Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy.

PubMed

Peltoniemi, Marko A; Hagelberg, Nora M; Olkkola, Klaus T; Saari, Teijo I

2016-09-01

Ketamine is a phencyclidine derivative, which functions primarily as an antagonist of the N-methyl-D-aspartate receptor. It has no affinity for gamma-aminobutyric acid receptors in the central nervous system. Ketamine shows a chiral structure consisting of two optical isomers. It undergoes oxidative metabolism, mainly to norketamine by cytochrome P450 (CYP) 3A and CYP2B6 enzymes. The use of S-ketamine is increasing worldwide, since the S(+)-enantiomer has been postulated to be a four times more potent anesthetic and analgesic than the R(-)-enantiomer and approximately two times more effective than the racemic mixture of ketamine. Because of extensive first-pass metabolism, oral bioavailability is poor and ketamine is vulnerable to pharmacokinetic drug interactions. Sublingual and nasal formulations of ketamine are being developed, and especially nasal administration produces rapid maximum plasma ketamine concentrations with relatively high bioavailability. Ketamine produces hemodynamically stable anesthesia via central sympathetic stimulation without affecting respiratory function. Animal studies have shown that ketamine has neuroprotective properties, and there is no evidence of elevated intracranial pressure after ketamine dosing in humans. Low-dose perioperative ketamine may reduce opioid consumption and chronic postsurgical pain after specific surgical procedures. However, long-term analgesic effects of ketamine in chronic pain patients have not been demonstrated. Besides analgesic properties, ketamine has rapid-acting antidepressant effects, which may be useful in treating therapy-resistant depressive patients. Well-known psychotomimetic and cognitive adverse effects restrict the clinical usefulness of ketamine, even though fewer psychomimetic adverse effects have been reported with S-ketamine in comparison with the racemate. Safety issues in long-term use are yet to be resolved.

Some considerations of the tolerability of ketamine for ECT anesthesia: a case series and review of the literature.

PubMed

Rasmussen, Keith G; Ritter, Matthew J

2014-12-01

Most anesthetic agents used for electroconvulsive therapy (ECT) have few intrinsic adverse effects. Ketamine, however, is well known to be associated with a variety of adverse effects including nausea, dizziness, and psychotomimetic phenomena. Over the past several decades, there have been numerous reports on the use of ketamine for ECT anesthesia, with varied assessments on how prominent these adverse effects are in the ECT situation. Ketamine has received a resurgence of interest as an ECT anesthetic of late owing to its established independent antidepressant effects and to theoretical reasons why it might lessen the cognitive adverse effects of ECT. In this case series, the author reviews the experience with 14 patients who had undergone ECT who were switched to ketamine as anesthetic from methohexital at the preference of the treating anesthesiologist. All 14 patients spontaneously reported a strong preference not to be given ketamine again due to bothersome adverse effects. The latter consisted of either vestibular-type symptoms (nausea/vomiting, dizziness, and vertigo) or psychotomimetic effects (dissociative phenomena). It is concluded that ketamine is not free of adverse effects when used as an ECT anesthetic. Electroconvulsive therapy clinicians should be vigilant about assessing for these effects when ketamine is used, and consideration should be given to using a benzodiazepine such as diazepam or midazolam at seizure termination when ketamine anesthesia is used to prevent bothersome adverse effects seen upon awakening.

Regional cerebral energy metabolism during intravenous anesthesia with etomidate, ketamine or thiopental

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, D.W.

1987-01-01

Regional brain glucose utilization (rCMRglc) was measured in rats during steady-state levels of intravenous anesthesia to determine if alterations in brain function due to anesthesia could provide information on the mechanisms of anesthesia. Intravenous anesthetics from three different chemical classes were studied: etomidate, ketamine and thiopental. All rCMRglc experiments were conducted in freely moving rats in isolation chambers, with the use of (6-/sup 14/C) glucose and guantitative autoradiography. Etomidate caused a rostral-to-caudal gradient of depression of rCMRglc. The four doses of etomidate did not differ in their effects on energy metabolism. Sub-anesthetic (5 mg kg/sup -1/) and anesthetic (30 mgmore » kg /sup -1/) doses of ketamine produced markedly different patterns of behavior. Brain energy metabolism during the sub-anesthetic dose was stimulated in most regions, while the anesthetic dose selectively stimulated the hippocampus, leaving most brain regions unaffected. Thiopental produced a dose-dependent reduction of rCMRglc in all gray matter regions. No brain region was selectively affected. Comparison of the drug-specific alterations of cerebral energy metabolism suggests these anesthetics do not act through a common mechanism. The hypothesis that each acts by binding to specific cell membrane receptors is consistent with these observations.« less

Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial.

PubMed

Salehi, B; Mohammadbeigi, A; Kamali, A R; Taheri-Nejad, M R; Moshiri, I

2015-01-01

Electroconvulsive therapy (ECT) is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD). In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2 nd , 4 th , 6 th , and 8 th ECT. Depression was assessed by Hamilton depression scale. The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain at the injection site, short-term delirium, and long-term delirium were higher in ketamine group (P > 0.05). But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05). The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05). Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD.

The changes of cerebral hemodynamics during ketamine induced anesthesia in a rat model.

PubMed

Bae, Jayyoung; Shin, Teo J; Kim, Seonghyun; Choi, Dong-Hyuk; Cho, Dongrae; Ham, Jinsil; Manca, Marco; Jeong, Seongwook; Lee, Boreom; Kim, Jae G

2018-05-25

Current electroencephalogram (EEG) based-consciousness monitoring technique is vulnerable to specific clinical conditions (eg, epilepsy and dementia). However, hemodynamics is the most fundamental and well-preserved parameter to evaluate, even under severe clinical situations. In this study, we applied near-infrared spectroscopy (NIRS) system to monitor hemodynamic change during ketamine-induced anesthesia to find its correlation with the level of consciousness. Oxy-hemoglobin (OHb) and deoxy-hemoglobin concentration levels were continuously acquired throughout the experiment, and the reflectance ratio between 730 and 850 nm was calculated to quantify the hemodynamic changes. The results showed double peaks of OHb concentration change during ketamine anesthesia, which seems to be closely related to the consciousness state of the rat. This finding suggests the possibility of NIRS based-hemodynamic monitoring as a supplementary parameter for consciousness monitoring, compensating drawbacks of EEG signal based monitoring. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of the cardiopulmonary effects of anesthesia maintained by continuous infusion of romifidine, guaifenesin, and ketamine with anesthesia maintained by inhalation of halothane in horses.

PubMed

McMurphy, Rose M; Young, Lesley E; Marlin, David J; Walsh, Karen

2002-12-01

To compare cardiopulmonary responses during anesthesia maintained with halothane and responses during anesthesia maintained by use of a total intravenous anesthetic (TIVA) regimen in horses. 7 healthy adult horses (1 female, 6 geldings). Each horse was anesthetized twice. Romifidine was administered IV, and anesthesia was induced by IV administration of ketamine. Anesthesia was maintained for 75 minutes by administration of halothane (HA) or IV infusion of romifidine, guaifenesin, and ketamine (TIVA). The order for TIVA or HA was randomized. Cardiopulmonary variables were measured 40, 60, and 75 minutes after the start of HA orTIVA. Systolic, diastolic, and mean carotid arterial pressures, velocity time integral, and peak acceleration of aortic blood flow were greater, and systolic, diastolic, and mean pulmonary arterial pressure were lower at all time points for TIVA than for HA. Pre-ejection period was shorter and ejection time was longer for TIVA than for HA. Heart rate was greater for HA at 60 minutes. Minute ventilation and alveolar ventilation were greater and inspiratory time was longer for TIVA than for HA at 75 minutes. The PaCO2 was higher at 60 and 75 minutes for HA than forTIVA. Horses receiving a constant-rate infusion of romifidine, guaifenesin, and ketamine maintained higher arterial blood pressures than when they were administered HA. There was some indication that left ventricular function may be better during TIVA, but influences of preload and afterload on measured variables could account for some of these differences.

Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial

PubMed Central

Salehi, B.; Mohammadbeigi, A.; Kamali, A. R.; Taheri-Nejad, M. R.; Moshiri, I.

2015-01-01

Background: Electroconvulsive therapy (ECT) is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD). Materials and Methods: In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2nd, 4th, 6th, and 8th ECT. Depression was assessed by Hamilton depression scale. Results: The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain at the injection site, short-term delirium, and long-term delirium were higher in ketamine group (P > 0.05). But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05). The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05). Conclusion: Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD. PMID:26440233

Comparison of the effects of intravenous premedication: Midazolam, Ketamine, and combination of both on reducing anxiety in pediatric patients before general anesthesia

PubMed Central

Sajedi, Parvin; Habibi, Bashir

2015-01-01

Objective: In some medical circumstances, pediatric patients may need premedication for transferring to the operating room. In these situations, using intravenous premedication is preferred. We assessed the efficacy and safety of intravenous midazolam, intravenous ketamine, and combination of both to reduce the anxiety and improve behavior in children undergoing general anesthesia. Methods: In a double-blind randomized clinical trial, 90 pediatric patients aged 6 months to 6 years with American Society of Anesthesiologist grade I or II were enrolled. Before anesthesia, children were randomly divided into three groups to receive intravenous midazolam 0.1 mg/kg, or intravenous ketamine 1 mg/kg, or combination of half doses of both. Behavior types and sedation scores were recorded before premedication, after premedication, before anesthesia, and after anesthesia in the postanesthesia care unit. Anesthesia time, recovery duration, blood pressure, and heart rate were also recorded. For comparing distribution of behavior types and sedation scores among three groups, we used Kruskal–Wallis test, and for comparing mean and standard deviation of blood pressure and heart rates, we used analysis of variance. Findings: After premedication, children's behavior was significantly better in the combination group (P < 0.001). After anesthesia, behavior type was same among three groups (P = 0.421). Sedation scores among three groups were also different after premedication and the combination group was significantly more sedated than the other two groups (P < 0.001). Conclusion: Combination of 0.05 mg/kg of intravenous midazolam and 0.5 mg/kg of intravenous ketamine as premedication produced more deep sedation and more desirable behavior in children compared with each midazolam 0.1 mg/kg or ketamine 1 mg/kg. PMID:26645024

Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol (KMP-TIVA) in horses undergoing surgery

PubMed Central

UMAR, Mohammed Ahmed; FUKUI, Sho; KAWASE, Kodai; ITAMI, Takaharu; YAMASHITA, Kazuto

2014-01-01

Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol drug combination (KMP-TIVA) were determined in 5 Thoroughbred horses undergoing surgery. The horses were anesthetized with intravenous administration (IV) of ketamine (2.5 mg/kg) and midazolam (0.04 mg/kg) following premedication with medetomidne (5 µg/kg, IV) and artificially ventilated. Surgical anesthesia was maintained by controlling propofol infusion rate (initially 0.20 mg/kg/min following an IV loading dose of 0.5 mg/kg) and constant rate infusions of ketamine (1 mg/kg/hr) and medetomidine (1.25 µg/kg/hr). The horses were anesthetized for 175 ± 14 min (range from 160 to 197 min). Propofol infusion rates ranged from 0.13 to 0.17 mg/kg/min, and plasma concentration (Cpl) of propofol ranged from 11.4 to 13.3 µg/ml during surgery. Cardiovascular measurements during surgery remained within clinically acceptable ranges in the horses (heart rate: 33 to 37 beats/min, mean arterial blood pressure: 111 to 119 mmHg, cardiac index: 48 to 53 ml/kg/min, stroke volume: 650 to 800 ml/beat and systemic vascular resistance: 311 to 398 dynes/sec/cm5). The propofol Cpl declined rapidly after the cessation of propofol infusion and was significantly lower at 10 min (4.5 ± 1.5 µg/ml), extubation (4.0 ± 1.2 µg/ml) and standing (2.4 ± 0.9 µg/ml) compared with the Cpl at the end of propofol administration (11.4 ± 2.7 µg/ml). All the horses recovered uneventfully and stood at 74 ± 28 min after the cessation of anesthesia. KMP-TIVA provided satisfactory quality and control of anesthesia with minimum cardiovascular depression in horses undergoing surgery. PMID:25409552

Anesthetic efficacy of ketamine-diazepam, ketamine-xylazine, and ketamine-acepromazine in Caspian Pond turtles (Mauremys caspica).

PubMed

Adel, Milad; Sadegh, Amin Bigham; Arizza, Vincenzo; Abbasi, Hossein; Inguglia, Luigi; Saravi, Hasan Nasrollahzadeh

2017-01-01

The objective of this study was to assess the efficacy of different anesthetic drug combinations on the Caspian Pond turtles ( Mauremys caspica ). Three groups of the Caspian Pond turtles ( n = 6) were anesthetized with three different drug combinations. Initially, a pilot study was conducted to determine the best drug doses for the anesthetization of the turtles, and according to these results, ketamine-diazepam (120 mg/kg ketamine hydrochloride [5%] and 2 mg/kg diazepam [5%]), ketamine-acepromazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg acepromazine [1%]), and ketamine-xylazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg xylazine [2%]) were injected intramuscularly. The onset times of anesthetization and the recovery time were measured. Statistical analysis of the data was performed using one-way analysis of variance followed by t -tests, and P < 0.05 was considered statistically significant. There were statistically significant differences in the mean of the onset times of anesthesia and recovery time among the three drug combinations depending on the treatment used. The onset of anesthesia of the animals treated with the ketamine-diazepam combination was 60% and 42% shorter, for male and female turtles, respectively, compared to that obtained with the ketamine-acepromazine combination and 64% (male turtles) and 50% (female turtles) shorter than that obtained with the ketamine-xylazine combination. Further, the recovery time, in male turtles, was 17% shorter in animals treated with the first drug combination than those treated with the ketamine-acepromazine combination and 37% shorter than those treated with the ketamine-xylazine combination. The recovery time, in female turtles, did not seem to be significantly different among treatments. The study showed that the ketamine-diazepam drug combination is the anesthetic combination with the fastest onset time and shortest recovery time.

[Materno-fetal acid-base equilibrium evaluation in parturients submitted to ketamine anesthesia (author's transl)].

PubMed

Mauad Filho, F; Meirelles, R S

1975-01-01

In the present work ketamine was used as anesthetic during the labor in order to evaluate the effect of this anesthetic on the binominal fetus-mother. Two groups of parturients and their fetuses, were studied: 1) The experimental group, with 22 parturients and their fetuses submitted to ketamine anesthesia during the labord, and 2) The control group, with 20 parturients and their fetuses without any analgesic treatment during the labor. In 20 cases of the experimental group the anesthetic was injected during the delivery labor and the other two just before it. It were evaluated in the mother's blood the biochemical parameters of the acid-base balance and others collateral effects of the anesthesia; on the fetus's side the same parameters also and the cardiac frequency. The newborn were evaluated by Apgar Score during the first and fifth minutes of life. The incidence of the spontaneous delivery in the experimental group, was 78%; in 22% of these patients the forceps of relief was used. In 22 cases in which Ketamine was applied it were observed, the following events: elevation of the blood pressure (50%), perineum rigidness (18%), dreams and or hallucinations (18%), increase of the cardiac frequency (9%), apneia (4%) and nausea (4%). It was also observed an increase of uterine tonus an abolishment of abdominal press during the delivery labor, studied through the uterine electromyography register. It was noted after the Ketamine application a fall in the pH of the maternal peripherical venous blood, fetal skull blood and the pH of the blood of the umbilical vein. 22% of the newborns, from the experimental group, presented a depression in the first minute of life (Apgar less than or equals to 6). The pCO2 values in the blood of the umbilical artery were higher in the experimental group than in the control one.

Effects of ketamine, dexmedetomidine and propofol anesthesia on emotional memory consolidation in rats: Consequences for the development of post-traumatic stress disorder.

PubMed

Morena, Maria; Berardi, Andrea; Peloso, Andrea; Valeri, Daniela; Palmery, Maura; Trezza, Viviana; Schelling, Gustav; Campolongo, Patrizia

2017-06-30

Intensive Care Unit (ICU) or emergency care patients, exposed to traumatic events, are at increased risk for Post-Traumatic Stress Disorder (PTSD) development. Commonly used sedative/anesthetic agents can interfere with the mechanisms of memory formation, exacerbating or attenuating the memory for the traumatic event, and subsequently promote or reduce the risk of PTSD development. Here, we evaluated the effects of ketamine, dexmedetomidine and propofol on fear memory consolidation and subsequent cognitive and emotional alterations related to traumatic stress exposure. Immediately following an inhibitory avoidance training, rats were intraperitoneally injected with ketamine (100-125mg/kg), dexmedetomidine (0.3-0.4mg/kg) or their vehicle and tested for 48h memory retention. Furthermore, the effects of ketamine (125mg/kg), dexmedetomidine (0.4mg/kg), propofol (300mg/kg) or their vehicle on long-term memory and social interaction were evaluated two weeks after drug injection in a rat PTSD model. Ketamine anesthesia increased memory retention without altering the traumatic memory strength in the PTSD model. However, ketamine induced a long-term reduction of social behavior. Conversely, dexmedetomidine markedly impaired memory retention, without affecting long-lasting cognitive or emotional behaviors in the PTSD model. We have previously shown that propofol anesthesia enhanced 48h memory retention. Here, we found that propofol induced an enduring traumatic memory enhancement and anxiogenic effects in the PTSD model. These findings provide new evidence for clinical studies showing that the use of ketamine or propofol anesthesia in emergency care and ICU might be more likely to promote the development of PTSD, while dexmedetomidine might have prophylactic effects. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparison of romifidine and xylazine when used with diazepam/ketamine for short duration anesthesia in the horse.

PubMed Central

Kerr, C L; McDonell, W N; Young, S S

1996-01-01

The purpose of this study was to compare and evaluate sedation with intravenous xylazine (1.1 mg/kg bodyweight [BW]) versus intravenous romifidine (100 micrograms/kg BW) followed by induction of anesthesia with intravenous diazepam (0.04 mg/kg BW) and ketamine (2.2 mg/kg BW). Twelve healthy horses were used in a blinded, randomized, cross-over design. Heart rate, presence of 2nd degree atrioventricular heart blocks (2 degrees AVB), respiratory rate, arterial blood pressures, blood gases, packed cell volume, total serum proteins, and duration of anesthesia and recumbency were recorded. Induction and recovery quality was evaluated using a 0 to 4 score. Response to stimulation with noise, pressure, and cutaneous electrical stimulation was assessed at 5 minute intervals during recumbency to evaluate the depth of anesthesia. Heart rate was lower and 2 degrees AVB more frequent in the romifidine group, while blood pressure was lower in the xylazine group. Duration of anesthesia was longer in the romifidine group (mean 20.8, s mean 2.3 min) versus the xylazine group (mean 15.8, s mean 1.6 min), while induction and recovery were excellent in both groups. Respiratory rates, blood gas values, packed cell volumes, and total protein levels did not differ between groups. The results indicate that romifidine premedication followed by diazepam and ketamine is a very satisfactory regime for short duration intravenous anesthesia in horses. PMID:8896874

Long-lasting behavioral effects in neonatal mice with multiple exposures to ketamine-xylazine anesthesia

PubMed Central

Huang, Lianyan; Hayes, Scott; Yang, Guang

2016-01-01

Anesthetic agents are often administered in the neonatal period, a time of rapid brain development and synaptogenesis. Mounting evidence suggests that anesthetics can disrupt neurocognitive development, particularly in cases of multiple or prolonged anesthetic exposure. Previous studies have shown that administering multiple doses of ketamine-xylazine (KX) anesthesia to neonatal mice can induce long-term changes to synaptic plasticity in the cortex, but the effect on neurocognitive function remains unclear. In this study, we exposed neonatal mice to single dose and multiple doses of KX anesthesia in the neonatal period (postnatal days 7, 9, 11), and conducted a series of behavioral tests in young adulthood (1 month of age). Mice receiving multiple doses of KX anesthesia showed deficits in novel object recognition, sociability, preference for social novelty and contextual fear response, but no effect on auditory-cued fear response. Single dose of KX anesthesia had no effect on these behaviors except for contextual fear response. We also observed that multiple exposures to KX anesthesia were associated with decreased CaMKII phosphorylation, which is known to play a role in synapse development and long-term potentiation, likely contributing to learning impairment. PMID:27622724

Electroconvulsive therapy with S-ketamine anesthesia for catatonia in coexisting depression and dementia.

PubMed

Litvan, Zsuzsa; Bauer, Martin; Kasper, Siegfried; Frey, Richard

2017-07-01

Information on efficacy and safety of electroconvulsive therapy in patients with dementia is sparse. The current case report describes a patient suffering from severe depression and dementia who received electroconvulsive therapy with S-ketamine anesthesia at our psychiatric intensive care unit for the treatment of her therapy-resistant catatonic stupor. The patient's condition improved remarkably through the treatment. By the end of 16 electroconvulsive therapy sessions, her catatonic symptoms remitted entirely, her affect was brighter and she performed markedly better at the cognitive testing.

Ketamine: 50 Years of Modulating the Mind

PubMed Central

Li, Linda; Vlisides, Phillip E.

2016-01-01

Ketamine was introduced into clinical practice in the 1960s and continues to be both clinically useful and scientifically fascinating. With considerably diverse molecular targets and neurophysiological properties, ketamine’s effects on the central nervous system remain incompletely understood. Investigators have leveraged the unique characteristics of ketamine to explore the invariant, fundamental mechanisms of anesthetic action. Emerging evidence indicates that ketamine-mediated anesthesia may occur via disruption of corticocortical information transfer in a frontal-to-parietal (“top down”) distribution. This proposed mechanism of general anesthesia has since been demonstrated with anesthetics in other pharmacological classes as well. Ketamine remains invaluable to the fields of anesthesiology and critical care medicine, in large part due to its ability to maintain cardiorespiratory stability while providing effective sedation and analgesia. Furthermore, there may be an emerging role for ketamine in treatment of refractory depression and Post-Traumatic Stress Disorder. In this article, we review the history of ketamine, its pharmacology, putative mechanisms of action and current clinical applications. PMID:27965560

Potential anesthesia protocols for space exploration missions.

PubMed

Komorowski, Matthieu; Watkins, Sharmila D; Lebuffe, Gilles; Clark, Jonathan B

2013-03-01

In spaceflight beyond low Earth's orbit, medical conditions requiring surgery are of a high level of concern because of their potential impact on crew health and mission success. Whereas surgical techniques have been thoroughly studied in spaceflight analogues, the research focusing on anesthesia is limited. To provide safe anesthesia during an exploration mission will be a highly challenging task. The research objective is thus to describe specific anesthesia procedures enabling treatment of pre-identified surgical conditions. Among the medical conditions considered by the NASA Human Research Program Exploration Medical Capability element, those potentially necessitating anesthesia techniques have been identified. The most appropriate procedure for each condition is thoroughly discussed. The substantial cost of training time necessary to implement regional anesthesia is pointed out. Within general anesthetics, ketamine combines the unique advantages of preservation of cardiovascular stability, the protective airway reflexes, and spontaneous ventilation. Ketamine side effects have for decades tempered enthusiasm for its use, but recent developments in mitigation means broadened its indications. The extensive experience gathered in remote environments, with minimal equipment and occasionally by insufficiently trained care providers, confirms its high degree of safety. Two ketamine-based anesthesia protocols are described with their corresponding indications. They have been designed taking into account the physiological changes occurring in microgravity and the specific constraints of exploration missions. This investigation could not only improve surgical care during long-duration spaceflights, but may find a number of terrestrial applications in isolated or austere environments.

Electroencephalogram Signatures of Ketamine-Induced Unconsciousness

PubMed Central

Akeju, Oluwaseun; Song, Andrew H.; Hamilos, Allison E.; Pavone, Kara J.; Flores, Francisco J.; Brown, Emery N.; Purdon, Patrick L.

2016-01-01

Objectives Ketamine is an N-methyl-D-aspartate receptor antagonist commonly administered as a general anesthetic. However, circuit level mechanisms to explain ketamine-induced unconsciousness in humans are yet to be clearly defined. Disruption of frontal-parietal network connectivity has been proposed as a mechanism to explain this brain state. However, this mechanism was recently demonstrated at subanesthetic doses of ketamine in awake-patients. Therefore we investigated whether there is an electroencephalogram (EEG) marker for ketamine-induced unconsciousness. Methods We retrospectively studied the EEG in 12 patients who received ketamine for the induction of general anesthesia. We analyzed the EEG dynamics using power spectral and coherence methods. Results Following the administration of a bolus dose of ketamine to induce unconsciousness, we observed a “gamma burst” EEG pattern that consisted of alternating slow-delta (0.1-4 Hz) and gamma (~27-40 Hz) oscillations. This pattern was also associated with increased theta oscillations (~4-8 Hz) and decreased alpha/beta oscillations (~10-24 Hz). Conclusions Ketamine-induced unconsciousness is associated with a gamma burst EEG pattern. Significance We postulate that the gamma burst pattern is a thalamocortical rhythm based on insights previously obtained from cat neurophysiological experiments. This EEG signature of ketamine-induced unconsciousness may offer new insights into general anesthesia induced brain states. PMID:27178861

Effects of xylazine-ketamine anesthesia on plasma levels of cortisol and vital signs during laparotomy in dogs.

PubMed

Naddaf, H; Varzi, H Najafzade; Sabiza, S; Falah, H

2014-01-01

This study was designed to evaluate effects of xylazine-ketamine anesthesia on plasma levels of cortisol and vital signs during and after laparotomy in dogs. Eight clinically healthy, adult male dogs, weighing 20 kg were used. All dogs were initially sedated by acepromazine. Thirty minutes later, ketamine plus xylazine was used to induce anesthesia. Surgical incision of laparotomy was done. After a 5 min manipulation of the abdominal organs, the incision was sutured. Vital signs including heart rate, respiratory rate and rectal temperature (RT) were recorded at the times of -30: premedication, 0: induction and Surgical incision, 30: End of surgery, 60, 90 and 120 min. Blood was sampled at the above mentioned times and analyzed using a commercial ELISA kit for cortisol. A significant decreasing trend in RT was observed during the studied times. No significant changes were observed in heart rate and respiratory rate (p>0.05), except at the time of 60 respiratory rate significantly decreased when compared to the time of 90 (p=0.026) and 120 (p=0.041). A non-significant but increasing trend in plasma levels of cortisol was observed.

Effects of xylazine-ketamine anesthesia on plasma levels of cortisol and vital signs during laparotomy in dogs

PubMed Central

Naddaf, H.; Varzi, H. Najafzade; Sabiza, S.; Falah, H.

2014-01-01

This study was designed to evaluate effects of xylazine-ketamine anesthesia on plasma levels of cortisol and vital signs during and after laparotomy in dogs. Eight clinically healthy, adult male dogs, weighing 20 kg were used. All dogs were initially sedated by acepromazine. Thirty minutes later, ketamine plus xylazine was used to induce anesthesia. Surgical incision of laparotomy was done. After a 5 min manipulation of the abdominal organs, the incision was sutured. Vital signs including heart rate, respiratory rate and rectal temperature (RT) were recorded at the times of -30: premedication, 0: induction and Surgical incision, 30: End of surgery, 60, 90 and 120 min. Blood was sampled at the above mentioned times and analyzed using a commercial ELISA kit for cortisol. A significant decreasing trend in RT was observed during the studied times. No significant changes were observed in heart rate and respiratory rate (p>0.05), except at the time of 60 respiratory rate significantly decreased when compared to the time of 90 (p=0.026) and 120 (p=0.041). A non-significant but increasing trend in plasma levels of cortisol was observed. PMID:26623345

Pharmacokinetics of Ketamine and Xylazine in Young and Old Sprague–Dawley Rats

PubMed Central

Veilleux-Lemieux, Daphnée; Castel, Aude; Carrier, Denise; Beaudry, Francis; Vachon, Pascal

2013-01-01

To compare the pharmacokinetics of coadministered intraperitoneal ketamine and xylazine in young (8 to 10 wk; n = 6) and old rats (2 to 2.4 y; n = 6), blood samples obtained at 15 and 30 min and 1, 2, and 4 h after drug administration were analyzed by HPLC–tandem mass spectrometry. In both groups, the withdrawal reflex was absent during anesthesia and was present at 1.1 (± 0.2) and 2.6 (± 0.7) h after drug administration in young and old rats, respectively, with the first voluntary movement at 1.5 ± 0.2 and 4.9 ± 1.0 h. Drug availability of ketamine and xylazine was 6.0 and 6.7 times greater, respectively, in old than young rats. The rate constant of elimination of both drugs was greatly decreased and the elimination half-life was significantly greater in old compared with young rats. In conclusion, age and associated factors affect the availability of ketamine and xylazine when coadministered to attain clinical anesthesia, changing the pharmacokinetics of these drugs and prolonging anesthesia duration and recovery times with aging. Compared with their young counterparts, aged rats required much higher doses to attain a similar level of anesthesia. Finally, the long half-life of both ketamine and xylazine, when coadministered to old rats, may be a factor in research protocols because residual plasma concentrations could still be present for as long as 3 and 5 d, respectively, after administration. PMID:24041212

Consciousness and Complexity during Unresponsiveness Induced by Propofol, Xenon, and Ketamine.

PubMed

Sarasso, Simone; Boly, Melanie; Napolitani, Martino; Gosseries, Olivia; Charland-Verville, Vanessa; Casarotto, Silvia; Rosanova, Mario; Casali, Adenauer Girardi; Brichant, Jean-Francois; Boveroux, Pierre; Rex, Steffen; Tononi, Giulio; Laureys, Steven; Massimini, Marcello

2015-12-07

A common endpoint of general anesthetics is behavioral unresponsiveness, which is commonly associated with loss of consciousness. However, subjects can become disconnected from the environment while still having conscious experiences, as demonstrated by sleep states associated with dreaming. Among anesthetics, ketamine is remarkable in that it induces profound unresponsiveness, but subjects often report "ketamine dreams" upon emergence from anesthesia. Here, we aimed at assessing consciousness during anesthesia with propofol, xenon, and ketamine, independent of behavioral responsiveness. To do so, in 18 healthy volunteers, we measured the complexity of the cortical response to transcranial magnetic stimulation (TMS)--an approach that has proven helpful in assessing objectively the level of consciousness irrespective of sensory processing and motor responses. In addition, upon emergence from anesthesia, we collected reports about conscious experiences during unresponsiveness. Both frontal and parietal TMS elicited a low-amplitude electroencephalographic (EEG) slow wave corresponding to a local pattern of cortical activation with low complexity during propofol anesthesia, a high-amplitude EEG slow wave corresponding to a global, stereotypical pattern of cortical activation with low complexity during xenon anesthesia, and a wakefulness-like, complex spatiotemporal activation pattern during ketamine anesthesia. Crucially, participants reported no conscious experience after emergence from propofol and xenon anesthesia, whereas after ketamine they reported long, vivid dreams unrelated to the external environment. These results are relevant because they suggest that brain complexity may be sensitive to the presence of disconnected consciousness in subjects who are considered unconscious based on behavioral responses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of ketamine versus thiopental sodium anesthetic induction and a small dose of fentanyl on emergence agitation after sevoflurane anesthesia in children undergoing brief ophthalmic surgery.

PubMed

Jung, Hyun Ju; Kim, Jong Bun; Im, Kyong Shil; Oh, Seung Hwa; Lee, Jae Myeong

2010-02-01

Emergence agitation (EA) in children after sevoflurane anesthesia is common. The purpose of this study was to compare the incidences of EA between ketamine and thiopental sodium induction in children underwent sevoflurane anesthesia. We also evaluated if a small dose of fentanyl could reduce the incidence of EA. The patients who were scheduled for strabismus or entropion surgery were divided into 4 groups. The patients in Groups 1 and 2 were induced anesthesia with ketamine 1.5 mg/kg; those in Groups 3 and 4 were induced with thiopental sodium 5 mg/kg. The patients in Groups 1 and 3 received an injection of fentanyl 1.5 microg/kg, whereas the patients in Groups 2 and 4 received IV saline of the same volume. Anesthesia was maintained with sevoflurane. The recovery characteristics and EA in recovery room were assessed. The incidence of EA was significantly higher in Groups 2 and 4 and there was no difference between Groups 2 and 4. Group 2 had almost an eleven-fold higher risk of developing EA than did Group 1, and the incidence of EA in Group 4 was sixty-nine-fold higher than that of Group 1. The risk factor for EA was only the kind of medication. Preoperative anxiety had no significant correlation with EA. The incidence of EA after sevoflurane anesthesia is similar between ketamine and thiopental sodium anesthetic induction in children undergoing pediatric ophthalmic surgery. Also, the addition of a small dose of fentanyl after anesthetic induction decreases the incidence of EA.

Hesperetin-5,7,3'-O-triacetate suppresses airway hyperresponsiveness in ovalbumin-sensitized and challenged mice without reversing xylazine/ketamine-induced anesthesia in normal mice.

PubMed

Yang, You-Lan; Chen, Chi-Li; Chen, Chi-Ming; Ko, Wun-Chang

2017-05-30

We recently reported that hesperetin-5,7,3'-O-triacetate (HTA) dually inhibited phosphodiesterase (PDE)3/4 with a therapeutic ratio of 20.8. The application and development of PDE4 inhibitors for treating asthma or COPD are limited by their side effects, such as nausea, vomiting and gastric hypersecretion. PDE4 inhibitors were reported to reverse xylazine/ketamine-induced anesthesia in rats and triggered vomiting in ferrets. Thus the reversing effect of HTA on xylazine/ketamine-induced anesthesia in mice was studied to assess emetic effect of HTA. The aim of this study was to prove the therapeutic effect of HTA without vomiting effect at an effective dose for treating COPD. Ten female BALB/c mice in each group were sensitized by ovalbumin (OVA) on days 0 and 14. On day 21, these mice were emphasized the sensitization by Freund's complete adjuvant. Mice were challenged by 1% OVA nebulization on days 28, 29, and 30. Airway hyperresponsiveness (AHR) was assessed on day 32 in each group, using the FlexiVent system to determine airway resistance (R L ) and lung dynamic compliance (C dyn ) in anesthetized ovalbumin (OVA)-sensitized and challenged mice. Each group was orally administered HTA (10 ~ 100 μmol/kg), roflumilast (1 and 5 mg/kg) or vehicles (controls) 2 h before and 6 and 24 h after OVA provocation. For comparison, sham-treated mice were challenged with saline instead of 1% OVA. The ability to reverse xylazine/ketamine-induced anesthesia by HTA or roflumilast for 3 h was determined in normal mice. We used roflumilast, a selective PDE4 inhibitor and bronchodilator for severe COPD approved by the US Food and Drug Administration, as a reference drug. In the results, HTA (100 μmol/kg, p.o.) or roflumilast (5 mg/kg, p.o.) significantly suppressed all R L values of MCh at 0.78 ~ 25 mg/mL and enhanced C dyn values of MCh at 3.125 ~ 25 mg/mL compared to OVA-sensitized and -challenged control mice. Orally administered 1, 3 or 10 mg/kg roflumilast

Physiological, pharmacokinetic and liver metabolism comparisons between 3-, 6-, 12- and 18-month-old male Sprague Dawley rats under ketamine-xylazine anesthesia

PubMed Central

Giroux, Marie-Chantal; Santamaria, Raphael; Hélie, Pierre; Burns, Patrick; Beaudry, Francis; Vachon, Pascal

2015-01-01

The main objective of this study was to compare the physiological changes (withdrawal and corneal reflexes, respiratory and cardiac frequency, blood oxygen saturation, and rectal temperature) following intraperitoneal administration of ketamine (80 mg/kg) and xylazine (10 mg/kg) to 3-, 6-, 12- and 18-month-old male Sprague Dawley rats (n=6/age group). Plasma pharmacokinetics, liver metabolism, and blood biochemistry were examined for a limited number of animals to better explain anesthetic drug effects. Selected organs were collected for histopathology. The results for the withdrawal and corneal reflexes suggest a shorter duration and decreased depth of anesthesia with aging. Significant cardiac and respiratory depression, as well as decreased blood oxygen saturation, occurred in all age groups however, cardiac frequency was the most affected parameter with aging, since the 6-, 12-, and 18-month-old animals did not recuperate to normal values during recovery from anesthesia. Pharmacokinetic parameters (T1/2 and AUC) increased and drug clearance decreased with aging, which strongly suggests that drug exposure is associated with the physiological results. The findings for liver S9 fractions of 18-month-old rats compared with the other age groups suggest that following a normal ketamine anesthetic dose (80 mg/kg), drug metabolism is impaired, leading to a significant increase of drug exposure. In conclusion, age and related factors have a substantial effect on ketamine and xylazine availability, which is reflected by significant changes in pharmacokinetics and liver metabolism of these drugs, and this translates into shorter and less effective anesthesia with increasing age. PMID:26489361

Ketamine in the treatment of acute pain.

PubMed

Brinck, Elina; Kontinen, Vesa

2017-01-01

Ketamine is an old anesthetic agent that relieves pain by reducing central sensitization in the central nervous system. This is advantageous for patients suffering from severe pain prior to surgery or are using a strong opioid. The S enantiomer of ketamine used for anesthesia is more powerful than racemic ketamine. The ideal dose of ketamine for pain relief is not yet known, and its adverse effects on the central nervous system, including hallucinations, sedation, and diplopia have limited its use in pain management. The significance of these effects at low doses is probably less than expected, particularly if benzodiazepines or an alpha-2 agonist, such as dexmedetomidine, are administered in addition to ketamine.

Effect of Etomidate Versus Combination of Propofol-Ketamine and Thiopental-Ketamine on Hemodynamic Response to Laryngoscopy and Intubation: A Randomized Double Blind Clinical Trial.

PubMed

Gholipour Baradari, Afshin; Firouzian, Abolfazl; Zamani Kiasari, Alieh; Aarabi, Mohsen; Emadi, Seyed Abdollah; Davanlou, Ali; Motamed, Nima; Yousefi Abdolmaleki, Ensieh

2016-02-01

Laryngoscopy and intubation frequently used for airway management during general anesthesia, is frequently associated with undesirable hemodynamic disturbances. The aim of this study was to compare the effects of etomidate, combination of propofol-ketamine and thiopental-ketamine as induction agents on hemodynamic response to laryngoscopy and intubation. In a double blind, randomized clinical trial a total of 120 adult patients of both sexes, aged 18 - 45 years, scheduled for elective surgery under general anesthesia were randomly assigned into three equally sized groups. Patients in group A received etomidate (0.3 mg/kg) plus normal saline as placebo. Patients in group B and C received propofol (1.5 mg/kg) plus ketamine (0.5 mg/kg) and thiopental sodium (3 mg/kg) plus ketamine (0.5 mg/kg), respectively for anesthesia induction. Before laryngoscopy and tracheal intubation, immediately after, and also one and three minutes after the procedures, hemodynamic values (SBP, DBP, MAP and HR) were measured. A repeated measurement ANOVA showed significant changes in mean SBP and DBP between the time points (P < 0.05). In addition, the main effect of MAP and HR were statistically significant during the course of study (P < 0.05). Furthermore, after induction of anesthesia, the three study groups had significantly different SBP, DBP and MAP changes overtime (P < 0.05). However, HR changes over time were not statistically significant (P > 0.05). Combination of propofol-ketamine had superior hemodynamic stability compared to other induction agents. Combination of propofol-ketamine may be recommended as an effective and safe induction agent for attenuating hemodynamic responses to laryngoscopy and intubation with better hemodynamic stability. Although, further well-designed randomized clinical trials to confirm the safety and efficacy of this combination, especially in critically ill patients or patients with cardiovascular disease, are warranted.

Influence of cadmium on ketamine-induced anesthesia and brain microsomal Na[sup +], K[sup +]-ATPase in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Y.; Sangiah, S.

1994-10-01

Cadmium is a rare metallic element, present in almost all types of food. Shellfish, wheat and rice accumulate very high amounts. Occupational and environmental pollutants are the main sources of cadmium exposure. Cadmium has a very long biologic half-life. Exposure to Cadmium causes anemia, hypertension, hepatic, renal, pulmonary and cardiovascular disorders as well as being a possible mutagen, teratogen and carcinogen. Acute cadmium treatment increased the hexobarbital sleeping time and inhibited hepatic microsomal drug metabolism due to a decrease in cytochrome P[sub 450] content. Cadmium potentiated ethanol-induced sleep in a dose-dependent manner. Cadmium has been shown to inhibit brain microsomalmore » Na[sup +], K[sup +]-ATPase activity in vitro and in vivo. Cadmium and ethanol additively inhibited brain Na[sup +], K[sup +]-ATPase. This might be a direct interaction between cadmium and ethanol in the central nervous system. Ketamine is an intravenous anesthetic agent. It acts on central nervous system and produces [open quotes]dissociative anaesthesia.[close quotes] Ketamine provides adequate surgical anesthesia and is used alone in humans and/or combination with xylazine, an [alpha][sub 2]-adrenergic agonist in animals. It produces CNS depression, analgesia, amnesia, immobility and a feeling of dissociation from the environment. Ketamine is a non-competitive antagonist of the NMDA subset of the glutamate receptor. This perhaps results in an increase in neuronal activity leading to disorganization of normal neurotransmission and produces dissociative anesthetic state. Because it is different from most other anesthetics, ketamine may be expected to have a unique effect on brain biochemical parameters and enzymes. The purpose of this study was to examine the interactions between cadmium and ketamine on the central nervous system and ATPase, in an attempt to further understand the mechanism of action. 12 refs., 3 figs.« less

Anesthesia in a Baird's tapir (Tapirus bairdii).

PubMed

Trim, C M; Lamberski, N; Kissel, D I; Quandt, J E

1998-06-01

A Baird's tapir (Tapirus bairdii) was satisfactorily immobilized on two occasions with i.m. detomidine (0.065-0.13 mg/kg) and butorphanol (0.13-0.2 mg/kg). On the second occasion, anesthesia was induced by i.v. administration of ketamine (2.2 mg/kg). Twenty minutes later, endotracheal intubation was performed after an additional i.v. injection of ketamine (1.5 mg/kg). Anesthesia was maintained with isoflurane, which provided excellent conditions for radiology and surgery. Anesthesia was associated with hypoxemia when the tapir was allowed to breathe air and with hypoventilation. Mean arterial pressure remained satisfactory. No antagonist drugs were administered, and recovery from anesthesia was rapid and smooth.

Intraperitoneal Continuous-Rate Infusion for the Maintenance of Anesthesia in Laboratory Mice (Mus musculus)

PubMed Central

Erickson, Rebecca L; Terzi, Matthew C; Jaber, Samer M; Hankenson, F Claire; McKinstry-Wu, Andrew; Kelz, Max B; Marx, James O

2016-01-01

Intraperitoneal injectable anesthetics are often used to achieve surgical anesthesia in laboratory mice. Because bolus redosing of injectable anesthetics can cause unacceptably high mortality, we evaluated intraperitoneal continuous-rate infusion (CRI) of ketamine with or without xylazine for maintaining surgical anesthesia for an extended period of time. Anesthesia was induced in male C57BL/6J mice by using ketamine (80 mg/kg) and xylazine (8 mg/kg) without or with acepromazine at 0.1 mg/kg or 0.5 mg/kg. At 10 min after induction, CRI for 90 min was initiated and comprised 25%, 50%, or 100% of the initial ketamine dose per hour or 50% of the initial doses of both ketamine and xylazine. Anesthetic regimens were compared on the basis of animal immobility, continuous surgical depth of anesthesia as determined by the absence of a pedal withdrawal reflex, and mortality. Consistent with previous studies, the response to anesthetics was highly variable. Regimens that provided the longest continuous surgical plane of anesthesia with minimal mortality were ketamine–xylazine–acepromazine (0.1 mg/kg) with CRI of 100% of the initial ketamine dose and ketamine–xylazine–acepromazine (0.5 mg/kg) with CRI of 50% of the initial ketamine and xylazine doses. In addition, heart rate and respiratory rate did not increase consistently in response to a noxious stimulus during CRI anesthesia, even when mice exhibited a positive pedal withdrawal reflex, suggesting that these parameters are unreliable indicators of anesthetic depth during ketamine–xylazine anesthesia in mice. We conclude that intraperitoneal CRI anesthesia in mice prolongs injectable anesthesia more consistently and with lower mortality than does bolus redosing. PMID:27657709

Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration.

PubMed

Vullo, Cecilia; Carluccio, Augusto; Robbe, Domenico; Meligrana, Marina; Petrucci, Linda; Catone, Giuseppe

2017-10-11

In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO 2 ) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded. Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively. The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration.

Properties of slow oscillation during slow-wave sleep and anesthesia in cats

PubMed Central

Chauvette, Sylvain; Crochet, Sylvain; Volgushev, Maxim; Timofeev, Igor

2011-01-01

Deep anesthesia is commonly used as a model of slow-wave sleep (SWS). Ketamine-xylazine anesthesia reproduces the main features of sleep slow oscillation: slow, large amplitude waves in field potential, which are generated by the alternation of hyperpolarized and depolarized states of cortical neurons. However, direct quantitative comparison of field potential and membrane potential fluctuations during natural sleep and anesthesia is lacking, so it remains unclear how well the properties of sleep slow oscillation are reproduced by the ketamine-xylazine anesthesia model. Here, we used field potential and intracellular recordings in different cortical areas in the cat, to directly compare properties of slow oscillation during natural sleep and ketamine-xylazine anesthesia. During SWS cortical activity showed higher power in the slow/delta (0.1-4 Hz) and spindle (8-14 Hz) frequency range, while under anesthesia the power in the gamma band (30-100 Hz) was higher. During anesthesia, slow waves were more rhythmic and more synchronous across the cortex. Intracellular recordings revealed that silent states were longer and the amplitude of membrane potential around transition between active and silent states was bigger under anesthesia. Slow waves were largely uniform across cortical areas under anesthesia, but in SWS they were most pronounced in associative and visual areas, but smaller and less regular in somatosensory and motor cortices. We conclude that although the main features of the slow oscillation in sleep and anesthesia appear similar, multiple cellular and network features are differently expressed during natural SWS as compared to ketamine-xylazine anesthesia. PMID:22016533

Properties of slow oscillation during slow-wave sleep and anesthesia in cats.

PubMed

Chauvette, Sylvain; Crochet, Sylvain; Volgushev, Maxim; Timofeev, Igor

2011-10-19

Deep anesthesia is commonly used as a model of slow-wave sleep (SWS). Ketamine-xylazine anesthesia reproduces the main features of sleep slow oscillation: slow, large-amplitude waves in field potential, which are generated by the alternation of hyperpolarized and depolarized states of cortical neurons. However, direct quantitative comparison of field potential and membrane potential fluctuations during natural sleep and anesthesia is lacking, so it remains unclear how well the properties of sleep slow oscillation are reproduced by the ketamine-xylazine anesthesia model. Here, we used field potential and intracellular recordings in different cortical areas in the cat to directly compare properties of slow oscillation during natural sleep and ketamine-xylazine anesthesia. During SWS cortical activity showed higher power in the slow/delta (0.1-4 Hz) and spindle (8-14 Hz) frequency range, whereas under anesthesia the power in the gamma band (30-100 Hz) was higher. During anesthesia, slow waves were more rhythmic and more synchronous across the cortex. Intracellular recordings revealed that silent states were longer and the amplitude of membrane potential around transition between active and silent states was bigger under anesthesia. Slow waves were mostly uniform across cortical areas under anesthesia, but in SWS, they were most pronounced in associative and visual areas but smaller and less regular in somatosensory and motor cortices. We conclude that, although the main features of the slow oscillation in sleep and anesthesia appear similar, multiple cellular and network features are differently expressed during natural SWS compared with ketamine-xylazine anesthesia.

[Locoregional anesthesia for pediatric surgery in remote rural settings: experience of an NGO in Bangladesh].

PubMed

Sleth, J C; Coulon, M; Fesseau, R; Rami, L

2010-12-01

Performing safe pediatric anesthesia in developing countries is a technical challenge for NGOs working in remote locations. The aim of this study is to describe our experience aboard a hospital ship working off the coast of northern Bangladesh. Anesthesia protocol records for a 3-year period were retrospectively reviewed. A total of 463 procedures were performed with no severe anesthetic complications. Regional anesthesia was performed in 83% of patients. It was carried out alone in 15% of patients and in association with IV or IM ketamine sedation in 68%. General anesthesia was performed using ketamine in 17% of patients. Tracheal intubation was carried out in only 3 cases. These findings indicate that regional anesthesia in association with ketamine as sedation agent is a simple and safe technique for pediatric anesthesia in remote rural settings.

Does systemic lidocaine reduce ketamine requirements for endotracheal intubation in calves?

PubMed

Lauper, Josiane; Marolf, Vincent; Levionnois, Olivier; Schelling, Esther; Meylan, Mireille; Spadavecchia, Claudia

2017-03-01

To investigate whether an intravenous (IV) lidocaine bolus in calves premedicated with xylazine-butorphanol reduces the amount of ketamine required to allow endotracheal intubation. Randomized, prospective clinical study. In total, 41 calves scheduled for elective umbilical surgery. Calves were randomly assigned to one of two groups (L: lidocaine or S: saline). The calves were administered xylazine (0.07 mg kg -1 ) and butorphanol (0.1 mg kg -1 ) intramuscularly and 10 minutes later lidocaine (2 mg kg -1 ; group L) or saline (group S) IV over 1 minute. After 2 minutes, ketamine (2.5 mg kg -1 ) was injected IV. If the depth of anaesthesia was insufficient for intubation, additional ketamine (1 mg kg -1 ) was administered every minute until intubation was successful. The amount of ketamine required for intubation, respiratory rate, pulse rate, arterial pressures, the depth of sedation and conditions of endotracheal intubation after induction of anaesthesia were compared between the two groups. The calves in group L were sedated more deeply than those in group S; however, neither the median (range) amount of ketamine required for intubation, 3.5 (2.5-4.5) mg kg -1 and 3.5 (2.5-3.5) mg kg -1 , respectively, nor the induction quality differed significantly between the groups. A bolus of lidocaine (2 mg kg -1 ) administered 10 minutes after xylazine-butorphanol in calves deepened the degree of sedation but did not decrease the requirement of ketamine for endotracheal intubation. No adverse effects were recorded in the physiological variables measured. Copyright © 2017. Published by Elsevier Ltd.

Anorectal manometry with and without ketamine for evaluation of defecation disorders in children.

PubMed

Keshtgar, A S; Choudhry, M S; Kufeji, D; Ward, H C; Clayden, G S

2015-03-01

Anorectal manometry (ARCM) provides valuable information in children with chronic constipation and fecal incontinence but may not be tolerated in the awake child. This study aimed to evaluate the effect of ketamine anesthesia on the assessment of anorectal function by manometry and to evaluate defecation dynamics and anal sphincter resting pressure in the context of pathophysiology of chronic functional (idiopathic) constipation and soiling in children. This was a prospective study of children who were investigated for symptoms of chronic constipation and soiling between April 2001 and April 2004. We studied 52 consecutive children who had awake ARCM, biofeedback training and endosonography (awake group) and 64 children who had ketamine anesthesia for ARCM and endosonography (ketamine group). We age matched 31 children who had awake anorectal studies with 27 who had ketamine anesthesia. The children in awake and ketamine groups were comparable for age, duration of bowel symptoms and duration of laxative treatments. ARCM profile was comparable between the awake and the ketamine groups with regard to anal sphincter resting pressure, rectal capacity, amplitude of rectal contractions, frequency of rectal and IAS contractions and functional length of anal canal. Of 52 children who had awake ARCM, dyssynergia of the EAS muscles was observed in 22 (42%) and median squeeze pressure was 87mm Hg (range 25-134). The anal sphincter resting pressure was non-obstructive and comparable to healthy normal children. Rectoanal inhibitory reflex was seen in all children excluding diagnosis of Hirschsprung disease. Ketamine anesthesia does not affect quantitative or qualitative measurements of autonomic anorectal function and can be used reliably in children who will not tolerate the manometry while awake. Paradoxical contraction of the EAS can only be evaluated in the awake children and should be investigated further as the underlying cause of obstructive defecation in patients with

A review of the use of ketamine in pain management.

PubMed

Tawfic, Qutaiba A

2013-01-01

Ketamine is a noncompetitive antagonist of N-methyl-d-aspartate receptor. It has been widely used in anesthesia and pain management. Ketamine has been administered via the intravenous, intramuscular, subcutaneous, oral, rectal, topical, intranasal, sublingual, epidural, and caudal routes. Ketamine improves postoperative and posttrauma pain scores and reduces opioid consumption. It has special indication for patients with opioid tolerance, acute hyperalgesia, and neuropathic pain. It also has a role in the management of chronic pain including both cancer and noncancer pain. Recreational use of ketamine is increasing as well through different routes of administration like inhalation, smoking, or intravenous injection. Long-time exposure to ketamine, especially in the abusers, may lead to serious side effects. This review is trying to define the role of ketamine in pain management.

Prevention of Emergence Agitation with Ketamine in Rhinoplasty.

PubMed

Demir, Canser Yilmaz; Yuzkat, Nureddin

2018-06-01

Emergence agitation (EA), defined as restlessness, disorientation, excitation, and/or inconsolable crying, is a common phenomenon during early recovery from general anesthesia. In this study, we aimed to determine the (1) EA incidence after rhinoplasty operations in adults; (2) the effects of ketamine administered at sub-anesthetic doses just 20 min before the end of the surgery in rhinoplasty operations on agitation level, postoperative pain, side effects, and complications; and (3) to determine the risk factors for EA in adults after rhinoplasty. Totally 140 patients scheduled to undergo elective rhinoplasty were enrolled in this prospective study. Patients were equally and randomly divided into two groups: saline group (control group) (n = 70) and ketamine group (n = 70). Twenty minutes before surgery completion, 1 ml saline was administered via the intravenous (i.v.) route to the saline group, while 0.5 mg/kg ketamine was administered via i.v. patients in the ketamine group. The emergence agitation level of the patients was evaluated using the Richmond Agitation-Sedation Scale just after extubation and in the post-anesthesia care unit (PACU). For postoperative pain evaluation, the Numerical Rating Scale (NRS) was scored (from 0 to 10) every 10 min until the patients were discharged from PACU. EA incidence in the control group was as high as 54.3%, while in the ketamine group it was 8.6% just after extubation (p < 0.001). In the PACU, EA incidence was 28.6% in the control group, while none of the patients had EA in the PACU in the ketamine group (p < 0.001). Male gender, severe pain (NRS ≥ 5), and smoking were defined as significant risk factors for EA both after extubation and during follow-ups in the PACU (p < 0.001). Emergence agitation after rhinoplasty is a common complication, likely disturbing operative outcomes in adults. Ketamine at sub-anesthetic doses is highly effective in preventing EA. Further, larger-scale prospective studies are

Does intravenous ketamine enhance analgesia after arthroscopic shoulder surgery with ultrasound guided single-injection interscalene block?: a randomized, prospective, double-blind trial.

PubMed

Woo, Jae Hee; Kim, Youn Jin; Baik, Hee Jung; Han, Jong In; Chung, Rack Kyung

2014-07-01

Ketamine has anti-inflammatory, analgesic and antihyperalgesic effect and prevents pain associated with wind-up. We investigated whether low doses of ketamine infusion during general anesthesia combined with single-shot interscalene nerve block (SSISB) would potentiate analgesic effect of SSISB. Forty adult patients scheduled for elective arthroscopic shoulder surgery were enrolled and randomized to either the control group or the ketamine group. All patients underwent SSISB and followed by general anesthesia. During an operation, intravenous ketamine was infused to the patients of ketamine group continuously. In control group, patients received normal saline in volumes equivalent to ketamine infusions. Pain score by numeric rating scale was similar between groups at 1, 6, 12, 24, 36, and 48 hr following surgery, which was maintained lower than 3 in both groups. The time to first analgesic request after admission on post-anesthesia care unit was also not significantly different between groups. Intraoperative low dose ketamine did not decrease acute postoperative pain after arthroscopic shoulder surgery with a preincisional ultrasound guided SSISB. The preventive analgesic effect of ketamine could be mitigated by SSISB, which remains one of the most effective methods of pain relief after arthroscopic shoulder surgery.

[Economical benefit of continuous total intravenous anesthesia].

PubMed

Onaka, M; Yamamoto, H; Akatsuka, M; Mori, H

1999-05-01

Total intravenous anesthesia (TIVA) has been recommended in view of avoiding air pollution. However, intermittent administration of anesthetic agents has a large disadvantage of delayed emergence. We reported that continuous TIVA with propofol, ketamine, vecuronium and buprenorphine (PKBp) could bring rapid emergence. In this study, we calculated and compared the cost of anesthesia in the subjects who had undergone general anesthesia either with continuous PKBp or nitrous oxide-oxygen-sevoflurane. In group PKBp subjects, after induction with propofol, ketamine, vecuronium and buprenorphine, anesthesia was maintained with continuous intravenous administration of propofol corresponding to the patient's age using twice step down method; ketamine (240 micrograms.kg-1.h-1), vecuronium (80 micrograms.kg-1.h-1) and buprenorphine (0.4 microgram.kg-1.h-1). Group GOS subjects, after the same induction method, received nitrous oxide, sevoflurane and vecuronium. Moreover, the group GOS subjects were divided to two groups; the high flow GOS (N2O:O2:sevoflurane = 4 l:2 l:30 ml) and the low flow GOS (N2O:O2:sevoflurane = 2 l:1 l:15 ml). Continuous PKBp group showed lower cost than the high flow GOS group. The PKBp group showed lower cost than the low flow GOS group except in patients weighing more than 100 kg. Furthermore, we calculated the cost of continuous PKBp anesthesia in Japan, U.S.A. and U.K. The U.S.A. cost of PKBp was higher than the Japanese and the U.K., because the cost of ketamine in U.S.A. is higher than in the other countries. Continuous PKBp is more economical than the high flow GOS, and continuous PKBp in Japan is more economical than in U.S.A.

Spinal conduction block by intrathecal ketamine in dogs.

PubMed

Iida, H; Dohi, S; Tanahashi, T; Watanabe, Y; Takenaka, M

1997-07-01

In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.

Anesthesia of captive African wild dogs (Lycaon pictus) using a medetomidine-ketamine-atropine combination.

PubMed

Ward, David G; Blyde, David; Lemon, John; Johnston, Steve

2006-06-01

Seven captive male African wild dogs (Lycaon pictus) weighing 25-32 kg each, were anesthetized by i.m. injection via hand syringe with a combination of 1.5 mg/kg ketamine, 40 microg/kg medetomidine, and 0.05 mg/kg atropine. Following endotracheal intubation, each animal was connected to a bain closed-circuit system that delivered 1.5% isoflurane and 2 L/min oxygen. Atipamezole (0.1 mg/kg i.v.; 0.1 mg/kg i.m.) was given at the end of each procedure (60 min following injection of medetomidine/ketamine/atropine). Time to sternal recumbency was 5-8 min. Times to standing after atipamezole administration were 8-20 min. This anesthetic regimen was repeated on three separate occasions (September 2000, February 2002, and October 2002) on all males to perform electroejaculation procedures. Each procedure was <80 min from injection to standing. Dogs showed excellent muscle relaxation during the procedures. Arterial blood samples were collected at 10-min intervals for blood gases in one procedure (September 2000). Separate venous samples were taken from each dog during each procedure for hematology and biochemistry. These values were within the normal range for this species. Arterial hemoglobin oxygen saturation (SpO2) and heart rate (HR) were monitored continuously in addition to other anesthesia monitoring procedures (body temperature, respiratory rate [RR], capillary refill time, blink response, pupil position, deep pain perception reflex). All dogs maintained relatively stable SpO2 profiles during monitoring, with a mean (+/-SD) SpO2 of 92% +/-5.4%. All other physiological variables (HR, RR, body temperature, blood pressure) were within normal limits. Following each procedure, normal behavior was noted in all dogs. All the dogs were reunited into the pack at completion of their anesthetic procedures. An injectable medetomidine-ketamine-atropine combination with maintenance by gaseous isoflurane and oxygen provides an inexpensive, reliable anesthetic for captive African

Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy: Effects on postoperative pain and recovery profiles

PubMed Central

Kim, Dong-Ho; Choi, June Young; Kim, Byoung-Gook; Hwang, Jin-Young; Park, Seong-Joo; Oh, Ah-Young; Jeon, Young-Tae; Ryu, Jung-Hee

2016-01-01

Abstract Background: Robotic or endoscopic thyroidectomy using bilateral axillo-breast approach (BABA) is frequently performed for excellent cosmesis. However, postoperative pain is remained as concerns due to the extent tissue dissection and tension during the operation. Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that reduces acute postoperative pain. We evaluated the effects of intraoperative ketamine infusion on postoperative pain control and recovery profiles following BABA robotic or endoscopic thyroidectomy. Methods: Fifty-eight adult patients scheduled for BABA robotic or endoscopic thyroidectomy were randomized into a control group (n = 29) and ketamine group (n = 29). Following induction of anesthesia, patients in each group were infused with the same volume of saline or ketamine solution (1 mg/kg bolus, 60 μg/kg/h continuous infusion). Total intravenous anesthesia with propofol and remifentanil was used to induce and maintain anesthesia. Pain scores (101-point numerical rating scale, 0 = no pain, 100 = the worst imaginable pain), the consumption of rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 hours postoperatively. Results: Patients in the ketamine group reported lower pain scores than those in the control group at 6 hours (30 [30] vs 50 [30]; P = 0.017), 24 hours (20 [10] vs 30 [20]; P < 0.001), and 48 hours (10 [10] vs 20 [15]; P < 0.001) in neck area. No statistically significant differences were found between the 2 groups in terms of the requirements for rescue analgesics or the occurrence of adverse events. Conclusion: Intravenous ketamine infusion during anesthesia resulted in lower postoperative pain scores following BABA robotic or endoscopic thyroidectomy, with no increase in adverse events. PMID:27930531

Effects of anesthetic induction with a benzodiazepine plus ketamine hydrochloride or propofol on hypothermia in dogs undergoing ovariohysterectomy.

PubMed

Bornkamp, Jennifer L; Robertson, Sheilah; Isaza, Natalie M; Harrison, Kelly; DiGangi, Brian A; Pablo, Luisito

2016-04-01

To assess the effect of anesthetic induction with a benzodiazepine plus ketamine or propofol on hypothermia in dogs undergoing ovariohysterectomy without heat support. 23 adult sexually intact female dogs undergoing ovariohysterectomy. Baseline rectal temperature, heart rate, and respiratory rate were recorded prior to premedication with buprenorphine (0.02 mg/kg, IM) and acepromazine (0.05 mg/kg, IM). Anesthesia was induced with midazolam or diazepam (0.25 mg/kg, IV) plus ketamine (5 mg/kg, IV; n = 11) or propofol (4 mg/kg, IV; 12) and maintained with isoflurane in oxygen. Rectal temperature was measured at hospital intake, prior to premedication, immediately after anesthetic induction, and every 5 minutes after anesthetic induction. Esophageal temperature was measured every 5 minutes during anesthesia, beginning 30 minutes after anesthetic induction. After anesthesia, dogs were covered with a warm-air blanket and rectal temperature was measured every 10 minutes until normothermia (37°C) was achieved. Dogs in both treatment groups had lower rectal temperatures within 5 minutes after anesthetic induction and throughout anesthesia. Compared with dogs that received a benzodiazepine plus ketamine, dogs that received a benzodiazepine plus propofol had significantly lower rectal temperatures and the interval from discontinuation of anesthesia to achievement of normothermia was significantly longer. Dogs in which anesthesia was induced with a benzodiazepine plus propofol or ketamine became hypothermic; the extent of hypothermia was more profound for the propofol combination. Dogs should be provided with adequate heat support after induction of anesthesia, particularly when a propofol-benzodiazepine combination is administered.

Inconsistency of allometric scaling for dissociative anesthesia of wild felids.

