UMLS:C0030193 - FACTA Search

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

Ketamine, an N-methyl-D-aspartate receptor antagonist, is known to be analgesic and to induce psychomimetic effects. Benefits and risks of ketamine for the control of postoperative pain are not well understood. We systematically searched for randomised comparisons of ketamine with inactive controls in surgical patients, reporting on pain outcomes, opioid sparing, and adverse effects. Data were combined using a fixed effect model. Fifty-three trials (2839 patients) from 25 countries reported on a large variety of different ketamine regimens and surgical settings. Sixteen studies tested prophylactic intravenous ketamine (median dose 0.4 mg/kg, range (0.1-1.6)) in 850 adults. Weighted mean difference (WMD) for postoperative pain intensity (0-10 cm visual analogue scale) was -0.89 cm at 6 h, -0.42 at 12 h, -0.35 at 24 h and -0.27 at 48 h. Cumulative morphine consumption at 24 h was significantly decreased with ketamine (WMD -15.7 mg). There was no difference in morphine-related adverse effects. The other 37 trials tested in adults or children, prophylactic or therapeutic ketamine orally, intramuscularly, subcutaneously, intra-articulary, caudally, epidurally, transdermally, peripherally or added to a PCA device; meta-analyses were deemed inappropriate. The highest risk of hallucinations was in awake or sedated patients receiving ketamine without benzodiazepine; compared with controls, the odds ratio (OR) was 2.32 (95%CI, 1.09-4.92), number-needed-to-harm (NNH) 21. In patients undergoing general anaesthesia, the incidence of hallucinations was low and independent of benzodiazepine premedication; OR 1.49 (95%CI 0.18-12.6), NNH 286. Despite many published randomised trials, the role of ketamine, as a component of perioperative analgesia, remains unclear.
Pain 2005 Jan
PMID:Ketamine and postoperative pain--a quantitative systematic review of randomised trials. 1562 65

Diazepam is an effective drug that is used widely in modern anesthesia. Venous irritation is one of its major side effects attributed to its acqueous insolubility and requisite solvents. There is some evidence that ketamine may acts as a local anesthetic drug, because of its effect on N-methyl-D-aspartate receptors. Fentanyl also may reduce the pain of diazepam injection by blocking the opiate receptors in vessels walls. To determine the effectiveness of ketamine and fentanyl in reducing the pain of diazepam injection, 150 patients (ASA I, II) were randomly assigned to one of three Groups and before intravenous diazepam injection. 2 ml normal saline, 2 ml fentanyl or 10 mg ketamine were administered for Groups 1, 2, 3 respectively. The pain of diazepam injection was then evaluated at 30 minutes intervals. Our results showed that ketamine and fentanyl reduce the pain of diazepam dramaticaly (p < 0.001) in comparison with placebo. Ketamine is more effective than fentanyl in reducing such pain (p < 0.001).
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PMID:The effect of ketamine and fentanyl in reducing the pain of diazepam injection. 1565 16

Our previous studies have shown that 100 Hz electroacupuncture (EA) produced antinociception through the release of endogenous opioids (mainly dynorphin) and the activated kappa-opioid receptors in normal rats. Acupuncture is an effective treatment in relieving pain, but it develops tolerance after repeated administration. It has been reported that N-methyl-D-aspartate (NMDA) receptor antagonists could increase the antinociceptive effects induced by morphine and delay the development of tolerance to morphine but nothing has yet been described to reduce EA tolerance. Here we test whether ketamine, a non-competitive NMDA receptor antagonist, would enhance 100 Hz EA antinociception as well as prevent or delay the development of chronic tolerance to 100 Hz EA in normal rats. The results are as follows: (1) ketamine injected intraperitoneally (i.p.) 15 min prior to EA enhanced the antinociceptive effects of 100 Hz EA at a dose of 5.0 mg/kg, but not 0.2 or 1.0 mg/kg. However, ketamine at either dose did not affect the basal nociceptive threshold (represented by tail-flick latency). (2) Ketamine at a dose of 5.0 mg/kg delayed the development of chronic tolerance to 100 Hz EA antinociception. We conclude that ketamine can enhance antinociception of 100 Hz EA and delay the tolerance to 100 Hz EA in rats. These results suggest that the development of 100 Hz EA tolerance to antinociception was mediated, at least in part, through peripheral NMDA receptors, which may be useful in improving the therapeutic effects of EA in the treatment of pain when EA tolerance occurs.
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PMID:Ketamine enhances the efficacy to and delays the development of tolerance to electroacupuncture-induced antinociception in rats. 1567 Jun 57

