【原】【经典高分文献阅读】择期全髋关节置换术后的急性疼痛轨迹:系统回顾和数据综合

经典高分文献阅读·择期全髋关节置换术后的急性疼痛轨迹:系统回顾和数据综合

PXL/Riozhou/LY

Editor’s key points

Ø Understanding when acute pain is likely to be problematic after surgery allows targeted management.

Ø 了解术后急性疼痛可能出现问题的时间有助于进行有针对性的治疗。

Ø Acute pain trajectories after total hip replacement were calculated from published literature, which displayed significant heterogeneity in analgesic approaches.

Ø 全髋关节置换术后急性疼痛轨迹的计算来自于已发表的文献，这些文献显示了镇痛方法的显著异质性。

Ø With a basic analgesic approach, pain peaked up to 2 h after surgery, and declined thereafter. By identifying the acute pain trajectory, a range of additional analgesic approaches may be planned to minimise pain peaks.

Ø 在基本的镇痛方法下，疼痛在术后2小时达到高峰，随后逐渐下降。通过确定急性疼痛轨迹，可以计划一系列额外的镇痛方法，以尽量减少疼痛峰值。

Ø There are very limited data on postoperative analgesia for chronic pain patients or those on long-term opioids, with a need for further research in this area.

Ø 关于慢性疼痛患者或长期服用阿片类药物患者术后镇痛的资料非常有限，这方面还需要进一步研究。

Ø Abstract

Ø Background: For most procedures, there is insufficient evidence to guide clinicians in the optimal timing of advanced analgesic methods, which should be based on the expected time course of acute postoperative pain severity and aimed at time points where basic analgesia has proven insufficient.

Ø 背景：对于大多数手术来说，没有足够的证据来指导临床医生选择高级镇痛方法的最佳时机，这些方法应基于急性术后疼痛严重程度的预期时间过程，并针对基本镇痛效果不充分的时间点。

Ø Methods: We conducted a systematic search of the literature of analgesic trials for total hip arthroplasty (THA), extracting and pooling pain scores across studies, weighted for study size. Patients were grouped according to basic anaesthetic method used (general, spinal), and adjuvant analgesic interventions such as nerve blocks, local infiltration analgesia, and multimodal analgesia. Special consideration was given to high-risk populations such as chronic pain or opioid-dependent patients.

Ø 方法：我们对全髋关节置换术（THA）镇痛试验的文献进行了系统的检索，提取并汇总了不同研究的疼痛评分，并根据研究规模进行加权。根据所使用的基本麻醉方法（全身麻醉、脊髓麻醉）和辅助性镇痛干预（如神经阻滞、局部浸润镇痛和多模式镇痛）对患者进行分组。对慢性疼痛或阿片依赖患者等高危人群给予了特别考虑。

Ø Results: We identified and analysed 71 trials with 5973 patients and constructed pain trajectories from the available pain scores. In most patients undergoing THA under general anaesthesia on a basic analgesic regimen, postoperative acute pain recedes to a mild level (<4/10) by 4 h after surgery. We note substantial variability in pain intensity even in patients subjected to similar analgesic regimens. Chronic pain or opioid-dependent patients were most often actively excluded from studies, and never analysed separately.

Ø 结果：我们确定并分析了71项试验，共5973名患者，并根据可用的疼痛评分构建了疼痛轨迹。在大多数全麻基础镇痛方案下接受全髋关节置换术的患者中，术后4小时，术后急性疼痛减轻至轻度（<4/10）。我们注意到，即使在接受类似镇痛方案的患者中，疼痛强度也存在显著差异。慢性疼痛或阿片类药物依赖性患者通常被排除在研究之外，从未单独分析。

Ø Conclusions: We have demonstrated that it is feasible to construct procedure-specific pain curves to guide clinicians on the timing of advanced analgesic measures. Acute intense postoperative pain after THA should have resolved by 4-6 h after surgery in most patients. However, there is a substantial gap in knowledge on the management of patients with chronic pain and opioid-dependent patients.

