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 . kg(-1) . 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). CONCLUSIONS: Very-low-dose ketamine (0.05 mg . kg(-1) . h(-1)) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain.     

Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery

We designed this double-blinded, randomized, controlled study to evaluate the effect of small-dose ketamine IV in combination with epidural morphine and bupivacaine on postoperative pain after renal surgery. An epidural catheter was inserted, and the administration of morphine and bupivacaine was started before surgery. Forty patients were assigned to one of two groups (ketamine or control). The ketamine group was administered a ketamine bolus and infusion during surgery. The median visual analog pain scale (VAS) scores at rest were significantly lower in the ketamine group during the first 6 h (P < 0.01). VAS pain scores on coughing were also significantly lower in the ketamine group (P < 0.01). Cumulative postoperative total analgesic consumption was less in the ketamine group on Days 1 and 2 (P < 0.001). The first analgesic demand time was shorter in the control group (9.2 +/- 11.5 min) than in the ketamine group (22.3 +/- 17.1 min) (P < 0.0001). The incidence of nausea and pruritus was more frequent in the control group (P < 0.05). In conclusion, postoperative analgesia was more effective when spinal cord and brain sensitization were blocked by a combination of epidural morphine/bupivacaine and IV ketamine. IMPLICATIONS: Renal nociception conducted multisegmentally by both the spinal nerves (T10 to L1) and the vagus nerve cannot be blocked by epidural analgesia alone. We demonstrated that IV ketamine had an improved analgesic or opioid-sparing effect when it was combined with epidural bupivacaine and morphine after renal surgery.     

Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia

N-methyl-D-aspartate (NMDA) receptor antagonists enhance opioid-induced analgesia. The plasma concentration of ketamine, an NMDA receptor antagonist that enhances epidural morphine-and-bupivacaine-induced analgesia, is not known. We examined 24 patients with lung carcinoma or metastatic lung tumor who underwent video-assisted thoracic surgery in a placebo-controlled, double-blind manner 4 h after emergence from anesthesia. The morphine + ketamine group (n = 8) and morphine + placebo group (n = 8) received 5 mL volume of 2.5 mg morphine and 0.25% bupivacaine and the placebo + ketamine group (n = 8) received 5 mL volume of saline and 0.25% bupivacaine epidurally at the end of skin closure. Four hours after this anesthesia, in the morphine + ketamine and placebo + ketamine groups, ketamine was administered to successively maintain a stable plasma ketamine concentration of 0, 10, 20, 30, 40, and 50 ng/mL by a target-controlled infusion device, and patients assessed the levels of pain at rest, pain on coughing, somnolence (drowsiness), and nausea using a 100-mm visual analog scale (VAS). In the morphine + placebo group, a placebo (saline) was similarly administered instead of ketamine. In the morphine + ketamine group, the VAS scores for pain at rest and pain on coughing significantly decreased on ketamine administration at a plasma concentration of 20 ng/mL or larger compared with the respective baseline VAS scores (P < 0.05 each). In the placebo + ketamine group, the VAS scores for pain at rest and pain on coughing did not significantly change at any plasma concentration of ketamine as compared to the morphine + placebo group. In the morphine + ketamine group, a plasma concentration of ketamine larger than 20 ng/mL did not further reduce VAS scores for pain at rest and pain on coughing. The VAS scores for drowsiness were comparable among the three groups at any plasma concentration of ketamine. Ketamine at a plasma concentration of 20 ng/mL or larger may enhance epidural morphine-and-bupivacaine-induced analgesia. As an adjunct with epidural morphine-and-bupivacaine and considering the safety of small doses, the minimal plasma concentration of ketamine given IV may be approximately 20 ng/mL.     

A Comparison of Remifentanil and Morphine Sulfate for Acute Postoperative Analgesia after Total Intravenous Anesthesia with Remifentanil and Propofol

Background: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized micro-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol.

Methods: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 micro gram [center dot] kg sup -1 [center dot] min sup -1 remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 micro gram [center dot] kg sup -1 [center dot] min sup -1 and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed.

