Preemptive analgesia I: physiological pathways and pharmacological modalities

PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. Principal findings: The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (N-methyl-D-aspartate) - and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.     

Preemptive analgesia II: recent advances and current trends

PURPOSE: This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia. SOURCE: Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents. Principal findings: In Part I of this review article, techniques and agents that attenuate or prevent central and peripheral sensitization were reviewed. In Part II, the conditions required for effective preemptive techniques are evaluated. Specifically, preemptive analgesia may be defined as an antinociceptive treatment that prevents establishment of altered central processing of afferent input from sites of injury. The most important conditions for establishment of effective preemptive analgesia are the establishment of an effective level of antinociception before injury, and the continuation of this effective analgesic level well into the post-injury period to prevent central sensitization during the inflammatory phase. Although single-agent therapy may attenuate the central nociceptive processing, multi-modal therapy is more effective, and may be associated with fewer side effects compared with the high-dose, single-agent therapy. CONCLUSION: The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input require individualization of the technique(s) chosen. Multi-modal analgesic techniques appear more effective.     

Update zur präemptiven Analgesie

Background

Wall created the term preemptive analgesia in 1988 and in doing so set in motion a movement to prevent acute and chronic postsurgical pain. The concept of preemptive analgesia implies the administration of analgesic drugs or an intervention before a surgical procedure. A preemptive analgesic approach can comprise non-steroidal anti-inflammatory drugs (NSAID) and cyclo-oxygenase-2 inhibitors (coxibs) used to decrease the production of prostaglandins, local anesthetics (e.g. epidural) to reduce nociceptive input to the spinal cord as well as opioids, N-methyl-D-aspartate (NMDA) antagonists, antidepressants and anticonvulsants, all of which have an inhibitory influence on the central nervous system.

Aim

The aim of this article is to present the current possibilities and limits of preoperative pain therapy.

Material and methods

Since 2002 several meta-analyses on the effectiveness of preemptive analgesia have been published which came to varying conclusions on the supportive use of preemptive analgesia. The S3 guidelines on current perioperative pain management developed by the German Interdisciplinary Association for Pain Management (DIVS) specify the preemptive analgesic interventions found to be effective and will be discussed in detail in this article. Furthermore, the results of a current meta-analysis which follows the principle of preventive analgesia will be presented and which have not yet been considered in the S3 guidelines.

Results

Preemptive analgesia can reduce acute postoperative pain; however, minimizing the development of chronic pain conditions can only be successful in combination with intraoperative and postoperative pain therapy as well as social and psychological support when indicated (preventive analgesia).

Conclusion

Reduction of chronic postoperative pain is an important medical function which is also justified from socioeconomic perspectives. Future studies should combine several procedures for perioperative pain therapy in order to do justice to the multifactorial aspects of pain chronification and should also be planned over a sufficiently long observation time period.     

The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis

Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.     

Analgesic agents for the postoperative period. Nonopioids.

For many reasons, nonopioid analgesics have proven to be of immense benefit in postoperative pain relief. Consideration of the limitations and side effects of opioids confirms the need for alternative, complementary analgesics. The current understanding of pain pathophysiology recognizes that many tissue and neuronal factors and changes are invoked by tissue damage, producing peripheral and central sensitization, and some of these may be modulated by the use of NSAIDs, NMDA antagonists, and local anesthetic agents. If successful preemptive analgesic techniques are developed, they will likely include the use of NSAIDs and perhaps NMDA antagonists. Nonopioids are of benefit in multimodal analgesia and allow acute rehabilitation of surgical patients. Acetaminophen, NSAIDs, alpha 2-antagonists, and NMDA antagonists are in routine use as components of multimodal analgesia, in combination with opioids or local anesthetic techniques. Tramadol is interesting because it has nonopioid and opioid actions that can be attributed to the two isomers found in the racemic mixture. Spinal neostigmine and the use of adenosine represent completely different mechanisms of nonopioid analgesia being investigated. Nonopioids, including lidocaine, ketamine, the anticonvulsants, and the antidepressants, are necessary for the treatment of patients with the difficult clinical problem of neuropathic pain that can present in the postoperative period.     

Do we need preemptive analgesia for the treatment of postoperative pain?

