Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization

BACKGROUND: The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control. METHODS: Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia. RESULTS: One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg). CONCLUSIONS: Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use, lower cumulative morphine consumption, and reduced hyperalgesia compared with a sham epidural condition. These results highlight the importance of including a standard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia (preincisional vs. postsurgery) fail to find the anticipated effects.     

Postoperative Morphine Use and Hyperalgesia Are Reduced by Preoperative but Not Intraoperative Epidural Analgesia: Implications for Preemptive Analgesia and the Prevention of Central Sensitization

Background: The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control.

Methods: Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia.

Results: One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg).     

Epidural naloxone reduces intestinal hypomotility but not analgesia of epidural morphine

PURPOSE: Epidural morphine is associated with decreased bowel motility and increased transit time. Low doses of intravenous naloxone reduce morphine-induced pruritus without reversing analgesia, but the effect of epidural naloxone on bowel motility has not been studied. Therefore we evaluated bowel motility and analgesia when naloxone was co-administered with morphine into the epidural space. METHODS: Forty-three patients having combined thoracic epidural and general anesthesia for subtotal gastrectomy were randomly assigned to one of two study groups. All received a bolus dose of 3 mg epidural morphine at the beginning of surgery, followed by a continuous epidural infusion containing 3 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (control group, n = 18) or a calculated dose of 0.208 microg x kg(-1) x hr(-1) of naloxone (experimental group, n = 25) for 48 hr. We measured the time to the first postoperative passage of flatus and feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain during rest and movement. Scores were assessed at 2, 4, 8, 16, 24, 36 and 48 hr postoperatively. RESULTS: The experimental group had a shorter time to the first postoperative passage of flatus (5 1.9 +/- 1 6.6 hr vs 87.0 +/- 19.5 hr, P < 0.001 ) and feces (95.3 +/- 25.0 hr vs 132.9 +/- 29.4 hr, P < 0.001). No differences were found in either resting or active VAS between the two groups. CONCLUSION: Epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing its analgesic effects.     

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.     

Lumbar Epidural Morphine in Humans and Supraspinal Analgesia to Experimental Heat Pain

Background: Epidural administration of morphine is a common analgesic technique to manage pain. Morphine spreads from the epidural space to the cerebrospinal fluid and then rostrally, causing side effects mediated by the brain stem. However, data on the rostral spread of morphine-mediated analgesia are sparse. This study examined the rostral spread of analgesic effects on heat and electrical pain after epidural administration of morphine.

Methods: In a randomized, double-blinded, placebo-controlled, crossover study, 5 mg morphine or saline placebo were injected into the lumbar epidural space in nine healthy volunteers. Correct needle placement was confirmed with fluoroscopy. Analgesia to experimental nociceptive heat and electrical stimuli was measured at lumbar (L4), thoracic (T10), cervical (C2), and trigeminal (V2) levels before and 2, 5, 10, and 24 h after epidural injection. Plasma samples for assaying morphine concentrations were drawn before and after each analgesic evaluation.

Results: Epidural morphine significantly attenuated experimental heat pain at all dermatomes tested compared with saline placebo. Analgesic effects were significant at L4 after 2, 5, and 10 h, at T10 after 5, 10, and 24 h, and at V2 after 10 h. Electrical pain was attenuated at the lumbar and thoracic but not at the cervical dermatome. Analgesic effects were significant at L4 after 2, 5, and 10 h and at T10 after 5 and 10 h. Morphine plasma concentrations were below the detection limit (1 ng/ml) in eight of the nine subjects 10 h after epidural injection.     

Combination of low-dose epidural morphine and intramuscular diclofenac sodium in postcesarean analgesia.

