

导　语浙江大学医学院附属第二医院骨科沈炜亮

一、定　义

骨膜、骨基质、韧带或关节损伤后产生的躯体深部疼痛即为骨骼痛。大量前列腺素的释放激活伤害性感受器，产生神经冲动，经由髓鞘神经纤维或无髓鞘神经纤维传导，经脊髓最终到达大脑体感皮层。理解神经系统是如何在产生疼痛刺激，并将冲动从外周传至大脑的机制，有助于更好地理解如何对骨科患者进行疼痛管理。

Skeletal pain is a deep somatic pain resulting from injuries to the periosteum, matrix, ligaments, or joints.Nociceptors activated by release of potent prostaglandins relay nervous impulses through myelinated or unmyelinated fibers via the spinal cord to the somatosensory cortex. Understanding the mechanism by which the nervous system produces and transmits pain impulses from the periphery to the brain can aid in better understanding how to manage pain in the orthopaedic patient.

疼痛管理常用的药物包括阿片类药物、NSAIDs药物、非阿片类中枢镇痛药及局麻药。阿片类药物通过中枢神经系统阻滞疼痛，NSAIDs药物通过减少炎症反应减轻疼痛，非阿片类中枢镇痛药同时影响中枢神经递质和NMDA受体（对乙酰氨基酚，曲马多），局麻药阻止疼痛冲动向脊髓传导。

Agents used to manage pain include opioids, NSAIDs, centrally acting nonopioids, and local anesthetics. Opioids block pain in the central nervous system, NSAIDs decrease pain by reducing the inflammatory response, centrally acting nonopioid analgesics interact with certain neurotransmitters and N-methyl-D-aspartate(NMDA) receptors (acetaminophen, tramadol), and local anesthetics prevent pain impulses from reaching the spinal cord.

1.阿片类药物

阿片类药物是治疗中重度疼痛最有效、使用最广泛的药物。该类药物与大脑、脊髓和胃肠道中的特异性受体结合，产生剂量依赖性痛觉丧失、嗜睡、呼吸抑制、尿潴留、恶心、呕吐及便秘。阿片类药物可以经静脉、口服、直肠或经皮给药。给药方式对起效快慢和药效持续时间有影响。

Opioids are the most effective and widely used medicines for the treatment of moderate to severe pain. They bind to specific receptors in the brain, spinal cord, and gastrointestinal (GI) tract, causing dose-dependent analgesia, drowsiness,respiratory depression, urinary retention, nausea, vomiting, and constipation. Opioids can be administered via intravenous, oral, rectal, or transcutaneous means. Delivery method has an effect on the onset and duration of the drug.

除此之外，阿片类药物的效果还受到同时服用的其他具有中枢作用的药物的影响，特别是酒精对阿片类药物影响较大。对于高龄患者和需要长期使用的患者，强烈建议个体化调整药物剂量。

In addition, the effect of opioids can be affected by the concomitant use of other centrally acting drugs and by alcohol in particular. Individualized dosing is strongly advised in the elderly population and in patients with long-standing opioid use.

静脉给药会使血药浓度迅速上升，迅速起效，而口服药物会慢慢出现止痛效果。芬太尼透皮贴能够在最长3天时间里持续释放止痛活性物质。但是芬太尼透皮贴应当严格遵守适应症，例如转移癌的患者或某些特定的慢性疼痛状态。

Intravenous administration causes a rapid rise in plasma levels and fast onset, whereas oral administration results in a more gradual onset of analgesia. Transdermal fentanyl consists of a patch that releases a predetermined dose of the active substance over a period of up to 3 days; this patch should only be used for a select group of patients, such as those with metastatic disease or certain chronic pain conditions.

目前，有短效阿片类药物的缓释制剂，如羟考酮和氢考酮缓释片，可以在较长的时间里维持更稳定的血药浓度。然而，这些阿片类药物是受严格监管的处方药，原因在于该类药物有成瘾风险。因此，严格遵守用药指南，对使用阿片类药物的患者进行密切随访，对于保障用药安全和良好的治疗效果很有必要。

Short-acting opioids such as oxycodone and hydrocodone are now availableas extended release tablets, which allows for more stable plasma levels over a longer period of time. However, prescription of these opioids is carefully monitored because of the potential for abuse. Adherence to strict guidelines and thorough follow-up with patients taking opioids is necessary to ensure a safe and successful therapy.

