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

Ketamine and midazolam can produce analgesia following intrathecal administration in rabbits. However, neurotoxicity studies are required before these agents can be considered safe for clinical use. The aim of this study was to evaluate by histologic and blood-brain barrier (BBB) studies whether ketamine or midazolam could be used as an alternative to local anesthetics or opioids to produce spinal analgesia. Forty white New Zealand rabbits were randomly assigned to four groups of 10. In the conscious animal, 0.3 ml 0.9% saline solution, 1% lidocaine, 1% ketamine, or 0.1% midazolam was intrathecally injected intracisternally using a modification of the technique of Yaksh et al. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of the administered agents. All spinal cord section slides were scored within four zones: upper cervical, lower cervical, median thoracic, and lumbar segments. Spinal cord homogeneous lesions with higher scores than those of lidocaine-treated animals were considered abnormal. The BBB study showed evidence of neurotoxicity for ketamine, whereas light microscopy indicated no significant differences in comparison with saline and lidocaine. Midazolam-treated rabbits showed significant changes in both BBB and light microscopy studies. In view of these results, the intrathecal use of midazolam should be avoided in humans. Lesions observed following ketamine suggest the need for further experimental studies of the solvent and different ketamine enantiomers to establish definitively the safety of intrathecal free ketamine in humans.
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PMID:Ketamine and midazolam neurotoxicity in the rabbit. 818 31

Propofol (Diprivan), a modern intravenous hypnotic, produces a reduction in both cardiac index (CI) and mean arterial pressure (MAP). Ketamine (Ketanest), a potent analgesic, in contrast, causes an increase in MAP and CI. The aim of the present study was to investigate whether the combination of propofol and ketamine can give better hemodynamic stability during the induction and maintenance of general anesthesia than propofol used with fentanyl, whose cardiodepressant actions may cumulate. METHODS. For induction of general anesthesia 10 patients (ASA I and II) each received 3-5 boluses of propofol (0.5 mg.kg-1 during 35 s until predetermined level of anesthesia was reached (stage D2/E0 according to [20]) followed by a continuous propofol infusion (0.120 mg.kg-1.min). Fentanyl 0.1 mg was administered to each patient in group A for induction of anesthesia and again if evident pain was present. In group B ketamine was given following a pharmacokinetic model based on computer-simulated calculation. After an initial bolus of 38 mg injected within 2 min further doses of 42 mg, 35 mg, 32 mg and 28 mg ketamine were administered over 30 min at a time. Signs of evident pain were treated by means of supplementary doses of 0.5 mg.kg-1. RESULTS. In both groups a moderate drop of MAP was observed after the induction of general anesthesia. Two patients in each group showed a distinct decrease in MAP (-32%). The heart rate dropped slightly (-9%) in group A, but did not change in group B. Following intubation the MAP rose by less in group A (+8%) than in group B (+21%). After the beginning of the operation the group treated with propofol/fentanyl showed major hemodynamic changes; in particular, bradycardia with less than 40 bpm was observed in more patients than in the propofol/ketamine group. Postoperatively, fewer patients in group B required rescue doses of analgesics (1 of 10) than these in group A (7 of 10), though vigilance was better in group B. DISCUSSION. The dose of ketamine administered during the induction of general anesthesia may have been not high enough to neutralize the cardiodepressant effect of propofol. But during the maintenance of anesthesia there was in fact better hemodynamic stability in group B than in group A as a result of the neutralization of opposing actions. Fentanyl even intensified the fall in MAP after propofol. Patients in group B showed better vigilance as well as better pain relief postoperatively. The population of the fentanyl group was obviously more deeply sedated and analgesia was still inadequate. In our study general intravenous anesthesia with propofol and ketamine offered the advantages of better analgesia, a higher state of vigilance and the absence of respiratory depression during the postoperative phase compared with the combination of propofol and fentanyl.
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PMID:[The effect of propofol-ketamine anesthesia on hemodynamics and analgesia in comparison with propofol-fentanyl]. 207 45

The concept of combined anaesthesia, the centrally-acting muscle relaxant guaifenesin (My 301) in a 5% solution with ketamine (and/or fentanyl) in addition to the inhalation of nitrous oxide and halothane is based upon the principle of "balanced anaesthesia". Guaifenesin amplifies the effect of several anaesthetics, which complement one another, allowing the dosage to be decreased and thereby reducing the cardiovascular stress. To induce anaesthesia, the combination of a cataleptic anaesthetic (ketamine = Ketanest, Ketolar) and a centrally acting skeletal muscle relaxant (guaifenesin = Myolaxin, My 301) is used. Because of the risk of aspiration the animal should be intubated as soon as possible. Anaesthesia will be prolonged by the carrier gas nitrous oxide (65%, weakly analgesic)/oxygen (65%), low concentrations of halothane (1.0 to 0.6 to 0.4%, weakly hypnotic and analgesic) and by a continuous drip infusion of 5% guaifenesin (relaxing, mild analgesic and sedative). The effect of all the other anaesthetics is increased by guaifenesin. To increase the analgesia and to control the cardiovascular parameters the additional injection of ketamine or fentanyl is recommended. The recovery period is short and the general condition is good both after a lengthy anaesthesia of 9 hours (n = 32) and after anaesthesia of 2 hours. No significant adverse effects on the cardiovascular system were detected.
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PMID:[Combination anesthesia in sheep with ketamine-(fentanyl)-guaifenesin (My 301)-laughing gas-halothane]. 208 May 2