Epidural morphine is used for postcesarean analgesia, and nonsteroidal antiinflammatory drugs are frequently administered to relieve uterine cramps after vaginal delivery. To assess the efficacy of a combination of low-dose epidural morphine and intramuscular diclofenac sodium in postcesarean analgesia, a double-blind, randomized study was conducted. Epidural anesthesia was given to 120 parturients who were randomly allocated into four treatment groups: group A received normal saline solution, 10 mL epidurally and 3 mL intramuscularly (IM); group B received 10 mL of epidural saline solution and 75 mg (3 mL) of diclofenac IM; group C received 2 mg of morphine in 10 mL of epidural saline solution and 3 mL of saline solution IM; and group D received 2 mg of morphine in 10 mL of epidural saline solution and 75 mg of diclofenac IM. Epidural injections were given after delivery of the placenta, and IM injections were given on arrival in the recovery room. Verbal analogue pain scores were recorded at 2, 4, 8, 12, 18, and 24 h after epidural injection. Subjective scores of overall pain relief were also recorded at 24 h. Results showed that scores of overall pain relief were significantly better in group D compared with group A, B, or C (P less than 0.05). Groups A and B required more supplemental meperidine than groups C and D. None of the subjects in group D requested supplemental analgesia. Compared with the other three groups, group D experienced a better analgesic effect for both wound pain and uterine cramping pain from 4 to 18 h (P less than 0.05). Incidence of nausea or vomiting, or both, and pruritus occurred more frequently in groups C and D compared with group A or B (P less than 0.05). No bradypnea was observed during the study period. Diclofenac alone was not effective in postcesarean analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preemptive analgesia by intravenous low-dose ketamine and epidural morphine in gastrectomy: a randomized double-blind study

BACKGROUND: Morphine and ketamine may prevent central sensitization during surgery and result in preemptive analgesia. The reliability of preemptive analgesia, however, is controversial. METHODS: Gastrectomy patients were given preemptive analgesia consisting of epidural morphine, intravenous low-dose ketamine, and combinations of these in a randomized, double-blind manner. Postsurgical pain intensity was rated by a visual analog scale, a categoric pain evaluation, and cumulative morphine consumption. RESULTS: Preemptive analgesia by epidural morphine and by intravenous low-dose ketamine were significantly effective but not definitive. With epidural morphine, a significant reduction in visual analog scale scores at rest was observed at 24 and 48 h, and morphine consumption was significantly lower at 6 and 12 h, compared with control values. With intravenous ketamine, visual analog scale scores at rest and morphine consumption were significantly lower at 6, 12, 24, and 48 h than those in control subjects. The combination of epidural morphine and intravenous ketamine provided definitive preemptive analgesia: Visual analog scale scores at rest and morphine consumption were significantly the lowest at 6, 12, 24, and 48 h, and the visual analog scale score during movement and the categoric pain score also were significantly the lowest among the groups. CONCLUSION: The results suggest that for definitive preemptive analgesia, blockade of opioid and N-methyl-d-aspartate receptors is necessary for upper abdominal surgery such as gastrectomy; singly, either treatment provided significant, but not definitive, postsurgical pain relief. Epidural morphine may affect the spinal cord segmentally, whereas intravenous ketamine may block brain stem sensitization via the vagus nerve during upper abdominal surgery.     

Epidural dexamethasone reduces postoperative pain and analgesic requirements

PURPOSE: Epidural steroids may have potential advantages for providing postoperative analgesia. We therefore undertook a study to evaluate the efficacy of epidurally administered dexamethasone in reducing postoperative morphine requirements, as a measure of analgesia following laparoscopic cholecystectomy. METHODS: In a randomized, double-blind study, 94 patients undergoing laparoscopic cholecystectomy were randomly assigned to one of three groups. Group 1 (Control) patients received dexamethasone 5 mg iv with epidural injection of 0.25% bupivacaine 8 mL and normal saline 2 mL, Group 2 (D1) patients received normal saline 2 mL iv with epidural injection of 0.25% bupivacaine 8 mL and dexamethasone 5 mg in normal saline 2 mL, and Group 3 (D2) patients received normal saline 2 mL iv with epidural injection of dexamethasone 5 mg in normal saline 10 mL. After surgery, morphine 2-4 mg iv was administered as needed for analgesia. Postoperative morphine requirements, visual analogue scale (VAS) pain scores at rest and with effort, and time to first analgesic administration were recorded by a blinded observer. RESULTS: Total morphine consumption for the first 24 hr following surgery was lower in both epidural dexamethasone groups (D1, D2) compared to the control group (P < 0.05). The percentage reduction in morphine consumption in Group D1 was 53.9% and in Group D2 was 52.9% in the first 24 hr. Postoperatively at 12 hr, 18 hr and 24 hr, the VAS scores at rest and during effort were also lower in the epidural dexamethasone groups (D1, D2) compared to the control group (P < 0.05). The percentage reductions in VAS scores with effort at 12 hr, 18 hr and 24 hr in Group D1 were 50%, 52.9% and 50% respectively, and in Group D2 percentage reductions in pain scores with effort were 54.8%, 58.8% and 55.5% at corresponding sampling intervals. CONCLUSION: Preoperative epidural administration of dexamethasone 5 mg, with or without bupivacaine, reduces postoperative pain and morphine consumption following laparoscopic cholecystectomy.     