Preemptive analgesia means that an analgesic intervention is started before the noxious stimulus arises in order to block peripheral and central nociception. This afferent blockade of nociceptive impulses is maintained throughout the intra-operative and post-operative period. The goals of preemptive analgesia are, first, to decrease acute pain after tissue injury, second, to prevent pain-related pathologic modulation of the central nervous system, and third, to inhibit the persistence of postoperative pain and the development of chronic pain. So far, the promising results from animal models have not been translated into clinical practice. Therefore, clinicians should rely on conventional anaesthetic and analgesic methods with proven efficacy, i.e. a multimodal approach including the combination of strong opioids, non-opioid analgesics, and peripheral or neuraxial local anaesthetics that act at different sites of the pain pathways.     

Preemptive analgesia or balanced periemptive analgesia?

"Preemptive analgesia" means that analgesia given before the painful stimulus prevents or reduces subsequent pain. The concept of preemptive analgesia originates from basic science and experimental studies. However, in some clinical studies preemptive effect is not always present. The authors think that it happens for: differences among experimental models and clinical reality, wrong use of some pharmacological knowledges, some methodological errors in clinical research. The authors analyze these factors and review in a critical manner clinical studies on preemptive analgesia. In some operations, only one administration of an analgesic drug, before surgery, is not sufficient to produce an evident preemptive effect. Postoperative pain can be reduced making a pharmacological treatment before surgery, for the whole time of painful stimulus. For this reason, the term "preemptive analgesia", like "analgesia given before surgery" is not adequate. The authors suggest that the concept of prevention of postoperative pain is well defined by the term of "balanced periemptive analgesia"; it is a new approach that use many modalities of analgesia in different times to prevent and control painful stimulus for the whole time of its origin: before and/or during operation and, if necessary, in the postoperative period for the residual pain.     

Preemptive ketamine during general anesthesia for postoperative analgesia in patients undergoing laparoscopic cholecystectomy

AIM: Preemptive analgesia is currently in use in the management of postoperative pain and no more under search. The administration of ketamine as intraoperative analgesic agent is well-known since a long time; the analgesic properties of this drug are related to its actions as a non-competitive N-methyl-D-aspartate receptors antagonist; these receptors present an excitatory function on pain transmission and this binding seems to prevent or reverse the central sensitisation of every kind of pain, including postoperative pain. In literature, the use of this anesthetic for the preemptive analgesia in the management of postoperative pain is controversial; for this reason the aim of our study was the clinical evaluation of preemptive perioperative analgesia with low-doses ketamine. METHODS: This trial involved 40 patients undergoing laparoscopic cholecystectomy, with the same surgical operator; postoperative analgesia was performed with the intraoperative administration of ketamine (0.7 mg/kg) or tramadol (15 mg/kg). A randomized, double-blind study was performed; after an inhalatory/analgesic general anesthesia (sevofluorane + remifentanyl) the postoperative-pain control was clinically evaluated through algometric measurements (Visual Analog Scale, Verbal Rating Scale, Pain Intensity Difference); supplemental doses of tramadol were administered if required, also to quantify the adequacy of analgesia, and adverse effects were evaluated. RESULTS: The results show that preemptive intraoperative analgesia with ketamine produces a good analgesia at the awakening, despite low duration (approximately 1 hour), and upgrades the analgesic effect of tramadol in the postoperative period. Among the adverse effects, some (for example nausea) were related to the administration of both analgesics and to the kind of surgery, others (hallucinosis, nystagmus, photophobia, psychomotor excitation, psychotic symptoms) were due to ketamine, and others (respiratory depression and hypotension) could be related to tramadol. Although the adverse effects due to ketamine are more numerous than those related to tramadol, the second could potentially be more dangerous. CONCLUSION: Our study suggests that preemptive low-doses ketamine is able to produce an adequate postoperative analgesia and increases the analgesic effect of tramadol; furthermore, ketamine adverse effects could be reduced by intraoperative administration of benzodiazepines and/or antiemetic drugs, or by the association of ketamine and a peripheral analgesic (ketorolac).     

