Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sedation and analgesia can be routinely prescribed in head injury patients. The goals of such sedation are three: brain protection, prevention and treatment of intracranial hypertension and therapeutic facilitation. In such situation, the use of sedative and analgesic therapy should respect the rate of cerebral blood flow/cerebral oxygen consumption coupling while preserving cerebral perfusion pressure and decreasing the intracranial pressure. This treatment should have an analgesic and myorelaxing action with short and predictable time of action. The ideal sedation agent with all these properties does not exist. Only the combination of several different pharmacological classes of compounds may reach this goal. Benzodiazepines are the most frequently used agents. In most of the cases they are associated with analgesic agents such as opioid or ketamine. Opioids may be the basic analgesic agents because they do not produce brain haemodynamic modifications if arterial pressure is maintained. Among them, sufentanil, thanks to its pharmacokinetics properties, remains the most prescribed opioid. However, in the future, remifentanil that presents a fast elimination may be more frequently used for neurological follow up of patients. Ketamine whose use is subject of debate, has the main advantage of maintaining haemodynamic status. Ketamine has no side effects on brain haemodynamic when used with propofol or midazolam. Taking into account their deleting effect on haemodynamic status and immune system, barbituric are no longer used as long term sedative agents. However, their use is still recommended in the cases of refractory intracranial hypertension. Propofol remains the ideal sedative agent because of its short duration action but its use is limited by its cost. Its use may be recommended for short time sedations with or without an opioid drug. The curare use should be restrain to refractory intracranial hypertension to usual treatments and happening during stimulation.
 ...
PMID:[The agents used for sedation in neurointensive care unit]. 1515 48

A 2.8-year-old female patient (11.6 kg) was admitted to the hospital for uncontrolled pain and swelling in the left leg relating to a metastatic neuroblastoma. Initially, her pain was managed with oral morphine 2 mg (approx. 0.2 mg/kg) every 4 hours. Because she was quite somnolent but still in significant pain, analgesia was then changed to methadone 1 mg orally every 6 hours (approximately 0.1 mg/kg/dose) and was eventually increased over 36 hours to 2 mg every 6 hours (approximately 0.2 mg/kg/dose). She received oral methadone 0.6 mg (approximately 0.05 mg/kg) every 4 hours as needed for breakthrough pain. She continued to have severe pain and experienced side effects, including respiratory depression, sedation, visual hallucinations, and vomiting. An intravenous ketamine infusion was started at 100 microg/kg/hour. Regular opioid administration was ceased, but she was given intravenous morphine 0.5 to 0.75 mg for breakthrough pain. She required only zero to three doses of breakthrough morphine per day, initially. After starting the ketamine infusion, her pain control improved and her symptoms of opioid toxicity abated. She was more alert and able to partake in limited activities. As a result of pain from progressive disease, the ketamine infusion was increased to 200 microg/kg/hour after 6 days with positive results. Her condition continued to deteriorate. An intravenous morphine infusion was initiated 2 weeks after starting the ketamine infusion and was eventually increased to 50 microg/kg/hour. One week later, she died with reasonable pain control. This case illustrates the use of ketamine as an effective analgesic in an adjuvant setting in a pediatric patient with advanced poorly controlled cancer pain. Ketamine not only eased the child's suffering while preserving life but also improved her quality of life by maintaining the child's ability to communicate and engage in activities.
 ...
PMID:Intravenous ketamine infusion as an adjuvant to morphine in a 2-year-old with severe cancer pain from metastatic neuroblastoma. 1545 42

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.
 ...
PMID:Ketamine and postoperative pain--a quantitative systematic review of randomised trials. 1562 65