Epidural levobupivacaine 0.1% or ropivacaine 0.1% combined with morphine provides comparable analgesia after abdominal surgery

Ropivacaine appears attractive for epidural analgesia because it produces less motor block than racemic bupivacaine. The potential benefits of levobupivacaine with regard to motor blockade require further investigations. In this study, we compared the efficacy, dose requirements, side effects, and motor block observed with epidural levobupivacaine and ropivacaine when given in combination with small-dose morphine for 60 h after major abdominal surgery. Postoperatively, 50 patients were randomly allocated, in a double-blinded manner, to patient-controlled epidural analgesia with the same settings and without basal infusion, using 0.1% levobupivacaine or 0.1% ropivacaine. Both were combined with an epidural infusion of 0.1 mg/h morphine. Pain scores, side effects, motor block, and local anesthetic consumption were measured for 60 h. Pain scores measured on a 100-mm visual analog scale were approximately 20 mm at rest and 40 mm during mobilization in both groups. Bromage scores were 1 for all patients after the fourth postoperative hour. Consumption of levobupivacaine and ropivacaine were similar: 344 +/- 178 mg levobupivacaine versus 347 +/- 199 mg ropivacaine 48 h postoperatively. On postoperative day 2, 19 patients in the ropivacaine group versus 12 in the levobupivacaine group were able to ambulate (P < 0.05). No difference was noted concerning incidence of side effects. We conclude that when used as patient-controlled epidural analgesia and combined with small-dose epidural morphine, 0.1% levobupivacaine and 0.1% ropivacaine produce comparable postoperative analgesia with a similar incidence of side effects. IMPLICATIONS: Small concentrations (0.1%) of epidural levobupivacaine and ropivacaine combined with morphine (0.1 mg/h) produce comparable analgesia and have similar side effects for similar dose requirements.     

Preoperative epidural ketamine in combination with morphine does not have a clinically relevant intra- and postoperative opioid-sparing effect

In this prospective, randomized, and double-blinded clinical trial, we evaluated the efficacy of preincisional administration of epidural ketamine with morphine compared with epidural morphine alone for postoperative pain relief after major upper-abdominal surgery. We studied 50 ASA I and II patients undergoing major upper-abdominal procedures. These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine 30 min before incision. Intraoperative analgesia was provided in addition, with IV morphine, and the requirement was noted. A blinded observer using a visual analog scale for pain assessment observed patients for 48 h after surgery. Additional doses of epidural morphine were provided when the visual analog scale score was more than 4. Analgesic requirements and side effects were compared between the two groups. There were no differences between the two groups with respect to age, sex, weight, or duration or type of the surgical procedures. The intraoperative morphine requirement was significantly (P = 0.018) less in Group 2 patients (median, 6.8 mg; range, 3-15 mg) compared with patients in Group 1 (median, 8.3 mg; range, 4.5-15 mg). The time for the first requirement of analgesia was significantly (P = 0.021) longer (median, 17 h; range, 10-48 h) in Group 2 patients than in Group 1 (median, 12 h; range, 4-36 h). The total number of supplemental doses of epidural morphine required in the first 48 h after surgery was comparable (P = 0.1977) in both groups. Sedation scores were similar in both groups. One patient in Group 2 developed hallucinations after study drug administration. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. Although the addition of ketamine had synergistic analgesic effects with morphine (reduced intraoperative morphine consumption and prolonged time for first requirement of analgesia), there was no long- lasting preemptive benefit seen with this combination (in terms of reduction in supplemental analgesia) for patients undergoing major upper-abdominal procedures. IMPLICATIONS: Ketamine added to epidural morphine given before surgery can decrease postoperative pain by its preemptive effect, opioid potentiation, and prevention of acute opioid tolerance. A single epidural bolus of 1 mg/kg of ketamine with morphine given before major upper-abdominal surgery did not result in a clinically relevant reduction in postoperative pain relief.     

