Ching Tang Wu

Pre-incisional epidural ketamine, morphine and bupivacaine combined with epidural and general anaesthesia provides pre-emptive analgesia for upper abdominal surgery.

Background: Previous studies have shown that N‐methyl‐D‐asparate (NMDA) receptor antagonists provide a pre‐emptive analgesic effect in humans. This study investigated the benefits of pre‐emptive analgesia for upper abdominal surgery, using pre‐incisional epidural ketamine + morphine + bupivacaine (K+M+B) treatment for achieving postoperative pain relief.

The effect of epidural clonidine on perioperative cytokine response, postoperative pain, and Bowel function in patients undergoing colorectal surgery

The postoperative period is associated with an increased production of cytokines, which augment pain sensitivity. We investigated the hypothesis that epidural clonidine premedication and postoperative patient-controlled epidural analgesia (PCEA) including clonidine would decrease the release of proinflammatory (interleukin (IL)-6, IL-1β, IL-8, and tumor necrosis factor (TNF)-&agr;) and antiinflammatory (IL-1 receptor antagonist (RA)) cytokines in patients who underwent elective colorectal surgery and that they would provide better postoperative analgesia. Forty patients were randomly assigned to 1 of 2 groups of 20 each: the control group received normal saline 10 mL, whereas the clonidine group received epidural clonidine 150 μg diluted with 9 mL of normal saline 30 min before surgery. Venous blood samples for cytokine levels were obtained before induction, at the end of surgery, and after surgery at 12 and 24 h. After surgery, the clonidine group patients received PCEA with morphine (0.1 mg/mL) and clonidine (1.5 μg/mL) in 0.2% ropivacaine 100 mL, whereas control group patients received only PCEA morphine and ropivacaine. Patients in the clonidine group exhibited longer PCEA trigger times, lower pain scores at rest and while coughing, less morphine consumption, and a faster return of bowel function throughout the 72-h postoperative observation period, compared with patients in the control group. For patients in the clonidine group, production of IL-1RA, IL-6, and IL-8 was significantly less increased at the end of the surgical procedure and at 12 and 24 h after surgery. However, the concentrations of IL-1β and TNF-&agr; were not significantly increased.

Prolonged Injection Time and Light Smoking Decrease the Incidence of Fentanyl-induced Cough

We designed this study to evaluate the effect of injection time and smoking on fentanyl-induced cough. Four-hundred-fifty ASA class I–II patients, aged 18–80 yr and weighing 40–90 kg, scheduled for elective surgery were included. All patients received fentanyl (100 &mgr;g for patients weighing 40–69 kg and 150 &mgr;g for patients weighing 70–90 kg for clinical convenience) via the proximal port of a peripheral IV line on the forearm. Patients were randomly assigned to 3 groups of 150 patients each. Patients in Group I received fentanyl injection over 2 s, whereas for patients in Groups II and III the fentanyl was injected at a constant rate over 15 s and 30 s, respectively. We recorded the number of coughs of each patient during and 30 s after fentanyl injection. The incidence of cough was 18% in group I, 8% in Group II, and 1.3% in Group III, significantly less (P < 0.05) with a longer injection time. Current smokers had a less frequent incidence of cough than nonsmokers; however, this effect was only significant in light smokers (<10 cigarettes per day or <10 smoking years or <10 pack-years). In conclusion, a longer injection time reduces the incidence of fentanyl-induced cough, and light smoking may be a protective factor against fentanyl-induced cough.

Preincisional dextromethorphan treatment decreases postoperative pain and opioid requirement after laparoscopic cholecystectomy.

UNLABELLED In the present study, we examined whether preincisional treatment with dextromethorphan (DM) provides preemptive analgesia. Ninety patients scheduled for laparoscopic cholecystectomy were included. Patients receiving chlorpheniramine maleate (CPM) 20 mg via an IM injection 30 min before skin incision were designated as the control group. Patients in Group A received DM 40 mg (containing CPM 20 mg) IM after removal of the gallbladder, whereas in Group B, DM 40 mg (containing CPM 20 mg) was administered IM 30 min before skin incision. Meperidine (1 mg/kg IM) was given for postoperative pain relief as required. Times to first meperidine injection, total meperidine consumption, worst pain score, bed rest time, and side effects were recorded for 48 h after surgery. Times to first meperidine injection were 9.3+/-15.9, 17.4+/-3.4, and 28.6+/-3.9 h for the control group and Groups A and B, respectively. The total meperidine consumption was 90.7+/-11.9, 77.5+/-12.7, and 20.0+/-4.4 mg for the control group and Groups A and B, respectively. The worst visual analog pain scores were 6.0+/-0.2, 6.0+/-0.2, and 4.0+/-0.4 for the control group and Groups A and B, respectively. The bed rest times were 21.0+/-0.5, 20.0+/-0.5, and 19.0+/-0.4 h for the control group and Groups A and B, respectively. The number of patients who required meperidine injection was 26, 22, and 12 for the control group and Groups A and B, respectively. We conclude that DM is more effective in producing postoperative analgesia when it is administered preincision rather than after the gallbladder removal treatment, which suggests a preemptive analgesic effect. IMPLICATIONS Preincisional dextromethorphan (40 mg IM) treatment offers a preemptive analgesic effect, thus improving the postoperative pain management.