Ketamine in perioperative analgesia for knee surgeries: Review of evidence from randomized controlled trials

Successful perioperative analgesia for knee surgeries results in improved patient satisfaction and promotes successful rehabilitation. However, effective perioperative pain control is commonly a challenging task for knee surgeries. Such surgical procedures as total knee replacement or knee arthroscopy may be accompanied by severe postoperative pain. As opioids and nonsteroidal anti-inflammatory drugs are commonly used, the side effects of these types of medicines are quite common as well, especially in patients with chronic pain, as they are commonly dissatisfied with regular analgesia. Patients with chronic pain tend to have lower tolerance to pain, and be dependent and tolerant to opioids. These patients typically require higher doses of analgesics, which further negatively affect patients’ safety and the overall perioperative experience. Multimodal perioperative analgesia helps to spare opioids and promote successful rehabilitation. Ketamine is a noncompetitive N-Methyl-d-aspartate (NMDA) receptor antagonist that has been used for multimodal perioperative analgesia as an adjunct to opioids and nonsteroidal anti-inflammatory drugs. Despite the significant number of papers evaluating the role of ketamine in perioperative analgesia, the feasibility of ketamine for perioperative pain control in knee surgeries remains a subject of debate. There are only a limited number of high-quality studies on the topic. We used a systematic approach to evaluate randomized controlled trials with perioperative ketamine used for knee surgeries. The majority of the studies confirmed that the utilization of ketamine in perioperative analgesia was associated with lower pain scores, reduced opioid use, improved knee joint mobility, and an increase in patient tolerance for physical therapy and rehabilitation. The techniques for ketamine administration and dosing varied significantly, which may explain the inconsistencies between the reports. In addition, some of the studies, even those of high quality, used nitrous oxide in both the study and control groups. Nitrous oxide has NMDA receptor antagonist properties, as does ketamine. None of the studies reported whether patients were taking methadone, dextromethorphan, memantine, or magnesium sulfate, which are NMDA receptor antagonists too. The concomitant use of NMDA receptor antagonists, other than ketamine, may have interfered with the realization of analgesic effects of ketamine. Although it is largely accepted that NMDA receptor antagonism at the spinal level explains most of the analgesic effects of ketamine, it also interacts at other multiple receptors centrally, including, cholinergic receptors, nicotinic and muscarinic, adrenergic, central NMDA, and non-NMDA glutamate receptors. These influences may potentially explain why patients treated with other NMDA receptor antagonists had improved with ketamine as well. Ketamine also interacts with opioid receptors at supraspinal sites, where it produces supraspinal antinociception. Some of the studies did not report whether the participants were opioid naïve or opioid dependent. That might be an important determinant of the analgesic effect because opioid dependent patients are shown to benefit from the ketamine significantly. None of the examined randomized controlled trials assessed the effects of ketamine on opioid dependent patients. The variability between the outcomes of ketamine utilization for perioperative analgesia for knee surgeries might be, at least partially, explained by these findings.     

Review article: Preventive analgesia: quo vadimus?

The classic definition of preemptive analgesia requires 2 groups of patients to receive identical treatment before or after incision or surgery. The only difference between the 2 groups is the timing of administration of the drug relative to incision. The constraint to include a postincision or postsurgical treatment group is methodologically appealing, because in the presence of a positive result, it provides a window of time within which the observed effect occurred, and thus points to possible mechanisms underlying the effect: the classic view assumes that the intraoperative nociceptive barrage contributes to a greater extent to postoperative pain than does the postoperative nociceptive barrage. However, this view is too restrictive and narrow, in part because we know that sensitization is induced by factors other than the peripheral nociceptive barrage associated with incision and subsequent noxious intraoperative events. A broader approach to the prevention of postoperative pain has evolved that aims to minimize the deleterious immediate and long-term effects of noxious perioperative afferent input. The focus of preventive analgesia is not on the relative timing of analgesic or anesthetic interventions, but on attenuating the impact of the peripheral nociceptive barrage associated with noxious preoperative, intraoperative, and/or postoperative stimuli. These stimuli induce peripheral and central sensitization, which increase postoperative pain intensity and analgesic requirements. Preventing sensitization will reduce pain and analgesic requirements. Preventive analgesia is demonstrated when postoperative pain and/or analgesic use are reduced beyond the duration of action of the target drug, which we have defined as 5.5 half-lives of the target drug. This requirement ensures that the observed effects are not direct analgesic effects. In this article, we briefly review the history of preemptive analgesia and relate it to the broader concept of preventive analgesia. We highlight clinical trial designs and examples from the literature that distinguish preventive analgesia from preemptive analgesia and conclude with suggestions for future research.     