Ketamine has been widely used in the operation as intravenous and intramuscular injections, since ketamine has dissociative anesthetic properties. When it is given in sub-anesthetic dose, ketamine is known to have an analgesic effect. The analgesic effect is observed for patients with neuropathic pain when administrated not only by injection but also orally. In Japan, since ketamine is not commercially available except injection forms, patients have to take it as solution of injections for the oral medication. Since the solution of injections has extremely bitter taste, patients intensely desire the development of preparations without the bitterness. In the present study, we prepared oral gel dosage forms of ketamine using agar. It is simple to prepare this dosage form, and most pharmacists can prepare it easily in many hospitals. This gel dosage form met content uniformity requirements and the shape of that was maintained intact during the dissolution test (for 10 hours). The release rate was reduced by additions of additives such as sugar and a flavor in the gel. The reason for the reduction in release could be the suppression of ketamine diffusion depended on the micro-viscosity of solution in the gel. The ketamine contents and the release profile of the gel preparations were unchanged at the room temperature for 12-week storage. The gel preparations in this study would be useful for the oral medication of ketamine, since it is easy for patients to carry them when they go out and the intensely bitter taste could be improved by the addition of a flavor.
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PMID:[Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar]. 1568 73

BACKGROUND: Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids. METHODS: Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed. RESULTS: The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given. CONCLUSION: A serum concentration of ketamine that did not alter indices of sedation potentiated the antinociceptive effect of fentanyl. This potentiation of antinociception occurred without an increase in sedation suggesting that low steady doses of ketamine (30-120 ng/ml) might be combined with mu opioid agonists to improve their analgesic effect in a clinical setting. (296 words).
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PMID:Investigation of the potentiation of the analgesic effects of fentanyl by ketamine in humans: a double-blinded, randomised, placebo controlled, crossover study of experimental pain[ISRCTN83088383]. 1580 61

We evaluated whether preadministration of low-dose ketamine could attenuate tourniquet pain and arterial pressure increase using high tourniquet pressure in ten healthy awake volunteers. Ketamine, 0.1 mg x kg(-1), or normal saline was given intravenously in a double-blind fashion before tourniquet inflation with a pressure of 400 mmHg at the thigh. Visual analog scale (VAS) scores and systolic blood pressure (SBP) were measured at 5-min intervals. Ketamine significantly reduced VAS scores compared to saline just after tourniquet inflation [90 (64-100) mm, median (range), with saline versus 66 (50-81) mm with ketamine, P < 0.01] and at 30 min [92 (61-100) mm with saline versus 70 (50-100) mm with ketamine, P < 0.03), and significantly prolonged tourniquet time (28 +/- 6 min with saline, mean +/- SD, versus 37 +/- 7 min with ketamine, P < 0.01). SBP (120 +/- 9 mmHg) significantly increased before tourniquet deflation (133 +/- 16 mmHg) in the saline trial, but not in the ketamine trial. The results show that preadministration of low-dose ketamine attenuates tourniquet pain and arterial pressure increase during high-pressure tourniquet application and prolongs tourniquet time in healthy volunteers.
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PMID:Preadministration of low-dose ketamine reduces tourniquet pain in healthy volunteers. 1587 41

N-methyl-D-aspartate (NMDA) receptor antagonists enhance opioid-induced analgesia. The plasma concentration of ketamine, an NMDA receptor antagonist that enhances epidural morphine-and-bupivacaine-induced analgesia, is not known. We examined 24 patients with lung carcinoma or metastatic lung tumor who underwent video-assisted thoracic surgery in a placebo-controlled, double-blind manner 4 h after emergence from anesthesia. The morphine + ketamine group (n = 8) and morphine + placebo group (n = 8) received 5 mL volume of 2.5 mg morphine and 0.25% bupivacaine and the placebo + ketamine group (n = 8) received 5 mL volume of saline and 0.25% bupivacaine epidurally at the end of skin closure. Four hours after this anesthesia, in the morphine + ketamine and placebo + ketamine groups, ketamine was administered to successively maintain a stable plasma ketamine concentration of 0, 10, 20, 30, 40, and 50 ng/mL by a target-controlled infusion device, and patients assessed the levels of pain at rest, pain on coughing, somnolence (drowsiness), and nausea using a 100-mm visual analog scale (VAS). In the morphine + placebo group, a placebo (saline) was similarly administered instead of ketamine. In the morphine + ketamine group, the VAS scores for pain at rest and pain on coughing significantly decreased on ketamine administration at a plasma concentration of 20 ng/mL or larger compared with the respective baseline VAS scores (P < 0.05 each). In the placebo + ketamine group, the VAS scores for pain at rest and pain on coughing did not significantly change at any plasma concentration of ketamine as compared to the morphine + placebo group. In the morphine + ketamine group, a plasma concentration of ketamine larger than 20 ng/mL did not further reduce VAS scores for pain at rest and pain on coughing. The VAS scores for drowsiness were comparable among the three groups at any plasma concentration of ketamine. Ketamine at a plasma concentration of 20 ng/mL or larger may enhance epidural morphine-and-bupivacaine-induced analgesia. As an adjunct with epidural morphine-and-bupivacaine and considering the safety of small doses, the minimal plasma concentration of ketamine given IV may be approximately 20 ng/mL.
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PMID:Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia. 1611 91