2.NSAIDs药物

NSAIDs药物可以比较容易获得，广泛使用已经超过50年了。它们主要通过减少损伤部位前列腺素的产生，从而影响疼痛的神经传导。

NSAIDs are readily available and have been widely used over the past 50 years. They affect transmission of pain by primarily reducing the production of prostaglandins at the site of injury.

所有NSAIDs药物在同等剂量下具有相似的特点和耐受度。NSAIDs药物基于不同化学结构或作用机制进行分类。众所周知，COX-1受体抑制剂会产生消化道和肾脏的副作用，同时还会干扰血小板的粘附。而COX-2抑制剂会增加心血管事件发生的风险。

All NSAIDs exhibit similar characteristics and tolerability when used at a comparable dosing regimen. They are classified based on their chemical structure or mechanism of action. Cyclooxygenase(COX)-1 inhibitors are known for producing adverse effects in the GI tract and the kidney and for interfering with platelet adhesion. The use of COX-2 inhibitors has been shown to increase the risk of cardiovascular events.

在众多被批准使用的COX-1抑制剂中，布洛芬和萘普生似乎是相对安全的两种药物。塞来昔布（西乐葆【辉瑞制药】）是广泛应用的COX-2抑制剂。对于有消化道问题或确定过敏反应病史的患者，塞来昔布是通常给予患者推荐的药物。

Among the many COX-1 inhibitors currently available, ibuprofen and naproxen seem to be reasonably safe. Celecoxib (Celebrex [Pfizer]) is an extensively used COX-2 inhibitor. It is most commonly prescribed to patients with a history of GI problems or certain allergic reactions.

NSAIDs药物和其他常用药物之间的交叉敏感性已有明确记录，如华法林、血压药物（血管紧张素转化酶[ACE]抑制剂）及抗抑郁药物（选择性五羟色胺再摄取抑制剂），因此医生在给患者开具NSAIDs药物前必须详细询问患者既往的用药史。

Cross-sensitivity between NSAIDs and other commonly used drugs such as warfarin, blood pressure medicines(angiotensin-converting enzyme [ACE] inhibitors), and antidepressants(selective serotonin reuptake inhibitors [SSRIs]) are well documented, and the physician must take a careful medication history before prescribing NSAIDs.

2015年，美国FDA再次强调：非甾体类消炎药有诱发心脏疾病和中风的可能，并指出：即便在开始使用一种非甾体类消炎药的数周内也可发生。然而，NSAIDs药物可以减少阿片类药物的使用，是强效中枢性阿片类药物的良好补充药物，同时能够减少阿片类药物的副作用。

In 2015, the FDA strengthened its warning linking NSAIDs with the risk of heart attack or stroke, even in the first weeks of use of an NSAID. However,the opioid-sparing effect of NSAIDs makes them an excellent adjunct to the more potent centrally acting opioids and may reduce side effects.

3.非阿片类中枢性镇痛药物

对乙酰氨基酚和曲马多是最常使用的非阿片类中枢性镇痛药物。虽然曲马多与阿片类受体有较弱的亲和性，但其镇痛特性主要是通过抑制五羟色胺释放和阻止去甲肾上腺素的再摄取起作用。

Acetaminophen and tramadol are the most widely prescribed centrally acting nonopioid analgesics. Although tramadol has a weak affinity to opioid receptors, its analgesic properties are mostly a resultof inhibiting the release of serotonin and blocking the reuptake of norepinephrine.

除此之外，曲马多还能阻断脊髓中的NMDA受体，阻止或调解传入神经的冲动从外周传输至大脑。尽管曲马多大约只有吗啡十分之一的镇痛效果，但其对轻至中度疼痛的效果与吗啡相似。

In addition, tramadol has the abilityto block NMDA receptors in the spinal cord, which prevents or modulates the transmission of afferent nervous impulses from the periphery to the brain. Although tramadol has approximately one-tenth the potency of morphine, it shows similar effectiveness for mild to moderate pain.

