Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy

BACKGROUND: Intravenous infusion of lidocaine decreases postoperative pain and speeds the return of bowel function. The authors therefore tested the hypothesis that perioperative lidocaine infusion facilitates acute rehabilitation protocol in patients undergoing laparoscopic colectomy. METHODS: Forty patients scheduled to undergo laparoscopic colectomy were randomly allocated to receive intravenous lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia, then a continuous infusion of 2 mg.kg.h intraoperatively and 1.33 mg.kg.h for 24 h postoperatively) or an equal volume of saline. All patients received similar intensive postoperative rehabilitation. Postoperative pain scores, opioid consumption, and fatigue scores were measured. Times to first flatus, defecation, and hospital discharge were recorded. Postoperative endocrine (cortisol and catecholamines) and metabolic (leukocytes, C-reactive protein, and glucose) responses were measured for 48 h. Data (presented as median [25-75% interquartile range], lidocaine vs. saline groups) were analyzed using Mann-Whitney tests. P<0.05 was considered statistically significant. RESULTS: Patient demographics were similar in the two groups. Times to first flatus (17 [11-24] vs. 28 [25-33] h; P<0.001), defecation (28 [24-37] vs. 51 [41-70] h; P=0.001), and hospital discharge (2 [2-3] vs. 3 [3-4] days; P=0.001) were significantly shorter in patients who received lidocaine. Lidocaine significantly reduced opioid consumption (8 [5-18] vs. 22 [14-36] mg; P=0.005) and postoperative pain and fatigue scores. In contrast, endocrine and metabolic responses were similar in the two groups. CONCLUSIONS: Intravenous lidocaine improves postoperative analgesia, fatigue, and bowel function after laparoscopic colectomy. These benefits are associated with a significant reduction in hospital stay.     

Lack of Impact of Intravenous Lidocaine on Analgesia, Functional Recovery, and Nociceptive Pain Threshold after Total Hip Arthroplasty

Background: The analgesic effect of perioperative low doses of intravenous lidocaine has been demonstrated after abdominal surgery. This study aimed to evaluate whether a continuous intravenous low-dose lidocaine infusion reduced postoperative pain and modified nociceptive pain threshold after total hip arthroplasty.

Methods: Sixty patients participated in this randomized double-blinded study. Patients received lidocaine 1% (lidocaine group) with a 1.5 mg/kg-1 intravenous bolus in 10 min followed by a 1.5 mg [middle dot] kg-1 [middle dot] h-1 intravenous infusion or saline (control group). These regimens were started 30 min before surgical incision and stopped 1h after skin closure. Lidocaine blood concentrations were measured at the end of administration. In both groups, postoperative analgesia was provided exclusively by patient-controlled intravenous morphine. Pain scores, morphine consumption, and operative hip flexion were recorded over 48 h. In addition, pressure pain thresholds and the extent of hyperalgesia around surgical incision were systematically measured at 24 and 48 h.

Results: In comparison with the placebo, lidocaine did not induce any opioid-sparing effect during the first 24 h (median [25-75% interquartile range]; 17 mg [9-28] vs. 15 mg [8-23]; P = 0.54). There was no significant difference regarding the effects of lidocaine and placebo on pain score, pressure pain thresholds, extent in the area of hyperalgesia, and maximal degree of active hip flexion tolerated. Mean plasma lidocaine concentration was 2.1 +/- 0.4 [mu]g/ml.     

Acute Rehabilitation Program after Laparoscopic Colectomy using Intravenous Lidocaine

Background: The concept of postoperative acute rehabilitation was introduced to accelerate postoperative recovery and improve outcome. We investigated whether intravenous lidocaine infusion, which decreases postoperative pain and speeds the return of bowel function, can be used instead of epidural analgesia in an acute rehabilitation protocol for patients undergoing laparoscopic colectomy.