PubMed

Carregaro, Adriano B; Freitas, Gabrielle C; Bisetto, Shayne P; Xavier, Nathalia V; Sterzo, Elton V

2016-05-01

To evaluate allometric scaling for ketamine-xylazine (KX) anesthesia in wild felids using domestic cats for reference. Prospective single-phase non-blinded study. Six domestic cats and 13 wild felids (five Leopardus pardalis, five Puma concolor, one Panthera onca and two Panthera leo). Six domestic cats (4.1 ± 0.8 kg, REF1) were anesthetized by intramuscular administration of ketamine (15 mg kg(-1) ) and xylazine (1 mg kg(-1) ). Wild cats were divided into three groups based on body weight: 12.9 ± 2.4 kg (G1; n = 7), 43.0 ± 15.7 kg (G2; n = 4) and 126.0 ± 7.8 kg (G3; n = 2). Ketamine and xylazine doses were calculated based on allometric scaling of the basal metabolic rate (BMR = 70 × body mass(0.75) ). Afterwards, the six domestic cats were administered mean KX doses calculated for G1 and G2 (REF2). The heart rate, systolic arterial pressure, respiratory frequency, pH, the venous partial pressure of carbon dioxide, bicarbonate and lactate concentrations were recorded for up to 60 minutes. Additional doses were required in 12 out of the 13 wild cats. Anesthesia was not achieved in G3. Latency periods in wild felids were longer than REF1 and REF2. Anesthesia duration in REF1 was longer than that in the other groups. Recovery from anesthesia in REF1 and REF2 was longer than G1 and G2. Physiological variables remained within the range limits for the species. G1 baseline lactate concentration was higher than in the other groups. KX anesthesia established by allometric scaling of BMR from doses administered to domestic cats did not predict reliable anesthetic doses for wild cats. Dose rates calculated with this method must not be applied to these species. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Suppressive effects of ketamine on macrophage functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang Yi; Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Chen, T.-L.

2005-04-01

Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 {mu}M ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 {mu}M, ketamine caused a release of lactate dehydrogenasemore » and cell death. Ketamine, at 10 and 100 {mu}M, did not affect the chemotactic activity of macrophages. Administration of 1000 {mu}M ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-{alpha}, IL-1{beta}, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 {mu}M) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity.« less

[Ketamine as anesthetic agent in electroconvulsion therapy].

PubMed

Janke, C; Bumb, J M; Aksay, S S; Thiel, M; Kranaster, L; Sartorius, A

2015-05-01

Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment for severe psychiatric disorders. Ketamine is known as a core medication in anesthesiology and has recently gained interest in ECT practice as there are three potential advantages: (1) ketamine has no anticonvulsive actions, (2) according to recent studies ketamine could possess a unique intrinsic antidepressive potential and (3) ketamine may exhibit neuroprotective properties, which again might reduce the risk of cognitive side effects associated with ECT. The use of ketamine in psychiatric patients has been controversially discussed due to its dose-dependent psychotropic and psychotomimetic effects. This study was carried out to test if the occurrence of side effects is comparable and if seizure quality is better with ketamine when compared to thiopental. This retrospective study analyzed a total of 199 patients who received ketamine anesthesia for a total of 2178 ECT sessions. This cohort was compared to patients who were treated with thiopental for 1004 ECT sessions. A repeated measurement multiple logistic regression analysis revealed significant advantages in the ketamine group for seizure concordance and postictal suppression (both are surrogates for central inhibition). S-ketamin also necessitated the use of a higher dose of urapidil and a higher maximum postictal heart frequency. Clinically relevant psychiatric side effects were rare in both groups. No psychiatric side effects occurred in the subgroup of patients with schizophrenia (ketamine: n = 30). The mean dose of S-ketamine used increased in the first years but stabilized at 63 mg per patient in 2014. From these experiences it can be concluded that S-ketamine can be recommended at least as a safe alternative to barbiturates.

Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy: Effects on postoperative pain and recovery profiles: A consort compliant article.

PubMed

Kim, Dong-Ho; Choi, June Young; Kim, Byoung-Gook; Hwang, Jin-Young; Park, Seong-Joo; Oh, Ah-Young; Jeon, Young-Tae; Ryu, Jung-Hee

2016-12-01

Robotic or endoscopic thyroidectomy using bilateral axillo-breast approach (BABA) is frequently performed for excellent cosmesis. However, postoperative pain is remained as concerns due to the extent tissue dissection and tension during the operation. Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that reduces acute postoperative pain. We evaluated the effects of intraoperative ketamine infusion on postoperative pain control and recovery profiles following BABA robotic or endoscopic thyroidectomy. Fifty-eight adult patients scheduled for BABA robotic or endoscopic thyroidectomy were randomized into a control group (n = 29) and ketamine group (n = 29). Following induction of anesthesia, patients in each group were infused with the same volume of saline or ketamine solution (1 mg/kg bolus, 60 μg/kg/h continuous infusion). Total intravenous anesthesia with propofol and remifentanil was used to induce and maintain anesthesia. Pain scores (101-point numerical rating scale, 0 = no pain, 100 = the worst imaginable pain), the consumption of rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 hours postoperatively. Patients in the ketamine group reported lower pain scores than those in the control group at 6 hours (30 [30] vs 50 [30]; P = 0.017), 24 hours (20 [10] vs 30 [20]; P < 0.001), and 48 hours (10 [10] vs 20 [15]; P < 0.001) in neck area. No statistically significant differences were found between the 2 groups in terms of the requirements for rescue analgesics or the occurrence of adverse events. Intravenous ketamine infusion during anesthesia resulted in lower postoperative pain scores following BABA robotic or endoscopic thyroidectomy, with no increase in adverse events.

Addition of low-dose ketamine to midazolam and low-dose bupivacaine improves hemodynamics and postoperative analgesia during spinal anesthesia for cesarean section

PubMed Central

Basuni, Ahmed Sobhy

2016-01-01

Background and Aims: Spinal anesthesia for cesarean section (CS) is associated with an incidence of hypotension of 60-94%. This study hypothesizes that intrathecal combination of low-dose ketamine, midazolam, and low-dose bupivacaine improves hemodynamics and postoperative analgesia compared with fentanyl and low-dose bupivacaine during CS. Material and Methods: Fifty parturients undergoing elective CS were randomized equally to receive ketamine (10 mg), midazolam (2 mg) and 0.5% hyperbaric bupivacaine (8 mg) in group ketamine-midazolam-bupivacaine (KMB) or fentanyl (25 μg) and 0.5% hyperbaric bupivacaine (8 mg) in group fentanyl-bupivacaine (FB). Heart rate (HR), mean arterial blood pressure (MAP), oxygen saturation, sensorimotor block characteristics, pain-free period, side-effects including: hypotension, bradycardia, nausea, vomiting, sedation, pruritus, respiratory depression and dissociative manifestations, Apgar score at 1 and 5 min, and patients' satisfaction visual analog scores (VAS) were recorded. Patients in group KMB were followed for 6 months in order to assess any neurological disorder. Results: Group KMB showed higher sensory level (P = 0.006), rapid sensory (P = 0.001) and motor (P = 0.005) onsets, prolonged sensory (P = 0.008) and motor (P = 0.002) blocks, and prolonged pain free period (P = 0.002). Ketamine-midazolam stabilized HR and MAP, and significantly reduced incidence of hypotension (P = 0.002), bradycardia (P = 0.013) and vomiting (P = 0.019). Apgar scores at 1 and 5 min were comparable in both groups (P = 0.699 and 0.646 respectively). Patients' satisfaction VAS scores were significantly higher in group KMB (P = 0.001). No patients in KMB group showed dissociative or neurotoxic manifestations. Conclusion: Intrathecal low-dose ketamine combined with midazolam and low-dose bupivacaine stabilizes hemodynamics and prolongs postoperative analgesia without significant side-effects in parturients undergoing CS. PMID:27006540

Anesthetic Activity of Alfaxalone Compared with Ketamine in Mice

PubMed Central

Siriarchavatana, Parkpoom; Ayers, Jessica D; Kendall, Lon V

2016-01-01

Alfaxalone encased in hydroxypropyl-β-cyclodextrin is a neuroactive steroid compound that has recently been approved in the United States for use as an anesthetic in dogs and cats. We evaluated the use of alfaxalone compared with ketamine, both alone and in combination with xylazine, for anesthesia of C57BL/6 mice. We assessed time to onset of anesthesia, duration of action, reflex responses, respiratory rate, and clinical signs. Alfaxalone (80 mg/kg IP) induced a light surgical plane of anesthesia in all mice, with a time to onset of 2.2 ± 0.2 min and duration of 57.1 ± 3.8 min, whereas ketamine (80 mg/kg IP) provided only sedative effects (time to onset, 5.4 ± 0.4 min; duration, 6.9 ± 0.8 min). Clinically, alfaxalone caused a spectrum of activities, including popcorn-like jumping movements after injection, intense scratching of the face, hyperresponsiveness to noise or touch, and marked limb jerking during recovery. Adding xylazine to the single-agent protocols achieved deep surgical anesthesia (duration: alfaxalone + xylazine, 80.3 ± 17.8 min; ketamine + xylazine, 37.4 ± 8.2 min) and ameliorated the adverse clinical signs. Our preliminary analysis suggests that, because of its side effects, alfaxalone alone is not a viable anesthetic option for mice. Although alfaxalone combined with xylazine appeared to be a more viable option, some mice still experienced mild adverse reactions, and the long duration of action might be problematic regarding the maintenance of body temperature and monitoring of recovery. Further studies evaluating different routes of administration and drug combinations are warranted. PMID:27423149

Evaluation of medetomidine, ketamine and buprenorphine for neutering feral cats.

PubMed

Harrison, Kelly A; Robertson, Sheilah A; Levy, Julie K; Isaza, Natalie M

2011-12-01

A combination of medetomidine (M, 100 μg/kg), ketamine (K, 10 mg/kg) and buprenorphine (B, 10 μg/kg), administered by intramuscular injection, was evaluated for spaying and castration (neutering) of feral cats (n = 101). Eleven animals (11%) required supplemental anesthesia (isoflurane by mask) to maintain an adequate plane of surgical anesthesia. Atipamezole (A, 125 μg/kg) was administered subcutaneously at the completion of surgery. All cats recovered from surgery and were released the following day. A hemoglobin saturation (SpO(2)) value of < 95% was recorded at least once during anesthesia in all cats. This MKB combination can be used in a feral cat sterilization clinic, but isoflurane supplementation may be necessary. Further research is indicated to determine the clinical significance of the low SpO(2) values associated with this anesthetic regimen. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

PubMed

Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

2017-07-01

Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

Cerebral responses to local and global auditory novelty under general anesthesia

PubMed Central

Uhrig, Lynn; Janssen, David; Dehaene, Stanislas; Jarraya, Béchir

2017-01-01

Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI. Both, propofol, a GABAA-agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the cortical response to auditory inputs. The local effect vanished during propofol anesthesia and shifted spatially during ketamine anesthesia compared with wakefulness. Under increasing levels of propofol, we observed a progressive disorganization of the global effect in prefrontal, parietal and cingulate cortices and its complete suppression under ketamine anesthesia. Anesthesia also suppressed thalamic activations to the global effect. These results suggest that anesthesia preserves initial auditory processing, but disturbs both short-term and long-term auditory predictive coding mechanisms. The disorganization of auditory novelty processing under anesthesia relates to a loss of thalamic responses to novelty and to a disruption of higher-order functional cortical networks in parietal, prefrontal and cingular cortices. PMID:27502046

Ketamine induces toxicity in human neurons differentiated from embryonic stem cells via mitochondrial apoptosis pathway

PubMed Central

Bosnjak, Zeljko J.; Yan, Yasheng; Canfield, Scott; Muravyeva, Maria Y.; Kikuchi, Chika; Wells, Clive; Corbett, John; Bai, Xiaowen

2013-01-01

Ketamine is widely used for anesthesia in pediatric patients. Growing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models. Our understanding of anesthesia neurotoxicity in humans is currently limited by difficulties in obtaining neurons and performing developmental toxicity studies in fetal and pediatric populations. It may be possible to overcome these challenges by obtaining neurons from human embryonic stem cells (hESCs) in vitro. hESCs are able to replicate indefinitely and differentiate into every cell type. In this study, we investigated the toxic effect of ketamine on neurons differentiated from hESCs. Two-week-old neurons were treated with different doses and durations of ketamine with or without the reactive oxygen species (ROS) scavenger, Trolox. Cell viability, ultrastructure, mitochondrial membrane potential (ΔΨm), cytochrome c distribution within cells, apoptosis, and ROS production were evaluated. Here we show that ketamine induced ultrastructural abnormalities and dose- and time-dependently caused cell death. In addition, ketamine decreased ΔΨm and increased cytochrome c release from mitochondria. Ketamine also increased ROS production and induced differential expression of oxidative stress-related genes. Specifically, abnormal ultrastructural and ΔΨm changes occurred earlier than cell death in the ketamine-induced toxicity process. Furthermore, Trolox significantly decreased ROS generation and attenuated cell death caused by ketamine in a dose-dependent manner. In conclusion, this study illustrates that ketamine time- and dose-dependently induces human neurotoxicity via ROS-mediated mitochondrial apoptosis pathway and that these side effects can be prevented by the antioxidant agent Trolox. Thus, hESC-derived neurons might provide a promising tool for studying anesthetic-induced developmental neurotoxicity and prevention strategies. PMID:22873495

Comparison of the Effect of Thiopental Sodium with Midazolam-ketamine on Post-tonsillectomy Agitation in Children.

PubMed

Toliyat, Maryam; Zangoee, Maliheh; Ahrari, Shahnaz; Zangoee, Reza

2015-10-01

The aim of this study was to determine the effect of thiopental sodium with that of midazolam-ketamine on relieving agitation after tonsillectomy in children. In a clinical trial, 50 children aged 5-10 years, candidates for tonsillectomy, were randomly divided into two 25-member groups. In the first group, thiopental sodium 5mg/kg/IV, and in the second group combination of midazolam 0.01 mg/kg/IV and ketamine 1 mg/kg/IV were used to induce anesthesia. The level of sedation was assessed after surgery with the Ramsay scale. There were no significant differences between the two groups in terms of heart rate, arterial oxygen pressure (PO2), and duration of anesthesia. The Ramsay sedation score was significantly higher in the thiopental sodium group than in the midazolam-ketamine group (P=0.01). Thiopental sodium can be more effective than the combination of midazolam-ketamine for controlling agitation after tonsillectomy in children.

Up-regulation of insulin-like growth factor 2 by ketamine requires glycogen synthase kinase-3 inhibition.

PubMed

Grieco, Steven F; Cheng, Yuyan; Eldar-Finkelman, Hagit; Jope, Richard S; Beurel, Eléonore

2017-01-04

An antidepressant dose of the rapidly-acting ketamine inhibits glycogen synthase kinase-3 (GSK3) in mouse hippocampus, and this inhibition is required for the antidepressant effect of ketamine in learned helplessness depression-like behavior. Here we report that treatment with an antidepressant dose of ketamine (10mg/kg) increased expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect that required ketamine-induced inhibition of GSK3. Ketamine also inhibited hippocampal GSK3 and increased expression of hippocampal IGF2 in mice when administered after the induction of learned helplessness. Treatment with the specific GSK3 inhibitor L803-mts was sufficient to up-regulate hippocampal IGF2 expression. Administration of IGF2 siRNA reduced ketamine's antidepressant effect in the learned helplessness paradigm. Mice subjected to the learned helplessness paradigm were separated into two groups, those that were resilient (non-depressed) and those that were susceptible (depressed). Non-depressed resilient mice displayed higher expression of IGF2 than susceptible mice. These results indicate that IGF2 contributes to ketamine's antidepressant effect and that IGF2 may confer resilience to depression-like behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

Up-regulation of insulin-like growth factor 2 by ketamine requires glycogen synthase kinase-3 inhibition

PubMed Central

Grieco, Steven F.; Cheng, Yuyan; Eldar-Finkelman, Hagit; Jope, Richard S.; Beurel, Eléonore

2016-01-01

An antidepressant dose of the rapidly-acting ketamine inhibits glycogen synthase kinase-3 (GSK3) in mouse hippocampus, and this inhibition is required for the antidepressant effect of ketamine in learned helplessness depression-like behavior. Here we report that treatment with an antidepressant dose of ketamine (10 mg/kg) increased expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect that required ketamine-induced inhibition of GSK3. Ketamine also inhibited hippocampal GSK3 and increased expression of hippocampal IGF2 in mice when administered after the induction of learned helplessness. Treatment with the specific GSK3 inhibitor L803-mts was sufficient to up-regulate hippocampal IGF2 expression. Administration of IGF2 siRNA reduced ketamine's antidepressant effect in the learned helplessness paradigm. Mice subjected to the learned helplessness paradigm were separated into two groups, those that were resilient (non-depressed) and those that were susceptible (depressed). Non-depressed resilient mice displayed higher expression of IGF2 than susceptible mice. These results indicate that IGF2 contributes to ketamine's antidepressant effect and that IGF2 may confer resilience to depression-like behavior. PMID:27542584

Ketamine. A solution to procedural pain in burned children.

PubMed

Groeneveld, A; Inkson, T

1992-09-01

Our experience has shown ketamine to be a safe and effective method of providing pain relief during specific procedures in burned children. It renders high doses of narcotics unnecessary and offers children the benefit of general anesthesia without the requirement of endotracheal intubation and a trip to the operating room. The response of parents and staff to the use of ketamine has been positive. Parents often experience feelings of guilt following injury to a child and are eager to employ methods that reduce their child's pain. So far, no parent has refused the administration of ketamine; some have even asked that it be used during subsequent procedures on their child. With adequate pre-procedure teaching, parents are prepared for the possible occurrence of emergent reactions and can assist in reorienting the child during recovery. Staff have found that the stress of doing painful procedures on children is reduced when ketamine is used. The procedures tend to be quicker and the predicament of working on a screaming, agitated child is eliminated. At the same time, nursing staff have had to get used to the nystagmic gaze of the children and accept that these patients are truly anesthetized even though they might move and talk. Despite the success we and others have had with ketamine, several questions about its use in burn patients remain unanswered. The literature does not answer such questions as: Which nursing measures reduce the incidence of emergent reactions? How many ketamine anesthetics can safely be administered to one individual? How does the frequency of administration relate to tolerance in a burn patient? Are there detrimental effects of frequent or long-term use? Clearly, an understanding of these questions is necessary to determine the safe boundaries of ketamine use in burn patients. Ketamine is not a panacea for the problem of pain in burned children. But it is one means of managing procedural pain, which is, after all, a significant clinical

Molecular recognition of ketamine by a subset of olfactory G protein–coupled receptors

PubMed Central

Saven, Jeffery G.; Matsunami, Hiroaki; Eckenhoff, Roderic G.

2015-01-01

Ketamine elicits various neuropharmacological effects, including sedation, analgesia, general anesthesia, and antidepressant activity. Through an in vitro screen, we identified four mouse olfactory receptors (ORs) that responded to ketamine. In addition to their presence in the olfactory epithelium, these G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) are distributed throughout the central nervous system. To better understand the molecular basis of the interactions between ketamine and ORs, we used sequence comparison and molecular modeling to design mutations that (i) increased, reduced, or abolished ketamine responsiveness in responding receptors, and (ii) rendered non-responding receptors responsive to ketamine. We showed that olfactory sensory neurons (OSNs) that expressed distinct ORs responded to ketamine in vivo, suggesting that ORs may serve as functional targets for ketamine. The ability to both abolish and introduce responsiveness to ketamine in GPCRs enabled us to identify and confirm distinct interaction loci in the binding site, which suggested a signature ketamine-binding pocket that may guide exploration of additional receptors for this general anesthetic drug. PMID:25829447

Prenatal ketamine exposure causes abnormal development of prefrontal cortex in rat

PubMed Central

Zhao, Tianyun; Li, Chuanxiang; Wei, Wei; Zhang, Haixing; Ma, Daqing; Song, Xingrong; Zhou, Libing

2016-01-01

Ketamine is commonly used for anesthesia and as a recreational drug. In pregnant users, a potential neurotoxicity in offspring has been noted. Our previous work demonstrated that ketamine exposure of pregnant rats induces affective disorders and cognitive impairments in offspring. As the prefrontal cortex (PFC) is critically involved in emotional and cognitive processes, here we studied whether maternal ketamine exposure influences the development of the PFC in offspring. Pregnant rats on gestational day 14 were treated with ketamine at a sedative dose for 2 hrs, and pups were studied at postnatal day 0 (P0) or P30. We found that maternal ketamine exposure resulted in cell apoptosis and neuronal loss in fetal brain. Upon ketamine exposure in utero, PFC neurons at P30 showed more dendritic branching, while cultured neurons from P0 PFC extended shorter neurites than controls. In addition, maternal ketamine exposure postponed the switch of NR2B/2A expression, and perturbed pre- and postsynaptic protein expression in the PFC. These data suggest that prenatal ketamine exposure impairs neuronal development of the PFC, which may be associated with abnormal behavior in offsprings. PMID:27226073

Efficacy of Opioid-free Anesthesia in Reducing Postoperative Respiratory Depression in Children Undergoing Tonsillectomy

ClinicalTrials.gov

2018-05-04

Anesthesia; General Anesthesia; Analgesics, Opioid; Postoperative Complications; Pathologic Processes; Physiologic Effects of Drugs; Narcotics; Analgesics; Sleep Disordered Breathing; Obstructive Sleep Apnea of Child; Tonsillectomy; Respiratory Depression; Dexmedetomidine; Ketamine; Lidocaine; Gabapentin; Pulse Oximetry

Comparison of detomidine and romifidine as premedicants before ketamine and halothane anesthesia in horses undergoing elective surgery.

PubMed

Taylor, P M; Bennett, R C; Brearley, J C; Luna, S P; Johnson, C B

2001-03-01

To compare detomidine hydrochloride and romifidine as premedicants in horses undergoing elective surgery. 100 client-owned horses. After administration of acepromazine (0.03 mg/kg, IV), 50 horses received detomidine hydrochloride (0.02 mg/kg of body weight, IV) and 50 received romifidine (0.1 mg/kg, IV) before induction and maintenance of anesthesia with ketamine hydrochloride (2 mg/kg) and halothane, respectively. Arterial blood pressure and blood gases, ECG, and heart and respiratory rates were recorded. Induction and recovery were timed and graded. Mean (+/- SD) duration of anesthesia for all horses was 104 +/- 28 minutes. Significant differences in induction and recovery times or grades were not detected between groups. Mean arterial blood pressure (MABP) decreased in both groups 30 minutes after induction, compared with values at 10 minutes. From 40 to 70 minutes after induction, MABP was significantly higher in detomidine-treated horses, compared with romifidine-treated horses, although more romifidine-treated horses received dobutamine infusions. In all horses, mean respiratory rate ranged from 9 to 11 breaths/min, PaO2 from 200 to 300 mm Hg, PaCO2 from 59 to 67 mm Hg, arterial pH from 7.33 to 7.29, and heart rate from 30 to 33 beats/min, with no significant differences between groups. Detomidine and romifidine were both satisfactory premedicants. Romifidine led to more severe hypotension than detomidine, despite administration of dobutamine to more romifidine-treated horses. Both detomidine and romifidine are acceptable alpha2-adrenoceptor agonists for use as premedicants before general anesthesia in horses; however, detomidine may be preferable when maintenance of blood pressure is particularly important.

Ketamine for Pain Management-Side Effects & Potential Adverse Events.

PubMed

Allen, Cheryl A; Ivester, Julius R

2017-12-01

An old anesthetic agent, ketamine is finding new use in lower doses for analgesic purposes. There are concerns stemming from its potential side effects-specifically psychomimetic effects. These side effects are directly related to dose amount. The doses used for analgesic purposes are much lower than those used for anesthesia purposes. A literature review was performed to ascertain potential side effects and/or adverse events when using ketamine for analgesia purposes. The search included CINAHL, PubMed, and Ovid using the search terms "ketamine," "ketamine infusion," "pain," "adverse events," "practice guideline," and "randomized controlled trial." Searches were limited to full-text, peer-reviewed articles and systematic reviews. Initially 1,068 articles were retrieved. The search was then narrowed by using the Boolean connector AND with various search term combinations. After adjusting for duplication, article titles and abstracts were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion criteria were then applied. The literature supports the use of ketamine for analgesic purposes, and ketamine offers a nonopioid option for the management of some pain conditions. Because ketamine is still classified as an anesthetic agent, health care institutions should develop their own set of policies and protocols for the administration of ketamine. By using forethought and understanding of the properties of ketamine, appropriate care may be planned to mitigate potential side effects and adverse events so that patients are appropriately cared for and their pain effectively managed. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Total intravenous anesthesia with midazolam, ketamine, and xylazine or detomidine following induction with tiletamine, zolazepam, and xylazine in red deer (Cervus elaphus hippelaphus) undergoing surgery.

PubMed

Auer, Ulrike; Wenger, Sandra; Beigelböck, Christoph; Zenker, Wolfgang; Mosing, Martina

2010-10-01

Sixteen captive female red deer were successfully anesthetized to surgically implant a telemetry system. The deer were immobilized with (mean±SD) 1.79±0.29 mg/kg xylazine and 1.79±0.29 mg/kg tiletamine/zolazepam given intramuscularly with a dart gun. Anesthesia was maintained for 69±2 min using a total intravenous protocol with a catheter placed in the jugular vein. Group X received xylazine (0.5±0.055 mg/kg/hr) and group D, detomidine (2±0.22 μg/kg/hr), both in combination with ketamine (2±0.02 mg/kg/hr) and midazolam (0.03±0.0033 mg/kg/hr), as a constant rate infusion. Anesthesia was reversed with 0.09±0.01 mg/kg atipamezole and 8.7±1.21 μg/kg sarmazenil given intravenously in both groups. These drug combinations provided smooth induction, stable anesthesia for surgery, and rapid recovery. Respiratory depression and mild hypoxemia were seen, and we, therefore, recommend using supplemental intranasal oxygen.

Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice.

PubMed

Lin, Jen-Cheng; Lee, Mei-Yi; Chan, Ming-Huan; Chen, Yi-Chyan; Chen, Hwei-Hsien

2016-09-01

Ketamine is emerging as a new hope against depression, but ketamine-associated psychotomimetic effects limit its clinical use. An adjunct therapy along with ketamine to alleviate its adverse effects and even potentiate the antidepressant effects might be an alternative strategy. Betaine, a methyl derivative of glycine and a dietary supplement, has been shown to have antidepressant-like effects and to act like a partial agonist at the glycine site of N-methyl-D-aspartate receptors (NMDARs). Accordingly, betaine might have potential to be an adjunct to ketamine treatment for depression. The antidepressant-like effects of ketamine and betaine were evaluated by forced swimming test and novelty suppressed feeding test in mice. Both betaine and ketamine produced antidepressant-like effects. Furthermore, we determined the effects of betaine on ketamine-induced antidepressant-like and psychotomimetic behaviors, motor incoordination, hyperlocomotor activity, and anesthesia. The antidepressant-like responses to betaine combined with ketamine were stronger than their individual effects. In contrast, ketamine-induced impairments in prepulse inhibition, novel object recognition test, social interaction, and rotarod test were remarkably attenuated, whereas ketamine-induced hyperlocomotion and loss of righting reflex were not affected by betaine. These findings revealed that betaine could enhance the antidepressant-like effects, yet block the psychotomimetic effects of ketamine, suggesting that betaine can be considered as an add-on therapy to ketamine for treatment-resistant depression and suitable for the treatment of depressive symptoms in patients with schizophrenia.

Anesthetic and pathological changes following high doses of ketamine and xylazine in Sprague Dawley rats

PubMed Central

GIROUX, Marie-Chantal; HÉLIE, Pierre; BURNS, Patrick; VACHON, Pascal

2015-01-01

The main objective of this study was to compare the effects of ketamine and xylazine in aging rats when coadministered intraperitoneally at high anesthetic doses. Three groups (n=6 rats/group) consisting of rats at 3, 6 and 12 months of age were used. During anesthesia, animals were monitored for heart rate, respiratory frequency, blood oxygen saturation, and rectal temperature. The corneal and paw withdrawal reflex were also examined during anesthesia. During anesthesia, withdrawal and corneal reflexes were absent for progressively longer durations with increasing age. Significant decreases in cardiac and respiratory frequency and, blood oxygen saturation occurred for the 6- and 12-month-old animals. Respiratory frequency and blood oxygen saturation returned to normal at the end of the anesthesia; however, the significant decrease in cardiac frequency persisted in the 6- and 12-month-old animals. Rectal temperature was decreased significantly only in the 3-month-old animals. Pulmonary edema and effusion occurred in 50% of the 12-month-old animals. In conclusion, if ketamine-xylazine are used for anesthesia, the doses should be optimized for the age of the subjects prior to initiation of the research project. PMID:25818316

Caudal anesthesia in pediatric surgical practice.

PubMed

Rahman, S; Siddiqui, M A; Haque, M; Majumder, S K; Ali, M S; Majid, M A; Hasan, M R

2006-07-01

Prospective study was carried out on 100 patients since May 2005 in my private practice and in the department of pediatric surgery of MMCH. Under caudal anesthesia along with or without ketaminie induction and gas inhalation all the patients underwent different surgical procedure namely anorectal surgery (eg. anoplasty, rectal polyp), urogenital surgery (Circumcision, hypospadias, meatotomy), groin surgery (hernia, hydrocele) and foot & leg surgery. Calculated dose schedule of drugs used in anesthesia and volume were maintained. Time of giving anesthesia and time of starting analgesia were recorded. Per-operative and postoperative analgesia were evaluated. Every parent was explained regarding the merit of caudal anesthesia calculated and compared with that of general anesthesia. Application of caudal anesthesia with or without ketamine & diazepam induction can be used safely and cost effectively and may be put into protocol in many of the pediatric surgical practice both in institute and also in private practice.

Analysis of print news media framing of ketamine treatment in the United States and Canada from 2000 to 2015.

PubMed

Zhang, Melvyn W B; Hong, Ying X; Husain, Syeda F; Harris, Keith M; Ho, Roger C M

2017-01-01

There are multifaceted views on the use of ketamine, a potentially addictive substance, to treat mental health problems. The past 15 years have seen growing media coverage of ketamine for medical and other purposes. This study examined the print news media coverage of medical and other uses of ketamine in North America to determine orientations and trends over time. Print newspaper coverage of ketamine from 2000 to 2015 was reviewed, resulting in 43 print news articles from 28 North American newspapers. A 55-item structured coding instrument was applied to assess news reports of ketamine. Items captured negative and positive aspects, therapeutic use of ketamine, and adverse side effects. Chi-squares tested for changes in trends over time. In the 15-year reviewed period, the three most frequent themes related to ketamine were: abuse (68.2%), legal status (34.1%), and clinical use in anesthesia (31.8%). There was significant change in trends during two periods (2000-2007 and 2008-2015). In 2008-2015, print news media articles were significantly more likely to encourage clinical use of ketamine to treat depression (p = 0.002), to treat treatment resistant depression (p = 0.043), and to claim that ketamine is more effective than conventional antidepressants (p = 0.043). Our review found consistent positive changes in the portrayals of ketamine by the print news media as a therapeutic antidepressant that mirror the recent scientific publications. These changes in news media reporting might influence the popularity of ketamine use to treat clinical depression. Guidance is required for journalists on objective reporting of medical research findings, including limitations of current research evidence and potential risks of ketamine.

Post-electroconvulsive therapy recovery and reorientation time with methohexital and ketamine: a randomized, longitudinal cross-over design trial

PubMed Central

Yen, Tony; Khafaja, Mohamad; Lam, Nicholas; Crumbacher, James; Schrader, Ronald; Rask, John; Billstrand, Mary; Rothfork, Jacob; Abbott, Christopher C.

2014-01-01

Objectives Methohexital, a barbiturate anesthetic commonly used for electroconvulsive therapy (ECT), possesses dose-dependent anticonvulsant properties, and its use can interfere with effective seizure therapy in patients with high seizure thresholds. Ketamine, a NMDA-antagonist with epileptogenic properties not broadly used for ECT inductions, is a commonly used induction agent for general anesthesia. Recent studies suggest that the use of ketamine is effective in allowing successful ECT treatment in patients with high seizure thresholds without an increase in side-effects. In this preliminary study, we directly compared the recovery and re-orientation times of subjects receiving ketamine and methohexital for ECTs. Methods Twenty patients were randomized in a cross-over design to receive methohexital and ketamine for ECT inductions in alternating fashion for six trials. Primary outcome measures were recovery time (voluntary movement, respiratory effort, blood pressure, consciousness, and O2 saturation) and re-orientation time. Secondary outcome measures were individual recovery variables, side-effect occurrence, and seizure duration. Results: Overall recovery time was not significantly different between the two treatment arms (F(1,17) = 0.72, P = 0.41). Re-orientation time was faster in the methohexital arm (F(1,17) = 9.23, P = 0.007). Conclusion Ketamine inductions resulted in higher number of side-effects, higher subject dropout rates, and a longer reorientation time with respect to methohexital inductions. No significant difference in post-anesthesia recovery time was found between the ketamine and methohexital arms. Intolerability to ketamine affected a significant proportion of subjects, and suggests that ketamine should remain as an alternative or adjunctive agent for patients with high seizure thresholds. PMID:24755722

Analysis of print news media framing of ketamine treatment in the United States and Canada from 2000 to 2015

PubMed Central

2017-01-01

Objectives There are multifaceted views on the use of ketamine, a potentially addictive substance, to treat mental health problems. The past 15 years have seen growing media coverage of ketamine for medical and other purposes. This study examined the print news media coverage of medical and other uses of ketamine in North America to determine orientations and trends over time. Methods Print newspaper coverage of ketamine from 2000 to 2015 was reviewed, resulting in 43 print news articles from 28 North American newspapers. A 55-item structured coding instrument was applied to assess news reports of ketamine. Items captured negative and positive aspects, therapeutic use of ketamine, and adverse side effects. Chi-squares tested for changes in trends over time. Results In the 15-year reviewed period, the three most frequent themes related to ketamine were: abuse (68.2%), legal status (34.1%), and clinical use in anesthesia (31.8%). There was significant change in trends during two periods (2000–2007 and 2008–2015). In 2008–2015, print news media articles were significantly more likely to encourage clinical use of ketamine to treat depression (p = 0.002), to treat treatment resistant depression (p = 0.043), and to claim that ketamine is more effective than conventional antidepressants (p = 0.043). Conclusions Our review found consistent positive changes in the portrayals of ketamine by the print news media as a therapeutic antidepressant that mirror the recent scientific publications. These changes in news media reporting might influence the popularity of ketamine use to treat clinical depression. Guidance is required for journalists on objective reporting of medical research findings, including limitations of current research evidence and potential risks of ketamine. PMID:28257514

Effects of ketamine and alfaxalone on application of a feline pain assessment scale.

PubMed

Buisman, Mandy; Wagner, Marika C; Hasiuk, Michelle Mm; Prebble, Melanie; Law, Laura; Pang, Daniel Sj

2016-08-01

The objective of this study was to compare the effects of ketamine and alfaxalone on the application of a validated feline-specific multidimensional composite pain scale (UNESP-Botucatu MCPS). In a prospective, randomized, blinded, crossover trial, 11 adult cats (weight 4.4 ± 0.6 kg) were given dexmedetomidine (15 μg/kg) and hydromorphone (0.05 mg/kg) with either alfaxalone (2 mg/kg) or ketamine (5 mg/kg) as a single intramuscular injection for the induction of general anesthesia. After orotracheal intubation, general anesthesia (without surgery) was maintained for 32 mins with isoflurane, followed by atipamezole. The following parameters were recorded at baseline, 1-8 h and 24 h post-extubation: pain (pain expression and psychomotor subscales) and sedation scale scores. Alfaxalone treatment injection sites were examined for inflammation at baseline, postinjection, and 8 h and 24 h post-extubation. Psychomotor scores were higher with ketamine at hours 1 (3.5 [0-5.0], P <0.0001), 2 (2.5 [0-4.0], P <0.0001) and 3 (0.5 [0-4.0], P = 0.009) post-extubation compared with alfaxalone (hour 1, 0 [0-2]; hour 2, 0 [0-0]; hour 3, 0 [0-0]). Six cats in the ketamine group crossed the analgesic intervention threshold. In contrast, pain expression scores did not differ significantly between treatments at any time (P >0.05); one cat from each group crossed the analgesic intervention threshold. Sedation was greater with ketamine (1 [0-3], P = 0.02) than alfaxalone (0 [0-1]) 1 h post-extubation. No cats had visible inflammation at the injection sites at any time. Ketamine has a confounding effect on the psychomotor subscale of the pain scale studied, which may lead to erroneous administration of rescue analgesia. In contrast, alfaxalone was not associated with significant increases in either pain subscale. These effects of ketamine should be considered when evaluating acute postoperative pain in cats. © The Author(s) 2015.

Prophylactic use of intravenous ondansetron versus ketamine - midazolam combination for prevention of shivering during spinal anesthesia: A randomized double-blind placebo-controlled trial

PubMed Central

Safavi, Mohammadreza; Honarmand, Azim; Mohammadsadeqie, Sara

2015-01-01

Background: The aim of this study was to compare the efficacy intravenous (IV) ondansetron with ketamine plus midazolam for the prevention of shivering during spinal anesthesia (SA). Materials and Methods: Ninety patients, aged 18–65 years, undergoing lower extremity orthopedic surgery were included in the present study. SA was performed in all patients with hyperbaric bupivacaine 15 mg. The patients were randomly allocated to receive normal saline (Group C), ondansetron 8 mg IV (Group O) or ketamine 0.25 mg/kg IV plus midazolam 37.5 μg/kg IV (Group KM) immediately after SA. During surgery, shivering scores were recorded at 5 min intervals. The operating room temperature was maintained at 24°C. Results: The incidences of shivering were 18 (60%) in Group C, 6 (20%) in Group KM and 8 (26.6%) in Group O. The difference between Groups O and Group KM with Group C was statistically significant (P < 0.05). No significant difference was noted between Groups KM with Group O in this regard (P > 0.05). Peripheral and core temperature changes throughout surgery were not significantly different among three groups (P > 0.05). Incidence (%) of hallucination was not significantly different between the three groups (0, 3.3, 0 in Group O, Group KM, Group C respectively, P > 0.05). Conclusion: Prophylactic use of ondansetron 8 mg IV was comparable to ketamine 0.25 mg/kg IV plus midazolam 37.5 μg/kg IV in preventing shivering during SA. PMID:26605236

Reversible chemical restraint of free-range cattle with a concentrated combination of tiletamine-zolazepam, ketamine, and detomidine.

PubMed

Re, Michela; Blanco-Murcia, Francisco J; San Miguel, José Maria; Gómez de Segura, Ignacio A

2013-10-01

The aim of this study was to determine the efficacy of a concentrated combination of tiletamine-zolazepam [TZ, 0.53 mg/kg body weight (BW)], ketamine (Ket, 0.53 mg/kg BW), and detomidine (Det, 0.04 mg/kg BW) in the immobilization of free-range cattle for clinical procedures. The combination was administered intramuscularly to 53 animals. Anesthesia was reversed with the α2-adrenoceptor antagonist atipamezole. Locoregional anesthesia was provided with lidocaine when required. The TZKD combination induced suitable immobilization for minor surgical procedures or medical treatments. Anesthetic onset was rapid, taking a mean of 6.1 min [standard deviation (SD) 2.8 min]. The duration of anesthesia depended on the time of administration of the antagonist; the animals recovered in the standing position in 12.9 ± 8.9 min after the administration of atipamezole. The quality of anesthesia and analgesia were satisfactory. In conclusion, this TZKD combination can be used for both immobilization and minor surgical procedures in free-range cattle.

Reversible chemical restraint of free-range cattle with a concentrated combination of tiletamine–zolazepam, ketamine, and detomidine

PubMed Central

Re, Michela; Blanco-Murcia, Francisco J.; San Miguel, José Maria; Gómez de Segura, Ignacio A.

2013-01-01

The aim of this study was to determine the efficacy of a concentrated combination of tiletamine–zolazepam [TZ, 0.53 mg/kg body weight (BW)], ketamine (Ket, 0.53 mg/kg BW), and detomidine (Det, 0.04 mg/kg BW) in the immobilization of free-range cattle for clinical procedures. The combination was administered intramuscularly to 53 animals. Anesthesia was reversed with the α2-adrenoceptor antagonist atipamezole. Locoregional anesthesia was provided with lidocaine when required. The TZKD combination induced suitable immobilization for minor surgical procedures or medical treatments. Anesthetic onset was rapid, taking a mean of 6.1 min [standard deviation (SD) 2.8 min]. The duration of anesthesia depended on the time of administration of the antagonist; the animals recovered in the standing position in 12.9 ± 8.9 min after the administration of atipamezole. The quality of anesthesia and analgesia were satisfactory. In conclusion, this TZKD combination can be used for both immobilization and minor surgical procedures in free-range cattle. PMID:24124271

COMPARISON OF THE EFFECTS OF ORAL VS. PERITONSILLAR INFILTRATION OF KETAMINE IN PAIN REDUCTION AFTER TONSILLECTOMY: A RANDOMIZED CLINICAL TRIAL.

PubMed

Norouzi, Afsaneh; Jafari, Abolfazl; Vishteh, Hamid Reza Khoddami; Fateh, Shahin

2015-02-01

Although oral ketamine has been used in some cases to reduce pain in children, the use of this drug to reduce pain after tonsillectomy has not been studied yet. This double-blind clinical trial was conducted in 2009 in 92 children who were aged three to nine years old, met ASA I or II criteria, and were candidate for tonsillectomy. Patients were divided randomly into two groups. Half an hour before general anesthesia, 5 mg/kg ketamine mixed in 2 cc/kg apple juice was given to the children in oral ketamine group and 2 cc/kg of apple juice alone was given to the children in the peritonsillar group. After general anesthesia and three minutes before surgery 1 cc of 0.9% normal saline in the oral group and 1cc of ketamine (0.5 mg/kg) in the peritonsillar group was injected to the tonsil bed of patients. There was no difference between the two groups in terms of sex, age, and weight. Duration of surgery was significantly shorter in the peritonsillar group (P < 0.001) and the severity of postoperative bleeding was significantly higher in peritonsillar group (P = 0.022). However, postoperative bleeding recurred in 25 patients (27%) and there was no statistically significant difference between the two groups. The level of pain in children six hours after surgery according to CHEOPS criteria was significantly lower in the peritonsillar group (0.9 ± 0.8) than in the oral group (2.6 ± 1) (P < 0.001). The finding of this study showed that, compared with the peritonsillar infiltration of ketamine, the use of oral ketamine before general anesthesia was less effective in reducing postoperative pain of tonsillectomy in children.

Comparison between analgesic effect of bupivacaine thoracic epidural and ketamine infusion plus wound infiltration with local anesthetics in open cholecystectomy.

PubMed

Megahed, Nagwa Ahmed Ebrahim; Ellakany, Mohamed; Elatter, Ahmed Mohammed Ibrahim; Moustafa Teima, Mohamed Ahmed Ali

2014-01-01

Neuraxial blocks result in sympathetic block, sensory analgesia and motor block. Continuous epidural anesthesia through a catheter offers several options for perioperative analgesia. Local anesthetic boluses or infusions can provide profound analgesia. Although the role of low-dose ketamine (<2 mg/kg intramuscular, <1 mg/kg intravenous [IV] or ≤ 20 μg/kg/min by IV infusion) in the treatment of post-operative pain is controversial, perioperative administration of a small dose of ketamine may be valuable to a multimodal analgesic regimen. A local anesthetic can be used for wound infiltration intra-operative to minimized the surgical pain. A prospective randomized study was performed in which 40 patients scheduled for elective open cholecystectomy under general anesthesia admitted to the Medical Research Institute were included and further subdivided into two groups, group A, received thoracic epidural catheter at T7-8, activation was done 20 min before induction of anesthesia with plain bupivacaine at a concentration of 0.25% at a volume of 1 ml/segment aiming to block sensory supply from T4-L2, then received continuous thoracic epidural infusion intra and postoperatively with plain bupivacaine at a concentration of 0.125% at a rate of 5 ml/h for 24 h, group B received 0.3 mg/kg bolus of ketamine at the time of induction then 0.1 mg/kg/h ketamine IV infusion during surgery followed by wound infiltration with 15 ml of plain bupivacaine 0.5% at the time of skin closure. Bupivacaine thoracic epidural analgesia had better control on heart rate and mean arterial blood pressure than ketamine infusion plus wound infiltration with local anesthetic in patients undergoing open cholecystectomy. Thoracic epidural analgesia had better control on hemodynamic changes intra-and postoperatively than ketamine infusion with local wound infiltration in open cholecystectomy.

[Assessment of the use of racemic ketamine and its S(+) isomer, associated or not with low doses of fentanyl, in balneotherapy for major burn patients].

PubMed

Cantinho, Fernando Antônio de Freitas; Silva, Antonio Carlos Pereira da

2009-01-01

The care of the wounds of major burn patients triggers severe painful stimuli. The objective of this study was to assess the safety and efficacy of different drug combinations in anesthesia for balneotherapy. After approval by the Ethics Commission, 200 procedures of balneotherapy in 87 major burn adult patients were evaluated. Midazolam was used in all cases. The vials of ketamine were numbered and, therefore, at the time of the use, one did not know whether racemic or S(+)ketamine was being used. Each morning it was decided by drawing lots whether fentanyl would be used or not in the procedures of that day. Patients were included in one of four groups: ISO/sf (S(+) isomer without fentanyl), ISO/cf (S(+) isomer with fentanyl), RAC/sf (racemic ketamine without fentanyl), and RAC/cf (racemic ketamine with fentanyl). The initial doses proposed were as follows: midazolam, 0.06 mg.kg-1; ketamine, 1.0 to 1.1 mg.kg-1; and fentanyl, 0.8 (1/4)g.kg1-1; additional doses were administered as needed. Only one patient recalled the pain of balneotherapy. In the group that received S(+)ketamine, the use of fentanyl did not bring additional advantages; however, when associated with racemic ketamine, fentanyl reduced the total dose and the number of ketamine boluses. The extension of body surface burned was the main determinant of the severity of post-procedure pain. Reduced pain severity was the main factor considered by patients when grading their satisfaction with the anesthesia. The four different drug combinations proved to be safe and guaranteed the absence of pain during balneotherapy. Characteristics not directly related to the anesthetics proved to be more important in the incidence of post-procedure pain, which was the main factor considered by major burn patient to define their satisfaction with the anesthesia used.

Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood

PubMed Central

Huang, Lianyan; Yang, Guang

2014-01-01

Background Recent studies in rodents suggest that repeated and prolonged anesthetic exposure at early stages of development leads to cognitive and behavioral impairments later in life. However, the underlying mechanism remains unknown. In this study, we tested whether exposure to general anesthesia during early development will disrupt the maturation of synaptic circuits and compromise learning-related synaptic plasticity later in life. Methods Mice received ketamine/xylazine (20/3 mg/kg) anesthesia for one or three times, starting at either early [postnatal day 14 (P14)] or late (P21) stages of development (n=105). Control mice received saline injections (n=34). At P30, mice were subjected to rotarod motor training and fear conditioning. Motor learning-induced synaptic remodeling was examined in vivo by repeatedly imaging fluorescently-labeled postsynaptic dendritic spines in the primary motor cortex before and after training using two-photon microscopy. Results Three exposures to ketamine/xylazine anesthesia between P14–18 impair the animals’ motor learning and learning-dependent dendritic spine plasticity [new spine formation, 8.4 ± 1.3% (mean ± SD) versus 13.4 ± 1.8%, P = 0.002] without affecting fear memory and cell apoptosis. One exposure at P14 or three exposures between P21–25 has no effects on the animals’ motor learning or spine plasticity. Finally, enriched motor experience ameliorates anesthesia-induced motor learning impairment and synaptic deficits. Conclusion Our study demonstrates that repeated exposures to ketamine/xylazine during early development impair motor learning and learning-dependent dendritic spine plasticity later in life. The reduction in synaptic structural plasticity may underlie anesthesia-induced behavioral impairment. PMID:25575163

Guaifenesin alone or in combination with ketamine or sodium pentobarbital as an anesthetic in rabbits.

PubMed Central

Olson, M E; McCabe, K; Walker, R L

1987-01-01

Guaifenesin was administered alone and in combination with ketamine or sodium pentobarbital to adult New Zealand white rabbits. A solution of 5% guaifenesin in 5% dextrose given intravenously at a dosage of 200 mg/kg, abolished the pedal, palpebral and corneal reflexes for up to 15 minutes with little influence on cardiopulmonary function. Guaifenesin (200 mg/kg, intravenously) and ketamine (50 mg/kg, intramuscularly) produced effective and safe surgical anesthesia for over 30 minutes. This combination mildly depressed respiratory rate but heart rate and arterial blood pressure were not significantly affected. Guaifenesin (200 mg/kg, intravenously) was combined with sodium pentobarbital (20 mg/kg, intravenously) to produce surgical anesthesia for a period of more than 30 minutes. This combination depressed respiratory rate, produced a tachycardia and decreased arterial blood pressure. PMID:3651894

Comparison of cardiorespiratory variables in dorsally recumbent horses anesthetized with guaifenesin-ketamine-xylazine spontaneously breathing 50% or maximal oxygen concentrations.

PubMed

Karrasch, Nicole M; Hubbell, John A E; Aarnes, Turi K; Bednarski, Richard M; Lerche, Phillip

2015-04-01

This study compared cardiorespiratory variables in dorsally recumbent horses anesthetized with guaifenesin-ketamine-xylazine and spontaneously breathing 50% or maximal (> 90%) oxygen (O2) concentrations. Twelve healthy mares were randomly assigned to breathe 50% or maximal O2 concentrations. Horses were sedated with xylazine, induced to recumbency with ketamine-diazepam, and anesthesia was maintained with guaifenesin-ketamine-xylazine to effect. Heart rate, arterial blood pressures, respiratory rate, lithium dilution cardiac output (CO), inspired and expired O2 and carbon dioxide partial pressures, and tidal volume were measured. Arterial and mixed-venous blood samples were collected prior to sedation (baseline), during 30 minutes of anesthesia, 10 minutes after disconnection from O2, and 30 minutes after standing. Shunt fraction, O2 delivery, and alveolar-arterial O2 partial pressures difference [P(A-a)O2] were calculated. Recovery times were recorded. There were no significant differences between groups in cardiorespiratory parameters or in P(A-a)O2 at baseline or 30 minutes after standing. Oxygen partial pressure difference in the 50% group was significantly less than in the maximal O2 group during anesthesia.

Comparison of cardiorespiratory variables in dorsally recumbent horses anesthetized with guaifenesin-ketamine-xylazine spontaneously breathing 50% or maximal oxygen concentrations

PubMed Central

Karrasch, Nicole M.; Hubbell, John A.E.; Aarnes, Turi K.; Bednarski, Richard M.; Lerche, Phillip

2015-01-01

This study compared cardiorespiratory variables in dorsally recumbent horses anesthetized with guaifenesin-ketamine-xylazine and spontaneously breathing 50% or maximal (> 90%) oxygen (O2) concentrations. Twelve healthy mares were randomly assigned to breathe 50% or maximal O2 concentrations. Horses were sedated with xylazine, induced to recumbency with ketamine-diazepam, and anesthesia was maintained with guaifenesin-ketamine-xylazine to effect. Heart rate, arterial blood pressures, respiratory rate, lithium dilution cardiac output (CO), inspired and expired O2 and carbon dioxide partial pressures, and tidal volume were measured. Arterial and mixed-venous blood samples were collected prior to sedation (baseline), during 30 minutes of anesthesia, 10 minutes after disconnection from O2, and 30 minutes after standing. Shunt fraction, O2 delivery, and alveolar-arterial O2 partial pressures difference [P(A-a)O2] were calculated. Recovery times were recorded. There were no significant differences between groups in cardiorespiratory parameters or in P(A-a)O2 at baseline or 30 minutes after standing. Oxygen partial pressure difference in the 50% group was significantly less than in the maximal O2 group during anesthesia. PMID:25829559

Accelerated Recovery of Consciousness after General Anesthesia Is Associated with Increased Functional Brain Connectivity in the High-Gamma Bandwidth

PubMed Central

Li, Duan; Hambrecht-Wiedbusch, Viviane S.; Mashour, George A.

2017-01-01

Recent data from our laboratory demonstrate that high-frequency gamma connectivity across the cortex is present during consciousness and depressed during unconsciousness. However, these data were derived from static and well-defined states of arousal rather than during transitions that would suggest functional relevance. We also recently found that subanesthetic ketamine administered during isoflurane anesthesia accelerates recovery upon discontinuation of the primary anesthetic and increases gamma power during emergence. In the current study we re-analyzed electroencephalogram (EEG) data to test the hypothesis that functional cortical connectivity between anterior and posterior cortical regions would be increased during accelerated recovery induced by ketamine when compared to saline-treated controls. Rodents were instrumented with intracranial EEG electrodes and general anesthesia was induced with isoflurane anesthesia. After 37.5 min of continuous isoflurane anesthesia, a subanesthetic dose of ketamine (25 mg/kg intraperitoneal) was administered, with evidence of a 44% reduction in emergence time. In this study, we analyzed gamma and theta coherence (measure of undirected functional connectivity) and normalized symbolic transfer entropy (measure of directed functional connectivity) between frontal and parietal cortices during various levels of consciousness, with a focus on emergence from isoflurane anesthesia. During accelerated emergence in the ketamine-treated group, there was increased frontal-parietal coherence {p = 0.005, 0.05–0.23 [95% confidence interval (CI)]} and normalized symbolic transfer entropy [frontal to parietal: p < 0.001, 0.010–0.026 (95% CI); parietal to frontal: p < 0.001, 0.009–0.025 (95% CI)] in high-frequency gamma bandwidth as compared with the saline-treated group. Surrogates of cortical information exchange in high-frequency gamma are increased in association with accelerated recovery from anesthesia. This finding adds evidence

Accelerated Recovery of Consciousness after General Anesthesia Is Associated with Increased Functional Brain Connectivity in the High-Gamma Bandwidth.

PubMed

Li, Duan; Hambrecht-Wiedbusch, Viviane S; Mashour, George A

2017-01-01

Recent data from our laboratory demonstrate that high-frequency gamma connectivity across the cortex is present during consciousness and depressed during unconsciousness. However, these data were derived from static and well-defined states of arousal rather than during transitions that would suggest functional relevance. We also recently found that subanesthetic ketamine administered during isoflurane anesthesia accelerates recovery upon discontinuation of the primary anesthetic and increases gamma power during emergence. In the current study we re-analyzed electroencephalogram (EEG) data to test the hypothesis that functional cortical connectivity between anterior and posterior cortical regions would be increased during accelerated recovery induced by ketamine when compared to saline-treated controls. Rodents were instrumented with intracranial EEG electrodes and general anesthesia was induced with isoflurane anesthesia. After 37.5 min of continuous isoflurane anesthesia, a subanesthetic dose of ketamine (25 mg/kg intraperitoneal) was administered, with evidence of a 44% reduction in emergence time. In this study, we analyzed gamma and theta coherence (measure of undirected functional connectivity) and normalized symbolic transfer entropy (measure of directed functional connectivity) between frontal and parietal cortices during various levels of consciousness, with a focus on emergence from isoflurane anesthesia. During accelerated emergence in the ketamine-treated group, there was increased frontal-parietal coherence { p = 0.005, 0.05-0.23 [95% confidence interval (CI)]} and normalized symbolic transfer entropy [frontal to parietal: p < 0.001, 0.010-0.026 (95% CI); parietal to frontal: p < 0.001, 0.009-0.025 (95% CI)] in high-frequency gamma bandwidth as compared with the saline-treated group. Surrogates of cortical information exchange in high-frequency gamma are increased in association with accelerated recovery from anesthesia. This finding adds evidence

Pretreatment with minocycline restores neurogenesis in the subventricular zone and subgranular zone of the hippocampus after ketamine exposure in neonatal rats.

PubMed

Lu, Yang; Giri, P K; Lei, Shan; Zheng, Juan; Li, Weisong; Wang, Ning; Chen, Xinlin; Lu, Haixia; Zuo, Zhiyi; Liu, Yong; Zhang, Pengbo

2017-06-03

Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative disease models. In the present study, we investigated whether the disturbed neurogenesis and behavioral deficits after ketamine neonatal exposure could be alleviated by minocycline. Postnatal day (PND)7 Sprague-Dawley rat pups randomly received either normal saline, ketamine, or minocycline 30min prior to ketamine administration, respectively. The rats were decapitated at PND14 for the detection of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampus by immunostaining. The protein expression of p-Akt, p-GSK-3β in the SVZ and SGZ at 12h after anesthesia, PND10 and PND14 were assessed by western blotting analysis. At PND 42-47, spatial learning and memory abilities were measured by the Morris water maze in all groups. Our data showed that ketamine exposure in neonatal rats resulted in neurogenetic damage and persistent cognitive deficits, and that pretreatment with minocycline eliminated the brain development damage and improved the behavioral function in adult rats. Moreover, the protection of minocycline is associated with the PI3K/Akt signaling pathway. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Hippocampal Perineuronal Nets Are Required for the Sustained Antidepressant Effect of Ketamine.

PubMed

Donegan, Jennifer J; Lodge, Daniel J

2017-04-01

N-methyl-D-aspartate receptor antagonists, like ketamine, produce a rapid-acting and long-lasting antidepressant effect. Although the mechanism is not completely understood, ketamine is thought to preferentially target N-methyl-D-aspartate receptors on fast-spiking parvalbumin-containing interneurons. The function of parvalbumin-containing interneurons is dependent on perineuronal nets, a specialized form of extracellular matrix that surrounds these cells. Chondroitinase was used to enzymatically degrade perineuronal nets surrounding parvalbumin-containing interneurons in the ventral hippocampus, a region that is involved in the antidepressant response to ketamine. Rats were tested on the forced swim test 30 minutes and 1 week after ketamine administration. Thirty minutes after ketamine injection, both chondroitinase-treated and control animals had a decrease in immobility. One week later, however, the antidepressant-like response observed with ketamine was completely abolished in the chondroitinase-treated animals. This suggests that parvalbumin interneuron function in the ventral hippocampus is essential for the sustained antidepressant effect of ketamine. © The Author 2016. Published by Oxford University Press on behalf of CINP.

S -ketamine compared to etomidate during electroconvulsive therapy in major depression.

PubMed

Zavorotnyy, Maxim; Kluge, Ina; Ahrens, Kathrin; Wohltmann, Thomas; Köhnlein, Benjamin; Dietsche, Patricia; Dannlowski, Udo; Kircher, Tilo; Konrad, Carsten

2017-12-01

Objective of the study was to compare two commonly used anesthetic drugs, S-ketamine and etomidate, regarding their influence on seizure characteristics, safety aspects, and outcome of electroconvulsive therapy (ECT) in major depression. Treatment data of 60 patients who underwent a total number of 13 ECTs (median) because of the severe or treatment-resistant major depressive disorder (DSM-IV) were analyzed. Etomidate, mean dosage (SD) = 0.25 (0.04) mg/kg, was used for anesthesia in 29 participants; 31 patients received S-ketamine, mean dosage (SD) = 0.96 (0.26) mg/kg. Right unilateral brief pulse ECTs were performed. The number of ECTs was individually adjusted to clinical needs, mean (SD) = 13.0 (4.3). Seizure characteristics, adverse events, and the clinical global impression (CGI) scores were compared between the both groups during ECT series. In the S-ketamine group, a lower initial seizure threshold (p = 0.014), stimulation charge (p < 0.001), higher postictal suppression (p < 0.001), EEG ictal amplitude (p = 0.04), EEG coherence (p < 0.001) and maximum heart rate (p = 0.015) were measured. Etomidate was associated with more frequent abortive seizures (p = 0.02) and restimulations (p = 0.01). The CGI scores, the number of sessions within an ECT series, and the incidence of adverse events did not differ between groups. Due to its lower initial seizure threshold, S-ketamine might hold a potential to become a clinically favorable anesthetic agent during ECT. However, the current findings should be interpreted with caution, and further prospective randomized clinical trials are required. Also, specific adverse effects profile of S-ketamine, especially with regard to the cardiovascular risk, needs to be taken into account.

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway.

PubMed

Li, Xinran; Guo, Cen; Li, Yanan; Li, Lina; Wang, Yuxin; Zhang, Yiming; Li, Yue; Chen, Yu; Liu, Wenhan; Gao, Li

2017-05-16

Ketamine has been reported to impair the capacity for learning and memory. This study examined whether these capacities were also altered in the offspring and investigated the role of the CREB signaling pathway in pregnant rats, subjected to ketamine-induced anesthesia. On the 14th day of gestation (P14), female rats were anesthetized for 3 h via intravenous ketamine injection (200 mg/Kg). Morris water maze task, contextual and cued fear conditioning, and olfactory tasks were executed between the 25th to 30th day after birth (B25-30) on rat pups, and rats were sacrificed on B30. Nerve density and dendritic spine density were examined via Nissl's and Golgi staining. Simultaneously, the contents of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII), p-CaMKII, CaMKIV, p-CaMKIV, Extracellular Regulated Protein Kinases (ERK), p-ERK, Protein Kinase A (PKA), p-PKA, cAMP-Response Element Binding Protein (CREB), p-CREB, and Brain Derived Neurotrophic Factor (BDNF) were detected in the hippocampus. We pretreated PC12 cells with both PKA inhibitor (H89) and ERK inhibitor (SCH772984), thus detecting levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. The results revealed that ketamine impaired the learning ability and spatial as well as conditioned memory in the offspring, and significantly decreased the protein levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. We found that ERK and PKA (but not CaMKII or CaMKIV) have the ability to regulate the CREB-BDNF pathway during ketamine-induced anesthesia in pregnant rats. Furthermore, ERK and PKA are mutually compensatory for the regulation of the CREB-BDNF pathway.

Blood-Brain Barrier Disruption Caused by Ultrasound Bursts Combined with Microbubbles Depends on Anesthesia

NASA Astrophysics Data System (ADS)

McDannold, Nathan; Zhang, Yongzhi; Vykhodtseva, Natalia

2011-09-01

Prior works on BBB disruption via inter-arterial infusions of osmotic agents have shown a strong dependence on anesthesia. Here, we investigated whether different anesthesia agents can affect ultrasound-induced BBB disruption. A piston transducer fired through a rubber aperture (frequency: 532 kHz, diameter: 4 cm, aperture diameter: 16 mm) was used to generate the ultrasound fields, and sonications combined with an ultrasound contrast agent were performed at 5 power levels. BBB disruption was quantified by measuring the MRI contrast enhancement in T1-weighted MRI, and erythrocyte extravasation characterized in light microscopy. For each exposure level tested, experiments performed with ketamine/xylazine resulted in significantly greater (P<0.05) enhancement than with isoflurane/oxygen. The onset of severe red blood cell extravasation occurred at lower power levels with ketamine/xylazine. These results suggest ultrasound-induced BBB disruption can depend on anesthesia agent, possibly due effects on the vasculature. These results suggest that care is needed in comparing experiments with different anesthesia agents and physiological factors need to be considered with ultrasound-induced BBB disruption.

Ketamine-induced apoptosis in the mouse cerebral cortex follows similar characteristic of physiological apoptosis and can be regulated by neuronal activity.

PubMed

Wang, Qi; Shen, Feng-Yan; Zou, Rong; Zheng, Jing-Jing; Yu, Xiang; Wang, Ying-Wei

2017-06-17

The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry. To explore the effect of neural activity on ketamine-induced apoptosis, the approaches of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and an environmental enrichment (EE) were performed. Ketamine-induced apoptosis in S1 is most prominent at postnatal days 5 and 7 (P5 - P7), and becomes insignificant by P12. Physiological and ketamine-induced apoptosis follow similar developmental patterns, mostly comprised of layer V pyramidal neurons at P5 and shifting to mostly layer II to IV GABAergic neurons by P9. Changes in neuronal activity induced by the DREADD system bidirectionally regulated the pattern of ketamine-induced apoptosis, with reduced activity inducing increased apoptosis and shifting the lamination pattern to a more immature form. Importantly, rearing mice in an EE significantly reduced the magnitude of ketamine-induced apoptosis and shifted its developmental pattern to a more mature form. Together, these results demonstrate that lamination pattern and cell-type dependent vulnerability to ketamine-induced apoptosis follow the physiological apoptosis pattern and are age- and activity-dependent. Naturally elevating neuronal activity is a possible method for reducing the adverse effects of general anesthesia.

