Continuous epidural infusion of ropivacaine for the prevention of postoperative pain after major orthopaedic surgery: A dose-finding study

The present study investigated the dose relationship of ropivacaine with regard to analgesia and motor block when administered as a continuous 21 hour epidural infusion following major orthopaedic surgery.Forty six patients scheduled for elective total knee or hip arthroplasty were compared in this double-blind study. Patients were randomly assigned to one of four treatment groups: saline (n=12); ropivacaine 0.1% (n=11); ropivacaine 0.2% (n=12); ropivacaine 0.3% (n=11). Initial epidural analgesia was established with 0.5% ropivacaine and general anaesthesia was then induced for surgery. Within 30 minutes of the end of surgery, epidural infusions were commenced at a rate of 10 ml/hour for 21 hours. All patients had access to PCA morphine. Morphine consumption, VAS pain scores at rest, sensory and motor block and overall quality of treatment were assessed at regular intervals.The morphine consumption and VAS scores were lower overall in the ropivacaine groups than in the group receiving only PCA morphine. The difference was more evident during the first 8 hours of postoperative infusion, when significant differences between the ropivacaine 0.2% and 0.3% groups and the saline group were found. The incidence and degree of motor block were dose dependent. There was significantly higher patient satisfaction in all ropivacaine groups compared to the saline control group.In conclusion, 21 hour epidural infusion of ropivacaine, combined with PCA morphine, provides effective pain relief following major joint surgery and without significant adverse events. Morphine consumption and pain scores were lowest in the 0.3% ropivacaine group but this group had a higher degree of motor block. Pain relief with the combination of ropivacaine and PCA morphine is superior to that of PCA morphine alone.     

Intravenous morphine in postoperative infants: intermittent bolus dosing versus targeted continuous infusions

Eighty-three infants received i.v. morphine following surgery as a continuous infusion to a targeted morphine concentration of 20 ng ml(-1) (n = 56) or as intermittent bolus doses as needed (n = 27). Ventilation was compared in the two groups by continuous pulse oximetry, by venous blood gases on postoperative day 1 (POD 1) and by CO2 response curves. Infant pain scores were done to assess analgesia every 4 h. Both groups achieved pain scores consistent with analgesia but the bolus group showed a higher percentage of pain scores indicating distress (32 vs. 13%, P < 0.001). Room air saturations of < 90% were seen for 2.3% of POD1 in infusion-treated infants and for 2.5% of POD1 in bolus-treated infants. Mean venous PCO2S were normal in the two groups. Four infants showed ventilatory effects in the infusion group (4/ 56 = 7%); venous hypercarbia in two (2 days, 36 days), oximetry desaturation in one (240 days), both effects in one (6 days). Ventilatory effects were not statistically different between the intermittent bolus-treated and infusion-treated infants but may be clinically important. Monitoring with continuous oximetry is necessary. Morphine clearance increased with age. Infants with detectable morphine also had measurable morphine-6-glucuronide in both groups. Oral intake began at 16 h in both groups and other side effects were infrequent.     

Chronic Cancer-Related Pain: Continuous Perineural Infusion of Local Anesthetics as Alternative to Systemic Analgesic Drugs

Pain is a major concern for patients suffering from cancer. Although opioid drugs remain the gold standard for treatment of pain, little is known about the interest of continuous analgesia techniques as alternative. The aim of the present article is to detail the feasibility and to present the diversity of continuous perineural infusion of local anesthetic. A series of five patients suffering from different cancer-related pain is presented. A continuous perineural block was proposed to patients presenting with unbearable pain in an area innervated by a plexus or a nerve despite parenteral analgesic pharmacotherapy. All blocks were performed in a surgical theatre under sterile conditions. An initial bolus dose with 3.75 mg/mL ropivacaine was injected followed by a continuous infusion of 2 mg/mL of ropivacaine. Patient-controlled perineural analgesia was started at home by a nursing network. The technique, the efficacy, and the side effects were reported. Complete pain relief was noted 15 minutes after local anesthetic injection in the five cases, and efficacy was maintained during the following days at home, with no other analgesic treatment required. One patient restarted working a few weeks after catheter insertion. The catheter duration lasted for 12 to 110 days. One catheter was removed because of local anesthetic leak at the puncture point. Some paresthesia was noted in one patient. No other side effect was noted. No infection was reported. In selected patients, continuous perineural infusion of local anesthetics appears to be an attractive alternative to parenteral opioids for cancer-related pain. Further investigation is warranted to better define the place of these techniques in the armamentarium of cancer-related pain treatment.     