Methods: Twenty eight consecutive patients scheduled for laparoscopic colectomy were prospectively included in this case series study. Segmental colectomy was performed only for benign pathology. Intraoperative opioid use was restricted. After a bolus injection of lidocaine 1.5 mgkg^-1, an infusion (2 mgkg-1h-1, IV) was started before pneu-moperitoneum. Balanced analgesia was used to reduce postoperative opioid consumption. Patients were allowed to drink 6 h postoperatively. The day after surgery, patients were allowed to eat a normal breakfast. Enforced mobilisation and ambulation were required from the patients. Our goal was to discharge patients within 3 days after surgery. Postoperative pain was measured. Time to first flatus, defecation, and hospital discharge were recorded. Results: Mean postoperative pain at rest and mobilisation remained below 30 mm on a 100 mm visual analogue scale. Time to first flatus, defecation, and hospital discharge were 29 ± 13 h, 38 ± 13 h, and 3.0 ± 1.0 days, respectively. Conclusion: Acute rehabilitation after laparoscopic colectomy using IV lidocaine gives similar outcomes to those reported using epidural analgesia.     

Effect of Intraoperative Fluid Management on Outcome after Intraabdominal Surgery

Background: The debate over the correct perioperative fluid management is unresolved.

Methods: The impact of two intraoperative fluid regimes on postoperative outcome was prospectively evaluated in 152 patients with an American Society of Anesthesiologists physical status of I-III who were undergoing elective intraabdominal surgery. Patients were randomly assigned to receive intraoperatively either liberal (liberal protocol group [LPG], n = 75; bolus of 10 ml/kg followed by 12 ml [middle dot] kg-1 [middle dot] h-1) or restrictive (restrictive protocol group [RPG], n = 77; 4 ml [middle dot] kg-1 [middle dot] h-1) amounts of lactated Ringer's solution. The primary endpoint was the number of patients who died or experienced complications. The secondary endpoints included time to initial passage of flatus and feces, duration of hospital stay, and changes in body weight, hematocrit, and albumin serum concentration in the first 3 postoperative days.

Results: The number of patients with complications was lower in the RPG (P = 0.046). Patients in the LPG passed flatus and feces significantly later (flatus, median [range]: 4 [3-7] days in the LPG vs. 3 [2-7] days in the RPG; P < 0.001; feces: 6 [4-9] days in the LPG vs. 4 [3-9] days in the RPG; P < 0.001), and their postoperative hospital stay was significantly longer (9 [7-24] days in the LPG vs. 8 [6-21] days in the RPG; P = 0.01). Significantly larger increases in body weight were observed in the LPG compared with the RPG (P < 0.01). In the first 3 postoperative days, hematocrit and albumin concentrations were significantly higher in the RPG compared with the LPG.     

Interaction of Intrathecally Infused Morphine and Lidocaine in Rats (Part II): Effects on the Development of Tolerance to Morphine

Background: There has been little information regarding the effects of local anesthetics on tolerance to opioids, although chronic use of combination of opioids and local anesthetics is popular for pain control. This study was designed to examine the effects of lidocaine on morphine tolerance to somatic and visceral antinociception.

Methods: Rats received a continuous intrathecal infusion of morphine (0.3-10 [micro sign]g [middle dot] kg-1 [middle dot] h-1), lidocaine (30-1000 [micro sign]g [middle dot] kg-1 [middle dot] h-1), a combination of those, or saline. After 6- day infusion, intrathecal morphine challenge test (5 [micro sign]g/10 [micro sign]l) was performed, and time-response curve was constructed to assess the magnitude of tolerance. The tail flick (TF) test and colorectal distension (CD) test were used to measure somatic and visceral antinociceptive effects, respectively.

