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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At the beginning, the way intrathecal morphine was used for postoperative pain relief was quite unfortunate, because the doses derived from experience with morphine-tolerant cancer patients were considerably too high and respiratory depression occurred frequently. Subsequent dose-finding studies showed that the doses of morphine used initially could be reduced by a factor of ten without loss of the analgesic effect and with a marked reduction in side-effects. No respiratory depression has been reported when doses below 0.1 mg morphine are used. METHOD. In this prospective study the effect of 0.06 to 0.08 mg intrathecal morphine, mixed with the local anaesthetic for spinal anesthesia, was investigated in surgical patients aged 21 to 81 years, ASA grade I or II, scheduled for orthopaedic operations or herniorraphies. Thirty unpremedicated patients were enrolled in the study and were, after informed consent, randomly allocated to a control group without morphine or to a morphine group. The analgesic effect was assessed by the time interval between the administration of the spinal anaesthesia and the first demand for an analgesic medication. The mood state was evaluated with the adjective checklist of Janke and Debus 6 h after the spinal anaesthesia. RESULTS AND DISCUSSION. In the control group half of the patients asked for an analgesic medication within 275 min (median) after the spinal anaesthesia, and all patients within 420 min, whereas in the morphine group half of the patients asked for an analgesic within 1170 min (median). Seven patients had not required an analgesic at the termination of the observation period 20 h after the spinal anaesthesia. The mood status showed no difference between the two groups, in particular, no dizziness or drowsiness after morphine. There was no difference in the incidence of side-effects such as nausea or urinary retention between the two groups. Pruritus was not reported spontaneously but was found upon questioning in five patients. It was in no case disturbing. CONCLUSIONS. Morphine (0.06 to 0.08 mg) mixed with the local anaesthetic for spinal anaesthesia provided for an analgesia of more than 20 h duration in half of the patients. This technique is safe, simple, reliable and virtually free of side-effects. No particular supervision due to the administration of intrathecal morphine is necessary in this dose range if systemic opiates are avoided. If the analgesia is unsatisfactory, a non-opioid analgesic is recommended.
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PMID:[Intrathecal morphine for postoperative pain]. 146 57

Two independent clinical trials were conducted simultaneously. In one, tramadol and pethidine were compared in 30 patients by patient-controlled analgesia during the first 24 h following abdominal surgery. The mean 24 h consumption of tramadol and pethidine was 642 mg and 606 mg respectively, giving a potency estimate of tramadol relative to pethidine of 0.94 (95% confidence interval 0.72-1.17). In the second trial, the effect on respiration of three doses of tramadol (0.5, 1.0, and 2.0 mg.kg-1) was compared with that of morphine sulphate (0.143 mg.kg-1) by intravenous injection during stable halothane anaesthesia. At approximately 1.5 times the equipotent dose, as estimated from the first trial, tramadol transiently depressed the rate of respiration but had no effect on end-tidal carbon dioxide tension. Morphine caused apnoea or considerable depression of ventilation. The results suggest that mechanisms other than opioid receptor activity play a significant role in the analgesia produced by tramadol.
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PMID:Tramadol: pain relief by an opioid without depression of respiration. 151 77

The analgesic efficacy, side effects, and satisfaction of patient-controlled analgesia (PCA) with intravenous and epidural morphine for postoperative pain were evaluated in this study. Twenty patients undergoing major joint replacement surgery were randomly allocated to intravenous PCA (IPCA) group or epidural PCA (EPCA) group. All patients had a standardized balanced anesthesia, and an epidural catheter was introduced after the operation in EPCA group. Postoperative pain relief was evaluated with verbal pain scale. The result showed that pain intensity and pain relief were similar in either group without significant difference (p greater than 0.05). Morphine consumption in IPCA group was 1.72 +/- 0.30 mg/h in the postoperative 0 - 12 h and 1.14 +/- 0.44 mg/h in 12 - 24 h. In EPCA group, relatively low doses of morphine were used, i.e., 0.20 +/- 0.07 mg/h in the postoperative 0 - 12 h and 0.17 +/- 0.07 mg/h in 12 - 24 h. Both groups showed an "incomplete" but satisfactory analgesia with relatively low doses of morphine. The "equianalgesic dose ratio" of IPCA to EPCA with morphine was approximately 8.5:1. Sedation was minimal in both groups. No respiratory depression developed in all patients. Nausea and vomiting were the most prominent side effects which might limit the usefulness of PCA. The incidence was 5 out of 10 patients in IPCA group and 4 out of 10 patients in EPCA group, despite under the treatment of droperidol (15 micrograms/kg, iv, prn) for most of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Patient-controlled intravenous versus epidural analgesia after major joint replacement]. 152 2