Update on preemptive analgesia

Perioperative pain remains prevalent and poorly treated. Apart from its impact on the rate and unpleasantness of recovery from surgery, pain often remains as a residual aftereffect of surgery even though tissue healing appears complete. A growing appreciation for the underlying neurobiology of pain has identified mechanisms that can enhance the intensity of perioperative pain and even lead to more prolonged painful conditions. An essential observation is that tissue injury and the resulting nociceptor barrage initiates a cascade of events that can indelibly alter pain perception. Preemptive analgesia is the concept of initiating analgesic therapy before the onset of the noxious stimulus so as to prevent the nociceptor barrage and its consequences. However, preemptive analgesia, though firmly grounded in the neurobiology of pain, has yet to realize its anticipated clinical potential. As data accumulates, it has become clear that clinical studies emulating those from the laboratory and designed around a relatively narrow definition of preemptive analgesia have been largely unsupportive of its use. Nevertheless, preemptive analgesic interventions that recognize the intensity, duration, and somatotopic extent of major surgery can help reduce perioperative pain and its longer-term sequelae.     

Amantadine, a N-methyl-D-aspartate receptor antagonist, does not enhance postoperative analgesia in women undergoing abdominal hysterectomy.

N-methyl-D-aspartate (NMDA) antagonists administered before surgery will improve postoperative analgesia, presumably by inhibiting spinal sensitization processes. However, current clinical formulations of NMDA antagonists either enable only an oral application (i.e., dextromethorphan) or are associated with psychotropic side effects, as with the IV delivery of ketamine. Because of its noncompetitive NMDA receptor antagonist characteristics, amantadine may improve postoperative analgesia when administered before surgically induced trauma. In this prospective, randomized clinical study, we examined whether female patients undergoing elective abdominal hysterectomy experienced less postoperative pain when IV amantadine was applied in comparison with placebo before the start of surgery. Thirty patients were randomly assigned to receive 500 mL saline IV before the induction of standardized general anesthesia in Group 1 (Control group) or, in a double-blinded manner, 200 mg amantadine IV in 500 mL saline in Group 2 (Treatment group). Postoperative pain control was provided via IV patient-controlled analgesia with piritramide. During the first 48 h after tracheal extubation, pain perception was assessed by visual analog scales, and all analgesic requirements were documented. There were no significant differences between the two groups with respect to pain scores, postoperative analgesic requirements, and the incidence of side effects. Because of no differences in postoperative pain or opioid consumption, we conclude that a preoperative dose of 200 mg amantadine IV fails to enhance postoperative analgesia in patients undergoing elective abdominal hysterectomy. Implications: Because of no differences in postoperative pain or opioid consumption, we conclude that a preoperative dose of 200 mg amantadine IV fails to enhance postoperative analgesia in patients undergoing elective abdominal hysterectomy.     

Preemptive analgesia and local anesthesia as a supplement to general anesthesia: a review

General anesthesia (GA) and local anesthesia (LA) evolved on separate tracks. Procedures that could not be performed under LA were typically conducted under GA. Decoding of afferent linkage of peripheral noxious stimuli has provided important understanding that may change the way we traditionally treat surgical pain. In the 1980s, animal studies suggested that preemptive peripheral blocking of painful (nociceptive) stimuli to the central nervous system with regional anesthesia or LA and nonsteroidal analgesics could be beneficial in attenuating postoperative pain. Clinical studies based on this knowledge suggest combining LA with GA, and perhaps non-steroidal analgesics with or without narcotics, to reduce the severity of postoperative pain. General anesthetics can be given in lower minimal alveolar concentration when combined with LA, and recovery characteristics are superior. Increasing evidence suggests that the combined use of GA and LA may reduce the afferent barrage of surgery, and that preemptive analgesia may reduce postoperative pain and should be used in patient care. This article reviews the evidence supporting the combined use of LA or analgesics with GA or sedation to provide improved pain management after surgery.     

A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia

We evaluated in a qualitative systematic review the effect of N-methyl-D-aspartate (NMDA) receptor antagonists on reducing postoperative pain and analgesic consumption beyond the clinical duration of action of the target drug (preventive analgesia). Randomized trials examining the use of an NMDA antagonist in the perioperative period were sought by using a MEDLINE (1966-2003) and EMBASE (1985-2003) search. Reference sections of relevant articles were reviewed, and additional articles were obtained if they evaluated postoperative analgesia after the administration of NMDA antagonists. The primary outcome was a reduction in pain, analgesic consumption, or both in a time period beyond five half-lives of the drug under examination. Secondary outcomes included time to first analgesic request and adverse effects. Forty articles met the inclusion criteria (24 ketamine, 12 dextromethorphan, and 4 magnesium). The evidence in favor of preventive analgesia was strongest in the case of dextromethorphan and ketamine, with 67% and 58%, respectively, of studies demonstrating a reduction in pain, analgesic consumption, or both beyond the clinical duration of action of the drug concerned. None of the four studies examining magnesium demonstrated preventive analgesia. IMPLICATIONS: We evaluated, in a qualitative systematic review, the effect of N-methyl D-aspartate antagonists on reducing postoperative pain and analgesic consumption beyond the clinical duration of action of the target drug (preventive analgesia). Dextromethorphan and ketamine were found to have significant immediate and preventive analgesic benefit in 67% and 58% of studies, respectively.     