Results: Antinociceptive effects in the TF and CD tests caused by morphine challenge were reduced (P < 0.01) in the morphine infused groups. The magnitude of the tolerance was inversely associated with the amount of morphine infused. Lidocaine infusion induced no different change in the morphine challenge test from that seen in the saline infusion group. Development of tolerance was greater in morphine 3 [micro sign]g [middle dot] kg-1 [middle dot] h-1 than in morphine 0.75 [micro sign]g [middle dot] kg-1 [middle dot] h-1 + lidocaine 150 [micro sign]g [middle dot] kg-1 [middle dot] h-1 despite their similar antinociceptive effects during intrathecal infusion. The infusion of a low dose of morphine (0.3 [micro sign]g [middle dot] kg-1 [middle dot] h-1) did not reduce the antinociceptive effects in the challenge test.     

Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy

Background: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg [middle dot] kg-1 [middle dot] h-1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).     

Postoperative Pain Facilitates Nonthermoregulatory Tremor

Background: Spontaneous tremor is relatively common in normothermic patients after operation and has been attributed to many causes. The hypothesis that nonthermoregulatory shivering-like tremor is facilitated by postoperative pain was tested. In addition, the effects of intravenous lidocaine on nonthermoregulatory tremor were evaluated.

Methods: Patients undergoing knee surgery were anesthetized with 2 [mu]g/kg intravenous fentanyl and 0.2 mg/kg etomidate. Anesthesia was maintained with 1.7 +/- 0.8% (mean +/- SD) isoflurane. Intraoperative forced-air heating maintained normothermia. The initial 44 patients were randomly allocated to receive an intra-articular injection of 20 ml saline (n = 23) or lidocaine, 1.5% (n = 21). The subsequent 30 patients were randomly allocated to receive an intravenous bolus of 250 [mu]g/kg lidocaine followed by an infusion of 13 [mu]g [middle dot] kg-1 [middle dot] h-1 lidocaine or an equivalent volume of saline when shivering was observed. Patient-controlled analgesia was provided for all patients: 3.5 mg piritramide, with a lockout interval of 5 min, for an unlimited total dose. Shivering was graded by a blinded investigator using a four-point scale. Pain was assessed by a 100-mm visual analog scale (0 = no pain and 100 = worst pain). The arteriovenous shunt status was evaluated with forearm-minus-fingertip skin-temperature gradients.

Results: Morphometric characteristics and hemodynamic responses were similar in the four groups. Core and mean skin temperature remained constant or increased slightly compared with preoperative values, and postoperative skin-temperature gradients were negative (indicating vasodilation) in nearly all patients. After intra-articular injection of saline, pain scores for the first postoperative hour averaged 46 +/- 32 mm (mean +/- SD), and 10 of the 23 (43%) patients shivered. In contrast, the pain scores of patients who received intra-articular lidocaine were significantly reduced to 5 +/- 9 mm and shivering was absent in this group (P < 0.05). In the second portion of the study, neither intravenous lidocaine nor saline reduced the magnitude or duration of nonthermoregulatory tremor or the patients' pain scores.     

静注利多卡因对行腹腔镜胆总管探查术患者镇痛和肠蠕动的影响

目的观察静脉输注利多卡因对行腹腔镜胆管探查术患者术后镇痛和肠功能的影响。方法择期腹腔镜胆总管探查术患者80例,年龄23～55岁,ASAⅠ或Ⅱ级,随机均分为治疗组和对照组。治疗组诱导期静注利多卡因1.5mg/kg,术中以2mg·kg-1·h-1持续输注,术后24h内改为1.2mg·kg-1·h-1持续静脉输注。对照组给予等剂量的生理盐水。记录两组患者术中七氟醚总量,术后抽取静脉血检测利多卡因浓度并记录术后2h(T1)、4h(T2)、8h(T3)、12h(T4)、24h(T5)、术后第2天(T6)和第3天(T7)两组VAS评分以及术后首次排气、排便时间,住院天数和恶心呕吐发生率。结果与对照组比较,T1～T5时治疗组VAS评分均明显下降(P<0.05);治疗组术中七氟醚总量降低,术后首次排气时间、排便时间以及住院天数均缩短(P<0.05)。结论小剂量利多卡因静注可促进腹腔镜胆管探查术患者肠蠕动恢复,缩短患者住院时间,有利于术后康复。     

