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. CONCLUSIONS: Lumbar epidural injection of morphine attenuated cutaneous heat pain up to the trigeminal dermatome during a 24-h observation period. In a clinical context, this implies that some types of pain may be attenuated up to the supraspinal level after lumbar epidural administration of morphine.     

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)     

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.     

Does morphine premedication influence the pain and consumption of postoperative analgesics after total knee arthroplasty?

Evidence of pre-emptive analgetic effect of opioid would offer great potential benefit to patients with postoperative pain, a better pain relief with less opioid. The aim of this double blind randomised trial was to study the effect of intramuscular morphine premedication on postoperative pain.
Forty-one patients undergoing total knee arthroplasty were randomly allocated to four groups. Two groups received epidural morphine, 4 mg immediately after operation and 3 mg ten hours later, and two groups the same volume of saline. All patients had access to intravenous PCA-fentanyl. One epidural morphine and one epidural saline group (PreEpiMo and PreMo, respectively) received morphine, 0.14 mg/kg i.m. as premedication. Pain was measured with a visual analogue scale (VAS). Respiration was monitored by means of pulseoximetry, arterial blood gas analysis and rate of breathing.
Morphine premedication reduced postoperative pain in the immediate postoperative period in patients with epidural placebo (PreMo), hut the effect was absent in patients with PreEpiMo. Epidural morphine (EpiMo) provided stable analgesia with reduced need of PCA-fentanyl. Two patients (10%) (one in EpiMo and one in PreEpiMo) developed respiratory depression requiring naloxone treatment. The dosage of epidural morphine used in this study was a likely explanation of this depression. Nausea, vomiting, itching and urinary retention were the most frequent side effects without significant differences between the groups. In conclusion, morphine premedication had a temporary rest effect on the postoperative pain. Epidural morphine provides a better analgesia than intravenous PCA-fentanyl.     

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.     

Epidural morphine causes delayed and prolonged ventilatory depression

We measured ventilation, PETCO2 and the Ventilatory response to added carbon dioxide before and at intervals up to six hours after epidural morphine 3.5 mg and 7.0 mg, and before and after subcutaneous injections of the same dose in volunteers. Subcutaneous morphine increased PETCO2 slightly, but did not alter the sensitivity of the response to added carbon dioxide. Epidural morphine reduced ventilation and increased PETCO2 progressively with time and, six hours after injection, reduced the ventilatory response to carbon dioxide considerably. In two subjects tested, these ventilatory effects persisted for twenty-four hours. The added effects of epidural morphine were due primarily to reductions in tidal volume and the tidal volume response to added carbon dioxide. We conclude that epidural morphine causes delayed and very prolonged ventilatory depression, which is of a greater magnitude and a different ventilatory pattern than that which follows the same does of morphine given subcutaneously. Ventilatory depression after lumbar epidural morphine develops slowly, as the lower limb analgesic effect is waning.     

Postoperative pain and pulmonary complications: comparison of three analgesic regimens

In a prospective study, patients undergoing cholecystectomy were randomly allocated to receive (a) intermittent intramuscular morphine (n = 25), (b) continuous intravenous morphine infusion (n = 25) or (c) epidural bupivacaine (n = 25) for postoperative pain relief. Morphine by intravenous infusion provided comparable pain relief to intermittent intramuscular morphine; there was no significant difference in the incidence of postoperative pulmonary complications. Patients receiving epidural bupivacaine for 12 h had better analgesia than patients receiving morphine (P less than 0.001). Arterial oxygen tensions were also significantly higher in the epidural group for the first three postoperative days (P less than 0.05). Epidural analgesia was associated with a significant reduction in the incidence of pulmonary complications (P less than 0.01) and chest infection (P less than 0.05).     

