Preemptive Analgesia by Intravenous Low-dose Ketamine and Epidural Morphine in Gastrectomy: A Randomized Double-blind Study

Background: Morphine and ketamine may prevent central sensitization during surgery and result in preemptive analgesia. The reliability of preemptive analgesia, however, is controversial.

Methods: Gastrectomy patients were given preemptive analgesia consisting of epidural morphine, intravenous low-dose ketamine, and combinations of these in a randomized, double-blind manner. Postsurgical pain intensity was rated by a visual analog scale, a categoric pain evaluation, and cumulative morphine consumption.

Results: Preemptive analgesia by epidural morphine and by intravenous low-dose ketamine were significantly effective but not definitive. With epidural morphine, a significant reduction in visual analog scale scores at rest was observed at 24 and 48 h, and morphine consumption was significantly lower at 6 and 12 h, compared with control values. With intravenous ketamine, visual analog scale scores at rest and morphine consumption were significantly lower at 6, 12, 24, and 48 h than those in control subjects. The combination of epidural morphine and intravenous ketamine provided definitive preemptive analgesia: Visual analog scale scores at rest and morphine consumption were significantly the lowest at 6, 12, 24, and 48 h, and the visual analog scale score during movement and the categoric pain score also were significantly the lowest among the groups.     

Post-operative Analgesia by Epidural Versus Intramuscular Nicomorphine after Thoracotomy. Part II

One hundred and sixty-three patients subjected to three different types of thoracic operation were allocated randomly either to balanced intravenous anaesthesia including i.v. opiates with post-operative intramuscular opiates (intramuscular group) or to balanced intravenous anaesthesia without i.v. opiates but with high thoracic epidural regional block during the operation as well as epidural nicomorphine post-operatively (epidural group). Post-operative nicomorphine in either group was given only at the request of the patient and as frequently as needed to obtain satisfactory pain relief. Patients in the epidural group were given nicomorphine exclusively by epidural injection. Patients in the epidural group required significantly less nicomorphine for effective pain relief (29 mg (sd = 10) over a period of 3 days compared to 52 mg (sd = 27) in the intramuscular group. Significantly fewer pulmonary complications in the epidural group were observed (9 atelectases in 83 patients in the epidural group compared to 24 atelectases in 80 patients in the intramuscular group). Only one patient developed pneumonia (intramuscular group). Although the epidural catheter was inserted at the T3-T4 level, no signs of ventilatory depression were found; on the contrary, respiration in the epidural group was significantly better than the intramuscular group. None of the patients, in either analgesia group, needed to be ventilated post-operatively.     

Post-operative Analgesia by Epidural Versus Intramuscular Nicomorphine after Thoracotomy. Part I

One hundred and sixty-three patients subjected to three different types of thoracic operation were allocated randomly either to balanced intravenous anaesthesia including i.v. opiates with post-operative intramuscular opiates (intramuscular group) or to balanced intravenous anaesthesia without i.v. opiates but with high thoracic epidural regional block during the operation as well as epidural nicomorphine post-operatively (epidural group). Post-operative nicomorphine was given only at the request of the patient and as frequently as needed to obtain satisfactory pain relief. Patients in the epidural group received nicomorphine exclusively by epidural injection. In this paper (Part I), general parameters between the epidural group and the im. group are compared. The epidural group showed acceptable cardiovascular stability during the operation. With the catheter tip at the T3-T4 level, there was apparently a preferential spread downwards of the local anaesthetics. Post-operatively both groups (i.m. and epidural) provided effective and rapid onset of analgesia. There were no major differences in post-operative pain assessment, either by the patient or by the team.     

Comparison of Intravenous or Epidural Patient-controlled Analgesia in the Elderly after Major Abdominal Surgery

Background: Patient-controlled analgesia (PCA) with intravenous morphine and patient-controlled epidural analgesia (PCEA), using an opioid either alone or in combination with a local anesthetic, are two major advances in the management of pain after major surgery. However, these techniques have been evaluated poorly in elderly people. This prospective, randomized study compared the effectiveness on postoperative pain and safety of PCEA and PCA after major abdominal surgery in the elderly patient.

Methods: Seventy patients older than 70 yr of age and undergoing major abdominal surgery were assigned randomly to receive either combined epidural analgesia and general anesthesia followed by postoperative PCEA, using a mixture of 0.125% bupivacaine and sufentanil (PCEA group), or general anesthesia followed by PCA with intravenous morphine (PCA group). Pain intensity was tested three times daily using a visual analog scale. Postoperative evaluation included mental status, cardiorespiratory and gastrointestinal functions, and patient satisfaction scores.