Results: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] >or= to 8 breaths/min and pulse oximetry >or= to 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 micro gram [center dot] kg sup -1 [center dot] min sup -1 (range, 0.05-0.23 micro gram [center dot] kg sup -1 [center dot] min sup -1), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, >or= to 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05).     

Patient-controlled epidural analgesia with morphine or morphine plus ketamine for post-operative pain relief

Sixty patients were randomly assigned to two equal groups. Group I received epidural morphine 1 mg after surgery and used a patient-controlled analgesia device programmed to deliver morphine 0. 2 mg h-1, 0.2 mg per bolus. Group II received an epidural loading dose of morphine 1 mg plus ketamine 5 mg and used a patient-controlled analgesia device programmed to deliver morphine 0. 2 mg+ketamine 0.5 mg h-1, morphine 0.2 mg+ketamine 0.5 mg per bolus with a lockout time of 10 min. The mean morphine consumption was 8. 6+/-0.7 mg for group I and 6.2+/-0.2 mg for group II. Although group II utilized significantly less morphine (P < 0.05), pain relief was significantly better in group II than in group I (P < 0.05) in the first 3 h. Vomiting occurred more frequently in group I (26%) than in group II (13%). The frequency and severity of pruritus and level of sedation were similar in the two groups. These findings suggest that patient-controlled epidural analgesia with morphine plus ketamine may provide effective analgesia with a lesser dose of morphine and fewer subsequent side effects, compared with patient-controlled epidural analgesia with morphine alone after lower abdominal surgery.     

Postoperative pain relief after hepatic resection in cirrhotic patients: the efficacy of a single small dose of ketamine plus morphine epidurally

In cirrhotic patients undergoing hepatic surgery, postoperative analgesia remains a challenge. In this study, we evaluated the efficacy of a single dose of morphine combined with small-dose ketamine given epidurally for postoperative pain relief. One-hundred-four classification "Child A" cirrhotic patients were randomly assigned to two groups: 1) (MKG, n = 54): epidural morphine (3.5-5 mg) plus ketamine (20/30 mg); and 2) epidural morphine (3.5/5 mg) (MG, n = 50). The level of analgesia, side effects, psychomimetic and neurological disorders, additional analgesic needs, and overall quality of the analgesia were recorded. The mean duration of analgesia was longer in the MKG group (27.2 +/- 8 h versus 16.4 +/- 10 h; P < 0.05). In the MKG group, the visual analog scale (VAS) score began to be significantly lower from 14 h at rest and 12 h on coughing until the end of the study. The need for additional analgesia was also smaller in the MKG group (P < 0.05): at 24 h, only 10% of patients in the MKG group needed complementary analgesia, whereas in the MG group it was 100% (P = 0.003). Side effects were similar in both groups. Psychomimetic side effects and neurological disorders were not detected. These results suggest that postoperative analgesia provided by a single dose of epidural morphine with small-dose ketamine is effective in cirrhotic Child's A patients having major upper abdominal surgery.     

Thoracic epidural anesthesia for cardiac surgery: the effects on tracheal intubation time and length of hospital stay.

Improvements in analgesia after major surgery may allow a more rapid recovery and shorter hospital stay. We performed a prospective randomized trial to study the effects of epidural analgesia on the length of hospital stay after coronary artery surgery. The anesthetic technique and postoperative mobilization were altered to facilitate early intensive care discharge and hospital discharge. Fifty patients received high (T1 to T4) thoracic epidural anesthesia (TEA) with ropivacaine 1% (4-mL bolus, 3-5 mL/h infusion), with fentanyl (100-microg bolus, 15-25 microg/h infusion) and a propofol infusion (6 mg x kg(-1) x h(-1)). Another 50 patients (the General Anesthesia group) received fentanyl 15 microg/kg and propofol (5 mg x kg(-1) x h(-1)), followed by IV morphine patient-controlled analgesia. The TEA group had lower visual analog scores with coughing postextubation (median, 0 vs 26 mm; P < 0.0001) and were extubated earlier (median hours [interquartile range], 3.2 [2.1-4.6] vs 6.7 [3.3-13.2]; P < 0.0001). More than half of all patients were discharged home on Postoperative Day 4 (24%) or 5 (33%), but there was no difference in the length of stay between the TEA group (median [interquartile range], Day 5 [5-6]) and the General Anesthesia group (median [interquartile range], Day 5 [4-7]). There were no differences in postoperative spirometry or chest radiograph changes or in markers for postoperative myocardial ischemia or infarction. No significant TEA-related complications occurred. In summary, TEA provided better analgesia and allowed earlier tracheal extubation but did not reduce the length of hospital stay after coronary artery surgery. IMPLICATIONS: We found that epidural analgesia was more effective than IV morphine for cardiac surgery. Epidural anesthesia also allowed earlier weaning from mechanical ventilation, but it did not affect hospital discharge time.     