罗哌卡因两种给药方案在分娩镇痛中的应用比较

目的　比较罗哌卡因 2种连续输注方案在产科硬膜外分娩镇痛中的应用。方法　 60例产妇随即均分为A组和B组 ,两组于宫口开 2cm时行硬膜外镇痛 ,负荷量均为 0 . 2 %罗哌卡因 7～ 10ml。A组为 0 .1%罗哌卡因 (10ml/h) ,B组为0 2 %罗哌卡因 (5ml/h) ,同时分别加入 2mg/L芬太尼 ,待宫口近开全 (8～ 9cm)停药。检测两组产妇的生命体征 ,疼痛程度 ,下肢运动能力 ,宫缩感觉变化 ,产程及分娩结果等。结果　 2组均获得满意镇痛 ,两组满意度分别为 93 %、96%。运动能力 :两组产妇Bromega分级均未超过I级 ,但行走至产床时A组 5例 ,B组 7例感觉腿软无力 (P >0 . 0 1)。感觉能力 :两组对宫缩的感觉无明显下降 ,第二产程时均可良好的屏气用力 ,产钳助产率分别为 7%和 10 %。产程时间及分娩结果 :两组产程时间均在正常范围 ,组间无明显差异。结论　罗哌卡因两种给药方案均可安全有效应用于无痛分娩。     

A comparison of motor block between ropivacaine and bupivacaine for continuous labor epidural analgesia.

The aim of the present study was to compare the amount of motor block produced by different loading doses of ropivacaine and bupivacaine when delivered in a dilute solution with added opioid. Sixty-eight healthy term primigravid parturients were randomized to receive an initial bolus dose of 10 mL of 1 of the following: 0.25% bupivacaine (high bupivacaine), 0.25% ropivacaine (high ropivacaine), 0.125% bupivacaine (low bupivacaine), or 0.125% ropivacaine (low ropivacaine). Each loading dose had 10 micrograms of sufentanil added to it. All groups received a continuous infusion of a 0.1% study drug infusion with 0.6 microgram/mL of sufentanil at a rate of 8 to 14 mL/h to maintain analgesia. Supplemental doses of 10 mL of a 0.125% study solution with 10 micrograms of sufentanil were given as needed. Pain scores and a modified Bromage scale were used to assess analgesia and motor block. A statistically significant greater percentage of parturients receiving bupivacaine had motor block than those who received ropivacaine, with a marked decrease in the occurrence of motor block in the low ropivacaine group. The pain relief seemed to be less satisfactory in the ropivacaine groups, but the difference was not statistically significant. Ropivacaine produced significantly less motor block than bupivacaine in the 0.25% and the 0.125% loading doses, with the greatest difference seen in the lower concentration loading dose of ropivacaine.     

Treatment of Ischemic Pain in Patients Suffering from Peripheral Vasculopathy with Transdermal Buprenorphine Plus Epidural Morphine with Ropivacaine vs. Epidural Morphine with Ropivacaine

Aim:   This study compared the efficacy and safety of buprenorphine transdermal delivery system with peridural infusion of morphine and ropivacaine to peridural infusion alone for the control of ischemic pain in patients suffering from peripheral vasculopathy.
Methods:   Eighty-six patients were randomized into two groups. In the first group, a buprenorphine patch 35 µg/hour TTDS (transtec transdermal device plus ropivacaine and morphine) was applied, and a peridural infusion of ropivacaine/morphine (200 mg + 2 mg) was established. In the second group, ropivacaine and morphine analgesia was obtained using a peridural infusion and a placebo patch. The primary efficacy parameter was the visual analog scale score for pain. Secondary parameters of efficacy were the short-form McGill Pain Questionnaire scores and a score for pain interference with sleep obtained from patient diaries evaluated every week for a period of 4 weeks.
Results:   Subjects in the TTDS group reported a reduction in pain, increased sleep, and a lower incidence of side effects compared with the control group.
Conclusion:   Transdermal buprenorphine use resulted in significant pain relief with excellent patient satisfaction, which may translate into improvement in mood and quality of life.     