Influence of ketamine on regional brain glucose use

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, D.W.; Mans, A.M.; Biebuyck, J.F.

1988-08-01

The purpose of this study was to determine the effect of different doses of ketamine on cerebral function at the level of individual brain structures as reflected by glucose use. Rats received either 5 or 30 mg/kg ketamine intravenously as a loading dose, followed by an infusion to maintain a steady-state level of the drug. An additional group received 30 mg/kg as a single injection only, and was studied 20 min later, by which time they were recovering consciousness (withdrawal group). Regional brain energy metabolism was evaluated with (6-/sup 14/C)glucose and quantitative autoradiography during a 5-min experimental period. A subhypnotic,more » steady-state dose (5 mg/kg) of ketamine caused a stimulation of glucose use in most brain areas, with an average increase of 20%. At the larger steady-state dose (30 mg/kg, which is sufficient to cause anesthesia), there was no significant effect on most brain regions; some sensory nuclei were depressed (inferior colliculus, -29%; cerebellar dentate nucleus, -18%; vestibular nucleus, -16%), but glucose use in the ventral posterior hippocampus was increased by 33%. In contrast, during withdrawal from a 30-mg/kg bolus, there was a stimulation of glucose use throughout the brain (21-78%), at a time when plasma ketamine levels were similar to the levels in the 5 mg/kg group. At each steady-state dose, as well as during withdrawal, ketamine caused a notable stimulation of glucose use by the hippocampus.« less

Ketamine

MedlinePlus

... Staying Safe Videos for Educators Search English Español Ketamine KidsHealth / For Teens / Ketamine Print en español Ketamina What It Is: Ketamine hydrochloride is a quick-acting anesthetic that is ...

Clinically Relevant Concentrations of Ketamine Inhibit Osteoclast Formation In Vitro in Mouse Bone Marrow Cultures.

PubMed

Du, Erxia; McAllister, Patrick; Venna, Venugopal Reddy; Xiao, Liping

2017-04-01

Ketamine has been used safely in clinics for decades for analgesia and anesthesia. It is increasingly popular in clinical practice due to its new uses and importance for emergency procedures. It is known that ketamine is sequestered in the bone marrow and the major receptors for ketamine, noncompetitive N-methyl-d-aspartate receptors (NMDARs), are expressed in osteoclasts (OCs) and osteoblasts. However, the impact of ketamine on OCs or osteoblasts is unknown. In this study, we investigated the effects of ketamine on osteoclastogenesis and regulation of NMDARs expression in vitro. Bone marrows (BMs) or bone marrow macrophages (BMMs) were cultured in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) with or without ketamine for up to 6 days. OC formation peaked at day 5. On day 5 of culture, ketamine inhibited OC formation from both BM and BMM cultures at clinically relevant concentrations (3-200 µM). Ketamine inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) in BMM cultures. Inhibition of ketamine on RANKL-induced osteoclastogenesis is associated with down-regulation of NMDARs. In addition, ketamine significantly inhibited the M-CSF induced migration of BMMs, inhibited cell fusion and significantly increased mature OC apoptosis. We conclude that clinically relevant concentrations of ketamine inhibit OC formation in both BM and BMM cultures in vitro through inhibiting migration and fusion process and enhancing mature OC apoptosis. It is likely that ketamine regulates osteoclastogenesis, at least in part, via its effects on NMDAR expression. J. Cell. Biochem. 118: 914-923, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ketamine: An Update on Cellular and Subcellular Mechanisms with Implications for Clinical Practice.

PubMed

Iacobucci, Gary J; Visnjevac, Ognjen; Pourafkari, Leili; Nader, Nader Djalal

2017-02-01

Ketamine is one of the oldest hypnotic agents used to provide an anesthetic agent with analgesic properties and minimal suppressive effects on respiration. The ability of ketamine in modulating glutamatergic (N-methyl D-aspartate) pain receptors has made this anesthetic drug a new option for the management of patients with chronic pain syndromes. Further preclinical and clinical findings suggest ketamine may have wide ranging effects on both cognition and development. Recent advances have revealed an unprecedented role for ketamine in the acute management of depression. The purpose of this review is to integrate a number of basic science, preclinical, and clinical studies with the goal of providing insight into the possible signaling events underlying ketamine's biological effects in pain management, depression, cognition and memory, and neurodevelopment. Narrative literature review. Health science library. A comprehensive literature search was performed for the following medical subject headings and keywords (ketamine, anesthesia, pain, analgesia, depression, NMDA receptors) on PubMed, Google Scholar, and Medline from 1966 to the present time. The search was then limited to those in the English language. The full text of the relevant articles were printed and reviewed by all authors. We provided a comprehensive review of the literature that explored the pharmacologic aspects of ketamine from its conception as an anesthetic to its evolution as a drug used for treatment of depression and pain. To address the patient response variability observed in clinical studies, we have provided possible patient-specific factors that could contribute to outcome variability. Like any review, this study was limited by publication bias and missing information on negative studies which were denied publication. Ketamine, an old anesthetic agent with analgesic properties, is currently being considered for treating patients with chronic pain and depression. The complex pharmacological

General Anesthesia Inhibits the Activity of the "Glymphatic System".

PubMed

Gakuba, Clement; Gaberel, Thomas; Goursaud, Suzanne; Bourges, Jennifer; Di Palma, Camille; Quenault, Aurélien; de Lizarrondo, Sara Martinez; Vivien, Denis; Gauberti, Maxime

2018-01-01

INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent.

Efficacy of Ketamine in Pediatric Sedation Dentistry: A Systematic Review.

PubMed

Oh, Samuel; Kingsley, Karl

2018-05-01

Ketamine has been used as a safe and effective sedative to treat adults and children exhibiting high levels of anxiety or fear during dental treatment. Pediatric dentistry often involves patients with high levels of anxiety and fear and possibly few positive dental experiences. Patient management can involve behavioral approaches, as well as the use of sedation or general anesthesia with a variety of agents, including midazolam, diazepam, hydroxyzine, meperidine, and ketamine. The aim of this study was to investigate the clinical efficacy of ketamine use in pediatric sedation dentistry through systematic review and analysis. A systematic review of publications between 1990 and 2015 was conducted using PubMed and MEDLINE databases maintained by the US National Library of Medicine and the National Institutes of Health. The keywords used were (ketamine) AND (dental OR dentistry) AND (sedation). The abstract and title of all potential publications were then screened for clinical trials and to remove non-English articles, non-human or animal trials, and other non-dental or non-relevant studies. A total of 1,657 citations were initially identified, reviewed, and screened, eventually resulting in inclusion of 25 clinical trials in this systematic review. Nineteen studies evaluated ketamine effects in pediatric dental sedation using oral (non-invasive) administration, three involved subcutaneous or intramuscular injection, and three were completed intravenously. Evidence analysis of these trials revealed the majority (n = 22/25) provided strong, positive evidence for the use of ketamine (alone or in combination) to reduce dental anxiety and behavioral non-compliance with the remainder suggesting equivocal results. Additional endpoints evaluated in some studies involved dosage, as well as time to achieve sedation effect. The use of ketamine (alone or in combination) can provide safe, effective, and timely sedation in pediatric patients regardless of the route of

Drug Residues after Intravenous Anesthesia and Intrathecal Lidocaine Hydrochloride Euthanasia in Horses.

PubMed

Aleman, M; Davis, E; Knych, H; Guedes, A; Smith, F; Madigan, J E

2016-07-01

Intrathecal lidocaine hydrochloride under general anesthesia has been used as an alternative method of euthanasia in equids. Carnivore, scavenger, and even human consumption of horse meat from carcasses have been anecdotally reported in rural areas after this method of euthanasia. The presence of drug residues in horse meat has not been investigated. To investigate if drug residues are found in horse tissues and determine their concentrations. Of 11 horses requiring euthanasia for medical reasons. Prospective descriptive study. Horses were anesthetized with total IV dose of xylazine (mean, 2.5 mg/kg), midazolam (0.1 mg/kg), and ketamine hydrochloride (mean, 5.8 mg/kg). An atlanto-occipital cisterna centesis for the collection of cerebrospinal fluid (CSF) and administration of lidocaine hydrochloride (4 mg/kg) was performed. Blood samples for both serum and plasma, skeletal muscle (triceps brachii, gluteus medius), and CSF were collected for the determination of drug residues. Frozen skeletal muscle available from 5 additional horses that received standard dosages of drugs for short-term anesthesia (xylazine 1.1 mg/kg, midazolam 0.1 mg/kg, and ketamine 2.2 mg/kg) also were analyzed. Drug residues were found in the tissues of all horses, but at extremely low concentrations. Euthanasia by administration of lidocaine intrathecally to horses under IV anesthesia poses a low risk of toxicity to carnivores and scavengers that might consume muscle tissue from a carcass in which this protocol has been used. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Immobilization of swift foxes with ketamine hydrochloride-xylazine hydrochloride

USGS Publications Warehouse

Telesco, R.L.; Sovada, Marsha A.

2002-01-01

There is an increasing need to develop field immobilization techniques that allow researchers to handle safely swift foxes (Vulpes velox) with minimal risk of stress or injury. We immobilized captive swift foxes to determine the safety and effectiveness of ketamine hydrochloride and xylazine hydrochloride at different dosages. We attempted to determine appropriate dosages to immobilize swift foxes for an adequate field-handling period based on three anesthesia intervals (induction period, immobilization period, and recovery period) and physiologic responses (rectal temperature, respiration rate, and heart rate). Between October 1998–July 1999, we conducted four trials, evaluating three different dosage ratios of ketamine and xylazine (2.27:1.2, 5.68:1.2, and 11.4:1.2 mg/kg ketamine:mg/kg xylazine, respectively), followed by a fourth trial with a higher dosage at the median ratio (11.4 mg/kg ketamine:2.4 mg/kg xylazine). We found little difference in induction and recovery periods among trials 1–3, but immobilization time increased with increasing dosage (P<0.08). Both the immobilization period and recovery period increased in trial 4 compared with trials 1–3 (P≤0.03). There was a high variation in responses of individual foxes across trials, making it difficult to identify an appropriate dosage for field handling. Heart rate and respiration rates were depressed but all physiologic measures remained within normal parameters established for domestic canids. We recommend a dosage ratio of 10 mg/kg ketamine to 1 mg/kg xylazine to immobilize swift foxes for field handling.

Hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in coronary artery bypass graft surgery patients with low ejection fraction: a double-blind, randomized, clinical trial.

PubMed

Habibi, Mohammad Reza; Baradari, Afshin Gholipour; Soleimani, Aria; Emami Zeydi, Amir; Nia, Hamid Sharif; Habibi, Ali; Onagh, Naser

2014-10-01

During induction of anesthesia and intubation, hemodynamic changes are very important; especially in patients with coronary artery disease (CAD) and left ventricular dysfunction. A little information is available on the hemodynamic effects of a combination of ketamine-thiopental for induction of anesthesia in patients undergoing coronary artery bypass graft (CABG) surgery, with impaired ventricular function. The aim of this study was to compare the hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in CABG surgery patients with low ejection fraction (EF<45%). In a double blind randomized clinical trial, a total of 100 patients, scheduled for elective CABG surgery were randomly assigned into two groups. These patients received either etomidate or ketamine-thiopental sodium combination at induction of anesthesia. Hemodynamics variable were measured and recorded at baseline, immediately before and after laryngoscopy and intubation, one, two and three minutes after intubation. Also, muscle twitching incidence among patients in two groups was evaluated. No significant differences between the two groups regarding the changes of hemodynamic variables including systolic and diastolic arterial blood pressure, mean arterial pressure and heart rate, were notice (p>0.05). Muscle twitching was not observed in the two groups. Hemodynamic stability after administration of ketamine-thiopental sodium combination for induction of anesthesia in patients undergoing CABG surgery, with impaired ventricular function, supports the clinical impression that this combination is safe in CABG surgery patients with low EF.

Ketamine versus Ketamine / magnesium Sulfate for Procedural Sedation and Analgesia in the Emergency Department: A Randomized Clinical Trial

PubMed Central

Azizkhani, Reza; Bahadori, Azadeh; Shariati, Mohammadreza; Golshani, Keyhan; Ahmadi, Omid; Masoumi, Babak

2018-01-01

Background: The present study was designed to evaluate the effectiveness of magnesium sulfate (MgSO4) in procedural sedation and analgesia (PSA) when combined with ketamine in patients with fractures in emergency departments and required short and painful emergency procedures. Materials and Methods: In this study, 100 patients with fractures and dislocations who were presented to the emergency departments and required PSA for short and painful emergency procedures were randomly allocated to groups of ketamine plus MgSO4 or ketamine alone. Train of four (TOF) stimulation pattern was assessed using nerve stimulator machine and compared between groups. Results: The mean age of studied patients was 46.9 ± 9.3 years old. 48% were male and 52% were female. No significant differences were noted between groups in demographic variables. The status of TOF, 2 min after the injection of ketamine (1.5 mg/kg), in both groups was similar. After the injection of the second dose of ketamine (1 mg/kg) the status of TOF in four patients in ketamine plus MgSO4 (0.45 mg/kg) group changed, it was three quarters but in ketamine group, the status of TOF in all patients was four quarters. The difference between groups was not statistically significant (P = 0.12). Conclusion: The findings revealed that for muscle relaxation during medical procedures in the emergency department, ketamine in combination with MgSO4 with this dose was not effective for muscle relaxation during procedures. PMID:29456990

Ketamine versus Ketamine / magnesium Sulfate for Procedural Sedation and Analgesia in the Emergency Department: A Randomized Clinical Trial.

PubMed

Azizkhani, Reza; Bahadori, Azadeh; Shariati, Mohammadreza; Golshani, Keyhan; Ahmadi, Omid; Masoumi, Babak

2018-01-01

The present study was designed to evaluate the effectiveness of magnesium sulfate (MgSO 4 ) in procedural sedation and analgesia (PSA) when combined with ketamine in patients with fractures in emergency departments and required short and painful emergency procedures. In this study, 100 patients with fractures and dislocations who were presented to the emergency departments and required PSA for short and painful emergency procedures were randomly allocated to groups of ketamine plus MgSO 4 or ketamine alone. Train of four (TOF) stimulation pattern was assessed using nerve stimulator machine and compared between groups. The mean age of studied patients was 46.9 ± 9.3 years old. 48% were male and 52% were female. No significant differences were noted between groups in demographic variables. The status of TOF, 2 min after the injection of ketamine (1.5 mg/kg), in both groups was similar. After the injection of the second dose of ketamine (1 mg/kg) the status of TOF in four patients in ketamine plus MgSO 4 (0.45 mg/kg) group changed, it was three quarters but in ketamine group, the status of TOF in all patients was four quarters. The difference between groups was not statistically significant ( P = 0.12). The findings revealed that for muscle relaxation during medical procedures in the emergency department, ketamine in combination with MgSO 4 with this dose was not effective for muscle relaxation during procedures.

The comparison of preincisional peritonsillar infiltration of ketamine and tramadol for postoperative pain relief on children following adenotonsillectomy.

PubMed

Ugur, Kadriye Serife; Karabayirli, Safinaz; Demircioğlu, Rüveyda İrem; Ark, Nebil; Kurtaran, Hanifi; Muslu, Bunyamin; Sert, Hüseyin

2013-11-01

To investigate and compare the effectiveness of preincisional peritonsillar infiltration of ketamine and tramadol for post-operative pain on children following adenotonsillectomy. Prospective randomized double blind controlled study. Seventy-five children aged 3-10 years undergoing adenotonsillectomy were included in study. Patients received injections in peritonsillar fossa of tramadol (2 mg/kg-2 ml), ketamine (0.5 mg/kg-2 ml) or 2 ml serum physiologic. During operation heart rate, oxygen saturation, average mean blood pressures were recorded in every 5 min. Operation, anesthesia and the time that Alderete scores 9-10, patient satisfaction, analgesic requirements were recorded. Postoperatively nausea, vomiting, sedation, dysphagia, bleeding scores were recorded at 0, 10, 30, 60 min and 2, 4, 8, 12, 18, 24h postoperatively. Pain was evaluated using modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS) at fixed intervals after the procedure (15 min and 1, 4, 12, 16, and 24h postoperatively). The recordings of heart rate, mean arterial pressure, nausea, vomiting, sedation and bleeding scores were similar in all groups (p>0.05). The mCHEOPS scores at 10 min, 30 min, 1h, 8h were significantly lower in both tramadol and ketamine group when compared with control (p<0.05). Use of additional analgesia at 10 min and 18 h were higher in control group than ketamine, tramadol group (p<0.05). Dysphagia scores were significantly lower for both ketamine and tramadol group when compared with control group (p<0.05). mCHEOPS, additional analgesia, dysphagia, patient satisfaction scores were similar in tramadol, ketamine groups (p>0.05). Preincisional injection of ketamine and tramadol prior to tonsillectomy is safe, effective method and equivalent for post-tonsillectomy pain, patient satisfaction, postoperative nausea, vomiting, dysphagia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Cellular registration without behavioral recall of olfactory sensory input under general anesthesia.

PubMed

Samuelsson, Andrew R; Brandon, Nicole R; Tang, Pei; Xu, Yan

2014-04-01

Previous studies suggest that sensory information is "received" but not "perceived" under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. One hundred seven rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. The olfactory sensory processing centers could distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Reexposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity, which was similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the "cellular memory," however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. Histologically distinguishable registration of sensory processing continues to occur at the cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications.

Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

PubMed Central

2013-01-01

Background This study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred mares weighing 320–400 kg were anesthetized on three different occasions. Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was maintained with 37.5 μg/kg/min of xylazine and 87.5 μg/kg/min of ketamine both administered intravenously for 75 min. The three treatments consisted of: lidocaine (loading dose: 5 mg/kg, CRI: 100 μg/kg/min; THL); lidocaine (loading dose: 2.5 mg/kg; CRI: 50 μg/kg/min: TLL); and saline (TS); all given 15 min after induction and maintained for 1 h. Antinociception was measured by response to electrical stimulation and bispectral index (BIS) was recorded during anesthesia. Parametric and non-parametric data were compared using ANOVA followed by Student-Newman-Keuls and Friedman tests, respectively. Results Plasma lidocaine concentrations peaked at the end of lidocaine loading dose and was greater in THL (9.61 ± 2.75 μg/mL) vs TLL (4.50 ± 3.34 μg/mL). Electrical noxious stimulation caused purposeful movement in all horses from TS, but no response in THL. The BIS was decreased in THL only and was less when compared to the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2 increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein and temperature decreased during anesthesia in all treatments. PaCO2 and HR were greater and RR and pH less in THL compared to TLL and TS at 30 min during anesthesia. All recoveries were considered excellent. Time to standing was longer after THL (60 ± 20 min) than following TLL and TS (32 ± 17 and 30 ± 15 min, respectively

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knobloch, M.; Portier, C.J.; Levionnois, O.L.

2006-11-01

Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 {mu}g/ml S-ketamine over 120 min under isoflurane anesthesia was performed inmore » Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses)« less

General Anesthesia Inhibits the Activity of the “Glymphatic System”

PubMed Central

Gakuba, Clement; Gaberel, Thomas; Goursaud, Suzanne; Bourges, Jennifer; Di Palma, Camille; Quenault, Aurélien; Martinez de Lizarrondo, Sara; Vivien, Denis; Gauberti, Maxime

2018-01-01

INTRODUCTION: According to the “glymphatic system” hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent. PMID:29344300

Prolonged Perioperative Low-Dose Ketamine Does Not Improve Short and Long-term Outcomes After Pediatric Idiopathic Scoliosis Surgery.

PubMed

Perelló, Marina; Artés, David; Pascuets, Cristina; Esteban, Elisabeth; Ey Batlle, Ana M

2017-03-01

A randomized, double-blind, placebo-controlled study, with a six-month follow-up period. The aim of this study was to test the hypothesis that a 72-hour dose of subanesthetic ketamine in this surgical procedure reduces postoperative morphine use and to assess whether there are fewer adverse effects, if postoperative recovery is faster, if there is less peri-incisional hyperalgesia, or if there is lower incidence of persistent postsurgical pain. Tissue injury and high opioid requirements following posterior spinal fusion surgery produce central sensitization, which can in turn be associated with hyperalgesia and chronic pain. Clinical trials involving this type of procedure using subanesthetic ketamine doses have assessed pain and morphine requirements with contradictory results. The effects of prolonged subanesthetic ketamine doses on postoperative recovery, mechanical hyperalgesia, and the incidence of chronic pain are unknown. A total of 48 pediatric patients between 10 and 18 years diagnosed with idiopathic scoliosis were randomized to receive perioperative low-dose ketamine or placebo for 72 hours. They received general anesthesia, intraoperative remifentanil, and morphine postoperatively (patient-controlled analgesia). We measured morphine consumption, pain at rest and during movement (coughing), undesirable effects, and sedation during morphine treatment. The onset of oral intake, ambulation, and hospital stay were recorded. The extent of the peri-incisional hyperalgesia was measured at 72 hours and pain controls were conducted postsurgery. Primary endpoint results (total cumulative morphine consumption while admitted) were obtained in 44 patients. Results were 2.72 (SD 1.13) in the placebo group and 3.13 (SD 1.13) in the study group (P = 0.2903), with no significant differences. Moreover, differences were not found between the experimental group and the placebo group in the secondary endpoints analyzed. Our findings do not support the routine

Antagonism of methoxyflurane-induced anesthesia in rats by benzodiazepine inverse agonists.

PubMed

Miller, D W; Yourick, D L; Tessel, R E

1989-11-28

Injection of the partial benzodiazepine inverse agonist Ro15-4513 (1-32 mg/kg i.p.) or nonconvulsant i.v. doses of the full benzodiazepine inverse agonist beta-CCE immediately following cessation of exposure of rats to an anesthetic concentration of methoxyflurane significantly antagonized the duration of methoxyflurane anesthesia as measured by recovery of the righting reflex and/or pain sensitivity. This antagonism was inhibited by the benzodiazepine antagonist Ro15-1788 at doses which alone did not alter the duration of methoxyflurane anesthesia. In addition, high-dose Ro15-4513 pretreatment (32 mg/kg) antagonized the induction and duration of methoxyflurane anesthesia but was unable to prevent methoxyflurane anesthesia or affect the induction or duration of anesthesia induced by the dissociative anesthetic ketamine (100 mg/kg). These findings indicate that methoxyflurane anesthesia can be selectively antagonized by the inverse agonistic action of Ro15-4513 and beta-CCE.

Safety and Feasibility of a Ketamine Package to Support Emergency and Essential Surgery in Kenya when No Anesthetist is Available: An Analysis of 1216 Consecutive Operative Procedures.

PubMed

Burke, Thomas F; Suarez, Sebastian; Sessler, Daniel I; Senay, Ayla; Yusufali, Taha; Masaki, Charles; Guha, Moytrayee; Rogo, Debora; Jani, Pankaj; Nelson, Brett D; Rogo, Khama

2017-12-01

Lack of access to emergency and essential surgery is widespread in low- and middle-income countries. Scarce anesthesia services contribute to this unmet need. The aim of this study was to evaluate the safety and feasibility of the Every Second Matters for Emergency and Essential Surgery-Ketamine (ESM-Ketamine) package for emergency and essential procedures when no anesthetist was available. From November 2013 to September 2017, the ESM-Ketamine package was used for patients requiring emergency or life-improving surgeries in fifteen selected facilities across Kenya when no anesthetist was available. A mixed-methods approach was used to assess safety and feasibility of the ESM-Ketamine package, including demand, acceptability, and practicality. The primary outcome was ketamine-related adverse events. Key-informant interviews captured perceptions of providers, hospital administrators, and surgeons/proceduralists. Non-anesthetist mid-level providers used ESM-Ketamine for 1216 surgical procedures across the fifteen study facilities. The median ketamine dose was 2.1 mg/kg. Brief (<30 s) oxygen desaturations occurred in 39 patients (3%), and prolonged (>30 s) oxygen desaturations occurred in seven patients (0.6%). There were 157 (13%) reported cases of hallucinations and agitation which were treated with diazepam. All patients recovered uneventfully, and no ketamine-related deaths were reported. Twenty-seven key-informant interviews showed strong support for the program with four main themes: financial considerations, provision of services, staff impact, and scaling considerations. The ESM-Ketamine package appears safe and feasible and is capable of expanding access to emergency and essential surgeries in rural Kenya when no anesthetist is available.

Repeated chemical immobilization of a captive greater one-horned rhinoceros (Rhinoceros unicornis), using combinations of etorphine, detomidine, and ketamine.

PubMed

Atkinson, Mark W; Hull, Bruce; Gandolf, A Rae; Blumer, Evan S

2002-06-01

An adult, 23 yr-old, male greater one-horned rhinoceros (Rhinoceros unicornis) was repeatedly immobilized with combinations of etorphine, detomidine, and ketamine to provide medical and surgical care to chronic, bilateral, soft tissue lesions on the hind feet and to collect semen by electroejaculation. The rhinoceros was successfully immobilized on 24 occasions over a 55 mo period at approximately 8-10 wk intervals, 17 times with a combination of etorphine and detomidine (M99-D, i.m.) by projectile dart and seven times with a combination of etorphine, ketamine, and detomidine (M99-K-D, i.m.) by pole syringe. The combination of etorphine, detomidine, and ketamine repeatedly and safely induced prolonged anesthesia, and a suitable drug combination includes 3.5-3.8 mg etorphine, 14 mg detomidine, and 400 mg ketamine (M99-K-D) administered i.m. into the neck.

Cellular Registration Without Behavioral Recall Of Olfactory Sensory Input Under General Anesthesia

PubMed Central

Samuelsson, Andrew R.; Brandon, Nicole R.; Tang, Pei; Xu, Yan

2014-01-01

Background Previous studies suggest that sensory information is “received” but not “perceived” under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. Methods 107 rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. Results The olfactory sensory processing centers can distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Re-exposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the “cellular memory,” however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. Conclusions Histologically distinguishable registration of sensory process continues to occur at cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications. PMID:24694846

Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine.

PubMed

Fukumoto, Kenichi; Toki, Hidetoh; Iijima, Michihiko; Hashihayata, Takashi; Yamaguchi, Jun-Ichi; Hashimoto, Kenji; Chaki, Shigeyuki

2017-04-01

The rapid-acting and long-lasting antidepressant effects of ( R,S )-ketamine have recently gained much attention. Although ( S )-ketamine has been studied as an active isomer, recent evidence suggests that ( R )-ketamine exhibits longer-lasting antidepressant effects than ( S )-ketamine in rodents. However, the antidepressant potential of ( R )-ketamine has not been fully addressed. In the present study, we compared the antidepressant effects of ( R )-ketamine with those of ( S )-ketamine in animal models of depression, including a model that is refractory to current medications. Both ( R )-ketamine and ( S )-ketamine exhibited antidepressant effects at 30 minutes as well as at 24 hours after administration in forced-swimming and tail-suspension tests in mice. At 48 hours after administration, however, ( R )-ketamine still exerted a significant antidepressant effect in the tail-suspension test, whereas the effect of ( S )-ketamine was no longer observed. Moreover, ( R )-ketamine, but not ( S )-ketamine, significantly reversed the depressive-like behavior induced by repeated treatments with corticosterone in rats at 24 hours after a single administration. This effect was attenuated by an α -amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, suggesting the involvement of AMPA receptor stimulation in the effects. Both ( R )-ketamine and ( S )-ketamine exhibited practically the same exposure levels in plasma, brain, and cerebrospinal fluid in mice and rats, and both compounds were rapidly eliminated from plasma (<4-8 hours). The present results confirmed the previous findings that ( R )-ketamine exerted longer-lasting antidepressant effects than ( S )-ketamine in animal models of depression. Moreover, our study is the first to demonstrate that ( R )-ketamine exerted a sustained antidepressant effect even in a model that is refractory to currently prescribed antidepressants. Copyright © 2017 by The American Society for Pharmacology and

Effects of ketamine and lidocaine in combination on the sevoflurane minimum alveolar concentration in alpacas

PubMed Central

Queiroz-Williams, Patricia; Doherty, Thomas J.; da Cunha, Anderson F.; Leonardi, Claudia

2016-01-01

This study investigated the effects of ketamine and lidocaine in combination on the minimum alveolar concentration of sevoflurane (MACSEVO) in alpacas. Eight healthy, intact male, adult alpacas were studied on 2 separate occasions. Anesthesia was induced with SEVO, and baseline MAC (MACB) determination began 45 min after induction. After MACB determination, alpacas were randomly given either an intravenous (IV) loading dose (LD) and infusion of saline or a loading dose [ketamine = 0.5 mg/kg body weight (BW); lidocaine = 2 mg/kg BW] and an infusion of ketamine (25 μg/kg BW per minute) in combination with lidocaine (50 μg/kg BW per minute), and MACSEVO was re-determined (MACT). Quality of recovery, time-to-extubation, and time-to-standing, were also evaluated. Mean MACB was 1.88% ± 0.13% and 1.89% ± 0.14% for the saline and ketamine + lidocaine groups, respectively. Ketamine and lidocaine administration decreased (P < 0.05) MACB by 57% and mean MACT was 0.83% ± 0.10%. Saline administration did not change MACB. Time to determine MACB and MACT was not significantly different between the treatments. The quality of recovery, time-to-extubation, and time-to-standing, were not different between groups. The infusion of ketamine combined with lidocaine significantly decreased MACSEVO by 57% and did not adversely affect time-to-standing or quality of recovery. PMID:27127341

Effects of ketamine and lidocaine in combination on the sevoflurane minimum alveolar concentration in alpacas.

PubMed

Queiroz-Williams, Patricia; Doherty, Thomas J; da Cunha, Anderson F; Leonardi, Claudia

2016-04-01

This study investigated the effects of ketamine and lidocaine in combination on the minimum alveolar concentration of sevoflurane (MACSEVO) in alpacas. Eight healthy, intact male, adult alpacas were studied on 2 separate occasions. Anesthesia was induced with SEVO, and baseline MAC (MACB) determination began 45 min after induction. After MACB determination, alpacas were randomly given either an intravenous (IV) loading dose (LD) and infusion of saline or a loading dose [ketamine = 0.5 mg/kg body weight (BW); lidocaine = 2 mg/kg BW] and an infusion of ketamine (25 μg/kg BW per minute) in combination with lidocaine (50 μg/kg BW per minute), and MACSEVO was re-determined (MACT). Quality of recovery, time-to-extubation, and time-to-standing, were also evaluated. Mean MACB was 1.88% ± 0.13% and 1.89% ± 0.14% for the saline and ketamine + lidocaine groups, respectively. Ketamine and lidocaine administration decreased (P < 0.05) MACB by 57% and mean MACT was 0.83% ± 0.10%. Saline administration did not change MACB. Time to determine MACB and MACT was not significantly different between the treatments. The quality of recovery, time-to-extubation, and time-to-standing, were not different between groups. The infusion of ketamine combined with lidocaine significantly decreased MACSEVO by 57% and did not adversely affect time-to-standing or quality of recovery.

The Modification and Performance of a Large Animal Anesthesia Machine (Tafonius®) in Order to Deliver Xenon to a Horse.

PubMed

Santangelo, Bruna; Robin, Astrid; Simpson, Keith; Potier, Julie; Guichardant, Michel; Portier, Karine

2017-01-01

Xenon, due to its interesting anesthetic properties, could improve the quality of anesthesia protocols in horses despite its high price. This study aimed to modify and test an anesthesia machine capable of delivering xenon to a horse. An equine anesthesia machine (Tafonius, Vetronic Services Ltd., UK) was modified by including a T-connector in the valve block to introduce xenon, so that the xenon was pushed into the machine cylinder by the expired gases. A xenon analyzer was connected to the expiratory limb of the patient circuit. The operation of the machine was modeled and experimentally tested for denitrogenation, wash-in, and maintenance phases. The system was considered to consist of two compartments, one being the horse's lungs, the other being the machine cylinder and circuit. A 15-year-old, 514-kg, healthy gelding horse was anesthetized for 70 min using acepromazine, romifidine, morphine, diazepam, and ketamine. Anesthesia was maintained with xenon and oxygen, co-administered with lidocaine. Ventilation was controlled. Cardiorespiratory variables, expired fraction of xenon (FeXe), blood gases were measured and xenon was detected in plasma. Recovery was unassisted and recorded. FeXe remained around 65%, using a xenon total volume of 250 L. Five additional boli of ketamine were required to maintain anesthesia. PaO 2 was 45 ± 1 mmHg. The recovery was calm. Xenon was detected in blood during the entire administration time. This pilot study describes how to deliver xenon to a horse. Although many technical problems were encountered, their correction could guide future endeavors to study the use of xenon in horses.

Comparison of ketamine and ketofol for deep sedation and analgesia in children undergoing laser procedure.

PubMed

Stevic, Marija; Ristic, Nina; Budic, Ivana; Ladjevic, Nebojsa; Trifunovic, Branislav; Rakic, Ivan; Majstorovic, Marko; Burazor, Ivana; Simic, Dusica

2017-09-01

The aim of our study was to research and evaluate cardiovascular and respiratory stability, clinical efficacy, and safety of two different anesthetic agents in pediatric patients who underwent Pulse dye (wavelength 595 nm, pulse duration 0-40 ms, power 0-40 J) and CO 2 (wavelength 10,600 nm, intensity-fraxel mod with SX index 4 to 8, power 0-30 W) laser procedure. This prospective non-blinded study included 203 pediatric patients ASA I-II, aged between 1 month and 12 years who underwent short-term procedural sedation and analgesia for the laser procedure. After oral premedication with midazolam, 103 children were analgo-sedated with ketamine and fentanyl (K group) and 100 with ketofol and fentanyl (KT group). Vital signs, applied drug doses, pulse oximetry, and parental satisfaction questionnaire were used to compare these two groups. Statistical differences were tested using Student's t test, Mann-Whitney U test, chi-square test, and Fisher's exact test. Receiver operating characteristic (ROC) curve analysis was used to assess the cut-off value of the duration of anesthesia predicting apnea. Tachycardia was recorded in a significantly higher number of patients who received ketamine as the anesthetic agent (35.9 vs. 3% respectively). Hypertension was also significantly more frequent in patients who received ketamine in comparison with patients who received ketofol (25.2 vs. 3%). Laryngospasm was not observed in both examined groups. There was no statistically significant difference between groups in satisfaction of parents and doctors. Apnea and respiratory depression occurred significantly more frequent in ketofol than in ketamine group (12 vs. 0.97% and 13 vs. 0%). Based on ROC analysis for apnea, we found a significantly higher number of patients with apnea in the ketofol group when duration of anesthesia was longer than 17 min. Our study has shown that ketofol is more comfortable than ketamine in short-term laser procedures in children, causing less

The Future of Intensive Care Unit Sedation: A Report of Continuous Infusion Ketamine as an Alternative Sedative Agent.

PubMed

Benken, Scott T; Goncharenko, Alexandra

2017-10-01

This report describes a patient case utilizing a nontraditional sedative, continuous infusion ketamine, as an alternative agent for intensive care unit (ICU) sedation. A 27-year-old female presented for neurosurgical management of a coup contrecoup injury, left temporal fracture, epidural hemorrhage (EDH), and temporal contusion leading to sustained mechanical ventilation. The patient experienced profound agitation during mechanical ventilation and developed adverse effects with all traditional sedatives: benzodiazepines, dexmedetomidine, opioids, and propofol. Ketamine was titrated to effect and eliminated the need for other agents. This led to successful ventilator weaning, extubation, and transition of care. Given the unique side effect profile of ketamine, it is imperative that information is disseminated on potential utilization of this agent. More information is needed regarding dosing, monitoring, and long-term effects of utilizing ketamine as a continuous ICU sedative, but given the analgesia, anesthesia, and cardiopulmonary stability, future utilization of this medication for this indication seems promising.

Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression.

PubMed

Zhong, Xiaomei; He, Hongbo; Zhang, Chunping; Wang, Zhijie; Jiang, Miaoling; Li, Qirong; Zhang, Minling; Huang, Xiong

2016-09-01

Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects. Ninety TRD patients (36 males, 54 females; average age, 30.6 years old) were randomly assigned to receive either ketamine (0.8mg/kg) (n=30), subanesthetic ketamine (0.5mg/kg) plus propofol (0.5mg/kg) (n=30) or propofol (0.8mg/kg) (n=30) as an anesthetic and underwent 8 ECT sessions. The primary outcome measures were the 17-item Hamilton Depression Rating Scale (HDRS-17), cognitive assessments and seizure parameters. The ketamine group had an earlier improvement in HDRS-17, longer seizure duration, lower electric quantity, a higher remission rate, and a lower degree of executive cognitive impairment compared to the ketamine+propofol and propofol groups. The ketamine+propofol group showed earlier improvement in the HDRS-17, a longer seizure duration and a different seizure energy index when compared to the propofol group. The postoperative dissociative side effect was not assessed. Both anesthetic and subanesthetic concentrations of ketamine have rapid mood enhancing actions in ECT for TRD, while anesthetic concentrations results in larger magnitudes of antidepression and cognitive protection. ECT with ketamine anesthesia might be an optimized therapy for patients with TRD. Copyright © 2016 Elsevier B.V. All rights reserved.

Tiletamine-zolazepam, ketamine, and xylazine anesthesia of captive cheetah (Acinonyx jubatus).

PubMed

Lewandowski, Albert H; Bonar, Christopher J; Evans, Sara E

2002-12-01

Thirty-two anesthetic episodes used a combination of tiletamine-zolezepam (50 mg/ml each), ketamine (80 mg/ml), and xylazine (20 mg/ml) at various dosages for routine diagnostic and minor surgical procedures in 13 captive cheetahs (Acinonyx jubatus). The mean dosage (0.023 +/- 0.003 ml/kg) provided rapid induction with a single i.m. injection along with safe predictable working time, good muscle relaxation, and analgesia. Yohimbine administration subsequently accelerated smooth and rapid recovery.

Effect of sub-anesthetic xylazine and ketamine ('ketamine stun') administered to calves immediately prior to castration.

PubMed

Coetzee, Johann F; Gehring, Ronette; Tarus-Sang, Jepkoech; Anderson, David E

2010-11-01

To describe the pharmacokinetics, cortisol response and behavioral changes associated with administration of sub-anesthetic xylazine and ketamine prior to castration. Prospective, randomized experiment. Twenty-two male beef calves (260-310 kg). Calves were randomly assigned to receive the following treatment immediately prior to surgical or simulated castration; 1) uncastrated, placebo-treated control (CONT) (n=4),2) Castrated, placebo treated control (CAST) (n=6), 3) castrated with intravenous xylazine (X) (0.05 mg kg(-1)) (n=6), and 4) castrated with IV xylazine (X) (0.05 mg kg(-1) ) combined with ketamine (K) (0.1 mg kg(-1)) (n=6). Blood samples collected over 10 hours post-castration were analyzed by LC-MS-MS for drug concentrations and chemiluminescent immunoassay for cortisol determination. Drug concentrations during the first 60 minutes post-castration fit a one-compartment open model with first-order elimination. The harmonic mean elimination half-lives (± pseudo SD) for X, X with K and K were 12.9 ± 1.2, 11.2 ± 3.1 and 10.6 ± 2.8 minutes, respectively. The proportion of the total area under the effect curve (AUEC) for cortisol during this period was significantly lower in the X group (13 ± 3%; p=0.006) and the X+K group (14 ± 2%; p=0.016) compared with the CAST calves (21 ± 2%). However, after 300 minutes the AUEC in the X group was higher than CAST. Significantly more calves demonstrated attitude that was unchanged from pre-manipulation behavior in the CONT (p=0.021) and X+K treated calves (p=0.0051) compared with the CAST calves. Behavioral changes and lower serum cortisol concentrations during the first 60 minutes post-castration were associated with quantifiable xylazine and ketamine concentrations. Low doses of xylazine and ketamine administered immediately prior to castration may offer a safe, efficacious and cost-effective systemically administered alternative or adjunct to local anesthesia. © 2010 The Authors. Veterinary Anaesthesia and

Ketamine

MedlinePlus

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Ketamine administration in depressive disorders: a systematic review and meta-analysis.

PubMed

Fond, Guillaume; Loundou, Anderson; Rabu, Corentin; Macgregor, Alexandra; Lançon, Christophe; Brittner, Marie; Micoulaud-Franchi, Jean-Arthur; Richieri, Raphaelle; Courtet, Philippe; Abbar, Mocrane; Roger, Matthieu; Leboyer, Marion; Boyer, Laurent

2014-09-01

Ketamine's efficacy in depressive disorders has been established in several controlled trials. The aim of the present study was to determine whether or not ketamine administration significantly improves depressive symptomatology in depression and more specifically in major depressive disorder (MDD), bipolar depression, resistant depression (non-ECT studies), and as an anesthetic agent in electroconvulsive therapy (ECT) for resistant depression (ECT studies). Secondary outcomes were the duration of ketamine's effect, the efficacy on suicidal ideations, the existence of a dose effect, and the safety/tolerance of the treatment. Studies were included if they met the following criteria (without any language or date restriction): design: randomized controlled trials, intervention: ketamine administration, participants: diagnosis of depression, and evaluation of severity based on a validated scale. We calculated standardized mean differences (SMDs) with 95 % confidence intervals (CIs) for each study. We used fixed and random effects models. Heterogeneity was assessed using the I2 statistic. We included nine non-ECT studies in our quantitative analysis (192 patients with major depressive disorder and 34 patients with bipolar depression). Overall, depression scores were significantly decreased in the ketamine groups compared to those in the control groups (SMD = -0.99; 95 % CI -1.23, -0.75; p < 0.01). Ketamine's efficacy was confirmed in MDD (resistant to previous pharmacological treatments or not) (SMD = -0.91; 95 % CI -1.19,-0.64; p < 0.01), in bipolar depression (SMD = -1.34; 95 % CI -1.94, -0.75), and in drug-free patients as well as patients under medication. Four ECT trials (118 patients) were included in our quantitative analysis. One hundred and three patients were diagnosed with major depressive disorder and 15 with bipolar depression. Overall, depression scores were significantly improved in the 58 patients receiving ketamine in ECT anesthesia

The effects of subarachnoid administration of preservative-free S(+)-ketamine on spinal cord and meninges in dogs.

PubMed

Rojas, Alfredo Cury; Alves, Juliana Gaiotto; Moreira E Lima, Rodrigo; Esther Alencar Marques, Mariângela; Moreira de Barros, Guilherme Antônio; Fukushima, Fernanda Bono; Modolo, Norma Sueli Pinheiro; Ganem, Eliana Marisa

2012-02-01

The N-methyl-d-aspartate receptor antagonist ketamine and its active enantiomer, S(+)-ketamine, have been injected in the epidural and subarachnoid spaces to treat acute postoperative pain and relieve neuropathic pain syndrome. In this study we evaluated the effects of a single dose of preservative-free S(+)-ketamine, in doses usually used in clinical practice, in the spinal cord and meninges of dogs. Under anesthesia (IV etomidate (2 mg/kg) and fentanyl (0.005 mg/kg), 16 dogs (6 to 15 kg) were randomized to receive a lumbar intrathecal injection (L5/6) of saline solution of 0.9% (control group) or S(+)-ketamine 1 mg/kg(-1) (ketamine group). All doses were administered in a volume of 1 mL over a 10-second interval. Accordingly, injection solution ranged from 0.6% to 1.5%. After 21 days of clinical observation, the animals were killed; spinal cord, cauda equina root, and meninges were removed for histological examination with light microscopy. Tissues were examined for demyelination (Masson trichrome), neuronal death (hematoxylin and eosin) and astrocyte activation (glial fibrillary acidic protein). No clinical or histological alterations of spinal tissue or meninges were found in animals from either control or ketamine groups. A single intrathecal injection of preservative-free S(+)-ketamine, at 1 mg/kg(-1) dosage, over a concentration range of 6 to 15 mg/mL injected in the subarachnoid space in a single puncture, did not produce histological alterations in this experimental model.

Transient central diabetes insipidus induced by ketamine infusion.

PubMed

Hatab, Sarah Z; Singh, Arun; Felner, Eric I; Kamat, Pradip

2014-12-01

Report a case of central diabetes insipidus (DI) associated with ketamine infusion. A 2-year-old girl with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and stable hypertrophic cardiomyopathy was admitted to the pediatric intensive care with pneumonia. She subsequently developed respiratory failure and required intubation. Continuous ketamine infusion was used for the sedation and facilitation of mechanical ventilation. Shortly after infusion of ketamine, the patient developed DI and responded appropriately to vasopressin. The Naranjo adverse drug reaction probability scale indicated a probable relationship between the development of central DI and ketamine. The most likely mechanism involves ketamine's antagonist action on N-methyl-d-aspartate receptors, resulting in inhibition of glutamate-stimulated arginine vasopressin release from the neurohypophysis. This is the second case report of ketamine-induced central DI and the only report in children. Clinicians who sedate children with continuous ketamine infusions should monitor patients for developing signs and symptoms of DI by measuring serum sodium and urine output prior to, during, and after ketamine infusion in order to make a timely diagnosis of this potentially serious complication. © The Author(s) 2014.

An effective dose of ketamine for eliminating pain during injection of propofol: a dose response study.

PubMed

Wang, M; Wang, Q; Yu, Y Y; Wang, W S

2013-09-01

Ketamine can completely eliminate pain associated with propofol injection. However, the effective dose of ketamine to eliminate propofol injection pain has not been determined. The purpose of this study was to determine the effective dose of ketamine needed to eliminate pain in 50% and 95% of patients (ED50 and ED95, respectively) during propofol injections. This study was conducted in a double-blinded fashion and included 50 patients scheduled for elective gynecological laparoscopy under general anesthesia. The initial dose of ketamine used in the first patient was 0.25mg/kg. The dosing modifications were in increments or decrements of 0.025 mg/kg. Ketamine was administered 15 seconds before injecting propofol (2.5mg/kg), which was injected at a rate of 1mL/s. Patients were asked to rate their pain during propofol injection every 5s econds using a 0-3 pain scale. The highest pain score was recorded. The ED50, ED95 and 95% confidence intervals (CI) were determined by probit analyses. The dose of ketamine ranged from 0.175 to 0.275 mg/kg. The ED50 and ED95 of ketamine for eliminating pain during propofol injection were 0.227 mg/kg and 0.283 mg/kg, respectively (95%CI: 0.211-0.243 mg/kg and 0.26-0.364 mg/kg, respectively). Ketamine at an approximate dose of 0.3mg/kg was effective in eliminating pain during propofol injection. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Cardiopulmonary effects of administration of a combination solution of xylazine, guaifenesin, and ketamine or inhaled isoflurane in mechanically ventilated calves.

PubMed

Kerr, Carolyn L; Windeyer, Claire; Bouré, Ludovic P; Mirakhur, Kuldip K; McDonell, Wayne

2007-12-01

To compare the cardiopulmonary effects of administration of a solution of xylazine, guaifenesin, and ketamine (XGK) or inhaled isoflurane in mechanically ventilated calves undergoing surgery. 13 male calves 2 to 26 days of age. Procedures-In calves in the XGK group, anesthesia was induced (0.5 mL/kg) and maintained (2.5 mL/kg/h) with a combination solution of xylazine (0.1 mg/mL), guaifenesin (50 mg/mL), and ketamine (1.0 mg/mL). For calves in the isoflurane group, anesthesia was induced and maintained with isoflurane in oxygen. The rates of XGK infusion and isoflurane administration were adjusted to achieve suitable anesthetic depth. All calves received 100% oxygen and were mechanically ventilated to maintain end-tidal carbon dioxide concentrations from 35 to 40 mm Hg and underwent laparoscopic bladder surgery through an abdominal approach. Cardiopulmonary variables were measured before induction and at intervals up to 90 minutes after anesthetic induction. The quality of induction was excellent in all calves. The XGK requirements were 0.57 +/- 0.18 mL/kg and 2.70 +/- 0.40 mL/kg/h to induce and maintain anesthesia, respectively. Heart rate was significantly lower than baseline throughout the anesthetic period in the XGK group. Systolic arterial blood pressure was significantly higher in the XGK group, compared with the isoflurane group, from 5 to 90 minutes. Cardiac index was lower than baseline in both groups. Differences between groups in cardiac index and arterial blood gas values were not significant. Administration of XGK resulted in excellent anesthetic induction and maintenance with cardiopulmonary alterations similar to those associated with isoflurane in mechanically ventilated calves.

Ketamine for chronic pain: risks and benefits

PubMed Central

Niesters, Marieke; Martini, Christian; Dahan, Albert

2014-01-01

The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4–14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. PMID:23432384

Ketamine and international regulations.

PubMed

Liao, Yanhui; Tang, Yi-Lang; Hao, Wei

2017-09-01

Ketamine is an anesthetic commonly used in low-income countries and has recently been shown to be effective for treatment-resistant depression. However, the illicit manufacturing, trafficking, and nonmedical use of ketamine are increasing globally, and its illicit use poses major public health challenges in many countries. To review the nonmedical use of ketamine in selected countries and its regulatory control. We conducted a review of literature identified from searches of the China National Knowledge Infrastructure (CNKI) (1979-2016) and PubMed databases, supplemented by additional references identified by the authors. Special attention was given to the regulation of ketamine. Illicit manufacturing, trafficking, and use of ketamine appear to have begun on a large scale in several Asian nations, and it has subsequently spread to other regions. Regulations governing availability of ketamine vary across countries, but there is a clear trend toward tighter regulations. As nonmedical use of ketamine and its harmful consequences have worsened globally, stricter controls are necessary. Appropriate regulation of ketamine is important for international efforts to control ketamine's cross-border trafficking and its nonmedical use.

Ketamine for chronic pain: risks and benefits.

PubMed

Niesters, Marieke; Martini, Christian; Dahan, Albert

2014-02-01

The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4-14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

The Relationship Between Creatine and Whey Protein Supplements Consumption and Anesthesia in Rats.

PubMed

Saberi, Kianoush; Gorji Mahlabani, Mohammad Amin; Tashayoie, Mohammad; Nasiri Nejad, Farinaz

2016-02-01

Because the trend of pharmacotherapy is toward controlling diet rather than administration of drugs, in our study we examined the probable relationship between Creatine (Cr) or Whey (Wh) consumption and anesthesia (analgesia effect of ketamine). Creatine and Wh are among the most favorable supplements in the market. Whey is a protein, which is extracted from milk and is a rich source of amino acids. Creatine is an amino acid derivative that can change to ATP in the body. Both of these supplements result in Nitric Oxide (NO) retention, which is believed to be effective in N-Methyl-D-aspartate (NMDA) receptor analgesia. The main question of this study was whether Wh and Cr are effective on analgesic and anesthetic characteristics of ketamine and whether this is related to NO retention or amino acids' features. We divided 30 male Wistar rats to three (n = 10) groups; including Cr, Wh and sham (water only) groups. Each group was administered (by gavage) the supplements for an intermediate dosage during 25 days. After this period, they became anesthetized using a Ketamine-Xylazine (KX) and their time to anesthesia and analgesia, and total sleep time were recorded. Data were analyzed twice using the SPSS 18 software with Analysis of Variance (ANOVA) and post hoc test; first time we expunged the rats that didn't become anesthetized and the second time we included all of the samples. There was a significant P-value (P < 0.05) for total anesthesia time in the second analysis. Bonferroni multiple comparison indicated that the difference was between Cr and Sham groups (P < 0.021). The data only indicated that there might be a significant relationship between Cr consumption and total sleep time. Further studies, with rats of different gender and different dosage of supplement and anesthetics are suggested.

Cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane and low-dose S-ketamine or medetomidine infusions.

PubMed

Menzies, M Paula Larenza; Ringer, Simone K; Conrot, Aude; Theurillat, Regula; Kluge, Katharina; Kutter, Annette Pn; Jackson, Michelle; Thormann, Wolfgang; Bettschart-Wolfensberger, Regula

2016-11-01

To evaluate cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane receiving medetomidine or S-ketamine infusions. Randomized, blinded, prospective clinical trial. Fifty horses undergoing elective surgery. After acepromazine and flunixin meglumine premedication, horses received medetomidine (7 μg kg -1 ) intravenously (IV). Anaesthesia was induced with midazolam and racemic ketamine (Med treatment group; 2.2 mg kg -1 ; n = 25) or S-ketamine (S-ket treatment group; 1.1 mg kg -1 ; n = 25) IV and maintained with isoflurane in oxygen/air and medetomidine (Med; 3.5 μg kg -1 hour -1 ) or S-ketamine (S-ket; 0.5 mg kg -1 hour -1 ). All horses were mechanically ventilated. Cardiopulmonary variables were evaluated. Isoflurane end-tidal concentrations (Fe'Iso), dobutamine requirements and thiopental boli were recorded. Plasma samples were collected in six horses to evaluate S-ketamine and S-norketamine concentrations. After surgery, medetomidine 2 μg kg -1 was administered IV. Four independent observers scored recovery using a visual analogue scale and a numerical rating scale. Both groups required similar mean Fe'Iso (1%). However, S-ket horses needed more thiopental boli. Median intraoperative cardiac index values were higher with S-ket (4.5 L minute -1  m -2 ) than Med (3.9 L minute -1  m -2 ). Overall, there were no differences in heart rate, blood pressure or dobutamine requirements; however, horses in S-ket showed higher heart rate values at 30 minutes after anaesthesia induction. Compared with Med horses, S-ket horses showed decreased PaO 2 and increased pulmonary venous admixture values estimated with the Fshunt calculation. Recoveries were shorter and of poorer quality with S-ket. During infusion, S-ketamine and S-norketamine plasma concentrations lay in the ranges of 0.209-0.917 μg mL -1 and 0.250-0.723 μg mL -1 , respectively. Despite the higher intraoperative cardiac index with S-ket, both

Remifentanil in combination with ketamine versus remifentanil in spinal fusion surgery--a double blind study.

PubMed

Hadi, B A; Al Ramadani, R; Daas, R; Naylor, I; Zelkó, R

2010-08-01

This study is aimed at conducting a program for two different anesthetic methods used during a spinal fusion surgery to ensure better intra-operative hemodynamic stability and post-operative pain control. A prospective, randomized, double blind study in patients scheduled for spinal fusion surgery, who were randomly allocated to two groups, G1 and G2, (n = 15 per group), class I-II ASA, was carried out. Both groups received pre-operatively midazolam, followed intra-operatively by propofol, sevoflurane, atracurium, and either remifentanil infusion 0.2 microg/kg/min (G1), or the same dose of remifentanil infusion and low doses of ketamine infusion 1 microg/kg/min (G2) anesthetics, antidote medication and post-operative morphine doses. HR, MAP, vital signs, surgical bleeding, urine output, duration of surgery and duration of anesthesia were recorded. In a 24-h recovery period in a post-anesthesia care unit (PACU) the recovery time, the first pain score and analgesic requirements were measured. Intra-operative HR and arterial BP were significantly less (p < 0.05) in G1 as compared to G2. In the PACU the first pain scores were significantly less (p < 0.05) in G2 than in G1. The time for the first patient analgesia demand dose was greater in G2, as also morphine consumption which was greater in G1 than G2 (p < 0.05). Other results were the same. None of the patients had any adverse drug reaction. Adding low doses of ketamine hydrochloride could be a routine therapy to improve the hemodynamic stability and reduce the post-operative morphine consumption during spinal fusion surgery.

Intravenous dexamethasone versus ketamine gargle versus intravenous dexamethasone combined with ketamine gargle for evaluation of post-operative sore throat and hoarseness: A randomized, placebo-controlled, double blind clinical trial

PubMed Central

Safavi, Mohammadreza; Honarmand, Azim; Fariborzifar, Arghavan; Attari, Mohammadali

2014-01-01

Background: Sore throat and hoarseness are the most frequent subjective complaints after tracheal intubation for general anesthesia. We conducted a prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intravenous (IV) dexamethasone plus ketamine gargle for reducing the incidence and severity of post-operative sore throat (POST) and hoarseness. Materials and Methods: 140 patients (aged 16-65 year) scheduled for elective surgery were enrolled. Patients were randomly allocated into four groups of 35 subjects each: Group K, gargled 40 mg ketamine in 30 ml saline; Group D, were infused 0.2 mg/kg IV dexamethasone; Group KD, gargled 40 mg ketamine in 30 ml saline plus 0.2 mg/kg IV dexamethasone; Group P (placebo) that received saline (gargle and IV). POST was graded at 0, 2, 4, 8, 16 and 24 h after operation on a four-point scale (0-3). Results: The incidence and severity of POST were significantly lower in Group KD, compared with the other groups at all times after tracheal extubation for up to 24 h (P < 0.05). Also the incidence and severity of hoarseness were significantly lower in each Groups of KD and K and D compared with group placebo (P < 0.05). Conclusion: The prophylactic use of 0.2 mg/kg of IV dexamethasone plus ketamine gargle significantly reduced the incidence and severity of POST compared with using each of these drugs alone or using placebo. PMID:25371869

Study protocol for the randomised controlled trial: Ketamine augmentation of ECT to improve outcomes in depression (Ketamine-ECT study).

PubMed

Trevithick, Liam; McAllister-Williams, R Hamish; Blamire, Andrew; Branton, Tim; Clark, Ross; Downey, Darragh; Dunn, Graham; Easton, Andrew; Elliott, Rebecca; Ellwell, Clare; Hayden, Katherine; Holland, Fiona; Karim, Salman; Lowe, Jo; Loo, Colleen; Nair, Rajesh; Oakley, Timothy; Prakash, Antony; Sharma, Parveen K; Williams, Stephen R; Anderson, Ian M

2015-10-21

adjunctive ketamine used together with standard anaesthesia for ECT will significantly reduce the adverse cognitive effects observed after ECT. Potential efficacy benefits of increased speed of symptom improvement and a reduction in the number of ECT treatments required will also be assessed, as will safety and tolerability of adjunctive ketamine. This study will provide important evidence as to whether adjunctive ketamine is routinely indicated for ECT given for depression in routine NHS clinical practice. Current Controlled Trials: ISRCTN14689382 (assigned 30/07/2012); EudraCT Number: 2011-005476-41.

Complete recovery from intractable complex regional pain syndrome, CRPS-type I, following anesthetic ketamine and midazolam.

PubMed

Kiefer, Ralph-Thomas; Rohr, Peter; Ploppa, Annette; Altemeyer, Karl-Heinz; Schwartzman, Robert Jay

2007-06-01

To describe the treatment of an intractable complex regional pain syndrome I (CRPS-I) patient with anesthetic doses of ketamine supplemented with midazolam. A patient presented with a rapidly progressing contiguous spread of CRPS from a severe ligamentous wrist injury. Standard pharmacological and interventional therapy successively failed to halt the spread of CRPS from the wrist to the entire right arm. Her pain was unmanageable with all standard therapy. As a last treatment option, the patient was transferred to the intensive care unit and treated on a compassionate care basis with anesthetic doses of ketamine in gradually increasing (3-5 mg/kg/h) doses in conjunction with midazolam over a period of 5 days. On the second day of the ketamine and midazolam infusion, edema, and discoloration began to resolve and increased spontaneous movement was noted. On day 6, symptoms completely resolved and infusions were tapered. The patient emerged from anesthesia completely free of pain and associated CRPS signs and symptoms. The patient has maintained this complete remission from CRPS for 8 years now. In a patient with severe spreading and refractory CRPS, a complete and long-term remission from CRPS has been obtained utilizing ketamine and midazolam in anesthetic doses. This intensive care procedure has very serious risks but no severe complications occurred. The psychiatric side effects of ketamine were successfully managed with the concomitant use of midazolam and resolved within 1 month of treatment. This case report illustrates the effectiveness and safety of high-dose ketamine in a patient with generalized, refractory CRPS.

Effects of propofol, sevoflurane, remifentanil, and (S)-ketamine in subanesthetic concentrations on visceral and somatosensory pain-evoked potentials.

PubMed

Untergehrer, Gisela; Jordan, Denis; Eyl, Sebastian; Schneider, Gerhard

2013-02-01

Although electroencephalographic parameters and auditory evoked potentials (AEP) reflect the hypnotic component of anesthesia, there is currently no specific and mechanism-based monitoring tool for anesthesia-induced blockade of nociceptive inputs. The aim of this study was to assess visceral pain-evoked potentials (VPEP) and contact heat-evoked potentials (CHEP) as electroencephalographic indicators of drug-induced changes of visceral and somatosensory pain. Additionally, AEP and electroencephalographic permutation entropy were used to evaluate sedative components of the applied drugs. In a study enrolling 60 volunteers, VPEP, CHEP (amplitude N2-P1), and AEP (latency Nb, amplitude Pa-Nb) were recorded without drug application and at two subanesthetic concentration levels of propofol, sevoflurane, remifentanil, or (s)-ketamine. Drug-induced changes of evoked potentials were analyzed. VPEP were generated by electric stimuli using bipolar electrodes positioned in the distal esophagus. For CHEP, heat pulses were given to the medial aspect of the right forearm using a CHEP stimulator. In addition to AEP, electroencephalographic permutation entropy was used to indicate level of sedation. With increasing concentrations of propofol, sevoflurane, remifentanil, and (s)-ketamine, VPEP and CHEP N2-P1 amplitudes decreased. AEP and electroencephalographic permutation entropy showed neither clinically relevant nor statistically significant suppression of cortical activity during drug application. Decreasing VPEP and CHEP amplitudes under subanesthetic concentrations of propofol, sevoflurane, remifentanil, and (s)-ketamine indicate suppressive drug effects. These effects seem to be specific for analgesia.

Development and validation of an HPLC-MS/MS method for the detection of ketamine in Calliphora vomitoria (L.) (Diptera: Calliphoridae).

PubMed

Magni, Paola A; Pazzi, Marco; Droghi, Jessica; Vincenti, Marco; Dadour, Ian R

2018-05-03

Entomotoxicology is a branch of forensic entomology that studies the detection of drugs or other toxic substances from insects developing on the decomposing tissues of a human corpse or animal carcass. Entomotoxicology also investigates the effects of these substances on insect development, survival and morphology to provide an estimation of the minimum time since death. Ketamine is a medication mainly used for starting and maintaining anesthesia. In recent years ketamine has also been used as a recreational drug, and occasionally as a sedating drug to facilitate sexual assault. In both activities, it has resulted in several deaths. Furthermore, ketamine has been also implicated in suspicious deaths of animals. The present research describes for the first time the development and validation of an analytical method suited to detect ketamine in larvae, pupae, empty puparia, and adults of Calliphora vomitoria L. (Diptera: Calliphoridae), using liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). This research also considers the effects of ketamine on the survival, developmental rate and morphology (length and width of larvae and pupae) of C. vomitoria. The larvae were reared on liver substrates homogeneously spiked with ketamine concentrations consistent with those found in humans after recreational use (300 ng/mg) or allegedly indicated as capable of causing death in either humans or animals (600 ng/mg). The results demonstrated that (a) HPLC-MS/MS method is applicable to ketamine detection in C. vomitoria immatures, not adults; (b) the presence of ketamine at either concentration in the food substrate significantly delays the developmental time to pupal and adult instar; (d) the survival of C. vomitoria is negatively affected by the presence of ketamine in the substrate; (e) the length and width of larvae and pupae exposed to either ketamine concentration were significantly larger than the control samples. Copyright © 2018. Published by Elsevier Ltd.

Ketamine reduces the need for intubation in patients with acute severe mental illness and agitation requiring transport to definitive care: An observational study.