The effect of intravenous ketoprofen on postoperative epidural sufentanil analgesia in children.

We compared the effect of IV ketoprofen and placebo as an adjuvant to epidural sufentanil analgesia after major surgery. We used a prospective, randomized, double-blinded, placebo-controlled, parallel-group study design in 54 children aged 1-15 yr who received a standardized anesthetic. Either IV ketoprofen or saline was administered in addition to an epidural sufentanil infusion, which was adjusted as required clinically. The study drug infusions were discontinued when pain scores were <3 on 0-10 scale for 6 h at a sufentanil infusion rate of 0.03 microg x kg(-1) x h(-1). Children in the ketoprofen group had a better analgesic effect, as shown by decreased need for sufentanil (mean [10th-90th percentiles] 8.3 [3.1-15.1] microg/kg vs 12.5 [6.2-18.9] microg/kg; P = 0.002) and earlier possibility to discontinuation of the epidural sufentanil (11 [46%] vs 3 [13%]; P = 0.014) before the end of the 72-h study period. In the ketoprofen group, median (range) pain scores were lower during activity at 24 h (2 [0-5] vs 5 [0-7]; P = 0.01) and at 72 h (0 [0-3] vs 2 [0-6]; P = 0.033), and fewer children had inadequate pain relief during activity at 24 h (0 vs 5; P = 0.037). Children who received ketoprofen required fewer infusion rate adjustments (12 [4-20] vs 17 [6-42]; P = 0.016). In the ketoprofen group, the incidence of desaturation (1 [4%] vs 6 [26%]; P = 0.035) and fever (3 [12%] vs 11 [48%]; P = 0.008) was less than that in the placebo group. We conclude that ketoprofen improved postoperative pain in children. IMPLICATIONS: We compared the effect of the IV nonsteroidal antiinflammatory drug ketoprofen versus placebo as adjuvants to epidural opioid analgesia with sufentanil. The continuous IV nonsteroidal antiinflammatory drug improved pain after major surgery in children receiving an epidural opioid. Although ketoprofen reduced epidural sufentanil requirements, the incidence of opioid-related adverse effects was not changed.     

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).     

A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain

We compared the analgesic effect of lumbar intrathecal (IT) 0.5 mg morphine (Group M, n = 10), 50 microg sufentanil (Group S, n = 10), and their combination (Group S-M, n = 10) given before general anesthesia and patient-controlled analgesia with IV morphine (Group C, n = 19) in a randomized, double-blinded study performed in patients undergoing thoracotomy. Pain visual analog scale (VAS) and morphine consumption were assessed for 24 h. In Group S-M the number of patients initially titrated with IV morphine was less than in group C (30 vs 84%, P < 0.05). Morphine requirement was higher in Group C (71 +/- 30 mg) than in Groups S (46 +/- 34 mg, P < 0.05), M (38 +/- 31 mg, P < 0.05) and S-M (23 +/- 16 mg, P < 0.01). VAS scores were significantly decreased during the first 0-11 postoperative h at rest and during the first 0-8 postoperative h on coughing in Groups M and S-M rather than in Group C. The incidence of side effects was infrequent except for urinary retention. Preoperative IT morphine or combined sufentanil and morphine could be given as a booster to achieve rapidly effective analgesia in the immediate postoperative period. Implications: As compared with IV patient-controlled analgesia, intrathecal morphine or combined sufentanil and morphine provided superior postoperative pain relief both at rest (11 h) and on coughing (8 h) than did IV patient-controlled analgesia morphine alone. IV morphine requirement was decreased during the first postoperative day after posterolateral thoracotomy.     