不同术后镇痛方法对老年患者认知功能的影响

目的探讨不同的术后镇痛方法对老年患者认知功能的影响的差异性,为提高老年患者术后生活质量,减轻认知功能扰乱提供依据。方法选择行腹部手术患者64例,年龄60岁以上术前无明显认知障碍,不合并脑血管疾患,无呼吸功能障碍,无肝肾功能障碍。实施连续硬膜外麻醉,随机分为2组,每组32例。经硬膜外自控镇痛组（PCEA组）：术后先给0．25％罗哌卡因6ml＋吗啡1～1．5mg＋氟哌利多1．25mg负荷镇痛剂量,尔后用100m10．25％罗哌卡因＋吗啡5mg＋氟哌利多2．5mg作术后2dPCEA。持续注入速率2．0ml／h,PCEA量1．0ml／次,锁定时间为15min。经外周静脉自控镇痛组（PCIA组）：吗啡1．0mg／ml＋氟哌利多0．2mg／ml,负荷镇痛剂量5．0ml,PCIA量1．0ml／次,持续注入速率1．0ml／h,锁定时间为15min。分别于术前、术后1d和3d进行认知功能测定。结果两组患者术后自控镇痛,其疼痛视觉评分无差异,均达到满意效果。术后1dPCIA组有近半数患者认知功能测试异常,与PCEA组比较：P〈0．01,PCIA术后镇痛对认知功能改变更加明显。由此说明,术后镇痛单从认知功能改变考量,PCEA较PCIA优越。结论PCIA与PCEA应用于老年患者下腹部手术术后镇痛,均能达到满意的术后镇痛,但PCIA影响术后认知功能较PCEA明显。因此,术后镇痛选用PCEA较PCIA优越。     

Comparison of intermittent bolus with continuous infusion of epidural morphine in the treatment of severe cancer pain.

Twenty-eight patients with severe pain due to cancer, who could no longer obtain acceptable pain relief from optimised doses of oral opioids, were entered into a study which compared pain relief, satisfaction with pain therapy and estimates of neuropsychological functioning during treatment with spinally administered (i.e., epidural and intrathecal) morphine as either repeated bolus doses or as a continuous infusion. These measures of efficacy and side effects were repeated every 2 weeks until either the patient died (82% of patients), withdrew from the study or were no longer able to complete the tests due to deterioration of their condition. The mean (range) duration of treatment was 169 (6-537) days for those patients receiving continuous infusion and 140 (28-378) days for those patients receiving repeated bolus doses. There was no significant difference in visual analogue pain scores, pain relief scores and satisfaction scores between the bolus and infusion groups. Furthermore, low pain scores and high pain relief scores indicated that both treatment modalities provided effective pain control. Similarly, there was no significant difference between the two groups in the various tests used to assess depression or neuropsychological function (i.e., memory, vigilance, attention and processing). There was a significantly greater degree of dose escalation in patients receiving continuous infusion compared to patients receiving repeated bolus doses. For 6 patients in the infusion group the catheter was sited in the intrathecal space, as the dose requirements by the epidural route exceeded the delivery capacity of the pump. For 4 patients in the bolus group the catheter was similarly sited, due to pain on injection and leakage/blockage.(ABSTRACT TRUNCATED AT 250 WORDS)     

舒芬太尼及芬太尼与吗啡用于子宫切除术后硬膜外镇痛的比较

目的：比较舒芬太尼、芬太尼与吗啡用于子宫切除术后持续硬膜外镇痛的临床镇痛效果和不良反应。方法：选择ASAⅠ或Ⅱ级,在连续硬膜外麻醉下行子宫切除术,术后行硬膜外镇痛的患者120例,随机分为4组,S1组（舒芬太尼0．5μg／mL复合甲磺酸罗哌卡因0．237mg／mL）、S2组（舒芬太尼0．75μg／mL复合甲磺酸罗哌卡因0．237mg／mL）、F组（芬太尼5μg／mL复合甲磺酸罗哌卡因0．237mg／mL）、M组（吗啡0．06mg／mL复合甲磺酸罗哌卡因0．237mg／mL）;负荷剂量5mL,速度2mL／h,单次给药0．5mL,锁定时间15min。观察患者术后疼痛视觉模拟评分（VAS）、不良反应以及Ramsay评分。结果：4组患者术后4hVAS评分差异无统计学意义（P〉0．05）,S2,M组术后8h,16h评分低于S1组（P〈0．05）,S2,M组镇痛满意率更高（P〈0．05）。M组恶心、呕吐、瘙痒发生率高（P〈0．05）。结论：舒芬太尼0．75μg／mL复合甲磺酸罗哌卡因0．237mg／kg用于子宫切除术后镇痛效果满意,不良反应发生率低。     