The effects of the major morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, on nociception were assessed by the tail-flick, hot-plate and writhing tests in the rat. Morphine-3-glucuronide (M3G) 1.1 x 10(-9) mol (0.5 micrograms) or saline was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.) followed by a second injection of 2.0 x 10(-10) mol (0.1 microgram) or 2.0 x 10(-11) mol (0.01 microgram) morphine-6-glucuronide (M6G) 10 min later. Administration of M3G (i.c.v.) significantly attenuated the antinociceptive effects of M6G in the hot-plate test. After i.t. administration, the antinociceptive effect of M6G in all three tests was significantly reduced in the M3G pretreated group compared to the group receiving saline. The ventilatory effects of 4.0 x 10(-9)-1.0 x 10(-8) mol (2-5 micrograms) M6G and 1.7-2.2 x 10(-8) mol (8-10 micrograms) M3G given i.c.v. were studied by a whole-body plethysmographic technique in halothane anaesthetized rats. Separate groups of rats received M3G followed by M6G injection or vice versa. In animals receiving M3G there was a prevention or attenuation of the M6G induced depression of respiratory frequency, tidal volume and minute ventilation compared to control groups receiving M6G in combination with saline. These results show that M3G may functionally antagonize the central antinociceptive effects as well as the ventilatory depression induced by M6G. Interestingly, M3G was more potent in antagonizing the M6G-induced analgesia after i.t. administration than that after i.c.v. administration, which may suggest that the spinal cord is more sensitive to the non-opioid excitatory effects of M3G than supraspinal structures.
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PMID:Morphine-3-glucuronide may functionally antagonize morphine-6-glucuronide induced antinociception and ventilatory depression in the rat. 145 98

Thirty elderly patients undergoing major hip surgery under spinal analgesia were randomly allocated in a double-blind manner into three groups. The aim was to evaluate the influence of intrathecal morphine and postoperative naloxone infusion on the regulation of ventilation. The Bupivacaine Group received spinal analgesia with 20 mg bupivacaine intrathecally. The Morphine Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally. The Naloxone Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally + postoperative naloxone infusion intravenously (1 microgram/kg/h over 12 h, 0.25 micrograms/kg/h over the next 12 h). Evaluation of resting ventilation and the ventilatory responses to hypercarbia and hypoxaemia was made on three occasions: before surgery, and 8, and 24 h after the intrathecal injection. Intrathecal morphine had no significant effect on ventilatory regulation in elderly patients undergoing major hip surgery performed under bupivacaine spinal analgesia. Postoperative administration of opioids or sedatives after intrathecal morphine as well as postoperative blood loss associated with a fall in blood pressure appeared to increase the risk of developing respiratory depression. Naloxone infusion seemed to reduce the risk of developing respiratory depression. Furthermore, one third of the elderly had a poor response to hypoxaemia before surgery.
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PMID:Influence of intrathecal morphine and naloxone intervention on postoperative ventilatory regulation in elderly patients. 163 66

The sites of action of spinally administered opiates are specific receptors (mu kappa delta) located in the spinal dorsal horn. Pharmacokinetics of spinally administered opiates are determined by their lipophilic property. Morphine has a weak octanol-water partition coefficient and remains in the CSF during a long period following the cephalic movements of lumbar CSF to the supraspinal structures. More lipophilic opiates are rapidly eliminated from the CSF. Nevertheless, significant pethidine concentrations are documented in the ventricular CSF, due to vascular absorption of the drug. Pharmacokinetics features of different opiates determine the duration of analgesia and the risk of respiratory depression after spinal injection.
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PMID:[Pharmacology and mechanism of action of opiates administered by the subarachnoid route]. 167 77

The process of nociception, the anatomy of the epidural space, and the placement of the epidural catheter are reviewed, and the pharmacology and pharmacokinetics, analgesic efficacy, and potential adverse effects of epidurally administered narcotics and local anesthetics are discussed, as well as patient monitoring standards and solution preparation guidelines for these agents. The epidural space is located between the dura mater (the outer-most membrane surrounding the spinal cord) and the vertebral canal. The site of catheter placement is determined by the dermatomes corresponding to the site of desired analgesia. The primary factors that differentiate epidural narcotics are related to their pharmacokinetic profiles. Morphine, which is hydrophilic, has a slower onset of action and a longer duration of analgesia than lipophilic compounds such as fentanyl; morphine also results in less segmentalization (the degree to which analgesia is limited to discrete dermatomal segments corresponding to the level of the epidural narcotic injection) than is seen with lipophilic compounds. Studies have shown that epidural narcotics provide superior pain relief compared with systemic narcotics. Common adverse effects associated with therapeutic doses of intraspinal narcotics include itching, nausea and vomiting, urinary retention, and sedation; respiratory depression is uncommon after epidural administration of narcotics. The most bothersome adverse effect encountered with analgesic doses of local anesthetics is paresthesia. Solutions for epidural administration must be sterile and preservative free. Epidural administration of narcotics and local anesthetics seems to provide better pain relief than conventional methods but may be associated with more bothersome adverse effects.
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PMID:Epidural analgesia. 174 84

