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).     

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.     

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.     

Role of magnesium sulfate in postoperative pain management for patients undergoing thoracotomy

OBJECTIVE: The purpose of this study was to investigate the effect of magnesium sulfate on pain management for post-thoracotomy patients. DESIGN: A prospective, randomized, controlled clinical study. SETTING: University hospital. PARTICIPANTS: Twenty-four patients undergoing thoracotomy. INTERVENTIONS: After thoracotomy operations, patients were assigned to 2 groups. The control group received intravenous morphine (0.5 mg/h infusion, 0.3 mg patient-controlled anesthesia dose, 15-minute lockout time) via patient-controlled analgesia, and the magnesium group received magnesium sulfate (30-mg/kg bolus, 10 mg/kg/h infusion for 48 hours) plus the same patient-controlled analgesia protocol. MEASUREMENTS AND MAIN RESULTS: Visual analog scale for pain score, sedation score, mean arterial pressure, heart rate, and valid and invalid analgesic demand were recorded. Serum magnesium levels were determined at postanesthesia care unit admission, at 24 hours, and at 48 hours. Side effects were also recorded. There were no significant differences between groups with respect to demographics, sedation score, and pain score. Cumulative mean morphine consumption was found to be higher in the control group compared with the magnesium group at 4, 8, and 48 hours (5.6 +/- 1 mg v 3.2 +/- 0.6 mg [p < 0.0001], 10.2 +/- 1.8 mg v 7.2 +/- 1.6 mg [p = 0.0003), and 40.2 +/- 4.5 mg v 34.8 +/- 6.3 mg [p = 0.02], respectively). CONCLUSION: Postoperative use of magnesium sulfate reduced opioid consumption for pain after thoracotomy operations.     

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.     

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。     

Quality of postoperative pain using an intraoperatively placed epidural catheter after major lumbar spinal surgery

BACKGROUND: Major spinal surgery is associated with high postoperative pain scores and opioid requirement. The aim of the current prospective, randomized, placebo-controlled, double-blind study was to assess the reduction of opioid requirement and pain scores using an intraoperatively placed epidural catheter with infusion of 0.1% ropivacaine during the postoperative period. METHODS: Thirty patients undergoing major lumbar spinal surgery from a dorsal approach were included in this study. Before wound closure, the orthopedic surgeon inserted an epidural catheter. Postoperatively, patients were randomly assigned to receive an infusion of 12 ml/h ropivacaine, 0.1% (group R), or 12 ml/h saline (group N) after an initial bolus of 10 ml of the respective study solution. Additional pain relief was provided using an intravenous patient-controlled analgesia pump with the opioid piritramide. Patients were assessed with respect to pain scores (visual analog scale of 0-100), cumulative opioid requirement, side effects, and satisfaction with pain management. RESULTS:: Demographic data, duration of surgery, and type of surgery were comparable between groups. Pain scores were assessed as follows (group R vs. group N: 6 h: 24 +/-20 vs. 51 +/- 20, P = 0.002; 24 h: 33 +/- 19 vs. 53 +/- 27, P = 0.04; 48 h: 21 +/-17 vs. 40 +/- 26, P = 0.04; 72 h: 14 +/- 13 vs. 38 +/- 25, P = 0.02). The cumulative piritramide requirement after 72 h was 97 +/- 23 mg in group R and 157 +/-72 mg in group N (P = 0.03). The incidence of side effects was comparable between groups, and patient satisfaction was always higher in group R (P < 0.05). CONCLUSION: Continuous epidural infusion of 0.1% ropivacaine results in lower pain scores and opioid consumption and higher patient satisfaction when compared with placebo. Application of ropivacaine using an epidural catheter seems to be a highly effective treatment for postoperative pain after major lumbar spinal surgery.     

