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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both epidural and intravenous clonidine are used to provide postoperative analgesia, but in predetermined doses. This double-blind randomized study was designed to 1) determine the clonidine dose inducing pain relief after major orthopedic surgery, when controlled by patient, either intravenously or epidurally; and 2) assess whether these two administration routes are clinically equivalent. At the first complaint of pain after scoliosis correction, patients received an initial dose of 8 micrograms/kg clonidine during 30 min either intravenously (n = 12) or epidurally (n = 12). Then, clonidine was given using a patient-controlled analgesia pump via the corresponding administration route. In both cases, the bolus dose was set at 30 micrograms and the lockout interval at 15 min. Pain (0-100 scale), clonidine requirements, sedation (0-4 scale), and hemodynamics (by fiberoptic pulmonary artery catheter) were measured before and 15, 30, 120, 240, 360, 480, and 600 min after the loading dose was started. Plasma clonidine concentrations and arterial blood gases were determined at the 15th, 30th, 240th, and 480th min. Self-administered and total clonidine doses were larger in the intravenous group than in the epidural group (at 600 min: 372 +/- 110 vs 235 +/- 144 micrograms, and including the initial dose, 814 +/- 114 vs 652 +/- 187 micrograms; mean +/- SD). Clonidine administration resulted in pain relief and sedation in both groups but, for comparable pain relief, sedation scores were lower in the epidural group. No intergroup differences in hemodynamic data were observed, although the decrease in blood pressure occurred earlier in the intravenous group. Plasma clonidine concentrations were higher in the intravenous group than in the epidural group (2.5 +/- 0.6 vs 1.5 +/- 0.5 ng/mL after the initial dose and 2.1 +/- 0.5 vs 1.5 +/- 0.4 ng/mL during self-administration; mean +/- SD). We conclude that analgesia can be achieved postoperatively by both epidural and intravenous clonidine administration. The epidural route is associated with significant reductions in self-administered clonidine dose, and thus in the plasma clonidine concentration, and the level of sedation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of intravenous and epidural clonidine for postoperative patient-controlled analgesia. 757 98

The dorsal raphe (DR) nucleus is a system of nuclei in the midline of the lower brainstem, which is considered one of the most important nuclei in the modulation of pain in the central nervous system. Central noradrenergic systems play an important role in the control of cardiovascular regulation and pain transmission. Clonidine, an alpha 2-adrenergic agonist is used extensively in anesthesia research. In this study, we evaluated the involvement of clonidine in the activity of DR nucleus and its possible role in pain modulation. Seventy-four neurons within the DR nucleus in the rat brainstem slice preparation were tested using extracellular recording techniques. Application of noradrenaline (NA), 50 mumol/L, induced firing activity in 68 neurons tested (92%). NA produced a regular long-lasting firing activity on the DR neurons. Fifty-six neurons (88%) previously excited by NA were inhibited by clonidine, 20 mumol/L. Clonidine suppressed the firing activity of neurons. The results indicate that the firing of DR neurons was under noradrenergic influence and was inhibited by clonidine, which in turn alters nociception by modifying the central serotonergic system.
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PMID:The effect of clonidine on the activity of neurons in the rat dorsal raphe nucleus in vitro. 763 60

Although the epidural administration of clonidine and fentanyl provides pain relief after surgery, the interaction between the two drugs has not been examined formally. This study used an isobolographic method to determine whether epidurally administered fentanyl and clonidine interact in an additive or synergistic manner. Ninety women with moderate to severe pain after elective cesarean section under epidural anesthesia were studied. Using a randomized, double-blind protocol, we assigned each patient to receive a single epidural injection of one of three doses of fentanyl, clonidine, or a fixed ratio combination. Pain relief, blood pressure (BP), heart rate (HR), and sedation were measured 15 min after injection. Each drug alone and in combination produced analgesia, as measured by pain relief scores, and reduced need for intravenous morphine. Although the effective dose producing analgesia in 50% of patients (ED50) for the mixture was only 52% of that predicted by an additive interaction, this did not differ significantly from additivity, likely due to large variability. Clonidine, alone or in combination with fentanyl, produced a minor reduction in BP, but did not affect HR or cause more sedation than fentanyl. Unlike studies in rodents, this clinical study did not demonstrate synergy between fentanyl and clonidine. This could reflect a true species difference or differences in methodologies used. Nonetheless, a reduced dose of fentanyl and clonidine can be combined for excellent analgesia.
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PMID:An isobolographic study of epidural clonidine and fentanyl after cesarean section. 763 65