Postoperative extradural analgesia with morphine and ropivacaine. A double-blind comparison between placebo and ropivacaine 10 mg/h or 16 mg/h

BACKGROUND: Some controversy exists in the literature on the benefit of epidurals compared to patient-controlled intravenous analgesia (PCA). Also, the dose of ropivacaine for epidural analgesia when combined with morphine remains uncertain. The aim of this study was to compare the epidural vs. PCA technique and high-dose vs. low-dose ropivacaine combined with morphine during knee replacement surgery. METHODS: In this prospective, randomized, double-blind study, postoperative pain relief with a combination of epidural ropivacaine (Group L: 10 mg h-1, Group H: 16 mg h-1) and morphine (0.16 mg h-1) was evaluated in 30 patients. A placebo group (Group PL) of 15 patients having PCA morphine served as the control. Visual analog pain (VAS), morphine consumption, sensory and motor block and side-effects were recorded during 48 h. RESULTS: VAS scores at rest were significantly lower in Groups L and H compared to Group PL. On movement, Group H had lower VAS scores than Group PL during 3-27 h (P<0.05) and Group L during 4-9 h (P<0.05), while Group L had lower a VAS than Group PL during 9-18 h (P<0.05). Morphine consumption after 48 h was greater in Group PL (64.6+/-36.3 mg) vs. Group L (23.3+/-33.9 mg) (P<0.001) and Group H (4.3+/-9.6 mg) (P<0.0001). Mild motor block was seen in Group H in 20% and 14% patients at 24 h and 48 h, respectively, but time to mobilization was similar between the groups. Pruritus was more common in the ropivacaine groups (P<0.05). CONCLUSION: Lumbar epidural analgesia using a combination of ropivacaine (16 mg h-1) and morphine (0.16 mg h-1) provides superior analgesia compared to the PCA technique or ropivacaine (10 mg h-1) and morphine (0.16 mg h-1). Although this resulted in a mild motor block during the first 12 h, patient mobilization was similar in all groups.     

Reversal of epidural morphine-induced respiratory depression and pruritus with nalbuphine

The effect of nalbuphine on the respiratory depression, pruritus and analgesia induced by epidural morphine was determined in a randomized, prospective, double-blind, placebo-controlled fashion. Twenty ASA physical status I women received 0.1 mg.kg-1 epidural morphine at induction of general anaesthesia for elective total abdominal hysterectomy. Group 1 (n = 14) received 0.3 mg.kg-1 nalbuphine intravenously six hours after the epidural morphine administration. Group 2 (n = 6) received saline. Prior to agent administration, six patients from the nalbuphine group and four patients from the saline group had respiratory depression indicated by a PaCO2 greater than 45 mmHg. After nalbuphine administration the PaCO2 (mean +/- SE) decreased from 49.5 +/- 1.2 mmHg to 42.5 +/- 0.7 mmHg (p less than 0.005) while there was no significant change after saline administration. Nine of the 14 patients receiving nalbuphine appeared to become more sedated, despite an improvement in ventilation. Pruritus was antagonized by 0.1 mg.kg-1 nalbuphine (p less than 0.006). There was no reversal of analgesia after administration of 0.3 mg.kg-1 nalbuphine.     

Preemptive Analgesia by Intravenous Low-dose Ketamine and Epidural Morphine in Gastrectomy: A Randomized Double-blind Study

Background: Morphine and ketamine may prevent central sensitization during surgery and result in preemptive analgesia. The reliability of preemptive analgesia, however, is controversial.

Methods: Gastrectomy patients were given preemptive analgesia consisting of epidural morphine, intravenous low-dose ketamine, and combinations of these in a randomized, double-blind manner. Postsurgical pain intensity was rated by a visual analog scale, a categoric pain evaluation, and cumulative morphine consumption.