Dexmedetomidine infusion is associated with enhanced renal function after thoracic surgery

STUDY OBJECTIVE: To test the hypothesis that dexmedetomidine, a selective alpha-2 agonist, enhances urine flow rate and perioperative renal function, a post hoc analysis was conducted on a recently completed study of dexmedetomidine used as an adjunct to epidural analgesia after thoracotomy. DESIGN: Post hoc analysis of a randomized, placebo-controlled, double-blind clinical trial. SETTING: Tertiary-care university medical center. PATIENTS: 28 patients undergoing elective thoracotomy. INTERVENTIONS: Patients were prospectively randomized to receive a supplemental 24-hour intravenous infusion of either dexmedetomidine (0.4 microg kg(-1) h(-1), n = 14) or saline placebo (equivalent infusion rate, n = 14). MEASUREMENTS: Available renal parameters including urine output, calculated creatinine clearance (cCl(Cr)), daily serum creatinine level (S(Cr)), and the fractional change in S(Cr) level (DeltaS(Cr)%, [peak postoperative S(Cr) - baseline S(Cr)] / baseline S(Cr)) x 100) were recorded. MAIN RESULTS: Values are expressed as means +/- SD. There were no significant differences in baseline values between the groups. The dexmedetomidine group had significantly greater cumulative urine output at postoperative hour 4 (473 +/- 35 vs 290 +/- 122 mL, P = 0.001) and 12 (1033 +/- 240 vs 822 +/- 234 mL, P = 0.02), although only 14% of the group received diuretic agents, compared with 43% in the control group. The dexmedetomidine group had significantly better preserved perioperative renal function compared with the control group, as assessed by DeltaS(Cr)% (0.04% decrease vs 21% increase, P = 0.0007) and cCl(Cr) (75.3 +/- 13.2 vs 62.5 +/- 15.5 mL/min, P = 0.02). CONCLUSION: Dexmedetomidine infusion administered as a supplement to epidural analgesia induced diuresis in postthoracotomy patients with normal preoperative renal function and undergoing fluid restriction. Although this finding may represent simple reversal of a tubular antidiuresis, the lower DeltaS(Cr)% and preservation of cCl(Cr) suggest a beneficial effect on glomerular filtration compared with controls.     

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.     

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.     

Comparison of analgesic efficacy of subcostal transversus abdominis plane blocks with epidural analgesia following upper abdominal surgery

Subcostal transversus abdominis plane (TAP) catheters have been reported to be an effective method of providing analgesia after upper abdominal surgery. We compared their analgesic efficacy with that of epidural analgesia after major upper abdominal surgery in a randomised controlled trial. Adult patients undergoing elective open hepatobiliary or renal surgery were randomly allocated to receive subcostal TAP catheters (n=29) or epidural analgesia (n=33), in addition to a standard postoperative analgesic regimen comprising of regular paracetamol and tramadol as required. The TAP group patients received bilateral subcostal TAP catheters and 1 mg.kg(-1) bupivacaine 0.375% bilaterally every 8 h. The epidural group patients received an infusion of bupivacaine 0.125% with fentanyl 2 μg.ml(-1) . The primary outcome measure was visual analogue pain scores during coughing at 8, 24, 48 and 72 h after surgery. We found no significant differences in median (IQR [range]) visual analogue scores during coughing at 8 h between the TAP group (4.0 (2.3-6.0 [0-7.5])) and epidural group (4.0 (2.5-5.3) [0-8.5])) and at 72 h (2.0 (0.8-4.0 [0-5]) and 2.5 (1.0-5.0 [0-6]), respectively). Tramadol consumption was significantly greater in the TAP group (p=0.002). Subcostal TAP catheter boluses may be an effective alternative to epidural infusions for providing postoperative analgesia after upper abdominal surgery.     

Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery: a randomized, double-blind, placebo-controlled study

BACKGROUND: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial. METHODS: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia. RESULTS: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed. CONCLUSIONS: Continuous preperitoneal administration of 0.2% ropivacaine at 10 ml/h during 48 h after open colorectal resection reduced morphine consumption, improved pain relief, and accelerated postoperative recovery.     

Quality of Postoperative Pain Using an Intraoperatively Placed Epidural Catheter after Major Lumbar Spinal Surgery

Background: Major spinal surgery is associated with high postoperative pain scores and opioid requirement. The aim of the current prospective, randomized, placebo-controlled, double-blind study was to assess the reduction of opioid requirement and pain scores using an intraoperatively placed epidural catheter with infusion of 0.1% ropivacaine during the postoperative period.

Methods: Thirty patients undergoing major lumbar spinal surgery from a dorsal approach were included in this study. Before wound closure, the orthopedic surgeon inserted an epidural catheter. Postoperatively, patients were randomly assigned to receive an infusion of 12 ml/h ropivacaine, 0.1% (group R), or 12 ml/h saline (group N) after an initial bolus of 10 ml of the respective study solution. Additional pain relief was provided using an intravenous patient-controlled analgesia pump with the opioid piritramide. Patients were assessed with respect to pain scores (visual analog scale of 0-100), cumulative opioid requirement, side effects, and satisfaction with pain management.

