Thoracic epidural clonidine and morphine for postoperative pain relief

This study was undertaken to evaluate the potentiation of the postoperative analgesic effect of thoracic epidural morphine by coadministration of thoracic epidural clonidine in a randomized double-blinded design. Twenty patients underwent radical gastrectomy under combined general anaesthesia (enflurane and nitrous oxide/oxygen) and epidural anaesthesia with local anaesthetics. They received a thoracic epidural bolus injection of either 0.05 mg · kg^?1 morphine plus 3 μg · kg^?1 clonidine (M+C group; n =10) or 0.05 mg · kg^?1 morphine alone, (M group; n = 10) immediately before completion of surgery. All patients received iv morphine via patient-controlled analgesia (PCA) equipment for 24 hr postoperative period, and the PCA iv consumption of morphine was the primary variable of efficacy of the analgesic regimen. In addition, data analyses included mean arterial blood pressure, heart rate, respiratory rate, arterial blood gas measurement, sedation score, and visual analogue pain scale score (VAS). The cumulative number of iv morphine injections via PCA was less in the M+C group than in the M group at each hour for 24 hr postoperative period (P < 0.05), while the numbers of PCA morphine injections per hour beyond nine hours after surgery were higher in the M group than in the M+C group (P < 0.05). Sedation score was higher, and VAS and mean blood pressure were lower in the M+C group only at one hour after surgery compared with the M group. We conclude that the combined single thoracic epidural administration of morphine plus clonidine produces a more potent and longer lasting analgesia than does morphine alone.     

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.     

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.     

Continuous epidural infusion of bupivacaine and morphine for postoperative pain relief

Forty-five patients admitted to the intensive care unit following thoracic or abdominal surgery received continuous epidural infusion of bupivacaine and morphine for 48 hours. During the first 10 hours, the patients received 0.25% bupivacaine solution with 0.005% morphine at the rate of 4 ml.h-1, and bupivacaine concentration was decreased to 0.125% with the same morphine concentration. The mean infusion rate of bupivacaine during 48 hours was 0.12 +/- 0.03 (SD) mg.kg-1.h-1 and that of morphine was 4.0 +/- 1.0 micrograms.kg-1.h-1. Thirty-one patients (69%) complained no pain on deep breathing at 24 hours and 33 patients (74%) required no other type of analgesics during this study. The mean plasma bupivacaine concentration was 0.6 +/- 0.3 microgram.ml-1 at 48 hours. Hypotension defined as systolic arterial pressure below 90 mmHg and itching were observed in 15 patients (33%), but no other severe side effects were noted. Continuous epidural infusion of bupivacaine and morphine mixture for 48 hours postoperatively provided effective pain relief with a low incidence of side effects.     

Implantable continuous epidural morphine infusion system for relief of chronic cancer pain

Chronic cancer pain remains intractable by standard treatment in many patients and interferes with their mobility and independence. Epidural morphine infusion therapy is adopted for providing adequate analgesia in patients who are generally morphine independent and have intractable pain. A totally implantable pump system, Infusaid, has allowed continuous epidural morphine infusion without wound care or frequent percutaneous injections and with a potentially lowered risk of adverse reactions including respiratory suppression. Since December 1984, the authors have used this totally implantable drug delivery system for continuous epidural morphine infusion in two patients who had been suffering from chronic pain caused by pelvic cancer associated with metastatic and/or invasive lesions: Case 1: a 61-year-old man with rectum cancer; and Case 2: a 44-year-old man with colon cancer. Before system implantation, a therapeutic response to epidural morphine was confirmed by a one-shot test injection. Pain relief was evaluated by use of Visual Pain Analogue Scale Scores (VPASS). In spite of the presence of an artificial anus on the left abdomen in both patients and of pus discharge from a sacral infectious fistula on admission in Case 2, no infectious complication occurred in either case. Urinary retention developed after the implantation in Case 2, but this improved following the reduction of morphine concentration. No other adverse reaction was observed. In Case 1, the system was effective for 6 months until his death from advancing malignancy, and the patient was able to return to work three months after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tramadol infusion for postthoracotomy pain relief: a placebo-controlled comparison with epidural morphine

We compared continuous IV tramadol as an alternative to neuraxial or systemic opioids for the management of postthoracotomy pain in a prospective, randomized, double-blinded, controlled study. General anesthesia was supplemented by thoracic epidural analgesia with 0.25% bupivacaine. At rib approximation, patients received one of the following: IV tramadol (150-mg bolus followed by infusion, total 450 mg/24 h, n = 29), epidural morphine (2 mg, then 0.2 mg/h, n = 30), or patient-controlled analgesia (PCA) morphine only (n = 30). All patients received PCA morphine and rescue morphine as necessary postoperatively. For the first 24 h, pain and sedation scores and respiratory, cardiovascular, and side effect measures were monitored. There was no significant difference in pain scores and PCA morphine use between tramadol and epidural morphine. Pain scores at rest and on coughing were lower in the Tramadol and Epidural Morphine groups than in the PCA Morphine group at various time points over the first 12 h. The Tramadol and Epidural Morphine groups used significantly less hourly PCA morphine than the PCA Morphine group at specific time points in the first 10 h. Vital capacities in the Tramadol group were significantly closer to baseline values at the 20-h point than in the PCA Morphine group. We conclude that an intraoperative bolus of tramadol followed by an infusion was as effective as epidural morphine and avoided the necessity of placing a thoracic epidural catheter. IMPLICATIONS: A prospective, randomized, double-blinded, placebo-controlled study of postthoracotomy pain relief showed that IV tramadol in the form of a bolus followed by continuous infusion was as effective as epidural morphine. The use of tramadol avoids the necessity of placing a thoracic epidural catheter.     