Pre‐medication with intravenous clonidine suppresses fentanyl‐induced cough

Background:  A reflex cough is often observed after an intravenous bolus of fentanyl. This study was conducted to determine whether pre‐treatment with intravenous clonidine could effectively attenuate fentanyl‐induced cough.

Attenuation of morphine tolerance by intrathecal gabapentin is associated with suppression of morphine-evoked excitatory amino acid release in the rat spinal cord

This study was designed to investigate the effect of acute and chronic intrathecal (i.t.) injection of gabapentin (GBP) on the antinociceptive effect of morphine and tolerance development using a tail-flick latency test. Levels of excitatory amino acids (EAA) in i.t. CSF dialysates were also measured by high performance liquid chromatography. Male Wistar rats were implanted with either one or two i.t. catheters for drug injection or pump infusion and with a microdialysis probe for CSF dialysate collection. The effect of acute GBP (10 microg i.t.) injection on the morphine dose response was examined in both naïve rats and rats made tolerant by continuous infusion of morphine (15 microg/h i.t.) for 5 days. At such a low dose (10 microg i.t.), GBP did not enhance morphines antinociception in naïve rats. In morphine-tolerant rats, however, acute GBP (10 microg i.t.) injection potentiated morphines antinociception and yielded a 14.6-fold shift in morphines dose-response curve. When GBP (10 microg/h i.t.) was co-infused with morphine (15 microg/h i.t.) to examine its effect on the development of morphine tolerance, GBP attenuated the development of morphine tolerance. The effect of GBP and morphine on CSF glutamate and aspartate levels was examined in naïve rats, and the effect of morphine challenge on CSF glutamate and aspartate levels was examined in rats previously infused for 5 days with morphine alone or morphine plus GBP. Acute injection of GBP (10 microg i.t.), morphine (50 microg i.t.), or GBP (10 microg i.t.) followed by morphine (50 microg i.t.) 30 min later had no significant effect on CSF EAA concentration in naïve rats; however, in tolerant rats, morphine challenge (50 microg i.t.) increased aspartate and glutamate levels to 221 +/- 22% and 296 +/- 43%, respectively, of those before morphine challenge, and this phenomenon was inhibited by GBP co-infusion. Our results show that GBP, at a dose without enhanced effect on morphines antinociception in naïve rats, not only potentiates morphines antinociceptive effect in morphine-tolerant rats but also attenuates the development of morphine tolerance. The mechanism of the effect of GBP on morphine tolerance might be via suppression of the EAA concentration in spinal CSF dialysate.

Preincisional dextromethorphan combined with thoracic epidural anesthesia and analgesia improves postoperative pain and bowel function in patients undergoing colonic surgery.

Colonic surgery is associated with severe postoperative pain and postoperative ileus, which contribute to delayed hospital discharge. In previous studies, we demonstrated that IM dextromethorphan (DM) provided preemptive analgesia and improved postoperative pain. The benefit of thoracic epidural anesthesia (TEA) and postoperative epidural analgesia on postoperative pain was well demonstrated. The goal of this study was to investigate the effect of preincisional IM DM combined with intraoperative TEA and postoperative patient-controlled epidural analgesia (PCEA) on pain and bowel function after colonic surgery. Patients were randomized into 3 equal groups to receive: 1) chlorpheniramine maleate (CPM) 20 mg and general anesthesia (CPM-GA); 2) CPM 20 mg and GA combined with TEA (CPM-TEA); or 3) DM 40 mg (containing 20 mg of CPM) and GA combined with TEA (DM-TEA). The CPM, DM, and TEA with lidocaine were administered after GA induction via an IM injection and 30 min before the skin incision. All patients received postoperative PCEA for pain control. Analgesic effects were evaluated for 72 h after surgery using visual analog scale pain scores at rest and moving, time to first PCEA request for pain relief, total PCEA consumption, and the time to first passage of flatus. Statistically significant improvement of postoperative pain and bowel function was observed in the following order: DM-TEA > CPM-TEA > CPM-GA. Compared with the CPM-TEA group, the DM-TEA group averaged 1.6 points lower on first-hour pain scores, 40 min longer to first PCEA request, 15.8 mL less PCEA drug over 72 h, and 14.7 h earlier bowel function (all P < 0.01). We conclude that the combination of preincisional DM (40 mg IM), intraoperative TEA, and postoperative PCEA enhances analgesia and facilitates recovery of bowel function, suggesting possible synergistic interaction with local anesthetics and opioids.