对曲马多止痛效果产生干扰并减弱止痛效果的最常见药物包括抗抑郁药物（SSRIs）、哌替啶及止吐药物昂丹司琼。对乙酰氨基酚广泛用于骨关节炎患者的止痛治疗。其止痛特性与阿司匹林相似，但没有抗炎作用。推荐剂量（最大剂量<4,000mg/day）的对乙酰氨基酚与弱阿片类药物合用具有更好的效果和更少的副作用。

The most common interaction occurs with antidepressants (SSRIs), meperidine, and the antinausea medication ondansetron,which may antagonize the effect of tramadol. Acetaminophen is widely used as an analgesic in patients with osteoarthritis. It has analgesic properties similar to aspirin but is not considered an anti-inflammatory medication. Acetaminophenis more effective when used in combination with weak opioids and has few side effects when taken in recommended doses (maximum dose < 4,000 mg/day).

与NSAIDs药物不同，对乙酰氨基酚可用于第三妊娠期的孕妇，而无导致胎儿动脉导管过早闭合的风险。开具止痛药物处方时需要考虑多种因素，具体如表1所示。

Unlike NSAIDs, acetaminophen can be prescribed to pregnant patients in their third trimester for management of pain without running the risk of premature closure of the ductus arteriosus in the fetus. Factors to consider when prescribing pain medication are listed in Table 1.

4.局麻药

使用长效局麻药物实施周围神经阻滞消除上肢或下肢骨科手术后疼痛已经成为常规程序。关注的增加和技术的进步，包括超声的应用，联合或不联合神经刺激，在手术部位可以选择性地产生强大的麻醉和止痛效果。

It has become routine to administer peripheral nerve blocks with long-acting local anesthetics to eliminate pain after orthopaedic procedures in the upper or lower extremities. Increased interest and technical advances such as the use of ultrasound with or without nerve stimulation have made it possible to selectively produce profound anesthesia and analgesia at the surgical site.

单次注射产生的止痛效果最长可以持续24小时，而留置管技术能够在几天中发挥出色的疼痛缓解作用。周围神经损伤或局麻药中毒需要特别关注，但通过严格遵守美国麻醉医师协会制定的指南能够避免这些并发症。

Duration of analgesia with a single injection lasts up to 24 hours, whereas techniques using an indwelling catheter can provide excellent pain relief for several days. Peripheral nerve injury or local anesthetic toxicity is of concern, but these complications can be avoided with meticulous adherence to guidelines published by the American Society of Anesthesiologists.

椎管内麻醉和硬膜外麻醉均能够提供术中良好的止痛效果，在硬膜外隙或脑脊液中加入阿片类药物能够增强其术后止痛效果。椎管内麻醉和硬膜外麻醉更适合进行手术的住院病人，术中需要持续的呼吸和心血管功能监测。

Both spinal and epidural anesthesia provide excellent pain relief intraoperatively,and their postoperative effect can be augmented by the addition of opioids into the epidural space or the spinal fluid. Spinal and epidural anesthesia are more appropriate for inpatient surgical procedures, which require continuous monitoring of respiratory and cardiovascular functions.

然而，强效血液稀释剂在术后早期的应用是硬膜外麻醉技术的禁忌症，原因是硬膜外血肿的发生风险会显著提高。

However, the use of potent blood thinners in the early postoperative phaseis considered a contraindication for neuraxial anesthetic techniques because it markedly increases the risk of epidural hematomas.

将长效局麻药布比卡因加入脂质混悬液，适当地在手术部位进行注射浸润，能够使术后止痛效果延长数天时间。需要注意的是，FDA仍未批准布比卡因用于周围神经阻滞麻醉。

Addition of the long-actinglocal anesthetic bupivacaine in a liposomal suspension enables several-dayextension of postoperative analgesia when the drug is appropriately infiltrated at the surgical site. The FDA has not yet approved the use of bupivacaine in peripheral nerve blocks.

除了休息、抬高患肢和冰敷，经皮神经电刺激和针灸治疗有助于减轻疼痛，且没有副作用。像放松技巧和催眠疗法等心理学方法需要接受过心理治疗培训的医生参与。

In addition to rest, elevation, and ice, the use of transcutaneous electrical nerve stimulation and acupuncture has been shown to be beneficial in reducing pain without adverse effects. Psychological methods such as relaxation techniques and hypnosis may require the participation of a physician trained in psychologic care.