PubMed

Parsch, Cathrin S; Boonstra, Adrianne; Teubner, David; Emmerton, Wade; McKenny, Brian; Ellis, Daniel Y

2017-06-01

The aim of this study was to review mental health patients transported by a dedicated statewide critical care retrieval team before and after the implementation of a ketamine sedation guideline. This is a a retrospective cohort study of mental health patients with acute behavioural disturbance, transported between January 2010 and December 2015. A total of 78 patients were transported in the study period, 50 before and 28 after implementation of the ketamine guideline in June 2013. The introduction of the ketamine guideline was associated with a significant reduction in intubation for transport (36.00 vs 7.14%) (odds ratio 0.14, 95% confidence interval 0.02-0.71, P < 0.01). The likelihood of utilising ketamine for non-intubated patients (n = 58) was higher in the period after implementation (37.50 vs 84.62%, odds ratio 9.17, 95% confidence interval 2.54-33.08, P < 0.005). The incidence of complications in our series was low. The implementation of a ketamine clinical practice guideline for agitated mental health patients was associated with an increase in the number of patients receiving ketamine as part of their sedation regime and a reduction in the number of patients requiring intubation for transport. Appropriately trained critical care retrieval teams should consider ketamine as part of the sedation regime for agitated mental health patients. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Repeated ketamine administration alters N-methyl-d-aspartic acid receptor subunit gene expression: Implication of genetic vulnerability for ketamine abuse and ketamine psychosis in humans

PubMed Central

Lipsky, Robert H

2015-01-01

For more than 40 years following its approval by the Food and Drug Administration (FDA) as an anesthetic, ketamine, a non-competitive N-methyl-d-aspartic acid (NMDA) receptor antagonist, has been used as a tool of psychiatric research. As a psychedelic drug, ketamine induces psychotic symptoms, cognitive impairment, and mood elevation, which resemble some symptoms of schizophrenia. Recreational use of ketamine has been increasing in recent years. However, little is known of the underlying molecular mechanisms responsible for ketamine-associated psychosis. Recent animal studies have shown that repeated ketamine administration significantly increases NMDA receptor subunit gene expression, in particular subunit 1 (NR1 or GluN1) levels. This results in neurodegeneration, supporting a potential mechanism where up-regulation of NMDA receptors could produce cognitive deficits in chronic ketamine abuse patients. In other studies, NMDA receptor gene variants are associated with addictive behavior. Here, we focus on the roles of NMDA receptor gene subunits in ketamine abuse and ketamine psychosis and propose that full sequencing of NMDA receptor genes may help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis. PMID:25245072

Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial.

PubMed

Cengiz, Pelin; Gokcinar, Derya; Karabeyoglu, Isil; Topcu, Hulya; Cicek, Gizem Selen; Gogus, Nermin

2014-05-01

To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. A randomized, double-blind comparative study. Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6 μg/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects.

Ketamine for Analgosedation in the Intensive Care Unit: A Systematic Review.

PubMed

Patanwala, Asad E; Martin, Jennifer R; Erstad, Brian L

2017-07-01

To evaluate the evidence for the use of intravenous ketamine for analgosedation in the intensive care unit. MEDLINE and EMBASE were queried from inception until July 2015. Search terms used included ketamine, intensive care, and critical care. The search retrieved 584 articles to be screened for inclusion. The intent was to include randomized controlled studies using sustained intravenous infusions (>24 hours) of ketamine in the critically ill patients. One trial evaluated opioid consumption as an outcome in postoperative critically ill patients who were randomized to ketamine or saline infusions. The mean cumulative morphine consumption at 48 hours was significantly lower in the ketamine group (58 ± 35 mg) compared to the morphine-only group (80 ± 37 mg; P < .05). Other trials showed the potential safety of ketamine in terms of cerebral hemodynamics in patients with traumatic brain injury, improved gastrointestinal motility, and decreased vasopressor requirements. The observational study and case reports suggest that ketamine is safe and effective and may have a role in patients who are refractory to other therapies. Ketamine use may decrease analgesic consumption in the intensive care unit. Additional trials are needed to further delineate the role of ketamine for analgosedation.

Effect of low-dose ketamine on post-operative serum IL-6 production among elective surgical patients: a randomized clinical trial.

PubMed

Luggya, Tonny Stone; Roche, Tony; Ssemogerere, Lameck; Kintu, Andrew; Kasumba, John Mark; Kwizera, Arthur; Tindimwebwa, Jose Vb

2017-06-01

Surgery and Anesthesia cause an excessive pro-inflammatory response. Mulago Hospital is faced with staff shortage making post-operative pain management difficult.Interleukin-6 (IL-6) drives inflammatory pain, endothelial cell dysfunction and fibrogenesis. Ketamine is cheap and, readily available. We hypothesized that its attenuation of serum IL-6 was a surrogate for clinical benefit. Institutional Review Board's approval was sought and RCT was registered at clinical trials.gov (identifier number: NCT01339065). Consenting patients were randomized to receive pre-incision intravenous ketamine - 0.5mg/kg or 0.9% saline placebo in weighted dosing. Blood samples were collected and laboratory analyzed at baseline, post-operatively in PACU, 24 and 48 hours respectively. We recruited 39 patients of whom 18 were randomized to the ketamine arm and 21 in the placebo arm with follow up at 24 and 48 hours. Serum IL-6 and IL-1β levels were analyzed using ELIZA assay of pre-coated micro wells. Ketamine suppressed serum IL-6 at PACU with reduced increase at 24 hours. There was no reaction in 98% of IL-1β assayed. Low-dose ketamine attenuated early serum IL-6 levels due to surgical response with reduced 24 hour increase, but the difference was not statistically significant and we recommend more studies.

Nefopam and Ketamine Comparably Enhance Postoperative Analgesia

PubMed Central

Kapfer, Barbara; Alfonsi, Pascal; Guignard, Bruno; Sessler, Daniel I.; Chauvin, Marcel

2005-01-01

Summary Opioids alone sometimes provide insufficient postoperative analgesia. Co-administration of drugs may reduce opioid use and to improve opioid efficacy. We therefore tested the hypothesis that administration of ketamine or nefopam, to postoperative patients with pain only partly alleviated by morphine, limits the amount of subsequent opioid necessary to produce adequate analgesia. Patients (n=77) recovering from major surgery were given up to 9 mg intravenous morphine. Those still suffering from pain were randomly assigned to blinded administration of: 1) isotonic saline (Control, n=21); 2) ketamine 10 mg (Ketamine, n=22); or, 3) nefopam 20 mg (Nefopam, n=22). Three-mg morphine boluses were subsequently given at 5-minute intervals until adequate analgesia was obtained, or 60 minutes elapsed after the beginning of the study drug administration, or ventilation became insufficient (respiratory rate < 10 breath/minute or saturation by pulse oxymetery < 95%). Supplemental morphine (i.e., after test drug administration) requirements were significantly greater in the Control group [17 ± 10 (SD) mg] than in the Nefopam (10 ± 5 mg, P < 0.005) or Ketamine (9 ± 5 mg, P < 0.001) groups. Morphine titration was successful in all Ketamine and Nefopam patients, but failed in four Control patients (two from respiratory toxicity and two from persistent pain). Tachycardia and profuse sweating were more frequent in patients given nefopam and sedation was greater with ketamine; however, the incidence of other potential complications did not differ between groups. Implications We conclude that ketamine 10 mg and nefopam 20 mg comparably potentiate opioid analgesia, each reducing opioid need by approximately 40%. Ketamine administration was associated with sedation whereas nefopam produced tachycardia and sweating. However, none of the side effects was serious. Either drug can thus be used to potentiate opioid analgesia. PMID:15616073

[Anesthesia in bronchial asthma].

PubMed

Bremerich, D H

2000-09-01

Asthma is defined as a chronic inflammatory airway disease in response to a wide variety of provoking stimuli. Characteristic clinical symptoms of asthma are bronchial hyperreactivity, reversible airway obstruction, wheezing and dyspnea. Asthma presents a major public health problem with increasing prevalence rates and severity worldwide. Despite major advances in our understanding of the clinical management of asthmatic patients, it remains a challenging population for anesthesiologists in clinical practice. The anesthesiologist's responsibility starts with the preoperative assessment and evaluation of the pulmonary function. For patients with asthma who currently have no symptoms, the risk of perioperative respiratory complications is extremely low. Therefore, pulmonary function should be optimized preoperatively and airway obstruction should be controlled by using steroids and bronchodilators. Preoperative spirometry is a simple means of assessing presence and severity of airway obstruction as well as the degree of reversibility in response to bronchodilator therapy. An increase of 15% in FEV1 is considered clinically significant. Most asymptomatic persons with asthma can safely undergo general anesthesia with and without endotracheal intubation. Volatile anesthetics are still recommended for general anesthetic techniques. As compared to barbiturates and even ketamine, propofol is considered to be the agent of choice for induction of anesthesia in asthmatics. The use of regional anesthesia does not reduce perioperative respiratory complications in asymptomatic asthmatics, whereas it is advantageous in symptomatic patients. Pregnant asthmatic and parturients undergoing anesthesia are at increased risk, especially if regional anesthetic techniques are not suitable and prostaglandin and its derivates are administered for abortion or operative delivery. Bronchial hyperreactivity associated with asthma is an important risk factor of perioperative bronchospasm. The

KETAMINE-MEDETOMIDINE AND KETAMINE-MEDETOMIDINE-MIDAZOLAM ANESTHESIA IN CAPTIVE CHEETAHS (ACINONYX JUBATUS)-COMPARISON OF BLOOD PRESSURE AND KIDNEY BLOOD FLOW.

PubMed

Stagegaard, Julia; Hørlyck, Arne; Hydeskov, Helle B; Bertelsen, Mads F

2017-06-01

Six clinically healthy captive cheetahs ( Acinonyx jubatus ) were anesthetized twice using two different drug combinations to investigate if blood pressure and kidney blood flow are affected by medetomidine dosage. Protocol KM (2.0 mg/kg ketamine and 0.05 mg/kg medetomidine) was compared with protocol KMM (2.0 mg/kg ketamine, 0.02 mg/kg medetomidine, and 0.1 mg/kg midazolam). Heart rate (HR), respiratory rate (RR), body temperature, end-tidal carbon dioxide pressure (ETCO 2 ), and anesthetic depth were monitored every 10 min. Noninvasive mean (MAP), systolic (SAP), and diastolic (DAP) arterial blood pressure were measured, and Duplex Doppler ultrasonography was performed on the kidneys. The mean arterial resistive index (RI) was determined and the pulse pressure index (PPI) was calculated, as indicators for kidney blood flow. There were no significant differences in induction and recovery times. MAP was significantly higher with KM than KMM at 35 min, and in both protocols decreased significantly after atipamezole administration. DAP was significantly higher at 25 and 35 min in animals anesthetized with KM; it also decreased significantly with both protocols after atipamezole administration. The PPI was significantly lower throughout the procedure with KM, and with both protocols increased significantly after atipamezole administration. Both the higher blood pressure and the reduced PPI with KM were likely a direct effect of the higher medetomidine dosage, and these findings indicate that lower medetomidine dosages might reduce hypertension and lead to a better PPI in cheetah immobilization.

[Ketamine--dreams and realities].

PubMed

Arditti, J; Spadari, M; de Haro, L; Brun, A; Bourdon, J H; Valli, M

2002-01-01

Ketamine is an anaesthetic used in human medicine and veterinary practice, synthesised on 1962 and marketed on 1970 in France. Recreational uses were described during 1992 in the medical community and in 1996 in the dance settings. The chemical name of ketamine is 2--(2chlorophenyl)2-(methylamine)-cyclohexanone, an aryl cyclohexylamine, structurally related to phencyclidine. Ketamine is known under the following street names: Keta K, Kate, Special K, Vitamin K, la Golden, la Vétérinaire. Ketamine is used intranasally, orally and intramusculary in recreational use. Ketamine is manufactured by the chemical industry. Due to the complicated synthesis, it is sold illicitly for recreational use. Ketamine is a dissociative drug, and the user enters in a psychedelic dream with hallucinations, floating sensation, feeling of dissociation of the mind from the body. The dream is forgotten, the user full in reality with loss of self control, risk of acute intoxication. In long-term exposure, tolerance, dependence, withdrawal signs and flash back are described. Ketamine trademarks are subject to control in France through medicine legislation Ketamine and its salts are subject to control under the national legislation on narcotics and psychotropics substance. From September 2001, the theft of medical and veterinary trademarks have to be declared to police, care health authority Pharmacy control authority and French Health Products Safety Agency.

21 CFR 522.1222 - Ketamine.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ketamine. 522.1222 Section 522.1222 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222 Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg) ketamine base...

Risk and safety of pediatric sedation/anesthesia for procedures outside the operating room.

PubMed

Cravero, Joseph P

2009-08-01

Sedation and anesthesia outside the operating room represents a rapidly growing field of practice that involves a number of different specialty providers including anesthesiology. The literature surrounding this work is found in a variety of journals - many outside anesthesiology. This review is intended to inform readers about the current status of risk and safety involving sedation/anesthesia for tests and minor procedures utilizing a wide range of sources. Two large database studies have helped to define the frequency and nature of adverse events in pediatric sedation/anesthesia practice from a multispecialty perspective. A number of papers describing respiratory and hemodynamic aspects of dexmedetomidine sedation have also been published. Finally, a number of studies relating to training sedation providers, reporting of sedation adverse events, sedation for vulnerable populations, and (in particular) ketamine sedation adverse respiratory events have also come to light. The latest publications continue to document a relatively low risk to pediatric sedation yet also warn us about the potential adverse events in this field. The results help to define competencies required to deliver pediatric sedation and make this practice even safer. Particularly interesting are new jargon and methodologies for defining adverse events and the use of new methods for training sedation providers.

Dose Regimens, Variability, and Complications Associated with Using Repeat-Bolus Dosing to Extend a Surgical Plane of Anesthesia in Laboratory Mice

PubMed Central

Jaber, Samer M; Hankenson, F Claire; Heng, Kathleen; McKinstry-Wu, Andrew; Kelz, Max B; Marx, James O

2014-01-01

Extending a surgical plane of anesthesia in mice by using injectable anesthetics typically is accomplished by repeat-bolus dosing. We compared the safety and efficacy of redosing protocols administered either during an anesthetic surgical plane (maintaining a continuous surgical plane, CSP), or immediately after leaving this plane (interrupted surgical plane, ISP) in C57BL/6J mice. Anesthesia was induced with ketamine, xylazine, and acepromazine (80, 8, and 1 mg/kg IP, respectively), and redosing protocols included 25% (0.25K), 50% (0.5K), or 100% (1.0K) of the initial ketamine dose or 25% (0.25KX) or 50% (0.5KX) of the initial ketamine–xylazine dose. In the ISP group, the surgical plane was extended by 13.8 ± 2.1 min (mean ± SEM) after redosing for the 0.25K redose with 50% returning to a surgical plane, 42.7 ± 4.5 min for the 0.5K redose with 88% returning to a surgical plane, and 44.3 ± 15.4 min for the 1.0K redose, 52.8 ± 7.2 min for the 0.25KX redose, and 45.9 ± 2.9 min for the 0.5KX redose, with 100% of mice returning to a surgical plane of anesthesia in these 3 groups. Mortality rates for ISP groups were 0%, 12%, 33%, 12%, and 18%, respectively. Mice in CSP groups had 50% mortality, independent of the repeat-dosing protocol. We recommend redosing mice with either 50% of the initial ketamine dose or 25% of the initial ketamine–xylazine dose immediately upon return of the pedal withdrawal reflex to extend the surgical plane of anesthesia in mice, optimize the extension of the surgical plane, and minimize mortality. PMID:25650976

Prevention of propofol-induced pain in children: pretreatment with small doses of ketamine.

PubMed

Zhao, Guang-yi; Guo, Yao; Bao, Shu-min; Meng, Ling-xin; Zhang, Li-hong

2012-06-01

To evaluate the efficacy of ketamine in preventing propofol injection pain in children. Prospective, randomized, double-blinded, placebo-controlled study. University-affiliated hospital. 192 ASA physical status 1 and 2 pediatric patients. Patients were randomly assigned to 4 groups. Group S (control) received normal saline as a placebo; Group K1, Group K3, and Group K5 received 0.1 mg/kg, 0.3 mg/kg, and 0.5 mg/kg of ketamine, respectively. Fifteen seconds after the ketamine injection, patients were injected with propofol at a rate of 12 mL/min until loss-of-eyelash reflex. Pain was evaluated blindly at the time of induction using a 4-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain. Adverse effects were recorded. Characteristics of induction of anesthesia, such as dose of propofol and time from propofol injection to loss of consciousness (induction duration), were noted. 39 (84.8%) Group S (control) patients had pain. Pretreatment with ketamine reduced the frequency of pain significantly to 56.5%, 17.0%, and 14.9% in Groups K1, K3, and K5, respectively. Furthermore, the frequency of moderate and severe pain in Group K1 (21.8%), Group K3 (6.4%), and Group K5 (4.3%) was significantly (P < 0.001, respectively) reduced compared with Group S (76.1%). Moreover, the dose of propofol for induction in Group K5 was smaller than in Group S, Group K1, and Group K3 (P < 0.05). One patient in Group K5 had emergence agitation. Pretreatment with a small dose of ketamine (0.3 mg/kg) reduced the frequency and intensity of propofol injection pain without severe adverse effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Ketamine versus alfentanil combined with propofol for sedation in colonoscopy procedures: a randomized prospective study.

PubMed

Türk, Hacer Şebnem; Aydoğmuş, Meltem; Ünsal, Oya; Işıl, Canan Tülay; Citgez, Bülent; Oba, Sibel; Açık, Mehmet Eren

2014-12-01

Different drug combinations are used for sedation in colonoscopy procedures. A ketamine-propofol (ketofol) mixture provides effective sedation and has minimal adverse effects. Alfentanil also provides anesthesia for short surgical procedures by incremental injection as an adjunct. However, no study has investigated the use of ketofol compared with an opioid-propofol combination in colonoscopic procedures. A total of 70 patients, ASA physical status I-II, scheduled to undergo elective colonoscopy, were enrolled in this prospective randomized study and allocated to two groups. After premedication, sedation induction was performed with 0.5 mg/kg ketamine +1 mg/kg propofol in Group KP, and 10 mg/kg alfentanil +1 mg/kg propofol in Group AP. Propofol was added when required. Demographic data, colonoscopy duration, recovery time, discharge time, mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation, Ramsey Sedation Scale values, colonoscopy patients' satisfaction scores, and complications were recorded. The need for additional propofol doses was significantly higher in Group AP than in Group KP. MAP at minute 1 and 5, Ramsey Sedation Scale at minute 5, and discharge time were significantly higher in Group KP than in Group AP. Additional propofol doses and total propofol dose were significantly lower in Group KP than in Group AP. Ketofol provided better hemodynamic stability and quality of sedation compared with alfentanil-propofol combination in elective colonoscopy, and required fewer additional propofol; however, it prolonged discharge time. Both combinations can safely be used in colonoscopy sedation.

Ketamine abuse potential and use disorder.

PubMed

Liu, Yu; Lin, Deyong; Wu, Boliang; Zhou, Wenhua

2016-09-01

Ketamine is a noncompetitive antagonist of N-methyl-d-asparate (NMDA) receptor and has been long used as an anesthetic agent in humans and veterinary medicine. The present article reviews the epidemiology, pharmacology, neurochemistry, and treatment of ketamine abuse. Ketamine has a unique mood controlling property and a number of studies have demonstrated a significant and rapid antidepressant effect of ketamine. However, the therapeutic value of ketamine to treat psychiatric disorders faces a major challenge that ketamine also owns significant reinforcing and toxic effects. Its abuse has posted severe harms on individuals and society. Disrupted learning and memory processing has long been related with ketamine use. It is hypothesized that ketamine blocks NMDA receptors on gamma-aminobutyric acid (GABA) neurons inside the thalamic reticular nucleus, which leads to disinhibition of dopaminergic neurons and increased release of dopamine. Currently, there is no specific treatment for treating every ketamine patient presenting peripheral toxicity. Interestingly, ketamine psychotherapy has been suggested to be a promising approach to treat addiction of other drugs. Future research can continue to develop creative ways to investigate potential mechanism and treatments related to ketamine abuse that have posted severe individual and social harms. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical immobilization of free-ranging and captive Sunda clouded leopards (Neofelis diardi) with two anesthetic protocols: medetomidine-ketamine and tiletamine-zolazepam

PubMed Central

NÁJERA, Fernando; HEARN, Andrew J.; ROSS, Joanna; RAMÍREZ SALDIVAR, Diana A.; EVANS, Meaghan N.; GUERRERO-SÁNCHEZ, Sergio; NATHAN, Senthilvel K.S.S.; DE GASPAR SIMÓN, Ignacio; MACDONALD, David W.; GOOSSENS, Benoit; REVUELTA RUEDA, Luis

2017-01-01

There is currently no available information regarding the veterinary management of Sunda clouded leopards (Neofelis diardi), either in captivity or in the wild. In this study, 12 Sunda clouded leopards were anesthetized between January 2008 and February 2014 for medical exams, and/or GPS-collaring. Seven wild-caught individuals were kept in captivity and 5 free-ranging animals were captured by cage traps. Two anesthesia combinations were used: medetomidine-ketamine (M-K) or tiletamine-zolazepam (T-Z). Atipamezole (0.2 mg/kg im) was used as an antagonist for medetomidine. Medetomidine (range: 0.039–0.054 mg/kg) and ketamine (range: 3–4.39 mg/kg) were administered during 5 immobilizations, resulting in median induction times of 7 min. After a median anesthesia time of 56 min, atipamezole was injected, observing effects of antagonism at a median time of 12 min. T-Z (range: 6.8–10.8 mg/kg) was administered on 7 occasions. Median induction times observed with this combination were shorter than with M-K (4 min vs 7 min; P=0.04), and anesthesia and recovery times were significantly longer (244 and 35 min vs 56 and 16 min, respectively; P=0.02). Lower heart rates were measured in the M-K group, while lower rectal temperatures were found in the T-Z group. Both combinations resulted in safe and reliable immobilizations, although given the favorable anesthesia and recovery times of M-K, we recommend this approach over T-Z for the veterinary handling of Sunda clouded leopards. PMID:28904261

Tablet e-Logbooks: Four Thousand Clinical Cases and Complications e-Logged by 14 Nondoctor Anesthesia Providers in Nepal.

PubMed

Shah, Shristi; Ross, Oliver; Pickering, Stephen; Knoble, Stephen; Rai, Indra

2017-10-01

were usually under ketamine anesthesia requiring basic airway maneuvers; 4 difficult intubations were recorded under general anesthesia. Anesthesia outcomes were good with overall mortality of 0.1% (total 4 cases). Causes of death included severe preeclampsia, sepsis postlaparotomy, and patients with multiorgan failure for minor procedure. The tablet-based electronic anesthesia logbook was successfully used to record cases, complications, and outcomes across rural Nepal. The nondoctor anesthesia providers had trust and confidence in recording outcomes. It remains to be tested whether an e-logbook would be routinely completed outside of a specific training course. Such a logbook could be incorporated into all continuous professional development programs for rural nondoctor anesthetists.

[No inhibition of intestinal motility following ketamine-midazolam anesthesia. A comparison of anesthesia with enflurane and fentanyl/midazolam].

PubMed

Freye, E; Knüfermann, V

1994-02-01

Postoperative intestinal atonia is a complication which is likely to occur in patients predisposed for constipation and in patients after intra-abdominal operations. The postoperative delay of bowel movement, however, is often also related to the type of anaesthesia being used. In order to evaluate the magnitude of an anaesthetic-induced postoperative delay of bowel movement, two types of intravenous-based anaesthesia using fentanyl/midazolam (1 mg/25 mg; dosage 0.1 ml/kg/h), and ketamine/midazolam (250 mg/25 mg; dosage 0.1 ml/kg/h) respectively were compared with a volatile anaesthetic technique (enflurane; mean concentration 1.5 vol%). METHODS. In three groups of patients (each n = 15) undergoing elective surgery of the lower extremities, induction of anaesthesia was accomplished with methohexital (1-1.5 mg/kg) to facilitate intubation. For the maintenance of muscle relaxation vecuronium bromide was used. All patients were given droperidol to prevent postoperative emesis, and they were artificially ventilated with N2O/O2 (60:40) to normal end-expiratory CO2 concentrations. No anticholinergic agents were used at the end of operation since they are known to interfere with bowel motility. In order to determine gastro-intestinal motility, the H2 exhalation test was used. For this purpose 40 g lactulose in 100 ml of water was given to all patients via a gastral tube shortly before extubation. Lactulose is broken down by bacteria once it enters the colon, and H2 is released, taken up by the vascular system and exhaled. Postoperatively, patients were asked to exhale into a 20-ml syringe every 10 min. The content was analysed for hydrogen (ppm), using an electrochemical sensor (GMI exhaled hydrogen monitor). From the time of lactulose instillation to a threefold increase in end-expiratory hydrogen concentration (compared to the preoperative value), gastro-coecal transit time was computed. RESULTS. All three groups of patients were comparable in age, height and body

Ketamine for pain

PubMed Central

Jonkman, Kelly; Dahan, Albert; van de Donk, Tine; Aarts, Leon; Niesters, Marieke; van Velzen, Monique

2017-01-01

The efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as an analgesic agent is still under debate, especially for indications such as chronic pain. To understand the efficacy of ketamine for relief of pain, we performed a literature search for relevant narrative and systematic reviews and meta-analyses. We retrieved 189 unique articles, of which 29 were deemed appropriate for use in this review. Ketamine treatment is most effective for relief of postoperative pain, causing reduced opioid consumption. In contrast, for most other indications (that is, acute pain in the emergency department, prevention of persistent postoperative pain, cancer pain, and chronic non-cancer pain), the efficacy of ketamine is limited. Ketamine’s lack of analgesic effect was associated with an increase in side effects, including schizotypical effects. PMID:28979762

Ayanin, a non-selective phosphodiesterase 1-4 inhibitor, effectively suppresses ovalbumin-induced airway hyperresponsiveness without affecting xylazine/ketamine-induced anesthesia.

PubMed

Lee, Fei-Peng; Shih, Chwen-Ming; Shen, Hsin-Yi; Chen, Chien-Ming; Chen, Chi-Ming; Ko, Wun-Chang

2010-06-10

In recent in vitro reports, the IC(50) value of ayanin (quercetin-3,7,4'-O-trimethylether) was 2.2microM for inhibiting interleukin (IL)-4 production from purified basophils, and its therapeutic ratio was >19. Therefore, we were interested in investigating the effects on ovalbumin induced airway hyperresponsiveness in vivo, and to clarify its potential for treating asthma. Ayanin (30-100micromol/kg, orally (p.o.)) dose-dependently and significantly attenuated the enhanced pause (P(enh)) value induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including IL-2, IL-4, IL-5, and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid of these mice. However, at 100micromol/kg, it significantly enhanced the level of interferon (IFN)-gamma. In addition, ayanin (30-100micromol/kg, p.o.) dose-dependently and significantly suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and bronchoalveolar lavage fluid, and enhanced the IgG(2a) level in serum of these mice. In the present results, ayanin did not affect xylazine/ketamine-induced anesthesia, suggesting that ayanin has few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, the above results suggest that ayanin may have the potential for use in treating allergic asthma.

Ketamine - A Multifaceted Drug.

PubMed

Meng, Lingzhong; Li, Jian; Lu, Yi; Sun, Dajin; Tao, Yuan-Xiang; Liu, Renyu; Luo, Jin Jun

There is a petition for tight control of ketamine from the Chinese government to classify ketamine as a Schedule I drug, which is defined as a drug with no currently accepted medical use but a high potential for abuse. However, ketamine has unique properties that can benefit different patient populations. Scholars from the Translational Perioperative and Pain Medicine and the International Chinese Academy of Anesthesiology WeChat groups had an interactive discussion on ketamine, including its current medical applications, future research priorities, and benefits versus risks. The discussion is summarized in this manuscript with some minor edits.

Recovery from desflurane anesthesia in horses with and without post-anesthetic xylazine.

PubMed

Aarnes, Turi K; Bednarski, Richard M; Bertone, Alicia L; Hubbell, John A E; Lerche, Phillip

2014-04-01

The objective of this study was to compare recovery from desflurane anesthesia in horses with or without post-anesthetic xylazine. Six adult horses were anesthetized on 2 occasions, 14 d apart using a prospective, randomized crossover design. Horses were sedated with xylazine, induced to lateral recumbency with ketamine and diazepam, and anesthesia was maintained with desflurane. One of 2 treatments was administered intravenously at the end of anesthesia: xylazine [0.2 mg/kg body weight (BW)] or an equivalent volume of saline. Recovery parameters were recorded and assessed by 2 blinded observers. A Wilcoxon signed-rank test was used to analyze recovery data. Heart rate, arterial blood pressures, and arterial blood gas data were analyzed using 2-way analysis of variance (ANOVA) for repeated measures. Values of P < 0.05 were considered significant. Duration of anesthesia was not different between groups. Administration of xylazine at the end of desflurane anesthesia was associated with significantly longer times to first movement, endotracheal tube removal, first attempt to achieve sternal recumbency, sternal recumbency, first attempt to stand, and standing. Number of attempts to stand and quality of recovery scores were not different between groups. Administering xylazine after desflurane anesthesia resulted in longer recovery times. Recovery scores were not significantly different between groups.

Recovery from desflurane anesthesia in horses with and without post-anesthetic xylazine

PubMed Central

Aarnes, Turi K.; Bednarski, Richard M.; Bertone, Alicia L.; Hubbell, John A.E.; Lerche, Phillip

2014-01-01

The objective of this study was to compare recovery from desflurane anesthesia in horses with or without post-anesthetic xylazine. Six adult horses were anesthetized on 2 occasions, 14 d apart using a prospective, randomized crossover design. Horses were sedated with xylazine, induced to lateral recumbency with ketamine and diazepam, and anesthesia was maintained with desflurane. One of 2 treatments was administered intravenously at the end of anesthesia: xylazine [0.2 mg/kg body weight (BW)] or an equivalent volume of saline. Recovery parameters were recorded and assessed by 2 blinded observers. A Wilcoxon signed-rank test was used to analyze recovery data. Heart rate, arterial blood pressures, and arterial blood gas data were analyzed using 2-way analysis of variance (ANOVA) for repeated measures. Values of P < 0.05 were considered significant. Duration of anesthesia was not different between groups. Administration of xylazine at the end of desflurane anesthesia was associated with significantly longer times to first movement, endotracheal tube removal, first attempt to achieve sternal recumbency, sternal recumbency, first attempt to stand, and standing. Number of attempts to stand and quality of recovery scores were not different between groups. Administering xylazine after desflurane anesthesia resulted in longer recovery times. Recovery scores were not significantly different between groups. PMID:24688171

Comparison of the effect of intravenous anesthetics used for anesthesia during electroconvulsive therapy on the hemodynamic safety and the course of ECT.

PubMed

Wojdacz, Rafał; Święcicki, Łukasz; Antosik-Wójcińska, Anna

2017-12-30

Electroconvulsive therapy (ECT) is the treatment method widely used in psychiatric disorders such as depression, bipolar disorder, schizophrenia and schizoaffective disorder. The advantage of ECT is therapeutic response that occurs significantly earlier than during pharmacotherapy. Initially ECTwas used without anesthesia. Then, in the 1950s procedures with general anesthesia were introduced to reduce the complications that may occur during a seizure caused by ECT, such as broken bones, teeth, tendon rupture, muscle damage. Currently, in general anesthesia for ECTseveral medications are used interchangeably: thiopental, propofol, etomidate and ketamine. In different resorts and different countries different anestethics are used, the choice is determined mainly by the experience of each resort and a kind of tradition. The authors provide an overview of objective data showing how various anesthetics affect the quality of ECT and the presence of any hemodynamic complications after ETC. Selection of articles included in this paper was made by searching Medline and PubMed databases using specific keywords: electroconvulsive therapy, general anesthesia, the risks and benefits of thiopental, ketamine, propofol and etomidate. The results of this review are inconclusive when it comes to the effect of intravenous anesthetics on the quality of the ECT treatment and side effects relating to respiratory and cardiovascular system. On this basis it is impossible to determine which of intravenous anesthetics is most advantageous from the point of view of the patient. To develop the optimum scheme of anesthesia for ECT, it is necessary to conduct further, methodologically correct studies.

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

PubMed Central

Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

2016-01-01

Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

Propofol-medetomidine-ketamine total intravenous anaesthesia in thiafentanil-medetomidine-immobilized impala (Aepyceros melampus).

PubMed

Buck, Roxanne K; Meyer, Leith R C; Stegmann, George F; Kästner, Sabine B R; Kummrow, Maya; Gerlach, Christina; Fosgate, Geoffrey T; Zeiler, Gareth E

2017-01-01

To characterize a propofol-medetomidine-ketamine total intravenous anaesthetic in impala (Aepyceros melampus). Prospective clinical study. Ten adult female impala. Impala were immobilized at 1253 m above sea level with 2.0 mg thiafentanil and 2.2 mg medetomidine via projectile darts. Propofol was given to effect (0.5 mg kg -1 boluses) to allow endotracheal intubation, following which oxygen was supplemented at 2 L minute -1 . Anaesthesia was maintained with a constant-rate infusion of medetomidine and ketamine at 5 μg kg -1 hour -1 and 1.5 mg kg -1 hour -1 , respectively, and propofol to effect (initially 0.2 mg kg -1 minute -1 ) for 120 minutes. The propofol infusion was titrated according to reaction to nociceptive stimuli every 15 minutes. Cardiopulmonary parameters were monitored continuously and arterial blood gas samples were analysed intermittently. After 120 minutes' maintenance, the thiafentanil and medetomidine were antagonized using naltrexone (10:1 thiafentanil) and atipamezole (5:1 medetomidine), respectively. All impala were successfully immobilized. The median dose [interquartile range (IQR)] of propofol required for intubation was 2.7 (1.9-3.3) mg kg -1 . The propofol-medetomidine-ketamine combination abolished voluntary movement and ensured anaesthesia for the 120 minute period. Propofol titration showed a generally downward trend. Median (IQR) heart rate [57 (53-61) beats minute -1 ], respiratory rate [10 (9-12) breaths minute -1 ] and mean arterial blood pressure [101 (98-106) mmHg] were well maintained. Arterial blood gas analysis indicated hypoxaemia, hyper- capnia and acidaemia. Butorphanol (0.12 mg kg -1 ) was an essential rescue drug to counteract thiafentanil-induced respiratory depression. All impala regurgitated frequently during the maintenance period. Recovery was calm and rapid in all animals. Median (IQR) time to standing from antagonist administration was 4.4 (3.2-5.6) minutes. A propofol-medetomidine-ketamine combination could

Current Ketamine Practice: Results of the 2016 American Society of Pain Management Nursing Survey on Ketamine.

PubMed

Klaess, Cynthia C; Jungquist, Carla R

2018-06-01

Ketamine is increasingly utilized for a variety of pain management challenges. Audience comments from a ketamine presentation at the 2015 American Society of Pain Management Nursing (ASPMN) Conference reflected wide variation in ketamine practices as well as barriers to use. The goal was to gain a greater understanding of ASPMN member practice patterns and barriers related to ketamine as adjunctive therapy for pain management. A questionnaire survey design was used. Respondents represented 35 states and 2 countries. The participants were 146 respondents from ASPMN membership (1,485 members). The survey was distributed by ASPMN on SurveyMonkey. Practice setting and ketamine administration practices were assessed with areas for comments. Results were reviewed using frequencies to describe responses and formatted into tables. Comments were individually reviewed and grouped into common themes. Administration of ketamine as an analgesic was reported by 63% of respondents. Continuous intravenous ketamine infusions were the most common route of administration (65%); however, wide variability in dosing and length of therapy was reported. A wide variety of practices and challenges related to ketamine utilization were noted. Numerous studies have indicated the analgesic benefits of ketamine in pain management. The lack of practice standardization has created challenges to its consistent use and outcome measurement. Additionally, the off-label use of ketamine for pain management creates its own unique challenges. However, given the current national climate with intense focus on pain management, interdisciplinary practitioners have an ideal opportunity to evaluate ketamine's use in a comprehensive approach to pain management. Copyright © 2018 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters

PubMed Central

Can, Adem; Zanos, Panos; Moaddel, Ruin; Kang, Hye Jin; Dossou, Katinia S. S.; Wainer, Irving W.; Cheer, Joseph F.; Frost, Douglas O.; Huang, Xi-Ping

2016-01-01

Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine’s antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine’s side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system. Here, brain and blood distribution/clearance and pharmacodynamic analyses at DA receptors (D1–D5) and the DA, norepinephrine, and serotonin transporters were assessed for ketamine and its major metabolites (norketamine, dehydronorketamine, and HNKs). Additionally, we measured electrically evoked mesolimbic DA release and decay using fast-scan cyclic voltammetry following acute administration of subanesthetic doses of ketamine (2, 10, and 50 mg/kg, i.p.). Following ketamine injection, ketamine, norketamine, and multiple hydroxynorketamines were detected in the plasma and brain of mice. Dehydronorketamine was detectable in plasma, but concentrations were below detectable limits in the brain. Ketamine did not alter the magnitude or kinetics of evoked DA release in the nucleus accumbens in anesthetized mice. Neither ketamine’s enantiomers nor its metabolites had affinity for DA receptors or the DA, noradrenaline, and serotonin transporters (up to 10 μM). These results suggest that neither the side effects nor antidepressant actions of ketamine or ketamine metabolites are associated with direct effects on mesolimbic DAergic neurotransmission. Previously observed in vivo changes in DAergic neurotransmission following ketamine administration are likely indirect. PMID

Effects of anesthesia and blood sampling techniques on plasma metabolites and corticosterone in the rat.

PubMed

Arnold, Myrtha; Langhans, Wolfgang

2010-04-19

Blood is routinely sampled from laboratory animals in biomedical research, and many of the commonly applied sampling techniques require anesthesia. Acute effects of many sampling and anesthesia procedures may confound the results, but those effects are incompletely characterized. We here compare the effects of four common anesthesia procedures (inhalation anesthesia with ether (EA) or isoflurane (IA) and intraperitoneal injection anesthesia with xylazin/ketamine (XKA) or medetomidine/midazolam/fentanyl (MMFA)) on plasma concentrations of glucose, lactate, non-esterified fatty acids (NEFAs), and corticosterone in blood obtained from a previously implanted jugular vein (JV) catheter with the effect of JV blood sampling from non-anesthetized, freely-moving rats (JV-NA). Also, we included in the comparison two other blood sampling procedures usually performed without anesthesia (NA), i.e., puncture of the saphenic vein (SV) and tail incision (TI). Whereas the control procedure (JV-NA) did not significantly affect any of the target parameters, plasma glucose increased from 14 (JV-IA) to 44 (JV-MMFA) % (all Ps=0.05 when compared with the control procedure) in all blood samples collected in anesthesia and was 12 and 14% lower (both Ps<0.05) in SV-NA and TI-NA samples, respectively. Plasma lactate increased from 74 (JV-IA) to 226% (SV-NA) (all Ps<0.05) with all sampling and anesthesia procedures except for JV-XKA and JV-MMF. Plasma NEFAs increased to 52% (P<0.05) with the TI-NA procedure and appeared to decrease with the JV-IA and JV-MMFA procedures (both Ps>0.05). Finally, only the JV-EA and the JV-MMFA procedures increased plasma corticosterone (+525 and +353%, respectively, both Ps< 0.05). The JV-IA and JV-XKA procedures appeared to increase it as well, but these differences did not reach statistical significance. Thus, anesthesia and blood sampling procedures can have profound acute effects on plasma metabolite and hormone concentrations. This must be considered for

COMPARISON OF INTRAMUSCULAR FENTANYL-MIDAZOLAM, FENTANYL-MIDAZOLAM-KETAMINE, AND KETAMINE-MEDETOMIDINE FOR IMMOBILIZATION OF JAPANESE MACAQUES ( MACACA FUSCATA).

PubMed

Ølberg, Rolf-Arne; Sinclair, Melissa; Barker, Ian K; Crawshaw, Graham

2018-03-01

The combination of fentanyl and midazolam is commonly used as a sedative in humans. The objective of this study was to evaluate the sedative properties and physiological effects of fentanyl-midazolam and fentanyl-midazolam-ketamine compared with medetomidine-ketamine given intramuscularly in Japanese macaques ( Macaca fuscata). In a randomized crossover design, eight Japanese macaques were hand-injected with either 30 μg/kg fentanyl + 0.3 mg/kg midazolam (FM), 15 μg/kg fentanyl + 0.3 mg/kg midazolam + 5.0 mg/kg ketamine (FMK), or 0.05 mg/kg medetomidine + 5.0 mg/kg ketamine (MedK). Heart rate; indirect systolic, mean, and diastolic arterial pressure; respiratory rate; blood gas concentrations; rectal temperature; and duration of immobilization were recorded. Mixed linear models were used to evaluate the effects of drug treatment on all continuous variables, with a significance level of P < 0.05. Only three of seven animals receiving FM were successfully immobilized. All eight animals in both the FMK and MedK treatment groups had a rapid, smooth induction and were successfully immobilized. Both FMK and MedK treatments resulted in significant hypoxia and the animals required supplemental oxygen via face mask. The mean duration of FMK immobilization was 42 ± 10 min, significantly shorter than the 65 ± 14 min for the animals receiving MedK. Immobilization with MedK resulted in significantly lower heart rates, and significantly higher arterial pressure compared with FMK. Hypoventilation was significantly more pronounced in FMK-treated animals compared with MedK treatments. Immobilization with FMK resulted in a gradual, slow recovery whereas MedK-treated animals woke up more rapidly. Fentanyl-midazolam alone is not a useful sedative in Japanese macaques. A combination of fentanyl and midazolam with ketamine can be used as an alternative to medetomidine-ketamine in this species.

Evaluation of medetomidine-ketamine and atipamezole for reversible anesthesia of free-ranging gray wolves (Canis lupus).

PubMed

Arnemo, Jon M; Evans, Alina L; Ahlqvist, Per; Segerström, Peter; Liberg, Olof

2013-04-01

Twenty-eight anesthetic events were carried out on 24 free-ranging Scandinavian gray wolves (Canis lupus) by darting from a helicopter with 5 mg medetomidine and 250 mg ketamine during winter in 2002 and 2003. Mean±SD doses were 0.162±0.008 mg medetomidine/kg and 8.1±0.4 mg ketamine/kg in juveniles (7-10 mo old) and 0.110±0.014 mg medetomidine/kg and 5.7±0.5 mg ketamine/kg in adults (>19 mo old). Mean±SD induction time was shorter (P<0.01) in juveniles (2.3±0.8 min) than in adults (4.1±0.6 min). In 26 cases, the animals were completely immobilized after one dart. Muscle relaxation was good, palpebral reflexes were present, and there were no reactions to handling or minor painful stimuli. Mild to severe hyperthermia was detected in 14/28 anesthetic events. Atipamezole (5 mg per mg medetomidine) was injected intramuscularly for reversal 98±28 and 94±40 min after darting in juveniles and adults, respectively. Mean±SD time from administration of atipamezole to coordinated walking was 38±20 min in juveniles and 41±21 min in adults. Recovery was uneventful in 25 anesthetic events, although vomiting was observed in five animals. One adult that did not respond to atipamezole was given intravenous fluids and was fully recovered 8 hr after darting. Two animals died 7-9 hr after capture, despite intensive care. Both mortalities were attributed to shock and circulatory collapse following stress-induced hyperthermia. Although effective, this combination cannot be recommended for darting free-ranging wolves from helicopter at the doses presented here because of the severe hyperthermia seen in several wolves, two deaths, and prolonged recovery in one individual.

Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial

PubMed Central

Ayatollahi, Vida; Behdad, Shekoufeh; Hatami, Maryam; Moshtaghiun, Hossein; Baghianimoghadam, Behnam

2012-01-01

Aim To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects. Methods The double-blind randomized clinical trial was performed on 126 patients aged 5-12 years who had been scheduled for elective tonsillectomy. The patients were randomly divided into 3 groups to receive either ketamine, tramadol, or placebo. They had American Society of Anesthesiologists physical status class I and II. All patients underwent the same method of anesthesia and surgical procedure. The three groups did not differ according to their age, sex, and duration of anesthesia and surgery. Post operative pain was evaluated using CHEOPS score. Other parameters such as the time to the first request for analgesic, hemodynamic elements, sedation score, nausea, vomiting, and hallucination were also assessed during 12 hours after surgery. Results Tramadol group had significantly lower pain scores (P = 0.005), significantly longer time to the first request for analgesic (P = 0.001), significantly shorter time to the beginning of liquid regimen (P = 0.001), and lower hemodynamic parameters such as blood pressure (P = 0.001) and heart rate (P = 0.001) than other two groups. Ketamine group had significantly greater presence of hallucinations and negative behavior than tramadol and placebo groups. The groups did not differ significantly in the presence of nausea and vomiting. Conclusion Preoperative peritonsillar infiltration of tramadol can decrease post-tonsillectomy pain, analgesic consumption, and the time to recovery without significant side effects. Registration No: IRCT201103255764N2 PMID:22522994

mTOR activation is required for the anti-alcohol effect of ketamine, but not memantine, in alcohol-preferring rats

PubMed Central

Sabino, Valentina; Narayan, Aditi R.; Zeric, Tamara; Steardo, Luca; Cottone, Pietro

2013-01-01

Glutamate NMDA receptors mediate many molecular and behavioral effects of alcohol, and they play a key role in the development of excessive drinking. Uncompetitive NMDA receptor antagonists may, therefore, have therapeutic potential for alcoholism. The first aim was to compare the effects of the NMDA antagonists memantine and ketamine on ethanol and saccharin drinking in alcohol-preferring rats. The second aim was to determine whether the effects of the two NMDA receptor antagonists were mediated by the mammalian target of rapamycin (mTOR). TSRI Sardinian alcohol-preferring rats were allowed to self-administer either 10% w/v ethanol or 0.08% w/v saccharin, and water. Operant responding and motor activity were assessed following administration of either memantine (0–10 mg/kg) or ketamine (0–20 mg/kg). Finally, ethanol self-administration was assessed in rats administered with either memantine or ketamine but pretreated with the mTOR inhibitor rapamycin (2.5 mg/kg). The uncompetitive NMDA receptor antagonists memantine and ketamine dose-dependently reduced ethanol drinking in alcohol-preferring rats; while memantine had a preferential effect on alcohol over saccharin, ketamine reduced responding for both solutions. Neither antagonist induced malaise, as shown by the lack of effect on water intake and motor activity. The mTOR inhibitor rapamycin blocked the effects of ketamine, but not those of memantine. Memantine and ketamine both reduce alcohol drinking in alcohol-preferring rats, but only memantine is selective for alcohol. The effects of ketamine, but not memantine, are mediated by mTOR. The results support the therapeutic potential of uncompetitive NMDA receptor antagonists, especially memantine, in alcohol addiction. PMID:23466691

Laparoscopic Surgery Using Spinal Anesthesia

PubMed Central

Gurwara, A. K.; Gupta, S. C.

2008-01-01

Background: Laparoscopic abdominal surgery is conventionally done under general anesthesia. Spinal anesthesia is usually preferred in patients where general anesthesia is contraindicated. We present our experience using spinal anesthesia as the first choice for laparoscopic surgery for over 11 years with the contention that it is a good alterative to anesthesia. Methods: Spinal anesthesia was used in 4645 patients over the last 11 years. Laparoscopic cholecystectomy was performed in 2992, and the remaining patients underwent other laparoscopic surgeries. There was no modification in the technique, and the intraabdominal pressure was kept at 8mm Hg to 10mm Hg. Sedation was given if required, and conversion to general anesthesia was done in patients not responding to sedation or with failure of spinal anesthesia. Results were compared with those of 421 patients undergoing laparoscopic surgery while under general anesthesia. Results: Twenty-four (0.01%) patients required conversion to general anesthesia. Hypotension requiring support was recorded in 846 (18.21%) patients, and 571(12.29%) experienced neck or shoulder pain, or both. Postoperatively, 2.09% (97) of patients had vomiting compared to 29.22% (123 patients) of patients who were administered general anesthesia. Injectable diclofenac was required in 35.59% (1672) for abdominal pain within 2 hours postoperatively, and oral analgesic was required in 2936 (63.21%) patients within the first 24 hours. However, 90.02% of patients operated on while under general anesthesia required injectable analgesics in the immediate postoperative period. Postural headache persisting for an average of 2.6 days was seen in 255 (5.4%) patients postoperatively. Average time to discharge was 2.3 days. Karnofsky Performance Status Scale showed a 98.6% satisfaction level in patients. Conclusions: Laparoscopic surgery done with the patient under spinal anesthesia has several advantages over laparoscopic surgery done with the patient under

Ketamine Infusions for Treatment Refractory Headache.

PubMed

Pomeroy, Jared L; Marmura, Michael J; Nahas, Stephanie J; Viscusi, Eugene R

2017-02-01

Management of chronic migraine (CM) or new daily persistent headache (NDPH) in those who require aggressive outpatient and inpatient treatment is challenging. Ketamine has been suggested as a new treatment for this intractable population. This is a retrospective review of 77 patients who underwent administration of intravenous, subanesthetic ketamine for CM or NDPH. All patients had previously failed aggressive outpatient and inpatient treatments. Records were reviewed for patients treated between January 2006 and December 2014. The mean headache pain rating using a 0-10 pain scale was an average of 7.1 at admission and 3.8 on discharge (P < .0001). The majority (55/77, 71.4%) of patients were classified as acute responders defined as at least 2-point improvement in headache pain at discharge. Some (15/77, 27.3%) acute responders maintained this benefit at their follow-up office visit but sustained response did not achieve statistical significance. The mean length of infusion was 4.8 days. Most patients tolerated ketamine well. A number of adverse events were observed, but very few were serious. Subanesthetic ketamine infusions may be beneficial in individuals with CM or NDPH who have failed other aggressive treatments. Controlled trials may confirm this, and further studies may be useful in elucidating more robust benefit in a less refractory patient population. © 2016 American Headache Society.

Cost-Effectiveness of Postoperative Ketamine in Chiari Decompression.

PubMed

McDowell, Michael M; Alhourani, Ahmad; Pearce-Smith, Beverly A; Mazurkiewicz, Anna; Friedlander, Robert M

2018-02-01

In Chiari I patients, postoperative pain and discomfort frequently slow the transition back to the home setting. We sought to determine the effect of standardized ketamine infusion protocols on hospital length of stay (LOS). This retrospective cohort study reviewed 100 consecutive adult patients undergoing Chiari I decompression. Fifty-nine patients were placed on a 2-3 mg/hr ketamine drip until postoperative day 1. This group was compared with a group who received 2-3 mg/hr of ketamine until postoperative day 2 (19 patients) and patients who did not receive ketamine at all (22 patients). Clinical characteristics, opioid use, LOS, and relative hospitalization costs were assessed. All narcotic amounts were converted into milligram equivalents of morphine. LOS of the short-ketamine group was 46.5 hours when compared with the long-ketamine group (66.8 hours) and no-ketamine group (56.9 hours). There was a statistically significant difference when comparing the short-ketamine group with the long-ketamine group and no-ketamine group together (P < 0.001), as well as when compared individually (P = 0.001 and 0.004). The mean cost of hospitalization was 20% less when a short-ketamine protocol was used (P < 0.001). Mean morphine milligram equivalents used postoperatively were 148 mg in the short-ketamine group, 196 mg in the long-ketamine group, and 187 mg in the no-ketamine group (P = 0.65). No adverse events from ketamine were noted. Ketamine at subanesthetic levels may be an effective tool to facilitate early return home postoperatively and may significantly reduce medical costs. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses

PubMed Central

Gideons, Erinn S.; Kavalali, Ege T.; Monteggia, Lisa M.

2014-01-01

Ketamine is an NMDA receptor (NMDAR) antagonist that elicits rapid antidepressant responses in patients with treatment-resistant depression. However, ketamine can also produce psychotomimetic effects that limit its utility as an antidepressant, raising the question of whether the clinically tolerated NMDAR antagonist memantine possesses antidepressant properties. Despite its similar potency to ketamine as an NMDAR antagonist, clinical data suggest that memantine does not exert rapid antidepressant actions for reasons that are poorly understood. In this study, we recapitulate the ketamine and memantine clinical findings in mice, showing that ketamine, but not memantine, has antidepressant-like effects in behavioral models. Using electrophysiology in cultured hippocampal neurons, we show that ketamine and memantine effectively block NMDAR-mediated miniature excitatory postsynaptic currents in the absence of Mg2+. However, in physiological levels of extracellular Mg2+, we identified key functional differences between ketamine and memantine in their ability to block NMDAR function at rest. This differential effect of ketamine and memantine extends to intracellular signaling coupled to NMDAR at rest, in that memantine does not inhibit the phosphorylation of eukaryotic elongation factor 2 or augment subsequent expression of BDNF, which are critical determinants of ketamine-mediated antidepressant efficacy. These results demonstrate significant differences between the efficacies of ketamine and memantine on NMDAR-mediated neurotransmission that have impacts on downstream intracellular signaling, which we hypothesize is the trigger for rapid antidepressant responses. These data provide a novel framework on the necessary functional requirements of NMDAR-mediated neurotransmission as a critical determinant necessary to elicit rapid antidepressant responses. PMID:24912158

A prospective study of ketamine versus haloperidol for severe prehospital agitation.

PubMed

Cole, Jon B; Moore, Johanna C; Nystrom, Paul C; Orozco, Benjamin S; Stellpflug, Samuel J; Kornas, Rebecca L; Fryza, Brandon J; Steinberg, Lila W; O'Brien-Lambert, Alex; Bache-Wiig, Peter; Engebretsen, Kristin M; Ho, Jeffrey D

2016-08-01

Ketamine is an emerging drug for the treatment of acute undifferentiated agitation in the prehospital environment, however no prospective comparative studies have evaluated its effectiveness or safety in this clinical setting. We hypothesized 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation, with time to adequate sedation as the primary outcome measure. This was a prospective open label study of all patients in an urban EMS system requiring chemical sedation for severe acute undifferentiated agitation that were subsequently transported to the EMS system's primary Emergency Department. All paramedics were trained in the Altered Mental Status Scale and prospectively recorded agitation scores on all patients. Two 6-month periods where either ketamine or haloperidol was the first-line therapy for severe agitation were prospectively compared primarily for time to adequate sedation. Secondary outcomes included laboratory data and adverse medication events. 146 subjects were enrolled; 64 received ketamine, 82 received haloperidol. Median time to adequate sedation for the ketamine group was 5 minutes (range 0.4-23) vs. 17 minutes (range 2-84) in the haloperidol group (difference 12 minutes, 95% CI 9-15). Complications occurred in 49% (27/55) of patients receiving ketamine vs. 5% (4/82) in the haloperidol group. Complications specific to the ketamine group included hypersalivation (21/56, 38%), emergence reaction (5/52, 10%), vomiting (5/57, 9%), and laryngospasm (3/55, 5%). Intubation was also significantly higher in the ketamine group; 39% of patients receiving ketamine were intubated vs. 4% of patients receiving haloperidol. Ketamine is superior to haloperidol in terms of time to adequate sedation for severe prehospital acute undifferentiated agitation, but is associated with more complications and a higher intubation rate.

Alfaxalone or ketamine-medetomidine in cats undergoing ovariohysterectomy: a comparison of intra-operative parameters and post-operative pain.

PubMed

Kalchofner Guerrero, Karin S; Reichler, Iris M; Schwarz, Andrea; Jud, Rahel S; Hässig, Michael; Bettschart-Wolfensberger, Regula

2014-11-01

To compare post-operative pain in cats after alfaxalone or ketamine- medetomidine anaesthesia for ovariohysterectomy (OHE) and physiologic parameters during and after surgery. Prospective 'blinded' randomized clinical study. Twenty-one healthy cats. Cats were assigned randomly into two groups: Group A, anaesthesia was induced and maintained with alfaxalone [5 mg kg(-1) intravenously (IV) followed by boli (2 mg kg(-1) IV); Group MK, induction with ketamine (5 mg kg(-1) IV) after medetomidine (30 μg kg(-1) intramuscularly (IM)], and maintenance with ketamine (2 mg kg(-1) IV). Meloxicam (0.2 mg kg(-1) IV) was administered after surgery. Basic physiological data were collected. At time T = -2, 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, and 24 hours post-operatively pain was assessed by three methods, a composite pain scale (CPS; 0-24 points), a visual analogue scale (VAS 0-100 mm), and a mechanical wound threshold (MWT) device. Butorphanol (0.2 mg kg(-1) IM) was administered if CPS was scored ≥13. Data were analyzed using a general linear model, Kruskal-Wallis analyses, Bonferroni-Dunn test, unpaired t-test and Fisher's exact test as relevant. Significance was set at p < 0.05. VASs were significantly higher at 0.5, 1, 2, 4, and 20 hours in group A; MWT values were significantly higher at 8 and 12 hours in group MK. Post-operative MWT decreased significantly compared to baseline in both groups. There was no difference in CPS at any time point. Five cats required rescue analgesia (four in A; one in MK). Anaesthesia with ketamine-medetomidine was found to provide better post-surgical analgesia than alfaxalone in cats undergoing OHE; however, primary hyperalgesia developed in both groups. Alfaxalone is suitable for induction and maintenance of anaesthesia in cats undergoing OHE, but administration of additional sedative and analgesic drugs is highly recommended. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Effect of the α2 -receptor agonists medetomidine, detomidine, xylazine, and romifidine on the ketamine metabolism in equines assessed with enantioselective capillary electrophoresis.

PubMed

Sandbaumhüter, Friederike A; Theurillat, Regula; Bettschart-Wolfensberger, Regula; Thormann, Wolfgang

2017-08-01

The combination of ketamine and an α 2 -receptor agonist is often used in veterinary medicine. Four different α 2 -receptor agonists, medetomidine, detomidine, xylazine, and romifidine, which differ in their chemical structure and thus in selectivity for the α 2 -receptor and in the sedative and analgesic potency, are typically employed during surgery of equines. Recovery following anesthesia with ketamine and an α 2 -receptor agonist is dependent on the α 2 -receptor agonist. This prompted us to investigate (i) the inhibition characteristics for the N-demethylation of ketamine to norketamine and (ii) the formation of the ketamine metabolites norketamine, 6-hydroxynorketamine (6HNK), and 5,6-dehydronorketamine (DHNK) in presence of the four α 2 -receptor agonists and equine liver microsomes. Samples were analyzed with enantioselective capillary electrophoresis using highly sulfated γ-cyclodextrin as chiral selector. All four α 2 -receptor agonists have an impact on the ketamine metabolism. Medetomidine was found to be the strongest inhibitor, followed by detomidine, whereas xylazine and romifidine showed almost no effect on the ketamine N-demethylation in the inhibition studies with a short-incubation period of the reaction mixture. After prolonged incubation, inhibition with xylazine and romifidine was also observed. The formation of 6HNK and DHNK is affected by all selected α 2 -receptor agonists. With medetomidine, levels of these metabolites are reduced compared to the case without an α 2 -receptor agonist. For detomidine, xylazine, and romifidine, the opposite was found. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ketamine-induced apoptosis in cultured rat cortical neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takadera, Tsuneo; Ishida, Akira; Ohyashiki, Takao

2006-01-15

Recent data suggest that anesthetic drugs cause neurodegeneration during development. Ketamine is frequently used in infants and toddlers for elective surgeries. The purpose of this study is to determine whether glycogen synthase kinase-3 (GSK-3) is involved in ketamine-induced apoptosis. Ketamine increased apoptotic cell death with morphological changes which were characterized by cell shrinkage, nuclear condensation or fragmentation. In addition, insulin growth factor-1 completely blocked the ketamine-induced apoptotic cell death. Ketamine decreased Akt phosphorylation. GSK-3 is known as a downstream target of Akt. The selective inhibitors of GSK-3 prevented the ketamine-induced apoptosis. Moreover, caspase-3 activation was accompanied by the ketamine-induced cellmore » death and inhibited by the GSK-3 inhibitors. These results suggest that activation of GSK-3 is involved in ketamine-induced apoptosis in rat cortical neurons.« less

21 CFR 522.1222a - Ketamine.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

21 CFR 522.1222a - Ketamine.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

21 CFR 522.1222a - Ketamine.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

21 CFR 522.1222a - Ketamine.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

Ketamine for Depression: Where Do We Go from Here?

PubMed Central

aan het Rot, Marije; Zarate, Carlos A.; Charney, Dennis S.; Mathew, Sanjay J.

2012-01-01

Since publication of the first randomized controlled trial describing rapid antidepressant effects of ketamine, several reports have confirmed the potential utility of this dissociative anesthetic medication for treatment of major depressive episodes, including those associated with bipolar disorder and resistant to other medications and electroconvulsive therapy. These reports have generated several questions with respect to who might respond to ketamine, how, and for how long. To start answering these questions. We used PubMed.gov and ClinicalTrials.gov to perform a systematic review of all available published data on the antidepressant effects of ketamine and of all recently completed, ongoing, and planned studies. To date, 163 patients, primarily with treatment-resistant depression, have participated in case studies, open-label investigations, or controlled trials. All controlled trials have used a within-subject, crossover design with an inactive placebo as the control. Ketamine administration has usually involved an anaesthesiologist infusing a single, subanesthetic, intravenous dose, and required hospitalization for at least 24 hours postinfusion. Response rates in the open-label investigations and controlled trials have ranged from 25% to 85% at 24 hours postinfusion and from 14% to 70% at 72 hours postinfusion. Although adverse effects have generally been mild, some patients have experienced brief changes in blood pressure, heart rate, or respiratory rate. Risk–benefit analyses support further research of ketamine for individuals with severe mood disorders. However, given the paucity of randomized controlled trials, lack of an active placebo, limited data on long-term outcomes, and potential risks, ketamine administration is not recommended outside of the hospital setting. PMID:22705040

Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting.

PubMed

Linder, Lauren M; Ross, Clint A; Weant, Kyle A

2018-01-01

Traditional first-line therapy in the prehospital setting for the acutely agitated patient includes an antipsychotic in combination with a benzodiazepine. Recently, interest has grown regarding the use of ketamine in the prehospital setting as an attempt to overcome the limitations of the traditional medications and provide a more safe and effective therapy. This review provides an overview of the pharmacology of ketamine, evaluates the literature regarding ketamine use for prehospital agitation, and proposes an algorithm that may be used within the prehospital setting. A literature review was conducted to identify articles utilizing ketamine in the prehospital setting. The review was limited to English-language articles identified in Embase (1988-June 2017) and the U.S. National Library of Medicine (1970-June 2017). References of all pertinent articles were also reviewed. Ten articles were identified including 418 patients receiving ketamine for agitation. The most commonly utilized route for administration was intramuscular (IM), with five of the seven IM administration studies using a ketamine dose of 5 mg/kg. Ketamine administered in this fashion was efficacious to achieve proper sedation during transport and did not require repeat dosing. Three studies applied a ketamine protocol to outline dosing and the management of ketamine adverse events. The most common adverse events identified were respiratory-related events and hypersalivation. Ketamine has a role for agitation management in the prehospital setting; however, emergency personnel education and ketamine protocols should be utilized to aid in safe and effective pharmacotherapy and provide guidance on the management of adverse events. Future prospective comparative studies, with protocolized standard ketamine regimens, are needed to further delineate the role of ketamine in agitation management and identify accurate adverse event incidence rates. © 2017 Pharmacotherapy Publications, Inc.

New Hippocampal Neurons Mature Rapidly in Response to Ketamine But Are Not Required for Its Acute Antidepressant Effects on Neophagia in Rats123

PubMed Central

Soumier, Amelie; Carter, Rayna M.; Schoenfeld, Timothy J.

2016-01-01

Abstract Virtually all antidepressant agents increase the birth of granule neurons in the adult dentate gyrus in rodents, providing a key basis for the neurogenesis hypothesis of antidepressant action. The novel antidepressant ketamine, however, shows antidepressant activity in humans within hours, far too rapid for a mechanism involving neuronal birth. Ketamine could potentially act more rapidly by enhancing maturation of new neurons born weeks earlier. To test this possibility, we assessed the effects of S-ketamine (S-(+)-ketamine hydrochloride) injection on maturation, as well as birth and survival, of new dentate gyrus granule neurons in rats, using the immediate-early gene zif268, proliferating cell nuclear antigen, and BrdU, respectively. We show that S-ketamine has rapid effects on new neurons, increasing the proportion of functionally mature young granule neurons within 2 h. A single injection of S-ketamine also increased cell proliferation and functional maturation, and decreased depressive-like behavior, for at least 4 weeks in rats treated with long-term corticosterone administration (a depression model) and controls. However, the behavioral effects of S-ketamine on neophagia were unaffected by elimination of adult neurogenesis. Together, these results indicate that ketamine has surprisingly rapid and long-lasting effects on the recruitment of young neurons into hippocampal networks, but that ketamine has antidepressant-like effects that are independent of adult neurogenesis. PMID:27066531

21 CFR 522.1223 - Ketamine, promazine, and aminopentamide.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ketamine, promazine, and aminopentamide. 522.1223... § 522.1223 Ketamine, promazine, and aminopentamide. (a) Specifications. Each milliliter of solution contains ketamine hydrochloride equivalent to 100 milligrams (mg) ketamine base activity, 7.5 (mg) of...

