Ketamine In Concentrations Research Articles

Compatibility of intravenous acetaminophen with morphine, fentanyl and ketamine in acute pediatric pain setting.

Intravenous acetaminophen and opioid analgesics are routinely given concurrently to children after major surgery, where intravenous access can be limited. There is limited information about the compatibility of acetaminophen with opioid analgesics and ketamine in concentrations commonly used in pediatric setting. We aimed to determine the physical and chemical compatibility in mixtures of intravenous acetaminophen 10mg/mL with morphine (0.025, 0.05, 0.1, 0.2, 1, and 2mg/ml), fentanyl (0.5, 0.75, 1, 1.5, 2, and 5mcg/ml) and ketamine (0.01, 0.1, 0.5, 1, 1.5, and 3mg/ml). Acetaminophen was mixed with all 18 solutions and was examined at time 0, 15, 30, and 60 min. In Phase one of the study, we used a colorimetric method to assess preliminary feasibility and acetaminophen recovery. In Phase two study, we used high-performance liquid chromatography to evaluate the recovery of all components of the mixtures. All solutions tested, for both acetaminophen and the three analgesics, had more than 90% of the drug recovery, up to 60 min after mixing. Our data demonstrated the stability of acetaminophen, in combination with fentanyl, morphine, and ketamine at clinical concentrations used in acute pediatric pain setting.

Intravitreal ketamine promotes neuroprotection in rat eyes after experimental ischemia

Retinal ischemia, one of the most common cause of visual loss, is associated with blood flow inadequacy and subsequent tissue injury. In this setting, some treatments that can counteract glutamate increase, arouse interest in ischemic pathogenesis. Ketamine, a potent N-methyl-d-aspartate (NMDA) receptor antagonist, provides a neuroprotective pathway via decreasing the excitotoxicity triggered by excess glutamatergic. Thus, the goal of this study was to evaluate the safety of intravitreal use of ketamine and their potential protective effects on retinal cells in retinal ischemia/reperfusion model. Initially, ketamine toxicity was evaluated by cytotoxicity assay and Hen's egg chorioallantoic membrane (HET-CAM) method. Afterward, some ketamine concentrations were tested in rat's eyes to verify the safety of the intravitreal use. To investigate the neuroprotective effect on retinal, a single intravitreal injection of ketamine in concentrations of 0.059 mmol.L−1 and 0.118 mmol.L−1 was performed one day before the retinal injury by ischemia/reperfusion model. After 7 and 15 days, the retina activity was evaluated by electroretinogram (ERG) records and, lastly, by morphological analyzes. Cytotoxicity assay reveals that the maximum ketamine concentration that could reach retinal pigmented epithelium cells is 0.353 mmol.L−1. HET-CAM assay showed that concentrations above 0.237 mmol.L−1 are irritants to the eye. Thus, Ketamine in concentrations of 0.0237 mmol.L−1, 0.118 mmol.L-1, and 0.059 mmol.L-1 were selected for in vivo toxicity test. ERG records reveal a tendency of b-wave amplitude to decrease as the luminous intensity increased, in the group receiving ketamine at 0.237 mmol.L−1. Therefore, ketamine in concentrations at 0.059 mmol.L−1 and 0.118 mmol.L-1 were chosen for the following tests. In the ischemia retinal degeneration model, pretreatment with ketamine was capable to promote a recovery of retinal electrophysiological function minimizing the ischemic effects. In histological analysis, the groups that received intravitreal ketamine showed a number of retinal cells significantly higher than the vehicle group. In TUNEL assay a reduction on TUNEL-positive cells was observed in all the layers for both concentrations which allow to affirm that ketamine contributes to reducing cell death in the retina. Transmission electron microscopy (TEM) reaffirms this finding. Ketamine intravitreal pretreatment showed reduced ultrastructural changes. Our findings demonstrate that ketamine is safe for intravitreal use in doses up to 0.118 mmol.L−1. They seem to be particularly efficient to protect the retina from ischemic injury.

Electrophysiological demonstration of N-methyl- d-aspartate receptors at the afferent synapse of catfish electroreceptor organs

An excitatory amino acid, most probably l-glutamate, acts as a neurotransmitter at the receptor cell–afferent fibre synapses in the ampullary electroreceptor organs of the freshwater catfish Ictalurus nebulosus. In the present study, we have used an electrophysiological approach to investigate the presence of N-methyl- d-aspartate receptors at this level. N-Methyl- d-aspartate, dissolved in an Mg 2+-containing (normal) solution, had no effect on afferent activity, not even at 5 mM. However, addition of 5 mM N-methyl- d-aspartate to an Mg 2+-free solution evoked an enduring increase in firing rate. The application of N-methyl- d-aspartate combined with electrical sine wave stimulation produced a firing increase in the primary afferents, even in the presence of Mg 2+ (1.5 mM). Glycine (0.01–0.001 mM) significantly potentiated the N-methyl- d-aspartate responses. Addition of antagonists of the actions of N-methyl- d-aspartate, 7-chlorokynurenic acid, dl-2-amino-5-phosphonovaleric acid and ketamine in concentrations of 0.5–2.0 mM led to a decrease in resting and stimulus-evoked activity. 7-Chlorokynurenic acid also blocked the responses to application of N-methyl- d-aspartate. The glycine agonist d-serine (0.01 mM) prevented the 7-chlorokynurenic inhibitory effect. These results suggest the involvement of N-methyl- d-aspartate receptors in mediating the actions of l-glutamate at the afferent synapses of the electroreceptor organs of the catfish.

