Chronopharmacological studies of ketamine in normal and NMDA epsilon1 receptor knockout mice

Background. The effectiveness and toxicity of many drugs dependson the dosing-time schedule, relative to the circadian rhythmsof biochemical, physiological, and behavioural processes. Previousstudies have found chronopharmacology of ketamine, which isa N-methyl-D-aspartate (NMDA) receptor antagonist. The in vivocontribution of the NMDA receptor     

Racemic ketamine does not abolish cerebrovascular autoregulation in the pig

BACKGROUND: Little is known about the influence of racemic ketamine on autoregulation of cerebral blood flow (CBF), and available reports regarding its influence on cerebral hemodynamics are contradictory. This study was designed to evaluate cerebrovascular responses to changes in the mean arterial pressure (MAP) during ketamine anesthesia. METHODS: In eight normoventilated pigs anesthesia was induced with propofol and maintained by i.v. infusion of ketamine (15.0 mg kg(-1) x h(-1)) during measurements. The intra-arterial xenon clearance technique was used to calculate CBF. Balloon-tipped catheters were introduced in the inferior caval vein and mid-aorta, and increases or decreases by up to 40% in mean arterial pressure (MAP) in random order were achieved by titrated inflation of these balloon catheters. Cerebral blood flow was determined at each MAP level. Regression coefficients of linear pressure-flow curves were calculated in all animals. RESULTS: From the mean baseline level (101 mmHg) MAP was reduced by 20% and 40%, and increased by 26% and 43%. The maximal mean increase and decrease in MAP induced a 12% increase and a 15% decrease, respectively, of CBF from the mean baseline level (52.6 ml.100 g(-1) x min1). The 95% confidence interval (-0.02; 0.38) of the mean regression coefficient of individual pressure-flow curves does not include the regression coefficient (0.64) of a linear correlation between MAP and CBF including origo (correlation coefficient 0.99), which indicates complete lack of cerebrovascular autoregulation. CONCLUSIONS: We conclude that autoregulation of CBF is not abolished during continuous ketamine infusion in normoventilated pigs and that previous divergent conclusions are unlikely to be associated with severe impairment of cerebrovascular autoregulation.     

Uvulopalatopharyngoplasty for sleep apnea in mentally retarded obese 14-year-old: an anaesthetic challenge

Anaesthetic management of patients with obstructive sleep apnea for upper airway surgery has always been a challenging task. We report our anaesthetic approach for a young, mentally retarded obese patient with documented obstructive sleep apnea undergoing uvulopalatopharyngoplasty. The therapeutic intervention before, during and after operation is discussed.     

Ketamine and midazolam is an inappropriate preinduction combination in uncooperative children undergoing brief ambulatory procedures

BACKGROUND: We prospectively studied the effects of intramuscular (i.m.) ketamine alone, or combined with midazolam, on mask acceptance and recovery in young children who were uncooperative during induction of anaesthesia. METHODS: The Institutional Review Board (IRB) approval was obtained to study 80 children, 1-3 years, scheduled for bilateral myringotomies and tube insertion (BMT). Mask induction was attempted in all the children. Those who were uncooperative were randomly assigned to one of the four preinduction treatment groups: group I, ketamine 2 mg.kg(-1); group II, ketamine 2 mg.kg(-1) combined with midazolam 0.1 mg.kg(-1); group III, ketamine 2 mg.kg(-1) with midazolam 0.2 mg.kg(-1); or group IV, ketamine 1 mg.kg(-1) with midazolam 0.2 mg.kg(-1). Anaesthesia was continued with nitrous oxide and halothane by facemask. RESULTS: Children in all treatment groups achieved satisfactory sedation in less than 3 min following the administration of the preinduction drug(s). Compared with patients who received halothane induction (comparison group), the use of ketamine alone did not significantly (P > 0.0167, a Bonferroni corrected significance level) delay recovery and discharge times (18.8 +/- 2.5 and 82.5 +/- 30.7 min vs 12.6 +/- 4.6 and 81.0 +/- 33.8 min, P = 0.030 and P = 0.941, respectively). Patients who received ketamine/midazolam combinations, however, had significantly longer recovery and discharge times vs halothane (32.3 +/- 14.0 and 128.0 +/- 36.6 min, P = 0.001, P = 0.007, respectively). These times were so clinically unacceptable, that the study had to be terminated with only 17 patients receiving study drugs. CONCLUSIONS: It is concluded that ketamine/midazolam combination is not appropriate for preinduction of anaesthesia in paediatric ambulatory patients because of unacceptably prolonged recovery and delayed discharge times.     