不同脊麻药对术后持续输注镇痛和尿潴留的影响

目的 观察不同的脊麻药对脊椎-硬膜外腔联合麻醉后硬膜外镇痛的尿潞留的影响。方法 60例下肢择期手术患，选择脊椎-硬膜外腔联合麻醉，以布比卡因和罗哌卡因行脊麻，然后以布比卡因 吗啡行术后硬膜外镇痛，观察其视觉模拟镇痛评分和对尿潴留的影响。结果 两组病人镇痛效果均好，无明显差别；以0．5％罗哌卡因重比重液行脊麻，尿潴留发生率明显比以0．5％布比卡因重比重液行脊麻低，有显性差异。结论 蛛网膜下隙-硬膜外腔联合麻醉后硬膜外镇痛，脊麻选择0．5％罗哌卡因重比重液镇痛效果好，尿潴留发生率较低，值得临床推广应用。     

Treatment of severe cancer pain by low-dose continuous subcutaneous morphine

In a prospective and intraindividually controlled trial, we have compared the efficacy and safety of a continuous subcutaneous morphine infusion with conventional intermittent oral or subcutaneous morphine application. Twenty-eight in-patients with cancer pain received a short-term infusion lasting 2-42 days, and 8 out-patients underwent long-term infusion from 49 to 197 days during the terminal stage of their disease. Continuous subcutaneous morphine infusion significantly (P less than 0.001) improved both pain and quality of life when compared to conventional morphine application. With continuous infusion, 5-48 mg (median 19 mg) of morphine was required daily, significantly (P less than 0.001) less than the 10-90 mg (median 50 mg) necessary with conventional use. As a result of lower dosage, side effects under continuous infusion were infrequent and mild. Constipation occurred in 3 of the 36 patients and was always controlled by the addition of laxatives; no nausea, sedation or respiratory depression were observed. Signs of tolerance developed in 2 patients on long-term infusion, but the use of continuous subcutaneous methadone for 2 weeks reversed the tolerance. The study presented indicates that low-dose continuous subcutaneous morphine provides a valuable treatment modality for severe terminal cancer pain exhibiting a high degree of both efficacy and safety.     

Continuous intravenous infusion of morphine for severe dyspnea

We describe eight patients who had terminal lung cancer causing severe dyspnea unrelieved by oxygen, nonnarcotic drugs, or intermittent bolus narcotics. We treated these patients with continuous intravenous infusion of morphine, beginning with bolus IV injections of 1 or 2 mg of morphine every 5 to 10 minutes until the patient reported relief. A continuous morphine infusion was then started, with the hourly dose equal to 50% of the cumulative bolus dose. Vital signs, degree of sedation, and blood gases were serially followed. Six patients achieved good dyspnea relief, one had moderate relief, and one had a poor response. Variable changes were noted in the PaO2, whereas PaCO2 steadily increased in five of seven patients, and pH decreased in six. There was little change in systolic blood pressure or pulse, and only one individual had less than 10 respirations per minute. The major side effect of treatment was sedation, treated by temporarily discontinuing morphine until the patients' mental status improved and then restarting the infusion at a 50% lower hourly morphine dose. Mean time of study was 30 hours (range 16 to 87 hours). Seven of the eight study patients died during treatment. Whether morphine therapy shortened survival is uncertain. We conclude that continuous morphine infusion is effective therapy for severe dyspnea. The treatment is ethically justified. Relief of suffering is the primary goal of therapy, and less risky treatments are unavailable.     