Clonidine in spinal and epidural blocks prolongs anesthesia, but can cause hypotension and bradycardia. The aim of our study was to compare hemodynamic and analgesic effects of spinal versus epidural clonidine alone and after repetitive dosing. In a prospective, randomized, double-blind study, we evaluated 40 patients scheduled for lower extremity orthopedic surgery under continuous spinal or epidural anesthesia with bupivacaine 0.5% (initial dose 5 mg and 50 mg, respectively). In either spinal or epidural technique one-half of patients received clonidine (150 micrograms) in addition to bupivacaine. Repeat doses of the same anesthetic mixture were allowed in cases of subsequent pain. Mean arterial pressure (MAP) and heart rate were recorded for 6 h after each injection. Duration of clinically useful anesthesia was defined as the time from drug administration to first sensation of pain. Intrathecal, but not epidural, clonidine decreased MAP significantly compared with bupivacaine alone. MAP after intrathecal clonidine with bupivacaine was lower than epidural clonidine with bupivacaine 5 and 6 h after injection. Repetitive administration caused no further decrease in MAP. Onset time required to surgical anesthesia (sensory block of T11) did not differ among the four groups. Duration of spinal and epidural anesthesia was increased more than two fold by clonidine. In summary, the addition of clonidine prolongs analgesia by either route. These results may be explained by clonidine's sites of action in hemodynamic control and the density of bupivacaine-induced block.
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PMID:Hemodynamic and analgesic effects of clonidine added repetitively to continuous epidural and spinal blocks. 781 20

Anomalous responses to morphine are common in patients with unexplained pain in the upper abdomen after cholecystectomy and may be linked to activation of the sympathetic nervous system. The hypothesis that sympathetic suppression would attenuate anomalous responses to morphine was tested by a randomized, cross-over trial using a standard challenge with morphine, with and without pretreatment with clonidine (300 micrograms orally, 1 h prior to the administration of morphine). In 13 of the 15 patients who completed the study, pre-treatment with clonidine decreased plasma concentrations of noradrenaline, dopamine and adrenaline by 56, 15 and 25% respectively. This was associated with a significant reduction in morphine-induced pain (p = 0.02) and nausea (p = 0.04) and attenuated increases in plasma aspartate aminotransferase (AST) activity (p = 0.03). Clonidine attenuates anomalous responses to morphine, perhaps through effects on sympathetic nervous activity or plasma concentrations of catecholamines.
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PMID:Sympathetic suppression attenuates anomalous responses to morphine in unexplained pain after cholecystectomy. 784 98

Epidural opioids provide a potent analgesia not devoided of side effects. In addition, epidural administration of lipid soluble opioids has no clear advantage over the IV route. Combination of epidural opioids with other analgesics may strengthen analgesia and may decrease the incidence of side effects because of a reduction in the amount of opioid administered. Improvement in analgesia quality is documented when local anaesthetics are associated to opioids. Low concentrations of local anaesthetics may potentiate the effect of opioids on ions membrane channels at the level of the dorsal horn of the spinal cord. Alpha adrenergic agonists provide an alternative to local anaesthetics, allowing to improve pain control achieved with opioids. Epinephrine decreases plasma absorption of opioids and is especially useful to prolong the effect of short acting lipid soluble opioids. Alpha adrenergic agonists atc on alpha-2-adrenergic receptors of the spinal cord dorsal horn to depress pain nociceptive transmission. This effect potentiates the one of opioids at this level. Clonidine, which is a selective alpha-2-adrenergic agonist has been demonstrated to improve and to prolong analgesia produced by opioids in postoperative patients. Clonidine administration induces side effects, like sedation, bradycardia and hypotension, but allows to highly reduce the opioid dose. None of the combined techniques of analgesia implies that monitoring of the side effects of opioids has to be reduced.
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PMID:[Is there an advantage to using opioid combinations by the peridural route?]. 790 34

Mechanisms of the analgesic actions of alpha 2-adrenergic agonists are likely related to various modulating systems of nociceptive neurotransmission, especially those dependent on opiate receptors. Analgesic action of alpha 2-adrenergic agonists implies alpha 2-adrenergic receptors, strategically located on the dorsal horn neurones of the spinal cord to inhibit the release of substance P in response to peripheral stimuli. However, these receptors are included in the control that supraspinal sites exert via the descending medullospinal noradrenergic pathway. Because of its high lipophilic structure, alpha 2-adrenergic agonist can easily penetrate into the central nervous system, reproducing the effects of activation of medullospinal noradrenergic pathway. Alpha 2-adrenergic agonists have been found to be efficient in human pain treatment after systemic, spinal or troncular administration, but there were few randomized clinical studies comparing analgesia potency and adverse effects of either systemic or regional administrations. Clonidine added to local anaesthetic agents increases the analgesic effects in a greater extent than systemic administration of similar dose, probably because this effect depends on the local clonidine concentration. Extradural administration of clonidine is also more efficient than systemic administration, at least when high doses are injected. This superiority is questionable when low-dose clonidine is used. Adverse effects are quite similar in both systemic and spinal routes. Invasiveness of extradural route may be considered in regard to the gain which may be expected in analgesia efficiency.
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PMID:[Which way for the administration of alpha 2-adrenergic agents to obtain the best analgesia?]. 791 62