Ø 结论：我们已经证明了构建程序特异性疼痛曲线来指导临床医生进行高级镇痛措施的时机是可行的。大多数患者全髋关节置换术后急性剧烈疼痛应在术后4-6h内消失。然而，在对慢性疼痛患者和阿片依赖患者的管理知识方面存在很大差距。

（一）研究背景

For most procedures, there is insufficient evidence to guide clinicians in the optimal timing of advanced analgesic methods, which should be based on the expected time course of acute postoperative pain severity and aimed at time points where basic analgesia has proven insufficient.

何时才是选择更进一步镇痛方法的最佳时机？

基础镇痛已被证明不足；

（二）研究方案

1) 纳入标准：(1)已发表的临床随机对照试验和非随机对照试验；(2)接受选择性单侧全髋关节置换术的任何年龄的患者；(3)脊髓麻醉或全身麻醉被报告为所使用的主要麻醉类型；(4)报告术后疼痛管理的类型和持续时间(5)主要结果包括术后5天内休息时的术后疼痛评分，次要结果包括每小时和累积的术后阿片类药物消耗量。

2) 排除标准：（1）数据不明确的研究、综述文章和病例报告被排除在外；（2）没有足够详细地描述疼痛评分以纳入加权数据汇总的研究被排除在外。

3) 具体流程

Our two literature searches identified 1631 potentially relevant studies, of which 793 duplicates were removed. A total of 513 trials were excluded after screening their titles and abstracts because they did not meet the inclusion criteria. We assessed the full-text articles of the remaining 325 studies, and an additional 20 studies were identified by reviewing references. We excluded 274 studies where postoperative pain was not reported on a 10- or 100-point scale or that did not fulfil the inclusion criteria. At the end of the selection period, a total of 71 studies were included in our analysis.

These studies had a total of 5973 patients, of whom 2327 underwent neuraxial block and 3646 underwent GA. The time window during which reproducible data could be aggregated and which, in our view, well reflects the clinical course after hip surgery, was 72 h

两次文献搜索确定了1631个潜在相关研究，其中793个重复被删除。在筛选标题和摘要后，共有513项试验被排除在外，因为它们不符合纳入标准。评估了其余325项研究的全文，并通过查阅参考文献确定了另外20项研究。排除了274项术后疼痛未在10或100分量表上报告或不符合纳入标准的研究。在选择期结束时，共有71项研究被纳入分析.研究共有5973名患者，其中2327名接受了神经轴型阻滞，3646名接受了GA,时间窗为72小时。

（三）研究步骤

1）流程图：

2）干预措施/Interventions:

· There was considerable heterogeneity in the way analgesic interventions were performed, we grouped  them into five broad categories of interventions, which had been investigated in a sufficient number of studies to allow for the creation of pain trajectories:(1) LIA (1209 patients); (2) single shot nerve block (S-block, 515 patients);(3) continuous nerve block (C-block, 1430 patients);(4) multimodal drug therapy (1198 patients); and (5) a primarily opioid-focused analgesic regimen representing the control group (C, 1621 patients).

· 作者将其分为五大类干预措施，这些干预措施已经在足够数量的研究中进行了调查，以允许创建疼痛轨迹:(1) 局部浸润阻滞（LIA） (1209名患者)；(2)单发神经阻滞(S型阻滞，515例)；(3)持续神经阻滞(C-阻滞，1430例)；(4)多模式药物治疗(1198例)；和(5)对照组(C，1621名患者)：主要以阿片样物质为焦点的镇痛方案。

干预措施部分定义补充

· (1)LIA: The optimal technique and location of LIA is a subject of debate, with surgical practice varying widely, reflected also in the broad spectrum of different approaches among the 23 analysed studies. The LIA interventions differed in respect to the infiltration site, the type of the local anaesthetic and other adjuvant drugs, the timing of infiltration, and the accompanying systemic analgesic regimen. (LIA干预在浸润部位、局部麻醉剂和其他辅助药物的类型、浸润时间和伴随的全身镇痛方案方面有所不同)