不同浓度罗哌卡因配伍连续股神经阻滞用于全膝关节置换术后镇痛的效果

目的：观察不同浓度罗哌卡因配伍连续股神经阻滞用于全膝关节置换术后镇痛的效果。方法：选择美国麻醉医师协会（ASA）分级Ⅰ～Ⅱ级行单侧全膝关节置换患者60例,随机分为2组：高浓度组（0.25%罗哌卡因）和低浓度组（0.125%罗哌卡因）,每组30例。所有患者均实施气管插管全身麻醉,术后采用连续股神经阻滞进行镇痛。记录患者在静息、主动和持续被动功能训练时的视觉模拟评分（VAS）疼痛评分,同时记录开始下床活动时间,肌力分级和并发症发生率。结果：高浓度组患者在术后6h、24h、48h及72h的静息、主动和持续被动功能训练时的VAS疼痛评分均显著低于低浓度组患者（P〈0.05）;2组患者下床活动时间无显著差异[（25±2）h比（27±4）h,P〉0.05];2组患者的术后24～72h肌力评分平均大于3级;2组术中和术后均未出现并发症。结论：相对于0.125%的罗哌卡因,采用浓度0.25%的罗哌卡因配伍连续股神经阻滞可提供满意的术后镇痛。     

Epidural Labor Analgesia: Continuous Infusion Versus Patient-Controlled Epidural Analgesia With Background Infusion Versus Without a Background Infusion

The purpose of this study was to compare the total epidural dose of 3 commonly used labor epidural modalities. After local institutional review board approval, 195 laboring parturients received an epidural catheter for labor analgesia. All patients received an initial bolus of 0.1% ropivacaine (10 mL) and fentanyl (100 microg). Maintenance of labor analgesia consisted of ropivacaine 0.1% with fentanyl 2 microg/mL. Patients were then randomly assigned into 3 groups: Group 1 (continuous epidural infusion [CEI]), continuous infusion at 10 mL/h; group 2 (CEI + patient-controlled epidural analgesia [PCEA]), CEI at 5 mL/h with a demand dose of 5 mL allowed every 20 minutes with a 20 mL/h maximum dose; group 3 (PCEA), demand doses only of 5 mL every 15 minutes with a 20 mL/h maximum dose. Measured variables included total epidural dose, total bolus requests and boluses delivered, number of staff interventions, pain Visual Analog Scale (VAS; 0-100), modified Bromage scores, stage I and II labor duration, delivery outcome, and maternal satisfaction after delivery. No differences were noted with respect to pain VAS, modified Bromage scores, stage I and II labor duration, number of staff interventions, delivery outcome, and maternal satisfaction score. Total infusion dose was lower in demand dose only PCEA compared with CEI and CEI + PCEA groups (P = < .01). Demand dose-only PCEA results in less total epidural dose compared with CEI and CEI + PCEA without affecting labor duration, motor block, pain VAS, maternal and neonatal outcomes, and maternal satisfaction. PERSPECTIVE: This article compares 3 commonly used labor epidural delivery modalities (traditional continuous epidural infusion, patient-controlled epidural analgesia with a background infusion, and demand dose-only patient-controlled epidural analgesia). Benefits in epidural dose reduction with demand dose only PCEA does not translate into improved maternal and neonatal outcome.     

罗哌卡因联合镇痛药蛛网膜下隙阻滞用于剖宫产术

目的：比较不同剂量罗哌卡因以及与芬太尼或吗啡联合用于蛛网膜下隙阻滞，剖剖宫产患者阻滞效果、血压、心率和不良反应的影响。方法：选择急诊剖宫产患者60例，随机分成四组，每组15例。经侧卧位L2－3间隙穿刺行阻滞麻醉。A组：罗哌卡因10mg，B组：罗吡卡因7．5mg 芬太尼25μg，C组：罗吡卡因7．5mg 吗啡0．2mg,D组：罗吡卡因5mg 芬太尼25μg。用针刺法测感觉阻滞平面，用改良Bromage法测运动阻滞，术后随访并记录开始出现切口疼痛的时间，以及头痛，恶心、呕吐等并发症。结果：A组的感觉阻滞平面上界为T2－6，高于其他组（P＜0．05），下肢运动完全阻滞百分率明显大于其他组，差异有显著性（P＜0．05），但A组感觉阻滞时间与B组相比没有差异（P＞0．05）。四组中。C组感觉阻滞持续时间最长，与其他组比较差异有显著性（P＜0．05），运动阻滞时间与B组比较没有差异（P＞0．05），明显比A组短（P＜0．05）。在D组中，有66．7％的患者因感觉阻滞平面不完善，需在硬膜外导管内注入局麻药。血流动力学的影响以A组最为明显，在注药后的5min，血压，心率显著降低，与基础值比较，差异有意义（P＜0．05），术后恶心、呕吐发生率C组最高，与其他组比较，差异有显著性（P＜0．05）；四组患者术后均无头痛症状。结论：罗吡卡因加入芬太尼25μg，能减少局麻药的用量，达到良好的麻醉效果，对机体血流动力学影响小，能延长术后镇痛时间，并且不增加术后呕吐的发生率。     