Interaction of Intrathecally Infused Morphine and Lidocaine in Rats (Part I): Synergistic Antinociceptive Effects

Background: Synergistic antinociception of opioids and local anesthetics has been established in bolus injections but not in long-term use. The somatic and visceral antinociceptive effects of intrathecally infused morphine or lidocaine were characterized, and the nature of the interaction of those agents in rats was evaluated.

Methods: Intrathecal catheters were implanted in rats. Morphine (0.3 to 10 [micro sign]g [middle dot] kg-1 [middle dot] h-1), lidocaine (30-1,000 [micro sign]g [middle dot] kg-1 [middle dot] h-1), a combination of those, or saline was infused intrathecally at a constant rate of 1 [micro sign]l/h for 6 days. The tail flick and colorectal distension tests were used to measure the somatic and visceral antinociceptive effects, respectively. Nociceptive tests and motor function tests were repeated on days 1, 2, 3, 4, and 6. Isobolographic analysis was performed on the results of the tail flick test to determine the magnitude of the interaction.

Results: Intrathecally infused morphine produced dose-dependent antinociceptive effects in both the tail flick and the colorectal distension tests. Morphine showed a lower peak percentage maximum possible effect (%MPE) in the colorectal distension test than in the tail flick test. Intrathecal lidocaine also produced dose-dependent antinociceptive effects. Lidocaine infusion at 1,000 [micro sign]g [middle dot] kg-1 [middle dot] h-1 caused motor impairment. Coinfusion of morphine 0.3 [micro sign]g [middle dot] kg-1 [middle dot] h-1 and lidocaine 200 [micro sign]g [middle dot] kg-1 [middle dot] h-1, which had no effects by themselves, significantly increased the percentage maximum possible effects (P < 0.01). Coinfused lidocaine potentiated the duration and the magnitude of morphine antinociception. Isobolographic analysis of the tail flick test on day 1 showed a synergistic interaction between morphine and lidocaine.     

Epidural Clonidine Used as the Sole Analgesic Agent during and after Abdominal Surgery: A Dose-Response Study

Background: Many studies have shown the beneficial effect of epidural clonidine in postoperative pain management. In these studies, the patients received local anesthetics, opioids, or both in combination with clonidine. Due to the interactive potentiation of those drugs, the importance of the intrinsic analgesic properties of the alpha2 -adrenoceptor agonist is difficult to establish. The authors investigated the analgesic potency of epidural clonidine when used as the sole analgesic agent during and after major abdominal surgery.

Methods: Fifty young adult patients undergoing intestinal surgery under general anesthesia with propofol were studied. At induction, the patients received epidurally either an initial dose of 2 micro gram/kg clonidine followed by an infusion of 0.5 micro gram [center dot] kg-1 [center dot] h-1 (group 1, n = 10) or 4 micro gram/kg followed by 1 micro gram [center dot] kg-1 [center dot] h-1 (group 2, n = 20) or 8 micro gram [center dot] kg-1 [center dot] h-1 followed by an infusion of 2 micro gram [center dot] kg-1 [center dot] h-1 (group 3, n = 20). During the operation, increases in arterial blood pressure or heart rate that did not respond to a propofol bolus (0.5 mg/kg) were treated with a bolus of intravenous lidocaine (1 mg/kg). Three successive injections were allowed. When baseline values were not restored, opioids were added and the patient was removed from the study. After operation, the clonidine infusions were maintained for 12 h. During this period and at every 30 min, sedation scores and visual analog scale values at rest and at cough were noted. In case of subjective scores up to 5 cm at rest or up to 8 cm at cough, the patients were given access to a patient-controlled analgesia device that delivered epidural bupivacaine. The end point of the study was reached once the patient activated the analgesic delivery button.