The reduction of capillary hemorrhage obtained with ketamine induced us to use this agent in anaesthesia for eardrum plastic surgery. During a period of 8 years 278 operations of this type were performed with this method. Its results were very satisfactory especially with regard to postoperative analgesia. No increase of capillary bleeding was observed after a temporary rise of arterial pressure following induction. Premedication consisted of atropine 0.5 mg intravenous and diazepam (later substituted by midazolam) according to age and weight. Induction was realized with fentanyl 0.1 mg intravenously followed by ketamine 3 mg.kg-1 intravenously. Anaesthesia was maintained by infusion of ketamine (500 mg in 500 ml of saline solution), nitrous oxide-oxygen (50% each) inhalation and pancuronium or vecuronium. Ketamine infusion was stopped approximately 45 min before operation was completed. Most patients regained consciousness in about 15 to 30 min after nitrous oxide was discontinued. Side effects such as bad dreams were noticed only in 29 patients (10.43%). Perturbed recovery from ketamine anaesthesia might be largely prevented by psychological preoperative preparation and adequate dosage of the benzodiazepine used for premedication.
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PMID:[Ketamine infusion in tympanoplasty]. 225 64

There were different opinions about whether ketamine has an antagonistic effect on electroacupuncture (EA) analgesia. The aim of this paper was to investigate the effect of ketamine on EA. The rats were divided into three groups: 4 mg/kg, 20 mg/kg of ketamine in doses, and normal saline groups. Ketamine was injected peritoneally in dosage of 4 mg/kg and 20 mg/kg respectively. Tail flick latency (TFL) and vocalization threshold (VT) were taken as the indices of pain responses. Changqiang and Yaoshu acupoints were selected for electroacupuncture. It was observed that the analgesia effects of EA were attenuated after injection of ketamine either in 4 mg/kg group of 20 mg/kg group. The results indicate that 4 mg/kg or 20 mg/kg ketamine in doses has an antagonistic effect on EA analgesia, suggesting that attention should be paid to the dosage when ketamine is used for EA analgesia.
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PMID:[Effect of ketamine on acupuncture analgesia]. 251 6

In nearly 25 years of clinical experience, the benefits and limitations of ketamine analgesia and anaesthesia have generally been well-defined. The extensive review of White et al. and the cardiovascular review of Reves et al. are broad in their scope and have advanced the understanding of dissociative anaesthesia. Nevertheless, recent research continues to illuminate different aspects of ketamine pharmacology, and suggests new clinical uses for this drug. The identification of the N-methylaspartate receptor gives further support to the concept that ketamine's analgesic and anaesthetic effects are mediated by separate mechanisms. The stereospecific binding of (+)ketamine to opiate receptors in vitro, more rapid emergence from anaesthesia, and the lower incidence of emergence sequelae, make (+)ketamine a promising drug for future research. Clinical applications of ketamine that have emerged recently, and are likely to increase in the future, are the use of oral, rectal, and intranasal preparations for the purposes of analgesia, sedation, and anaesthetic induction. Ketamine is now considered a reasonable option for anaesthetic induction in the hypotensive preterm neonate. The initial experience with epidural and intrathecal ketamine administration has not been very promising but the data are only preliminary in this area. The use of ketamine in military and catastrophic settings is likely to become more common. The clinical availability of midazolam will complement ketamine anaesthesia in several ways. This rapidly metabolized benzodiazepine reduces ketamine's cardiovascular stimulation and emergence phenomena, and does not have active metabolites. It is dispensed in an aqueous medium, which is usually non-irritating on intravenous injection, unlike diazepam. The combination of ketamine and midazolam is expected to achieve high patient acceptance, which never occurred with ketamine as a sole agent. Finally, it is necessary to point out the potential for abuse of ketamine. While ketamine is not a controlled substance (in the United States), the prudent physician should take appropriate precautions against the unauthorized use of this drug.
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PMID:Ketamine: an update on the first twenty-five years of clinical experience. 265 Aug 98