NMDA受体拮抗剂预防瑞芬太尼诱发术后痛觉过敏的效果:Meta分析

目的 采用Meta分析评价N-甲基-D-天冬氨酸(NMDA)受体拮抗剂预防瑞芬太尼诱发术后痛觉过敏的效果.方法 检索PubMed、EMBase、Springer及Cochrane图书馆,收集NMDA受体拮抗剂预防瑞芬太尼诱发术后痛觉过敏的临床随机对照研究.采用Cochrane协作网系统评价文献质量,并提取有关资料,主要包括术后镇痛药需要量、疼痛评分、手术结束至第1次需要镇痛治疗的时间以及术后不良反应的发生情况.采用RevMan 5.0软件进行Meta分析.结果 共纳入14项研究,包括623例患者,其中氯胺酮组223例,硫酸镁组87例,对照组313例.NMDA受体拮抗剂可降低术后4h时疼痛评分(P＜0.05),对术后镇痛药需要量、第1次需要镇痛治疗的时间及不良反应的发生率无影响(P＞0.05).结论 NMDA受体拮抗剂(氯胺酮和硫酸镁)不能预防瑞芬太尼诱发的术后痛觉过敏.     

The effects on postoperative oral surgery pain by varying NSAID administration times: comparison on effect of preemptive analgesia.

OBJECTIVE: Many studies on the efficacy of preemptive analgesia have been processed in different ways. But the value of preemptive analgesia is still controversial. The goal of this study was to compare analgesic effects of a nonsteroidal anti-inflammatory drug (NSAID) for oral surgical pain according to 3 different administration times. STUDY DESIGN: Using a randomized, parallel-group, single-center, and active-controlled test design, this study was conducted with 80 healthy patients undergoing a surgical removal of an impacted mandibular third molar requiring bone removal. The oral NSAID was first administered 1 hour preoperatively, or 1 hour postoperatively, or no scheduled administration pre- or postsurgery. Whenever patients felt at least moderate pain (score > or =5 on a 10-point scale) after surgery, they were instructed to take the same drug. Pain intensities and times to the first and second onsets of postoperative pain from the end of surgery were assessed for 24 hours. RESULTS: Of the 80 enrolled subjects in this study, 25 patients were assigned to the preemptive group, 26 to the posttreatment group, and 29 to the no-treatment group. The demographic distribution and duration of surgery in the 3 groups were statistically similar. The mean time to first onset of postoperative pain was significantly prolonged in the posttreatment group (277.2 minutes, P < .05) compared to the preemptive group (158.4 minutes) and the no-treatment group (196.5 minutes). The mean time to second onset of postoperative pain was not significantly different among the 3 groups. No significant statistical difference was found among the mean pain intensities at the first and second onsets of postoperative pain in the 3 groups. CONCLUSIONS: In this small selected group of subjects and limited study design, the analgesic effects of NSAID administered preoperatively were no longer effective for postoperative pain. The results in this population imply that scheduled postoperative analgesics before pain development are adequate for postoperative analgesia without preoperative administration.     

Low doses ketamine: antihyperalgesic drug, non-analgesic

Recent data in animal experiments as in clinical trials have clearly reported that pain modulation is related to an equilibrium between antinociceptive and pronociceptive systems. Therefore, the apparent pain level could not only be a consequence of a nociceptive input increase but could also result from a pain sensitization process. Glutamate, via NMDA receptors, plays a major role in the development of such a neuronal plasticity in the central nervous system, leading to a pain hypersensitivity that could facilitate chronic pain development. By an action on NMDA receptors opioids also induce, in a dose dependent manner, an enhancement of this postoperative hypersensitivity. "Antihyperalgesic" doses of ketamine, an NMDA receptor antagonist, were able to decrease this central sensitization not only in painful animal but also in human volunteers exposed to different pain models, or in the postoperative period. Many studies have reported that ketamine effects are elicited when this drug is administered the following manner: peroperative bolus (0.1 to 0.5 mg/kg), followed by a constant infusion rate (1 to 2 microg/kg per min) during the peroperative period and for 48 to 72 hours after anaesthesia. Those ketamine doses improved postoperative pain management by reducing hyperalgesia due to both surgical trauma and high peroperative opioid doses. This antihyperalgesic action of ketamine also limited the postoperative morphine tolerance leading to a decrease in analgesic consumption and an increase in the analgesia quality.     