Response of intractable pain to continuous intrathecal morphine: a retrospective study.

We have treated 37 patients with intractable pain (35 with cancer-related pain) by continuous intrathecal morphine infusion via implanted pump. These patients were carefully selected according to specific criteria, and each demonstrated a significant reduction in pain following a test dose of intrathecal morphine. All patients had good pain relief from intrathecal morphine infusion, even with pain located in cervical dermatomes. Systemic narcotics could be withdrawn from most patients. Significant side effects were rare and typically self-limited. Many patients required gradually increasing doses, seemingly related to disease progression. Two patients with non-malignant pain have had variable dose requirements over 28 and 44 months without clear tolerance. In these patients we observed a reduction in side effects associated with systemic opioids when continuous intrathecal opioid infusion was instituted. Intrathecal opioid administration may have fewer complications than ablative pain relief procedures. In properly selected patients, this method offers an effective alternative for pain relief.     

The effect of patient-controlled analgesia on coadministered red blood cells

BACKGROUND: Patient-controlled analgesia (PCA) provides effective pain control. The possibility of administrating opioids in the same line as red blood cells (RBCs) for patients with poor venous access has been entertained. The literature on this approach is not extensive, but generally cautionary. STUDY DESIGN AND METHODS: Standard concentrations of morphine, hydromorphone (Dilaudid), and meperidine (Demerol) were used to determine the effect on RBCs. Three in vitro approaches were used: 1) continuous low-dose opioid infusion with a single bolus, 2) continuous infusion with multiple boluses, and 3) assessment of RBCs with different concentrations of opioids in test tubes. Samples were assayed for hemoglobin (Hb), mean corpuscular volume (MCV), plasma Hb, potassium, and lactate dehydrogenase, and a peripheral blood smear was made. RESULTS: Addition of each drug as a single or multiple bolus(-es) with continuous infusion showed the same effects as normal saline. In vitro exposure of Demerol at a 1:2 ratio (drug:blood) increased the MCV (110 fL), at 1:1 the MCV was 120 fL, and there was 4.5 percent hemolysis. At 2:1, hemolysis increased to 9.2 percent. Both morphine and Dilaudid had similar effects as normal saline. CONCLUSION: Morphine, Dilaudid, and Demerol, given as a bolus in the intravenous line, have the same effects as those seen with saline. When mixed directly with the blood for more than 1 hour, however, Demerol caused increasing RBC swelling and at high, nontherapeutic concentrations, caused hemolysis. Our study suggests that analgesia delivered via PCA may be safely coadministered with RBCs. Further clinical study is warranted.     

Postoperative analgetische Wirksamkeit intraartikulärer Morphin- oder Ropivacaingabe nach Kniegelenkarthroskopie

INTRODUCTION: Recent studies for postoperative pain relief after arthroscopy by intraarticular morphine or bupivacaine showed controversial results. The aim of the study was to evaluate the analgesic effect of intraarticular morphine and ropivacaine. METHODS: 135 patients were randomized into 9 groups (n=15) after standardized knee-arthroscopy. They received either 1 mg or 5 mg morphine or 150 mg ropivacaine or a combination of 5 mg morphine and 75 mg ropivacaine. Drains were opened either after 10 or 30 minutes. A control-group received isotonic saline. Pain was assesed 1 h and 4 h after surgery, at 8 pm on the day of the operation and at 8am and 4 pm the following two days by a VAS scale. Tramadol consumption as rescue medication was registred. RESULTS: Ropivacaine showed the best pain relief after surgery. After 24 h the pain intensity approximated in all groups and after 48 h there was no difference. Tramadol consumption was highest in the control group and lowest in the ropivacaine group (p<0,05). Ropivacaine showed better pain reduction than morphine. An influence of the time, when drains were opened, could only be demostrated for the 75 mg ropivacain combination group. CONCLUSION: Intraarticular ropivacaine following elective knee-arthroscopy reduces postoperative analgetic consumption significantly and improves patient comfort.     

Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats

Ziconotide is a selective, potent and reversible blocker of neuronal N-type voltage-sensitive calcium channels (VSCCs). Morphine is an agonist of mu-opioid receptors and inhibits N-type VSCC channels via a G-protein coupling mechanism. Both agents are antinociceptive when they are administered intrathecally (spinally). The present study investigated the acute and chronic (7-day) interactions of intrathecally administered ziconotide and morphine on nociception in several animal models of pain. In the acute study, intrathecal bolus injections of morphine and ziconotide alone produced dose-dependent inhibition of formalin-induced tonic flinch responses and withdrawal responses to paw pressure. The combination of ziconotide and morphine produced an additive inhibition of formalin-induced tonic flinch responses and a significant leftward shift of the morphine dose-response curve in the paw pressure test. After chronic (7-day) intrathecal infusion, ziconotide enhanced morphine analgesia in the formalin test. In contrast, chronic intrathecal morphine infusion produced tolerance to analgesia, but did not affect ziconotide antinociception. Antinociception produced by ziconotide alone was the same as that observed when the compound was co-administered with morphine to morphine-tolerant rats. In the hot-plate and tail immersion tests, chronic intrathecal infusion of morphine lead to rapid tolerance whereas ziconotide produced sustained analgesia with no loss of potency throughout the infusion period. Although ziconotide in combination with morphine produced an apparent synergistic analgesic effects during the initial phase of continuous infusion, it did not prevent morphine tolerance to analgesia. These results demonstrate that (1) acute intrathecal administrations of ziconotide and morphine produce additive or synergistic analgesic effects; (2) chronic intrathecal morphine infusion results in tolerance to analgesia but does not produce cross-tolerance to ziconotide; (3) chronic intrathecal ziconotide administration produces neither tolerance nor cross-tolerance to morphine analgesia; (4) intrathecal ziconotide does not prevent or reverse morphine tolerance.     

'Balanced analgesia' in the perioperative period: is there a place for ketamine?

We investigated whether intraoperative 'subanesthetic doses' of ketamine have a postoperative anti-hyperalgesic and an analgesic effect and which is the preferential route of administration, either systemic (intravenous, i.v.) or epidural. One hundred patients scheduled for rectal adenocarcinoma surgery under combined epidural/general anesthesia were included. Before skin incision all the patients received an epidural bolus followed by an infusion of continuous bupivacaine/sufentanil/clonidine mixture. They were randomly assigned to receive no ketamine (group 1), i.v. ketamine at the bolus dose of 0.25 mg/kg followed by an infusion of 0.125 mg/kg per h (group 2), 0.5 mg/kg and 0.25 mg/kg per h (group 3), epidural ketamine 0.25 mg/kg and 0.125 mg/kg per h (group 4), or 0.5 mg/kg and 0.25 mg/kg per h (group 5). All i.v. and epidural analgesics were stopped at the end of surgery and patients were connected to an i.v. morphine patient-controlled analgesia (PCA) device. Short-term postoperative analgesia (72 h) was assessed by pain visual analog scale scores at rest, cough, and movements as well as by PCA requirements. Wound mechanical hyperalgesia was evaluated and residual pain was assessed by asking the patients at 2 weeks, and 1, 6, and 12 months. The area of hyperalgesia and morphine PCA requirements were significantly reduced in group 3. These patients reported significantly less residual pain until the sixth postoperative month. These observations support the theory that subanesthetic doses of i.v. ketamine (0.5 mg/kg bolus followed by 0.25 mg/kg per h) given during anesthesia reduce wound hyperalgesia and are a useful adjuvant in perioperative balanced analgesia. Moreover, they show that the systemic route clearly is the preferential route.