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

Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation ("empty head") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.
J Pain Symptom Manage 2000 Oct
PMID:Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. 1102 5

In recent years, there has been a great increase in our understanding of pain mechanisms and our awareness of pain in small animals. Despite increased knowledge, many animals still go undertreated or untreated. Small exotic animals are a unique group of patients, and can prove challenging for the practitioner concerned with their welfare. This article reviews the process of nociception and how one can intervene in the pain pathway. Newer analgesic drugs are discussed, along with some novel administration techniques that can be adapted for small mammals. Ketamine has been regarded primarily as a chemical restraining agent, but new information reveals that it may have an important place in pain management.
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PMID:Analgesia and analgesic techniques. 1121 56

Selective ligation of the L5/L6 spinal nerves produces a partial denervation of the hindpaw and has proved to be a useful model for studying the mechanisms underlying neuropathic pain. Two weeks after surgery, in vivo electrophysiological studies were performed in sham operated and nerve injured rats and the responses of spinal dorsal horn neurones to controlled electrical and natural (mechanical and heat) stimuli were recorded. The systemic effects of three N-methyl-D-aspartate receptor (NMDA) antagonists, ketamine (1-10 mg/kg), memantine (1-20 mg/kg) and MK-801 (0.1-5 mg/kg) were compared. Ketamine a clinically available NMDA receptor antagonist, produced greater reductions of the postdischarge, thermal (10 mg/kg, P=0.02), and mechanical evoked responses in spinal nerve ligated (SNL) rats (von Frey 9 g, 1 mg/kg, P=0.04; 5 mg/kg, P=0.01; 10 mg/kg, P=0.05; von Frey 50 g, 5 mg/kg, P=0.02; 10 mg/kg, P=0.003). The inhibition of wind-up was comparable in both animal groups. Memantine produced powerful inhibitions of wind-up after nerve injury with little effect in sham controls (5 mg/kg, P=0.02). The postdischarge, mechanical and thermal evoked responses were reduced to similar extents by memantine in both experimental groups. The effects of MK-801 were comparable between SNL and sham operated rats for all neuronal measures (wind-up, postdischarge, thermal and noxious mechanical evoked responses). The differential blocking abilities of these antagonists on the various neuronal responses may relate to the characteristics of their voltage-dependent blockage of the channel associated with the receptor. The favourable side effect profile of memantine supports its potential use for the treatment of neuropathic pain.
Pain 2001 Mar
PMID:Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy. 1124 82

Ketamine remains one of the most commonly used anaesthetic agents around the world. Despite it being the anaesthetic agent of choice in many developing nations, there is a paucity of literature describing ketamine in the developing world. In what we believe is the first randomized controlled trial to be performed in Vanuatu (formerly the New Hebrides) we compared the use of ketamine 0.9 mg/kg and diazepam 0.07 mg/kg with ketamine 0.3 mg/kg and 2% lignocaine infiltration in 50 Melanesian women undergoing post partum tubal ligation. All women received 0.5 mg/kg intramuscular pethidine. Visual analog pain scores and verbal numeric satisfaction scores were similar between the groups. However the time to obeyed command was significantly faster in the 0.3 mg/kg ketamine group (7.0+/-4.9 vs 13.0+/-9.2 min). The incidence of dreaming was similar and the content rated as pleasant by both groups. In institutions where post-anaesthesia care resources are limited, 0.3 mg/kg ketamine with local anaesthesia provides for earlier self-care of patients after tubal ligation, without compromise of analgesia, emergence or satisfaction. The implications of these findings extend to other procedures that require short general anaesthesia, which can be adequately performed with low-dose ketamine and local anaesthesia. The latter technique allows more rapid awakening.
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PMID:A randomized comparison of low-dose ketamine and lignocaine infiltration with ketamine-diazepam anaesthesia for post partum tubal ligation in Vanuatu. 1126 7