Ketamine for Treatment-Resistant Unipolar Depression

PubMed Central

Mathew, Sanjay J.; Shah, Asim; Lapidus, Kyle; Clark, Crystal; Jarun, Noor; Ostermeyer, Britta; Murrough, James W.

2013-01-01

Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action and significant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD. PMID:22303887

Case report: efficacy and tolerability of ketamine in opioid-refractory cancer pain.

PubMed

Amin, Priya; Roeland, Eric; Atayee, Rabia

2014-09-01

A 36-year-old female with metastatic breast cancer involving bones, liver, lung, and pleura/chest wall with worsening back pain received weight-based intravenous (IV) ketamine and was transitioned to oral ketamine for cancer-related neuropathic pain. She had responded poorly to outpatient pain regimen of oxycodone sustained and immediate release, hydromorphone, gabapentin, and duloxetine (approximate 480 mg total oral morphine equivalents [OME]), reporting an initial pain score of 10/10. She was started on hydromorphone parenteral patient-controlled analgesia (PCA) bolus dose in addition to her outpatient regimen. Despite escalating doses of opioids and the addition of a lidocaine 5% patch, the patient's pain remained uncontrolled 6 days after admission. On hospital day 7, utilizing a hospital weight-based ketamine protocol, the patient was started on subanesthetic doses of ketamine at 0.2 mg/kg/h (288 mg/24 h) and titrated over 2 days to 0.4 mg/kg/h (576 mg/24 h). Then, a 3-day rotation from intravenous to oral ketamine was initiated, and the patient was discharged on ketamine oral solution, 75 mg every 8 hours. When the patient's dose was increased to 0.4 mg/kg/h, adequate pain relief was charted by the nurse within 120 minutes, "patient pain free and resting comfortably." Her pain continued to be well managed, with an average pain score of 5/10 with the ketamine continuous infusion and sustained with conversion to oral ketamine without any report of side effects. This was a 37% reduction in pain scores. With the patient's stabilized dose of ketamine, opioid requirements decreased by 61.4% (1017.5 mg reduction in total OME). The use of weight-based dosing of IV continuous infusion and transition to oral ketamine was effective and tolerable in the management of opioid-refractory, neuropathic cancer pain. It is hoped that this case report promotes a discussion regarding ketamine dosing in refractory neuropathic cancer pain.

5-HT2A receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT.

PubMed

Waelbers, Tim; Polis, Ingeborgh; Vermeire, Simon; Dobbeleir, André; Eersels, Jos; De Spiegeleer, Bart; Audenaert, Kurt; Slegers, Guido; Peremans, Kathelijne

2013-08-01

Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of (123)I-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxybenzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT. This study was conducted on 6 cats using the radioligand (123)I-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 ± 1.2 mg kg(-1) followed by 0.22 mg kg(-1) min(-1)) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg(-1) min(-1)) was combined with ketamine (5 mg kg(-1) followed by 0.023 mg kg(-1) min(-1)), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics. The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 ± 0.22 vs. 1.45 ± 0.16; P = 0.028), left frontal cortex (1.34 ± 0.15 vs. 1.49 ± 0.10; P = 0.028), right temporal cortex (1.30 ± 0.17 vs. 1.45 ± 0.09; P = 0.046), and left temporal cortex (1.41 ± 0.20 vs. 1.52 ± 0.20; P = 0.046). This study showed that cats can be used as an animal model for studying alterations of the 5-HT2A receptor status with (123)I-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT2A receptors resulting in decreased binding of (123)I-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the

KETAMINE ABREACTION : A NEW APPROACH TO NARCOANALYSIS

PubMed Central

Golechha, G.R.; Sethi, I.C.; Misra, S.L.; Jayaprakash, N.P.

1986-01-01

SUMMARY Ketamine is a parenterally administered non barbiturate anaesthetic agent, in use for more than a decade. It is a safer than Na Pentothal. Administered intramuscularly, in dose of 6 to 15 mgm/Kg body wt. it produces dissociative anaesthesia. But, in smaller sub anaesthetic doses it may act as an abreactant. We report in this study the abreaction effect of Ketamine in dose of .5 to 1.5 mgm/kg body wt. given intramuscularly in 30 selected psychiatric cases requiring narcoanalysis for diagnostic or therapeutic purpose. The results are compared with another ten cases subjected to pentothal interview and five cases subjected to narcoanalysis with intravenous Na Amytal and methidrine. Our findings suggest that Ketamine has property of an efficacious abreactant in doses of 1 to 1.5 mgm/kg body wt. administered intramuscularly and can successfully be used for narcoanalysis in properly selected cases as a good substitute for intravenous pentothal or sodium amytal with methidrine. The relative cardio respiratory safety and ease of administration are its two added advantages. PMID:21927193

[Safety and efficacy of ketamine for pain relief].

PubMed

Niesters, Marieke; Dahan, Albert; van Kleef, Maarten

2016-01-01

Intravenous ketamine treatment is frequently used for the management of chronic pain, especially in those patients who do not benefit from other therapies. In this commentary we discuss the efficacy of ketamine for relief of chronic pain and ketamine's safety profile. A review of the literature indicates that only a few studies show that intravenous ketamine has analgesic effects that persist beyond the infusion period, an effect that occurs in about two-thirds of patients. Ketamine has multiple safety issues, ranging from psychotomimetic and schizotypal symptoms, sympathetic stimulation, tachycardia and hypertension, and damage to the liver and the urogenital tract. Damage to the urogenital tract seems to be restricted to individuals who chronically abuse ketamine. We indicate the need for large randomized trials in which ketamine is compared with an 'active' placebo.

Ketamine-snorting associated cystitis.

PubMed

Chen, Chung-Hsien; Lee, Ming-Huei; Chen, Yi-Chang; Lin, Ming-Fong

2011-12-01

Ketamine hydrochloride, commonly used as a pediatric anesthetic agent, is an N-methyl-D-aspartic (NMDA) acid receptor antagonist with rapid onset and short duration of action. It produces a cataleptic-like state where the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. It has emerged as an increasingly popular choice among young drug users, especially within dance club venues. Cases of bladder dysfunction among recreational ketamine users were reported since Shahani et al first reported nine cases of ketamine-associated ulcerative cystitis in 2007. We report on four patients who had history of ketamine abuse, presenting with dysuria, fluctuating lower urinary tract symptoms (LUTS), lower abdominal or perineal pain, and impaired functional bladder capacities. Urinalysis showed pyuria and microhematuria. Urine culture was sterile. Bladder ulceration with severe diffuse hemorrhage and low bladder capacity were noted under anesthetized cystoscopic examination. Transurethral bladder mucosa biopsy was consistent with chronic cystitis. Cessation of ketamine abuse was the milestone of treatment, followed by the administration of mucosal protective agents, such as pentosan polysulphate or hyaluronic acid. Suprapubic pain was improved in three patients during follow-up. However, the outcome of treatment depends on the severity of the disease process, similar to that of interstitial cystitis (IC). Copyright © 2011. Published by Elsevier B.V.

Cardiovascular changes in unanesthetized and ketamine-anesthetized Sprague-Dawley rats exposed to 2. 8-GHz radiofrequency radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jauchem, J.R.; Frei, M.R.

1991-01-01

Sprague-Dawley rats were exposed to 2.8-GHz radiofrequency radiation, first while unanesthetized and then while anesthetized with ketamine (150 mg/kg.I.M.). Irradiation at a power density of 60 mW/cm2 (whole-body average specific absorption rate of approximately 14 W/kg) was conducted for sufficient duration to increase colonic temperature from 38.5 to 39.5 degrees C. The time required for the temperature increase was significantly longer in the anesthetized state. During irradiation, heart rate increased significantly both with and without anesthesia, while mean arterial blood pressure increased only when the rats were unanesthetized. The heart rate increase in the anesthetized state contrasts with a lackmore » of change in a previous study of Fischer rats. This difference between anesthetized Sprague-Dawley and Fischer rats should be considered when comparing cardiovascular data obtained from these two strains of rats.« less

Adjuvant Agents in Regional Anesthesia in the Ambulatory Setting.

PubMed

Koyyalamudi, Veerandra; Sen, Sudipta; Patil, Shilpadevi; Creel, Justin B; Cornett, Elyse M; Fox, Charles J; Kaye, Alan D

2017-01-01

A majority of surgical practice has involved ambulatory centers with the number of outpatient operations in the USA doubling to 26.8 million per year. Local anesthesia delivery provides numerous benefits, including increased satisfaction, earlier discharge, and reduction in unplanned hospital admission. Further, with the epidemic of opioid mediated overdoses, local anesthesia can be a key tool in providing an opportunity to reduce the need for other analgesics postoperatively. Adjuvants such as epinephrine and clonidine enhance local anesthetic clinical utility. Further, dexmedetomidine prolongs regional blockade duration effects. There has also been a significant interest recently in the use of dexamethasone. Studies have demonstrated a significant prolongation in motor and sensory block with perineural dexamethasone. Findings are conflicting as to whether intravenous dexamethasone has similar beneficial effects. However, considering the possible neurotoxicity effects, which perineural dexamethasone may present, it would be prudent not to consider intravenously administered dexamethasone to prolong regional block duration. Many studies have also demonstrated neurotoxicity from intrathecally administered midazolam. Therefore, midazolam as an adjuvant is not recommended. Magnesium prolongs regional block duration but related to paucity of studies as of yet, cannot be recommended. Tramadol yields inconsistent results and ketamine is associated with psychotomimetic adverse effects. Buprenorphine consistently increases regional block duration and reduce opioid requirements by a significant amount. Future studies are warranted to define best practice strategies for these adjuvant agents. The present review focuses on the many roles of local anesthetics in current ambulatory practice.

Ketamine as an adjuvant to opioids for cancer pain.

PubMed

Bell, Rae F; Eccleston, Christopher; Kalso, Eija A

2017-06-28

second study with 10 participants examined the addition of intravenous ketamine bolus in two different doses to ongoing morphine therapy, compared with placebo. Both of these studies reported reduction in pain intensity and reduction in morphine requirements when ketamine was added to opioid for refractory cancer pain. The new study identified by the updated search had a parallel group design and 185 participants. This placebo-controlled study examined rapid titration of subcutaneous ketamine to high dose (500 mg) in participants who were using different opioids. There were no differences between groups for patient-reported pain intensity.Pooling of the data from the three included trials was not appropriate because of clinical heterogeneity.The study examining intrathecal drug administration reported no adverse events related to ketamine. In the study using intravenous bolus administration, ketamine caused hallucinations in four of 10 participants. In the rapid dose escalation/high-dose subcutaneous ketamine study, there was almost twice the incidence of adverse events in the ketamine group, compared to the placebo group, with the most common adverse events being needle site irritation and cognitive disturbance. Two serious adverse events (bradyarrhythmia and cardiac arrest) thought to be related to ketamine were also reported in this trial.For all three studies there was an unclear risk of bias overall. Using GRADE, we judged the quality of the evidence to be very low due to study limitations and imprecision due to the small number of participants in all comparisons. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of refractory cancer pain. The evidence was of very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is high. Rapid dose escalation of ketamine to high dose (500 mg) does not appear

Ketamine and ketamine metabolites as novel estrogen receptor ligands: Induction of cytochrome P450 and AMPA glutamate receptor gene expression.

PubMed

Ho, Ming-Fen; Correia, Cristina; Ingle, James N; Kaddurah-Daouk, Rima; Wang, Liewei; Kaufmann, Scott H; Weinshilboum, Richard M

2018-04-03

Major depressive disorder (MDD) is the most common psychiatric illness worldwide, and it displays a striking sex-dependent difference in incidence, with two thirds of MDD patients being women. Ketamine treatment can produce rapid antidepressant effects in MDD patients, effects that are mediated-at least partially-through glutamatergic neurotransmission. Two active metabolites of ketamine, (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-HNK, also appear to play a key role in ketamine's rapid antidepressant effects through the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. In the present study, we demonstrated that estrogen plus ketamine or estrogen plus active ketamine metabolites displayed additive effects on the induction of the expression of AMPA receptor subunits. In parallel, the expression of estrogen receptor alpha (ERα) was also significantly upregulated. Even more striking, radioligand binding assays demonstrated that [ 3 H]-ketamine can directly bind to ERα (K D : 344.5 ± 13 nM). Furthermore, ketamine and its (2R,6R)-HNK and (2S,6S)-HNK metabolites displayed similar affinity for ERα (IC 50 : 2.31 ± 0.1, 3.40 ± 0.2, and 3.53 ± 0.2 µM, respectively) as determined by [ 3 H]-ketamine displacement assays. Finally, induction of AMPA receptors by either estrogens or ketamine and its metabolites was lost when ERα was knocked down or silenced pharmacologically. These results suggest a positive feedback loop by which estrogens can augment the effects of ketamine and its (2R,6R)-HNK and (2S,6S)-HNK metabolites on the ERα-induced transcription of CYP2A6 and CYP2B6, estrogen inducible enzymes that catalyze ketamine's biotransformation to form the two active metabolites. These observations provide novel insight into ketamine's molecular mechanism(s) of action and have potential implications for the treatment of MDD. Copyright © 2018 Elsevier Inc. All rights reserved.

Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

PubMed

Pizon, Anthony F; Lynch, Michael J; Benedict, Neal J; Yanta, Joseph H; Frisch, Adam; Menke, Nathan B; Swartzentruber, Greg S; King, Andrew M; Abesamis, Michael G; Kane-Gill, Sandra L

2018-05-08

Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. Retrospective observational cohort study. Academic tertiary care hospital. Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13). Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was

Anesthesia for Cesarean Delivery: A Cross-Sectional Survey of Provincial, District, and Mission Hospitals in Zimbabwe.

PubMed

Lonnée, Herman A; Madzimbamuto, Farai; Erlandsen, Ole R M; Vassenden, Astrid; Chikumba, Edson; Dimba, Rutenda; Myhre, Arne K; Ray, Sunanda

2018-06-01

Cesarean delivery is the most common surgical procedure in low- and middle-income countries, so provision of anesthesia services can be measured in relation to it. This study aimed to assess the type of anesthesia used for cesarean delivery, the level of training of anesthesia providers, and to document the availability of essential anesthetic drugs and equipment in provincial, district, and mission hospitals in Zimbabwe. In this cross-sectional survey of 8 provincial, 21 district, and 13 mission hospitals, anesthetic providers were interviewed on site using a structured questionnaire adapted from standard instruments developed by the World Federation of Societies of Anaesthesiologists and the World Health Organization. The anesthetic workforce for the hospitals in this survey constituted 22% who were medical officers and 77% nurse anesthetists (NAs); 55% of NAs were recognized independent anesthetic providers, while 26% were qualified as assistants to anesthetic providers and 19% had no formal training in anesthesia. The only specialist physician anesthetist was part time in a provincial hospital. Spinal anesthesia was the most commonly used method for cesarean delivery (81%) in the 3 months before interview, with 19% general anesthesia of which 4% was ketamine without airway intubation. The mean institutional cesarean delivery rate was 13.6% of live births, although 5 district hospitals were <5%. The estimated institutional maternal mortality ratio was 573 (provincial), 251 (district), and 211 (mission hospitals) per 100,000 live births. Basic monitoring equipment (oximeters, electrocardiograms, sphygmomanometers) was reported available in theatres. Several unsafe practices continue: general anesthesia without a secure airway, shortage of essential drugs for spinal anesthesia, inconsistent use of recovery area or use of table tilt or wedge, and insufficient blood supplies. Postoperative analgesia management was reported inadequate. This study identified areas

Pharmacokinetics of ketamine and norketamine enantiomers after racemic or S-ketamine IV bolus administration in dogs during sevoflurane anaesthesia.

PubMed

Romagnoli, Noemi; Bektas, Rima N; Kutter, Annette P; Barbarossa, Andrea; Roncada, Paola; Hartnack, Sonja; Bettschart-Wolfensberger, Regula

2017-06-01

The aims of this study were to measure plasma levels of R- and S-ketamine and their major metabolites R- and S-norketamine following single intravenous bolus administration of racemic or S-ketamine in sevoflurane anaesthetised dogs and to calculate the relevant pharmacokinetic profiles. Six adult healthy beagle dogs were used in the study. An intravenous bolus of 4mg/kg racemic ketamine (RS-KET) or 2mg/kg S-ketamine (S-KET) was administered, with a three-weeks washout period between treatments. Venous blood samples were collected at fixed times until 900min and R- and S-ketamine as well as R- and S-norketamine plasma levels determined by liquid chromatography coupled with tandem mass spectrometry. Cardiovascular parameters were recorded during the anaesthesia until 240min. All dogs recovered well from anaesthesia. No statistical differences between groups were detected in any cardiovascular parameter. The pharmacokinetics of S-ketamine did not differ when injected intravenously alone or as part of the racemic mixture in dogs anaesthetised with sevoflurane. Following racemic ketamine, the area under the curve of R-norketamine was statistically higher than the one of S-norketamine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perioperative Ketamine Administration for Thoracotomy Pain.

PubMed

Moyse, Daniel W; Kaye, Alan D; Diaz, James H; Qadri, Muhammad Y; Lindsay, David; Pyati, Srinivas

2017-03-01

Of all the postsurgical pain conditions, thoracotomy pain poses a particular therapeutic challenge in terms of its prevalence, severity, and ensuing postoperative morbidity. Multiple pain generators contribute to the severity of post-thoracotomy pain, and therefore a multimodal analgesic therapy is considered to be a necessary strategy. Along with opioids, thoracic epidural analgesia, and paravertebral blocks, N-Methyl-D-Aspartate (NMDA) receptor antagonists such as ketamine have been used as adjuvants to improve analgesia. We reviewed the evidence for the efficacy of intravenous and epidural administration of ketamine in acute post-thoracotomy pain management, and its effectiveness in reducing chronic post-thoracotomy pain. Systematic literature review and an analytic study of a data subset were performed. We searched PubMed, Embase, and Cochrane reviews using the key terms "ketamine," "neuropathic pain," "postoperative," and "post-thoracotomy pain syndrome." The search was limited to human trials and included all studies published before January 2015. Data from animal studies, abstracts, and letters were excluded. All studies not available in the English language were excluded. The manuscript bibliographies were reviewed for additional related articles. We included randomized controlled trials and retrospective studies, while excluding individual case reports. This systematic literature search yielded 15 randomized control trials evaluating the efficacy of ketamine in the treatment of acute post-thoracotomy pain; fewer studies assessed its effect on attenuating chronic post-thoracotomy pain. The majority of reviewed studies demonstrated that ketamine has efficacy in reduction of acute pain, but the evidence is limited on the long-term benefits of ketamine to prevent post-thoracotomy pain syndrome, regardless of the route of administration. A nested analytical study found there is a statistically significant reduction in acute post-thoracotomy pain with IV or

Intravenous sub-anesthetic ketamine for perioperative analgesia

PubMed Central

Gorlin, Andrew W; Rosenfeld, David M; Ramakrishna, Harish

2016-01-01

Ketamine, an N-methyl-d-aspartate antagonist, blunts central pain sensitization at sub-anesthetic doses (0.3 mg/kg or less) and has been studied extensively as an adjunct for perioperative analgesia. At sub-anesthetic doses, ketamine has a minimal physiologic impact though it is associated with a low incidence of mild psychomimetic symptoms as well as nystagmus and double vision. Contraindications to its use do exist and due to ketamine's metabolism, caution should be exercised in patients with renal or hepatic dysfunction. Sub-anesthetic ketamine improves pain scores and reduces perioperative opioid consumption in a broad range of surgical procedures. In addition, there is evidence that ketamine may be useful in patients with opioid tolerance and for preventing chronic postsurgical pain. PMID:27275042

Adverse Events With Ketamine Versus Ketofol for Procedural Sedation on Adults: A Double-blind, Randomized Controlled Trial.

PubMed

Lemoel, Fabien; Contenti, Julie; Giolito, Didier; Boiffier, Mathieu; Rapp, Jocelyn; Istria, Jacques; Fournier, Marc; Ageron, François-Xavier; Levraut, Jacques

2017-12-01

The goal of our study was to compare the frequency and severity of recovery reactions between ketamine and ketamine-propofol 1:1 admixture ("ketofol"). We performed a multicentric, randomized, double-blind trial in which adult patients received emergency procedural sedations with ketamine or ketofol. Our primary outcome was the proportion of unpleasant recovery reactions. Other outcomes were frequency of interventions required by these recovery reactions, rates of respiratory or hemodynamic events, emesis, and satisfaction of patients as well as providers. A total of 152 patients completed the study, 76 in each arm. Compared with ketamine, ketofol determined a 22% reduction in recovery reactions incidence (p < 0.01) and less clinical and pharmacologic interventions required by these reactions. There was no serious adverse event in both groups. Rates in hemodynamic or respiratory events as well as satisfaction scores were similar. Significantly fewer patients experienced emesis with ketofol, with a threefold reduction in incidence compared with ketamine. We found a significant reduction in recovery reactions and emesis frequencies among adult patients receiving emergency procedural sedations with ketofol, compared with ketamine. © 2017 by the Society for Academic Emergency Medicine.

Ketamine use in current clinical practice

PubMed Central

Gao, Mei; Rejaei, Damoon; Liu, Hong

2016-01-01

After nearly half a century on the market, ketamine still occupies a unique corner in the medical armamentarium of anesthesiologists or clinicians treating pain. Over the last two decades, much research has been conducted highlighting the drug's mechanisms of action, specifically those of its enantiomers. Nowadays, ketamine is also being utilized for pediatric pain control in emergency department, with its anti-hyperalgesic and anti-inflammatory effects being revealed in acute and chronic pain management. Recently, new insights have been gained on ketamine's potential anti-depressive and antisuicidal effects. This article provides an overview of the drug's pharmacokinetics and pharmacodynamics while also discussing the potential benefits and risks of ketamine administration in various clinical settings. PMID:27018176

Ketamine for cancer pain: what is the evidence?

PubMed

Jonkman, Kelly; van de Donk, Tine; Dahan, Albert

2017-06-01

In this review, we assess the benefit of ketamine in the treatment of terminal cancer pain that is refractory to opioid treatment and/or complicated by neuropathy. While randomized controlled trials consistently show lack of clinical efficacy of ketamine in treating cancer pain, a large number of open-label studies and case series show benefit. Ketamine is an N-methyl-D-aspartate receptor antagonist that at low-dose has effective analgesic properties. In cancer pain, ketamine is usually prescribed as adjuvant to opioid therapy when pain becomes opioid resistant or when neuropathic pain symptoms dominate the clinical picture. A literature search revealed four randomized controlled trials that examined the benefit of oral, subcutaneous or intravenous ketamine in opioid refractory cancer pain. None showed clinically relevant benefit in relieving pain or reducing opioid consumption. This suggests absence of evidence of benefit for ketamine as adjuvant analgesic in cancer pain. These findings contrast the benefit from ketamine observed in a large number of open-label studies and (retrospective) case series. We relate the opposite outcomes to methodological issues. The complete picture is such that there is still insufficient evidence to state with certainty that ketamine is not effective in cancer pain.

Ketamine produces lasting disruptions in encoding of sensory stimuli.

PubMed

Maxwell, Christina R; Ehrlichman, Richard S; Liang, Yuling; Trief, Danielle; Kanes, Stephen J; Karp, Jonathan; Siegel, Steven J

2006-01-01

The current study analyzed the acute, chronic, and lasting effects of ketamine administration in four inbred mouse strains (C3H/HeHsd, C57BL/6Hsd, FVB/Hsd, and DBA/2Hsd) to evaluate vulnerability to ketamine as a drug of abuse and as a model of schizophrenia. Serum half-life of ketamine was similar between all strains (approximately 13 min). Also, the ratio of brain-to-serum ketamine levels was 3:1. Examination of multiple phases of auditory processing using auditory-evoked potentials (AEPs) following acute ketamine (0, 5, and 20 mg/kg) treatment revealed C3H/HeHsd mice to be most vulnerable to ketamine-induced alterations in AEPs, whereas FVB/Hsd mice exhibited the least electrophysiological sensitivity to ketamine. Overall, the precortical P1-evoked potential component increased in amplitude and latency, whereas the cortically generated N1 and P2 components decreased in amplitude and latency following acute ketamine across all strains. Brain catecholamine analyses indicated that ketamine decreased hippocampus epinephrine levels in C3H/HeHsd but elevated hippocampus epinephrine levels in FVB/Hsd, suggesting one potential mechanism for AEP vulnerability to ketamine. Based on results of the acute study, the immediate and lasting effects of chronic low-dose ketamine on AEPs were examined among C3H/HeHsd (sensitive) and FVB/Hsd (insensitive) mice. We observed a decrement of the N1 amplitude that persisted at least 1 week after the last exposure to ketamine across both strains. This lasting deficit in information processing occurred in the absence of acute changes among the FVB/Hsd mice. Implications for both ketamine abuse and N-methyl-D-aspartate hypofunction models of schizophrenia are discussed.

Beyond Ketamine: New Approaches to the Development of Safer Antidepressants.

PubMed

Chaki, Shigeyuki

2017-01-01

Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention. The first approach includes stereoisomers of ketamine, (R)-ketamine and (S)-ketamine. Although (S)-ketamine has been considered as the active stereoisomer of racemic ketamine, recently, (R)-ketamine has been demonstrated to exert even more prolonged antidepressant effects in animal models than (S)-ketamine. Moreover, ketamine is rapidly metabolized into several metabolites, and some metabolites are speculated as being active substances exerting antidepressant effects. Of such metabolites, one in particular, namely, (2R,6R)-hydroxynorketamine, has been reported to be responsible for the antidepressant effects of ketamine. The second approach includes agents acting on the NMDA receptor, such as glycine site modulators and GluN2B subunit-selective antagonists. These agents have been tested in patients with treatment-resistant depression, and have been found to exhibit rapid antidepressant effects like ketamine. The above approaches may be useful to overcome the drawbacks of ketamine. Elucidation of the mechanisms of action of ketamine may pave the way for the development of antidepressant that are safer, but as potent and rapidly acting as ketamine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Beyond Ketamine: New Approaches to the Development of Safer Antidepressants

PubMed Central

Chaki, Shigeyuki

2017-01-01

Background: Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Methods: Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention. Results: The first approach includes stereoisomers of ketamine, (R)-ketamine and (S)-ketamine. Although (S)-ketamine has been considered as the active stereoisomer of racemic ketamine, recently, (R)-ketamine has been demonstrated to exert even more prolonged antidepressant effects in animal models than (S)-ketamine. Moreover, ketamine is rapidly metabolized into several metabolites, and some metabolites are speculated as being active substances exerting antidepressant effects. Of such metabolites, one in particular, namely, (2R,6R)-hydroxynorketamine, has been reported to be responsible for the antidepressant effects of ketamine. The second approach includes agents acting on the NMDA receptor, such as glycine site modulators and GluN2B subunit-selective antagonists. These agents have been tested in patients with treatment-resistant depression, and have been found to exhibit rapid antidepressant effects like ketamine. Conclusion: The above approaches may be useful to overcome the drawbacks of ketamine. Elucidation of the mechanisms of action of ketamine may pave the way for the development of antidepressant that are safer, but as potent and rapidly acting as ketamine. PMID:28228087

Effects of vasoactive intestinal peptide on vascular conductance are unaffected by anesthesia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bouder, T.G.; Huffman, L.J.; Hedge, G.A.

1988-12-01

In rats anesthetized with ketamine and pentobarbital (KET/PB), vasoactive intestinal peptide (VIP) increases vascular conductance (VC) in the salivary gland, pancreas, and thyroid gland, whereas no changes in VC are observed in a number of other organs. Because anesthesia may alter the responsiveness of physiological systems, we compared the effects of VIP on organ VC in conscious or anesthetized rats. Chronically catheterized rats were studied in the conscious state or 30 min after induction of anesthesia with KET/PB, isoflurane, or Inactin. Blood flows were measured by the reference sample version of the radioactive microsphere (MS) technique using two MS injectionsmore » ({sup 141}Ce-MS/{sup 85}Sr-MS). Mean arterial blood pressure was monitored and used in the calculation of VC. Organ VCs were similar under basal conditions in conscious and anesthetized rats. VIP infusion caused systemic hypotension and increased VCs in the salivary gland, pancreas, and thyroid gland, and these responses were largely unaffected by anesthesia. These results indicate that the anesthetics used do not alter basal VC or the responsiveness of the vasculature to exogenous VIP.« less

Longitudinal Trajectories of Ketamine Use among Young Injection Drug Users

PubMed Central

Lankenau, Stephen E.; Bloom, Jennifer Jackson; Shin, Charles

2010-01-01

Background Ketamine is a dissociative anesthetic that became increasing popular in the club and rave scene in the 1980s and 1990s. Reports surfaced in the late 1990s indicating that ketamine was being injected in several U.S. cities by young injection drug users (IDUs). Since all studies on ketamine injection were cross-sectional, a longitudinal study was undertaken in 2005 to determine: characteristics of young IDUs who continue to inject ketamine; frequency of ketamine injection over an extended time period; risks associated with ongoing ketamine injection; and environmental factors that impact patterns of ketamine use. Methods Young IDUs aged 16 to 29 with a history of injecting ketamine (n=101) were recruited from public locations in Los Angeles and followed during a two-year longitudinal study. A semi-structured instrument captured quantitative and qualitative data on patterns of ketamine injection and other drug use. A statistical model sorted IDUs who completed three or more interviews (n=66) into three groups based upon patterns of ketamine injection at baseline and follow-up. Qualitative analysis focused on detailed case studies within each group. Results IDUs recruited at baseline were typically in their early 20s, male, heterosexual, white, and homeless. Longitudinal injection trajectories included: “Moderates,” who injected ketamine several times per year (n=5); “Occasionals,” who injected ketamine approximately once per year (n=21); and “Abstainers,” who did not inject any ketamine during follow-up (n=40). Findings suggest that ketamine is infrequently injected compared to other drugs such as heroin, cocaine, and methamphetamine. Most IDUs who begin injecting ketamine will stop or curb use due to: negative or ambivalent experiences associated with ketamine; an inability to find the drug due to declining supply; or maturing out of injecting drugs more generally. Conclusion Reducing ketamine injection among young IDUs may best be accomplished

Small Dose Ketamine Improves Postoperative Analgesia and Rehabilitation After Total Knee Arthroplasty.

PubMed Central

Chauvin, Marcel; Manoir, Bertrand Du; Langlois, Mathieu; Sessler, Daniel I.; Fletcher, Dominique

2005-01-01

We designed this study to evaluate the effect of small-dose intravenous ketamine in combination with continuous femoral nerve block on postoperative pain and rehabilitation after total knee arthroplasty. Continuous femoral nerve block with ropivacaine was started before surgery and continued in the surgical ward for 48 h. Patients were randomly assigned to receive an initial bolus of 0.5 mg/kg ketamine followed by a continuous infusion of 3 μg·kg-1·min-1 during surgery and 1.5 μg·kg-1·min-1 for 48 h (Ketamine group) or an equal volume of saline (Control group). Additional postoperative analgesia was provided by patient-controlled intravenous morphine. Pain scores and morphine consumption were recorded over 48 hours. The maximal degree of active knee flexion tolerated was recorded daily until hospital discharge. Follow up was performed 6 weeks and 3 months after surgery. The Ketamine group required significantly less morphine than the Control group (45 ± 20 mg versus 69 ± 30 mg; P < 0.02). Patients in the Ketamine group reached 90° of active knee flexion more rapidly than those in the Control group (P < 0.02). Outcomes at 6 weeks and 3 months were similar in each group. These results confirm that ketamine is a useful analgesic adjuvant in perioperative multimodal analgesia with a positive impact on early knee mobilization. PMID:15673878

[Live-threatening bronchospasm during anesthesia induction : when pure routine becomes a nightmare].

PubMed

Rüggeberg, A; Breckwoldt, J

2011-10-01

This article reports a case of live-threatening respiratory failure during induction of anesthesia. An 18-year-old female was admitted to hospital for an axillary abscess incision on a public holiday. The patient had a history of asthmatic episodes and an allergy to milk protein and 2 years previously an asthmatic attack had possibly been treated by mechanical ventilation. Retrospectively, this event turned out to be a cardiac arrest with mechanical ventilation for 24 h. During induction of anesthesia the patient suddenly developed massive bronchospasms and ventilation was impossible for minutes. Oxygen saturation fell below 80% over a period of 12 min with a lowest measurement of 13%. The patient was treated with epinephrine, prednisolone, antihistamine drugs, ß(2)-agonists, s-ketamine and methylxanthines and 15 min later the oxygen saturation returned to normal values. After mild therapeutic hypothermia for 24 h mechanical ventilation was still required for another 4 days. The patient recovered completely and was discharged home on day 19. Initially propofol was suspected of having caused an anaphylactic shock but in retrospect, the diagnosis of near fatal asthma was more likely. The onset of the event was facilitated by the patient playing down the history of asthmatic episodes due to a strong wish for independency and negation of the severity of the disease.

Comparison between the combination of gabapentin, ketamine, lornoxicam, and local ropivacaine and each of these drugs alone for pain after laparoscopic cholecystectomy: a randomized trial.

PubMed

Kotsovolis, Georgios; Karakoulas, Konstantinos; Grosomanidis, Vasileios; Tziris, Nikolaos

2015-04-01

The main purpose of the study was to test whether the combination of gabapentin (600 mg 4 hours before surgery, 600 mg after 24 hours), ketamine (0.3 mg/kg before anesthesia), lornoxicam (8 mg before anesthesia and 8 mg/12 hours), and local ropivacaine (5 mL 7.5% at insertion sites) provides superior analgesia to each of these drugs alone in the first 24 hours after laparoscopic cholecystectomy. The secondary purpose was to examine whether this combination has less opioid-related side effects. This was a 2-center randomized placebo-controlled trial. One hundred forty-eight patients, between 18 and 70 years of age, were randomly assigned to 6 groups (28 in each group) with the use of computer software: A(gabapentin/ketamine/lornoxicam/ropivacaine); B(gabapentin/placebo/placebo/placebo); C (placebo/ketamine/placebo/placebo); D (placebo/placebo/lornoxicam/placebo); E (placebo/placebo/placebo/ropivacaine); and F (placebo/placebo/placebo/placebo). Only the principal investigator was aware of patients' allocation and provided drugs and placebo in covered prefilled syringes. The primary outcome of the study was the 24-hour morphine consumption. Secondary outcomes were frequency of opioid-related side effects (nausea, vomiting, sedation, pruritus, and dysuria). Only groups A (6.4 mg), B (9.46 mg), and D (9.36 mg) had lower morphine consumption than control group (20.29 mg) (P < 0.001, P = 0.01, and P = 0.008, respectively). Group A was not different from B and D (P = 0.92, P = 0.93). The only difference was in episodes of nausea between groups A (n = 5) and the control group (n = 12) (P = 0.018). The combination of gabapentin, ketamine, lornoxicam, and local ropivacaine does not provide superior analgesia than gabapentin alone or lornoxicam alone after laparoscopic cholecystectomy. The combination reduces only the frequency of postoperative nausea, but larger studies are needed for safer results. © 2014 World Institute of Pain.

The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease.

PubMed

Tawfic, Qutaiba A; Faris, Ali S; Kausalya, Rajini

2014-02-01

Acute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration. We studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis. A retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2-0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5-1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis. Nine patients were assessed, with mean age of 27±11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean±SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6±16.5, and it was 112±12.2 on Day 1 (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P=0.01). Low-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Estimation of the contribution of norketamine to ketamine-induced acute pain relief and neurocognitive impairment in healthy volunteers.

PubMed

Olofsen, Erik; Noppers, Ingeborg; Niesters, Marieke; Kharasch, Evan; Aarts, Leon; Sarton, Elise; Dahan, Albert

2012-08-01

The N-methyl-D-aspartate receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. One approach to assess the ketamine and norketamine contributions is by measuring the ketamine effect at varying ketamine and norketamine plasma concentrations using the CYP450 inducer rifampicin. In 12 healthy male volunteers the effect of rifampicin versus placebo pretreatment on S-ketamine-induced analgesia and cognition was quantified; the S-ketamine dosage was 20 mg/h for 2 h. The relative ketamine and norketamine contribution to effect was estimated using a linear additive population pharmacokinetic-pharmacodynamic model. S-ketamine produced significant analgesia, psychotropic effects (drug high), and cognitive impairment (including memory impairment and reduced psychomotor speed, reaction time, and cognitive flexibility). Modeling revealed a negative contribution of S-norketamine to S-ketamine- induced analgesia and absence of contribution to cognitive impairment. At ketamine and norketamine effect concentrations of 100 ng/ml and 50 ng/ml, respectively, the ketamine contribution to analgesia is -3.8 cm (visual analog pain score) versus a contribution of norketamine of +1.5 cm, causing an overall effect of -2.3 cm. The blood-effect site equilibration half-life ranged from 0 (cognitive flexibility) to 11.8 (pain intensity) min and was 6.1 min averaged across all endpoints. This first observation that norketamine produces effects in the opposite direction of ketamine requires additional proof. It can explain the observation of ketamine-related excitatory phenomena (such as hyperalgesia and allodynia) upon the termination of ketamine infusions.

Ketamine Disrupts Frontal and Hippocampal Contribution to Encoding and Retrieval of Episodic Memory: An fMRI Study

PubMed Central

Honey, G.D.; Honey, R.A.E.; O’Loughlin, C.; Sharar, S.R.; Kumaran, D.; Suckling, J.; Menon, D.K.; Sleator, C.; Bullmore, E.T.; Fletcher, P.C.

2012-01-01

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine produces episodic memory deficits. We used functional magnetic resonance imaging to characterize the effects of ketamine on frontal and hippocampal responses to memory encoding and retrieval in healthy volunteers using a double-blind, placebo-controlled, randomized, within-subjects comparison of two doses of intravenous ketamine. Dissociation of the effects of ketamine on encoding and retrieval processes was achieved using two study-test cycles: in the first, items were encoded prior to drug infusion and retrieval tested, during scanning, on drug; in the second, encoding was scanned on drug, and retrieval tested once ketamine plasma levels had declined. We additionally determined the interaction of ketamine with the depth of processing that occurred at encoding. A number of effects upon task-dependent activations were seen. Overall, our results suggest that left frontal activation is augmented by ketamine when elaborative semantic processing is required at encoding. In addition, successful encoding on ketamine is supplemented by additional non-verbal processing that is incidental to task demands. The effects of ketamine at retrieval are consistent with impaired access to accompanying contextual features of studied items. Our findings show that, even when overt behaviour is unimpaired, ketamine has an impact upon the recruitment of key regions in episodic memory task performance. PMID:15537676

Ketamine blocks bursting in the lateral habenula to rapidly relieve depression.

PubMed

Yang, Yan; Cui, Yihui; Sang, Kangning; Dong, Yiyan; Ni, Zheyi; Ma, Shuangshuang; Hu, Hailan

2018-02-14

The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants.

Ketamine-dependent neuronal activation in healthy volunteers.

PubMed

Höflich, Anna; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S; Vanicek, Thomas; Ganger, Sebastian; Spies, Marie; Windischberger, Christian; Kasper, Siegfried; Winkler, Dietmar; Lanzenberger, Rupert

2017-04-01

Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S ® ) was administered intravenously to 35 healthy volunteers. Neural activation as indicated by the BOLD signal using the pharmacokinetic curve of ketamine plasma levels as a regressor was computed. Compared with placebo, ketamine-dependent increases of neural activation were observed in the midcingulate cortex, the dorsal part of the anterior cingulate cortex, the insula bilaterally, and the thalamus (t values ranging between 5.95-9.78, p < 0.05; FWE-corrected). A significant decrease of neural activation in the ketamine condition compared to placebo was found in a cluster within the subgenual/subcallosal part of the anterior cingulate cortex, the orbitofrontal cortex and the gyrus rectus (t = 7.81, p < 0.05, FWE-corrected). Using an approach combining pharmacological and fMRI data, important information about the neurobiological correlates of the clinical antidepressant effects of ketamine could be revealed.

Anesthesia for ambulatory anorectal surgery.

PubMed

Gudaityte, Jūrate; Marchertiene, Irena; Pavalkis, Dainius

2004-01-01

The prevalence of minor anorectal diseases is 4-5% of adult Western population. Operations are performed on ambulatory or 24-hour stay basis. Requirements for ambulatory anesthesia are: rapid onset and recovery, ability to provide quick adjustments during maintenance, lack of intraoperative and postoperative side effects, and cost-effectiveness. Anorectal surgery requires deep levels of anesthesia. The aim is achieved with 1) regional blocks alone or in combination with monitored anesthesia care or 2) deep general anesthesia, usually with muscle relaxants and tracheal intubation. Modern general anesthetics provide smooth, quickly adjustable anesthesia and are a good choice for ambulatory surgery. Popular regional methods are: spinal anesthesia, caudal blockade, posterior perineal blockade and local anesthesia. The trend in regional anesthesia is lowering the dose of local anesthetic, providing selective segmental block. Adjuvants potentiating analgesia are recommended. Postoperative period may be complicated by: 1) severe pain, 2) urinary retention due to common nerve supply, and 3) surgical bleeding. Complications may lead to hospital admission. In conclusion, novel general anesthetics are recommended for ambulatory anorectal surgery. Further studies to determine an optimal dose and method are needed in the group of regional anesthesia.

[The Analgesic Sparing Effect of Ketamine for Postoperative Pain Management after Pediatric Surgery on the Body Surface].

PubMed

Urabe, Tomoaki; Nakanuno, Ryuichi; Hayase, Kazuma; Sasada, Shogo; Iwamitsu, Reimi; Senami, Masaki

2016-04-01

It is reported that ketamine, a N-methyl-D-aspertate (NMDA) receptor antagonist, can provide analgesic effect improving postoperative pain management and decrease the supplementary analgesic requirement. We investigated the analgesic sparing effect of ketamine for postoperative pain in children undergoing surgery of body surface. Fifty eight patients (0-9 yrs) who had surgery of body surface were divided into two groups (ketamine : n = 27, Group K or control : n = 31, Group N). Postoperative analgesia extracted from charts was retrospectively evaluated by the times patients used analgesics until discharge after the operations. Chi-square and Mann-Whitney U tests were used for statistical analysis. Results : The ketamine group received an intrave- nous bolus of ketamine (1 mg - kg-1) before surgical skin incision. However, there were no significant differ- ences of usage (Group K vs Group N : 4/27 vs 7/31, P=0.45) and frequency of supplementary analgesic us- ages (P=0.85) among groups. In addition, there were also no significant demographic differences between the two groups. Conclusions : Our investigation suggests that the intravenous bolus of ketamine (1 mg - kg-1) before surgical skin incision does not decrease the supple- mentary analgesic requirements on postoperative pain management in pediatric surgery of the body surface.

Long-term neurocognitive dysfunction in offspring via NGF/ ERK/CREB signaling pathway caused by ketamine exposure during the second trimester of pregnancy in rats.

PubMed

Li, Yanan; Li, Xinran; Guo, Cen; Li, Lina; Wang, Yuxin; Zhang, Yiming; Chen, Yu; Liu, Wenhan; Gao, Li

2017-05-09

Early life exposure to ketamine caused neurohistopathologic changes and persistent cognitive dysfunction. For this study, a pregnant rat model was developed to investigate neurocognitive effects in the offspring, following ketamine exposure during the second trimester. Pregnant rats on gestational day 14 (equal to midtrimester pregnancy in humans), intravenously received 200 mg/kg ketamine for 3 h. Their behavior was tested (Morris water maze, odor recognition test, and fear conditioning) at postnatal days (P25-30). Furthermore, hippocampal morphology of the offspring (P30) was examined via Nissl staining and hippocampal dendritic spine density was determined via Golgi staining. The hippocampal protein levels of nerve growth factor (NGF), extracellular signal-regulated kinase (ERK), phosphorylated-ERK (p-ERK), cyclic adenosine monophosphate response element-binding (CREB), p-CREB, synaptophysin (SYP), synapsin (SYN), and postsynaptic density-95 (PSD95) were measured via western blot. Additionally, SCH772984 (an ERK inhibitor) was used to evaluate both role and underlying mechanism of the ERK pathway in PC12 cells. We found that ketamine caused long-term neurocognitive dysfunction, reduced the density of the dendritic spin, caused neuronal loss, and down-regulated the expression of NGF, ERK, p-ERK, mitogen, and stress-activated protein kinase (MSK), CREB, p-CREB, SYP, SYN, and PSD95 in the hippocampus. These results suggest that ketamine induced maternal anesthesia during period of the fetal brain development can cause long-term neurocognitive dysfunction in the offspring, which likely happens via inhibition of the NGF-ERK-CREB pathway in the hippocampus. Our results highlight the central role of ERK in neurocognition.

Two Components of Aversive Memory in Drosophila, Anesthesia-Sensitive and Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small GTPase.

PubMed

Murakami, Satoshi; Minami-Ohtsubo, Maki; Nakato, Ryuichiro; Shirahige, Katsuhiko; Tabata, Tetsuya

2017-05-31

Multiple components have been identified that exhibit different stabilities for aversive olfactory memory in Drosophila These components have been defined by behavioral and genetic studies and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies, which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact. SIGNIFICANCE STATEMENT Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model with which to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term, and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila , Rgk1, which plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N

Pediatric procedural sedation with ketamine: time to discharge after intramuscular versus intravenous administration.

PubMed

Ramaswamy, Preeti; Babl, Franz E; Deasy, Conor; Sharwood, Lisa N

2009-02-01

Ketamine is an attractive agent for pediatric procedural sedation. There are limited data on time to discharge comparing intramuscular (IM) vs. intravenous (IV) ketamine. The authors set out to determine whether IM or IV ketamine leads to quicker discharge from the emergency department (ED) and how side effect profiles compare. All patients who had received ketamine IM or IV at a tertiary children's hospital ED during the 3-year study period (2004-2007) were identified. Prospective sedation registry data, retrospective medical records, and administrative data were reviewed for drug dosages, use of additional agents, time of drug administration to discharge, total ED time (triage to discharge), and adverse events. A subgroup analysis for patients requiring five or fewer sutures (short suture group) was performed. A total of 229 patients were enrolled (60% male) with median age of 2.8 years (IQR =1.8-4.3 years) and median weight of 15.7 kg (range = 8.7-74 kg). Ketamine was most frequently employed for laceration repair (80%) and foreign body removal (9%). Overall, 48% received ketamine IM and 52% received it IV. In the short-suture subgroup, 52% received ketamine IM, while 48% received it IV. Multivariate linear regression analysis determined time from drug administration to patient discharge as 21 minutes shorter for IV compared with IM administration, adjusted for age and number of additional doses (R(2) = -0.35; 95% CI = -0.5 to -0.19; p < 0.001). Total time in the ED (triage to discharge) comparing IV versus IM administration, adjusting for age and gender and number of additional doses, was not significantly different (p = 0.16). In the short-suture subgroup, time to discharge from administration was also shorter in the IV ketamine group (R(2) = -0.454; 95%CI = -0.66 to -0.25; p < 0.001) but similar for total time in ED (p = 0.16). Overall, adverse events occurred in 35% (95% CI = 27% to 45%) of the IM group and 20% (95% CI = 13% to 28%) of the IV group (p = 0

Low-dose Ketamine Versus Morphine for Acute Pain In the ED: A Randomized Controlled Trial

DTIC Science & Technology

2015-03-01

fibromyalgia or other chronic pain condition requiring the use of opioids or tramadol as an outpatient, ischemic heart disease, heart failure or unstable...dysrhythmias, use of an opioid or tramadol within 4 hours prior to enrollment, an allergy to morphine or ketamine, required pain medication immediately...Original Contribution Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial☆,☆☆ Joshua P. Miller, MD a,b,⁎, Steven G

Restoring mood balance in depression: ketamine reverses deficit in dopamine-dependent synaptic plasticity.

PubMed

Belujon, Pauline; Grace, Anthony A

2014-12-15

One of the most novel and exciting findings in major depressive disorder research over the last decade is the discovery of the fast-acting and long-lasting antidepressant effects of ketamine. Indeed, the therapeutic effects of classic antidepressants, such as selective serotonin reuptake inhibitors, require a month or longer to be expressed, with about a third of major depressive disorder patients resistant to treatment. Clinical studies have shown that a low dose of ketamine exhibits fast-acting relatively sustained antidepressant action, even in treatment-resistant patients. However, the mechanisms of ketamine action at a systems level remain unclear. Wistar-Kyoto rats were exposed to inescapable, uncontrollable footshocks. To evaluate learned helplessness behavior, we used an active avoidance task in a shuttle box equipped with an electrical grid floor. After helplessness assessment, we performed in vivo electrophysiological recordings first from ventral tegmental area dopaminergic (DA) neurons and second from accumbens neurons responsive to fimbria stimulation. Ketamine was injected and tested on helpless behavior and electrophysiological recordings. We show that ketamine is able to restore the integrity of a network by acting on the DA system and restoring synaptic dysfunction observed in stress-induced depression. We show that part of the antidepressant effect of ketamine is via the DA system. Indeed, injection of ketamine restores a decreased dopamine neuron population activity, as well as synaptic plasticity (long-term potentiation) in the hippocampus-accumbens pathway, via, in part, activation of D1 receptors. This work provides a unique systems perspective on the mechanisms of ketamine on a disrupted limbic system. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Estimation of the contribution of norketamine to ketamine-induced acute pain relief and neurocognitive impairment in healthy volunteers

PubMed Central

Olofsen, Erik; Noppers, Ingeborg; Niesters, Marieke; Kharasch, Evan; Aarts, Leon; Sarton, Elise; Dahan, Albert

2012-01-01

Background The N-methyl-D-receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. One approach to assess the ketamine and norketamine contributions is by measuring ketamine-effect at varying ketamine and norketamine plasma concentrations using the CYP450 inducer rifampicin. Methods In 12 healthy male volunteers the effect of rifampicin versus placebo pretreatment on S-ketamine (a 2-h infusion of 20 mg/h)-induced analgesia and cognition was quantified. The relative ketamine and norketamine contribution to effect was estimated using a linear additive population pharmacokinetic-pharmacodynamic model. Results S-ketamine produced significant analgesia, psychotropic effects (drug high), and cognitive impairment (including memory impairment, reduced psychomotor speed, reduced reaction time, reduced cognitive flexibility). Modeling revealed a negative contribution of S-norketamine to S-ketamine-induced analgesia and absence of contribution to cognitive impairment. At ketamine and norketamine effect concentrations of 100 ng/ml and 50 ng/ml, respectievly, the ketamine contribution to analgesia is −3.8 cm (visual analogue pain score) versus a contribution of norketamine of +1.5 cm, causing an overall effect −2.3 cm. The blood-effect-site equilibration half-life ranged from 0 (cognitive flexibility) to 11.8 (pain intensity) min, and averaged across all end-points was 6.1 min. Conclusions This first observation that norketamine produces effects in the opposite direction of ketamine requires further proof. It can explain the observation of ketamine-related excitatory phenomena (such as hyperalgesia and allodynia) upon the termination of ketamine infusions. PMID:22692377

Cardiorespiratory effects of a tiletamine/zolazepam-ketamine-detomidine combination in horses.

PubMed

Muir, W W; Gadawski, J E; Grosenbaugh, D A

1999-06-01

To determine cardiorespiratory effects of a tiletamine/zolazepam-ketamine-detomidine (TZKD) combination in horses. 8 healthy adult horses. Horses were instrumented for measurement of cardiorespiratory, acid-base, and electrolyte values. Each horse was given xylazine (0.44 mg/kg of body weight, IV) 10 to 15 minutes prior to induction of recumbency by administration of the TZKD combination. Cardiorespiratory, acid-base, and electrolyte values were measured at 5-minute intervals for > or =30 minutes. All horses became recumbent within 1 minute after IV administration of TZKD. Mean +/- SD duration of recumbency was 40+/-8 minutes. All horses regained standing position after < or =2 attempts. Quality of anesthesia and analgesia was determined to be satisfactory in all horses. Xylazine induced decreases in respiratory rate, heart rate, cardiac output, maximum rate of increase of right ventricular pressure, and rate pressure product. The PaCO2, right atrial pressure, and peripheral vascular resistance increased, whereas blood temperature, PO2, pHa, HCO3-, PCV, total solids, Na, and K values remained unchanged. Subsequent administration of TZKD caused right atrial pressure and PaCO2 to increase and PaO2 to decrease, compared with values obtained after xylazine administration. Remaining cardiorespiratory, acid-base, hematologic, and electrolyte values did not differ from those obtained after xylazine administration. IV administration of TZKD induces short-term anesthesia in horses. Potential advantages of this drug combination are the small volume of drug administered; minimal cardiorespiratory depression; quality of induction and maintenance of, and recovery from, anesthesia; and duration of drug effects.

Blood-brain barrier disruption and vascular damage induced by ultrasound bursts combined with microbubbles can be influenced by choice of anesthesia protocol

PubMed Central

McDannold, Nathan; Zhang, Yongzhi; Vykhodtseva, Natalia

2011-01-01

Numerous animal studies have demonstrated that ultrasound bursts combined with a microbubble-based ultrasound contrast agent can temporarily disrupt the blood-brain barrier (BBB) with little or no other apparent effects to the brain. As the BBB is a primary limitation to the use of most drugs in the brain, this method could enable a noninvasive means for targeted drug delivery in the brain. This work investigated whether BBB disruption and vessel damage when overexposure occurs can be influenced by choice of anesthesia protocol, which have different vasoactive effects. Four locations were sonicated transcranially in each brain of 16 rats using an unfocused 532 kHz piston transducer. Burst sonications (10 ms bursts applied at 1 Hz for 60 s) were combined with intravenous Definity (10 μl/kg) injections. BBB disruption was evaluated using contrast-enhanced MRI. Half of the animals were anesthetized with i.p. ketamine and xylazine, and the other half with inhaled isoflurane and oxygen. Over the range of exposure levels tested, MRI contrast enhancement was significantly higher (P<0.05) for animals anesthetized with ketamine/xylazine. Furthermore, the threshold for extensive erythrocyte extravasation was lower with ketamine/xylazine. These results suggest that BBB disruption and/or vascular damage can be affected by vascular or other factors that are influenced by different anesthesia protocol. These experiments may also have been influenced by the recently reported findings that the circulation time for perfluorocarbon microbubbles is substantially reduced when oxygen is used as the carrier gas. PMID:21645965

Preventing Emergence Agitation Using Ancillary Drugs with Sevoflurane for Pediatric Anesthesia: A Network Meta-Analysis.

PubMed

Wang, Xin; Deng, Qi; Liu, Bin; Yu, Xiangdi

2017-11-01

Using sevoflurane for pediatric anesthesia plays a pivotal role in surgeries. Emergence agitation (EA) is a major adverse event accompanied with pediatric anesthesia. Other anesthetic adjuvants can be combined with sevoflurane in clinical practices for different purposes. However, it is uncertain that such a practice may have substantial influence on the risk of EA. We conducted a literature search in online databases, including PubMed, Embase, Cochrane Library, and Clinical Trials. Key data were extracted from eligible randomized control trials (RCTs). Both pairwise and network meta-analysis (NMA) were conducted for synthesizing data from eligible studies. The relative risk of EA was assessed using the odds ratios (ORs) and their corresponding 95 % confidence intervals (CI) or credible intervals (CrI). Ranking scheme based on the surface under the cumulative ranking curve (SUCRA) values was produced. Several key assumptions of NMA such as heterogeneity, degree of consistence, and publication bias were validated by different statistical or graphical approaches. Evidence from 67 randomized control trials was synthesized. The relative risk of EA associated with eight anesthetic adjuvants was analyzed, including ketamine, propofol, dexmedetomidine, clonidine, midazolam, fentanyl, remifentanil, and sufentanil. Patients with the following anesthetic adjuvants appeared to have significantly reduced risk of EA in relation to those with placebo: dexmedetomidine (OR = 0.18, 95 % CrI 0.12-0.25), fentanyl (OR = 0.19, 95 % CrI 0.12-0.30), sufentanil (OR = 0.20, 95 % CrI 0.08-0.50), ketamine (OR = 0.21, 95 % CrI 0.13-0.34), clonidine (OR = 0.25, 95 % CrI 0.14-0.46), propofol (OR = 0.32, 95 % CrI 0.18-0.56), midazolam (OR = 0.46, 95 % CrI 0.27-0.77), and remifentanil (OR = 0.29, 95 % CrI 0.13-0.68). The SUCRA values for each anesthetic adjuvant were: dexmedetomidine (73.65 %), fentanyl (68.04 %), sufentanil (60.81 %), ketamine (59.99 %), clonidine

Metaplastic Effects of Subanesthetic Ketamine on CA1 Hippocampal Function

PubMed Central

Izumi, Yukitoshi; Zorumski, Charles F.

2014-01-01

Ketamine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist of interest in neuropsychiatry. In the present studies, we examined the effects of subanesthetic, low micromolar ketamine on excitatory postsynaptic potentials (EPSPs), population spikes (PSs) and synaptic plasticity in the CA1 region of rat hippocampal slices. Ketamine acutely inhibited NMDAR-mediated synaptic responses with half-maximal effects near 10 µM. When administered for 15–30 min at 1–10 µM, ketamine had no effect on baseline dendritic AMPA receptor-mediated EPSPs, but persistently enhanced somatic EPSPs in the pyramidal cell body layer and augmented PS firing. Acute low micromolar ketamine also had no effect on the induction of long-term potentiation (LTP) but blocked long-term depression (LTD). Following 30 min administration of 1–10 µM ketamine, however, a slowly developing and persistent form of LTP inhibition was observed that took two hours following ketamine washout to become manifest. This LTP inhibition did not result from prolonged or enhanced NMDAR inhibition during drug washout. Effects of low ketamine on somatic EPSPs and LTP were not mimicked by a high ketamine concentration that completely inhibited NMDARs, and both of these effects were blocked by co-administration of low ketamine with a low concentration of the competitive NMDAR antagonist, 2-amino-5-phosphonovalerate or inhibitors of nitric oxide synthase. These results indicate that concentrations of ketamine relevant to psychotropic and psychotomimetic effects have complex metaplastic effects on hippocampal function that involve activation of unblocked NMDARs during ketamine exposure. PMID:25128848

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Bowers, Karen J; McAllister, Kelly B; Ray, Meredith; Heitz, Corey

2017-06-01

This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids; 2) to measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids; 3) to compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids; 4) to monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids; and 5) to identify effect variation between different subgroups of patients, with the purpose of focusing future research. We hypothesized that low-dose ketamine, compared to placebo, as an adjunctive treatment to opioids would result in better pain control over 2 hours and greater patient satisfaction with pain control; further, this protocol will result in a lower opioid dosage over 2 hours. This was a randomized, double-blinded, placebo-controlled trial at a single academic emergency department evaluating the use of ketamine versus placebo in conjunction with opioids for moderate to severe pain. Subjects with a continued high level of pain after an initial dose of opioid analgesia were randomized to receive either 0.1 mg/kg ketamine or placebo prior to protocol-based dosing of additional opioid analgesia, if required. Over 120 minutes, subjects were assessed for pain level (0-10), satisfaction with pain control (0-4), side effects, sedation level, and need for additional pain medication. Total opioid dose, including the initial dose, was compared between groups. Sixty-three subjects were randomized to the placebo group and 53 to the ketamine group. No significant differences were found in demographics between the groups. Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo (p = 0.015). Total opioid dose was lower in the ketamine group

Efficacy of a portable oxygen concentrator with pulsed delivery for treatment of hypoxemia during equine field anesthesia.

PubMed

Coutu, Paige; Caulkett, Nigel; Pang, Daniel; Boysen, Søren

2015-09-01

Hypoxemia is common during equine field anesthesia. Our hypothesis was that oxygen therapy from a portable oxygen concentrator would increase PaO2 during field anesthesia compared with the breathing of ambient air. Prospective clinical study. Fifteen yearling (250 - 400 kg) horses during field castration. Horses were maintained in dorsal recumbency during anesthesia with an intravenous infusion of 2000 mg ketamine and 500 mg xylazine in 1 L of 5% guaifenesin. Arterial samples for blood gas analysis were collected immediately post-induction (PI), and at 15 and 30 minutes PI. The control group (n = 6) breathed ambient air. The treatment group (n = 9) were administered pulsed-flow oxygen (192 mL per bolus) by nasal insufflation during inspiration for 15 minutes PI, then breathed ambient air. The study was performed at 1300 m above sea level. One-way and two-way repeated-measures anova with post-hoc Bonferroni tests were used for within and between-group comparisons, respectively. Significance was set at p ≤ 0.05. Mean ± SD PaO2 in controls at 0, 15 and 30 minutes PI were 46 ± 7 mmHg (6.1 ± 0.9 kPa), 42 ± 9 mmHg (5.6 ± 1.1 kPa), and 48 ± 7 mmHg (6.4 ± 0.1 kPa), respectively (p = 0.4). In treatment animals, oxygen administration significantly increased PaO2 at 15 minutes PI to 60 ± 13 mmHg (8.0 ± 1.7 kPa), compared with baseline values of 46 ± 8 mmHg (6.1 ± 1 kPa) (p = 0.007), and 30 minute PI values of 48 ± 7 mmHg (6.5 ± 0.9 kPa) (p = 0.003). These data show that a pulsed-flow delivery of oxygen can increase PaO2 in dorsally recumbent horses during field anesthesia with ketamine-xylazine-guaifenesin. The portable oxygen concentrator may help combat hypoxemia during field anesthesia in horses. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

A Comparative Study between the Effect of Combined Local Anesthetic and Low-dose Ketamine with Local Anesthetic on Postoperative Complications after Impacted Third Molar Surgery.

PubMed

Kumar, Anuj; Kale, Tejraj Pundalik

2015-12-01

Postoperative pain, swelling and trismus are the most common outcome after third molar surgery. Many methods have been tried to improve postoperative comfort after surgery. Ketamine is a phencyclidine derivative that induces a state of dissociative anesthesia. It is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and has a distinct suppression effect on central nervous system (CNS) sensitization. Ketamine in a subanesthetic dose is set to produce analgesic and anti-inflammatory effect. Sixty patients, between the age group of 18 and 38 years, undergoing the extraction of impacted mandibular third molar, reporting to the department of oral and maxillofacial surgery were included in the study. Patients were divided randomly into two groups: local anesthetic alone (LAA) and local anesthetic and ketamine (LAK). Statistical analysis was performed using the Mann-Whitney U/unpaired--t-test and Wilcoxon signed-rank test. There was a significant difference in mouth opening in the LAA and LAK group in the immediate postoperative period. There was a significant difference between the two groups after 1 hour (LAA: 2.37; LAK: 1.40), and 4 hours (LAA: 2.37; LAK: 1.40). There was a significant difference in terms of facial swelling in the immediate postoperative period and day 1 between the LAA and LAK group. Use of subanesthetic dose of ketamine is not only safe but also valuable in reducing patient morbidity after third molar surgery. Combination of a local anesthetic and subanesthetic dose of ketamine during surgical extraction of third molars provides good postoperative analgesia with less swelling and significantly less trismus.

Propofol anesthesia.