超前镇痛护理理念用于食管癌患者术后镇痛

目的探讨超前镇痛护理理念对食管癌患者术后疼痛控制的影响。方法随机将188例食管癌手术患者分为常规镇痛组(n=93)和超前镇痛组(n=95)。常规镇痛组实施常规镇痛护理,即术前行疼痛知识宣教,术后应用Prince-Henry评分法定时评估患者疼痛,根据评分行针对性镇痛护理;超前镇痛组实施超前镇痛护理,即在前者基础上增加术前超前镇痛知识宣教,术后在执行各临床操作前行预见性疼痛评估,根据评分行预见性镇痛处理。比较两组患者术后24h、48h、72h疼痛评分,术后首次下床活动时间,肺部并发症发生率。结果两组术后24h、48h、72h疼痛评分比较,干预主效应P<0.05;超前镇痛组下床活动时间较常规镇痛组显著提前,肺部并发症发生率显著低于常规镇痛组(P<0.05,P<0.01)。结论超前镇痛护理理念对食管癌患者术后疼痛控制有积极的作用,有利于患者早日康复。     

全膝关节置换术围手术期疼痛综合控制的临床研究

目的探讨采用围手术期疼痛综合控制方法进行全膝关节置换术术后镇痛的临床疗效。方法2006年3月至2007年6月期间对60例单侧全膝关节置换术的患者采用围手术期疼痛综合控制方法进行术后疼痛的治疗。围手术期疼痛综合控制包括：术前患者教育和应用COX-2抑制剂超前镇痛；术中手术技术改进和减少手术创伤，并行关节周围多模式药物镇痛注射；术后常规应用COX-2抑制剂、医患沟通、冰敷和主动功能锻炼。术中关节周围注射随机分成多模式药物注射（MI）组和非多模式药物周围注射（NMI）组。观察患者术后疼痛情况（VAS）包括静息痛、运动疼痛。监测术后阿片类药物使用量和并发症。结果MI组术后静息疼痛评分均比NMI组低，术后阿片类镇痛药物使用量比NMI组少，两者之间的差异有统计学意义。MI组术后运动疼痛评分均比NMI组低，两者之间的差异无统计学意义。结论采用围手术期疼痛综合控制和关节周围多模式药物注射，能有效地控制全膝关节置换手术后的疼痛，且术后并发症少，有利于关节功能的恢复。     

Effects of preemptive epidural analgesia on post-thoracotomy pain

OBJECTIVE: The purpose of this study was to determine whether preemptive thoracic epidural analgesia (TEA) initiated before surgical incision would reduce the severity of acute post-thoracotomy pain and the incidence of chronic post-thoracotomy pain. METHOD: Meta-analysis of randomized controlled trials (RCTs). SEARCH STRATEGY: MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE were searched from 1966 to December 2004 for prospective RCTs published in all languages using the following MeSH terms: post-thoracotomy pain, epidural analgesia, chronic pain, and preemptive analgesia. SELECTION CRITERIA: All RCTs that compared thoracic epidural analgesia initiated before surgical incision (preemptive group) versus thoracic epidural analgesia initiated after completion of surgery (control group) in adult patients undergoing unilateral thoracotomy. MEASUREMENTS AND MAIN RESULTS: Three authors reviewed all citations and simultaneously extracted data on sample size, patient characteristics, surgical and analgesic interventions, methods of pain assessment, and pain scores at 24 hours, 48 hours, and 6 months postoperatively. Six studies were included with a total of 458 patients. Pooled analyses indicated that preemptive TEA was associated with a statistically significant reduction in the severity of acute pain on coughing at 24 and 48 hours (weighted mean difference -1.17 [95% confidence interval (CI) -1.50 to -0.83] and -1.08 [95% CI -1.17 to -0.99]), respectively. Acute pain was a good predictor of chronic pain. However, there was no statistically significant difference in the overall incidence of chronic pain at 6 months between the preemptive TEA group (39.6%) and the control group (48.6%). CONCLUSION: Preemptive TEA appeared to reduce the severity of acute pain but had no effect on the incidence of chronic pain.