Ketamine may prevent postoperative hyperalgesia. In patients undergoing arthroscopic meniscectomy using general anesthesia, we tested whether a single intraoperative dose of ketamine enhanced postoperative analgesia and improved functional outcome compared with a typical multimodal analgesic regimen. After the induction of anesthesia, 50 patients were randomly assigned to ketamine (0.15 mg/kg IV just after the induction of anesthesia) or a vehicle placebo. Standardized general anesthesia included propofol, alfentanil, and nitrous oxide. Bupivacaine (0.5%) and morphine (5 mg) were given intraarticularly at the end of surgery. Postoperative analgesia was initially provided with morphine and subsequently with naproxen sodium (550 mg orally twice daily) and Di-Antalvic (400 mg acetaminophen and 30 mg dextropropoxyphene) as needed. Pain scores, analgesic requirements, side effects, and ability to walk were assessed in the ambulatory unit and at home for three postoperative days. Times to awakening and to discharge were similar in the two groups. However, the Ketamine group had significantly less postoperative pain at rest and during mobilization on Days 0, 1, and 2. Furthermore, they consumed significantly fewer Di-Antalvic tablets than the control group (13 [7-17] vs 27 [16-32], median [25%-75% interquartile range]). Patients given ketamine were also able to walk for longer periods of time on the first postoperative day. In conclusion, adding small-dose ketamine to a multimodal analgesic regimen improved postoperative analgesia and functional outcome after outpatient knee arthroscopy.
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PMID:Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy. 1152 27

Sedatives continue to be used on a routine basis in critically ill patients. Although many agents are available and some approach an ideal, none are perfect. Patients require continuous reassessment of their pain and need for sedation. Pathophysiologic abnormalities that cause agitation, confusion, or delirium must be identified and treated before unilateral administration of potent sedative agents that may mask potentially lethal insufficiencies. The routine use of standardized and validated sedation scales and monitors is needed. It is hoped that reliable objective monitors of patients' level of consciousness and comfort will be forthcoming. Each sedative agent discussed in this article seems to have a place in the ICU pharmacologic armamentarium to ensure the safe and comfortable delivery of care. Etomidate is an attractive agent for short-term use to provide the rapid onset and offset of sedation in critically ill patients who are at risk for hemodynamic instability but seem to need sedation or anesthesia to perform a procedure or manipulate the airway. Ketamine administered through intramuscular injection or intravenous infusion provides quick, intense analgesia and anesthesia and allows patients to tolerate limited but painful procedures. The risk/benefit ratio associated with the use of this neuroleptic agent must be weighed carefully. Ketamine is contraindicated in patients who lack normal intracranial compliance or who have significant myocardial ischemia. Barbiturates are reserved mainly to induce coma in patients at risk for severe CNS ischemia, which frequently is associated with refractory intracranial hypertension, or in patients with status epilepticus. When administered in high doses, these drugs have prolonged sedative and depressant effects. Judicious hemodynamic monitoring is required when barbiturate coma is induced. Haloperidol is indicated in the treatment of delirium. Patients should be monitored for extrapyramidal side effects and, when they require higher doses, for potential electrocardiographic prolongation of the QT interval. Dexmedetomidine may evolve into an agent with qualities comparable with midazolam and propofol, and it may even become a drug of choice in select patients. Further study is required, however. Propofol has many of the qualities of an ideal sedative agent. Benzodiazepines and narcotics often are used in concert with propofol to provide reliable amnesia and to relieve pain, respectively. Propofol frequently causes hypotension when administered as a bolus or infusion, particularly in patients with limited cardiac reserve or hypovolemia. More data must be obtained to identify potential deleterious effects of hypertriglyceridemia, and further evaluation of the potential benefits in certain patient populations, such as neurosurgical patients, is needed.
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PMID:Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit. 1176 65