A multicenter study of the analgesic effects of epidural chloroprocaine after lower limb orthopedic surgery

Study objectiveTo investigate the effects and optimal concentration of chloroprocaine for epidural analgesia after lower limb orthopedic surgery.DesignProspective, randomized, observational, multicenter clinical study.SettingOperating room, postoperative recovery area, university hospital.PatientsOne hundred and twenty patients from 4 hospitals were enrolled and randomized into 5 groups after lower limb orthopedic surgery under epidural anesthesia with lidocaine.InterventionsEpidural chloroprocaine mixed with 0.4 μg/mL fentanyl was administered via a patient-controlled analgesia pump at the concentration of 0.6%, 0.8%, 1.0%, 1.2%, or 1.4% after the surgery.MeasurementsSystolic blood pressure, heart rate, visual analog score at rest and during activity, as well as the Bromage score at 0 minute, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours after the surgery were recorded and compared. Use of morphine and incidence of adverse effects were also recorded.Main resultsPatients given 1.2% chloroprocaine showed the lowest visual analog score compared with other groups. There was no significant difference in the Bromage score among 5 groups. The Bromage score returned to 0 in 89.7% of the patients 48 hours after surgery. No difference in postoperative morphine usage, blood pressure, or heart rate was found among 5 groups.ConclusionsEpidural 1.2% chloroprocaine with 0.4 μg/mL fentanyl could generate proper analgesic effects with little influence on mobility in patients undergoing lower limb orthopedic surgery. In addition, it could generate a good sense and movement separation, facilitating the early functional training.     

Comparação entre as técnicas de bloqueio do plano do músculo eretor da espinha e bloqueio epidural para analgesia pós‐operatória em colecistectomias abertas: um ensaio clínico randomizado

Introduction and objectivesBlockade of the Erector Spinal Muscle (ESP block) is a relatively new block, initially described for chronic thoracic pain analgesia, but it has already been described for anesthesia and analgesia in thoracic surgical procedures and, more recently, for high abdominal surgeries. The aim of the study was to compare two techniques, ESP Block and Epidural block with morphine and local anesthetic for postoperative analgesia of open cholecystectomy surgeries.MethodsControlled single‐blind randomized clinical trial with 31 patients (ESP block, n = 15; Epidural, n = 16), of both genders, ages between 27 and 77 years. The ESP block was performed at the T8 level with injection of 20 mL of 0.5% ropivacaine bilaterally. The epidural block was performed at the T8‐T9 space with 20 mL of 0.5% ropivacaine and 1 mg of morphine.ResultsThe ESP block group presented higher mean Numeric Pain Scale (NPS) values for pain in the up to 2 hour (p = 0.001) and in the 24 hour (p = 0.001) assessments. The ESP block group had a three‐fold increased risk (43.7% vs. 13.3%) of rescue opioid use in the 24 postoperative hours when compared to the epidural group (RR = 3.72, 95% CI: 0.91 to 15.31, p = 0.046).ConclusionESP block did not prove to be an effective technique for postoperative analgesia of open cholecystectomy, at the doses performed in this study, having required more use of rescue opioid, and without differences in NPS. More comprehensive studies are required to assess the efficacy of ESP block for the visceral and abdominal somatic component, considering the specific blockade level.     

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.     

Controlled comparison of nalbuphine and morphine for post-tonsillectomy pain

A controlled investigation was conducted to compare the effectiveness of morphine and nalbuphine in the prevention of pain and restlessness after tonsillectomy in children. Sixty children between 4 and 12 years old were randomly allocated to receive intramuscular morphine 0.2 mg/kg, nalbuphine 0.3 mg/kg or no medication approximately 5 minutes before the conclusion of surgery. Pain and restlessness were assessed 1 and 2 hours after injection, and side effects were recorded. The assessments were made double-blind. Both nalbuphine and morphine decreased restlessness and pain 1 hour (p less than 0.01) and 2 hours (p less than 0.05) after surgery. No significant differences were found between the two groups of patients who received opioids. Both nalbuphine and morphine caused more drowsiness than placebo 2 hours after surgery (p less than 0.001). Other side effects were uncommon. Nalbuphine may offer advantages compared with morphine in regard to safety and convenience of use for the treatment of post-tonsillectomy pain in children.     

