Comparison of oral chloral hydrate with intramuscular ketamine, meperidine, and promethazine for pediatric sedation--preliminary report.
(9/1131)
Fifteen consecutive pediatric patients ranging from 3 to 5 years old were selected to receive one of three sedative/hypnotic techniques. Group 1 received oral chloral hydrate 50 mg/kg, and groups 2 and 3 received intramuscular ketamine 2 mg/kg and 3 mg/kg, respectively. In addition to ketamine, patients in groups 2 and 3 received transmucosal intramuscular injections of meperidine and promethazine into the masseter muscle. Sedation for the satisfactory completion of restorative dentistry was obtained for over 40 min on average in the chloral hydrate group, but completion of dental surgery longer than 40 min was achieved in groups 2 and 3 only by intravenous supplements of ketamine. (+info)
Oral ketamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for cancer pain management.
(10/1131)
BACKGROUND: Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner. This study was designed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine in cancer pain therapy. METHODS: After institutional approval and informed patient consent were obtained, 60 patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and any adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing "the worst possible pain" was introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime. The morphine regimen was adjusted individually to a maximal oral dose of 80-90 mg/day to keep the visual analog scale score less than 4. When patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4. RESULTS: The groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced were similar among the groups. The daily consumption of oral morphine was as follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20: CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG (P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and DG groups reported somnolence, but patients in the NG and KG groups did not. CONCLUSIONS: Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management. (+info)
The effect of naloxone on ketamine-induced effects on hyperalgesia and ketamine-induced side effects in humans.
(11/1131)
BACKGROUND: The (NMDA) receptor plays a significant role in wind-up and spinal hypersensitivity and is involved in the occurrence of secondary hyperalgesia. Ketamine is an NMDA-receptor antagonist and has proven effective in alleviating secondary hyperalgesia in humans. Although it is disputed, the actions of ketamine have been ascribed not only to NMDA receptor antagonism, but also to opioid receptor agonism. A study therefore was designed in which the abolishment of a previously demonstrated effect of ketamine on secondary hyperalgesia was sought by pretreatment with naloxone. METHODS: Twenty-five volunteers were subjected to three treatment regimens. A standardized first-degree burn injury was induced. On appearance of primary and secondary hyperalgesia, one of the following infusion schemes was applied in a randomized, double-blind, cross-over fashion: (1) infusion of naloxone (0.8 mg/15 min followed by 0.4 mg/h), succeeded by infusion of ketamine (0.3 mg x kg(-1) x 15 min(-1) followed by 0.3 mg x kg(-1) x h(-1)); (2) infusion of placebo, succeeded by infusion of ketamine (0.3 mg x kg(-1) x 15 min(-1) followed by 0.3 mg x kg(-1) x h(-1)); and (3) infusion of placebo, succeeded by infusion of placebo. Heat-pain detection thresholds, magnitude of secondary hyperalgesia around the burn injury, and side effects were determined. RESULTS: Ketamine reduced secondary hyperalgesia. Naloxone did not affect the action of ketamine. The magnitudes of side effects were equal if the subjects received ketamine, regardless of preceding infusion of naloxone. CONCLUSIONS: In this experimental setting, opioid receptor blockade does not inhibit ketamine-induced reductions of secondary hyperalgesia. (+info)
SI neuron response variability is stimulus tuned and NMDA receptor dependent.
(12/1131)
Skin brushing stimuli were used to evoke spike discharge activity in single skin mechanoreceptive afferents (sMRAs) and anterior parietal cortical (SI) neurons of anesthetized monkeys (Macaca fascicularis). In the initial experiments 10-50 presentations of each of 8 different stimulus velocities were delivered to the linear skin path from which maximal spike discharge activity could be evoked. Mean rate of spike firing evoked by each velocity (MFR) was computed for the time period during which spike discharge activity exceeded background, and an across-presentations estimate of mean firing rate (MFR) was generated for each velocity. The magnitude of the trial-by-trial variation in the response (estimated as CV; where CV = standard deviation in MFR/MFR) was determined for each unit at each velocity. MFR for both sMRAs and SI neurons (MFRsMRA and MFRSI, respectively) increased monotonically with velocity over the range 1-100 cm/s. At all velocities the average estimate of intertrial response variation for SI neurons (CVSI) was substantially larger than the corresponding average for sMRAs (CVsMRA). Whereas CVsMRA increased monotonically over the range 1-100 cm/s, CVSI decreased progressively with velocity over the range 1-10 cm/s, and then increased with velocity over the range 10-100 cm/s. The position of the skin brushing stimulus in the receptive field (RF) was varied in the second series of experiments. It was found that the magnitude of CVSI varied systematically with stimulus position in the RF: that is, CVSI was lowest for a particular velocity and direction of stimulus motion when the skin brushing stimulus traversed the RF center, and CVSI increased progressively as the distance between the stimulus path and the RF center increased. In the third series of experiments, either phencylidine (PCP; 100-500 microg/kg) or ketamine (KET; 0.5-7.5 mg/kg) was administered intravenously (iv) to assess the effect of block of N-methyl-D-aspartate (NMDA) receptors on SI neuron intertrial response variation. The effects of PCP on both CVSI and MFRSI were transient, typically with full recovery occurring in 1-2 h after drug injection. The effects of KET on CVSI and MFRSI were similar to those of PCP, but were shorter in duration (15-30 min). PCP and KET administration consistently was accompanied by a reduction of CVSI. The magnitude of the reduction of CVSI by PCP or KET was associated with the magnitude of CVSI before drug administration: that is, the larger the predrug CVSI, the larger the reduction in CVSI caused by PCP or KET. PCP and KET exerted variable effects on SI neuron mean firing rate that could differ greatly from one neuron to the next. The results are interpreted to indicate that SI neuron intertrial response variation is 1) stimulus tuned (intertrial response variation is lowest when the skin stimulus moves at 10 cm/s and traverses the neuron's RF center) and 2) NMDA receptor dependent (intertrial response variation is least when NMDA receptor activity contributes minimally to the response, and increases as the contribution of NMDA receptors to the response increases). (+info)
Excitatory actions of NMDA receptor antagonists in rat entorhinal cortex and cultured entorhinal cortical neurons.