In obstetric patients treated with epidural analgesia during labor and delivery, shivering is quite frequent due to stress, vasodilatation, infusion of fluids, low ambient temperature, and the direct effect of solution injected into the epidural space. Sixty obstetric patients who developed shivering after receiving epidural analgesia for delivery were randomly assigned to treatment with clonidine 0.150 mg i.v. (N = 20), meperidine 50 mg i.v. (N = 20), or saline solution (N = 20). Drug administration was double blind. The effect on shivering (graded as all or none), drowsiness, heart rate, and systolic arterial pressure was evaluated 5 min after the study drug was administered. Clonidine was as effective as meperidine in controlling shivering and caused a greater reduction in heart rate. Drowsiness occurred after clonidine as well as meperidine. Thus, clonidine proved to be effective in controlling shivering and adrenergic response after delivery using epidural analgesia and produced an acceptable level of drowsiness.
J Pain Symptom Manage 1994 Jul
PMID:Effect of clonidine on postpartum shivering after epidural analgesia: a randomized, controlled, double-blind study. 796 79

Phantom limb pain may appear in up to 85% of patients after amputation. There is no effective treatment. Perioperative epidural infusion of morphine and bupivacaine, alone or in combination, is effective in preventing phantom limb pain in patients with pre-existing limb pain. Serious side-effects, however, make them difficult to manage on a general ward. Clonidine has been shown to be an effective postoperative analgesia when applied epidurally. To mitigate the potentially serious side-effects of all these drugs, we have studied their combined efficiency in preventing phantom limb pain in a prospective controlled study of 24 patients undergoing lower limb amputation. In the study group (n = 13), an epidural infusion containing bupivacaine 75 mg, clonidine 150 micrograms and diamorphine 5 mg in 60 ml normal saline was given at 1-4 ml/h 24-48 h preoperatively and maintained for at least 3 days postoperatively. The control group (n = 11) received on-demand opioid analgesia. Pain was assessed by visual analogue scale at 7 days, 6 months and 1 year. At 1 year follow-up, one patient in the study group and eight patients in the control group had phantom pain (P < 0.002) and two patients in the study group versus eight patients in the control group had phantom limb sensation (P < 0.05). There was no significant improvement in stump pain. We conclude that perioperative epidural infusion of diamorphine, clonidine and bupivacaine is safe and effective in reducing the incidence of phantom pain after amputation.
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PMID:Prevention of phantom pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine. 771 55

The neurotransmitters adrenaline and noradrenaline are non-selective adrenergic agonists which interact with both subtypes of alpha- and beta-receptors. Clonidine, an alpha 2-adrenergic drug with a selectivity ratio of 200/1 for alpha 2/alpha 1 has been used in clinical practice for more than 20 years. Although alpha 2-agonists have vasoconstrictor properties, sympatholytic effects on the central nervous system predominate. As a result, the sympathetic outflow from the medullary pressor centres is decreased mediating the hypotensive effects of the alpha 2-agonists. These compounds also exhibit sedative, anxiolytic, analgesic, and haemodynamic stabilising properties. The identification of alpha 2-adrenoceptors has yielded information on their biochemical properties, signal transduction, modulation of the sympathetic nervous system and neurotransmission. The classification of alpha 2-receptors based on anatomical locations and identified as presynaptic alpha 2-receptors and postsynaptic alpha 1-receptors proved to be untenable after postsynaptic and extrasynaptic alpha 2-receptor locations had been identified. At least 3 isoreceptors which are heterologously distributed in the brain have been identified. Guanine nucleotide proteins (G proteins) couple the receptor to an effector mechanism (i.e. intracellular messenger cascade, ion channel). More selective for the alpha 2-adrenoceptor than clonidine is dexmedetomidine (1600/1 of alpha 2/alpha 1), a very potent agonist at the alpha 2-adrenoceptor. Imidazole derivatives (like clonidine and dexmedetomidine) also bind to other nonadrenergic receptors ("imidazoline receptors") which may produce some effects (i.e. vagotonia) previously ascribed to alpha 2-adrenoceptors. alpha 2-receptors exist in brain tissue and several peripheral organs and tissues including the liver, eye, kidney, pancreas and platelets. Anaesthetic interest has focussed on reductions in anaesthetic requirements since experimental and clinical studies have shown that alpha 2-agonists expert powerful analgesic and anaesthetic effects. The hypnotic response is probably mediated by activation of alpha 2-adrenoceptors in the locus coeruleus. Analgesia is induced by modulation of the nociceptive pathway at the level of the dorsal root neuron and other sites not yet unambiguously characterised. Dexmedetomidine reduces the anaesthetic requirements for halothane by more than 90%. Cerebral blood flow and intraocular pressure are reduced by alpha 2-agonists. Epidural, intrathecal, intravenous and transdermal application of clonidine resulted in pain reduction, during and following surgery and in patients with neurogenic or otherwise intractable cancer pain. Administration of alpha 2-agonists induces only minor respiratory effects. Salivary flow is reduced by alpha 2-agonists and gastric and small-bowel motility is decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Alpha 2-agonists in anesthesia and intensive medicine]. 809 70


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