Comparison of lumbar epidural tramadol and lumbar epidural morphine for pain relief after thoracotomy: a repeated-dose study

OBJECTIVE: The purpose of this study was to compare lumbar epidural morphine and lumbar epidural tramadol with respect to onset and duration of analgesia, analgesic efficacy, and drug-related side effects after muscle-sparing thoracotomy. DESIGN: Prospective, randomized, double-blind, clinical study. SETTING: Single university hospital. PARTICIPANTS: Forty patients who underwent elective muscle-sparing thoracotomy. INTERVENTIONS: Before anesthesia induction, an epidural catheter was placed in the L2-3 or L3-4 interspace using the loss-of-resistance technique. On arrival at the intensive care unit, patients were randomized to receive doses of either 100 mg of tramadol (group T) or 4 mg of morphine (group M) via the lumbar epidural catheter. Each dose was diluted in 10 mL of normal saline. On awakening from anesthesia, if the patient's pain score on a 0- to 100-mm visual analog scale was above 40 mm, the initial epidural drug dose was administered. The initial injection in each case was taken as time 0. Subsequent pain scores above 40 mm were considered indications for epidural dosing; each patient was allowed 2 doses in the first 12 hours postoperatively and 2 more in the second 12 hours. MEASUREMENTS AND MAIN RESULTS: The groups' analgesia onset times were similar, but duration of analgesia was significantly shorter in group T than in group M (p < 0.01). There were no differences between the groups with respect to pain scores at rest or during coughing at any of the time points investigated. Sedation scores were lower in group T than in group M at 1, 2, 3, 4, and 8 hours (p value range, 0.0001-0.05). Compared with group T, group M showed significantly greater drops in arterial oxygen tension from baseline at 3, 4, 8, and 12 hours (p value range, 0.0001-0.05). The group means for arterial carbon dioxide tension and respiratory rate were similar at all time points investigated. CONCLUSION: The study revealed that the quality of analgesia achieved with repeated doses of lumbar epidural tramadol after muscle-sparing thoracotomy is comparable to that achieved with repeated doses of lumbar epidural morphine. Compared with morphine, lumbar epidural tramadol results in less sedation and a less-pronounced decrease in oxygenation.     

A comparison of Depodur, a novel, single-dose extended-release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery

In this randomized, controlled, dose-ranging study, we evaluated the analgesic efficacy of a novel single-dose extended-release epidural morphine (Depodur) in patients undergoing lower abdominal surgery. Five-hundred-forty-one patients were randomly assigned to one of six epidural treatments administered approximately 30 min before surgery. The 6 treatments were 5 mg of standard epidural morphine sulfate (MS) (active comparator); 5 mg of single-dose extended-release epidural morphine (EREM) (dose control); and 10, 15, 20, and 25 mg of single-dose EREM. The main study objective was to assess the efficacy of single-dose EREM 10, 15, 20, or 25 mg versus single-dose EREM 5 mg for the management of postoperative pain. This was done by plotting a linear dose-response relationship to assess postoperative IV patient-controlled analgesia (PCA) fentanyl consumption for breakthrough pain for 48 h after surgery. Secondary safety and efficacy analyses compared the 10-, 15-, 20-, and 25-mg single-dose EREM groups with the 5-mg single-dose EREM group and compared each single-dose EREM group with 5 mg of MS. As shown by the dose-response relationship, there was a dose-related reduction in the use of postoperative IV fentanyl through 48 h (estimated slope, -22.2; P = 0.0002). Patients treated with 10, 20, and 25 mg of single-dose EREM used significantly less IV fentanyl (mean +/- sd: 995 +/- 987 microg, P = 0.0446; 972 +/- 982 microg, P = 0.0221; and 683 +/- 620 microg, P < 0.0001, respectively) through 48 h after surgery compared with the 5-mg single-dose EREM group (1218 +/- 894 microg). At 48 h postdose, significantly more single-dose EREM patients (13%) than MS patients (2%) had required no IV fentanyl (P < 0.01). Although all treatment groups had access to PCA fentanyl and there was more frequent PCA fentanyl use in the MS group, patients in the single-dose EREM 15, 20, and 25 mg groups reported significantly lower pain-intensity scores and greater satisfaction with their pain relief. Overall, single-dose EREM was well tolerated, with 97% of adverse events rated as mild to moderate. As expected, the adverse events reported were consistent with those of other epidural opioids (i.e., nausea, vomiting, pruritus, and hypotension). In conclusion, this controlled study demonstrated that single-dose EREM can provide up to 48 h of postoperative analgesia, but supplementation for breakthrough pain is still required in most patients. Within the context of this study, the side effect profile of single-dose EREM was acceptable and predictable.     

Cancer of prostate with osseous metastases prolonged pain relief with very high-dose epidural morphine

Summary Osseous metastases may cause severe unremitting pain that may be difficult to control. We report a case of severe pain due to metastases of prostate cancer into the vertebral column, which was well controlled for 93 days with b.i.d. bolus epidural morphine injections. The starting dose was 80 mg/day, which was increased during the 93-day period to 540 mg/day without producing any side effects.