Age-dependent differences in the anticonvulsant effects of 2-amino-7-phosphono-heptanoic acid or ketamine infusions into the substantia nigra of rats.

Infusions of 2-amino-7-phosphonoheptanoic acid (AP7) or ketamine into the substantia nigra pars reticulata (SNPR) of adult rats increase the latency of onset to seizures induced by the convulsant ether flurothyl. Nigral infusions of AP7 or ketamine in concentrations up to 10 times greater than the adult dose are ineffective in 16-day-old rats. These results suggest that differences in seizure susceptibility between adult and immature rats may be related to differences in excitatory amino acid neurotransmission in the SN.

Direct Effects of Ketamine on Isolated Canine Cerebral and Mesenteric Arteries

The effects of ketamine on isolated canine cerebral (middle cerebral and basilar) and mesenteric arteries were studied. In arteries contracted with KCl, ketamine in concentrations above 5 X 10(-6)M (cerebral arteries) or 2 X 10(-5)M (mesenteric arteries) caused significant relaxation in a dose-dependent manner. The relaxation was not significantly influenced by aminophylline, aspirin, atropine, or propranolol. In concentrations above 5 X 10(-6)M ketamine attenuated the contractile response to high concentrations of KCl in the middle cerebral arteries, and in concentrations above 5 X 10(-5)M it attenuated the contractile response to high concentrations of KCl in the basilar and mesenteric arteries. The attenuation was greater in cerebral than in mesenteric arteries. The contractile response of cerebral arteries to high concentrations of serotonin was also attenuated by ketamine in concentrations above 5 X 10(-5)M. Ketamine attenuated KCl-induced contraction of cerebral arteries more than it attenuated serotonin-induced contraction. When basilar arteries were exposed to Ca2+-free media and depolarized by KCl, the addition of Ca2+ caused biphasic (transient and sustained) contractions, while in the mesenteric arteries the addition of Ca2+ produced sustained contractions. Ketamine at 5 X 10(-5) and 5 X 10(-4)M attenuated both transient and sustained contractions in basilar arteries, while in mesenteric arteries 5 X 10(-4)M ketamine attenuated only sustained contractions. In both instances, ketamine-induced attenuation was partially reversed by excess Ca2+. It is concluded that ketamine has a direct dilating effect on both cerebral and mesenteric arteries, but the effect is more pronounced in cerebral than in mesenteric arteries. The direct action of ketamine on those arteries may be due in part to interference with transmembrane influx of Ca2+.

Ketamine: effects on the mechanical properties of the frog sartorius muscle.

Isolated frog sartorius muscles were exposed to ketamine in concentrations up to 15 X 10(-5) M and the mechanical response to directly and indirectly stimulated muscles was studied. The effect on the directly elicited action potential was also investigated. The amplitude of the indirectly elicited twitches was decreased in a dose-dependent manner with a 50% decrease in twitch amplitude, at a ketamine concentration of 7.3 X 10(-5) M. The twitch amplitude was not affected by ketamine during direct stimulation of the muscle. However, direct tetanic stimulation of the muscle (80 Hz, 200 ms) revealed a decrease in the tetanic force of 20% during exposure to 7.3 X 10(-5) M ketamine. This decrease in tetanic force can be explained on the basis of effects on the sarcoplasmic reticulum, and/or the effects of ketamine on the directly elicited action potentials (decrease in amplitude and increase in duration) seen in these experiments. At concentrations of ketamine below about 4 X 10(-5) M, small effects were seen in this nerve-muscle preparation. If the effects on the frog muscle are similar to mammalian striated muscle, clinical concentrations of ketamine would have very small effects on the nerve-muscle system.

Ketamine Acts on the Peripheral Sympathetic Nervous System of Guinea Pigs

The effects of ketamine on the peripheral sympathetic nervous system were studied in vitro by observing the amplitude of the nerve-mediated contraction of the vasa deferentia isolated from guinea pigs. Ketamine dissolved in the perfusate of an organ bath was applied to the tissues for 30 minutes and then washed out with a perfusate lacking ketamine for 90 minutes. Ketamine in concentrations of 10(-8) and 10(-7) g/ml had no effect on contraction induced by hypogastric nerve (preganglionic) stimulation. At 10(-6) g/ml, the drug had no significant effect during application but was associated with increased contractions during washout. At 10(-5) and 10(-4) g/ml, the drug showed a dose-related depression during application and an increase in contractions during washout after a 10(-5) g/ml. Ketamine, 10(-5) g/ml, increased contraction following transmural (postganglionic) stimulation and had a depressant effect at a concentration of 10(-4) g/ml. It is concluded (1) that ketamine has dual effects on the nerve-mediated contraction of the vasa defentia and (2) that cardiovascular responses to ketamine include peripheral effects of ketamine on sympathetic ganglia.