A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after thoracotomy

This study compared epidural and intravenous fentanyl infusions for pain relief for the first 20 h after thoracotomy, in order to examine whether an thoracic epidural fentanyl infusion offers clinical advantage over an intravenous infusion. Forty patients were assigned randomly to receive either fentanyl epidurally and saline intravenously or fentanyl intravenously and saline epidurally in a double-blind fashion. For each patient the fentanyl infusion was titrated to a rate required for pain relief (pain score less than 3, maximum 10). Patients reported similar median pain scores, but in the epidural group the required mean fentanyl infusion rate was less (0.95 +/- 0.23 vs. 1.67 +/- 0.46 micrograms.kg-1.h-1, P = 0.0001) and plasma fentanyl concentrations were less at 4 and 18 h (4 h: 0.81 +/- 0.27 vs. 1.38 +/- 0.36 ng.ml-1, P = 0.0001; 18 h: 0.94 +/- 0.32 vs. 1.54 +/- 0.65 ng.ml-1, P = 0.0007) than those in the intravenous group. Respiratory function was better preserved and the incidence of nausea and sedation was less in the epidural group than in the intravenous group. In conclusion there appears to be a clinical advantage to the epidural infusion over the intravenous infusion of fentanyl for analgesia after thoracotomy.     

Ropivacaine epidural anesthesia and analgesia versus general anesthesia and intravenous patient-controlled analgesia with morphine in the perioperative management of hip replacement. Ropivacaine Hip Replacement Multicenter Study Group.

The aim of our study was to compare epidural anesthesia and analgesia (EDA) with ropivacaine versus general anesthesia followed by IV patient-controlled analgesia with morphine (GA/PCA) after hip replacement regarding pain, side effects, and discharge from the postanesthesia care unit. After ethics committee approval, randomization, and informed consent, 90 patients were enrolled. In Group EDA, epidural anesthesia (ropivacaine 10 mg/mL, 15-25 mL) was followed by an epidural infusion (2 mg/mL, 4-6 mL/h for 24 h, plus top-up doses of 6-10 mL for 48 h). GA/PCA patients received general anesthesia (isoflurane/N2O/fentanyl) followed by IV patient-controlled analgesia with morphine postoperatively. Pain was assessed by using visual analog scales (0-100 mm) at rest and during physiotherapy. Pain at rest was less in the EDA (n = 43) group than in the GA/PCA (n = 45) group (at 10 h: 11.8+/-12.9 vs. 28.4+/-17.1 [P< 0.001]; at 24 h: 14.3+/-11.7 vs. 24.0+/-17 [P<0.01]; in 48 h: 14.3+/-9.3 vs. 21.1+/-17.4 [P = 0.1]). Whereas EDA patients were deemed ready for discharge from the postanesthesia care unit earlier than GA/PCA patients (5.6+/-8.9 vs. 39.7+/-41.5 min), the actual discharge time was comparable. The median time for first passage of flatus was shorter in the EDA group than in the GA/PCA group (26 vs. 47 h). Nausea and vomiting were more common in the GA/PCA group than in the EDA group (16% vs. 28% and 11% vs. 22%, respectively), whereas hypotension (11% vs. 4%) and bradycardia (14% vs. 2%) were less frequent. Under the conditions of the present study, EDA with ropivacaine provided pain control after hip replacement superior to that provided by IV patient-controlled analgesia with morphine, particularly during the first 24 h. Both approaches to pain management were equally safe. IMPLICATIONS: Compared with general anesthesia and postoperative IV patient-controlled analgesia with morphine, epidural anesthesia and analgesia with the new local anesthetic ropivacaine enables patients to be discharged sooner from a postanesthesia care unit and provides superior pain relief during the first 24 h after hip replacement.     