The efficacy of ketamine and bupivacaine in enhancing the epidural analgesia induced by medetomidine was evaluated in 10 buffalo calves utilized repeatedly after a gap of 10 days so that each drug combination was tested in 4 randomly selected animals. In group A, medetomidine (15 microg/kg), in group B ketamine (2.0 mg/kg), in group C bupivacaine (0.125 mg/kg), in group D medetomidine and ketamine (15 microg/kg and 2.0 mg/kg), and in group E medetomidine and bupivacaine (15 microg/kg and 0.125 mg/kg) was administered epidurally. Onset of analgesia was significantly earlier in animals of groups B and D compared to the animals of groups A, C and E. Medetomidine alone or in combination with ketamine/bupivacaine produced complete analgesia of the tail, perineum, inguinal region and upper parts of hind limbs. Ketamine produced a very short duration of complete analgesia at the tail and perineum. Bupivacaine alone produced only mild to moderate analgesia. Both ketamine and bupivacaine prolonged the duration of analgesia. Motor incoordination was mild to moderate in animals of all the groups, but animals remained standing throughout the period of observation. Animals of groups A, D and E showed mild to moderate sedation during the observation period. Ruminal movements decreased nonsignificantly in animals of groups A and E. Mild salivation was observed in animals of all the groups except group C. Significant decrease in heart rate (HR) was recorded after epidural administration of medetomidine or bupivacaine; however, ketamine caused short duration of tachycardia. The administration of ketamine with medetomidine caused lesser decrease in HR compared to medetomidine alone or in combination with bupivacaine. Significant fall in respiratory rate (RR) was recorded after epidural administration of medetomidine or bupivacaine alone, but an increase in RR was recorded after ketamine administration. The fall in RR was less pronounced in animals in which medetomidine was used with ketamine compared to the animals in which medetomidine was used alone or in combination with bupivacaine. Mean arterial pressure (MAP) decreased and central venous pressure (CVP) increased significantly after epidural administration of medetomidine in combination with ketamine or bupivacaine. The ECG changes included tall T wave, QS pattern, RS pattern and ST elevation and heart blocks at different intervals, which were more frequent and pronounced in animals given bupivacaine with medetomidine. It can be concluded that epidural administration of medetomidine can produce complete analgesia of the tail, perineum, inguinal region and upper hind limbs in buffaloes. However, significant depression of cardiovascular parameters was recorded. Administration of ketamine along with medetomidine resulted in significantly early onset and slightly longer duration of analgesia with lesser cardiopulmonary side-effects compared to medetomidine alone or medetomidine with bupivacaine. Addition of ketamine to medetomidine thus seems to be useful for producing epidural analgesia; however, addition of bupivacaine failed to provide any advantage over medetomidine alone.
 ...
PMID:Medetomidine with ketamine and bupivacaine for epidural analgesia in buffaloes. 1572 87

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).
 ...
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

Ketamine is a drug that is commonly used for anesthesia and analgesia worldwide. Although it has an excellent safety profile, cognitive and psychotomimetic adverse effects are commonly associated with its administration. This review describes the clinical applications, potential adverse events, neurobiological, and behavioral effects of ketamine used at subanesthetic doses in humans.
 ...
PMID:Subanesthetic ketamine: how it alters physiology and behavior in humans. 1601 30

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.
 ...
PMID:Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia. 1611 91

Various clinical situations may arise in the PICU that necessitate the use of sedation, analgesia, or both. Although there is a large clinical experience with midazolam in the PICU population and it remains the most commonly used benzodiazepine in this setting, lorazepam may provide an effective alternative, with a longer half-life and more predictable pharmacokinetics without the concern of active metabolites. However, there are limited reports regarding its use in the PICU population, and concerns exist regarding the potential for toxicity related to its diluent, propylene glycol. Although the synthetic opioid fentanyl frequently is chosen for use in the PICU setting because of its hemodynamic stability, preliminary data suggest morphine may have a slower development of tolerance and may cause fewer withdrawal symptoms than fentanyl. Morphine's safety profile includes long-term follow-up studies that have demonstrated no adverse central nervous system developmental effects from its use in neonates and infants. In the critically ill infant at risk following surgery for congenital heart disease, clinical experience supports the use of the synthetic opioids, given their ability to modulate PVR and prevent pulmonary hypertensive crisis. Alternatives to the benzodiazepines and opioids include ketamine, pentobarbital, or dexmedetomidine. Ketamine may be useful for patients with hemodynamic instability or airway reactivity. There are limited reports regarding the use of pentobarbital in the PICU, with one study raising concerns of a high incidence of adverse effects associated with its use. Propofol has gained great favor in the adult population as a means of providing deep sedation while allowing for rapid awakening; however, its routine use is not recommended because of its potential association with "propofol infusion syndrome." As the pediatric experience increases, it appears that there will be a role for newer agents such as dexmedetomidine.
 ...
PMID:Sedation and analgesia in the pediatric intensive care unit. 1614 52

Ketamine is a dissociative anaesthetic that is being used in non-medical contexts. The effects of ketamine are very similar to those of phencyclidine, another dissociative anaesthetic that has enjoyed considerable popularity as a recreational drug. The effects of ketamine include analgesia, cardiovascular and respiratory stimulation, dissociation, hallucinations and anaesthesia. The potential dangers of uncontrolled ketamine use include psychosis and violence, accidents and marked psychomotor and cognitive impairment. Although studies have shown potential for tolerance to and physical dependence on ketamine, further investigation of these phenomena is needed. Ketamine is thought to produce most of its effects through antagonist activity at the PCP site of the NMDA receptor complex. Ketamine has sympathomimetic properties resulting from enhancement of catecholamine, and particularly dopamine, activity. While opioid receptor activity has been identified, this is relatively weak and the contribution to the effects of ketamine is not clear. Although much is known of the clinical uses and effects of ketamine, as yet little is understood of ketamine as a recreational drug and potential drug of dependence.
 ...
PMID:Pharmacological properties of ketamine. 1620 65

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.
 ...
PMID:Ketamine: new indications for an old drug. 1630 57


<< Previous 1 2 3 4 5 6 7 8 9 10