PubMed

Short, C E; Bufalari, A

1999-05-01

Although questions may still remain regarding the use of this unique sedative-hypnotic drug with anesthetic properties in high-risk patients, our studies have provided cardiopulmonary and neurological evidence of the efficacy and safety of propofol when used as an anesthetic under normal and selected impaired conditions in the dog. 1. Propofol can be safely and effectively used for the induction and maintenance of anesthesia in normal healthy dogs. Propofol is also a reliable and safe anesthetic agent when used during induced cardiovascular and pulmonary-impaired conditions without surgery. The propofol requirements to induce the safe and prompt induction of anesthesia prior to inhalant anesthesia with and without surgery have been determined. 2. The favorable recovery profile associated with propofol offers advantages over traditional anesthetics in clinical situations in which rapid recovery is important. Also, propofol compatibility with a large variety of preanesthetics may increase its use as a safe and reliable i.v. anesthetic for the induction and maintenance of general anesthesia and sedation in small animal veterinary practice. Although propofol has proven to be a valuable adjuvant during short ambulatory procedures, its use for the maintenance of general anesthesia has been questioned for surgery lasting more than 1 hour because of increased cost and marginal differences in recovery times compared with those of standard inhalant or balanced anesthetic techniques. When propofol is used for the maintenance of anesthesia in combination with a sedative/analgesic, the quality of anesthesia is improved as well as the ease with which the practitioner can titrate propofol; therefore, practitioners are able to use i.v. anesthetic techniques more effectively in their clinical practices. 3. Propofol can induce significant depression of respiratory function, characterized by a reduction in the rate of respiration. Potent alpha 2 sedative/analgesics (e.g., xylazine

GLYX-13 (rapastinel) ameliorates subchronic phencyclidine- and ketamine-induced declarative memory deficits in mice

PubMed Central

Rajagopal, Lakshmi; Burgdorf, Jeffrey S.; Moskal, Joseph R.; Meltzer, Herbert Y.

2016-01-01

GLYX-13 (rapastinel), a tetrapeptide (Thr-Pro-Pro-Thr-amide), has been reported to have fast acting antidepressant properties in man based upon its N-methyl-d-aspartate receptor (NMDAR) glycine site functional partial agonism. Ketamine, a non-competitive NMDAR antagonist, also reported to have fast acting antidepressant properties, produces cognitive impairment in rodents and man, whereas rapastinel has been reported to have cognitive enhancing properties in rodents, without impairing cognition in man, albeit clinical testing has been limited. The goal of this study was to compare the cognitive impairing effects of rapastinel and ketamine in novel object recognition (NOR), a measure of declarative memory, in male C57BL/6J mice treated with phencyclidine (PCP), another NMDAR noncompetitive antagonist known to severely impair cognition, in both rodents and man. C57BL/6J mice given a single dose or subchronic ketamine (30 mg/kg. i.p.) showed acute or persistent deficits in NOR, respectively. Acute i.v. rapastinel (1.0 mg/kg), did not induce NOR deficit. Pre-treatment with rapastinel significantly prevented acute ketamine-induced NOR deficit. Rapastinel (1.0 mg/kg, but not 0.3 mg/kg, iv) significantly reversed both subchronic ketamine- and subchronic PCP-induced NOR deficits. Rapastinel also potentiated the atypical antipsychotic drug with antidepressant properties, lurasidone, to restore NOR in subchronic ketamine-treated mice. These findings indicate that rapastinel, unlike ketamine, does not induce a declarative memory deficit in mice, and can prevent or reverse the ketamine-induced NOR deficit. Further study is required to determine if these differences translate during clinical use of ketamine and rapastinel as fast acting antidepressant drugs and if rapastinel could have non-ionotropic effects as an add-on therapy with antipsychotic/antidepressant medications. PMID:26632337

Generalizable items of quantitative and qualitative cornerstones for personnel requirement of physicians in anesthesia

PubMed Central

Weiss, Manfred; Rossaint, Rolf; Iber, Thomas

2017-01-01

Anesthesiologists perform a broad spectrum of tasks. However, in many countries, there is no legal basis for personnel staffing of physicians in anesthesia. Also, the German diagnosis related groups system for refunding does not deliver such a basis. Thus, in 2006 a new calculation base for the personnel requirement that included an Excel calculation sheet was introduced by the German Board of Anesthesiologists (BDA) and the German Society of Anesthesiology and Intensive Care Medicine (DGAI), and updated in 2009 and 2015. Oriented primarily to organizational needs, in 2015, BDA/DGAI defined quantitative and qualitative cornerstones for personnel requirement of physicians in anesthesia, especially reflecting recent laws governing physician’s working conditions and competence in the field of anesthesia, as well as demands of strengthened legal rights of patients, patient care and safety. We present a workload-oriented model, integrating core working hours, shift work or standby duty, quality of care, efficiency of processes, legal, educational, controlling, local, organizational and economic aspects for calculating personnel demands. Auxiliary tables enable physicians to calculate personnel demands due to differing employee workload, non-patient oriented tasks and reimbursement of full-equivalents due to parental leave, prohibition of employment, or long-term illness. After 10 years of experience with the first calculation tool, we report the generalizable key aspects and items of a necessary calculation tool which may help physicians to justify realistic workload-oriented personnel staffing demands in anesthesia. A modular, flexible nature of a calculation tool should allow adaption to the respective legal and organizational demands of different countries. PMID:28529910

The Effect of Ketamine and Dexamethasone in Combination with Lidocaine on the Onset and Duration of Axillary Block in Hand and Forearm Soft Tissue Surgery.

PubMed

Zaman, Behrooz; Hojjati Ashrafi, Siavash; Seyed Siamdoust, Seyedalireza; Hassani, Valiollah; Mohamad Taheri, Siavash; Noorizad, Samad

2017-10-01

Using peripheral nerve block compared to general anesthesia has gained more popularity due to reduced postoperative pain, less need for post-surgery analgesic drugs, reduced incidence of nausea, shortness of PACU time, and increased patient satisfaction. The aim of this study was to compare the effect of ketamine and dexamethasone as additives to lidocaine on duration and onset of axillary block action. In this clinical trial, all patients who referred to Hazrat-e-Fatemeh hospital for forearm and hand soft tissue surgery with informed consent were randomly divided into three groups in order to examine the onset and duration of axillary block: lidocaine + ketamine, lidocaine + dexamethasone in axillary block, and lidocaine alone (control). Then, the onset and duration of sensory and motor blocks were measured and recorded every three minutes and after the surgery. Quantitative and qualitative variables were analyzed using ANOVA or Kruskal-Wallis test and Chi-square or Fisher exact test in SPSS v.22. Duration of sensory and motor block axillary was significantly higher in lidocaine + dexamethasone group than in lidocaine + ketamine group (P < 0.05); it was also significantly higher in lidocaine + ketamine group compared to lidocaine group (P < 0.05). However, there was no significant difference in the onset of sensory and motor block axillary between the three groups (P > 0.05). According to the results of our study, we can conclude that adding dexamethasone or ketamine to lidocaine could improve duration of sensory and motor axillary block in patients undergoing forearm and hand soft tissue surgery. However, dexamethasone had the highest effect on duration of block axillary. We proved that dexamethasone or ketamine added to lidocaine had no effect on the onset of block axillary.

In vivo neurometabolic profiling to characterize the effects of social isolation and ketamine-induced NMDA antagonism: a rodent study at 7.0 T.

PubMed

Napolitano, Antonio; Shah, Khalid; Schubert, Mirjam I; Porkess, Veronica; Fone, Kevin C F; Auer, Dorothee P

2014-05-01

Continued efforts are undertaken to develop animal models of schizophrenia with translational value in the quest for much needed novel drugs. Existing models mimic specific neurobiological aspects of schizophrenia, but not its full complexity. Here, we used proton magnetic resonance spectroscopy ((1)H-MRS) to assess the metabolic profile in the prefrontal cortex (PFC) of two established models, rearing in social isolation and acute N-methyl-D-aspartate receptor (NMDA-R) antagonism and their combination. Rats reared in social isolation or group housed underwent (1)H-MRS at baseline and dynamically after ketamine challenge (25mg/kg, intraperitoneal) under isoflurane anesthesia. A 7 T animal scanner was used to perform spectra acquisition from the anterior cingulate/medial PFC. LCModel was used for metabolite quantification and effects of rearing and ketamine injection were analyzed. Social isolation did not lead to significant differences in the metabolic profile of the PFC at baseline. Ketamine induced a significant increase in glutamine in both groups with significance specifically reached by the group-housed animals alone. Only rats reared in social isolation showed a significant 11% γ-aminobutyric acid (GABA) decrease. This study provides preliminary evidence that social interactions in early life predict the glutamatergic and GABAergic response to acute NMDA-R blockade. The similarity between the prefrontal GABA reduction in patients with schizophrenia and in rats reared as social isolates after challenge with ketamine suggests good potential translational value of this combined animal model for drug development.

Intraosseous anesthesia in hemodynamic studies in children with cardiopathy.

PubMed

Aliman, Ana Cristina; Piccioni, Marilde de Albuquerque; Piccioni, João Luiz; Oliva, José Luiz; Auler Júnior, José Otávio Costa

2011-01-01

Intraosseous (IO) access has been used with good results in emergency situations, when venous access is not available for fluids and drugs infusion. The objective of this study was to evaluate IO a useful technique for anesthesia and fluids infusion during hemodynamic studies and when peripheral intravascular access is unobtainable. The setting was an university hospital hemodynamics unit, and the subjects were twenty one infants with congenital heart disease enrolled for elective hemodynamic study diagnosis. This study compared the effectiveness of IO access in relation to IV access for infusion of anesthetics agents (ketamine, midazolam, and fentanyl) and fluids during hemodynamic studies. The anesthetic induction time, procedure duration, anesthesia recovery time, adequate hydration, and IV and IO puncture complications were compared between groups. The puncture time was significantly smaller in IO group (3.6 min) that in IV group (9.6 min). The anesthetic onset time (56.3 second) for the IV group was faster than IO group (71.3 second). No significant difference between groups were found in relation to hydration (IV group, 315.5 mL vs IO group, 293.2 mL), and anesthesia recovery time (IO group, 65.2 min vs IV group, 55.0 min). The puncture site was reevaluated after 7 and 15 days without signs of infection or other complications. Results showed superiority for IO infusion when considering the puncture time of the procedure. Due to its easy manipulation and efficiency, hydration and anesthesia by IO access was satisfactory for hemodynamic studies without the necessity of other infusion access. Copyright © 2011 Elsevier Editora Ltda. All rights reserved.

Use of Ketamine in Elderly Patients with Treatment-Resistant Depression.

PubMed

Medeiros da Frota Ribeiro, Carolina; Riva-Posse, Patricio

2017-11-15

The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown to be a promising treatment in TRD; however, data regarding the use of ketamine in the elderly includes only five case reports. We discuss the use of ketamine for late-life TRD and present two cases where ketamine led to a significant and sustained improvement in depressive symptoms. Ketamine is a promising treatment for geriatric patients with TRD. Further studies in the elderly will provide valuable insights into the use of ketamine for a population much in need of safe and effective treatments for TRD.

Repeated intranasal ketamine for treatment-resistant depression - the way to go? Results from a pilot randomised controlled trial.

PubMed

Gálvez, Verònica; Li, Adrienne; Huggins, Christina; Glue, Paul; Martin, Donel; Somogyi, Andrew A; Alonzo, Angelo; Rodgers, Anthony; Mitchell, Philip B; Loo, Colleen K

2018-04-01

Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment. Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (>45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups. IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD.

Ketamine-a returning option for procedural sedation and analgesia in adults.

PubMed

O'Malley, Patricia Anne

2014-01-01

I am a clinical nurse specialist in a busy trauma center. Increasingly, we are using ketamine for procedures and pain management in adults. I thought ketamine was appropriate only for pediatric patients. Why has ketamine emerged again for adults? Also, we have seen a few cases of ketamine abuse over the past 3 months. Is ketamine abuse becoming more prevalent?

A PK-PD Model of Ketamine-Induced High-Frequency Oscillations

PubMed Central

Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.

2017-01-01

Objective Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a High-Frequency Oscillation (HFO) which power is modulated non-linearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PD) of ketamine and the observed HFO power. Approach In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by a high-frequency oscillation (HFO) observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the

A PK-PD model of ketamine-induced high-frequency oscillations

NASA Astrophysics Data System (ADS)

Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.

2015-10-01

Objective. Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power. Approach. In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results. We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance. Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent

Oral ketamine for the treatment of pain and treatment-resistant depression†.

PubMed

Schoevers, Robert A; Chaves, Tharcila V; Balukova, Sonya M; Rot, Marije Aan Het; Kortekaas, Rudie

2016-02-01

Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications. To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain. Searches in PubMed with the terms 'oral ketamine', 'depression', 'chronic pain', 'neuropathic pain', 'intravenous ketamine', 'intranasal ketamine' and 'subcutaneous ketamine' yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality. Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects. Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials. © The Royal College of Psychiatrists 2016.

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

PubMed Central

Yang, C; Shirayama, Y; Zhang, J-c; Ren, Q; Yao, W; Ma, M; Dong, C; Hashimoto, K

2015-01-01

Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)–TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF–TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF–TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability. PMID:26327690

A consideration of ketamine dreams.

PubMed

Hejja, P; Galloon, S

1975-01-01

This study was designed to see whether covering of the eyes during and after ketamine anaesthesia would reduce the incidence of dreams. One hundred and fifty patients, randomly divided into three groups, underwent therapeutic abortion with ketamine as the sole anaesthesia. One hundred patients had their eyes completely covered, 50 in the operating room only and 50 in the operating room and in the recovery room. The third 50 were controls, with their eyes uncovered. All patients were questioned post-operatively about dreams, nausea and vomiting, headache, dizziness and experiences, and also how frequently they dreamed at home. Although covering the eyes in the recovery room only reduced the incidence of dreams marginally, it became obvious that the patients who dreamed after ketamine (in all 3 groups) were those who normally dreamed at home. There were 82 patients who were recorded as not being home-dreamers, and only two of these dreamed after ketamine. In contrast, of the 68 home-dreamers, 50 dreamed after ketamine, and 17 of these had unpleasant dreams. In the home-dreamers, covering the eyes reduced the incidence of dreams from 86 per cent in Group 1 to 72 per cent in Group 2 and 64 per cent in Group 3. It is suggested that goggles may be advantageous when dealing with home-dreamers, and a question about the patient's tendency to dream should be included in the preoperative questioning. Alterations in premedication and the use of a quiet dark room during recovery may even further reduce unpleasant dreams in this group.

Evaluating the Use of Ketamine for Pain Control With Sickle Cell Crisis in Pregnancy: A Report of 2 Cases.

PubMed

Gimovsky, Alexis C; Fritton, Kate; Viscusi, Eugene; Roman, Amanda

2018-01-01

Sickle cell crises occur frequently during pregnancy and are difficult to treat, even with high-dose opioids. Analgesia with ketamine has been suggested as an alternative, but its use during pregnancy is underreported. Two pregnant patients with uncontrolled sickle cell pain were treated with ketamine. Patient A reported no decrease in her pain, but her opioid requirements decreased. Patient B's pain resolved during ketamine administration. No serious maternal or neonatal adverse effects occurred. Ketamine may be considered as an adjunct analgesic in pregnant patients with sickle cell pain, although prospective clinical data are needed to fully assess its efficacy.

Towards an Explanation of Subjective Ketamine Experiences among Young Injection Drug Users

PubMed Central

LANKENAU, STEPHEN E.; SANDERS, BILL; BLOOM, JENNIFER JACKSON; HATHAZI, DODI

2008-01-01

Ketamine is a dissociative anesthetic with powerful sedative and hallucinogenic properties. Despite the wide variability in reported subjective experiences, no study has attempted to describe the particular factors that shape these experiences. This manuscript is based upon a sample of 213 young injection drug users recruited in New York, New Orleans, and Los Angeles with histories of ketamine use. Qualitative interviews focused on specific ketamine events, such as first injection of ketamine, most recent injection of ketamine, and most recent experience sniffing ketamine. Findings indicate that six factors impacted both positive and negative ketamine experiences: polydrug use, drug using history, mode of administration, quantity and quality of ketamine, user group, and setting. Most subjective experiences during any given ketamine event were shaped by a combination of these factors. Additionally, subjective ketamine experiences were particularly influenced by a lifestyle characterized by homelessness and traveling. PMID:18941540

Effect of Rifampicin on S-ketamine and S-norketamine Plasma Concentrations in Healthy Volunteers after Intravenous S-ketamine Administration

PubMed Central

Noppers, Ingeborg; Olofsen, Erik; Niesters, Marieke; Aarts, Leon; Mooren, René; Dahan, Albert; Kharasch, Evan; Sarton, Elise

2012-01-01

Background Low-dose ketamine is used as analgesic for acute and chronic pain. It is metabolized in the liver to norketamine via cytochrome P450 enzymes. There are few human data on the involvement of CYP enzymes on the elimination of norketamine and its possible contribution to analgesic effect. The aim of this study was to investigate the effect of cytochrome P450 enzyme induction by rifampicin on the pharmacokinetics of S-ketamine and its major metabolite, S-norketamine, in healthy volunteers. Methods Twenty healthy male subjects received 20 mg/70kg/h (n = 10) or 40 mg/70kg/h (n = 10) intravenous S-ketamine for 2-h following either 5 days of oral rifampicin (once daily 600 mg) or placebo treatment. During and 3-h following drug infusion arterial plasma concentrations of S-ketamine and S-norketamine were obtained at regular intervals. The data were analyzed with a compartmental pharmacokinetic model consisting of three compartments for S-ketamine, three sequential metabolism compartments and two S-norketamine compartments using the statistical package NONMEM version VII. Results Rifampcin caused a 10% and 50% reduction in the area-under-the-curve of the plasma concentrations of S-ketamine and S-norketamine, respectively. The compartmental analysis indicated a 13% and 200% increase in S-ketamine and S-norketamine elimination from their respective central compartments by rifampicin. Conclusions A novel observation is the large effect of rifampicin on S-norketamine concentrations and indicates that rifampicin induces the elimination of S-ketamine’s metabolite, S-norketamine, probably via induction of the CYP3A4 and/or CYP2B6 enzymes. PMID:21508826

Blood-brain barrier disruption and vascular damage induced by ultrasound bursts combined with microbubbles can be influenced by choice of anesthesia protocol.

PubMed

McDannold, Nathan; Zhang, Yongzhi; Vykhodtseva, Natalia

2011-08-01

Numerous animal studies have demonstrated that ultrasound bursts combined with a microbubble-based ultrasound contrast agent can temporarily disrupt the blood-brain barrier (BBB) with little or no other apparent effects to the brain. As the BBB is a primary limitation to the use of most drugs in the brain, this method could enable a noninvasive means for targeted drug delivery in the brain. This work investigated whether BBB disruption and vessel damage when overexposure occurs can be influenced by choice of anesthesia protocol, which have different vasoactive effects. Four locations were sonicated transcranially in each brain of 16 rats using an unfocused 532 kHz piston transducer. Burst sonications (10 ms bursts applied at 1 Hz for 60 s) were combined with intravenous Definity (10 μl/kg) injections. BBB disruption was evaluated using contrast-enhanced MRI. Half of the animals were anesthetized with i.p. ketamine and xylazine, and the other half with inhaled isoflurane and oxygen. Over the range of exposure levels tested, MRI contrast enhancement was significantly higher (p < 0.05) for animals anesthetized with ketamine/xylazine. Furthermore, the threshold for extensive erythrocyte extravasation was lower with ketamine/xylazine. These results suggest that BBB disruption and/or vascular damage can be affected by vascular or other factors that are influenced by different anesthesia protocol. These experiments may also have been influenced by the recently reported findings that the circulation time for perfluorocarbon microbubbles is substantially reduced when oxygen is used as the carrier gas. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Intravenous anaesthesia using detomidine, ketamine and guaiphenesin for laparotomy in pregnant pony mares.

PubMed

Taylor, Polly M; Luna, Stelio Pl; White, Kate L; Bloomfield, Malcolm; Fowden, Abigail L

2001-07-01

Objective To characterize intravenous anaesthesia with detomidine, ketamine and guaiphenesin in pregnant ponies. Animals Twelve pony mares, at 260-320 days gestation undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre-anaesthetic medication with intravenous (IV) acepromazine (30 µg kg -1 ), butorphanol (20 µg kg -1 ) and detomidine (10 µg kg -1 ) preceded induction of anaesthesia with detomidine (10 µg kg -1 ) and ketamine (2 mg kg -1 ) IV Maternal arterial blood pressure was measured directly throughout anaesthesia and arterial blood samples were taken at 20-minute intervals for measurement of blood gases and plasma concentrations of cortisol, glucose and lactate. Anaesthesia was maintained with an IV infusion of detomidine (0.04 mg mL -1 ), ketamine (4 mg mL -1 ) and guaiphenesin (100 mg mL -1 ) (DKG) for 140 minutes. Oxygen was supplied by intermittent positive pressure ventilation (IPPV) adjusted to maintain PaCO 2 between 5.0 and 6.0 kPa (38 and 45 mm Hg), while PaO 2 was kept close to 20.0 kPa (150 mm Hg) by adding nitrous oxide. Simultaneous fetal and maternal blood samples were withdrawn at 90 minutes. Recovery quality was assessed. Results DKG was infused at 0.67 ± 0.17 mL kg -1 hour -1 for 1 hour then reduced, reaching 0.28 ± 0.14 mL kg -1 hour -1 at 140 minutes. Arterial blood gas values and pH remained within intended limits. During anaesthesia there was no change in heart rate, but arterial blood pressure decreased by 10%. Plasma glucose and lactate increased (10-fold and 2-fold, respectively) and cortisol decreased by 50% during anaesthesia. Fetal umbilical venous pH, PO 2 and PCO 2 were 7.34 ± 0.06, 5.8 ± 0.9 kPa (44 ± 7 mm Hg) and 6.7 ± 0.8 kPa (50 ± 6 mm Hg); and fetal arterial pH, PO 2 and PCO 2 were 7.29 ± 0.06, 4.0 ± 0.7 kPa (30 ± 5 mm Hg) and 7.8 ± 1.7 kPa (59 ± 13 mm Hg), respectively. Surgical conditions were good but four ponies required a single additional dose of ketamine

Abnormalities in white matter microstructure associated with chronic ketamine use.

PubMed

Edward Roberts, R; Curran, H Valerie; Friston, Karl J; Morgan, Celia J A

2014-01-01

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to induce schizophrenia-type symptoms in humans and is a potent and fast-acting antidepressant. It is also a relatively widespread drug of abuse, particularly in China and the UK. Acute administration has been well characterized, but the effect of extended periods of ketamine use-on brain structure in humans-remains poorly understood. We measured indices of white matter microstructural integrity and connectivity in the brain of 16 ketamine users and 16 poly-drug-using controls, and we used probabilistic tractography to quantify changes in corticosubcortical connectivity associated with ketamine use. We found a reduction in the axial diffusivity profile of white matter in a right hemisphere network of white matter regions in ketamine users compared with controls. Within the ketamine-user group, we found a significant positive association between the connectivity profile between the caudate nucleus and the lateral prefrontal cortex and dissociative experiences. These findings suggest that chronic ketamine use may be associated with widespread disruption of white matter integrity, and white matter pathways between subcortical and prefrontal cortical areas may in part predict individual differences in dissociative experiences due to ketamine use.

Revealing past memories: proactive interference and ketamine-induced memory deficits.

PubMed

Chrobak, James J; Hinman, James R; Sabolek, Helen R

2008-04-23

Memories of events that occur often are sensitive to interference from memories of similar events. Proactive interference plays an important and often unexamined role in memory testing for spatially and temporally unique events ("episodes"). Ketamine (NMDA receptor antagonist) treatment in humans and other mammals induces a constellation of cognitive deficits, including impairments in working and episodic memory. We examined the effects of the ketamine (2.5-100 mg/kg) on the acquisition, retrieval, and retention of memory in a delayed-match-to-place radial water maze task that can be used to assess proactive interference. Ketamine (2.5-25 mg/kg, i.p.) given 20 min before the sample trial, impaired encoding. The first errors made during the test trial were predominantly to arms located spatially adjacent to the goal arm, suggesting an established albeit weakened representation. Ketamine (25-100 mg/kg) given immediately after the sample trial had no effect on retention. Ketamine given before the test trial impaired retrieval. First errors under the influence of ketamine were predominantly to the goal location of the previous session. Thus, ketamine treatment promoted proactive interference. These memory deficits were not state dependent, because ketamine treatment at both encoding and retrieval only increased the number of errors during the test session. These data demonstrate the competing influence of distinct memory representations during the performance of a memory task in the rat. Furthermore, they demonstrate the subtle disruptive effects of the NMDA antagonist ketamine on both encoding and retrieval. Specifically, ketamine treatment disrupted retrieval by promoting proactive interference from previous episodic representations.

Ketamine accelerates fear extinction via mTORC1 signaling.

PubMed

Girgenti, Matthew J; Ghosal, Sriparna; LoPresto, Dora; Taylor, Jane R; Duman, Ronald S

2017-04-01

Impaired fear extinction contributes to the persistence of post-traumatic stress disorder (PTSD), and can be utilized for the study of novel therapeutic agents. Glutamate plays an important role in the formation of traumatic memories, and in the pathophysiology and treatment of PTSD, highlighting several possible drug targets. Recent clinical studies demonstrate that infusion of ketamine, a glutamate NMDA receptor antagonist, rapidly and significantly reduces symptom severity in PTSD patients. In the present study, we examine the mechanisms underlying the actions of ketamine in a rodent model of fear conditioning, extinction, and renewal. Rats received ketamine or saline 24h after fear conditioning and were then subjected to extinction-training on each of the following three days. Ketamine administration enhanced extinction on the second day of training (i.e., reduced freezing behavior to cue) and produced a long-lasting reduction in freezing on exposure to cue plus context 8days later. Additionally, ketamine and extinction exposure increased levels of mTORC1 in the medial prefrontal cortex (mPFC), a region involved in the acquisition and retrieval of extinction, and infusion of the selective mTORC1 inhibitor rapamycin into the mPFC blocked the effects of ketamine on extinction. Ketamine plus extinction also increased cFos in the mPFC and administration of a glutamate-AMPA receptor antagonist blocked the effects of ketamine. These results support the hypothesis that ketamine produces long-lasting mTORC1/protein synthesis and activity dependent effects on neuronal circuits that enhance the expression of extinction and could represent a novel approach for the treatment of PTSD. Copyright © 2017 Elsevier Inc. All rights reserved.

Ketamine accelerates fear extinction via mTORC1 signaling

PubMed Central

Girgenti, Matthew J.; Ghosal, Sriparna; LoPresto, Dora; Taylor, Jane R.; Duman, Ronald S.

2018-01-01

Impaired fear extinction contributes to the persistence of post-traumatic stress disorder (PTSD), and can be utilized for the study of novel therapeutic agents. Glutamate plays an important role in the formation of traumatic memories, and in the pathophysiology and treatment of PTSD, highlighting several possible drug targets. Recent clinical studies demonstrate that infusion of ketamine, a glutamate NMDA receptor antagonist, rapidly and significantly reduces symptom severity in PTSD patients. In the present study, we examine the mechanisms underlying the actions of ketamine in a rodent model of fear conditioning, extinction, and renewal. Rats received ketamine or saline 24 h after fear conditioning and were then subjected to extinction-training on each of the following three days. Ketamine administration enhanced extinction on the second day of training (i.e., reduced freezing behavior to cue) and produced a long-lasting reduction in freezing on exposure to cue plus context 8 days later. Additionally, ketamine and extinction exposure increased levels of mTORC1 in the medial prefrontal cortex (mPFC), a region involved in the acquisition and retrieval of extinction, and infusion of the selective mTORC1 inhibitor rapamycin into the mPFC blocked the effects of ketamine on extinction. Ketamine plus extinction also increased cFos in the mPFC and administration of a glutamate-AMPA receptor antagonist blocked the effects of ketamine. These results support the hypothesis that ketamine produces long-lasting mTORC1/protein synthesis and activity dependent effects on neuronal circuits that enhance the expression of extinction and could represent a novel approach for the treatment of PTSD. PMID:28043916

Laparoscopic Cholecystectomy under Segmental Thoracic Spinal Anesthesia: A Feasible Economical Alternative.

PubMed

Kejriwal, Aditya Kumar; Begum, Shaheen; Krishan, Gopal; Agrawal, Richa

2017-01-01

Laparoscopic surgery is normally performed under general anesthesia, but regional techniques like thoracic epidural and lumbar spinal have been emerging and found beneficial. We performed a clinical case study of segmental thoracic spinal anaesthesia in a healthy patient. We selected an ASA grade I patient undergoing elective laparoscopic cholecystectomy and gave spinal anesthetic in T10-11 interspace using 1 ml of bupivacaine 5 mg ml -1 mixed with 0.5 ml of fentanyl 50 μg ml -1 . Other drugs were only given (systemically) to manage patient anxiety, pain, nausea, hypotension, or pruritus during or after surgery. The patient was reviewed 2 days postoperatively in ward. The thoracic spinal anesthetia was performed easily in the patient. Some discomfort which was readily treated with 1mg midazolam and 20 mg ketamine intravenously. There was no neurological deficit and hemodynamic parameters were in normal range intra and post-operatively and recovery was uneventful. We used a narrow gauze (26G) spinal needle which minimized the trauma to the patient and the chances of PDPH, which was more if 16 or 18G epidural needle had been used and could have increased further if there have been accidental dura puncture. Also using spinal anesthesia was economical although it should be done cautiously as we are giving spinal anesthesia above the level of termination of spinal cord.

Laparoscopic Cholecystectomy under Segmental Thoracic Spinal Anesthesia: A Feasible Economical Alternative

PubMed Central

Kejriwal, Aditya Kumar; Begum, Shaheen; Krishan, Gopal; Agrawal, Richa

2017-01-01

Laparoscopic surgery is normally performed under general anesthesia, but regional techniques like thoracic epidural and lumbar spinal have been emerging and found beneficial. We performed a clinical case study of segmental thoracic spinal anaesthesia in a healthy patient. We selected an ASA grade I patient undergoing elective laparoscopic cholecystectomy and gave spinal anesthetic in T10-11 interspace using 1 ml of bupivacaine 5 mg ml−1 mixed with 0.5 ml of fentanyl 50 μg ml−1. Other drugs were only given (systemically) to manage patient anxiety, pain, nausea, hypotension, or pruritus during or after surgery. The patient was reviewed 2 days postoperatively in ward. The thoracic spinal anesthetia was performed easily in the patient. Some discomfort which was readily treated with 1mg midazolam and 20 mg ketamine intravenously. There was no neurological deficit and hemodynamic parameters were in normal range intra and post-operatively and recovery was uneventful. We used a narrow gauze (26G) spinal needle which minimized the trauma to the patient and the chances of PDPH, which was more if 16 or 18G epidural needle had been used and could have increased further if there have been accidental dura puncture. Also using spinal anesthesia was economical although it should be done cautiously as we are giving spinal anesthesia above the level of termination of spinal cord. PMID:28928589

Oral ketamine/midazolam is superior to intramuscular meperidine, promethazine, and chlorpromazine for pediatric cardiac catheterization.

PubMed

Auden, S M; Sobczyk, W L; Solinger, R E; Goldsmith, L J

2000-02-01

An IM combination of meperidine, promethazine, and chlorpromazine (DPT) has been given as sedation for pediatric procedures for more than 40 years. We compared this IM combination to oral (PO) ketamine/midazolam in children having cardiac catheterization. A total of 51 children, ages 9 mo to 10 yr, were enrolled and randomized in this double-blinded study. All children received an IM injection at time zero and PO fluid 15 minutes later. We observed acceptance of medication, onset of sedation and sleep, and sedative efficacy. The cardiorespiratory changes were evaluated. Sedation was supplemented with IV propofol as required. Recovery time, parental satisfaction, and patient amnesia were assessed. Ketamine/midazolam given PO was better tolerated (P < 0.0005), had more rapid onset (P < 0.001), and provided superior sedation (P < 0.005). Respiratory rate decreased after IM DPT only. Heart rate and shortening fraction were stable. Oxygen saturation and mean blood pressure decreased minimally in both groups. Supplemental propofol was more frequently required (P < or = 0.02) and in larger doses (P < 0.05) after IM DPT. Parental satisfaction ratings were higher (P < 0.005) and amnesia was more reliably obtained (P = 0.007) with PO ketamine/midazolam. Two patients needed airway support after the PO medication, as did two other patients when PO ketamine/midazolam was supplemented with IV propofol. Although PO ketamine/midazolam provided superior sedation and amnesia compared to IM DPT, this regimen may require the supervision of an anesthesiologist for safe use. Oral medication can be superior to IM injections for sedating children with congenital heart disease; however, the safety of all medications remains an issue.

The Use of Prehospital Ketamine for Control of Agitation in a Metropolitan Firefighter-based EMS System.

PubMed

Keseg, David; Cortez, Eric; Rund, Douglas; Caterino, Jeffrey

2015-01-01

Abstract Introduction. Prehospital personnel frequently encounter agitated, combative, and intoxicated patients in the field. In recent years, ketamine has been described as an effective sedative agent to treat such patients; however, a paucity of research exists describing the use of prehospital ketamine. The objective of this study was to provide a descriptive analysis of the Columbus Division of Fire's experience with utilizing ketamine in the prehospital setting. We hypothesized that ketamine administration improves patient condition, is effective at sedating patients, and does not result in endotracheal intubation in the prehospital setting or in the emergency department (ED). Methods. We conducted a retrospective cohort chart review of Columbus Division of Fire patient care reports and hospital records from destination hospitals in the central Ohio region between October 2010 and October 2012. All patients receiving ketamine administered by Columbus Division of Fire personnel for sedation were included. Patients 17 years and younger were excluded. The primary outcome was the percentage of patients noted to have an "improved" condition recorded in the data field of the patient care report. The secondary outcomes were the effectiveness of sedation and the performance of endotracheal intubation. Results. A total of 36 patients met inclusion criteria over the study period. Data were available on 35 patients for analysis. The mean IV dose of ketamine was 138 mg (SD = 59.5, 100-200). The mean IM dose of ketamine was 324 mg (SD = 120, 100-500). Prehospital records noted an improvement in patient condition after ketamine administration in 32 cases (91%, 95% CI 77-98%). Six patients required sedation post-ketamine administration either by EMS (2) or in the ED (4) (17%, 95% CI 6.5-34%). Endotracheal intubation was performed in eight (23%, 95% CI 10-40%) patients post-ketamine administration. Conclusion. We found that in a cohort of patients administered ketamine

Dexmedetomidine Protects Neural Stem Cells from Ketamine-Induced Injury.

PubMed

Lu, Pan; Lei, Shan; Li, Weisong; Lu, Yang; Zheng, Juan; Wang, Ning; Xia, Yongjun; Lu, Haixia; Chen, Xinlin; Liu, Yong; Zhang, Peng-Bo

2018-06-19

Ketamine inhibits the proliferation of neural stem cells (NSCs) and disturbs normal neurogenesis. Dexmedetomidine provides neuroprotection against volatile anesthetic-induced neuroapoptosis and cognitive impairment in the developing brain. Whether it may protect NSCs from ketamine-induced injury remains unknown. In this study, we investigated the protective effects of dexmedetomidine on ketamine-exposed NSCs and explored the mechanisms potentially involved. Primary NSC cultures were characterized using immunofluorescence. Cell viability was determined using a Cell Counting Kit 8 assay. Proliferation and apoptosis were assessed with BrdU incorporation and TUNEL assays, respectively. Protein levels of cleaved caspase-3, phosphorylated protein kinase B (p-Akt), and glycogen synthase kinase-3β (p-GSK-3β) were quantified using western blotting. Ket-amine significantly decreased NSC viability and proliferation and increased their apoptosis. Dexmedetomidine increased NSC proliferation and decreased their apoptosis in a dose-dependent manner. Furthermore, dexmedetomidine pretreatment notably augmented the viability and proliferation of ketamine-exposed NSCs and reduced their apoptosis. Moreover, dexmedetomidine lessened caspase-3 activation and increased p-Akt and p-GSK-3β levels in NSCs exposed to ketamine. The protective effects of dexmedetomidine on ketamine-exposed NSCs could be partly reversed by the PI3K inhibitor LY294002. Collectively, these findings indicate that dexmedetomidine may protect NSCs from ketamine-induced injury via the PI3K/Akt/GSK-3β signaling pathway. © 2018 The Author(s). Published by S. Karger AG, Basel.

The prevalence and natural history of urinary symptoms among recreational ketamine users.

PubMed

Winstock, Adam R; Mitcheson, Luke; Gillatt, David A; Cottrell, Angela M

2012-12-01

Study Type--Symptom prevalence (prospective cohort) Level of Evidence 1b. What's known on the subject? and What does the study add? Case series have described lower urinary tract symptoms associated with ketamine use including severe pain, frequency, haematuria and dysuria. Little is known regarding the frequency of symptoms, relationship of symptoms with dose and frequency of use and natural history of symptoms once the ketamine user has stopped. This study describes the prevalence of ketamine use in a population of recreational drug users in a dance music setting. It shows a dose-frequency relationship with ketamine use. It shows that urinary symptoms associated with recreational ketamine use may lead to a considerable demand on health resources in the primary-, secondary- and emergency-care settings. It shows that symptoms may improve once ketamine use is decreased. • To investigate the prevalence and natural history of urinary symptoms in a cohort of recreational ketamine users. • A purposeful sampling technique was used. • Between November 2009 and January 2010 participants were invited to undertake an on-line questionnaire promoted by a national dance music magazine and website. • Data regarding demographics and illicit drug-use were collected. • Among respondents reporting recent ketamine use, additional information detailing their ketamine use, experience of urinary symptoms and use of related healthcare services was obtained. • In all, 3806 surveys were completed, of which 1285 (33.8%) participants reported ketamine use within the last year. • Of the ketamine users, 17% were found to be dependent on the drug; 26.6% (340) of recent ketamine users reported experiencing urinary symptoms. • Urinary symptoms were significantly related to both dose of ketamine used and frequency of ketamine use. • Of 251 users reporting their experience of symptoms over time in relationship to their use of ketamine, 51% reported improvement in urinary symptoms

Subanesthetic, Subcutaneous Ketamine Infusion Therapy in the Treatment of Chronic Nonmalignant Pain.

PubMed

Zekry, Olfat; Gibson, Stephen B; Aggarwal, Arun

2016-06-01

This study was designed to describe the efficacy and toxicity of subcutaneous ketamine infusions and sublingual ketamine lozenges for the treatment of chronic nonmalignant pain. Data were collected prospectively on 70 subjects managed in an academic, tertiary care hospital between 2007 and 2012 who received between 3 and 7 days of subanesthetic, subcutaneous ketamine infusion. Data were analyzed for efficacy, adverse effects, and reduction in use of opioid medication. We also analyzed whether subsequent treatment with sublingual ketamine lozenges resulted in longer-term efficacy of the beneficial effects of the initial ketamine infusion. There was a significant reduction in pain intensity measured by numerical rating scale (NRS) from mean of 6.38 before ketamine to 4.60 after ketamine (P < .005) that was sustained for between 3 months and 6 years. In subjects on opioids, there was a significant reduction in opioid use at the end of the ketamine infusion from a mean morphine equivalent dose (MMED) of 216 mg/day before ketamine to 89 mg/day after ketamine (P < .005). The overall reduction in opioid use after ketamine infusion was 59%. No subjects increased their use of opioids during their hospitalization for the ketamine infusion. A small proportion of subjects who responded to the infusion were continued on ketamine lozenges. This group was followed for between 3 months and 2 years. The use of ketamine lozenges after the infusion resulted in 31% of these subjects being able to cease their use of opioids compared with only 6% who did not receive ketamine lozenges. Eleven percent of subjects who received lozenges subsequently increased their opioid usage. Adverse effects were fairly common, but only mild, with 46% of patients experiencing light-headedness and dizziness, 25% tiredness and sedation, 12% headaches, 12% hallucinations, and 8% vivid dreams. Adverse effects were easily managed by reducing the rate of the ketamine infusion. The administration of

Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories.

PubMed

Kishimoto, T; Chawla, J M; Hagi, K; Zarate, C A; Kane, J M; Bauer, M; Correll, C U

2016-05-01

Ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear. We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges' g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all-cause discontinuation and adverse effects. A total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD = 554, BD = 34), lasting 10.0 ± 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g = -1.00, 95% CI -1.28 to -0.73, p < 0.001), and loosing superiority by days 10-12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5-8 (Hedges' g = -0.37, 95% CI -0.66 to -0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3-5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3-5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant. A single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting

Anesthesia and critical-care delivery in weightlessness: A challenge for research in parabolic flight analogue space surgery studies

NASA Astrophysics Data System (ADS)

Ball, Chad G.; Keaney, Marilyn A.; Chun, Rosaleen; Groleau, Michelle; Tyssen, Michelle; Keyte, Jennifer; Broderick, Timothy J.; Kirkpatrick, Andrew W.

2010-03-01

BackgroundMultiple nations are actively pursuing manned exploration of space beyond low-earth orbit. The responsibility to improve surgical care for spaceflight is substantial. Although the use of parabolic flight as a terrestrial analogue to study surgery in weightlessness (0 g) is well described, minimal data is available to guide the appropriate delivery of anesthesia. After studying anesthetized pigs in a 0 g parabolic flight environment, our group developed a comprehensive protocol describing prolonged anesthesia in a parabolic flight analogue space surgery study (PFASSS). Novel challenges included a physically remote vivarium, prolonged (>10 h) anesthetic requirements, and the provision of veterinary operating room/intensive care unit (ICU) equivalency on-board an aircraft with physical dimensions of <1.5 m 2 (Falcon 20). Identification of an effective anesthetic regime is particularly important because inhalant anesthesia cannot be used in-flight. MethodsAfter ethical approval, multiple ground laboratory sessions were conducted with combinations of anesthetic, pre-medication, and induction protocols on Yorkshire-cross specific pathogen-free (SPF) pigs. Several constant rate infusion (CRI) intravenous anesthetic combinations were tested. In each regimen, opioids were administered to ensure analgesia. Ventilation was supported mechanically with blended gradients of oxygen. The best performing terrestrial 1 g regime was flight tested in parabolic flight for its effectiveness in sustaining optimal and prolonged anesthesia, analgesia, and maintaining hemodynamic stability. Each flight day, a fully anesthetized, ventilated, and surgically instrumented pig was transported to the Flight Research Laboratory (FRL) in a temperature-controlled animal ambulance. A modular on-board surgical/ICU suite with appropriate anesthesia/ICU and surgical support capabilities was employed. ResultsThe mean duration of anesthesia (per flight day) was 10.28 h over four consecutive days

Sudden death in the presence of overt beta-adrenergic receptor activation in guinea pigs immediately following isoflurane anesthesia.

PubMed

Overholser, Brian R; Zheng, Xiaomei; Pell, Carrie; Blickman, Andrew

2010-05-01

A case series of sudden death is reported in five consecutive guinea pigs following anesthesia with inhalational isoflurane during beta-adrenergic receptor stimulation with isoproterenol. Sustained-release isoproterenol pellets or mini-osmotic pumps were implanted subcutaneously in male Dunkin-Hartley guinea pigs as part of a research study to assess the interplay of adrenergic receptor activation and the development of atrial arrhythmias. The continuous exposure to isoproterenol resulted in a similar presentation and eventual sudden death in all guinea pigs exposed to inhalational isoflurane between 15 to 40 minutes after discontinuation of anesthesia. Death occurred in guinea pigs in this case series despite the fact that doses of isoproterenol used were more than 10-fold lower than previously reported in guinea pigs in the absence of isoflurane anesthesia. The cause of death was suspected to be due to an interaction of isoproterenol with isoflurane anesthesia, as placebo implantation or anesthesia alone did not result in cardiac arrest. Of four subsequent guinea pigs anesthetized with the combination of xylazine and ketamine (X/K), three survived isoproterenol implantation for the full 21-day study period while one died perioperatively. There was an increased rate of post-anesthetic mortality associated with isoproterenol pellet implantation in guinea pigs anesthetized with isoflurane compared to X/K. This may be due to the detrimental effects of the combination of isoflurane during overt beta-adrenergic receptor activation or cardioprotective effects of X/K anesthesia during beta-adrenergic receptor hyperactivity.

How Ketamine Affects Livers of Pregnant Mice and Developing Mice?

PubMed

Cheung, Hoi Man; Chow, Tony Chin Hung; Yew, David Tai Wai

2017-05-19

It is well known that ketamine abuse can induce liver damage in adult addicts, but the effects of ketamine abuse in pregnant mothers on their offspring have received less attention. In this study, we investigated the effects of 5-day ketamine injections (30 mg/kg) to pregnant Institute for Cancer Research (ICR) mice during early gestation or mid-gestation on the aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities of the mothers and the offspring. We also looked into whether administering ketamine treatment to the mothers had any effects on the extent of fibrosis, cell proliferation and cell death in the livers of the newborns. No significant biochemical differences were found between treatment and control groups in the mothers. In the offspring, ketamine treatment mildly suppressed the gradual increase of hepatic AST activity in neonates during liver maturation. Measurements of hepatic ALP activity and lactic acid dehydrogenase (LDH) immunoreactivity revealed that ketamine treatment may lead to increased cell death. Proliferation of liver cells of the newborns was also retarded as shown by reduced proliferative cell nuclear antigen (PCNA) immunoreactivity in the ketamine groups. No obvious fibrosis was evident. Thus, we demonstrated that ketamine administration to pregnant mice suppressed hepatic development and also induced liver cell death of the offspring.

S-ketamine influences strategic allocation of attention but not exogenous capture of attention.

PubMed

Fuchs, Isabella; Ansorge, Ulrich; Huber-Huber, Christoph; Höflich, Anna; Lanzenberger, Rupert

2015-09-01

We investigated whether s-ketamine differentially affects strategic allocation of attention. In Experiment 1, (1) a less visible cue was weakly masked by the onsets of competing placeholders or (2) a better visible cue was not masked because it was presented in isolation. Both types of cue appeared more often opposite of the target (75%) than at target position (25%). With this setup, we tested for strategic attention shifts to the opposite side of the cues and for exogenous attentional capture toward the cue's side in a short cue-target interval, as well as for (reverse) cueing effects in a long cue-target interval after s-ketamine and after placebo treatment in a double-blind within-participant design. We found reduced strategic attention shifts after cues presented without placeholders for the s-ketamine compared to the placebo treatment in the short interval, indicating an early effect on the strategic allocation of attention. No differences between the two treatments were found for exogenous attentional capture by less visible cues, suggesting that s-ketamine does not affect exogenous attentional capture in the presence of competing distractors. Experiment 2 confirmed that the competing onsets of the placeholders prevented the strategic cueing effect. Taken together, the results indicate that s-ketamine affects strategic attentional capture, but not exogenous attentional capture. The findings point to a more prominent role of s-ketamine during top-down controlled forms of attention that require suppression of automatic capture than during automatic capture itself. Copyright © 2015 Elsevier Inc. All rights reserved.

Ketamine, sleep, and depression: current status and new questions.

PubMed

Duncan, Wallace C; Zarate, Carlos A

2013-09-01

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has well-described rapid antidepressant effects in clinical studies of individuals with treatment-resistant major depressive disorder (MDD). Preclinical studies investigating the effects of ketamine on brain-derived neurotrophic factor (BDNF) and on sleep slow wave activity (SWA) support its use as a prototype for investigating the neuroplastic mechanisms presumably involved in the mechanism of rapidly acting antidepressants. This review discusses human EEG slow wave sleep parameters and plasma BDNF as central and peripheral surrogate markers of plasticity, and their use in assessing ketamine's effects. Acutely, ketamine elevates BDNF levels, as well as early night SWA and high-amplitude slow waves; each of these measures correlates with change in mood in depressed patients who respond to ketamine. The slow wave effects are limited to the first night post-infusion, suggesting that their increase is part of an early cascade of events triggering improved mood. Increased total sleep and decreased waking occur during the first and second night post infusion, suggesting that these measures are associated with the enduring treatment response observed with ketamine.

Interpretation of Do Not Attempt Resuscitation Orders for Children Requiring Anesthesia and Surgery.

PubMed

Fallat, Mary E; Hardy, Courtney

2018-05-01

This clinical report addresses the topic of pre-existing do not attempt resuscitation or limited resuscitation orders for children and adolescents undergoing anesthesia and surgery. Pertinent considerations for the clinician include the rights of children, decision-making by parents or legally approved representatives, the process of informed consent, and the roles of surgeon and anesthesiologist. A process of re-evaluation of the do not attempt resuscitation orders, called "required reconsideration," should be incorporated into the process of informed consent for surgery and anesthesia, distinguishing between goal-directed and procedure-directed approaches. The child's individual needs are best served by allowing the parent or legally approved representative and involved clinicians to consider whether full resuscitation, limitations based on procedures, or limitations based on goals is most appropriate. Copyright © 2018 by the American Academy of Pediatrics.

Environmental enrichment and abstinence attenuate ketamine-induced cardiac and renal toxicity

PubMed Central

Li, Xingxing; Li, Shuangyan; Zheng, Wenhui; Pan, Jian; Huang, Kunyu; Chen, Rong; Pan, Tonghe; Liao, Guorong; Chen, Zhongming; Zhou, Dongsheng; Shen, Wenwen; Zhou, Wenhua; Liu, Yu

2015-01-01

The current study was designed to investigate the effect of abstinence in combination with environmental enrichment (EE) on cardiac and renal toxicity induced by 2 weeks of ketamine self-administration (SA) in rodents. In Experiment 1, one group of rats underwent ketamine SA for 14 days. In Experiment 2, the animals completed 2 weeks of ketamine SA followed by 2 and 4 weeks of abstinence. In Experiment 3, animals underwent 14 days of ketamine SA and 4 weeks of abstinence in which isolated environment (IE) and EE was introduced. The corresponding control groups were included for each experiment. Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1, and apoptotic level of heart and kidney. The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney. Finally, introduction of EE during the period of abstinence greatly promoted the effect of abstinence on ketamine-induced cardiac and renal toxicity. The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine. PMID:26112338

Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats.

PubMed

Koizuka, Shiro; Obata, Hideaki; Sasaki, Masayuki; Saito, Shigeru; Goto, Fumio

2005-05-01

Systemic ketamine suppresses several types of chronic pain. Although ketamine is used as a general anesthetic agent, the analgesic effect of systemic ketamine for early-stage postoperative pain is not clear. We investigated the efficacy and mechanism of systemic ketamine in a rat model of postoperative pain. An incision was made in the plantar aspect of the left hind paw in male Wistar rats. Mechanical hypersensitivity was measured using calibrated von Frey filaments. The anti-hypersensitivity effect of systemic or intrathecal administration of ketamine was determined every hour after making the incision. We examined the effects of intrathecal pretreatment with yohimbine, an alpha2-adrenoceptor antagonist, and methysergide, a serotonergic receptor antagonist, on the anti-hypersensitivity effect of ketamine. We also examined the effect of systemic ketamine on the c-fos immunoreactivity in the spinal cord. Systemic administration of ketamine at doses from 3 to 30 mg.kg(-1) produced anti-hypersensitivity effects in a dose-dependent manner. Intrathecal administration of ketamine had no effect. There was no significant difference between effects of pre- and post-incisional administration. Intrathecal pretreatment with yohimbine (10 microg) or methysergide (15 microg) completely reversed the anti-hypersensitivity effects of systemic ketamine. Systemic ketamine reduced fos expression in laminae I-II in the dorsal horn of the lumbar spinal cord ipsilateral to the paw incision. The results suggest that systemic administration of ketamine perioperatively suppresses early-stage postoperative pain via monoaminergic descending inhibitory pathways.

Other drug use does not impact cognitive impairments in chronic ketamine users.

PubMed

Zhang, Chenxi; Tang, Wai Kwong; Liang, Hua Jun; Ungvari, Gabor Sandor; Lin, Shih-Ku

2018-05-01

Ketamine abuse causes cognitive impairments, which negatively impact on users' abstinence, prognosis, and quality of life. of cognitive impairments in chronic ketamine users have been inconsistent across studies, possibly due to the small sample sizes and the confounding effects of concomitant use of other illicit drugs. This study investigated the cognitive impairment and its related factors in chronic ketamine users with a large sample size and explored the impact of another drug use on cognitive functions. Cognitive functions, including working, verbal and visual memory and executive functions were assessed in ketamine users: 286 non-heavy other drug users and 279 heavy other drug users, and 261 healthy controls. Correlations between cognitive impairment and patterns of ketamine use were analysed. Verbal and visual memory were impaired, but working memory and executive functions were intact for all ketamine users. No significant cognitive differences were found between the two ketamine groups. Greater number of days of ketamine use in the past month was associated with worse visual memory performance in non-heavy other drug users. Higher dose of ketamine use was associated with worse short-term verbal memory in heavy other drug users. Verbal and visual memory are impaired in chronic ketamine users. Other drug use appears to have no impact on ketamine users' cognitive performance. Copyright © 2018. Published by Elsevier B.V.

General anesthesia selectively disrupts astrocyte calcium signaling in the awake mouse cortex

PubMed Central

Thrane, Alexander Stanley; Zeppenfeld, Douglas; Lou, Nanhong; Xu, Qiwu; Nagelhus, Erlend Arnulf; Nedergaard, Maiken

2012-01-01

Calcium signaling represents the principle pathway by which astrocytes respond to neuronal activity. General anesthetics are routinely used in clinical practice to induce a sleep-like state, allowing otherwise painful procedures to be performed. Anesthetic drugs are thought to mainly target neurons in the brain and act by suppressing synaptic activity. However, the direct effect of general anesthesia on astrocyte signaling in awake animals has not previously been addressed. This is a critical issue, because calcium signaling may represent an essential mechanism through which astrocytes can modulate synaptic activity. In our study, we performed calcium imaging in awake head-restrained mice and found that three commonly used anesthetic combinations (ketamine/xylazine, isoflurane, and urethane) markedly suppressed calcium transients in neocortical astrocytes. Additionally, all three anesthetics masked potentially important features of the astrocyte calcium signals, such as synchronized widespread transients that appeared to be associated with arousal in awake animals. Notably, anesthesia affected calcium transients in both processes and soma and depressed spontaneous signals, as well as calcium responses, evoked by whisker stimulation or agonist application. We show that these calcium transients are inositol 1,4,5-triphosphate type 2 receptor (IP3R2)-dependent but resistant to a local blockade of glutamatergic or purinergic signaling. Finally, we found that doses of anesthesia insufficient to affect neuronal responses to whisker stimulation selectively suppressed astrocyte calcium signals. Taken together, these data suggest that general anesthesia may suppress astrocyte calcium signals independently of neuronal activity. We propose that these glial effects may constitute a nonneuronal mechanism for sedative action of anesthetic drugs. PMID:23112168

Are Anesthesia Providers Ready for Hypnosis? Anesthesia Providers' Attitudes Toward Hypnotherapy.

PubMed

Stone, Alexander B; Sheinberg, Rosanne; Bertram, Amanda; Seymour, Anastasia Rowland

2016-04-01

This study sought to measure current attitudes toward hypnosis among anesthesia providers using an in-person survey distributed at a single grand rounds at a single academic teaching hospital. One hundred twenty-six anesthesia providers (anesthesiologists and nurse anesthetists) were included in this study. A 10-question Institutional Review Board (IRB)-approved questionnaire was developed. One hundred twenty-six (73% of providers at the meeting) anesthesia providers completed the survey. Of the respondents, 54 (43%) were anesthesiologists, 42 (33%) were trainees (interns/residents/fellows) in anesthesia, and 30 (24%) were nurse anesthetists. Over 70% of providers, at each level of training, rated their knowledge of hypnosis as either below average or having no knowledge. Fifty-two (42%) providers agreed or strongly agreed that hypnotherapy has a place in the clinical practice of anesthesia, while 103 (83%) believed that positive suggestion has a place in the clinical practice of anesthesia (p < .0001). Common reasons cited against using hypnosis were that it is too time consuming (41%) and requires special training (34%). Only three respondents (2%) believed that there were no reasons for using hypnosis in their practice. These data suggest that there is a self-reported lack of knowledge about hypnosis among anesthesia providers, although many anesthesia providers are open to the use of hypnosis in their clinical practice. Anesthesia providers are more likely to support the use of positive suggestion in their practice than hypnosis. Practical concerns should be addressed if hypnosis and therapeutic verbal techniques are to gain more widespread use.

The relationship of muscle perfusion and metabolism with cardiovascular variables before and after detomidine injection during propofol-ketamine anaesthesia in horses.

PubMed

Edner, Anna; Nyman, Görel; Essén-Gustavsson, Birgitta

2002-10-01

heart rate and cardiac output had not. No difference in indices of muscle metabolism was found between dependent and independent muscles. Anaerobic muscle metabolism, indicated by decreased muscle and creatine phosphate levels was evident after anaesthesia. Muscle perfusion was closely related to cardiac output but not arterial blood pressure. Total intravenous anaesthesia with propofol-ketamine deserves further study despite its respiratory depression effects, as the combination preserves cardiovascular function. Decreases in high-energy phosphate stores during recovery show that muscle is vulnerable after anaesthesia. Continued research is required to clarify the course of muscle metabolic events during recovery. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Chronic postthoracotomy pain and perioperative ketamine infusion.

PubMed

Hu, Jie; Liao, Qin; Zhang, Fan; Tong, Jianbin; Ouyang, Wen

2014-06-01

The objectives of this study were to investigate whether continuous intravenous ketamine during the first 72 hours after thoracotomy could reduce the incidence and intensity of chronic postthoracotomy pain (CPTP) and to define the incidence and risk factors of CPTP. Seventy-eight patients receiving thoracotomy for lung tumor (benign or malignant) were randomly divided into two groups: ketamine group (n = 31) and control groups (n = 47). Patients in the ketamine group received intravenous ketamine 1 mg/kg before incision, followed by 2 μg/kg/minute infusion for 72 hours plus sufentanil patient-controlled intravenous analgesia after thoracotomy. Patients in the control group received intravenous a 0.9% normal saline and infusion plus sufentanil patient-controlled intravenous analgesia. The solutions patients received were blinded. The numerical rating scale (NRS) pain scores and the incidence and risk factors of CPTP were recorded during the first 6 months after surgery. Compared with control group, the incidence of chronic pain in the ketamine group did not decrease at 2 months (χ(2) = 1.599, P = .206) and 6 months (χ(2) = 0.368, P = .544) after surgery. Postoperative pain scores in the ketamine group were not significantly different from those of the control group patients at 2 months (U = 677.5, P = .593) and 6 months (U = 690.5, P = .680). The incidence of CPTP was 78.2% (61/78) at 2 months and 53.8% (42/78) at 6 months after surgery. Retractor used time (OR = 5.811, P = .002), inadequate acute pain control (NRS ≥ 5) (OR = 5.425, P = .048), and chemotherapy (OR = 3.784, P = .056) were independent risk factors for chronic postthoracotomy pain. The authors conclude that continuous intravenous ketamine (2 μg/kg/min) during the first 72 hours after thoracotomy was not beneficial to prevent chronic postthoracotomy pain. The independent risk factors for chronic postthoracotomy pain were retractor used time, inadequate acute pain control, and chemotherapy.

Cognitive impairments in poly-drug ketamine users.

PubMed

Liang, H J; Lau, C G; Tang, A; Chan, F; Ungvari, G S; Tang, W K

2013-11-01

Cognitive impairment has been found to be reversible in people with substance abuse, particularly those using ketamine. Ketamine users are often poly-substance users. This study compared the cognitive functions of current and former ketamine users who were also abusing other psychoactive substances with those of non-users of illicit drugs as controls. One hundred ketamine poly-drug users and 100 controls were recruited. Drug users were divided into current (n = 32) and ex-users (n = 64) according to the duration of abstinence from ketamine (>30 days). The Beck Depression Inventory (BDI), the Hospital Anxiety Depression Scale (HADSA) and the Severity of Dependence Scale (SDS) were used to evaluate depression and anxiety symptoms and the severity of drug use, respectively. The cognitive test battery comprised verbal memory (Wechsler Memory Scale III: Logic Memory and Word List), visual memory (Rey-Osterrieth Complex Figure, ROCF), executive function (Stroop, Wisconsin Card Sorting Test, and Modified Verbal Fluency Test), working memory (Digit Span Backward), and general intelligence (Information, Arithmetic and Digit-Symbol Coding) tests. Current users had higher BDI and HADSA scores than ex-users (p < 0.001 for BDI and p = 0.022 for HADSA) and controls (p < 0.001 for BDI and p = 0.002 for HADSA). Ex-users had higher BDI (p = 0.006) but equal HADSA scores (p = 1.000) compared to controls. Both current and ex-users had lower scores on Logical Memory delayed recall (p = 0.038 for current users and p = 0.032 for ex-users) and ROCF delayed recall (p = 0.033 for current users and p = 0.014 for ex-users) than controls. Current users also performed worse on ROCF recognition than controls (p = 0.002). No difference was found between the cognitive functions of current and ex-users. Ketamine poly-drug users displayed predominantly verbal and visual memory impairments, which persisted in ex-users. The interactive effect of ketamine and poly-drug use on memory needs further

Ketamine for pain management in France, an observational survey.

PubMed

Martinez, Valeria; Derivaux, Benoit; Beloeil, Helene

2015-12-01

Before updating the French guidelines on postoperative pain treatment in 2015, the Pain Committee of the French Society of Anaesthesiology and Intensive Care (SFAR) conducted a survey on the medical use of ketamine in France. An online questionnaire was nationally distributed to members of SFAR, the French Pain Society (SFETD) and the French Society of Emergency Medicine (SFMU). The questionnaire included questions on demographic data, the type of patients for whom ketamine was prescribed, the doses used, the side effects and safety measures associated with the administration of ketamine. A total of 1388 questionnaires were analysed. Ninety-two percent of the responders declared that they used ketamine. Ketamine was widely used as anti-hyperalgesic medication but the modalities of administration and the doses varied greatly and were not in accordance with the guidelines. Despite the lack of evidence and guidelines, ketamine has also been used to treat acute and chronic pain. Doses, duration and localization of the patients during administration have varied greatly. Psychedelic effects and hallucinations are the most feared side effects. In terms of monitoring during ketamine infusion, 15% of physicians declared that no monitoring was necessary while 59%, 55%, 59% and 77% monitored heart rate, SpO2, blood pressure and level of consciousness, respectively. Anaesthesiologists have integrated the benefit of ketamine in preventing hyperalgesia but there is no consensus on doses and duration. For other indications (acute and chronic pain treatment), toxicity and the absence of significant benefit call for guidelines from scientific societies. Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Increasing Ketamine Use for Refractory Status Epilepticus in US Pediatric Hospitals.

PubMed

Keros, Sotirios; Buraniqi, Ersida; Alex, Byron; Antonetty, Annalee; Fialho, Hugo; Hafeez, Baria; Jackson, Michele C; Jawahar, Rachel; Kjelleren, Stephanie; Stewart, Elizabeth; Morgan, Lindsey A; Wainwright, Mark S; Sogawa, Yoshimi; Patel, Anup D; Loddenkemper, Tobias; Grinspan, Zachary M

2017-06-01

Ketamine is an emerging therapy for pediatric refractory status epilepticus. The circumstances of its use, however, are understudied. The authors described pediatric refractory status epilepticus treated with ketamine from 2010 to 2014 at 45 centers using the Pediatric Hospital Inpatient System database. For comparison, they described children treated with pentobarbital. The authors estimated that 48 children received ketamine and pentobarbital for refractory status epilepticus, and 630 pentobarbital without ketamine. Those receiving only pentobarbital were median age 3 [interquartile range 0-10], and spent 30 [18-52] days in-hospital, including 17 [9-28] intensive care unit (ICU) days; 17% died. Median cost was $148 000 [81 000-241 000]. The pentobarbital-ketamine group was older (7 [2-11]) with longer hospital stays (51 [30-93]) and more ICU days (29 [20-56]); 29% died. Median cost was $298 000 [176 000-607 000]. For 71%, ketamine was given ≥1 day after pentobarbital. Ketamine cases per half-year increased from 2 to 9 ( P < .05). Ketamine is increasingly used for severe pediatric refractory status epilepticus, typically after pentobarbital. Research on its effectiveness is indicated.

Role of ketamine in acute postoperative pain management: a narrative review.