Results: During surgery, 60% of patients in group 1 compared with 33% of patients in group 2 and only 5% of patients in group 3 were removed from the study protocol because of inadequate anesthesia (P < 0.05). After operation, epidural clonidine provided complete analgesia lasting 30 +/- 21 min in group 1 compared with 251 + 237 min in group 2 or 369 +/- 256 min in group 3 (P < 0.05 for group 1 vs. groups 2 and 3 and group 2 vs. group 3).     

Effects of Perioperative Analgesic Technique on the Surgical Outcome and Duration of Rehabilitation after Major Knee Surgery

Background: Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain. The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence.

Methods: Before standardized general anesthesia, 56 adult scheduled for major knee surgery were randomly assigned to one of three groups, each to receive a different postoperative analgesic technique for 72 h: continuous epidural infusion, continuous femoral block, or intravenous patient-controlled morphine (dose, 1 mg; lockout interval, 7 min; maximum dose, 30 mg/4 h). The first two techniques were performed using a solution of 1% lidocaine, 0.03 mg/ml morphine, and 2 [micro sign]g/ml clonidine administered at 0.1 ml [middle dot] kg-1 [middle dot] h-1. Pain was assessed at rest and during continuous passive motion using a visual analog scale. The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon. To evaluate functional outcome, the maximal amplitudes were measured again on postoperative day 5, at hospital discharge (day 7), and at 1- and 3-month follow-up examinations. When the patients left the surgical ward, they were admitted to a rehabilitation center, where their length of stay depended on prospectively determined discharge criteria.

Results: The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group. The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group. On postoperative day 7, these values were 90 [degree sign] (60-100 [degree sign]) (median and 25th-27th percentiles) in the continuous epidural infusion group, 90 [degree sign] (60-100 [degree sign]) in the continuous femoral block group, and 80 [degree sign] (60-100 [degree sign]) in the patient-controlled morphine group (P < 0.05). The durations of stay in the rehabilitation center were significantly shorter: 37 days (range, 30-45 days) in the continuous epidural infusion group, 40 days (range, 31-60 days) in the continuous femoral block group, and 50 days (range, 30-80 days) in the patient-controlled morphine group (P < 0.05). Side effects were encountered more frequently in the continuous epidural infusion group.     

Narcotrend Monitoring Allows Faster Emergence and a Reduction of Drug Consumption in Propofol-Remifentanil Anesthesia

Background: The Narcotrend is a new electroencephalographic monitor designed to measure depth of anesthesia, based on a six-letter classification from A (awake) to F (increasing burst suppression) including 14 substages. This study was designed to investigate the impact of Narcotrend monitoring on recovery times and propofol consumption in comparison to Bispectral Index(R) (BIS(R)) monitoring or standard anesthetic practice.

Methods: With institutional review board approval and written informed consent, 120 adult patients scheduled to undergo minor orthopedic surgery were randomized to receive a propofol-remifentanil anesthetic controlled by Narcotrend, by BIS(R), or solely by clinical parameters. Anesthesia was induced with 0.4 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil and a propofol target-controlled infusion at 3.5 [mu]g/ml. After intubation, remifentanil was reduced to 0.2 [mu]g [middle dot] kg-1 [middle dot] min-1, whereas the propofol infusion was adjusted according to clinical parameters or to the following target values: during maintenance to D0 (Narcotrend) or 50 (BIS(R)); 15 min before the end of surgery to C1 (Narcotrend) or 60 (BIS(R)). Recovery times were recorded by a blinded investigator, and average normalized propofol consumption was calculated from induction and maintenance doses.