Results: Preemptive analgesia by epidural morphine and by intravenous low-dose ketamine were significantly effective but not definitive. With epidural morphine, a significant reduction in visual analog scale scores at rest was observed at 24 and 48 h, and morphine consumption was significantly lower at 6 and 12 h, compared with control values. With intravenous ketamine, visual analog scale scores at rest and morphine consumption were significantly lower at 6, 12, 24, and 48 h than those in control subjects. The combination of epidural morphine and intravenous ketamine provided definitive preemptive analgesia: Visual analog scale scores at rest and morphine consumption were significantly the lowest at 6, 12, 24, and 48 h, and the visual analog scale score during movement and the categoric pain score also were significantly the lowest among the groups.     

Epidural morphine prophylaxis of postoperative pain: report of a double-blind multicentre study

In a double-blind placebo-controlled trial, 154 subjects, having intraperitoneal surgery or Caesarean section, and 53 patients undergoing lower limb orthopaedic surgery, received epidural morphine, 5 mg in 10 ml 0.9 per cent NaCl, or placebo, 10 ml 0.9 per cent NaCl, intraoperatively to determine duration of action and efficacy in preventing postoperative pain. Epidural morphine gave significantly longer postoperative analgesia (greater than 11 h) than placebo (3-6 h) in both groups (p less than 0.05) and patients who received morphine required less postoperative analgesic. Obstetric subjects experienced longer pain relief (18.3 +/- 1.3 h) than patients undergoing non-obstetric intraperitoneal surgery (9.2 +/- 1.2 h) (p less than 0.001). Generally mild pruritus affected more than 40 per cent of those receiving morphine, but over 90 per cent of obstetric patients receiving morphine. Respiratory depression occurred in 2-7 per cent of subjects who received morphine; unpredictable in onset, it responded rapidly to naloxone. Epidural bupivacaine, if employed for the surgical procedure, appeared to prolong epidural morphine analgesia. We consider epidural morphine useful in preventing postoperative pain, but its use demands close observation of respiratory rate in a high density nursing area.     

Peridural opiate analgesia. Clinical results of a 2-year study

Postoperative pain relief, consumption of analgesics and the incidence of postoperative complications were investigated in a retrospective cohort-study on 470 patients following abdominal surgery. 221 of these patients received epidural morphine or buprenorphine for postoperative pain relief (Group I). Another group of 249 patients received conventional opiate analgesics intravenously or intramuscularly (Group II). On average the analgesia lasted 14 h after epidural morphine and 11 h after epidural buprenorphine. The overall amount of morphine in the postoperative period was 13.3 +/- 14.9 mg and 0.89 +/- 0.55 mg buprenorphine respectively. 5 cases of pneumonia (2.3%) were seen in the epidural group (Group I). 22 pneumonia cases (8.8%) were registered in the group with conventional analgesics (Group II). Besides the advantage of stronger and longer duration, small dosage and minor central depressive side effects, epidural opiate analgesia has proven to result in positive clinical consequences. The low incidence of postoperative pneumonia is due to the strong regional pain relief, which improves mechanical pulmonary function and gas exchange.     

Pre-emptive analgesia with ketamine, morphine and epidural lidocaine prior to total knee replacement

Purpose

Pre-emptive analgesia can improve postoperative pain management. The purpose of this study was to examine the effectiveness of ketamine as a pre-emptive analgesic as previous studies have shown the involvement of N-methyl-D-Aspartate (NMDA) receptor in neuroplasticity.

Methods

Forty-five ASA 1–2 patients, undergoing unilateral total knee replacement were studied. In the study groups, epidural lidocaine was used as the primary anaesthestic. Patients received ketamine + morphine epidurally 30 min either before (group EB) or after skin incision (group EA). Group G patients received general anaesthesia and ketamine + morphine were given 30 min after skin incision via an epidural catheter used for postoperative pain control. Epidural morphine and ketamine in lidocaine was given to all patients at the end of surgery and every 12 hr for three days for analgesia supplemented with PCA morphine. The time until first PCA trigger, morphine consumption, pain scores, satisfaction scores, and morphine related side effects were recorded at 6, 12, 24, 48 and 72 hr after surgery.

Results

Epidural ketamine plus morphine with lidocaine before surgical incision produced better pain relief and patient satisfaction than when given after incision. A longer time to PCA and decreased morphine consumption were observed in group EB than in group G. In group EA, epidural anaesthesia also produced some pre-emptive analgesic effect compared with general anaesthesia shown by decreased morphine consumption.