The use of intrathecal morphine for postoperative pain relief after liver resection: a comparison with epidural analgesia

An epidural catheter is used in some institutions for postoperative analgesia after liver surgery. However, anesthesiologists may not feel comfortable leaving a catheter in the epidural space because of concern about coagulation disturbances and possible bleeding complications caused by impaired liver function. In this study, we tested a single-shot intrathecal morphine technique and compared it to a continuous epidural naropine infusion for postoperative analgesia in liver surgery. Fifty patients were randomly assigned to an epidural analgesia group (EP group; n = 25) and an intrathecal analgesia group (IN group; n = 25). The quality of analgesia assessed by a visual analog scale (VAS), the side effects, and the additional IV analgesic requirements were recorded. We did not observe any signs of cord compression. Time to first pain drug requirement was longer in the EP group compared to the IN group (25 +/- 18.5 h versus 12 +/- 10.3 h; P < 0.05). In both groups, the VAS remained less than 30 mm throughout the 48-h follow-up period. Consumption of IV morphine with a patient-controlled analgesia device in the IN group was larger (mostly from 24 to 48 h after surgery) than the EP group (12.0 +/- 5.54 mg versus 3.1 +/- 2.6 mg, respectively; P < 0.01). The incidence of vomiting was 4% in both groups, whereas the incidence of pruritus (16% versus 0%) and nausea (16% versus 4%) was more frequent in the IN group. No postdural puncture headache and no spinal hematoma occurred. After liver resection, a single dose of intrathecal morphine followed by patient-controlled morphine analgesia can provide satisfactory postoperative pain relief. The quality of this treatment, according to the VAS, is not inferior to continuous epidural analgesia up to 48 h after surgery.     

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).     

曲马多复合小剂量氯胺酮用于腹部手术患者的手术后镇痛：一项双盲、安慰剂对照的随机研究

背景鉴于氯胺酮联合曲马多用于患者手术后镇痛的研究较少，本文旨在验证曲马多复合氯胺酮能否改善腹部大手术的术后镇痛效果。方法在此项双盲、随机、对照研究中，行择期开腹手术的成年患者（n=120）随机分入氯胺酮组（氯胺酮手术中用量为0．3mg／kg，手术后以0．1mg·kg^-1·h^-1速度输注）或对照组（相同剂量和速度的生理盐水）。所有患者在手术中均使用曲马多3mg／kg，手术后48小时持续输注曲马多0．2mg·kg^-1·h^-1另以患者自控吗啡镇痛用于补救性镇痛。结果在整个48小时研究期间，氯胺酮组在静息（P=0．01）和活动（P=0．02）时的疼痛评分较低，吗啡的需求量较少（P=0．003）。在0～24小时期间，氯胺酮改善了患者主观的镇痛效果（P=0．008），镇静作用较小（P=0．03），需要医师干预的严重疼痛较少（P=0．01）。氯胺酮组中产生幻觉的患者较多，但两组的其他副作用均相似。结论腹部大手术后，小剂量氯胺酮是辅助吗啡和曲马多镇痛的有效药物。     

Epidural Ropivacaine versus Epidural Morphine and the Catabolic Response to Colonic Surgery: Stable Isotope Kinetic Studies in the Fasted State and during Infusion of Glucose

Background: The authors examined the hypothesis that epidural administration of local anesthetic, in contrast to epidural analgesia with morphine, inhibits postoperative protein oxidation during administration of glucose.

Methods: Fourteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding with 4 mg [middle dot] kg-1 [middle dot] min-1 glucose) on the second day after colorectal surgery using epidural analgesia with either continuous ropivacaine or intermittent morphine. Protein synthesis, breakdown and oxidation, and glucose production were measured by l-[1-13C]leucine and [6,6-2H2]glucose. Substrate oxidation rates were determined by indirect calorimetry. Plasma concentrations of metabolic substrates and hormones were also measured.

Results: Whole body protein breakdown, oxidation, synthesis, and glucose production in the fasted state were similar between the two groups. Glucose administration decreased protein breakdown (P = 0.01), protein synthesis (P = 0.001), and glucose production (P = 0.001) to the same extent in both groups, whereas protein oxidation was not significantly affected. The type of epidural analgesia did not significantly influence the circulating concentrations of metabolic substrates and hormones in the fasted or in the fed state. Carbohydrate oxidation rate in the ropivacaine group was greater than in patients receiving morphine (P = 0.04), regardless of whether glucose was infused.     