Results: The groups were comparable for demographic data, duration of anesthesia, and mean remifentanil dosages. Compared with standard practice, patients with Narcotrend or BIS(R) monitoring needed significantly less propofol (standard practice, 6.8 +/- 1.2 mg [middle dot] kg-1 [middle dot] h-1vs. Narcotrend, 4.5 +/- 1.1 mg [middle dot] kg-1 [middle dot] h-1 or BIS(R), 4.8 +/- 1.0 mg [middle dot] kg-1 [middle dot] h-1;P < 0.001), opened their eyes earlier (9.3 +/- 5.2 vs. 3.4 +/- 2.2 or 3.5 +/- 2.9 min), and were extubated sooner (9.7 +/- 5.3 vs. 3.7 +/- 2.2 or 4.1 +/- 2.9 min).     

Magnesium Sulfate Does Not Reduce Postoperative Analgesic Requirements

Background: Because magnesium blocks the N-methyl-d-aspartate receptor and its associated ion channels, it can prevent central sensitization caused by peripheral nociceptive stimulation. However, transport of magnesium from blood to cerebrospinal fluid (CSF) across the blood-brain barrier is limited in normal humans. The current study was designed to evaluate whether perioperative intravenous magnesium sulfate infusion affects postoperative pain.

Methods: Sixty patients undergoing abdominal hysterectomy received 50 mg/kg intravenous magnesium sulfate as a bolus dose followed by a continuous infusion of 15 mg [middle dot] kg-1 [middle dot] h-1 for 6 h (magnesium group) or the same volume of isotonic saline (control group). At the end of surgery, serum and CSF magnesium concentration were measured in both groups. The cumulative postoperative analgesic consumption was measured to assess the analgesic effect using a patient-controlled epidural analgesia device. Pain intensities at rest and during forced expiration were evaluated at 6, 24, 48, and 72 h postoperatively.

Results: At the end of surgery, patients in the magnesium group had significantly greater postoperative serum magnesium concentrations compared with both preoperative and control group values (P < 0.001). Despite significantly higher serum magnesium concentrations in the magnesium group, there was no significant difference in magnesium concentration measured in postoperative CSF. Cumulative postoperative analgesic doses were similar in both groups. However, there was observed an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration in both groups. Visual analog pain scores at rest and during forced expiration were similar and less than 4 in both groups.     

Tranexamic Acid Administration after Cardiac Surgery: A Prospective, Randomized, Double-blind, Placebo-controlled Study

Background: Many different doses and administration schemes have been proposed for the use of the antifibrinolytic drug tranexamic acid during cardiac surgery. This study evaluated the effects of the treatment using tranexamic acid during the intraoperative period only and compared the results with the effects of the treatment continued into the postoperative period.

Methods: Patients undergoing elective cardiac surgery with use of cardiopulmonary bypass (N = 510) were treated intraoperatively with tranexamic acid and then were randomized in a double-blind fashion to one of three postoperative treatment groups: group A: 169 patients, infusion of saline for 12 h; group B: 171 patients, infusion of tranexamic acid, 1 mg [middle dot] kg-1 [middle dot] h-1 for 12 h; group C: 170 patients, infusion of tranexamic acid, 2 mg [middle dot] kg-1 [middle dot] h-1 for 12 h. Bleeding was considered to be a primary outcome variable. Hematologic data, allogeneic transfusions, thrombotic complications, intubation time, and intensive care unit and hospital stay duration also were evaluated.

Results: No differences were found among groups regarding postoperative bleeding and outcomes; however, the group treated with 1 mg[middle dot]kg-1[middle dot]h-1 tranexamic acid required more units of packed red blood cells because of a significantly lower basal value of hematocrit, as shown by multivariate analysis.     

Acute Opioid Tolerance: Intraoperative Remifentanil Increases Postoperative Pain and Morphine Requirement

Background: Rapid development of acute opioid tolerance is well established in animals and is more likely to occur with large doses of short-acting drugs. The authors therefore tested the hypothesis that intraoperative remifentanil administration results in acute opioid tolerance that is manifested by increased postoperative pain and opioid requirement.