Nonopioid additives to local anaesthetics for caudal blockade in children: a systematic review

BACKGROUND: Caudal epidural injection with local anaesthetics is a popular regional technique used in infants and children. A disadvantage of caudal blockade is the relatively short duration of postoperative analgesia. Opioids have traditionally been added to increase the duration of analgesia but have been associated with unacceptable side-effects. A number of nonopioid additives have been suggested to increase the duration of analgesia. METHODS: A systematic review was conducted to identify randomized control trials comparing the use of local anaesthetic to local anaesthetic with nonopioid additives for caudal blockade in children. The increase in duration of analgesia and side-effects were compared. RESULTS: The addition of clonidine to the local anaesthetic solution produces an increase in the duration of analgesia following caudal blockade in children (pooled weighted mean difference of 145 min with 95% confidence interval of 132-157 min). Side-effects include sedation and the potential for neonatal respiratory depression. Ketamine and midazolam further increase the duration of analgesia, however, the potential for neurotoxicity remains a concern. CONCLUSION: The evidence examined shows an increased duration of analgesia with clonidine, ketamine and midazolam. However, we are not convinced that the routine use of these adjuvants in the setting of elective outpatient surgery shows improved patient outcome. It is unclear if the potential for neurotoxicity is outweighed by clinical benefits. Further testing, including large clinical trials, is required before recommending routine use of nonopioid additives for caudal blockade in children.     

Does ketamine or magnesium affect posttonsillectomy pain in children?

BACKGROUND: Many previous studies have suggested a role for the N-methyl-D-aspartate (NMDA) receptor antagonists ketamine and magnesium in decreasing postoperative pain and analgesic requirements in adults, but none has investigated these medications in children. METHODS: This randomized, double-blind, placebo-controlled study evaluated the effects of ketamine and magnesium in children undergoing tonsillectomy. Eighty patients, aged 3-12 years, were randomly assigned to four groups. Patients received either ketamine 0.15 mg.kg-1, magnesium sulphate 30 mg.kg-1, ketamine 0.15 mg.kg-1 plus magnesium sulphate 30 mg.kg-1, or placebo intravenously 5 min prior to the start of surgery. Intraoperative analgesia was standardized, and included fentanyl and dexamethasone. RESULTS: There were no differences among the groups with respect to pain assessment postoperatively. Compared with placebo, the treatment groups did not require less fentanyl in the postanaesthesia recovery room or consume less codeine in the first 24-h postoperatively. There was no evidence of synergism between ketamine and magnesium. There were no differences among the groups in the incidence of nausea, vomiting, sedation, bleeding, or dreaming postoperatively. CONCLUSION: This study did not demonstrate a decrease in pain or analgesic consumption in children undergoing tonsillectomy when pretreated with a small dose of ketamine and/or magnesium.     

Anesthetics inhibit high-affinity states of dopamine D2 and other G-linked receptors

The high-affinity states of dopamine D2 and D3 receptors, serotonin 5HT-2A receptors, beta-2-adrenoceptors, alpha-1 and alpha-2 adrenoceptors, opiate receptors, and muscarinic receptors were inhibited by clinical concentrations of anesthetics, including isoflurane, halothane, chloral hydrate, ketamine, and ethanol. The inhibition occurred not only in vitro, but also in vivo in rats anesthetized with isoflurane, with the high-affinity states recovering at different rates. Because the high-affinity states of G-protein-linked receptors are physiologically functional, their general inhibition by clinical concentrations of anesthetics may underlie general anesthesia and may explain some of the side effects of anesthetics. Subanesthetic concentrations of the anesthetics, including ketamine, stimulated the incorporation of GTP into the cloned dopamine D2 receptors. It is possible that the classical stage 2 excitement phase which occurs with subanesthetic concentrations of general anesthetics and ketamine may be associated with this general stimulation of a variety of G-protein-linked receptors, as found in the present study, while the stage 3 level of surgical anesthesia may be associated with the inhibition of the high-affinity states of several receptors.     

氯胺酮复合麻醉合并硬膜外阻滞在小儿腹部手术的应用

目的　比较氯胺酮复合麻醉合并硬膜外阻滞和单纯氯胺酮复合麻醉在小儿腹部手术中的应用效果。方法　对 40例随机分为复合组 (A组 ) 2 0例 ,单纯氯胺酮复合麻醉组 (B组 ) 2 0例。观察术中麻醉效果及并发症 ,并记录氯胺酮用量 ,术毕作清醒程度的判断。结果　麻醉效果满意率A组明显优于B组 (P <0 .0 5 )。术中氯胺酮用量A组 (80± 15 )mg比B组 (15 0± 10 )mg显著少 (P <0 .0 1)。与B组比较 ,A组术毕未醒例数极显著减少 ,完全清醒例数大大增多 (P <0 .0 1)。A组无呼吸抑制、恶心、呕吐 ,而B组肌颤 2例、呕吐 3例。结论　氯胺酮复合麻醉合并硬膜外阻滞 ,镇痛完善 ,肌肉松驰 ,用药量明显减少 ,术后并发症少 ,清醒快     

Quantifying the Psychological Effects of Ketamine: From Euphoria to the k-Hole

52 ketamine users were “opportunistically” recruited to take part in a survey of the psychological effects of the drug, in Manchester, United Kingdom in 2008. Twenty-seven ketamine-naïve respondents were also recruited for comparison in respect of “other” recreational drug use and level of schizotypy. Ketamine users attributed a wide range of appetitive, aversive, after-effect, and dissociative experiences to the drug. They also reported using a much wider range of other recreational drugs than ketamine non-users. Former users reported significantly fewer positive or dissociative experiences than current users.