Results: Pain relief was better at rest (P = 0.001) and after coughing (P = 0.002) in the PCEA group during the 5 postoperative days. Satisfaction scores were better in the PCEA group. Although incidence of delirium was comparable in the PCA and PCEA groups (24%vs. 26%, respectively), mental status was improved on the fourth and fifth postoperative days in the PCEA group. The PCEA group recovered bowel function more quickly than did the PCA group. Cardiopulmonary complications were similar in the two groups.     

Postoperative Analgesia after Radical Retropubic Prostatectomy: A Double-blind Comparison between Low Thoracic Epidural and Patient-controlled Intravenous Analgesia

Background: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study.

Methods: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 [mu]g/ml fentanyl, and 2 [mu]g/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl.

Results: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group x time interaction was found in the Short Form-36.     

Long-term Pain and Activity during Recovery from Major Thoracotomy Using Thoracic Epidural Analgesia

Background: Pain following thoracotomy can persist for years with an undetermined impact on quality of life. Factors hypothesized to modulate this painful experience include analgesic regimen, gender, and type of incision.

Methods: A total of 157 generally healthy patients of both genders scheduled for segmentectomy, lobectomy, or bilobectomy through a posterolateral or muscle-sparing incision were randomly assigned to receive thoracic epidural analgesia initiated prior to incision or at the time of rib approximation. Pain and activity scores were obtained 4, 8, 12, 24, 36, and 48 weeks after surgery.

Results: Overall, there were no differences in pain scores between the control and intervention groups during hospitalization (P >= 0.165) or after discharge (P >= 0.098). The number of patients reporting pain 1 yr following surgery (18 of 85; 21.2%) was not significantly different (P = 0.122) from the number reporting preoperative pain (15 of 120; 12.5%). During hospitalization, women reported greater pain than men (worst pain, P = 0.007; average pain, P = 0.016). Women experienced fewer supraventricular tachydysrhythmias (P = 0.013) and were thus discharged earlier (P = 0.002). After discharge women continued to report greater discomfort than men (P <= 0.016), but did not differ from men in their level of physical activity (P = 0.241).     

Intraoperative Epidural Analgesia Combined with Ketamine Provides Effective Preventive Analgesia in Patients Undergoing Major Digestive Surgery

Background: As a broader definition of preemptive analgesia, preventive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. To demonstrate benefits from preventive treatment, objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated. The current study assessed the role and timing of epidural analgesia in this context.

Methods: In a randomized, double-blinded trial, 85 patients scheduled to undergo neoplastic colonic resection were included. All the patients received a thoracic epidural catheter, systemic ketamine at a antihyperalgesic dose, and general anesthesia. Continuous infusion of analgesics belonging to the same class was administered by either intravenous or epidural route before incision until 72 h after surgery. Patients were allocated to four groups to receive intraoperative intravenous lidocaine-sufentanil-clonidine or epidural bupivacaine-sufentanil-clonidine followed postoperatively by either intravenous (lidocaine-morphine-clonidine) or epidural (bupivacaine-sufentanil-clonidine) patient-controlled analgesia. Postoperative pain scores (visual analog scale), analgesic consumption, wound area of punctuate hyperalgesia, residual pain, and analgesics needed from 2 weeks until 12 months were recorded.

Results: Analgesic requirements, visual analog scale scores, and area of hyperalgesia were significantly higher in the intravenous treatment group (intravenous-intravenous), and more patients reported residual pain from 2 weeks until 1 yr (28%). Although postoperative pain measurements did not differ, postoperative epidural treatment (intravenous-epidural) was less effective to prevent residual pain at 1 yr (11%; P = 0.2 with intravenous-intravenous group) than intraoperative one (epidural-epidural and epidural-intravenous groups) (0%; P = 0.01 with intravenous-intravenous group).     

Intravenous Versus Epidural Administration of Hydromorphone: Effects on Analgesia and Recovery after Radical Retropubic Prostatectomy

Background: It remains unclear whether epidural administration of hydromorphone results in spinal analgesia or clinical benefit when compared with intravenous administration. Therefore, we undertook this study to determine whether epidural administration of hydromorphone resulted in decreased opioid requirement, improved analgesia, reduced side effects, more rapid return of gastrointestinal function, or shorter duration of hospital stay than intravenous administration.

Methods: Sixteen patients undergoing radical retropubic prostatectomy were randomized in a double-blind manner to receive either intravenous or epidural hydromorphone via patient-controlled analgesia (PCA) for postoperative analgesia. All patients underwent a standardized combined epidural and general anesthetic and all received ketorolac for 72 h postoperatively. To decrease variability, patients were cared for according to a standardized protocol and were deemed ready for discharge according to prospectively defined criteria.