PubMed

Radvansky, Brian M; Shah, Khushbu; Parikh, Anant; Sifonios, Anthony N; Le, Vanny; Eloy, Jean D

2015-01-01

The objective of this narrative review was to examine the usage of ketamine as a postoperative analgesic agent across a wide variety of surgeries. A literature search was performed using the phrases "ketamine" and "postoperative pain." The authors analyzed the studies that involved testing ketamine's effectiveness at controlling postoperative pain. Effectiveness was assessed through various outcomes such as the amount of opiate consumption, visual analog scale (VAS) pain scores, and persistent postoperative pain at long-term follow-up. While many different administration protocols were evaluated, delivering ketamine both as a pre- or perioperative bolus and postoperative infusion for up to 48 hours appeared to be the most effective. These effects are dose-dependent. However, a number of studies analyzed showed no benefit in using ketamine versus placebo for controlling postoperative pain. While ketamine is a safe and well-tolerated drug, it does have adverse effects, and there are concerns for possible neurotoxicity and effects on memory. In a number of limited situations, ketamine has shown some efficacy in controlling postoperative pain and decreasing opioid consumption. More randomized controlled trials are necessary to determine the surgical procedures and administrations (i.e., intravenous, epidural) that ketamine is best suited for.

Suppressed neural complexity during ketamine- and propofol-induced unconsciousness.

PubMed

Wang, Jisung; Noh, Gyu-Jeong; Choi, Byung-Moon; Ku, Seung-Woo; Joo, Pangyu; Jung, Woo-Sung; Kim, Seunghwan; Lee, Heonsoo

2017-07-13

Ketamine and propofol have distinctively different molecular mechanisms of action and neurophysiological features, although both induce loss of consciousness. Therefore, identifying a common feature of ketamine- and propofol-induced unconsciousness would provide insight into the underlying mechanism of losing consciousness. In this study we search for a common feature by applying the concept of type-II complexity, and argue that neural complexity is essential for a brain to maintain consciousness. To test this hypothesis, we show that complexity is suppressed during loss of consciousness induced by ketamine or propofol. We analyzed the randomness (type-I complexity) and complexity (type-II complexity) of electroencephalogram (EEG) signals before and after bolus injection of ketamine or propofol. For the analysis, we use Mean Information Gain (MIG) and Fluctuation Complexity (FC), which are information-theory-based measures that quantify disorder and complexity of dynamics respectively. Both ketamine and propofol reduced the complexity of the EEG signal, but ketamine increased the randomness of the signal and propofol decreased it. The finding supports our claim and suggests EEG complexity as a candidate for a consciousness indicator. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of ketamine-xylazine and isoflurane on insulin sensitivity in dehydroepiandrosterone sulfate-treated minipigs (Sus scrofa domestica).

PubMed

Heim, Kelly E; Morrell, Jesse S; Ronan, Anne M; Tagliaferro, Anthony R

2002-06-01

Isoflurane and ketamine-xylazine (KX) combinations are widely used veterinary anesthetics, KX being the particularly common agent for immobilizing swine. Results of previous studies indicate that KX and xylazine suppress insulin release. The steroid hormones, dehydroepiandrosterone (DHEA) and its sulfated form, dehydroepiandrosterone-sulfate (DHEAS), have variable effects on insulin sensitivity in animals. We evaluated the effect of DHEAS on plasma glucose and insulin concentrations in female Yucatan swine under KX and isoflurane anesthesia. A 2 x 2 factorial design was used. Twenty-four 17-week-old gilts were randomly assigned to receive vehicle (placebo) or DHEAS as part of an ongoing study. The KX was given intramuscularly to all animals prior to blood sample collection at weeks two and four. At week three, all animals received isoflurane by inhalation. During KX anesthesia, mean insulin concentration in DHEAS-treated and control groups approximated half the postisoflurane values (P < 0.001). While under isoflurane, the DHEAS group had significantly higher mean plasma insulin concentration and mean insulin-to-glucose ratio, compared with values for controls (P < 0.05). These findings are consistent with changes in insulin values following DHEAS treatment observed previously in nonanesthetized swine. The effect of DHEAS treatment was absent in animals under KX anesthesia. These results suggest that KX significantly decreases plasma insulin concentration and blunts DHEAS-associated insulin resistance in female minipigs.

[Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar].

PubMed

Kaneuchi, Miki; Kohri, Naonori; Senbongi, Kaname; Sakai, Hideo; Iseki, Ken

2005-02-01

Ketamine has been widely used in the operation as intravenous and intramuscular injections, since ketamine has dissociative anesthetic properties. When it is given in sub-anesthetic dose, ketamine is known to have an analgesic effect. The analgesic effect is observed for patients with neuropathic pain when administrated not only by injection but also orally. In Japan, since ketamine is not commercially available except injection forms, patients have to take it as solution of injections for the oral medication. Since the solution of injections has extremely bitter taste, patients intensely desire the development of preparations without the bitterness. In the present study, we prepared oral gel dosage forms of ketamine using agar. It is simple to prepare this dosage form, and most pharmacists can prepare it easily in many hospitals. This gel dosage form met content uniformity requirements and the shape of that was maintained intact during the dissolution test (for 10 hours). The release rate was reduced by additions of additives such as sugar and a flavor in the gel. The reason for the reduction in release could be the suppression of ketamine diffusion depended on the micro-viscosity of solution in the gel. The ketamine contents and the release profile of the gel preparations were unchanged at the room temperature for 12-week storage. The gel preparations in this study would be useful for the oral medication of ketamine, since it is easy for patients to carry them when they go out and the intensely bitter taste could be improved by the addition of a flavor.

Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions.

PubMed

Riva-Posse, Patricio; Reiff, Collin M; Edwards, Johnathan A; Job, Gregory P; Galendez, Gail C; Garlow, Steven J; Saah, Tammy C; Dunlop, Boadie W; McDonald, William M

2018-08-15

The dissociative anesthetic agent ketamine is increasingly being utilized to treat depression, despite not having FDA (Food and Drug Administration) approval for this indication. There are many questions about the potential risks of this treatment and hence the proper setting and degree of monitoring required to ensure patient safety. There is limited data about the cardiovascular safety of ketamine when administered at subanesthetic doses to treat depression. 66 patients in the Department of Psychiatry at Emory University received a total of 684 ketamine infusions between 2014 and 2016. Ketamine was dosed at 0.5 mg/kg body weight and infused over 40 min. Blood pressure was measured every 10 min during the infusions and every 15 min thereafter. Mean age of the patients was 56.7 years, 87.9% had unipolar depression and 36.1% had essential hypertension. No infusions were discontinued due to instability of vital signs, adverse physiological consequences or acute psychotomimetic effects. The biggest increases in blood pressure were measured at 30 min (systolic 3.28 mmHg, diastolic 3.17 mmHg). Hypertensive patients had higher blood pressure peaks during the infusions. Blood pressures returned to baseline during post-infusion monitoring. There was no development of tolerance to the blood pressure elevating effects of ketamine between the first and sixth infusions. This is a single site, retrospective analysis, of patients who were spontaneously seeking clinical care. The blood pressure changes observed when ketamine is administered over 40 min at 0.5 mg/kg for the treatment of depression are small, well tolerated and clinically insignificant. Copyright © 2018 Elsevier B.V. All rights reserved.

Ketamine as a first-line treatment for severely agitated emergency department patients.

PubMed

Riddell, Jeff; Tran, Alexander; Bengiamin, Rimon; Hendey, Gregory W; Armenian, Patil

2017-07-01

Emergency physicians often need to control agitated patients who present a danger to themselves and hospital personnel. Commonly used medications have limitations. Our primary objective was to compare the time to a defined reduction in agitation scores for ketamine versus benzodiazepines and haloperidol, alone or in combination. Our secondary objectives were to compare rates of medication redosing, vital sign changes, and adverse events in the different treatment groups. We conducted a single-center, prospective, observational study examining agitation levels in acutely agitated emergency department patients between the ages of 18 and 65 who required sedation medication for acute agitation. Providers measured agitation levels on a previously validated 6-point sedation scale at 0-, 5-, 10-, and 15-min after receiving sedation. We also assessed the incidence of adverse events, repeat or rescue medication dosing, and changes in vital signs. 106 patients were enrolled and 98 met eligibility criteria. There was no significant difference between groups in initial agitation scores. Based on agitation scores, more patients in the ketamine group were no longer agitated than the other medication groups at 5-, 10-, and 15-min after receiving medication. Patients receiving ketamine had similar rates of redosing, changes in vital signs, and adverse events to the other groups. In highly agitated and violent emergency department patients, significantly fewer patients receiving ketamine as a first line sedating agent were agitated at 5-, 10-, and 15-min. Ketamine appears to be faster at controlling agitation than standard emergency department medications. Copyright © 2017 Elsevier Inc. All rights reserved.

Memantine and Ketamine Differentially Alter NMDA Receptor Desensitization

PubMed Central

Povysheva, Nadezhda V.; Azofeifa, Andrea M.

2017-01-01

Memantine and ketamine are clinically useful NMDA receptor (NMDAR) open channel blockers that inhibit NMDARs with similar potency and kinetics, but display vastly different clinical profiles. This discrepancy has been hypothesized to result from inhibition by memantine and ketamine of overlapping but distinct NMDAR subpopulations. For example, memantine but not ketamine may inhibit extrasynaptic NMDARs more effectively than synaptic NMDARs. However, the basis for preferential NMDAR inhibition depending on subcellular location has not been investigated systematically. We integrated recordings from heterologously expressed single NMDAR subtypes, kinetic modeling, and recordings of synaptically evoked NMDAR responses in acute brain slices to investigate mechanisms by which channel blockers may distinguish NMDAR subpopulations. We found that memantine and ketamine differentially alter NMDAR desensitization and that memantine stabilizes a Ca2+-dependent desensitized state. As a result, inhibition by memantine of GluN1/2A receptors in tsA201 cells and of native synaptic NMDARs in cortical pyramidal neurons from mice of either sex increased in conditions that enhanced intracellular Ca2+ accumulation. Therefore, differential inhibition by memantine and ketamine based on NMDAR location is likely to result from location dependence of the intensity and duration of NMDAR activation. Modulation of Ca2+-dependent NMDAR desensitization is an unexplored mechanism of inhibitory action with the potential to endow drugs with NMDAR selectivity that leads to superior clinical profiles. Our results suggest that designing compounds to target specific receptor states, rather than specific receptor types, may be a viable strategy for future drug development. SIGNIFICANCE STATEMENT Memantine and ketamine are NMDA receptor (NMDAR) channel-blocking drugs with divergent clinical effects. Understanding mechanistically their differential actions may advance our understanding of nervous system

Memantine and Ketamine Differentially Alter NMDA Receptor Desensitization.

PubMed

Glasgow, Nathan G; Povysheva, Nadezhda V; Azofeifa, Andrea M; Johnson, Jon W

2017-10-04

Memantine and ketamine are clinically useful NMDA receptor (NMDAR) open channel blockers that inhibit NMDARs with similar potency and kinetics, but display vastly different clinical profiles. This discrepancy has been hypothesized to result from inhibition by memantine and ketamine of overlapping but distinct NMDAR subpopulations. For example, memantine but not ketamine may inhibit extrasynaptic NMDARs more effectively than synaptic NMDARs. However, the basis for preferential NMDAR inhibition depending on subcellular location has not been investigated systematically. We integrated recordings from heterologously expressed single NMDAR subtypes, kinetic modeling, and recordings of synaptically evoked NMDAR responses in acute brain slices to investigate mechanisms by which channel blockers may distinguish NMDAR subpopulations. We found that memantine and ketamine differentially alter NMDAR desensitization and that memantine stabilizes a Ca 2+ -dependent desensitized state. As a result, inhibition by memantine of GluN1/2A receptors in tsA201 cells and of native synaptic NMDARs in cortical pyramidal neurons from mice of either sex increased in conditions that enhanced intracellular Ca 2+ accumulation. Therefore, differential inhibition by memantine and ketamine based on NMDAR location is likely to result from location dependence of the intensity and duration of NMDAR activation. Modulation of Ca 2+ -dependent NMDAR desensitization is an unexplored mechanism of inhibitory action with the potential to endow drugs with NMDAR selectivity that leads to superior clinical profiles. Our results suggest that designing compounds to target specific receptor states, rather than specific receptor types, may be a viable strategy for future drug development. SIGNIFICANCE STATEMENT Memantine and ketamine are NMDA receptor (NMDAR) channel-blocking drugs with divergent clinical effects. Understanding mechanistically their differential actions may advance our understanding of nervous

Preincisional and postoperative epidural morphine, ropivacaine, ketamine, and naloxone treatment for postoperative pain management in upper abdominal surgery.

PubMed

Lai, Hou-Chuan; Hsieh, Chung-Bao; Wong, Chih-Shung; Yeh, Chun-Chang; Wu, Zhi-Fu

2016-09-01

Previous studies have shown that preincisional epidural morphine, bupivacaine, and ketamine combined with epidural anesthesia (EA) and general anesthesia (GA) provided pre-emptive analgesia for upper abdominal surgery. Recent studies reported that ultralow-dose naloxone enhanced the antinociceptive effect of morphine in rats. This study investigated the benefits of preincisional and postoperative epidural morphine + ropivacaine + ketamine + naloxone (M + R + K + N) treatment for achieving postoperative pain relief in upper abdominal surgery. Eighty American Society of Anesthesiology I-II patients scheduled for major upper abdominal surgery were allocated to four groups in a randomized, single-blinded study. All patients received combined GA and EA with a continuous epidural infusion of 2% lidocaine (6-8 mL/h) 30 minutes after pain regimen. After GA induction, in Group I, an epidural pain control regimen (total 10 mL) was administered using 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg; M + R); in Group II, 1% lidocaine 8 (mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg; M + R + K); in Group III, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + naloxone (2 μg; M + R + N); and in Group IV, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg) + naloxone (2 μg; M + R + K + N), respectively. All patients received patient-controlled epidural analgesia (PCEA) with different pain regimens to control subsequent postoperative pain for 3 days following surgery. During the 3-day period following surgery, PCEA consumption (mL), numerical rating scale (NRS) score while cough/moving, and analgesic-related adverse effects were recorded. Total PCEA consumption for the 3-day observation period was 161.5±17.8 mL, 103.2±21.7 mL, 152.4±25.6 mL, and 74.1±16.9 mL for Groups I, II, III, and IV, respectively. (p < 0.05). The cough/moving NRS

Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner.

PubMed

Holubova, Kristina; Kleteckova, Lenka; Skurlova, Martina; Ricny, Jan; Stuchlik, Ales; Vales, Karel

2016-06-01

The aim of our study was to test whether ketamine produces an antidepressant effect in animal model of olfactory bulbectomy and assess the role of mammalian target of rapamycin (mTOR) pathway in ketamine's antidepressant effect. Bulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they received (ketamine, saline, ketamine + rapamycin, and saline + rapamycin). The animals were subjected to open field (OF), elevated plus maze (EPM), passive avoidance (PA), Morris water maze (MWM), and Carousel maze (CM) tests. Blood samples were collected before and after drug administration for analysis of phosphorylated mTOR level. After behavioral testing, brains were removed for evaluation of brain-derived neurotrophic factor (BDNF) in prefrontal cortex (PFC) and hippocampus. Ketamine normalized hyperactivity of OBX animals in EPM and increased the time spent in open arms. Rapamycin pretreatment resulted in elimination of ketamine effect in EPM test. In CM test, ketamine + rapamycin administration led to cognitive impairment not observed in saline-, ketamine-, or saline + rapamycin-treated OBX rats. Prefrontal BDNF content was significantly decreased, and level of mTOR was significantly elevated in OBX groups. OBX animals significantly differed from sham controls in most of the tests used. Treatment had more profound effect on OBX phenotype than controls. Pretreatment with rapamycin eliminated the anxiolytic and antidepressant effects of ketamine in task-dependent manner. The results indicate that ketamine + rapamycin application resulted in impaired stress responses manifested by cognitive deficits in active place avoidance (CM) test. Intensity of stressor (mild vs. severe) used in the behavioral tests had opposite effect on controls and on OBX animals.

Repetitive Pediatric Anesthesia in a Non-Hospital Setting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchsbaum, Jeffrey C., E-mail: jbuchsba@iupui.edu; Indiana University Health Proton Therapy Center, Bloomington, Indiana; McMullen, Kevin P.

2013-04-01

Purpose: Repetitive sedation/anesthesia (S/A) for children receiving fractionated radiation therapy requires induction and recovery daily for several weeks. In the vast majority of cases, this is accomplished in an academic center with direct access to pediatric faculty and facilities in case of an emergency. Proton radiation therapy centers are more frequently free-standing facilities at some distance from specialized pediatric care. This poses a potential dilemma in the case of children requiring anesthesia. Methods and Materials: The records of the Indiana University Health Proton Therapy Center were reviewed for patients requiring anesthesia during proton beam therapy (PBT) between June 1, 2008,more » and April 12, 2012. Results: A total of 138 children received daily anesthesia during this period. A median of 30 fractions (range, 1-49) was delivered over a median of 43 days (range, 1-74) for a total of 4045 sedation/anesthesia procedures. Three events (0.0074%) occurred, 1 fall from a gurney during anesthesia recovery and 2 aspiration events requiring emergency department evaluation. All 3 children did well. One aspiration patient needed admission to the hospital and mechanical ventilation support. The other patient returned the next day for treatment without issue. The patient who fell was not injured. No patient required cessation of therapy. Conclusions: This is the largest reported series of repetitive pediatric anesthesia in radiation therapy, and the only available data from the proton environment. Strict adherence to rigorous protocols and a well-trained team can safely deliver daily sedation/anesthesia in free-standing proton centers.« less

Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ke, J.-J.; Chen, H.-I.; Jen, C.J.

2008-03-01

We hereby report that repeated administration of ketamine (350 mg/kg in total) and methamphetamine (30 mg/kg in total) causes specific glutamatergic and dopaminergic neuron deficits, respectively, in adult mouse brain. Acute ketamine did not affect basal body temperature or the later methamphetamine-induced hyperthermia. However, pretreatment with repeated doses of ketamine aggravated methamphetamine-induced dopaminergic terminal loss as evidenced by a drastic decrease in the levels of dopamine, 3,4-dihydroxyphenylacetic acid, and dopamine transporter density as well as poor gait balance performance. In contrast, methamphetamine-induced serotonergic depletion was not altered by ketamine pretreatment. Likewise, the subsequent treatment with methamphetamine exacerbated the ketamine-induced glutamatergicmore » damage as indicated by reduced levels of the vesicular glutamate transporter in hippocampus and striatum and poor memory performance in the Morris water maze. Finally, since activation of the D1 and AMPA/kainate receptors has been known to be involved in the release of glutamate and dopamine, we examined the effects of co-administration of SCH23390, a D1 antagonist, and CNQX, an AMPA/kainate antagonist. Intraventricular CNQX infusion abolished ketamine's potentiation of methamphetamine-induced dopamine neurotoxicity, while systemic SCH23390 mitigated methamphetamine's potentiation of ketamine-induced glutamatergic toxicity. We conclude that repeated doses of ketamine potentiate methamphetamine-induced dopamine neurotoxicity via AMPA/kainate activation and that conjunctive use of methamphetamine aggravates ketamine-induced glutamatergic neurotoxicity possibly via D1 receptor activation.« less

Differential regulation of GluA1 expression by ketamine and memantine.

PubMed

Zhang, Ke; Yamaki, Vitor Nagai; Wei, Zhisheng; Zheng, Yu; Cai, Xiang

2017-01-01

Evidence from preclinical and clinical studies shows that ketamine, a noncompetitive NMDA receptor antagonist, exerts rapid and sustained antidepressant responses. However, ketamine's psychotomimetic side effects and abuse liability limit the clinical use of the compound. Interestingly, memantine, another NMDA receptor channel blocker, processes no defined antidepressant property but is much safer and clinical tolerated. Understanding why ketamine but not memantine exhibits rapid antidepressant responses is important to elucidate the cellular signaling underlying the fast antidepressant actions of ketamine and to design a new safer generation of fast-acting antidepressants. Here we show that ketamine but memantine caused a rapid and sustained antidepressant-like responses in forced swim test (FST). Both drugs enhanced GluA1 S845 phosphorylation and potentiated Schaffer collateral-CA1 synaptic transmission. However, ketamine but not memantine elevated the expression of GluA1. Incubating acutely prepared hippocampal slices with ketamine but not memantine enhanced mTOR phosphorylation in a time course parallel to the time course of GluA1 elevation. Our results suggest that distinct properties in regulation of mTOR phosphorylation and synaptic protein expression may underlie the differential effectiveness of ketamine and memantine in their antidepressant responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive behavior therapy may sustain antidepressant effects of intravenous ketamine in treatment-resistant depression

PubMed Central

Wilkinson, Samuel T.; Wright, DaShaun; Fasula, Madonna K.; Fenton, Lisa; Griepp, Matthew; Ostroff, Robert B.; Sanacora, Gerard

2017-01-01

Introduction Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivate the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine's antidepressant effects. Methods Patients who were pursuing ketamine infusion therapy for treatment-resistant depression (TRD) were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5mg/kg infused over 40 mins) provided under a standardized clinical protocol. Results Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first two weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow up, 5 of 8 subjects eventually relapsed, the median time-to-relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine non-responders did not appear to benefit from CBT. Conclusions CBT may sustain the antidepressant effects of ketamine in TRD. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine's antidepressant effects. PMID:28490030

Effect of ketamine on endogenous pain modulation in healthy volunteers.

PubMed

Niesters, Marieke; Dahan, Albert; Swartjes, Maarten; Noppers, Ingeborg; Fillingim, Roger B; Aarts, Leon; Sarton, Elise Y

2011-03-01

Inhibitory and facilitatory descending pathways, originating at higher central nervous system sites, modulate activity of dorsal horn nociceptive neurons, and thereby influence pain perception. Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain. The N-methyl-d-aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients. This effect is due to desensitization of sensitized N-methyl-d-aspartate receptors. Additionally, ketamine may modulate or enhance endogenous inhibitory control of pain perception. Diffuse noxious inhibitory control (DNIC) and offset analgesia (OA) are 2 mechanisms involved in descending inhibition. The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control. Ten healthy subjects (4 men/6 women) received a 1-hour placebo or S(+)-ketamine (40mg per 70kg) infusion on 2 separate occasions in random order. Upon the termination of the infusion, DNIC and OA responses were obtained. After placebo treatment, significant descending inhibition of pain responses was present for DNIC and OA. In contrast, after ketamine infusion, no DNIC was observed, but rather a significant facilitatory pain response (P<0.01); the OA response remained unchanged. These findings suggest that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation. The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC. Diffuse noxious inhibitory control responses following a 1-hour low-dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights

Subanesthetic ketamine for pain management in hospitalized children, adolescents, and young adults: a single-center cohort study

PubMed Central

Sheehy, Kathy A; Lippold, Caroline; Rice, Amy L; Nobrega, Raissa; Finkel, Julia C; Quezado, Zenaide MN

2017-01-01

Background Subanesthetic doses of ketamine, an N-methyl-d-aspartate receptor antagonist used as an adjuvant to opioid for the treatment of pain in adults with acute and chronic pain, have been shown, in some instances, to improve pain intensity and to decrease opioid intake. However, less is known about the role of ketamine in pain management in children, adolescents, and young adults. Purpose We examined the effects of subanesthetic ketamine on pain intensity and opioid intake in children, adolescents, and young adults with acute and chronic pain syndromes treated in an inpatient setting. Methods This is a longitudinal cohort study of patients treated with subanesthetic ketamine infusions in regular patient care units in a tertiary pediatric hospital. Primary outcomes included changes in pain scores and morphine-equivalent intake. Results The study cohort included 230 different patients who during 360 separate hospital admissions received subanesthetic ketamine infusions for pain management. Overall, ketamine infusions were associated with significant reductions in mean pain scores from baseline (mean pain scores 6.64 [95% CI: 6.38–6.90]) to those recorded on the day after discontinuation of ketamine (mean pain scores 4.38 [95% CI: 4.06–4.69]), p<0.001. Importantly, the effect of ketamine on pain scores varied according to clinical diagnosis (p=0.011), infusion duration (p=0.004), and pain location (p=0.004). Interestingly, greater reductions in pain scores were observed in patients with cancer pain and patients with pain associated with pancreatitis and Crohn’s disease. There were no records of psychotomimetic side effects requiring therapy. Conclusion These data suggest that administration of subanesthetic ketamine for pain management is feasible and safe in regular inpatient care units and may benefit children, adolescents, and young adults with acute and chronic pain. This study is informative and can be helpful in determining sample and effect sizes

The effects of ketamine on sexual behavior, anxiety, and locomotion in female rats.

PubMed

Guarraci, Fay A; Gonzalez, Chantal M F; Lucero, Devon; Womble, Paige D; Abdel-Rahim, Heba; DeVore, Jennie; Kunkel, Marcela Nicole; Quadlander, Emma; Stinnett, Morgan; Boyette-Davis, Jessica

2018-02-01

The present study characterized the effects of ketamine on sexual behavior and anxiety in female rats. In Experiment 1, female subjects received an injection of ketamine (10.0mg/kg) or saline 30min prior to a sexual partner-preference test during which each female subject was given the opportunity to interact with a female stimulus or a sexually vigorous male stimulus. Immediately afterwards, female subjects were tested for locomotion in an open field test. Ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects. No other measures of mating behavior (i.e., paced mating behavior, lordosis) were affected by ketamine. Ketamine also had no effect on locomotion. In Experiment 2, female subjects received an injection of ketamine (10.0mg/kg), or saline daily for 10days to investigate the possibility that sexual dysfunction emerges only after repeated exposure. Similar to the results of Experiment 1, ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects. Chronic ketamine treatment also decreased the likelihood of leaving the male after mounts, without affecting any other measures of sexual behavior. Chronic ketamine had no effect on locomotion. In Experiment 3, female subjects received an injection of ketamine (10.0mg/kg) or saline and were tested for anxiety in an elevated plus maze test and for locomotion in an open field test. Acute ketamine had no effect on anxiety or locomotion. In Experiment 4, female subjects received an injection of ketamine (10.0mg/kg) or saline daily for 10days to investigate the possibility that anxiety emerges only after repeated exposure. Chronic ketamine exposure had no effect on any measure of anxiety. However, chronic ketamine exposure increased locomotion. The results from these experiments indicate that unlike other medications prescribed for depression, neither acute nor chronic ketamine treatment causes anxiety or disruption of

Optogenetic stimulation of infralimbic PFC reproduces ketamine's rapid and sustained antidepressant actions.

PubMed

Fuchikami, Manabu; Thomas, Alexandra; Liu, Rongjian; Wohleb, Eric S; Land, Benjamin B; DiLeone, Ralph J; Aghajanian, George K; Duman, Ronald S

2015-06-30

Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.

REVIEWING THE KETAMINE MODEL FOR SCHIZOPHRENIA

PubMed Central

Frohlich, Joel

2014-01-01

The observation that antagonists of the N-methyl-D-aspartate glutamate receptor (NMDAR), such as phencyclidine (PCP) and ketamine, transiently induce symptoms of acute schizophrenia had led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. The glutamate hypothesis can explain negative and cognitive symptoms of schizophrenia better than the dopamine hypothesis, and has the potential to explain dopamine dysfunction itself. The pharmacological and psychomimetic effects of ketamine, which is safer for human subjects than phencyclidine, are herein reviewed. Ketamine binds to a variety of receptors, but principally acts at the NMDAR, and convergent genetic and molecular evidence point to NMDAR hypofunction in schizophrenia. Furthermore, NMDAR hypofunction can explain connectional and oscillatory abnormalities in schizophrenia in terms of both weakened excitation of inhibitory -aminobutyric acidergic (GABAergic) interneurons that synchronize cortical networks and disinhibition of principal cells. Individuals with prenatal aberrations of NMDAR might experience the onset of schizophrenia towards the completion of synaptic pruning in adolescence, when network connectivity drops below a critical value. We conclude that ketamine challenge is useful for studying the positive, negative, and cognitive symptoms, dopaminergic and GABAergic dysfunction, age of onset, functional dysconnectivity, and abnormal cortical oscillations observed in acute schizophrenia. PMID:24257811

Subanesthetic ketamine infusions for the treatment of children and adolescents with chronic pain: a longitudinal study.

PubMed

Sheehy, Kathy A; Muller, Elena A; Lippold, Caroline; Nouraie, Mehdi; Finkel, Julia C; Quezado, Zenaide M N

2015-12-01

Chronic pain is common in children and adolescents and is often associated with severe functional disability and mood disorders. The pharmacological treatment of chronic pain in children and adolescents can be challenging, ineffective, and is mostly based on expert opinions and consensus. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been used as an adjuvant for treatment of adult chronic pain and has been shown, in some instances, to improve pain and decrease opioid-requirement. We examined the effects of subanesthetic ketamine infusions on pain intensity and opioid use in children and adolescents with chronic pain syndromes treated in an outpatient setting. Longitudinal cohort study of consecutive pediatric patients treated with subanesthetic ketamine infusions in a tertiary outpatient center. Outcome measurements included self-reported pain scores (numeric rating scale) and morphine-equivalent intake. Over a 15-month period, 63 children and adolescents (median age 15, interquartile range 12-17 years) with chronic pain received 277 ketamine infusions. Intravenous administration of subanesthetic doses of ketamine to children and adolescents on an outpatient basis was safe and not associated with psychotropic effects or hemodynamic perturbations. Overall, ketamine significantly reduced pain intensity (p < 0.001) and yielded greater pain reduction in patients with complex regional pain syndrome (CRPS) than in patients with other chronic pain syndromes (p = 0.029). Ketamine-associated reductions in pain scores were the largest in postural orthostatic tachycardia syndrome (POTS) and trauma patients and the smallest in patients with chronic headache (p = 0.007). In 37% of infusions, patients had a greater than 20 % reduction in pain score. Conversely, ketamine infusions did not change overall morphine-equivalent intake (p = 0.3). These data suggest that subanesthetic ketamine infusion is feasible in an outpatient setting and may benefit children and

Ketamine changes the local resting-state functional properties of anesthetized-monkey brain.

PubMed

Rao, Jia-Sheng; Liu, Zuxiang; Zhao, Can; Wei, Rui-Han; Zhao, Wen; Tian, Peng-Yu; Zhou, Xia; Yang, Zhao-Yang; Li, Xiao-Guang

2017-11-01

Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties. We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions. Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05). These findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status. Copyright © 2017. Published by Elsevier Inc.

Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide

PubMed Central

Ozguven, Ali A.; Yılmaz, Omer; Taneli, Fatma; Ulman, Cevval; Vatansever, Seda; Onag, Ali

2014-01-01

Objective: To investigate the possible protective effect of a single dose of ketamine and the synergistic effect between ketamine and 2-mercaptoethane sulfonate (mesna) against ifosfamide-induced hemorrhagic cystitis. Materials and Methods: 35 adult female wistar rats were divided into five groups and pretreated with ketamine at 10 mg/kg and/or mesna 400 mg/kg 30 minutes before intraperitoneal injection of IFS (400 mg/kg) or with saline (control group). Hemorrhagic cystitis was evaluated 24 hours after IFS injection according to bladder wet weight (BWW), and microscopic changes, i.e. edema, hemorrhage, cellular infiltration, and urothelial desquamation. The markers of oxidative damage including nitric oxide (NO) and malondialdehyde (MDA) levels and the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (i-NOS) and endothelial nitric oxide synthase (e-NOS) were also assayed in the bladder tissues. Results: Pretreatment with ketamine alone or ketamine in combination with mesna reduced the IFS-induced increase of BWW (58,47% and 63,33%, respectively, P < 0.05). IFS- induced microscopic alterations were also prevented by ketamine with or without mesna (P < 0.05). In addition, also statistically insignificant, the bladder tissue expressions of IL-1β were lower in ketamine and/or mesna-receiving groups (P > 0,05). The parameters of oxidative stress, the NO and the MDA contents of the bladder tissues of the study groups were not different. Conclusion: The results of the present study suggest that a single dose of ketamine pretreatment attenuates experimental IFS-induced bladder damage. It is therefore necessary to investigate ketamine locally and systematically with various dosing schedulesin order to reduce the bladder damage secondary to oxazaphosphorine-alkylating agents and these results may widen the spectrum of ketamine. PMID:24741183

Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil.

PubMed

Bourgoin, Aurélie; Albanèse, Jacques; Wereszczynski, Nicolas; Charbit, Martine; Vialet, Renaud; Martin, Claude

2003-03-01

The aim of the study was to compare the safety concerning cerebral hemodynamics of ketamine and sufentanil used for sedation of severe head injury patients, both drugs being used in combination with midazolam. Prospective, randomized, double-blind study. Intensive care unit in a trauma center. Twenty-five patients with severe head injury. Twelve patients received sedation with a continuous infusion of ketamine-midazolam and 13 with a continuous infusion of sufentanil-midazolam. All patients were mechanically ventilated with moderate hyperventilation. Prognostic indicators (age, Glasgow Coma Scale scores, computed tomography diagnosis, and Injury Severity Scale score) were similar in the two groups at study entry. Measurements were carried out during the first 4 days of sedation. The average infusion rates during this time were 82 +/- 25 micro x kg x min ketamine and 1.64 +/- 0.5 microg x kg x min midazolam in the ketamine group and 0.008 +/- 0.002 microg x kg x min sufentanil and 1.63 +/- 0.37 microg x kg x min midazolam in the sufentanil group. No significant differences were observed between the two groups in the mean daily values of intracranial pressure and cerebral perfusion pressure. The numbers of intracranial pressure elevations were similar in both groups. The requirements of neuromuscular blocking agents, propofol, and thiopental were similar. Heart rate values were significantly higher in the ketamine group on therapy days 3 and 4 ( <.05). With regard to arterial pressure control, more fluids were given on the first therapy day and there was a trend toward greater use of vasopressors in the sufentanil group. Sedative costs were similar in the two groups. The results of this study suggest that ketamine in combination with midazolam is comparable with a combination of midazolam-sufentanil in maintaining intracranial pressure and cerebral perfusion pressure of severe head injury patients placed under controlled mechanical ventilation.

Behavioral alterations of zebrafish larvae after early embryonic exposure to ketamine.

PubMed

Félix, Luís M; Antunes, Luís M; Coimbra, Ana M; Valentim, Ana M

2017-02-01

Ketamine has been associated with pediatric risks that include neurocognitive impairment and long-term behavioral disorders. However, the neurobehavioral effects of ketamine exposure in early development remain uncertain. This study aimed to test stage- and dose-dependent effects of ketamine exposure on certain brain functions by evaluating alterations in locomotion, anxiety-like and avoidance behaviors, as well as socialization. Embryos were exposed to different concentrations of ketamine (0, 0.2, 0.4, and 0.8 mg mL -1 ) for 20 min during the 256-cell (2.5 h post fertilization-hpf), 50% epiboly (5.5 hpf), and 1-4 somites (10.5 hpf) stages. General exploratory activities, natural escape-like responses, and social interactions were analyzed under continuous light or under a moving light stimulus. A dose-dependent decrease in the overall mean speed was perceived in the embryos exposed during the 256-cell stage. These results were related to previously observed head and eye malformations, following ketamine exposure at this stage and may indicate possible neurobehavioral disorders when ketamine exposure is performed at this stage. Results also showed that ketamine exposure during the 50% epiboly and 1-4 somites stages induced a significant increment of the anxiety-like behavior and a decrease in avoidance behavior in all exposed groups. Overall, the results validate the neurodevelopmental risks of early-life exposure to ketamine.

Use of xylazine hydrochloride-ketamine hydrochloride for immobilization of wild leopards (Panthera pardus fusca) in emergency situations.

PubMed

Belsare, Aniruddha V; Athreya, Vidya R

2010-06-01

In India, leopards (Panthera pardus fusca) inhabit human-dominated landscapes, resulting in encounters that require interventions to prevent harm to people, as well as the leopards. Immobilization is a prerequisite for any such intervention. Such emergency field immobilizations have to be carried out with limited tools, often amidst large uncontrollable crowds. An effective and practicable approach is discussed, based on 55 wild leopard immobilizations undertaken between January 2003 and April 2008. A xylazine hydrochloride (1.4 +/- 0.3 mg/kg)--ketamine hydrochloride (5 +/- 2 mg/kg) mixture was used for immobilization of leopards, based on estimated body weight. When weight could not be estimated, a standard initial dose of 50 mg of xylazine--150 mg of ketamine was used. Supplemental doses (50-75 mg) of only ketamine were used as required. No life-threatening adverse effects of immobilization were documented for at least 1 mo postimmobilization.

Intravenous Anesthesia With Bispectral Index Monitoring vs Inhalational Anesthesia for Rhytidoplasty: A Randomized Clinical Trial.

PubMed

Jones, Kristin A; LaFerriere, Keith A

2015-01-01

Minor adverse effects related to anesthesia are common and worrisome to patients, including perioperative vomiting, gagging on the endotracheal tube, incisional pain, and nausea. A previously published intravenous anesthesia protocol reports extremely low rates of postoperative nausea and vomiting (<1%) and decreases in postoperative pain perception compared with rates reported following administration of inhalational anesthetics. To evaluate and compare postoperative outcomes in patients after administration of combined propofol and ketamine hydrochloride anesthesia with bispectral index monitoring (PKA-BIS protocol) vs inhalational anesthesia (IA) during lower rhytidoplasty. We performed a prospective, double-blind, randomized comparison trial of the PKA-BIS protocol and IA in 30 consecutive female patients undergoing rhytidoplasty by a single surgeon at a single outpatient surgery center from October 2013 to June 2014. Outcome measures included nausea, vomiting, pain, overall feeling of well-being, time to awaken, time to discharge, and cost. Patient measures were recorded using a combination of a 40-item validated postoperative quality of recovery questionnaire (QOR-40) and visual analog scales (VASs). Results were recorded immediately after surgery and on postoperative days 1 and 7. A statistically significant reduction in emergence time (mean [SD], 29.8 [10.6] vs 46.0 [10.2] minutes; P < .001) and time to meet discharge criteria (51.4 [19.3] vs 66.1 [12.9] minutes; P = .02) was seen in patients in the PKA-BIS group. Patient-reported (subjective) postoperative nausea (3 of 15 [20%] vs 7 of 15 patients [47%]; P = .12; χ2 = 2.40), vomiting (0 vs 2 of 15 patients [13%]; P = .14; χ2 = 2.14), and confusion on the day of surgery (3 of 15 [20%] vs 6 of 14 patients [43%]; P = .18; χ2 = 1.77) were also decreased in the PKA-BIS group, but these differences did not reach significance. Differences in global recovery scores (QOR-40 scores

Sub-dissociative-dose intranasal ketamine for moderate to severe pain in adult emergency department patients.

PubMed

Yeaman, Fiona; Meek, Robert; Egerton-Warburton, Diana; Rosengarten, Pamela; Graudins, Andis

2014-06-01

There are currently no studies assessing effectiveness of sub-dissociative intranasal (IN) ketamine as the initial analgesic for adult patients in the ED. The study aims to examine the effectiveness of sub-dissociative IN ketamine as a primary analgesic agent for adult patients in the ED. This is a prospective, observational study of adult ED patients presenting with severe pain (≥6 on 11-point scale at triage). IN ketamine dose was 0.7 mg/kg, with secondary dose of 0.5 mg/kg at 15 min if pain did not improve. After 6 months, initial dose was increased to 1.0 mg/kg with the same optional secondary dose. The primary outcomes are change in VAS rating at 30 min; percentage of patients reporting clinically significant reduction in VAS (≥20 mm) at 30 min; dose resulting in clinically significant pain reduction. Of the 72 patients available for analysis, median age was 34.5 years and 64% were men. Median initial VAS rating was 76 mm (interquartile range [IQR]: 65-82). Median total dose of IN ketamine for all patients was 0.98 mg/kg (IQR: 0.75-1.15, range: 0.59-1.57). Median reduction in VAS rating at 30 min was 24 mm (IQR: 2-45). Forty (56%, 95% CI: 44.0-66.7) reported VAS reduction ≥20 mm, these patients having had a total median ketamine dose of 0.94 mg/kg (IQR: 0.72-1.04). IN ketamine, at a dose of about 1 mg/kg, was an effective analgesic agent in 56% of study patients. The place of IN ketamine in analgesic guidelines for adults requires further investigation. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Allergic Reaction to Ketamine as Monotherapy for Procedural Sedation.

PubMed

Nguyen, Tammy T; Baker, Bethany; Ferguson, Jeffrey D

2017-04-01

Ketamine is a cyclohexamine derivative that acts as a noncompetitive N-methyl D-aspartate receptor antagonist. Its use for procedural sedation is recommended by national clinical policy. However, its immunogenic potential is not well documented. We report a case of allergic reaction associated with the administration of intravenous ketamine for procedural sedation in a 16-year-old male. Minutes after administration, the patient developed a morbilliform, erythematous rash that extended to the upper and lower torso and resolved with intravenous diphenhydramine. It is most likely that this allergic reaction was caused by a ketamine-induced histamine release that has been described in vitro. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This is the first case report in which ketamine was used as monotherapy in the emergency department for the facilitation of procedural sedation that resulted in an allergic reaction. Supportive measures, including advanced airway procedures and hemodynamic support, may be necessary in more severe anaphylactic cases. Providers should be aware of this potential adverse effect when using ketamine for procedural sedation. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults.

PubMed

Lofwall, Michelle R; Griffiths, Roland R; Mintzer, Miriam Z

2006-11-01

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) antagonist. Given the purported role of the NMDA receptor in long-term potentiation, the primary purpose of the present study was to further understand the dose-related effects of ketamine on memory. The study was also designed to provide information about the relative effects of ketamine on memory versus nonmemory effects and to more fully characterize ketamine's overall pattern and time course of effects. Single intramuscular injections of ketamine (0.2 mg/kg, 0.4 mg/kg) were administered to 18 healthy adult volunteers using a double-blind, placebo-controlled, crossover design. Word lists were used to evaluate episodic memory (free recall, recognition memory, source memory) and metamemory. Working memory, time estimation, psychomotor performance, and subjective effects were assessed repeatedly for 5 hours after drug administration. Ketamine selectively impaired encoding (as measured by free recall) while sparing retrieval, working memory while sparing attention, and digit symbol substitution task speed while sparing accuracy. Ketamine did not significantly impair recognition or source memory, metamemory, or time estimation. There were no hallucinations or increases in mystical experiences with ketamine. Memory measures were less sensitive to ketamine effects than subjective or psychomotor measures. Subjective effects lasted longer than memory and most psychomotor impairments. Ketamine produces selective, transient, dose- and time-related effects. In conjunction with previous studies of drugs with different mechanisms of actions, the observed selectivity of effects enhances the understanding of the pharmacological mechanisms underlying memory, attention, psychomotor performance, and subjective experience.

Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex.

PubMed

Abelaira, Helena M; Réus, Gislaine Z; Ignácio, Zuleide M; Dos Santos, Maria Augusta B; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Michels, Monique; Abatti, Mariane; Sonai, Beatriz; Dal Pizzol, Felipe; Carvalho, André F; Quevedo, João

2017-04-01

Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol), or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) - alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

To use or not to use: an update on licit and illicit ketamine use

PubMed Central

Li, Jih-Heng; Vicknasingam, Balasingam; Cheung, Yuet-Wah; Zhou, Wang; Nurhidayat, Adhi Wibowo; Jarlais, Don C Des; Schottenfeld, Richard

2011-01-01

Ketamine, a derivative of phencyclidine that was developed in the 1960s, is an anesthetic and analgesic with hallucinogenic effects. In this paper, the pharmacological and toxicological effects of ketamine are briefly reviewed. Ketamine possesses a wide safety margin but such a therapeutic benefit is somewhat offset by its emergence phenomenon (mind-body dissociation and delirium) and hallucinogenic effects. The increasing abuse of ketamine, initially predominantly in recreational scenes to experience a “k-hole” and other hallucinatory effects but more recently also as a drug abused during the workday or at home, has further pushed governments to confine its usage in many countries. Recently, urinary tract dysfunction has been associated with long-term ketamine use. In some long-term ketamine users, such damage can be irreversible and could result in renal failure and dialysis. Although ketamine has not yet been scheduled in the United Nations Conventions, previous studies using different assessment parameters to score the overall harms of drugs indicated that ketamine may cause more harm than some of the United Nations scheduled drugs. Some countries in Southeast and East Asia have reported an escalating situation of ketamine abuse. Dependence, lower urinary tract dysfunction, and sexual impulse or violence were the most notable among the ketamine-associated symptoms in these countries. These results implied that the danger of ketamine may have been underestimated previously. Therefore, the severity levels of the ketamine-associated problems should be scrutinized more carefully and objectively. To prevent ketamine from being improperly used and evolving into an epidemic, a thorough survey on the prevalence and characteristics of illicit ketamine use is imperative so that suitable policy and measures can be taken. On the other hand, recent findings that ketamine could be useful for treating major depressive disorder has given this old drug a new impetus. If

No-anesthesia clear corneal phacoemulsification versus topical and topical plus intracameral anesthesia. Randomized clinical trial.

PubMed

Pandey, S K; Werner, L; Apple, D J; Agarwal, A; Agarwal, A; Agarwal, S

2001-10-01

To compare the intraoperative pain scores during clear corneal phacoemulsification under no anesthesia, topical anesthesia, and topical plus intracameral anesthesia. Dr. Agarwal's Eye Hospital and Eye Research Center, Chennai, India. Seventy-five patients were randomized to have phacoemulsification under no anesthesia, topical anesthesia, or topical plus intracameral anesthesia. Uncooperative or illiterate patients and those with hard cataract, a shallow anterior chamber, or small pupils were excluded. A protocol was established for supplemental anesthesia in case of breakthrough pain during the surgery. Each patient was asked to grade the overall severity of intraoperative pain immediately after surgery on a 10-point visual analog scale. Also evaluated were the general discomfort during surgery, discomfort from the microscope lights, surgeon stress during surgery, and total surgical time. Comparison among the 3 groups was performed using an analysis of variance. No supplemental anesthesia was required in any group. No significant difference was noted in the mean scores of the subjective sensation of pain with or without topical anesthesia (P =.610). The mean scores of patient discomfort from the microscope lights and surgical time were also statistically insignificant. Patient discomfort and surgeon stress during surgery were significantly greater in the no-anesthesia group than in the topical and topical plus intracameral groups (P =.0235 and P = 0.0206, respectively). No-anesthesia clear corneal phacoemulsification was performed by a highly experienced, skilled surgeon without causing an unacceptable level of pain. However, this technique is not suitable for every cataract surgeon or patient.

Oral ketamine for sickle cell crisis pain refractory to opioids.

PubMed

Jennings, Cara A; Bobb, Barton T; Noreika, Danielle M; Coyne, Patrick J

2013-06-01

There is literature demonstrating that the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has analgesic properties that can be used as an adjuvant to opiates for pain relief in multiple various conditions and pain states. However, there is a lack of published information on ketamine used in persons with sickle cell disease in acute pain crises. The Virginia Commonwealth University Palliative Care team was consulted on a 38-year-old African American female with sickle cell thalassemia in severe acute pain crisis overlying chronic pain related to her disease. Pain control was unable to be achieved with escalating doses of opiates and other adjuvant medications. The patient responded well to an intravenous test dose of ketamine and was subsequently placed on an oral regimen of ketamine in addition to opiates. In the 24-hour period following ketamine initiation, the patient's pain was able to be controlled on decreased amounts of opiates. She was eventually transitioned to an oral opiate and ketamine regimen, which allowed her to be discharged home with pain levels close to her baseline and the ability to function and perform all activities of daily living.

Effective and Safe Anesthesia for Yorkshire and Yucatan Swine with and without Cardiovascular Injury and Intervention

PubMed Central

Linkenhoker, Jan R; Burkholder, Tanya H; Linton, CG Garry; Walden, April; Abusakran-Monday, Kim A; Rosero, Ana P; Foltz, Charmaine J

2010-01-01

The goal of this study was to identify an injectable anesthetic protocol that provides sedation sufficient for peripheral vascular catheterization, intubation, and transport while minimizing cardiovascular changes in Yorkshire and Yucatan pigs with and without cardiovascular injury and intervention (CI). Phase 1 examined the safety and efficacy of acepromazine–ketamine, diazepam–ketamine, midazolam–ketamine, and medetomidine–ketamine in 5 healthy Yorkshire pigs. For each drug combination, we obtained multiple measurements of heart rate, blood pressure, respiratory rate, temperature, sedation score, ability to catheterize and intubate, and recovery score. Phase 2 evaluated and refined the dose of the most effective Phase 1 anesthetic combination (midazolam–ketamine) in healthy and CI Yorkshire pigs (n = 53 trials). Phase 3 mirrored Phase 2 but tested midazolam–ketamine in healthy and CI Yucatan pigs (n = 34 trials). Midazolam (0.5 mg/kg)–ketamine (25 to 27 mg/kg) was the most effective anesthetic combination in healthy Yorkshire pigs, but this dose was less effective in healthy Yucatan pigs and CI Yorkshire and Yucatan pigs. Midazolam–ketamine resulted in tachycardia and apnea more frequently in CI pigs than healthy pigs. This combination also caused vomiting in one CI Yucatan pig. Overall, midazolam–ketamine provided safe and effective sedation for catheterization and intubation of both healthy and CI pigs. This study suggests Yucatan pigs may require a higher dose midazolam–ketamine to achieve the same level of sedation as that in Yorkshire pigs. Although anesthetic complication rates were higher in CI pigs, our results indicate that midazolam–ketamine can be safely used for sedation of both pig breeds with and without CI. PMID:20587167

Recent insights into the mode of action of memantine and ketamine

PubMed Central

Johnson, Jon W.; Glasgow, Nathan G.; Povysheva, Nadezhda V.

2014-01-01

The clinical benefits of the glutamate receptor antagonists memantine and ketamine have helped sustain optimism that glutamate receptors represent viable targets for development of therapeutic drugs. Both memantine and ketamine antagonize N-methyl-d-aspartate receptors (NMDARs), a glutamate receptor subfamily, by blocking the receptor-associated ion channel. Although many of the basic characteristics of NMDAR inhibition by memantine and ketamine appear similar, their effects on humans and to a lesser extent on rodents are strongly divergent. Some recent research suggests that preferential inhibition by memantine and ketamine of distinct NMDAR subpopulations may contribute to the drugs' differential clinical effects. Here we review studies that shed light on possible explanations for differences between the effects of memantine and ketamine. PMID:25462293

A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

PubMed Central

Lapidus, Kyle A.B.; Levitch, Cara F.; Perez, Andrew M.; Brallier, Jess W.; Parides, Michael K.; Soleimani, Laili; Feder, Adriana; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.

2014-01-01

Background The N-methyl-d-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Methods Twenty patients with major depression were randomized and 18 completed two treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution in a randomized, double-blind, crossover study. The primary efficacy outcome measure was change in depression severity 24 hours following ketamine or placebo, measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Results Patients showed significant improvement in depressive symptoms at 24 hours following ketamine compared to placebo [t=4.39, p<0.001; estimated mean MADRS score difference of 7.6 ± 3.7 (95% CI: 3.9 – 11.3)]. Eight of 18 patients (44%) met response criteria 24 hours following ketamine administration, compared to 1 of 18 (6%) following placebo (p=0.033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. Conclusions This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression. Trial Registration clinicaltrials.gov identifier NCT01304147 PMID:24821196

Previous Ketamine Produces an Enduring Blockade of Neurochemical and Behavioral Effects of Uncontrollable Stress

PubMed Central

Dolzani, Samuel D.; Tilden, Scott; Christianson, John P.; Kubala, Kenneth H.; Bartholomay, Kristi; Sperr, Katherine; Ciancio, Nicholas; Watkins, Linda R.; Maier, Steven F.

2016-01-01

Recent interest in the antidepressant and anti-stress effects of subanesthetic doses of ketamine, an NMDA receptor antagonist, has identified mechanisms whereby ketamine reverses the effect of stress, but little is known regarding the prophylactic effect ketamine might have on future stressors. Here we investigate the prophylactic effect of ketamine against neurochemical and behavioral changes that follow inescapable, uncontrollable tail shocks (ISs) in Sprague Dawley rats. IS induces increased anxiety, which is dependent on activation of serotonergic (5-HT) dorsal raphe nucleus (DRN) neurons that project to the basolateral amygdala (BLA). Ketamine (10 mg/kg, i.p.) administered 2 h, 1 week, or 2 weeks before IS prevented the increased extracellular levels of 5-HT in the BLA typically produced by IS. In addition, ketamine administered at these time points blocked the decreased juvenile social investigation produced by IS. Microinjection of ketamine into the prelimbic (PL) region of the medial prefrontal cortex duplicated the effects of systemic ketamine, and, conversely, systemic ketamine effects were prevented by pharmacological inhibition of the PL. Although IS does not activate DRN-projecting neurons from the PL, IS did so after ketamine, suggesting that the prophylactic effect of ketamine is a result of altered functioning of this projection. SIGNIFICANCE STATEMENT The reported data show that systemic ketamine, given up to 2 weeks before a stressor, blunts behavioral and neurochemical effects of the stressor. The study also advances understanding of the mechanisms involved and suggests that ketamine acts at the prelimbic cortex to sensitize neurons that project to and inhibit the DRN. PMID:26740657

Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction

PubMed Central

Rajandram, Retnagowri; Ong, Teng Aik; Razack, Azad H. A.; MacIver, Bryce; Zeidel, Mark

2016-01-01

Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg−1·day−1 ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis. PMID:26911853

Ketamine Causes Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Neurons

PubMed Central

Ito, Hiroyuki; Uchida, Tokujiro; Makita, Koshi

2015-01-01

Purpose Ketamine toxicity has been demonstrated in nonhuman mammalian neurons. To study the toxic effect of ketamine on human neurons, an experimental model of cultured neurons from human induced pluripotent stem cells (iPSCs) was examined, and the mechanism of its toxicity was investigated. Methods Human iPSC-derived dopaminergic neurons were treated with 0, 20, 100 or 500 μM ketamine for 6 and 24 h. Ketamine toxicity was evaluated by quantification of caspase 3/7 activity, reactive oxygen species (ROS) production, mitochondrial membrane potential, ATP concentration, neurotransmitter reuptake activity and NADH/NAD+ ratio. Mitochondrial morphological change was analyzed by transmission electron microscopy and confocal microscopy. Results Twenty-four-hour exposure of iPSC-derived neurons to 500 μM ketamine resulted in a 40% increase in caspase 3/7 activity (P < 0.01), 14% increase in ROS production (P < 0.01), and 81% reduction in mitochondrial membrane potential (P < 0.01), compared with untreated cells. Lower concentration of ketamine (100 μM) decreased the ATP level (22%, P < 0.01) and increased the NADH/NAD+ ratio (46%, P < 0.05) without caspase activation. Transmission electron microscopy showed enhanced mitochondrial fission and autophagocytosis at the 100 μM ketamine concentration, which suggests that mitochondrial dysfunction preceded ROS generation and caspase activation. Conclusions We established an in vitro model for assessing the neurotoxicity of ketamine in iPSC-derived neurons. The present data indicate that the initial mitochondrial dysfunction and autophagy may be related to its inhibitory effect on the mitochondrial electron transport system, which underlies ketamine-induced neural toxicity. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons. PMID:26020236

Ketamine Exhibits Different Neuroanatomical Profile After Mammalian Target of Rapamycin Inhibition in the Prefrontal Cortex: the Role of Inflammation and Oxidative Stress.

PubMed

Abelaira, Helena M; Réus, Gislaine Z; Ignácio, Zuleide M; Dos Santos, Maria Augusta B; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Danielski, Lucineia G; Petronilho, Fabricia; Carvalho, André F; Quevedo, João

2017-09-01

Studies indicated that mammalian target of rapamycin (mTOR), oxidative stress, and inflammation are involved in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been identified as a novel MDD therapy; however, the antidepressant mechanism is not fully understood. In addition, the effects of ketamine after mTOR inhibition have not been fully investigated. In the present study, we examined the behavioral and biochemical effects of ketamine in the prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens after inhibition of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol) or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). Immobility was assessed in forced swimming tests, and then oxidative stress parameters and inflammatory markers were evaluated in the brain and periphery. mTOR activation in the PFC was essential to ketamine's antidepressant-like effects. Ketamine increased lipid damage in the PFC, hippocampus, and amygdala. Protein carbonyl was elevated in the PFC, amygdala, and NAc after ketamine administration. Ketamine also increased nitrite/nitrate in the PFC, hippocampus, amygdala, and NAc. Myeloperoxidase activity increased in the hippocampus and NAc after ketamine administration. The activities of superoxide dismutase and catalase were reduced after ketamine administration in all brain areas studied. Inhibition of mTOR signaling pathways by rapamycin in the PFC was required to protect against oxidative stress by reducing damage and increasing antioxidant enzymes. Finally, the TNF-α level was increased in serum by ketamine; however, the rapamycin plus treatment group was not able to block this increase. Activation of mTOR in the PFC is involved in the antidepressant-like effects of ketamine; however, the inhibition of this pathway was able to protect certain brain areas against

Ketamine infusion for refractory status epilepticus: A case report of cardiac arrest.

PubMed

Koffman, Lauren; Yan Yiu, Ho; Farrokh, Salia; Lewin, John; Geocadin, Romergryko; Ziai, Wendy

2018-01-01

Refractory status epilepticus (RSE) has a high mortality rate and is often difficult to treat. When traditional therapies fail ketamine may be considered. There are limited reports of adverse cardiac events with the use of ketamine for RSE and no reports of cardiac arrest in this context. Evaluate the occurrence of cardiac arrhythmias associated with the use of ketamine for RSE. Retrospective chart review of nine patients who underwent ketamine infusion for RSE. Etiology of refractory status epilepticus included autoimmune/infectious process (Zeiler et al., 2014), ischemic stroke (Bleck, 2005) and subarachnoid hemorrhage (Bleck, 2005). Of the nine patients who received ketamine, two had documented cardiac events; one remained clinically stable and the other developed multiple arrhythmias, including recurrent episodes of asystole. Once ketamine was discontinued the latter patient stabilized with the addition of anti arrhythmic therapy. Ketamine is utilized to treat refractory status epilepticus, but should be used with caution in patients with subarachnoid hemorrhage, as there may be an increased risk of life threatening arrhythmias and cardiac arrest. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of Ketamine in Acute Postoperative Pain Management: A Narrative Review

PubMed Central

Radvansky, Brian M.; Shah, Khushbu; Parikh, Anant; Sifonios, Anthony N.; Eloy, Jean D.

2015-01-01

Objectives. The objective of this narrative review was to examine the usage of ketamine as a postoperative analgesic agent across a wide variety of surgeries. Design. A literature search was performed using the phrases “ketamine” and “postoperative pain.” The authors analyzed the studies that involved testing ketamine's effectiveness at controlling postoperative pain. Effectiveness was assessed through various outcomes such as the amount of opiate consumption, visual analog scale (VAS) pain scores, and persistent postoperative pain at long-term follow-up. Results. While many different administration protocols were evaluated, delivering ketamine both as a pre- or perioperative bolus and postoperative infusion for up to 48 hours appeared to be the most effective. These effects are dose-dependent. However, a number of studies analyzed showed no benefit in using ketamine versus placebo for controlling postoperative pain. While ketamine is a safe and well-tolerated drug, it does have adverse effects, and there are concerns for possible neurotoxicity and effects on memory. Conclusions. In a number of limited situations, ketamine has shown some efficacy in controlling postoperative pain and decreasing opioid consumption. More randomized controlled trials are necessary to determine the surgical procedures and administrations (i.e., intravenous, epidural) that ketamine is best suited for. PMID:26495312

Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit.

PubMed

Flint, Robert B; Brouwer, Carole N M; Kränzlin, Anne S C; Lie-A-Huen, Loraine; Bos, Albert P; Mathôt, Ron A A

2017-11-01

S-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S-ketamine is observed during long-term sedation. The aim of this study was to evaluate the pharmacokinetic variability of S-ketamine in children aged 0-18 years during long-term sedation. Twenty-five children (median age: 0.42 years, range: 0.02-12.5) received continuous intravenous administrations of 0.3-3.6 mg/kg/h S-ketamine for sedation during mechanical ventilation. Infusion rates were adjusted to the desired level of sedation and analgesia based on the COMFORT-B score and Visual Analog Scale. Blood samples were drawn once daily at random time-points, and at 1 and 4 hours after discontinuation of S-ketamine infusion. Time profiles of plasma concentrations of S-ketamine and active metabolite S-norketamine were analyzed using nonlinear mixed-effects modeling software. Clearance and volume of distribution were allometrically scaled using the ¾ power model. A total of 86 blood samples were collected. A 2-compartment and 1-compartment model adequately described the PK of S-ketamine and S-norketamine, respectively. The typical parameter estimates for clearance and central and peripheral volumes of distribution were: CL S - KETAMINE =112 L/h/70 kg, V1 S- KETAMINE =7.7 L/70 kg, V2 S- KETAMINE =545L/70 kg, Q S - kETAMINE =196 L/h/70 kg, and CL S - NORKETAMINE =53 L/h/70 kg. Interpatient variability of CL S - KETAMINE and CL S - NORKETAMINE was considerable with values of 40% and 104%, respectively, leading to marked variability in steady-state plasma concentrations. Substantial interpatient variability in pharmacokinetics in children complicates the development of adequate dosage regimen for continuous sedation. © 2017 John Wiley & Sons Ltd.

Gradual emergence of spontaneous correlated brain activity during fading of general anesthesia in rats: Evidences from fMRI and local field potentials

PubMed Central

Bettinardi, Ruggero G.; Tort-Colet, Núria; Ruiz-Mejias, Marcel; Sanchez-Vives, Maria V.; Deco, Gustavo

2015-01-01

Intrinsic brain activity is characterized by the presence of highly structured networks of correlated fluctuations between different regions of the brain. Such networks encompass different functions, whose properties are known to be modulated by the ongoing global brain state and are altered in several neurobiological disorders. In the present study, we induced a deep state of anesthesia in rats by means of a ketamine/medetomidine peritoneal injection, and analyzed the time course of the correlation between the brain activity in different areas while anesthesia spontaneously decreased over time. We compared results separately obtained from fMRI and local field potentials (LFPs) under the same anesthesia protocol, finding that while most profound phases of anesthesia can be described by overall sparse connectivity, stereotypical activity and poor functional integration, during lighter states different frequency-specific functional networks emerge, endowing the gradual restoration of structured large-scale activity seen during rest. Noteworthy, our in vivo results show that those areas belonging to the same functional network (the default-mode) exhibited sustained correlated oscillations around 10 Hz throughout the protocol, suggesting the presence of a specific functional backbone that is preserved even during deeper phases of anesthesia. Finally, the overall pattern of results obtained from both imaging and in vivo-recordings suggests that the progressive emergence from deep anesthesia is reflected by a corresponding gradual increase of organized correlated oscillations across the cortex. PMID:25804643

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.

PubMed

Taylor, Jerome H; Landeros-Weisenberger, Angeli; Coughlin, Catherine; Mulqueen, Jilian; Johnson, Jessica A; Gabriel, Daniel; Reed, Margot O; Jakubovski, Ewgeni; Bloch, Michael H

2018-01-01

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F 9,115 =2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F 10,141 =0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

Studies of Circulatory and Metabolic Changes during Ketamine Narcosis,

DTIC Science & Technology

1985-03-13

Braun, U., Hensel, I., Kettler, D., Lohr, B.: The effects of methoxyflurane , halothane, dipiritramide, barbiturate and ketamine on the total oxygen...narcosis caus- ed by ether, halothane, methoxyflurane , ketamine and piritranide, as well as neuroleptanalgesia. Lecture at the XIIth. General Con

Kynurenine pathway metabolism and the neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy.