Results: Demographic data, duration of surgery, and type of surgery were comparable between groups. Pain scores were assessed as follows (group R vs. group N: 6 h: 24 +/- 20 vs. 51 +/- 20, P = 0.002; 24 h: 33 +/- 19 vs. 53 +/- 27, P = 0.04; 48 h: 21 +/- 17 vs. 40 +/- 26, P = 0.04; 72 h: 14 +/- 13 vs. 38 +/- 25, P = 0.02). The cumulative piritramide requirement after 72 h was 97 +/- 23 mg in group R and 157 +/- 72 mg in group N (P = 0.03). The incidence of side effects was comparable between groups, and patient satisfaction was always higher in group R (P < 0.05).     

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.     

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 randomized, double-blind comparison of lumbar epidural and intravenous fentanyl infusions for postthoracotomy pain relief. Analgesic, pharmacokinetic, and respiratory effects.

Although epidural opioids frequently are used to provide postoperative analgesia, several articles have suggested that the analgesia after epidural fentanyl is similar to that after an equal dose of fentanyl given intravenously. To address this issue further, 29 postthoracotomy patients were studied in a randomized, double-blinded trial comparing a lumbar epidural fentanyl infusion with an intravenous fentanyl infusion for analgesia, plasma fentanyl pharmacokinetics, and respiratory effects for 20 h postoperatively. In all patients in both groups, good analgesia was achieved (pain score less than 3, maximum 10) over a similar time course, although the patients receiving epidural infusion required a significantly larger fentanyl infusion dose than did the patients receiving intravenous infusion (group receiving epidural fentanyl infusion: 1.95 +/- 0.45 micrograms.kg-1.h-1; group receiving intravenous fentanyl infusion: 1.56 +/- 0.36 micrograms.kg-1.h-1; P = 0.0002). The time course for the plasma fentanyl concentrations was similar in the two groups, and plasma fentanyl concentrations were not significantly different at any sampling period (T7-T20; group receiving epidural fentanyl infusion: 1.8 +/- 0.5 ng/ml; group receiving intravenous fentanyl infusion: 1.6 +/- 0.6 ng/ml; P = 0.06). Similarly, calculated clearance values for the two groups were not significantly different (group receiving epidural fentanyl infusion: 0.95 +/- 0.26 l.kg-1.h-1; group receiving intravenous fentanyl infusion: 0.87 +/- 0.25 l.kg-1.h-1; P = 0.3). Both groups demonstrated a similar degree of mild to moderate respiratory depression postoperatively, which was assessed with continuous respiratory inductance plethysmography and sequential arterial blood gas analysis. Side effects (nausea, vomiting, pruritus) were mild and did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous Preperitoneal Infusion of Ropivacaine Provides Effective Analgesia and Accelerates Recovery after Colorectal Surgery: A Randomized, Double-blind, Placebo-controlled Study

Background: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial.

Methods: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia.

Results: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed.     

Preoperative ketamine improves postoperative analgesia after gynecologic laparoscopic surgery

In this study, we evaluated the preemptive effect of a small dose of ketamine on postoperative wound pain. In a randomized, double-blinded, controlled trial, we compared the analgesic requirement in patients receiving preincision ketamine with ketamine after skin closure or placebo after gynecologic laparoscopic surgery. One-hundred-thirty-five patients were randomly assigned to receive preincision or postoperative ketamine 0.15 mg/kg or saline IV. Anesthetic technique was standardized. Patients were interviewed regularly up to 4 wk after surgery. Pain score, morphine consumption, side effects, and quality of recovery score were recorded. Patients receiving preincision ketamine had a lower pain score in the first 6 h after operation compared with the postoperative (P = 0.001) or placebo groups (P < 0.001). The mean (95% confidence intervals) time to first request for analgesia in the preincision group, 1.8 h (1.4-2.1), was longer than the postoperative group, 1.2 h (0.9-1.5; P < 0.001), or the placebo group, 0.7 h (0.4-0.9; P < 0.001). The mean +/- SD morphine consumption in the preincision group, 1.5 +/- 2.0 mg, was less than that in the postoperative group, 2.9 +/- 3.1 mg (P = 0.04) and the placebo group, 3.4 +/- 2.7 mg (P = 0.003). There was no significant difference among groups with respect to hemodynamic variables or side effects. No patient complained of hallucinations or nightmares. We conclude that a small dose of ketamine is not only safe, but it also provides preemptive analgesia in patients undergoing gynecologic laparoscopic surgery. IMPLICATIONS: In women undergoing laparoscopic gynecologic surgery, a small preoperative dose of ketamine (0.15 mg/kg) produced preemptive analgesia. There were no significant hemodynamic and psychological side effects with this dose.     