· (2) Peripheral nerve blocks(including single shot nerve block and continuous nerve block ):there was heterogeneity of regional anaes-thetic technique, including the type of block, the timing, the local anaesthetic used, and the means of needle guidance (ultrasound[US], landmarks, or nerve stimulation). Different peripheral nerve blocks re currently used for perioperative management in hipsurgery. Seven types were included in this study: psoas compartment block, fascia iliaca block, femoral nerve sheath block, lumbar plexus block, subcostal nerve block, lateral femoral cutaneous nerve (LFCN) block, and the three-in-one block.(区域麻醉技术也存在异质性，包括阻滞类型、时机、所用局部麻醉剂和针引导方式(超声、界标或神经刺激)。不同的周围神经阻滞目前用于髋关节手术的围手术期处理。本研究包括七种类型:腰大肌筋膜室阻滞、髂筋膜阻滞、股神经鞘阻滞、腰丛阻滞、肋下神经阻滞、股外侧皮神经(LFCN)阻滞和三合一阻滞)

· (3)multimodal drug therapy: The multimodal drug therapy group was defined by absence of use of LIA or peripheral nerve blocks. The drug regimens and the dosages varied between studies but consisted mainly of NSAIDs, ketamine, gabapentin, COX-2 in-hibitors, pregabalin, glucocorticoids, and clonidine. (多模式药物治疗组的定义是不使用LIA或周围神经阻滞。药物方案和剂量因研究而异，但主要由非甾体抗炎药、氯胺酮、加巴喷丁、环氧化酶-2抑制剂、普瑞巴林、糖皮质激素和可乐定组成)

3）数据提取：

ü The first outcome: the patient’s postoperative pain scores immediately after THA and up to 120 h postoperatively, both at rest and during activity, when available.

ü 主要提取数据:患者在全髋关节置换术后即刻和术后120小时的术后疼痛评分，包括休息时和活动时；

ü Secondary outcome: hourly and cumulative opioid consumption measured in milligrams of intravenous morphine equivalents according to the equianalgesic chart provided by the Pain Assessment and Management Initiative.

ü 次要提取数据：以静脉注射吗啡当量毫克数衡量的每小时和累计阿片类药物消耗量，从而绘制出的等效镇痛图；

4）统计分析:

Mean pain scores and standard deviation of pain scores were extracted from each study.(从每项研究中提取平均疼痛评分和疼痛评分的标准偏差)

(1) For studies that reported median pain scores with inter-quartile ranges or ranges, an approximate mean value and standard deviation were calculated. More specifically, suppose the reported median and inter-quartile ranges were m and q1to q3, the approximate mean value would be mean =(q1+m+q3)/3, and the standard deviation would be S=(q3-q1)/(2φ‾1)x(0.75n—0.125)/(n+0.25)。

对于报告具有四分位区间的疼痛评分中位数的研究，计算了近似的平均值和标准差。更具体地说，假设报告的中位数和四分位间距为m和q1到q3，近似平均值为mean=（q1+m+q3）/3，标准偏差为S=（q3-q1）/（2φ‾1）x（0.75n-0.125）/（n+0.25）

(2) For studies that reported median and mini-mum to maximum ranges (a to b, where a is the minimum and b is the maximum), the approximate mean would be mean=(a+2m+b)/4, and the standard deviation would be S=(b-a)/(2φ‾1)x(n—0.375)/(n+0.25).

对于报告中位数和最小到最大范围（a到b，其中a是最小值，b是最大值）的研究，近似平均值为平均值=（a+2m+b）/4，标准偏差为S=（b-a）/（2φ‾1）x（n-0.375）/（n+0.25）。

(3) In addition, for studies that reported mean values and the range between minimum and maximum values, the approximate standard deviation would be S=(b-a)/4. 