Methods: Fifty adult patients undergoing major abdominal surgery were randomly assigned to two anesthetic regimens: (1) desflurane was kept constant at 0.5 minimum alveolar concentrations and a remifentanil infusion was titrated to autonomic responses (remifentanil group); or (2) remifentanil at 0.1 [mu]g [middle dot] kg-1 [middle dot] min-1 and desflurane titrated to autonomic responses (desflurane group). All patients were given a bolus of 0.15 mg/kg morphine 40 min before the end of surgery. Morphine was initially titrated to need by postanesthesia care nurses blinded to group assignment. Subsequently, patients-who were also blinded to group assignment-controlled their own morphine administration. Pain scores and morphine consumption were recorded for 24 postoperative h.

Results: The mean remifentanil infusion rate was 0.3 +/- 0.2 [mu]g [middle dot] kg-1 [middle dot] min-1 in the remifentanil group, which was significantly greater than in the desflurane group. Intraoperative hemodynamic responses were similar in each group. Postoperative pain scores were significantly greater in the remifentanil group. These patients required morphine significantly earlier than those in the desflurane group and needed nearly twice as much morphine in the first 24 postoperative h: 59 mg (25-75% interquartile range, 43-71) versus 32 mg (25-75% interquartile range, 19-59;P < 0.01).     

Does dexamethasone improve the quality of intravenous regional anesthesia and analgesia? A randomized, controlled clinical study

We investigated the anesthetic and analgesic effectiveness of adding dexamethasone to lidocaine for IV regional anesthesia (IVRA). Seventy-five patients undergoing ambulatory hand surgery were randomly assigned to one of three groups: group L received 3 mg/kg lidocaine, group LD received 3 mg/kg lidocaine + 8 mg dexamethasone, and group LDc received 3 mg/kg lidocaine for IVRA and 8 mg dexamethasone IV to the nonsurgical arm. IVRA was established using 40 mL of a solution. Visual analog scale and verbal pain scores were recorded intraoperatively and for 2 h postoperatively. Postoperative pain was treated with oral acetaminophen 500 mg every 4 h when visual analog scale score was more than 3. Time to request for the first analgesic and the total dose in the first 24 h were noted. Times to onset of complete sensory and motor block were similar in the 3 groups. The times to recovery of motor block (L = 8 [5.91-10.08] min, LD = 13 [6.76-20.19] min, LDc = 6 [4.44-8.43] min) and sensory block (L = 7 [5.21-10.30] min, LD = 12 [6.11-19.40] min and LDc = 6 [4.2-8.11] min) were longer in group LD (P < 0.05). Patients in group LD reported significantly lower pain scores and required less acetaminophen in the first 24 h after surgery. In conclusion, the addition of 8 mg dexamethasone to lidocaine for IVRA in patients undergoing hand surgery improves postoperative analgesia during the first postoperative day.     

Acute Pain Induces Insulin Resistance in Humans

Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin.

Methods: Ten healthy male volunteers underwent two randomly sequenced hyperinsulinemic-euglycemic (insulin infusion rate, 0.6 mU [middle dot] kg-1 [middle dot] min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0-10, just before the clamp procedure (study P). In the other study, no pain was inflicted (study C).

Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 +/- 1.87 mg [middle dot] kg-1 [middle dot] min-1 (mean +/- SD) in study C to 4.97 +/- 1.38 mg [middle dot] kg-1 [middle dot] min-1 in study P (P < 0.01) because of a decrease in nonoxidative glucose disposal, as determined by indirect calorimetry (2.47 +/- 0.88 mg [middle dot] kg-1 [middle dot] min-1 in study P vs. 3.41 +/- 1.03 mg [middle dot] kg-1 [middle dot] min-1 in study C;P < 0.05). Differences in glucose oxidation rates were not statistically significant. The suppression of isotopically determined endogenous glucose output during hyperinsulinemia tended to be decreased after pain (1.67 +/- 0.48 mg [middle dot] kg-1 [middle dot] min-1 in study P vs. 2.04 +/- 0.45 mg [middle dot] kg-1 [middle dot] min-1 in study C;P = 0.06). Pain elicited a twofold to threefold increase in serum cortisol (P < 0.01), plasma epinephrine (P < 0.05), and serum free fatty acids (P < 0.05). Similarly, circulating concentrations of glucagon and growth hormone tended to increase during pain.     