Patient controlled analgesia (PCA) is a drug delivery system aimed to control acute pain using negative feedback technology in a closed loop system in which the patient plays an active role. It overcomes the inadequacies of traditional analgesic protocols due to marked differences in pharmacokinetic and dynamy of analgesis between patients. Moreover, doctors and nurses frequently underprescribe opioids in patients with severe pain for fear of dangerous side-effects. A safe and effective delivery of these drugs on patient demand can be achieved using various delivery systems, modes and dosing parameters. Most devices provide both demand dosing, where a constant predetermined dose is self administered, and constant rate infusion plus demand dosing, where the minimum administration rate is determined by the doctor, but can be supplemented by patient demand. Morphine sulphate remains the drug most commonly used in PCA therapy, but meperidine hydrochloride, alfentanil, nalbuphine and buprenorphine are also sometimes administered. The doctor determines the incremental dose per demand, the lockout interval, and the maximum dose per time unit, possibly also the loading dose and the minimum dose rate when a continuous flow is used. PCA provides improved analgesia, which is immediate and independent of nurse availability. This technique decreases opioid requirements, and the required total amounts are lowered. PCA gives patients both behavioural and decisional control. They can titrate the analgesic dose in such a way as to balance pain relief with the degree of side-effects, the patient is willing to tolerate. Patients often choose less than the available total dose of analgesic. The risks consists in the usual opioid side-effects, mainly respiratory depression. These may be due to mechanical problems, machine failure, or user incidents (misprogramming, or miscalculation of doses). Standards help to ensure consistent care and avoid errors that can occur even with handwritten orders. The principles of demand analgesia are now being investigated using other agents, such as local anaesthetics, and other routes of administration, mainly epidural injection. In most patients, even in children, PCA can replace intramuscular injections, which are the standard route for opioid administration. Today PCA and spinal opioids are the two main methods of analgesia for postoperative pain management.
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PMID:[Patient-controlled analgesia]. 185 55

Drug and toxicant effects on locomotor/exploratory activity can be quite variable depending on the test and the schedule of exposure. In neurobehavioral toxicology and teratology, these interactions can affect the inferences based on the use of selected drugs as probes to assess which regulatory mechanisms are affected by one or the other treatment. The present experiments were aimed at comparing morphine effects in CD-1 mice under three conditions, namely, Varimex apparatus (VAR), toggle floor box (TOGGLE), videotape recording (VIDEO) in a home cage environment. Morphine HCI (0, 10, 33, or 100 mg/kg) was given IP 20 min before the start of a 30-min test session. The same procedure was repeated 24 h later. Results of VAR and TOGGLE tests were: dose 10 was largely ineffective; dose 33 induced depression in VAR and hyperactivity in TOGGLE; dose 100 enhanced activity in TOGGLE. There were no differences between session 1 and 2. VIDEO: Univariate analysis results showed that morphine produced a dose-dependent depression of Rearing and Grooming, and an enhancement of Crossing, again without changes due to repeated exposure. Results of Principal Component Analysis supported a response competition model of the changes observed in the mouse behavioral profile. The videorecording (VIDEO) procedure is the one providing the most accurate picture of changes in locomotor/exploratory activity and drug effects thereon, also allowing a more comprehensive statistical analysis of the relationships between various types of response changes.
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PMID:Morphine effects on mouse locomotor/exploratory activity: test dependency, test reliability, uni- and multi-variate analyses. 187 Nov 96

We report the pharmacokinetics of morphine administered as intravenous boluses in newborn (less than 7 days) and 3- to 4-month-old macaque monkeys. Morphine was administered in a series of bolus doses until PaCO2 was elevated greater than 50 mm Hg. In newborns less than 7 days of age, a mean dose of 1.4 mg/kg was required (range 0.75-2.8 mg/kg), and in the 3-month-olds, a mean dose of 1.88 mg/kg was required (range 1.5-2.5 mg/kg). The respiratory effects measured by PaCO2 and respiratory rate did not correlate with declining serum or cerebrospinal fluid morphine levels. Both newborn and 3- to 4-month-old macaque monkeys show only mild respiratory depression after intravenous morphine, at serum concentrations as high as 300-400 ng/ml. Infant and young macaque monkeys appear to be less sensitive to the respiratory depressant effect of morphine than humans.
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PMID:Pharmacokinetics and pharmacodynamics of morphine in infant monkeys. 187 51


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