A series consisting of 32 women undergoing total abdominal hysterectomy received a standard narcotic-free anaesthetic. For the first 24 h postoperatively, eight were given the standard regimen of intramuscular morphine sulphate whilst the other three groups received continuous subcutaneous infusions of either morphine sulphate, ketamine hydrochloride or the two drugs combined. The amount of time they were pain free, the incidence of sleep and nausea, together with cardiovascular and respiratory changes were recorded. All three subcutaneous regimens produced significantly more pain-free readings than intramuscular morphine, but ketamine resulted in higher respiratory rates and less sleepiness. No patient reported psychomimetic side effects, but ketamine on its own produced feelings of malaise in three patients on the second postoperative day. Subcutaneous infusions provide better postoperative analgesia than intermittent intramuscular morphine. Ketamine on its own cannot be advocated, but combined with morphine it allows a single infusion rate to be used for all patients, decreasing the need for nursing and medical involvement.
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PMID:Subcutaneous ketamine analgesia: postoperative analgesia using subcutaneous infusions of ketamine and morphine. 277 59

Ketamine was the normal anaesthetic drug for carrying out the baths of severely burnt patients. It was compared with propofol in a study of 50 patients (greater than 50 UBS) randomly assigned to two groups: 2.5 mg . kg-1 propofol and 2 mg . kg-1 ketamine. The speed of induction was the same for both groups, surgery beginning within the same time intervals. In the propofol group, however, apnoea was seen more often and lasted longer (p less than 0.05) than in the ketamine group. The times between repeat injections were short (about 5 min) and constant with propofol, whereas they were larger and irregular with ketamine; this was due to the shorter distribution half-life and lack of accumulation of propofol. During anaesthesia with propofol, haemodynamic parameters remained steady after an initial period of cardiovascular depression. Respiratory rate increased, because of the lack of analgesia. Recovery was very quick, complete and with no bothersome adverse effects in the propofol group. These hypercatabolic patients could therefore be fed early postoperatively; also, there was no deleterious psychological interference in these deeply disturbed patients.
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PMID:[Comparative trial of propofol and ketamine in anesthesia for the baths of severely burnt patients]. 330 50

The newer neuromuscular blocking drugs include vecuronium and atracurium. Vecuronium is a competitive neuromuscular blocking drug with a steroid nucleus. A dose of 0.1 mg/kg has an onset time of 2 minutes and provides surgical paralysis for 20 minutes. Recovery to 90% twitch height occurs in 40 to 50 minutes. Vecuronium has few adverse effects and its use is associated with cardiovascular stability. Atracurium is a competitive neuromuscular blocking drug which undergoes Hofmann degradation and ester hydrolysis in plasma. A dose of 0.6 mg/kg has an onset time of around 2 minutes and provides surgical paralysis for 20 to 30 minutes. Recovery to 90% twitch height occurs in 60 to 80 minutes. Histamine release, usually only localised, has been reported in association with the use of atracurium. The organ-independent metabolism of atracurium allows its use in standard dosage in patients with renal or hepatic disease. Edrophonium, although not a new drug, has recently been re-evaluated for reversal of neuromuscular blockade. In a dose of 0.5 mg/kg it has been shown to be as effective as neostigmine at reversing neuromuscular blockade after recovery has started (greater than 25% twitch height recovery). However, if blockade is profound (less than 10% recovery), edrophonium is less effective. Among the newer intravenous anaesthetics are propofol (disoprofol) and midazolam. In a dose of 1.5 to 2.5 mg/kg, propofol produces sleep rapidly with a prompt recovery in 4 to 6 minutes. Induction of anaesthesia may be associated with a transient apnoea and a fall in systolic pressure. The rapid recovery has led to its use for maintenance of anaesthesia. Midazolam is a water-soluble benzodiazepine which has been used as an anaesthetic agent. The dose needed to induce sleep varies widely (0.15 to 0.5 mg/kg); onset is slow (1.5 to 5 minutes), and recovery may be prolonged. Midazolam is also used in lower doses as a sedative. Ketamine, an intravenous induction agent, has recently been used intrathecally and extradurally to provide analgesia.
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PMID:New intravenous anaesthetics and neuromuscular blocking drugs. A review of their properties and clinical use. 330 13

Ketamine 4 micrograms/kg/minute produced pain relief similar to that from morphine 33 micrograms/minute in a double-blind study that compared analgesia from constant-rate intravenous infusions of the two drugs in 60 patients. The analgesic efficacy of the infusions, as assessed by pain scores and the requirement for supplementary self-administered morphine, was poor. Ventilatory depression, the most significant side effect, occurred only in patients who received morphine infusion. The low dose ketamine infusion did not provide clinically useful analgesia even though adequate plasma concentrations were achieved.
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PMID:Analgesia from morphine and ketamine. A comparison of infusions of morphine and ketamine for postoperative analgesia. 331 43


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