The Anabolic Effect of Epidural Blockade Requires Energy and Substrate Supply

Background: The authors examined the hypothesis that continuous thoracic epidural blockade with local anesthetic and opioid, in contrast to patient-controlled intravenous analgesia with morphine, stimulates postoperative whole body protein synthesis during combined provision of energy (4 mg [middle dot] kg-1 [middle dot] min-1 glucose) and amino acids (0.02 ml [middle dot] kg-1 [middle dot] min-1 Travasol(TM) 10%, equivalent to approximately 2.9 g [middle dot] kg-1 [middle dot] day-1).

Methods: Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding) on the second day after colorectal surgery performed with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, glucose production, and clearance were measured by l-[1-13C]leucine and [6,6-2H2]glucose.

Results: Epidural blockade did not affect protein and glucose metabolism in the fasted state. Parenteral alimentation decreased endogenous protein breakdown and glucose production to the same extent in both groups. Administration of glucose and amino acids was associated with an increase in whole body protein synthesis that was modified by the type of analgesia, i.e., protein synthesis increased by 13% in the epidural group (from 93.3 +/- 16.6 to 104.5 +/- 11.1 [mu]mol [middle dot] kg-1 [middle dot] h-1) and by 4% in the patient-controlled analgesia group (from 90.0 +/- 27.1 to 92.9 +/- 14.8 [mu]mol [middle dot] kg-1 [middle dot] h-1;P = 0.054).     

Epidural Clonidine or Bupivacaine as the Sole Analgesic Agent during and after Abdominal Surgery: A Comparative Study

Background: The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine.

Methods: Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 mg/kg clonidine in 7 ml saline followed by an infusion of 6 mg [middle dot] kg-1 [middle dot] h-1 (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device.

Results: During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively.     

Epinephrine Increases the Extracellular Lidocaine Concentration in the Brain: A Possible Mechanism for Increased Central Nervous System Toxicity

Background: Local anesthetics exert central nervous system (CNS) toxicity by inhibiting intracerebral neuronal activity, while epinephrine augments the CNS toxicity of intravenously administered local anesthetics. Viewed together, increases of extracellular concentrations of local anesthetics in the brain may be directly associated with increased CNS toxicity. The authors examined the hypothesis that epinephrine enhances the CNS toxicity of lidocaine by increasing the extracellular concentration in the brain.

Methods: An awake, spontaneously breathing rat model was used. Twenty male Sprague-Dawley rats received an intravenous infusion of lidocaine (3 mg [middle dot] kg-1 [middle dot] min-1; group C) or lidocaine with epinephrine (3 mg [middle dot] kg-1 [middle dot] min-1 and 2 [mu]g [middle dot] kg-1 [middle dot] min-1, respectively; group E) for 10 min (n = 10 in each group). Effects of epinephrine on the convulsive dose and concentrations of total (protein-bound and unbound) and unbound lidocaine in plasma were examined. Concentrations of extracellular lidocaine in the cerebral nucleus accumbens were quantitatively determined by a microdialysis method.

Results: The convulsive dose of lidocaine was significantly lower in group E than in group C (22.4 +/- 5.5 vs. 27.9 +/- 3.1 mg/kg, respectively; P < 0.05). Overall concentrations and area under the plasma concentration-versus-time curve of unbound lidocaine in group E were significantly higher than those in group C. Concentrations of extracellular lidocaine in the nucleus accumbens in group E were comparable to those of unbound fraction in plasma and were also significantly higher than those in group C.