Conclusions

Administration of ketamine plus morphine with epidural lidocaine anaesthesia before surgery provided improved postoperative analgesia compared with general anaesthesia alone or when analgesics were given after skin incision.     

Plasma morphine levels during its continuous epidural infusion

We evaluated plasma levels of morphine during its continuous epidural infusion for postoperative analgesia in nine adult patients. A bolus injection of 3 mg of morphine was administered epidurally 3 hours prior to the proposed end of the surgery, and thereafter continuous epidural infusion of morphine was continued at a rate of 0.167-0.042 mg.hr-1 with a pump (CADD-PCA, 5200P, Pharmacia) during and after the surgery until the 3rd postoperative day. The dose of morphine was gradually decreased to 0.021-0.042 mg.hr-1 without reducing the quality of postoperative analgesia. Plasma morphine levels were measured by gas chromatography-mass spectrometry method. Plasma concentrations of morphine were 4.6 +/- 0.7 (Mean +/- SE) ng.ml-1 at the end of surgery and they decreased thereafter to 0.7 +/- 0.1 ng.ml-1, 0.3 +/- 0.1 ng.ml-1 and 0.1 +/- 0.1 ng.ml-1 on the 1st, 2nd and 3rd postoperative days, respectively. Plasma levels of morphine decreased gradually correlating with reduction of infused morphine. Adequate postoperative pain relief was obtained throughout the procedure without any severe complications such as respiratory depression. The analgesic effect of epidural morphine did not parallel with that of plasma concentration. Plasma concentrations of morphine administered by continuous epidural infusion with a pump were estimated to be lower than the minimum analgesic plasma concentration (10-40 ng.ml-1), and the toxic levels of morphine during continuous epidural infusion were not detected by our method.     

Effects of epidural naloxone on pruritus induced by epidural morphine: a randomized controlled trial

BACKGROUND: Epidural morphine produces prolonged analgesia but has many side effects including pruritus. Naloxone is an antagonist that can reverse the side effects of morphine. METHOD: We studied the effects of continuously administered epidural naloxone mixed with morphine on side effects and analgesia in a randomized, double blind, two-armed study. Fifty-eight pregnant women undergoing cesarean section were enrolled. All patients received a 4-mg epidural bolus of morphine in the post-anesthetic care unit. After this, patients in group M (n=28) received continuous epidural morphine (6 mg over 48 h) in 0.1% bupivacaine; patients in group N (n=30) received an epidural infusion containing naloxone (1.2 mg over 48 h) and morphine (6 mg over 48 h) in 0.1% bupivacaine. The infusion rate was 2 mL/h. RESULTS: The incidence (82% versus 47%) and severity of pruritus were lower in group N than group M (P=0.001). There were no significant differences in pain score or in the incidence of nausea, vomiting or urinary disturbance between groups. CONCLUSION: Continuous epidural infusion of naloxone combined with morphine is effective in reducing the incidence and severity of pruritus induced by epidural morphine.     

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.     

Continuous epidural infusion of morphine for pain relief after cardiac operations

Postoperative pain relief and stress hormones were examined during the use of continuous epidural infusion of morphine at a rate of 0.1 mg/hr in 30 patients (Group B) after coronary artery bypass grafting. This was compared to our routine method of postoperative analgesia of intravenous morphine 2 mg/2 hr and as needed in another 30 patients (Group A). Continuous epidural morphine infusion required occasional supplementation with intravenous morphine and achieved effective analgesia in 80% of the patients. Pain relief was adequate in 50% of the patients in Group A. The mean dose of morphine used in Group B during the first 3 postoperative days was 5 mg per patient per day and was significantly lower than that used in Group A (mean 18 mg per patient per day). Serum morphine was undetectable (below 2.5 ng/ml) in Group B and was significantly lower than that in Group A (17 ng/ml). Epidural analgesia was associated with adequate postoperative pulmonary and cardiovascular functions; nausea and vomiting occurred in two patients. Levels of postoperative stress, serum cortisol, and beta-endorphin were significantly lower in Group B than in Group A. This study shows that continuous epidural infusion of morphine at a rate of 0.1 mg/hr provides selective and effective pain relief and reduces postoperative stress after cardiac operations. This method of analgesia was also associated with minimal side effects and provides an alternate approach for treatment of pain after cardiac operations.