(13/1131)
We have characterized excitatory effects of non-competitive NMDA receptor antagonists MK-801, PCP, and ketamine in the rat entorhinal cortex and in cultured primary entorhinal cortical neurons using expression of immediate early gene c-fos as an indicator. NMDA receptor antagonists produced a strong and dose-dependent increase in c-fos mRNA and protein expression confined to neurons in the layer III of the caudal entorhinal cortex. Induction of c-fos mRNA is delayed and it is inhibited by antipsychotic drugs. Cultured entorhinal neurons are killed by high doses of MK-801 and PCP but c-fos expression is not induced in these neurons indicating that this in vitro model does not fully replicate the in vivo effects of PCP-like drugs in the entorhinal cortex. Excitatory effects of the NMDA receptor antagonists may be connected with the psychotropic side effects of these drugs and might become a useful model system to investigate neurobiology of psychosis. (+info)
Midazolam/ketamine sedative combination compared with fentanyl/propofol/isoflurane anaesthesia for oocyte retrieval.
(14/1131)
Assisted reproduction may be associated with repeated occasions of surgical intervention. Propofol, which is frequently used for induction of anaesthesia in such procedures, has been suspected of damaging oocytes. We compared in a randomized prospective design the use of general anaesthesia with fentanyl 0.017 mg/kg, propofol 2.5 mg/kg and isoflurane to that of sedation with midazolam 0.06 mg/kg and ketamine 0.75 mg/kg for transvaginal oocyte retrieval in 50 patients with no premedication. Overall, patient satisfaction was not different between the groups. Sedated patients were more arousable than anaesthetized patients during the procedure and experienced less postoperative abdominal pain at 30 min. Despite some movement in response to pain, oocyte retrieval was conveniently feasible in all sedated patients, of which none required a switch to general anaesthesia. A comparable number of oocytes was retrieved per cycle, 10.8 (+/-7.8) versus 9.6 (+/-10.9) with sedation and anaesthesia respectively. No patient recalled any pain sensation during the procedure. The rate of embryo transfers and pregnancies were not different between the two groups. We conclude that the sedative combination of midazolam and ketamine for oocyte retrieval may serve as an alternative for general anaesthesia. (+info)
Effects of diazepam and ketamine administered individually or in combination on regional rates of glucose utilization in rat brain.
(15/1131)
The effects of diazepam, which acts at GABAA receptors to enhance the effects of GABA, and ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, on local rates of cerebral glucose utilization (ICMRglc) were examined in unrestrained rats. Four groups were studied: vehicle-injected controls; and ketamine-treated, diazepam-treated and combined ketamine- and diazepam-treated animals. Ketamine alone produced a heterogeneous pattern of changes in ICMRglc (e.g. significant increases in the corpus callosum, olfactory tubercle and the entire Papez circuit, in addition to other limbic areas, and significant decreases in lateral habenula and some components of the auditory system). Diazepam alone statistically significantly decreased ICMRglc in the brain as a whole and in most areas of the cerebral cortex, thalamus and limbic system. The most remarkable effects of the two drugs administered together on ICMRglc occurred in the limbic system where the dramatic increases observed with ketamine alone were prevented by treatment with diazepam. (+info)
Stereospecific effects of ketamine on dopamine efflux and uptake in the rat nucleus accumbens.
(16/1131)
In addition to being a general anaesthetic, ketamine is a recognized drug of abuse. Many, if not all, drugs of abuse have been shown to increase dopamine efflux in the nucleus accumbens (NAc). As ketamine is optically active, we examined if its actions on dopamine efflux in the NAc were stereoselective. Slices of rat NAc were superfused with artificial CSF at 32 degrees C. Dopamine efflux was evoked by electrical stimulation (1 or 20 pulses, 100 Hz) and measured using fast cyclic voltammetry. (+/-)-Ketamine 100 mumol litre-1 increased dopamine efflux (to mean 174 (SEM 17)% of control, P < 0.05) and slowed dopamine uptake half-time (T1/2) to 164 (17)% of control, as did (+)-ketamine 100 mumol litre-1 (efflux 236 (16)% (P < 0.001); uptake T1/2 177 (25)% (P < 0.05)). The (-)-isomer was inactive. The effect of (+)-ketamine on dopamine efflux did not correlate with its action on dopamine uptake. (+)-Ketamine increased dopamine efflux on single pulse stimulation but to a lesser extent than on 20 pulse trains (P < 0.05). (+)-Ketamine was unable to block the inhibitory effect of quinpirole on single pulse dopamine efflux. Neither MK 801 10 mumol litre-1 nor metoclopramide 1 mumol litre-1 had any effect on dopamine release after short train stimuli (20 pulses, 100 Hz). We conclude that the (+)-isomer is the active form of ketamine and increases NAc dopamine efflux not by block of dopamine uptake; autoreceptors or NMDA receptors, but by mobilization of the dopamine storage pool to releasable sites. (+info)