PubMed

Allen, A P; Naughton, M; Dowling, J; Walsh, A; O'Shea, R; Shorten, G; Scott, L; McLoughlin, D M; Cryan, J F; Clarke, G; Dinan, T G

2018-05-01

Current first-line antidepressants can take weeks or months to decrease depressive symptoms. Low dose ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, shows potential for a more rapid antidepressant effect, with efficacy also evident in previously treatment-resistant populations. However, a greater understanding of the physiological mechanisms underlying such effects is required. We assessed the potential impact of ketamine infusion on neurobiological drivers of kynurenine pathway metabolism in major depression (HPA axis hyperactivity, inflammation) in patients with treatment-resistant depression compared to gender-matched healthy controls. Furthermore, we assessed these biomarkers before and after electroconvulsive therapy (ECT), which is currently the gold standard for management of treatment-resistant depression. As previously demonstrated, treatment with ketamine and ECT was associated with improved depressive symptoms in patients. At baseline, waking cortisol output was greater in the ECT cohort, kynurenine was greater in the ketamine cohort, and kynurenic acid was lower in patients compared to healthy controls, although inflammatory markers (IL-6, IL-8, IL-10 or IFN-γ) were similar in patients and controls. Furthermore, in patients who responded to ECT, the cortisol awakening response was decreased following treatment. Despite a trend towards reduced kynurenine concentrations in those who responded to ketamine, ketamine was not associated with significant alterations in any of the biomarkers assessed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rectal Thiopental versus Intramuscular Ketamine in Pediatric Procedural Sedation and Analgesia; a Randomized Clinical Trial.

PubMed

Azizkhani, Reza; Esmailian, Mehrdad; Shojaei, Azadeh; Golshani, Keihan

2015-01-01

Physicians frequently deal with procedures which require sedation of pediatric patients. Laceration repair is one of them. No study has been performed regarding the comparison between induction of sedation with sodium thiopental and ketamine in laceration repair. Therefore, the present study was aimed to comparison of induced sedation by rectal sodium thiopental and muscular injection of hydrochloride ketamine in pediatric patients need laceration repair. The presented study is a single-blinded clinical trial performed through 2013 to 2014 in Ayatollah Kashani and Alzahra Hospitals, Isfahan, Iran. Patients from 3 months to 14 years, needed sedation for laceration repair, were entered. Patients were sequentially evaluated and randomly categorized in two groups of hydrochloride ketamine with dose of 2-4 milligram per kilogram and sodium thiopental with dose of 25 milligram per kilogram. Demographic data and vital signs before drug administration and after induction of sedation, Ramsey score, time to onset of action, and sedation recovery time were evaluated. Chi-squared, Mann-Whitney, and Non-parametric analysis of covariance tests were used. P<0.05 was considered as a significant level. In this study 60 pediatric patients were entered. 30 patients with mean age of 42.8±18.82 months were received sodium thiopental and the rest with mean age of 30.08±16.88 months given ketamine. Mann-Whitney test was showed that time to onset of action in sodium thiopental group (28.23±5.18 minutes) was significantly higher than ketamine (7.77±4.13 minutes), (p<0.001). The sedation recovery time in ketamine group (29.83±7.70) was higher than sodium thiopental. Depth of sedation had no significant difference between two groups based on Ramsey score (p=0.87). No significant difference was seen between two groups in the respiratory rate (df=1, 58; F=0.002; P=0.96) and heart rate (df=1, 58; F=0.98; P=0.33). However, arterial oxygen saturation level (df=1, 58; F=6.58; P=0.013) was

Ketamine Alters Hippocampal Cell Proliferation and Improves Learning in Mice after Traumatic Brain Injury.

PubMed

Peters, Austin J; Villasana, Laura E; Schnell, Eric

2018-04-30

Traumatic brain injury induces cellular proliferation in the hippocampus, which generates new neurons and glial cells during recovery. This process is regulated by N-methyl-D-aspartate-type glutamate receptors, which are inhibited by ketamine. The authors hypothesized that ketamine treatment after traumatic brain injury would reduce hippocampal cell proliferation, leading to worse behavioral outcomes in mice. Traumatic brain injury was induced in mice using a controlled cortical impact injury, after which mice (N = 118) received either ketamine or vehicle systemically for 1 week. The authors utilized immunohistochemical assays to evaluate neuronal, astroglial, and microglial cell proliferation and survival 3 days, 2 weeks, and 6 weeks postintervention. The Morris water maze reversal task was used to assess cognitive recovery. Ketamine dramatically increased microglial proliferation in the granule cell layer of the hippocampus 3 days after injury (injury + vehicle, 2,800 ± 2,700 cells/mm, n = 4; injury + ketamine, 11,200 ± 6,600 cells/mm, n = 6; P = 0.012). Ketamine treatment also prevented the production of astrocytes 2 weeks after injury (sham + vehicle, 2,400 ± 3,200 cells/mm, n = 13; injury + vehicle, 10,500 ± 11,300 cells/mm, n = 12; P = 0.013 vs. sham + vehicle; sham + ketamine, 3,500 ± 4,900 cells/mm, n = 14; injury + ketamine, 4,800 ± 3,000 cells/mm, n = 13; P = 0.955 vs. sham + ketamine). Independent of injury, ketamine temporarily reduced neurogenesis (vehicle-exposed, 105,100 ± 66,700, cells/mm, n = 25; ketamine-exposed, 74,300 ± 29,200 cells/mm, n = 27; P = 0.031). Ketamine administration improved performance in the Morris water maze reversal test after injury, but had no effect on performance in sham-treated mice. Ketamine alters hippocampal cell proliferation after traumatic brain injury. Surprisingly, these changes were associated with improvement in a neurogenesis-related behavioral recall task, suggesting a possible benefit from ketamine

Intramuscular ketamine in acute depression: A report on two cases

PubMed Central

Harihar, Chilukuri; Dasari, Padmavathy; Srinivas, Jakka Sriramulu

2013-01-01

It takes about 2 weeks for the onset of antidepressant action of drugs while electroconvulsive therapy though faster, is a cumbersome procedure requiring an anaesthetist and at least a minor operation theatre. Recent studies have shown that Ketamine, when given to severely depressed patients in the dose of 0.5 mg/kg as a slow intravenous infusion over 40 minutes, brought about acute relief from depression and amelioration of suicidal risk within a few hours. The improvement, however, was transient and lasted for up to a week but could be sustained by further weekly or biweekly injections. As the dose of ketamine administered was found to be safe, it was now tried in the intramuscular route in two severely depressed patients with similar rapid improvement. The cases are reported here which pave way for an easier mode of treating acute depression. PMID:23825857

Low-Dose Ketamine Infusions for Highly Opioid-Tolerant Adults Following Spinal Surgery: A Retrospective Before-and-after Study.

PubMed

Vaid, Patrycja; Green, Theresa; Shinkaruk, Kelly; King-Shier, Kathryn

2016-04-01

Managing acute-on-chronic pain in opioid-tolerant individuals is complex and challenging; exploring new analgesia regimens for this population is essential. Ketamine is an N-methyl D-aspartate antagonist that blocks transmission of painful stimuli and could be a useful medication for this patient population. A new low-dose ketamine protocol as an adjunct to conventional pain therapy was implemented in a major urban Level 1 trauma center in Canada. A retrospective before-and-after chart review was conducted to explore the research question, "What is the effect of low-dose ketamine continuous intravenous infusions on pain of highly opioid-tolerant adults following spinal surgery?". All patients had spine surgery, used a minimum of 100 mg daily oral morphine equivalent preoperatively and were followed postoperatively by the hospital's Acute Pain Service. Data from individuals treated with conventional therapy during the year prior to protocol implementation were compared with data from patients who received conventional therapy plus ketamine post implementation. Outcome measures included pain scores and daily opioid consumption on postoperative days 0 through 5, time to ambulation, time to discharge, and adverse effects. There were no statistically significant differences between conventional therapy and conventional therapy plus ketamine. Ketamine may still be of benefit to patients with acute-on-chronic pain, although this was not evident in this study. Future research using more robust assessment tools to determine effectiveness of ketamine is required. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model.

PubMed

Yang, Chun; Ren, Qian; Qu, Youge; Zhang, Ji-Chun; Ma, Min; Dong, Chao; Hashimoto, Kenji

2018-01-01

The role of the mechanistic target of rapamycin (mTOR) signaling in the antidepressant effects of ketamine is controversial. In addition to mTOR, extracellular signal-regulated kinase (ERK) is a key signaling molecule in prominent pathways that regulate protein synthesis. (R)-Ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here we investigated whether mTOR signaling and ERK signaling play a role in the antidepressant effects of two enantiomers. The effects of mTOR inhibitors (rapamycin and AZD8055) and an ERK inhibitor (SL327) on the antidepressant effects of ketamine enantiomers in the chronic social defeat stress (CSDS) model (n = 7 or 8) and on those of ketamine enantiomers in these signaling pathways in mouse brain regions were examined. The intracerebroventricular infusion of rapamycin or AZD8055 blocked the antidepressant effects of (S)-ketamine, but not (R)-ketamine, in the CSDS model. Furthermore, (S)-ketamine, but not (R)-ketamine, significantly attenuated the decreased phosphorylation of mTOR and its downstream effector, ribosomal protein S6 kinase, in the prefrontal cortex of susceptible mice after CSDS. Pretreatment with SL327 blocked the antidepressant effects of (R)-ketamine but not (S)-ketamine. Moreover, (R)-ketamine, but not (S)-ketamine, significantly attenuated the decreased phosphorylation of ERK and its upstream effector, mitogen-activated protein kinase/ERK kinase, in the prefrontal cortex and hippocampal dentate gyrus of susceptible mice after CSDS. This study suggests that mTOR plays a role in the antidepressant effects of (S)-ketamine, but not (R)-ketamine, and that ERK plays a role in (R)-ketamine's antidepressant effects. Thus, it is unlikely that the activation of mTOR signaling is necessary for antidepressant actions of (R)-ketamine. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Oral ketamine for children with chronic pain: a pilot phase 1 study

PubMed Central

Bredlau, Amy-Lee; McDermott, Michael P.; Adams, Heather; Dworkin, Robert H; Venuto, Charles; Fisher, Susan; Dolan, James G; Korones, David N

2013-01-01

Objective To assess whether oral ketamine aids is is safe at higher dosages for sedating children and whether it may be an option for control of chronic pain in children. Study design A prospective study was performed on 12 children with chronic pain to identify the maximum tolerated dosage of oral ketamine. Participants were given 14 days of oral ketamine, three times daily, at dosages ranging from 0.25–1.5 mg/kg/dose. Participants were assessed for toxicity and for pain severity at baseline and on day 14 of treatment. Results Two participants, both treated at 1.5 mg/kg/dose, experienced dose-limiting toxicities (sedation and anorexia). One participant, treated at 1 mg/kg/dose, opted to stop ketamine treatment due to new pain on treatment. Nine participants completed their course of ketamine treatment. Of these 12 children, 5 experienced improvement in their pain scores, two with complete resolution of pain, lasting for more than 4 weeks off ketamine treatment. Conclusion Oral ketamine at dosages of 0.25–1 mg/kg/dose appears to be safe when given for 14 days to children with chronic pain. PMID:23403253

Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects.

PubMed

Nugent, Allison C; Ballard, Elizabeth D; Gould, Todd D; Park, Lawrence T; Moaddel, Ruin; Brutsche, Nancy E; Zarate, Carlos A

2018-02-27

Ketamine's mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms, and healthy control subjects exhibited modest but significant increases in depressive symptoms for up to 1 day after ketamine administration. Both groups showed increased resting gamma power following ketamine. In MDD subjects, gamma power was not associated with the magnitude of the antidepressant effect. However, baseline gamma power was found to moderate the relationship between post-ketamine gamma power and antidepressant response; specifically, higher post-ketamine gamma power was associated with better response in MDD subjects with lower baseline gamma, with an inverted relationship in MDD subjects with higher baseline gamma. This relationship was observed in multiple regions involved in networks hypothesized to be involved in the pathophysiology of MDD. This finding suggests biological subtypes based on the direction of homeostatic dysregulation and has important implications for inferring ketamine's mechanism of action from studies of healthy controls alone.

Ketamine PCA for treatment of end-of-life neuropathic pain in pediatrics.

PubMed

Taylor, Matthew; Jakacki, Regina; May, Carol; Howrie, Denise; Maurer, Scott

2015-12-01

Control of neuropathic pain (NP) for children at end of life is challenging. Ketamine improves control of NP, but its use in children is not well described. We describe a retrospective case review of 14 children with terminal prognoses treated with ketamine patient-controlled analgesia (PCA) for management of opioid-refractory NP at the end of life. Median ketamine dose was 0.06 mg/kg/h (range 0.014-0.308 mg/kg/h) with a 0.05 mg/kg (range 0.03-0.5mg/kg) demand dose available every 15 minutes (range 10-60 minutes). All patients noted subjective pain relief with ketamine, and 79% had no adverse effects. Benzodiazepines limited neuropsychiatric side effects. Ketamine treatment arrested dose escalation of opioids in 64% of patients, and 79% were discharged to home hospice. Ketamine PCA is an effective, well-tolerated therapy for opioid-refractory NP in pediatric end-of-life care. © The Author(s) 2014.

Low-Dose Ketamine Infusion for Adjunct Management during Vaso-occlusive Episodes in Adults with Sickle Cell Disease: A Case Series.

PubMed

Palm, Nicole; Floroff, Catherine; Hassig, Tanna B; Boylan, Alice; Kanter, Julie

2018-05-23

The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.

Breakdown of long-range temporal correlations in brain oscillations during general anesthesia.

PubMed

Krzemiński, Dominik; Kamiński, Maciej; Marchewka, Artur; Bola, Michał

2017-10-01

Consciousness has been hypothesized to emerge from complex neuronal dynamics, which prevails when brain operates in a critical state. Evidence supporting this hypothesis comes mainly from studies investigating neuronal activity on a short time-scale of seconds. However, a key aspect of criticality is presence of scale-free temporal dependencies occurring across a wide range of time-scales. Indeed, robust long-range temporal correlations (LRTCs) are found in neuronal oscillations during conscious states, but it is not known how LRTCs are affected by loss of consciousness. To further test a relation between critical dynamics and consciousness, we investigated LRTCs in electrocorticography signals recorded from four macaque monkeys during resting wakefulness and general anesthesia induced by various anesthetics (ketamine, medetomidine, or propofol). Detrended Fluctuation Analysis was used to estimate LRTCs in amplitude fluctuations (envelopes) of band-pass filtered signals. We demonstrate two main findings. First, during conscious states all lateral cortical regions are characterized by significant LRTCs of alpha-band activity (7-14 Hz). LRTCs are stronger in the eyes-open than eyes-closed state, but in both states they form a spatial gradient, with anterior brain regions exhibiting stronger LRTCs than posterior regions. Second, we observed a substantial decrease of LRTCs during loss of consciousness, the magnitude of which was associated with the baseline (i.e. pre-anesthesia) state of the brain. Specifically, brain regions characterized by strongest LRTCs during a wakeful baseline exhibited greatest decreases during anesthesia (i.e. "the rich got poorer"), which consequently disturbed the posterior-anterior gradient. Therefore, our results suggest that general anesthesia affects mainly brain areas characterized by strongest LRTCs during wakefulness, which might account for lack of capacities for extensive temporal integration during loss of consciousness. Copyright

Comparison between chloral hydrate and propofol-ketamine as sedation regimens for pediatric auditory brainstem response testing.

PubMed

Abulebda, Kamal; Patel, Vinit J; Ahmed, Sheikh S; Tori, Alvaro J; Lutfi, Riad; Abu-Sultaneh, Samer

2017-10-28

The use of diagnostic auditory brainstem response testing under sedation is currently the "gold standard" in infants and young children who are not developmentally capable of completing the test. The aim of the study is to compare a propofol-ketamine regimen to an oral chloral hydrate regimen for sedating children undergoing auditory brainstem response testing. Patients between 4 months and 6 years who required sedation for auditory brainstem response testing were included in this retrospective study. Drugs doses, adverse effects, sedation times, and the effectiveness of the sedative regimens were reviewed. 73 patients underwent oral chloral hydrate sedation, while 117 received propofol-ketamine sedation. 12% of the patients in the chloral hydrate group failed to achieve desired sedation level. The average procedure, recovery and total nursing times were significantly lower in the propofol-ketamine group. Propofol-ketamine group experienced higher incidence of transient hypoxemia. Both sedation regimens can be successfully used for sedating children undergoing auditory brainstem response testing. While deep sedation using propofol-ketamine regimen offers more efficiency than moderate sedation using chloral hydrate, it does carry a higher incidence of transient hypoxemia, which warrants the use of a highly skilled team trained in pediatric cardio-respiratory monitoring and airway management. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

The role of adipokines in the rapid antidepressant effects of ketamine.

PubMed

Machado-Vieira, R; Gold, P W; Luckenbaugh, D A; Ballard, E D; Richards, E M; Henter, I D; De Sousa, R T; Niciu, M J; Yuan, P; Zarate, C A

2017-01-01

We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine or as possible transducers of its therapeutic effects. Eighty treatment-resistant subjects who met DSM-IV criteria for either major depressive disorder (MDD) or bipolar disorder I/II and who were currently experiencing a major depressive episode received a single ketamine infusion (0.5 mg kg -1 for 40 min). Plasma adipokine levels were measured at three time points (pre-infusion baseline, 230 min post infusion and day 1 post infusion). Overall improvement and response were assessed using percent change from baseline on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower baseline levels of adiponectin significantly predicted ketamine's antidepressant efficacy, suggesting an adverse metabolic state. Because adiponectin significantly improves insulin sensitivity and has potent anti-inflammatory effects, this finding suggests that specific systemic abnormalities might predict positive response to ketamine. A ketamine-induced decrease in resistin was also observed; because resistin is a potent pro-inflammatory compound, this decrease suggests that ketamine's anti-inflammatory effects may be transduced, in part, by its impact on resistin. Overall, the findings suggest that adipokines may either predict response to ketamine or have a role in its possible therapeutic effects.

Ketamine treatment involves medial prefrontal cortex serotonin to induce a rapid antidepressant-like activity in BALB/cJ mice.

PubMed

Pham, T H; Mendez-David, I; Defaix, C; Guiard, B P; Tritschler, L; David, D J; Gardier, A M

2017-01-01

Unlike classic serotonergic antidepressant drugs, ketamine, an NMDA receptor antagonist, exhibits a rapid and persistent antidepressant (AD) activity, at sub-anaesthetic doses in treatment-resistant depressed patients and in preclinical studies in rodents. The mechanisms mediating this activity are unclear. Here, we assessed the role of the brain serotonergic system in the AD-like activity of an acute sub-anaesthetic ketamine dose. We compared ketamine and fluoxetine responses in several behavioral tests currently used to predict anxiolytic/antidepressant-like potential in rodents. We also measured their effects on extracellular serotonin levels [5-HT] ext in the medial prefrontal cortex (mPFCx) and brainstem dorsal raphe nucleus (DRN), a serotonergic nucleus involved in emotional behavior, and on 5-HT cell firing in the DRN in highly anxious BALB/cJ mice. Ketamine (10 mg/kg i.p.) had no anxiolytic-like effect, but displayed a long lasting AD-like activity, i.e., 24 h post-administration, compared to fluoxetine (18 mg/kg i.p.). Ketamine (144%) and fluoxetine (171%) increased mPFCx [5-HT] ext compared to vehicle. Ketamine-induced AD-like effect was abolished by a tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA) pointing out the role of the 5-HT system in its behavioral activity. Interestingly, increase in cortical [5-HT] ext following intra-mPFCx ketamine bilateral injection (0.25 μg/side) was correlated with its AD-like activity as measured on swimming duration in the FST in the same mice. Furthermore, pre-treatment with a selective AMPA receptor antagonist (intra-DRN NBQX) blunted the effects of intra-mPFCx ketamine on both the swimming duration in the FST and mPFCx [5-HT] ext suggesting that the AD-like activity of ketamine required activation of DRN AMPA receptors and recruited the prefrontal cortex/brainstem DRN neural circuit in BALB/c mice. These results confirm a key role of cortical 5-HT release in ketamine's AD-like activity following

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

An Observational Assessment of Anesthesia Capacity in Madagascar as a Prerequisite to the Development of a National Surgical Plan.

PubMed

Baxter, Linden S; Ravelojaona, Vaonandianina A; Rakotoarison, Hasiniaina N; Herbert, Alison; Bruno, Emily; Close, Kristin L; Andean, Vanessa; Andriamanjato, Hery H; Shrime, Mark G; White, Michelle C

2017-06-01

The global lack of anesthesia capacity is well described, but country-specific data are needed to provide country-specific solutions. We aimed to assess anesthesia capacity in Madagascar as part of the development of a Ministry of Health national surgical plan. As part of a nationwide surgical safety quality improvement project, we surveyed 19 of 22 regional hospitals, representing surgical facilities caring for 75% of the total population. The assessment was divided into 3 areas: anesthesia workforce density, infrastructure and equipment, and medications. Data were obtained by semistructured interviews with Ministry of Health officials, hospital directors, technical directors, statisticians, pharmacists, and anesthesia providers and through on-site observations. Interview questions were adapted from the World Health Organization Situational Analysis Tool and the World Federation of Societies of Anaesthesiologists International Standards for Safe Practice of Anaesthesia. Additional data on workforce density were collected from the 3 remaining regions so that workforce density data are representative of all 22 regions. Anesthesia physician workforce density is 0.26 per 100,000 population and 0.19 per 100,000 outside of the capital region. Less than 50% of hospitals surveyed reported having a reliable electricity and oxygen supply. The majority of anesthesia providers work without pulse oximetry (52%) or a functioning vaporizer (52%). All the hospitals surveyed had very basic pediatric supplies, and none had a pediatric pulse oximetry probe. Ketamine is universally available but more than 50% of hospitals lack access to opioids. None of the 19 regional hospitals surveyed was able to completely meet the World Federation of Societies of Anaesthesiologists' standards for monitoring. Improving anesthesia care is complex. Capacity assessment is a first step that would enable progress to be tracked against specific targets. In Madagascar, scale-up of the anesthesia

Synergistic interaction between ketamine and magnesium in lowering body temperature in rats.

PubMed

Vučković, Sonja M; Savić Vujović, Katarina R; Srebro, Dragana P; Medić, Branislava M; Vučetić, Cedomir S; Prostran, Milan Š; Prostran, Milica Š

2014-03-29

A large body of evidence supports the existence of an endogenous glutamate system that tonically modulates body temperature via N-methyl-d-aspartate (NMDA) receptors. Ketamine and magnesium, both NMDA receptor antagonists, are known for their anesthetic, analgesic and anti-shivering properties. This study is aimed at evaluating the effects of ketamine and magnesium sulfate on body temperature in rats, and to determine the type of interaction between them. The body temperature was measured by insertion of a thermometer probe 5cm into the colon of unrestrained male Wistar rats (200-250g). Magnesium sulfate (5 and 60mg/kg, sc) showed influence neither on baseline, nor on morphine-evoked hyperthermic response. Subanesthetic doses of ketamine (5-30mg/kg, ip) given alone, produced significant dose-dependent reduction in both baseline colonic temperature and morphine-induced hyperthermia. Analysis of the log dose-response curves for the effects of ketamine and ketamine-magnesium sulfate combination on the baseline body temperature revealed synergistic interaction, and about 5.3 fold reduction in dosage of ketamine when the drugs were applied in fixed ratio (1:1) combinations. In addition, fixed low dose of magnesium sulfate (5mg/kg, sc) enhanced the temperature lowering effect of ketamine (1.25-10mg/kg, ip) on baseline body temperature and morphine-induced hyperthermia by factors of about 2.5 and 5.3, respectively. This study is the first to demonstrate the synergistic interaction between magnesium sulfate and ketamine in a whole animal study and its statistical confirmation. It is possible that the synergy between ketamine and magnesium may have clinical relevance. Copyright © 2014 Elsevier Inc. All rights reserved.

Spinal anesthesia in infants: recent developments.

PubMed

Tirmizi, Henna

2015-06-01

Spinal anesthesia has long been described as a well-tolerated and effective means of providing anesthesia for infants undergoing lower abdominal surgery. Now, spinal anesthetics are being used for an increasing variety of surgeries previously believed to require a general anesthetic. This, along with increasing concerns over the neurocognitive effects of general anesthetics on developing brains, suggests that further exploration into this technique and its effects is essential. Exposure to spinal anesthesia in infancy has not shown the same suggestions of neurocognitive detriment as those resulting from general anesthesia. Ultrasound guidance has enhanced spinal technique by providing real-time guidance into the intrathecal space and confirming medication administration location, as well as helping avoid adverse outcomes by identifying aberrant anatomy. Spinal anesthesia provides benefits over general anesthesia, including cardiorespiratory stability, shorter postoperative recovery, and faster return of gastrointestinal function. Early findings of spinal anesthesia exposure in infancy have shown it to have no independent effect on neurocognitive delay as well as to provide sound cardiorespiratory stability. With safer means of administering a spinal anesthetic, such as with ultrasound guidance, it is a readily available and desirable tool for those providing anesthesia to infants.

Efficacy of ketamine in improving pain after tonsillectomy in children: meta-analysis.

PubMed

Cho, Hye Kyung; Kim, Kyu Won; Jeong, Yeon Min; Lee, Ho Seok; Lee, Yeon Ji; Hwang, Se Hwan

2014-01-01

The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children. Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0-24 hours after leaving the operation room were included in the analysis. The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics. Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study.

Distinct effects of ketamine and acetyl l-carnitine on the dopamine system in zebrafish

PubMed Central

Robinson, Bonnie L.; Dumas, Melanie; Cuevas, Elvis; Gu, Qiang; Paule, Merle G.; Ali, Syed F.; Kanungo, Jyotshna

2016-01-01

Ketamine, a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor antagonist is commonly used as a pediatric anesthetic. We have previously shown that acetyl L-carnitine (ALCAR) prevents ketamine toxicity in zebrafish embryos. In mammals, ketamine is known to modulate the dopaminergic system. NMDA receptor antagonists are considered as promising anti-depressants, but the exact mechanism of their function is unclear. Here, we measured the levels of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the zebrafish embryos exposed to ketamine in the presence and absence of 0.5 mM ALCAR. Ketamine, at lower doses (0.1–0.3 mM), did not produce significant changes in DA, DOPAC or HVA levels in 52 h post-fertilization embryos treated for 24 h. In these embryos, tyrosine hydroxylase (TH) mRNA expression remained unchanged. However, 2 mM ketamine (internal embryo exposure levels equivalent to human anesthetic plasma concentration) significantly reduced DA level and TH mRNA indicating that DA synthesis was adversely affected. In the presence or absence of 2 mM ketamine, ALCAR showed similar effects on DA level and TH mRNA, but increased DOPAC level compared to control. ALCAR reversed 2 mM ketamine-induced reduction in HVA levels. With ALCAR alone, the expression of genes encoding the DA metabolizing enzymes, MAO (monoamine oxidase) and catechol-O-methyltransferase (COMT), was not affected. However, ketamine altered MAO mRNA expression, except at the 0.1 mM dose. COMT transcripts were reduced in the 2 mM ketamine-treated group. These distinct effects of ketamine and ALCAR on the DA system may shed some light on the mechanism on how ketamine can work as an anti-depressant, especially at sub-anesthetic doses that do not affect DA metabolism and suppress MAO gene expression. PMID:26898327

Involvement of posterior cingulate cortex in ketamine-induced psychosis relevant behaviors in rats.

PubMed

Ma, Jingyi; Leung, L Stan

2018-02-15

The involvement of posterior cingulate cortex (PCC) on ketamine-induced psychosis relevant behaviors was investigated in rats. Bilateral infusion of muscimol, a GABA A receptor agonist, into the PCC significantly antagonized ketamine-induced deficit in prepulse inhibition of a startle reflex (PPI), deficit in gating of hippocampal auditory evoked potentials, and behavioral hyperlocomotion in a dose dependent manner. Local infusion of ketamine directly into the PCC also induced a PPI deficit. Systemic injection of ketamine (3mg/kg,s.c.) induced an increase in power of electrographic activity in the gamma band (30-100Hz) in both the PCC and the hippocampus; peak theta (4-10Hz) power was not significantly altered, but peak theta frequency was increased by ketamine. In order to exclude volume conduction from the hippocampus to PCC, inactivation of the hippocampus was made by local infusion of muscimol into the hippocampus prior to ketamine administration. Muscimol in the hippocampus effectively blocked ketamine-induced increase of gamma power in the hippocampus but not in the PCC, suggesting independent generation of gamma waves in PCC and hippocampus. It is suggested that the PCC is part of the brain network mediating ketamine-induced psychosis related behaviors. Copyright © 2017 Elsevier B.V. All rights reserved.

Anesthesia

MedlinePlus

... arm or leg. A common type is epidural anesthesia, which is often used during childbirth. General - makes ... afterwards. Sedation can be used with or without anesthesia. The type of anesthesia or sedation you get ...

Ketamine attenuates the glutamatergic neurotransmission in the ventral posteromedial nucleus slices of rats.

PubMed

Fu, Bao; Liu, Chengxi; Zhang, Yajun; Fu, Xiaoyun; Zhang, Lin; Yu, Tian

2017-08-23

Ketamine is a frequently used intravenous anesthetic, which can reversibly induce loss of consciousness (LOC). Previous studies have demonstrated that thalamocortical system is critical for information transmission and integration in the brain. The ventral posteromedial nucleus (VPM) is a critical component of thalamocortical system. Glutamate is an important excitatory neurotransmitter in the brain and may be involved in ketamine-induced LOC. The study used whole-cell patch-clamp to observe the effect of ketamine (30 μM-1000 μM) on glutamatergic neurotransmission in VPM slices. Ketamine significantly decreased the amplitude of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs), but only higher concentration of ketamine (300 μM and 1000 μM) suppressed the frequency of sEPSCs. Ketamine (100 μM-1000 μM) also decreased the amplitude of glutamatergic miniature excitatory postsynaptic currents (mEPSCs), without altering the frequency. In VPM neurons, ketamine attenuates the glutamatergic neurotransmission mainly through postsynaptic mechanism and action potential may be involved in the process.

Extrapedicular Infiltration Anesthesia as an Improved Method of Local Anesthesia for Unipedicular Percutaneous Vertebroplasty or Percutaneous Kyphoplasty.

PubMed

Liu, Liehua; Cheng, Shiming; Lu, Rui; Zhou, Qiang

2016-01-01

Aim. This report introduces extrapedicular infiltration anesthesia as an improved method of local anesthesia for unipedicular percutaneous vertebroplasty or percutaneous kyphoplasty. Method. From March 2015 to March 2016, 44 patients (11 males and 33 females) with osteoporotic vertebral compression fractures with a mean age of 71.4 ± 8.8 years (range: 60 to 89) received percutaneous vertebroplasty or percutaneous kyphoplasty. 24 patients were managed with conventional local infiltration anesthesia (CLIA) and 20 patients with both CLIA and extrapedicular infiltration anesthesia (EPIA). Patients evaluated intraoperative pain by means of the visual analogue score and were monitored during the procedure for additional sedative analgesia needs and for adverse nerve root effects. Results. VAS of CLIA + EPIA and CLIA group was 2.5 ± 0.7 and 4.3 ± 1.0, respectively, and there was significant difference ( P = 0.001). In CLIA group, 1 patient required additional sedative analgesia, but in CLIA + EPIA group, no patients required that. In the two groups, no adverse nerve root effects were noted. Summary. Extrapedicular infiltration anesthesia provided good local anesthetic effects without significant complications. This method deserves further consideration for use in unipedicular percutaneous vertebroplasty and percutaneous kyphoplasty.

Ketamine use in Taiwan: Moral panic, civilizing processes, and democratization.

PubMed

Hsu, Liang-Yin

2014-07-01

Ketamine use among young people in Taiwan has increased in recent years. Believing ketamine users to be a threat to social order and harsh punishment to be a deterrent, some legislators have called for upgrading ketamine use to a more serious criminal offence. These calls have been repeatedly rebuffed by the advisory council which sets drug policy, suggesting that the perceived problem does not correlate to the actual one. In this commentary, I argue that the calls of legislators constitute a 'moral panic,' and follow Rohloff (2011) in connecting the phenomenon to Elias' (2000) concept of civilizing and decivilizing processes. In addition, I demonstrate that moral panic - in the ketamine case at least - is shaped by the legacy of authoritarianism. Copyright © 2014 Elsevier B.V. All rights reserved.

Reinforcing properties of an intermittent, low dose of ketamine in rats: effects of sex and cycle.

PubMed

Wright, Katherine N; Strong, Caroline E; Addonizio, Marjorie N; Brownstein, Naomi C; Kabbaj, Mohamed

2017-02-01

Repeated intermittent exposure to ketamine has rapid and long-lasting antidepressant effects, but the abuse potential has only been assessed at high doses. Furthermore, while females are more susceptible to depression and more sensitive to ketamine's antidepressant-like effects, the abuse potential for ketamine in females is unknown. The objectives of this study are to determine the reinforcing properties of low-dose intermittent ketamine in adult rats of both sexes and determine whether cycling gonadal hormones influence females' response to ketamine. In male rats, we also aimed to determine whether reinstatement to intermittent ketamine is comparable to intermittent cocaine. Male rats intravenously self-administered cocaine (0.75 mg/kg/infusion) or ketamine (0.1 mg/kg/infusion) once every fourth day, while intact cycling female rats self-administered ketamine only during preidentified stages of their 4-day estrus cycle, when gonadal hormones are either high (proestrus) or low (diestrus). After acquiring self-administration, rats underwent daily extinction training followed by cue-primed and drug-primed reinstatement to assess drug-seeking behavior. Diestrus-trained females fail to maintain ketamine self-administration and did not display reinstatement to ketamine-paired cues. Males and proestrus-trained females reinstated to ketamine-paired cues. Ketamine-primed reinstatement was dependent on simultaneous cue presentation. Male rats reinstated to cocaine priming independent of cue presentation. These findings indicate that females's responsivity to this dose of ketamine depends on stage of cycle, as only proestrus-trained females and males respond to ketamine's reinforcing effects under this treatment paradigm.

Anaesthetic, analgesic and cardiorespiratory effects of intramuscular medetomidine-ketamine combination alone or with morphine or tramadol for orchiectomy in cats.

PubMed

Zeiler, Gareth E; Dzikiti, Brighton T; Fosgate, Geoffrey T; Stegmann, Frik G; Venter, Frans J; Rioja, Eva

2014-07-01

To compare the anaesthetic, analgesic and cardiorespiratory effects of intramuscular (IM) medetomidine and ketamine administered alone or combined with morphine or tramadol, for orchiectomy in cats. Randomised, blinded, prospective clinical study. Thirty client-owned cats. Cats (n = 10 in each group) received a combination of medetomidine (60 μgkg(-1) ) and ketamine (10 mg kg(-1) ) alone (MedK); combined with morphine (0.2 mg kg(-1) ) (MedKM), or combined with tramadol (2 mg kg(-1) ) (MedKT) IM. Time of induction, surgical and recovery events were recorded, and physiological parameters measured and recorded. Analgesia was evaluated with a visual analogue scale, a composite scoring system and the von Frey mechanical threshold device, every hour from three to eight hours post-drug administration injection. Data were analyzed with a linear mixed model, Kruskal-Wallis or Chi-square tests (p < 0.05). Median (IQR) induction and recovery times (minutes) were not significantly (p = 0.125) different between groups: 5.6 (2.7-8.0), 7.4 (5.1-9.6) and 8.0 (5.8-14.9) for induction and 128.5 (95.1-142.8), 166.4 (123.1-210.0) and 142.9 (123.4-180.2) for recovery, with MedK, MedKT and MedKM, respectively. Two cats (MedKM) required alfaxalone for endotracheal intubation. In all groups, three or four cats required additional isoflurane for surgery. Arterial oxygen tension overall (mean ± SD: 66 ± 2 mmHg) was low. Surgery resulted in increased systolic arterial blood pressure (p < 0.001), haemoglobin saturation (p < 0.001), respiratory (p = 0.003) and heart rates (p = 0.002). Pain scores did not differ significantly between groups. Von Frey responses decreased over time; changes over time varied by treatment (p < 0.001), MedK returning to baseline values more rapidly than MedKM and MedKT. No cat required rescue analgesics. All three protocols can provide adequate anaesthesia and analgesia for orchiectomy in cats. However, rescue intervention to maintain surgical anaesthesia may be

Surgery for esotropia under topical anesthesia.

PubMed

Tejedor, Jaime; Ogallar, Consuelo; Rodríguez, José M

2010-10-01

To compare a surgically adjusted dose of strabismus surgery using topical anesthesia in cooperative patients with dosage guidelines adapted to the surgeon's personal technique using sub-Tenon's anesthesia. Randomized, controlled, single-site clinical trial. Sixty patients with nonparalytic, nonrestrictive esotropia who were cooperative for surgery under topical anesthesia. Twenty-eight patients were assigned to topical anesthesia, and 32 patients were assigned to sub-Tenon's anesthesia. Visual acuity, refraction, and deviation angle were determined in all patients preoperatively and postoperatively, and stereoacuity was measured postoperatively. Deviation angle was measured by simultaneous and alternate prism and cover test, and stereoacuity was measured using Randot circles (Stereo Optical Co., Chicago, IL). The amount of surgery under topical anesthesia was adjusted intraoperatively. The amount of surgery used in the 2 treatment groups (measured in millimeters and millimeter/degree of deviation angle) and 6-month motor and stereoacuity outcomes. Patients in the topical group required 3.2 mm less surgery on average than those in the sub-Tenon's group (5.9 and 9.1 mm, respectively; 0.4 and 0.6 mm of recession/degree, respectively) (P<0.01). Motor success (84% and 75%, respectively, P=0.38) and stereoacuity (339.6 and 323.9 arc seconds, respectively, P=0.87) at 6 months were similar in the 2 groups. Topical anesthesia requires a smaller amount of surgery and number of operated muscles to correct esotropia compared with classic surgery guidelines adapted to the surgeon's personal technique. Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Use of a rapid brain-sampling technique in a physiologic preparation: effects of morphine, ketamine, and halothane on tissue energy intermediates.

PubMed

Dedrick, D F; Sherer, Y D; Biebuyck, J F

1975-06-01

A new method of rapid sampling of brain tissue, "freeze-blowing," has been used to compare the neurochemistry of the brain during anesthesia with that in the awake state. The method avoids anoxia associated with the sampling process. Physiologic variables, including body temperature, blood-gas tensions and blood pressure, were carefully monitored and controlled in the experimental animals. None of the agents tested (halothane, morphine, and ketamine) reduced the brain tissue high-energy phosphate reserved. All three drugs doubled glucose levels. Morphine lowered both lactate and the lactate/pyruvate ratio. Uniformly, the three anesthetic agents led to twofold increases of brain cyclic 3'-5' adenosine monophosphate concentrations. These changes suggest a possible role for cyclic nucleotides in central neurotransmission.

Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature.

PubMed

Uprety, Dipesh; Baber, Aurangzeb; Foy, Maria

2014-05-01

This article reports a rare case of the use of low-dose ketamine infusion as an adjuvant to opioids to treat pain in sickle cell disease. A 31-year-old African-American male with history of sickle cell disease presented to the emergency department with complaints of chest tightness, multiple joint pain, and headache for 1 week. His vital signs and physical examination were unremarkable. His admission lab included hemoglobin of 8.4 g/dl, reticulocyte count of 16.3%, bilirubin of 1.7 mg/dl, and LDH of 1,267 U/l. Chest X-ray showed middle and lower lobe opacity and interstitial thickening. He was treated for acute pain crisis and community-acquired pneumonia with intravenous fluids, supplemental oxygen, and intravenous levofloxacin. He was placed on fentanyl patient-controlled analgesia (PCA), oxycodone, ketorolac, and methadone with co-analgesic gabapentin and venlafaxine. Over the course of his hospitalization, his chest pain resolved, but the joint pains continued. He was then transferred to the ICU and was discharged a day later after 7 days of ketamine infusion. Ketamine is a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. This property has been shown to modulate opioid tolerance and opioid-induced hyperalgesia. There have been a very few published reports on the use of low-dose ketamine in sickle cell pain management. A PubMed search revealed four published articles (Table 1). Fourteen out of the 17 cases (82.35%) who received ketamine infusion showed improvement in self-reported pain intensity and significant reduction in opioid dosage. Only one patient (5.9%) developed serious side effect leading to discontinuation of the drug. A low-dose ketamine can be an option for pain control in sickle cell disease. Randomized trial is required to establish this benefit of ketamine over currently available therapies.

Studies of the biotransformation and pharmacology of ketamine and its metabolites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leung, Y.

1986-01-01

The first part of the research is concerned with the synthesis, resolution and metabolism of norketamine, the primary metabolite of ketamine. Incubations of racemic norketamine, individual enantiomers of norketamine and the pseudoracemates in rat liver microsomes revealed stereoselectivity and enantiomeric interactions during the metabolism of norketamine. The second part of the research describes the synthesis of 6-OH-norketamine, the major secondary metabolite of ketamine, and reports on its pharmacological activity and cerebral distribution in the rat. Primary deuterium isotope effects associated with the metabolism and pharmacological activity of ketamine-N-CD/sub 3/ were examined in the third part of this research. The lastmore » part of the research deals with the effect of diazepam on the metabolic transformation of ketamine to norketamine in the rat. The fractions of ketamine metabolized to norketamine were found not to be different in the presence or the absence of diazepam.« less

Population pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief of chronic pain.

PubMed

Dahan, Albert; Olofsen, Erik; Sigtermans, Marnix; Noppers, Ingeborg; Niesters, Marieke; Aarts, Leon; Bauer, Martin; Sarton, Elise

2011-03-01

Pharmacological treatment of chronic (neuropathic) pain is often disappointing. In order to enhance our insight in the complex interaction between analgesic drug and chronic pain relief, we performed a pharmacokinetic-pharmacodynamic (PK-PD) modeling study on the effect of S(+)-ketamine on pain scores in Complex Regional Pain Syndrome type 1 (CRPS-1) patients. Sixty CRPS-1 patients were randomly allocated to received a 100-h infusion of S(+)-ketamine or placebo. The drug infusion rate was slowly increased from 5 mg/h (per 70 kg) to 20 mg/h based upon the effect/side effect profile. Pain scores and drug blood samples were obtained during the treatment phase and pain scores were further obtained weekly for another 11 weeks. A population PK-PD model was developed to analyze the S(+)-ketamine-pain data. Plasma concentrations of S(+)-ketamine and its metabolite decreased rapidly upon the termination of S(+)-ketamine infusion. The chance for an analgesic effect from ketamine and placebo treatment was 67±10% and 23±9% (population value±SE), respectively. The pain data were well described by the PK-PD model with parameters C(50)=10.5±4.8 ng/ml (95% ci 4.37-21.2 ng/ml) and t½ for onset/offset=10.9±4.0 days (5.3-20.5 days). Long-term S(+)-ketamine treatment is effective in causing pain relief in CRPS-1 patients with analgesia outlasting the treatment period by 50 days. These data suggest that ketamine initiated a cascade of events, including desensitization of excitatory receptor systems in the central nervous system, which persisted but slowly abated when ketamine molecules were no longer present. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine.

PubMed

Liu, Shirley Yuk Wah; Ng, Stephen Ka Kei; Tam, Yuk Him; Yee, Samuel Chi Hang; Lai, Franco Pui Tak; Hong, Cindy Yuek Lam; Chiu, Philip Wai Yan; Ng, Enders Kwok Wai; Ng, Chi Fai

2017-09-01

Evaluations of upper gastrointestinal toxicity from ketamine abuse are uncommon. This study investigated the clinical pattern of upper gastrointestinal symptoms in patients inhaling ketamine. In a cross-sectional study of 611 consecutive patients who were seeking treatment for ketamine uropathy in a tertiary hospital setting between August 2008 and June 2016, their clinical pattern of upper gastrointestinal symptoms was evaluated and compared with a control population of 804 non-users. A total of 168 (27.5%) patients abusing ketamine (mean age 26.3 years, 58.9% female) reported the presence of upper gastrointestinal symptoms. These symptoms were significantly more prevalent in patients inhaling ketamine than in those who were not (27.5% vs 5.2%, P < 0.001). Their mean duration of ketamine abuse before symptom presentation was 5.0 ± 3.1 years. The presenting symptoms included epigastric pain (n = 155, 25.4%), recurrent vomiting (n = 48, 7.9%), anemia (n = 36, 5.9%) and gastrointestinal bleeding (n = 20, 3.3%). Uropathy symptoms were preceded by upper gastrointestinal symptoms for 4.4 ± 3.0 years in 141 (83.9%) patients. Logistic regression showed that elder age (odds ratio [OR] 1.06, P = 0.04), active abuser status (OR 1.60, P = 0.04) and longer duration of ketamine abuse (OR 1.00, P = 0.04) were independent factors associated with upper gastrointestinal toxicity. Although epigastric symptoms are unusual in the young population, upper gastrointestinal toxicity was highly prevalent in those inhaling ketamine. Enquiries about ketamine abuse are recommended when assessing young patients with epigastric symptoms. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Rapid and sensitive detection of ketamine in blood using novel fluorescence genosensor.

PubMed

Ding, Yanjun; Li, Xingmei; Guo, Yadong; Yan, Jie; Ling, Jiang; Li, Weichen; Lan, Lingmei; Chang, Yunfeng; Cai, Jifeng; Zha, Lagabaiyla

2017-12-01

In recent years, drug abuse has been considered as a most challenging social problem that aroused public attention. Ketamine has increased in unregulated use as a 'recreational drug' in teenagers. However, there is no suitable and maneuverable detection method for ketamine in situ at the moment. Fluorescence sensor technique, with predominant recognition and simple operation, is a good potential application in drug detection. Here, we first reported a highly sensitive and selective fluorescence genosensor for rapid detection of ketamine based on DNA-templated silver nanoclusters (DNA-AgNCs) probes, in which the DNA sequence could specially recognize ketamine with high affinity. Parameters affecting detection efficiency were investigated and optimized. Under optimum conditions, the as-prepared genosensor can allow for the determination of ketamine in the concentration range of 0.0001-20 μg/mL with two linear equations: one is y = 2.84x-7.139 (R 2 = 0.987) for 0.0001-0.1 μg/mL, and the other is y = 1.87x-0.091 (R 2 = 0.962) for 0.1-20 μg/mL, and the estimated detection limit of ketamine is 0.06 ng/mL. Moreover, the feasibility of this proposed method was also demonstrated by analyzing forensic blood samples. Compared with official gas chromatography/mass spectrometry (GC/MS), this fluorescence genosensor is simple, rapid, and accurate for quantitative determination of ketamine in blood for pharmaceutical and forensic analysis. Overall, it is the first report on a fluorescence genosensor for detecting ketamine directly in blood. This research may provide a new insight for the analyst to band fluorescence genosensor technology together with drug monitoring in the battle against drug abuse and forensic examination. Graphical abstract High selectively detection of ketamine using a novel fluorescence genosensor based on DNA-AgNCs probe.

Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial.

PubMed

Anderson, Ian M; Blamire, Andrew; Branton, Tim; Clark, Ross; Downey, Darragh; Dunn, Graham; Easton, Andrew; Elliott, Rebecca; Elwell, Clare; Hayden, Katherine; Holland, Fiona; Karim, Salman; Loo, Colleen; Lowe, Jo; Nair, Rajesh; Oakley, Timothy; Prakash, Antony; Sharma, Parveen K; Williams, Stephen R; McAllister-Williams, R Hamish

2017-05-01

The use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine. In this multicentre, randomised, parallel-group study in 11 ECT suites serving inpatient and outpatient care settings in seven National Health Service trusts in the North of England, we recruited severely depressed patients, who were diagnosed as having unipolar or bipolar depressive episodes defined as moderate or severe by DSM-IV criteria, aged at least 18 years, and were able and willing to provide written consent to participate in the study. Patients were randomly assigned (1:1) to ketamine (0·5 mg/kg intravenous bolus) or saline adjunctive to the anaesthetic for the duration of their ECT course. Patients and assessment and ECT treatment teams were masked to treatment allocation, although anaesthetists administering the study medication were not. We analysed the primary outcome, Hopkins Verbal Learning Test-Revised delayed verbal recall (HVLT-R-DR) after four ECT treatments, using a Gaussian repeated measures model in all patients receiving the first ECT treatment. In the same population, safety was assessed by adverse effect monitoring. This trial was registered with International Standard Randomised Controlled Trial Number, number ISRCTN14689382. Between early December, 2012, and mid-June, 2015, 628 patients were screened for eligibility, of whom 79 were randomly assigned to treatment (40 in the ketamine group vs 39 in the saline group). Ketamine (mean 5·17, SD 2·92), when compared with saline (5·54, 3·42), had no benefit on the primary outcome (HVLT-R-DR; difference in means -0·43 [95% CI -1·73 to 0·87]). 15 (45%) of 33 ketamine-treated patients compared with 10 (27%) of 37 patients receiving saline experienced at least

Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain?

PubMed

Mathews, Timothy J; Churchhouse, Antonia M D; Housden, Tessa; Dunning, Joel

2012-02-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'is the addition of ketamine to morphine patient-controlled analgesia (PCA) following thoracic surgery superior to morphine alone'. Altogether 201 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This consisted of one systematic review of PCA morphine with ketamine (PCA-MK) trials, one meta-analysis of PCA-MK trials, four randomized controlled trials of PCA-MK, one meta-analysis of trials using a variety of peri-operative ketamine regimes and two cohort studies of PCA-MK. Main outcomes measured included pain score rated on visual analogue scale, morphine consumption and incidence of psychotomimetic side effects/hallucination. Two papers reported the measurements of respiratory function. This evidence shows that adding ketamine to morphine PCA is safe, with a reported incidence of hallucination requiring intervention of 2.9%, and a meta-analysis finding an incidence of all central nervous system side effects of 18% compared with 15% with morphine alone, P = 0.31, RR 1.27 with 95% CI (0.8-2.01). All randomized controlled trials of its use following thoracic surgery found no hallucination or psychological side effect. All five studies in thoracic surgery (n = 243) found reduced morphine requirements with PCA-MK. Pain scores were significantly lower in PCA-MK patients in thoracic surgery papers, with one paper additionally reporting increased patient satisfaction. However, no significant improvement was found in a meta-analysis of five papers studying PCA-MK in a variety of surgical settings. Both papers reporting respiratory outcomes found improved oxygen saturations and PaCO(2) levels in PCA-MK patients following thoracic surgery

GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects

PubMed Central

Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

2013-01-01

Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054

Efficacy of Ketamine in Improving Pain after Tonsillectomy in Children: Meta-Analysis

PubMed Central

Cho, Hye Kyung; Kim, Kyu Won; Jeong, Yeon Min; Lee, Ho Seok; Lee, Yeon Ji; Hwang, Se Hwan

2014-01-01

Background and objectives The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children. Subjects and Methods Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0–24 hours after leaving the operation room were included in the analysis. Results The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics. Conclusion Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study. PMID:24979227

Chemical immobilization of chimpanzees (Pan troglodytes) using a combination of detomidine and ketamine.

PubMed

Melis, Sanne; Schauvliege, Stijn; van Bolhuis, Hester; Hoyer, Mark; Gasthuys, Frank

2012-09-01

To determine if a combination of detomidine and ketamine can be used for effective chemical immobilization of chimpanzees. Observational study. Twenty-one adult captive chimpanzees (12 males, nine females), age 8-46 years, weighing 40.4-68.4 kg. The chimpanzees were immobilized with intramuscular (IM) detomidine and ketamine by a darting system. Based on estimated weights, doses administered were 50 μg kg(-1) detomidine and 4 mg kg(-1) ketamine in groups 1 and 2, and 60 μg kg(-1) and 5 mg kg(-1) respectively in group 3. Eight minutes in group 1 and 15 minutes in groups 2 and 3 were allowed from the time of apparent immobilization before removing the animals from their enclosures. Body temperature, arterial haemoglobin saturation and pulse rate were measured. The time from injection to induction (recumbency and absence of voluntary movement), total anaesthetic and recovery times (with or without atipamezole) were recorded. Immobilization occurred within 5 minutes after darting in most animals. Early handling of the chimpanzees often resulted in arousal and required further doses of ketamine IM. Most animals were hypoxaemic and hypothermic. Occasionally, bradycardia was observed. Atipamezole resulted in an acceptable quality of recovery 10 minutes after IM injection. The duration of immobilization varied widely when no antagonist was administered. The combination detomidine (60 μg kg(-1) ) and ketamine (5-6 mg kg(-1) ) can be used for the immobilization of chimpanzees for non- to minimally invasive procedures. A period of 15 minutes should be allowed before handling to avoid unwanted arousal. Oxygen administration is recommended to reduce hypoxaemia. Administration of atipamezole is justified to hasten recovery. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Ketamine-induced ventricular structural, sympathetic and electrophysiological remodelling: pathological consequences and protective effects of metoprolol

PubMed Central

Li, Y; Shi, J; Yang, BF; Liu, L; Han, CL; Li, WM; Dong, DL; Pan, ZW; Liu, GZ; Geng, JQ; Sheng, L; Tan, XY; Sun, DH; Gong, ZH; Gong, YT

2012-01-01

BACKGROUND AND PURPOSE Growing evidence suggests that long-term abuse of ketamine does harm the heart and increases the risk of sudden death. The present study was performed to explore the cardiotoxicity of ketamine and the protective effects of metoprolol. EXPERIMENTAL APPROACH Rats and rabbits were divided into control, ketamine, metoprolol alone and ketamine plus metoprolol groups. Ketamine (40 mg·kg−1·day−1, i.p.) and metoprolol (20 mg·kg−1·day−1, p.o.) were administered continuously for 12 weeks in rats and 8 weeks in rabbits. Cardiac function, electrophysiological disturbances, cardiac collagen, cardiomyocte apoptosis and the remodelling-related proteins were evaluated. KEY RESULTS Rabbits treated with ketamine showed decreased left ventricular ejection fraction, slowed ventricular conduction velocity and increased susceptibility to ventricular arrhythmia. Metoprolol prevented these pathophysiological alterations. In ketamine-treated rats, cardiac collagen volume fraction and apoptotic cell number were higher than those of control animals; these effects were prevented by co-administration of metoprolol. Consistently, the expressions of poly (ADP-ribose) polymerases-1, apoptosis-inducing factor and NF-κB-light-chain-enhancer of activated B cells were all increased after ketamine treatment and sharply reduced after metoprolol administration. Moreover, ketamine enhanced sympathetic sprouting, manifested as increased growth-associated protein 43 and tyrosine TH expression. These effects of ketamine were prevented by metoprolol. CONCLUSIONS AND IMPLICATIONS Chronic treatment with ketamine caused significant ventricular myocardial apoptosis, fibrosis and sympathetic sprouting, which altered the electrophysiological properties of the heart and increased its susceptibility to malignant arrhythmia that may lead to sudden cardiac death. Metoprolol prevented the cardiotoxicity of ketamine, indicating a promising new therapeutic strategy. PMID:21883145

Ketamine and the metabolite norketamine: persistence and phototransformation toxicity in hospital wastewater and surface water.

PubMed

Lin, Angela Yu-Chen; Lee, Wan-Ning; Wang, Xiao-Huan

2014-04-15

Ketamine has been increasingly used both recreationally and medicinally around the world. Although the metabolic pathways to form its metabolite norketamine have been carefully investigated in humans and animals, knowledge of their environmental occurrence and fate is limited. In this study, we investigated the occurrence of ketamine and norketamine in 20 natural bodies of water, effluents from 13 hospitals, two wastewater treatment plants and one water supply plant. Ketamine was found at concentrations as high as 10 μg/L. Ketamine and norketamine were consistently found in similar concentrations (ketamine/norketamine ratio: 0.3-4.6) in the collected water samples, and this ratio similar to that found in urine samples. Dark incubation experiments have shown that ketamine is not susceptible to microbial degradation or hydrolysis. Phototransformation was demonstrated to significantly reduce the concentration of ketamine and norketamine in river waters (t(1/2) = 12.6 ± 0.4 and 10.1 ± 0.4 h, respectively) and resulted in byproducts that are similar to human metabolites. Both direct and indirect photolysis led to the N-demethylation of ketamine to form norketamine and other byproducts, including hydroxy-norketamine (HNK), dehydronorketamine (DNK), hydroxy-ketamine (HK) and isomer forms of ketamine and norketamine. Irradiated solutions exhibited higher toxicity (via the Microtox test). Although a final risk assessment could not be made due to a lack of studies on the chronic effects on aquatic organisms, the high and persistent environmental occurrences of ketamine and norketamine as well as the increasingly acute toxicity of the photo byproducts demonstrate the importance of including metabolites in evaluation of the overall risk of ketamine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predictors of failure of awake regional anesthesia for neonatal hernia repair: data from the General Anesthesia compared to Spinal anesthesia (GAS) study: comparing apnoea and neurodevelopmental outcomes

PubMed Central

Frawley, Geoff; Bell, Graham; Disma, Nicola; Withington, Davinia E.; de Graaff, Jurgen C.; Morton, Neil S.; McCann, Mary Ellen; Arnup, Sarah J.; Bagshaw, Oliver; Wolfler, Andrea; Bellinger, David; Davidson, Andrew J.

2015-01-01

Background Awake regional anesthesia (RA) is a viable alternative to general anesthesia (GA) for infants undergoing lower abdominal surgery. Benefits include lower incidence of postoperative apnea and avoidance of anesthetic agents that may increase neuroapoptosis and worsen neurocognitive outcomes. The General Anesthesia compared to Spinal anesthesia (GAS) study compares neurodevelopmental outcomes following awake RA or GA in otherwise healthy infants. Our aim was to describe success and failure rates of RA in this study and report factors associated with failure. Methods This was a nested cohort study within a prospective randomized, controlled, observer blind, equivalence trial. Seven hundred twenty two infants ≤ 60 weeks postmenstrual age, scheduled for herniorrhaphy under anesthesia were randomly assigned to receive RA (spinal, caudal epidural or combined spinal caudal anesthetic) or GA with sevoflurane. The data of 339 infants, where spinal or combined spinal caudal anesthetic was attempted, was analyzed. Possible predictors of failure were assessed including: patient factors, technique, experience of site and anesthetist and type of local anesthetic. Results RA was sufficient for the completion of surgery in 83.2% of patients. Spinal anesthesia was successful in 86.9% of cases and combined spinal caudal anesthetic in 76.1%. Thirty four patients required conversion to GA and an additional 23 (6.8%) required brief sedation. Bloody tap on the first attempt at lumbar puncture was the only risk factor significantly associated with block failure (OR = 2.46). Conclusions The failure rate of spinal anesthesia was low. Variability in application of combined spinal caudal anesthetic limited attempts to compare the success of this technique to spinal alone. PMID:26001028

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

PubMed

Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

2017-12-01

We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

Long-Term Antihyperalgesic and Opioid-Sparing Effects of 5-Day Ketamine and Morphine Infusion ("Burst Ketamine") in Diabetic Neuropathic Rats.

PubMed

Mak, Plato; Broadbear, Jillian H; Kolosov, Anton; Goodchild, Colin S

2015-09-01

"Burst ketamine" (BK) is the long-term infusion of subanesthetic ketamine in combination with an opioid. It is used clinically with mixed success to provide long-term pain relief and improve opioid response in patients. BK has not been simulated preclinically, therefore, its effectiveness was investigated in an animal model of neuropathic pain--streptozotocin-induced diabetic neuropathy. Diabetic neuropathic rats were randomized to receive a subcutaneous infusion of ketamine 20 mg/kg/day plus morphine 20 mg/kg/day (BK), either drug alone at the same dose, or sham treatment. Drugs were administered continuously over 5 days via osmotic minipump. Antihyperalgesic effects and antinociceptive responsiveness to morphine (0.625-10 mg/kg, i.p.) were assessed at 2, 4, 6, and 12 weeks post-treatment using paw withdrawal latency (PWL) from noxious heat (thermal hyperalgesia) and mechanical touch (tactile allodynia). Antihyperalgesic effects with significant increases in PWL from noxious heat occurred following BK and ketamine-only infusion, persisting 12 and 4 weeks, respectively. Opioid-sparing effects from noxious heat with increased sensitivity to morphine analgesia also occurred for 6 weeks after BK and 2 weeks after ketamine treatment; acute treatment with the maximum nonsedating dose of morphine (5 mg/kg) produced an antinociceptive effect in these two groups, but not in sham-treated rats. In morphine-only infusion rats, hyperalgesia and opioid insensitivity were both increased. This is the first preclinical study to use a model of neuropathic pain to demonstrate the utility of the BK procedure for delivering a long-lasting reduction in hyperalgesia and improved antinociceptive responsiveness to opioids. Wiley Periodicals, Inc.

Patterns of Polydrug Use Among Ketamine Injectors in New York City

PubMed Central

LANKENAU, STEPHEN E.; CLATTS, MICHAEL C.

2007-01-01

Polydrug use is an important public health issue since it has been linked to significant adverse health outcomes. Recently, club drugs, including ketamine and other drugs used in dance/rave scenes, have been identified as key substances in new types of polydrug using patterns. While seemingly a self-explanatory concept, “polydrug” use constitutes multiple drug using practices that may impact upon health risks. Ketamine, a club drug commonly administered intranasally among youth for its disassociative properties, has emerged as a drug increasingly prevalent among a new hidden population of injection drug users (IDUs). Using an ethno-epidemiological methodology, we interviewed 40 young (<25 years old) ketamine injectors in New York during 2000–2002 to describe the potential health risks associated with ketamine and polydrug use. Findings indicate that ketamine was typically injected or sniffed in the context of a polydrug using event. Marijuana, alcohol, PCP, and speed were among the most commonly used drugs during recent ketamine using events. Polydrug using events were often quite variable regarding the sequencing of drug use, the drug combinations consumed, the forms of the drug utilized, and the modes of administrating the drug combinations. Future research should be directed towards developing a more comprehensive description of the risks associated with combining ketamine with other drugs, such as drug overdoses, the transmission of bloodborne pathogens, such as HIV and HCV, the short- and long-term effects of drug combinations on cognitive functioning, and other unanticipated consequences associated with polydrug use. PMID:16048823

Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model

PubMed Central

Weber, Nina C.; van der Sluijs, Koen; Hackl, Florian; Hotz, Lorenz; Dahan, Albert; Hollmann, Markus W.; Berger, Marc M.

2014-01-01

We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (IV) bolus injection had no effect. The aim of the present study was to characterize whether continuous IV infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of IV S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered IV over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by IV lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by IV S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by IV S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of IV S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport. PMID:25386677

Ventral CA3 Activation Mediates Prophylactic Ketamine Efficacy Against Stress-Induced Depressive-like Behavior.

PubMed

Mastrodonato, Alessia; Martinez, Randy; Pavlova, Ina P; LaGamma, Christina T; Brachman, Rebecca A; Robison, Alfred J; Denny, Christine A

2018-02-23

We previously reported that a single injection of ketamine prior to stress protects against the onset of depressive-like behavior and attenuates learned fear. However, the molecular pathways and brain circuits underlying ketamine-induced stress resilience are still largely unknown. Here, we tested whether prophylactic ketamine administration altered neural activity in the prefrontal cortex and/or hippocampus. Mice were injected with saline or ketamine (30 mg/kg) 1 week before social defeat. Following behavioral tests assessing depressive-like behavior, mice were sacrificed and brains were processed to quantify ΔFosB expression. In a second set of experiments, mice were stereotaxically injected with viral vectors into ventral CA3 (vCA3) in order to silence or overexpress ΔFosB prior to prophylactic ketamine administration. In a third set of experiments, ArcCreER T2 mice, a line that allows for the indelible labeling of neural ensembles activated by a single experience, were used to quantify memory traces representing a contextual fear conditioning experience following prophylactic ketamine administration. Prophylactic ketamine administration increased ΔFosB expression in the ventral dentate gyrus and vCA3 of social defeat mice but not of control mice. Transcriptional silencing of ΔFosB activity in vCA3 inhibited prophylactic ketamine efficacy, while overexpression of ΔFosB mimicked and occluded ketamine's prophylactic effects. In ArcCreER T2 mice, ketamine administration altered memory traces representing the contextual fear conditioning experience in vCA3 but not in the ventral dentate gyrus. Our data indicate that prophylactic ketamine may be protective against a stressor by altering neural activity, specifically the neural ensembles representing an individual stressor in vCA3. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Evaluation of the use of midazolam as a co-induction agent with ketamine for anaesthesia in sedated ponies undergoing field castration.

PubMed

Allison, A; Robinson, R; Jolliffe, C; Taylor, P M

2018-05-01