Neutrophil-Mediated Secretion and Activation of Matrix Metalloproteinase-9 During Cardiac Surgery with Cardiopulmonary Bypass

Cardiopulmonary bypass (CPB) induces neutrophil activation, degranulation, and a systemic inflammatory response. Matrix metalloproteinase (MMP)-9 exists in neutrophils and is released on neutrophil activation. Increased levels of MMP-9 have been observed in patients undergoing CPB. We designed the present study to determine whether MMP-9 is derived from neutrophils during CPB. Twenty-one patients undergoing elective coronary artery bypass grafting with or without CPB were included in this study. Blood was collected and analyzed for MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1. Neutrophils were also isolated and examined for MMP-9 production and mRNA expression. Plasma levels and activity of MMP-9 increased significantly 2–6 h after beginning CPB, whereas the MMP-9 levels in patients with off-pump cardiac surgery did not increase. The neutrophil content of MMP-9 and mRNA increased significantly 2 h after beginning CPB. The plasma levels of TIMP-1 increased gradually for 6 h, whereas the MMP-9/TIMP-1 ratios were increased 2–4 h after beginning CPB. The present study demonstrated that CPB causes an increase in the concentration and activity of plasma MMP-9. The corresponding increase in neutrophil MMP-9 expression and production suggests that MMP-9 is derived primarily from neutrophils and may contribute to the inflammatory response associated with CPB.

Preincisional dextromethorphan treatment for postoperative pain management after upper abdominal surgery.

Abstract. Previous studies showed that ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, provides a preemptive analgesic effect and preemptive analgesia improves postoperative pain management. The aim of this study was to examine whether premedication with dextromethorphan (DM) improves postoperative pain management after upper abdominal surgery. Sixty (American Society of Anesthesiologists class 1 and 2 of either gender) patients scheduled for upper abdominal surgery were included in the study. Patients were randomly assigned to one of four groups: control, DM-10, DM-20, and DM-40. In the control group, chlorpheniramine maleate (CPM, 20 mg) was injected immediately before induction of anesthesia intramuscularly (IM). In the DM-10, DM-20, and DM-40 groups, patients were premedicated with DM 10 mg, 20 mg, and 40 mg IM, respectively. After operation, patient-controlled analgesia (PCA) with morphine was given for pain relief. The time to the first PCA trigger, morphine consumption, pain scores, and analgesic-related side effects were recorded at 1, 2, 4, 24, 48, and 72 hours after surgery. The time to first PCA trigger for the control group was 17.8 ± 1.4 minutes, for group DM-10 20.2 ± 1.6 minutes, for group DM-20 32.4 ± 1.9 minutes, and for DM-40 77.9 ± 6.5 minutes. The morphine delivered and PCA triggering frequency were 5.5 ± 0.5/11.3 ± 0.8 times for the controls, 5.5 ± 0.4/14.1 ± 1.3 times for DM-10, 3.1 ± 0.3/6.3 ± 1.2 times for DM-20, and 0.2 ± 0.1/0.3 ± 0.2 times for DM-40 during the first hour after operation. For the first day, the figures are 19.9 ± 1.2/23.9 ± 1.4 for the controls, 15.6 ± 1.2/17.3 ± 2.4 for DM-10, 12.6 ± 0.7/15.9 ± 1.6 for DM-20, and 5.0 ± 0.21/5.6 ± 0.9 for DM-40. On the first day, the cough pain scores were 6.67 ± 0.23, 6.53 ± 0.16, 6.67 ± 0.23, and 5.73 ± 0.18 for the controls, DM-10, DM-20, and DM-40 groups, respectively. All data showed dose-dependent better pain relief in DM-premedicated patients. We conclude that DM premedication offers preemptive analgesia and reduces postoperative pain and morphine requirement.

Epidural clonidine for postoperative pain after total knee arthroplasty: a dose-response study.

BACKGROUND: Combinations of epidural clonidine, local anesthetics, and opioids have improved postoperative analgesia after total knee arthroplasty. In this study we sought to determine the optimal epidural bolus dose of clonidine, which provides the best analgesia and fewest side effects. METHODS: Eighty ASA I–III patients, who underwent total knee arthroplasty were randomly assigned to one of four groups of 20 patients each. Identical epidural anesthesia procedures were used for all groups. After surgery, groups C0, C1, C2, and C4 received patient-controlled epidural analgesia (PCEA) with clonidine (0, 1.0, 2.0, or 4.0 &mgr;g/mL, respectively) and morphine (0.1 mg/mL) in 0.2% ropivacaine. The analgesia effect was estimated by PCEA consumption volume and visual analog pain scale at rest and with movement at 1, 2, 4, 12, 24, 48, and 72 h after surgery. Systolic blood pressure, heart rate, sedation, and sensory and motor blockade were also recorded for 72 h after surgery. RESULTS: The PCEA consumption volume for groups C0, C1, C2, and C4 were 71.8 ± 19.5 mL, 49.6 ± 12.3 mL, 48.1 ± 9.3 mL, and 39.4 ± 9.0 mL, respectively. The clonidine groups experienced less postoperative pain (P = 0.002). In the C4 group, four patients had prolonged sensory blockade and one patient had both severe sedation and prolonged sensory motor blockade. No significant statistical difference in analgesic consumption (P = 0.78) and pain intensity (P = 0.66) between groups C1 and C2 were noted. CONCLUSIONS: The optimal amount of epidural clonidine in a solution of morphine and ropivacaine for postoperative pain management is 1.0 &mgr;g/mL.