Ketamine shows, besides its general anaesthetic effect, a potent analgesic effect after spinal administration. We investigated the local anaesthetic-like action of ketamine and its enantiomers in Na+ and K+ channels and their functional consequences in dorsal horn neurones of laminae I-III, which are important neuronal structures for pain transmission receiving most of their primary sensory input from Adelta and C fibres. Combining the patch-clamp recordings in slice preparation with the 'entire soma isolation' method, we studied action of ketamine on Na+ and voltage-activated K+ currents. The changes in repetitive firing behaviour of tonically firing neurones were investigated in current-clamp mode after application of ketamine. Concentration-effect curves for the Na+ peak current revealed for tonic block half-maximal inhibiting concentrations (IC50) of 128 microM and 269 microM for S(+) and R(-)-ketamine, respectively, showing a weak stereoselectivity. The block of Na+ current was use-dependent. The voltage-dependent K+ current (K(DR)) was also sensitive to ketamine with IC50 values of 266 microM and 196 microM for S(+) and R(-)-ketamine, respectively. Rapidly inactivating K+ currents (K(A)) were less sensitive to ketamine. The block of K(DR) channels led to an increase in action potential duration and, as a consequence, to lowering of the discharge frequency in the neurones. We conclude that ketamine blocks Na+ and K(DR) channels in superficial dorsal horn neurones of the lumbar spinal cord at clinically relevant concentrations for local, intrathecal application. Ketamine reduces the excitability of the neurones, which may play an important role in the complex mechanism of its action during spinal anaesthesia.
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PMID:Ketamine impairs excitability in superficial dorsal horn neurones by blocking sodium and voltage-gated potassium currents. 1615 36

The neural correlates of consciousness must be identified, but how? Anesthetics can be used as tools to dissect the nervous system. Anesthetics not only allow for the experimental investigation into the conscious-unconscious state transition, but they can also be titrated to subanesthetic doses in order to affect selected components of consciousness such as memory, attention, pain processing, or emotion. A number of basic neuroimaging examinations of various anesthetic agents have now been completed. A common pattern of regional activity suppression is emerging for which the thalamus is identified as a key target of anesthetic effects on consciousness. It has been proposed that a neuronal hyperpolarization block at the level of the thalamus, or thalamocortical and corticocortical reverberant loops, could contribute to anesthetic-induced unconsciousness. However, all anesthetics do not suppress global cerebral metabolism and cause a regionally specific effect on thalamic activity. Ketamine, a so-called dissociative anesthetic agent, increases global cerebral metabolism in humans at doses associated with a loss of consciousness. Nevertheless, it is proposed that those few anesthetics not associated with a global metabolic suppression effect might still have their effects on consciousness mediated at the level of thalamocortical interactions, if such agents scramble the signals associated with normal neuronal network reverberant activity. Functional and effective connectivity are analysis techniques that can be used with neuroimaging to investigate the signal scrambling effects of various anesthetics on network interactions. Whereas network interactions have yet to be investigated with ketamine, a thalamocortical and corticocortical disconnection effect during unconsciousness has been found for both suppressive anesthetic agents and for patients who are in the persistent vegetative state. Furthermore, recovery from a vegetative state is associated with a reconnection of functional connectivity. Taken together these intriguing observations offer strong empirical support that the thalamus and thalamocortical reverberant network loop interactions are at the heart of the neurobiology of consciousness.
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PMID:General anesthesia and the neural correlates of consciousness. 1618 27

Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d-aspartate (NMDA) receptor for glutamate, though its effects are mediated by interaction with many others receptors. It has been introduced in clinical use since 1960's but today it is not largely employed as a general anaesthetic for its undesired psychic effects (emergence reactions) occurring in approximately 12% of patients. In the last decade, there has been a renewed interest in the use of subanaesthetic doses of ketamine for the treatment of acute and chronic pain. In the late 1990's, multiple prospective, randomised, controlled study has shown the efficacy of low dose of ketamine for postoperative pain relief, for analgesia during regional or local anaesthesia, and for opioid-sparing effect. At present, non-definitive conclusion can be drawn. More data are needed to define the possible long term effects and the clinical goal of ketamine use.
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PMID:Ketamine: new indications for an old drug. 1630 57

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