Epidural Morphine by the Caudal Route for Postoperative Pain Relief

In order to detect the ability of epidural morphine, administered by the caudal route, to produce pain relief and in order to compare pain relief by this method with intramuscular injections of opiates, 90 patients scheduled for surgery below the umbilical level were studied. Four milligrams of preservative-free morphine in 10 ml normal saline was compared with intramuscular injections of opiates, using a visual analogue scale. The average pain score was significantly lower in the epidural group during the first 12 postoperative hours. In the epidural group, 38% required additional intramuscular injections during the first 12 h, whereas 86% of the patients in the intramuscular group received opiate injections. No patients developed respiratory depression. Side effects were more common in the intramuscular group than in the epidural group. It is concluded that epidural morphine by the caudal route is a better choice than intramuscular injections in controlling postoperative pain below the umbilical level.     

Remarks on some analgesics used in the pain clinic

The mechanism of action of aspirin as an analgesic is an inhibition of biosynthesis of prostaglandins. Thus the site of action has been believed to be peripheral. However, when aspirin is injected intra- thecally, it produces an analgesic effect. Aspirin has a membrane-stabilizing effect and it is used locally for the treatment of post- herpetic neuralgia. Epidural opioids are frequently used for the management of post-operative pain or cancer pain. Pharmacokinetic studies have shown that delayed respiratory depression results from migration of morphine in the cerebrospinal fluid to the brain. Peak concentrations of morphine near the brain stem occur about 3 hours after lumbar epidural injection, whereas lipophilic opioids such as meperidine, peak concentration occur within 30 to 60 minutes. The clearance from cerebrospinal fluid of lipophilic opioids is more rapid than that of morphine. Besides opioids, alpha 2 receptor agonists such as clonidine also have analgesic action when administered into the epidural space. Somatostatin is one of many neuropeptides found in the spinal cord. It has dual action: a mediation of thermal nociception and a general antinociceptive action. When somatostatin is administered intrathecally or epidurally, it produces analgesic effect and its efficacy appears to be equal to that of morphine.     

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.     

A comparative study of techniques of postoperative analgesia following caesarean section and lower abdominal surgery

A double-blind, within-patient trial was carried out to compare intramuscular pethidine 100 mg, epidural pethidine 50 mg and epidural bupivacaine 25 mg for pain relief on the day after caesarean section or lower abdominal gynaecological surgery. Analgesia was assessed on a visual analogue pain scale. Forced expiratory volume in one second (FEV 1.0) and venous plasma catecholamine levels were measured immediately before and approximately thirty minutes after each treatment. At the completion of the study the treatments were ranked in order of patient preference. Nineteen patients completed the trial. Analgesia provided by epidural pethidine 50 mg was superior to intramuscular pethidine 100 mg (p less than 0.05) but not statistically better than epidural bupivacaine. There was no significant difference in the duration of analgesia between the active treatments. A mean increase in FEV 1.0 of 18% occurred after both of the epidural treatments, but this did not achieve statistical significance. There was no significant change in catecholamine levels after any of the treatments. Epidural pethidine was preferred by patients over and above intramuscular pethidine and epidural bupivacaine (p less than 0.05).     

Epidural morphine improves pain relief and maintains sensory analgesia during continuous epidural bupivacaine after abdominal surgery

Twenty patients scheduled for elective major abdominal surgery were matched into two groups with regard to age, sex, height, body weight, and surgical procedure. Both groups received general anesthesia plus lumbar epidural analgesia with similar loading doses of bupivacaine 0.5% (23.1 +/- 1.0 and 23.3 +/- 0.8 ml) (mean +/- SEM) followed by continuous infusion of plain bupivacaine 0.5% (8 ml/hr) plus, in one group, epidural morphine (0.5 mg/hr). Pain score on a 5-point scale and sensory analgesia (pin prick) were assessed hourly for 16 hours after skin incision. If sensory analgesia decreased more than 5 segments from preoperative levels or if pain scores reached 2 (moderate pain), the patients were removed from the study, and pain was treated with other methods. Preoperative mean (+/- SEM) sensory levels of analgesia were similar in the bupivacaine and the bupivacaine-morphine groups (T3.4 +/- 0.5 and T3.3 +/- 0.4, respectively). In the group receiving only bupivacaine, sensory analgesia regressed over time with a simultaneous increase in pain score. Thus, within 10 hr after skin incision, seven patients in this group were discharged from the study, and 16 hr after incision only one patient maintained initial level of sensory analgesia. In contrast, each patient receiving bupivacaine plus morphine had stable sensory analgesia and was completely free of pain as indicated by a mean pain score of zero during the 16-hr observation period. Thus epidural morphine may improve pain relief and maintain analgesia during continuous epidural bupivacaine administration after abdominal surgery.     