Ketamine does not decrease postoperative pain after remifentanil-based anaesthesia for tonsillectomy in adults

BACKGROUND: There are conflicting results concerning the pre-emptive effect of ketamine on central sensitization following surgery. The aim of this prospective, randomized, double-blind, placebo-controlled study was to assess the effect of the N-methyl-D-aspartate receptor antagonist ketamine on postoperative morphine consumption and pain score after remifentanil-based anaesthesia in adult patients scheduled for tonsillectomy. METHODS: We studied 40 adult patients undergoing elective tonsillectomy. Total intravenous anaesthesia was induced and maintained with remifentanil (0.125-1.0 microg kg(-1) min(-1)) and propofol target-controlled infusion. Patients in group K received a bolus dose of ketamine 0.5 mg kg(-1) immediately after anaesthetic induction, followed by a continuous infusion of 2 microg kg(-1) min(-1). Saline was administered in the same sequence in group S. Propofol, remifentanil, and the study drug infusions were discontinued at the end of surgery. RESULTS: Intraoperative remifentanil consumption (0.57 +/- 0.18 in group K vs. 0.55 +/- 0.14 microg kg(-1) min(-1) in group S), morphine requirement in the PACU (11 +/- 3 in group K vs. 9 +/- 4 mg in group S) and in the ward (22 +/- 11 in group K vs. 25 +/- 14 mg in group S), median time to first analgesia in the ward (338 +/- 126 in group K vs. 328 +/- 144 min in group S), and VAS pain scores were comparable in both groups. CONCLUSION: Small-dose of ketamine does not seem to be a useful adjunct to remifentanil-based anaesthesia during short, painful surgical procedures.     

A randomized,double-blinded comparison of thoracic epidural ropivacaine,ropivacaine/fentanyl,or bupivacaine/fentanyl for postthoracotomy analgesia

Epidural ropivacaine has not been compared with bupivacaine for postthoracotomy analgesia. Eighty patients undergoing elective lung surgery were randomized in a double-blinded manner to receive one of three solutions for high thoracic epidural analgesia. A continuous epidural infusion of 0.1 mL. kg(-1). h(-1) of either 0.2% ropivacaine, 0.15% ropivacaine/fentanyl 5 micro g/mL, or 0.1% bupivacaine/fentanyl 5 micro g/mL was started at admission to the intensive care unit. We assessed pain scores (rest and spirometry), IV morphine consumption, spirometry, hand grip strength, PaCO(2), heart rate, blood pressure, respiratory rate, and side effects (sedation, nausea, vomiting, and pruritus) for 48 h. Thoracic epidural ropivacaine/fentanyl provided adequate pain relief similar to bupivacaine/fentanyl during the first 2 postoperative days after posterolateral thoracotomy. The use of plain 0.2% ropivacaine was associated with worse pain control during spirometry, larger consumption of IV morphine, and increased incidence of postoperative nausea and vomiting. Morphine requirements were larger in the ropivacaine group, with no differences between bupivacaine/fentanyl and ropivacaine/fentanyl groups. Patients in the ropivacaine group experienced more pain and performed worse in spirometry than patients who received epidural fentanyl. There was no significant difference in motor block. We conclude that epidural ropivacaine/fentanyl offers no clinical advantage compared with bupivacaine/fentanyl for postthoracotomy analgesia. IMPLICATIONS: Thoracic epidural ropivacaine/fentanyl provided adequate pain relief and similar analgesia to bupivacaine/fentanyl during the first 2 postoperative days after posterolateral thoracotomy. Plain 0.2% ropivacaine was associated with worse pain control and an increased incidence of postoperative nausea and vomiting. We conclude that epidural ropivacaine/fentanyl offers no clinical advantage compared with bupivacaine/fentanyl for postthoracotomy analgesia.