Results: Patients in the intravenous PCA group required approximately twice as much opioid than the epidural PCA group (P < 0.008), but there were no differences between groups in pain scores or patient satisfaction. Epidural administration resulted in a greater incidence of pruritus (P - 0.02). Gastrointestinal function recovered quickly in all patients with little variation, and there were no differences between groups. All patients were deemed ready for discharge by the third postoperative day, and removal of surgical drains was the last discharge criterion reached in all patients.     

Transplacental Passage of Ketamine after Intravenous Administration

This study was designed to measure how fast and at what concentrations ketamine would enter the foeto-placental circulation, when administered intravenously to 10 healthy mothers immediately before forceps delivery, which was indicated by a delayed second stage of labour. It is shown that ketamine very rapidly passes the placenta, and that ketamine levels in cord blood exceed the levels in the maternal venous blood as early as 1 min 37 s after the injection. The ketamine levels in cord blood reach a maximum in the period 1 min 37 s to 2 min 5 s after the injection. Later they show a tendency to decline. A short-lasting, marked elevation of blood pressure was produced by the ketamine anaesthesia. Two of the newborn showed low Apgar scores at 1 min. In one of them this was probably attributable to the anaesthesia.     

PCEA技术在前列腺摘除术后的应用

目的:探讨硬膜外病人自控镇痛(PCEA)技术在前列腺摘除术后的镇痛效果及并发症。方法:选取耻骨上经膀胱前列腺摘除术患者80例,实验组采用低浓度罗哌卡因 小剂量吗啡行硬膜外病人自控镇痛,对照组采用肌注杜冷丁药物镇痛。观察两组各时段的镇痛效果及术后48h内发生膀胱痉挛次数、持续时间及膀胱冲洗量、冲洗时间等。结果:两组各时间段的镇痛评分呈显著性差异(P<0.01);48h内膀胱痉挛次数、持续时间、膀胱冲洗量、冲洗时间等有显著性差异(P<0.01);实验组所有患者均无明显伤口疼痛等症状,镇痛良好,心血管系统、呼吸系统与术前相比均无明显变化。结论:前列腺摘除术后利用低浓度罗哌卡因 小剂量吗啡行硬膜外病人自控镇痛效果确切,可以减轻或消除病人因手术创伤引起的疼痛和减少并发症,有利于病人生理功能的稳定和康复。     

小剂量氯胺酮吗啡及氯胺酮-吗啡配伍用于硬膜外腔术后镇痛作用的比较小剂量氯胺酮吗啡及氯胺酮-吗啡配伍用于硬膜外腔术后镇痛作用的比较

目的：探讨氯胺酮、吗啡硬膜外腔术后镇痛效应和伍用后是否可提高镇痛效果并减少副作用。方法：５０例硬膜外腔麻醉下行骨科手术的患者，随机分为５组，每组１０例。Ａ组：吗啡０．０１ｍｇ／ｋｇ；Ｂ组：氯胺酮０．４ｍｇ／ｋｇ；Ｃ组氯胺酮０．６ｍｇ／ｋｇ；Ｄ组：Ａ＋Ｂ；Ｅ组：Ａ＋Ｃ。于术后４、８、１２、２４、４８、７２ｈ记录疼痛评分（ＶＡＰＳ）及副作用的发生情况。结果：Ａ组ＶＡＰＳ评分平均为２．９５，有效镇痛７例，平均持续时间为５２．０ｈ；Ｂ组镇痛效果差，ＶＡＰＳ评分平均为７．２６，有效镇痛３例，与Ａ组比较有统计学显著差异（Ｐ＜０．０１）；Ｃ组ＶＡＰＳ评分平均为３．６０，与Ａ组比较无统计学差异，有效镇痛７例，平均持续时间为４４．４ｈ；Ｄ组ＶＡＰＳ平均评分为２．７３，与Ａ组比较无统计学差异，平均持续时间为５０．８ｈ；Ｅ组平均ＶＡＰＳ评分为１．５８，与Ａ组比较有统计学显著差异（Ｐ＜０．０１），持续时间为５８．１ｈ。结论：１．氯胺酮０．４ｍｇ／ｋｇ硬膜外腔术后镇痛效果差，剂量增至０．６ｍｇ／ｋｇ镇痛效果与吗啡０．０１ｍｇ／ｋｇ相近，恶心、呕吐发生较少，无精神方面的副作用；２．氯胺酮与吗啡配伍，随着氯胺酮剂量增加到０．６ｍｇ／ｋｇ