此外，对于报告平均值和最小值与最大值之间范围的研究，近似标准偏差为S=（b-a）/4。

（四）研究结果

图2：全麻患者仅接受最基本的镇痛，在术后0-2小时出现急性术后疼痛高峰，随后在术后4-8小时疼痛强度逐渐下降。椎管内麻醉患者在术后2 h休息时的疼痛明显减轻，在使用基本的围手术期镇痛药的情况下，大多数患者只会报告轻微疼痛。

图3：术后即刻，GA组的累积阿片类药物消耗量更高，术后48 h，SA组阿片类药物消耗量明显高于GA组

图4：多模式镇痛下接受人工髋关节置换的普通患者仍会立即出现术后疼痛高峰！

对于接受(a)全麻基础镇痛、(b)全麻多模式镇痛、(c)全麻 LIA或(d)全麻单次注射阻滞的患者，在三种主要干预措施与对照组并排的手术后静息至72小时的疼痛轨迹。

图5：运动时全麻与椎管内麻醉疼痛曲线与静息痛相似，术后急性期GA组运动痛明显高于SA组

（五）讨论部分

· “基本平均疼痛曲线”是由在全身麻醉下接受全髋关节置换并仅接受阿片类药物治疗的患者构建的，它有一个初始峰值，即使在基本镇痛下，最剧烈的疼痛也会在4-8小时内消退。

· 即使在相同镇痛方案下接受相同类型手术的患者中，疼痛反应也存在显著差异。在SA下接受THA的患者似乎完全不受这种早期高峰的影响。但是，这可能是以更高的阿片类药物消耗为代价实现的，因为脊髓麻醉剂逐渐消失，患者在PACU中和术后被阿片类镇痛药滴定。

· “基本平均疼痛曲线”可能是设计和评估镇痛干预的另一种方式，可以据此预期术后疼痛的强度和时间进程，以特定于手术的方式进行镇痛干预。其潜在价值是告知给定的干预措施是否可以“压平”疼痛曲线，而不会在疼痛消退之前使干预措施的效力减弱。通常，以快速方式引导患者度过围手术期的压力意味着给患者施用例如单次神经阻滞以促进出院。然而，在术后立即缓解疼痛的优势可能会被疼痛的出现所抵消，因为阻滞突然终止，通常是在不适合立即使用止痛剂的环境中(例如，门诊手术后在家，住院手术后在普通外科病房)。

· 大多数研究评估术后12小时和24小时等时间点的疼痛，但髋关节置换术后急性疼痛峰值已经降低。因此，在选择性全髋关节置换术的镇痛研究中，观察术后0-8小时的时间点可能会有所帮助，以确保考虑到术后早期的剧烈疼痛。

· 在全髋关节置换手术后，局部麻醉剂的渗透和单次神经阻滞在与人工髋关节置换联合使用时可有效缓解术后疼痛，而在多模式镇痛下接受人工髋关节置换的普通患者仍会立即出现术后疼痛高峰，通过单独使用多模式镇痛或将其与LIA结合，可以获得优异的疼痛缓解和功能恢复。

（六）研究结论

· The pain trajectories after a single surgical intervention provides a new way of defining the time period when directed pain management would actually make the most clinically significant difference for the patient.

· our analysis suggests that the period of intense postoperative pain after elective unilateral THA spans the first 0-4h, after which between 4 and 8 h, most patients’ pain shoul d have receded to acceptable levels even on a basic analgesic regimen.

· 疼痛曲线提供了一种新的方法来定义在疼痛管理中对患者产生最大临床意义的时间段。

· 择期单侧THA术后剧烈疼痛的时间跨度为最初0-4 h；此后4 ~ 8h，即使在基础镇痛方案下，大多数患者的疼痛也应已消退至可接受的水平。