Regional analgesic effect of epidural morphine in volunteers

Limb ischaemia induced by a sub-maximum effort tourniquet technique was used to characterize the analgesic effects of lumbar epidural morphine in volunteers. As an index of pain threshold, we measured the time to perception of pain in an upper and a lower limb before and at intervals up to six hours following epidural injections of morphine 3.5 mg and 7.0 mg, and before and after subcutaneous injections of the same doses. Subcutaneous morphine had no significant effect on the times to perception of pain in either limb. Lumbar epidural morphine did not alter upper limb times, but markedly delayed the onset of pain in the lower limbs. This lower limb analgesic effect was apparent thirty minutes after injection, peaked at about ninety minutes and was still present after six hours. Serum levels of morphine were nearly identical after subcutaneous and epidural injections of the same dose. We conclude that lumbar epidural morphine produces marked analgesia for this type of experimental pain primarily by a “regional” effect rather than as a result of systemic absorption. This regional effect develops slowly and is prolonged.     

Intravesical morphine analgesia is not effective after bladder surgery in children: results of a randomied double-blind study

PURPOSE: Intravesical morphine was recently recommended to reduce postoperative pain after reimplantation surgery for vesicoureteral reflux in children. The efficacy of such treatment, so far solely evaluated by open study, needed to be confirmed. MATERIALS AND METHODS: After parental informed consent was obtained, 80 children requiring Cohen cross-trigonal reimplantation were considered for inclusion in a double-blind study. On the day of surgery patients were randomly assigned to receive either 0.04 mg./kg. morphine per hour or placebo (normal saline) at a constant intravesical infusion rate of 0.08 ml./kg. per hour. Postoperative pain was assessed every 3 hours using a pain score adapted to patient age. If the score was above a predefined limit, patients received intravenous acetaminophen and nalbuphine alternately every 3 hours. Bladder infusion was discontinued after 48 hours. RESULTS: Mean and maximum pain scores as well as the number of scores above the limit were not statistically different when comparing the morphine and placebo groups. There was no difference in the number of doses of analgesics administered. Urine output, voiding frequency and the number of painful voiding episodes were not significantly different between the 2 groups. Plasma morphine concentrations were 3.0 +/- 2.7 and 1.9 +/- 1.9 ng./ml. at 24 and 48 hours in the morphine group and undetectable in the placebo group. CONCLUSIONS: Intravesical administration of morphine is not effective for relieving postoperative pain during the first 48 hours after intravesical ureteral reimplantation. This study emphasizes the importance of controlled studies in evaluating the effectiveness of a new drug or procedure before recommending its use for all patients.     

Epidural β-endorphin in treatment of pain

Epidural administration of 3 rag of synthetic β-endorphin produced analgesia in 10 patients with intractable pain due to disseminated cancer. Mean onset of relief of pain was 24 ± 3 minutes and the mean duration of analgesia was 19 ± 3 hours. The onset of analgesia produced by the epidural injection of β-endorphin was slower and the duration less than those observed after intrathecal injection.     

Epidural Morphine for Postoperative Pain Relief

Thirty-three patients were randomly assigned to two groups to study the analgesic potency, duration of action and side effects of epidural and intramuscular morphine after hip surgery. Two milligrams of preservative-free morphine chloride in 10 ml of normal saline in the epidural space was compared to 10 mg of intramuscularly administered morphine. There was a more rapid onset of action after intramuscular morphine. However, the quality of pain relief was substantially higher and the duration of action markedly longer after epidural morphine. The total dose required in the epidural group was 3.6 mg and in the intramuscular group 41 mg during the 15-h observation period. The side effects of epidural morphine were few and mild, the most embarrassing being urinary retention (20 %). Nausea and/or vomiting was less common after epidural morphine (20% versus 55%). Pruritus or respiratory depression which have been reported previously were not encountered. However, it is recommended that preservative-free solutions are used to avoid itching and that the patients are monitored, as respiratory depression may occur long after administration of epidural opiate.