To evaluate the role of oral ketamine as an adjuvant to oral morphine in cancer patients experiencing neuropathic pain, 9 cancer patients (5 men, 4 women) taking maximally tolerated doses of either morphine, amitriptyline, sodium valproate, or a combination of these drugs for intractable neuropathic pain, and reporting a pain score of >6 on a 0-10 scale, were studied prospectively to evaluate analgesia and adverse effects. Ketamine in the dose of 0.5 mg/kg body weight three times daily was added to the existing drug regimen. Patients were taught to maintain a pain diary wherein they daily recorded their pain, sedation, and vomiting scores, and other side effects. A decrease of more than 3 from the baseline in the average pain score, or a score of < or =3 was taken as a successful response. Seven patients exhibited a decrease of more than 3. Four patients experienced nausea, of which one had vomiting. Two developed loss of appetite. Eight patients reported drowsiness during the first two weeks of therapy (P = 0.001), and this gradually improved over the next two weeks in 5 of these 8 patients. Three patients withdrew from the study, two owing to excessive sedation and another due to a "feeling of unreality." None of the patients reported visual or auditory hallucinations. This experience suggests that low dose oral ketamine is beneficial and effective in the management of intractable neuropathic pain in patients with advanced cancer. However, its utility is limited in some patients by the adverse effects that accompany its use.
J Pain Symptom Manage 2002 Jan
PMID:Oral ketamine as an adjuvant to oral morphine for neuropathic pain in cancer patients. 1177 70

The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. Alfentanil significantly elevated cool and warm thresholds and decreased capsaicin-induced stroking hyperalgesia. Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.
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PMID:Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia. 1180 27

NMDA receptors are assumed to play an important role for neuronal plasticity. In vitro and animal experiments confirmed that NMDA antagonistic drugs can prevent hyperexitability of dorsal root neurons after strong pain stimuli. Clinical data, however, are more or less controversial in this respect. It was the aim of the present prospective, randomised, double-blind study to verify if low-dose preoperative ketamine, an NMDA antagonist, provides relevant postoperative analgesia in surgical patients and to re-examine positive results published by other investigators. 80 ASA I-II patients undergoing elective laparoscopic or proctologic surgery received at induction of general anaesthesia a single i.v. bolus dose of either ketamine 0.15 mg/kg or placebo (0.9% NaCl). Postoperative analgesia was provided by i.v. patient-controlled analgesia (PCA) using the opioid piritramide. Cardiovascular parameters, respiration, sedation, cumulative piritramide consumption and pain scores (visual analogue scale 1-10, verbal rating scale 0-4) were monitored at 1, 2, 3, 4, 5, 6, 12 and 24 hours after surgery. Additionally, a retrospective pain score was documented after the 24 hours observation period. There was no statistically significant difference in any study parameter. Cumulative PCA piritramide consumption after 24 hours was 25.0+/-16.2 mg in the ketamine group and 29.5+/-20.4 mg in the placebo group. Ketamine-specific side effects such as hallucinations or bad dreams were not observed. It is concluded that under the study conditions used, low dose ketamine, contrary to previously reported results [30], does not provide a clinically relevant pre-emptive analgesic effect in postoperative patients.
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PMID:[Lack of pre-emptive analgesic effect of low-dose ketamine in postoperative patients. A prospective, randomised double-blind study]. 1181 Mar 63

Ketamine is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist with analgesic and dissociative anesthetic properties. Low dose or sub-anesthetic doses of ketamine have been used effectively as either a primary analgesic or analgesic adjuvant in a variety of pain syndromes. In this paper, three patients with difficult to treat, predominantly neuropathic pain syndromes will be described. Their pain syndromes were initially managed successfully with the addition of low dose parenteral ketamine as an analgesic adjuvant. The strategy of concurrently starting ketamine at a low dose, i.e., 40-60 mg over 24 hours, with a benzodiazepine proved effective in preventing psychotomimetic side effects. An unavoidable shortage of ketamine prompted a literature search, which suggested that the equianalgesic dose of oral ketamine could be lower than the parenteral dose. Subsequently the patients were converted to oral ketamine at doses 30 to 40% of the previous parenteral dose. Their pain syndromes remained controlled on the lower dose of oral ketamine with remarkably few side effects. The implications of this warrant further discussion and study.
J Pain Symptom Manage 2002 Feb
PMID:Low dose ketamine as an analgesic adjuvant in difficult pain syndromes: a strategy for conversion from parenteral to oral ketamine. 1184 39


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