Postoperative protein sparing with epidural analgesia and hypocaloric dextrose

OBJECTIVE: We examined the hypothesis that epidural analgesia prevents the increase in amino acid oxidation after elective colorectal surgery in patients receiving hypocaloric infusion of dextrose. SUMMARY BACKGROUND DATA: Increased oxidative protein loss after surgery may adversely affect postoperative outcome. We have previously shown that effective segmental pain relief by epidural analgesia improves postoperative substrate utilization, resulting in less protein catabolism. METHODS: We randomly allocated 10 patients to receive general anesthesia combined with epidural analgesia using bupivacaine/fentanyl and 10 to receive general anesthesia followed by patient-controlled analgesia with intravenous morphine. All patients received a peripheral 72-hour infusion of dextrose 10% from the day before until the second day after surgery. The dextrose infusion rate was adjusted to provide 50% of the patients' resting energy expenditure. The primary end point was whole-body leucine oxidation as determined by a stable isotope tracer technique (l-[1-C]leucine). RESULTS: In the intravenous analgesia group, leucine oxidation increased from 19 +/- 4 to 28 +/- 6 micromol kg h after surgery. Epidural analgesia prevented this increase of leucine oxidation (preoperative 21 +/- 6 micromol kg h, postoperative 21 +/- 5 micromol kg h). This difference was statistically significant (P = 0.01; analysis of variance for repeated measures). CONCLUSION: Perioperative epidural analgesia and hypocaloric dextrose infusion suppress the postoperative increase in amino acid oxidation, thereby saving more than 100 g of lean body mass per day.     

Postoperative Wound Oxygen Tension with Epidural or Intravenous Analgesia: A Prospective, Randomized, Single-blind Clinical Trial

Background: Adequate tissue oxygen tension is an essential requirement for surgical-wound healing. The authors tested the hypothesis that epidural anesthesia and analgesia increases wound tissue oxygen tension compared with intravenous morphine analgesia.

Methods: In a prospective, randomized, blind clinical study, the authors allocated patients having major abdominal surgery (n = 32) to receive combined general and epidural anesthesia with postoperative patient-controlled epidural analgesia (epidural group, n = 16), or general anesthesia alone with postoperative patient-controlled intravenous analgesia (intravenous group, n = 16). An oxygen sensor and a temperature sensor were placed subcutaneously in the wound before closure. Wound oxygen tension (Pwo2) and temperature were measured continuously for 24 h. Other variables affecting wound tissue oxygenation and visual analogue scale (VAS) pain scores were also documented.

Results: Despite epidural patients having lower body temperatures at the end of surgery (35.7 +/- 0.3) versus 36.3 +/- 0.5 [degrees]C, P = 0.004), they had significantly higher mean Pwo2 over the 24 h period, compared with the intravenous group (64.4 +/- 14 vs. 50.7 +/- 15) mmHg, mean (SD), 95% CI difference, -22 to -5, P = 0.002). Area under the Pwo2 -24 h time curve was also significantly higher in the epidural group (930 +/- 278 vs. 749 +/- 257) mmHg x h, 95% CI difference -344 to -18, P = 0.03). VAS pain scores at rest and moving were significantly lower in the epidural group at all times.     

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.     

A comparison of patient-controlled epidural analgesia following gynaecological surgery with and without a background infusion

We conducted a randomised, controlled study to investigate the effect of adding a background infusion to patient-controlled epidural analgesia for postoperative pain relief. Forty-two patients scheduled for elective lower abdominal gynaecological surgery received patient-controlled epidural analgesia postoperatively using a mixture of 0.2% ropivacaine and 2.0 microg x ml-1 fentanyl. Patients in group B (n = 20) were given a background infusion of 5 ml x h-1, whereas those in group N (n = 21) were not. There was no difference in pain scores or patient satisfaction scores between the two groups. Patients in group B had a higher total drug consumption (156.8 +/- 34.8 ml vs. 89.5 +/- 41.0 ml; p < 0.0001) and incidence of side-effects (71.4% vs. 30.0%; p = 0.007). Motor blockade during the 24-h study period was also greater in group B (median [range] area under the curve 7.5 [0.0-39.0] h vs. 3.0 [0.0-36.0] h; p = 0.035). We conclude that the addition of a background infusion to patient-controlled epidural anaesthesia is not recommended as it confers no additional benefits.