鞘内注射不同剂量氯胺酮对切口痛大鼠痛行为的影响

目的:观察鞘内注射不同剂量氯胺酮(Ketamine)对趾部切口痛大鼠痛行为的影响。方法:48只雄性SD大鼠麻醉下鞘内置入聚乙烯导管并固定,7 d后按Brennan法制备趾部切口疼痛模型。随机分为对照组、K1、K2、K3组,每组12只。K1组、K2组和K3组在切口后30 min鞘内分别注射氯胺酮5μg、50μg和100μg,连续7 d,对照组在切口后30 min鞘内注射人工脑脊液10μL。分别于手术前、手术后1 h、手术后1,2,3,5,7 d在用药后30 min测定热刺激缩足反射潜伏期和累积疼痛评分的变化。结果:手术前各组大鼠热刺激缩足反射潜伏期和累计疼痛评分差异无显著性(P>0.05);与对照组相比,K1组上述各个时间点的热刺激缩足反射潜伏期和累计疼痛评分无差异(P>0.05);与对照组和K1组相比,K2组和K3组上述个各时间点的热刺激缩足反射潜伏期显著延长、累计疼痛评分明显降低(P<0.05或P<0.01)。结论:鞘内注射氯胺酮5μg无明显镇痛作用,而氯胺酮50μg或100μg则有明显的镇痛效应。     

阈下氯胺酮伍合异丙酚在肿瘤病人全麻诱导期对心血管系统的影响

目的：评估预注氯胺酮预防异丙酚在肿瘤病人全麻诱导插管期所致血压下降的作用。方法;２６例肿瘤择期手术全麻病人,随机分为Ｐ组和Ｋ＋Ｐ组各１３例,分别用工分太尼３μｇ／ｋｇ、异丙酚２ｍｇ／ｋｇ及氯胺酮０．８ｍｇ／ｋｇ,芬太尼３μｇ／ｋｇ,划丙酚２ｍｇ／ｋｇ,异丙酚２ｍｇ／ｋｇ行全麻诱导。比较两组病例在诱导前后及气管插管后收缩压（ＳＢＰ）、平均动脉压（ＭＡＰ）、舒张压（ＤＢＰ）和心率（ＨＲ）的变化。结果：     

氯胺酮麻醉复合眶下神经阻滞在小儿唇裂修补术中的应用

目的:观察氯胺酮麻醉复合眶下神经阻滞在小儿唇裂修补术中应用的麻醉效果并探讨其安全性。方法:50例行唇裂修补术患儿,随机分为对照组和实验组,每组各25例。对照组采用氯胺酮麻醉,实验组采用氯胺酮麻醉复合眶下神经阻滞,同时观察两组患儿麻醉过程中循环和呼吸参数的变化以及麻醉效果。结果:实验组麻醉效果优良率为96％,对照组为48％,实验组的优良率明显高于对照组,P<0.05。结论:在小儿唇裂修补术中,氯胺酮麻醉复合眶下神经阻滞,操作简便安全且麻醉效果好,临床上值得推广应用。     

The effects of a subanesthetic dose of ketamine on verbal memory in normal volunteers

Rationale N-methyl-d-aspartate (NMDA) glutamate receptor antagonists have been reported to induce schizophrenia-like symptoms in humans, including memory impairments. Although the NMDA receptor has been shown to impair memory acquisition by disrupting long-term potentiation (LTP), limited research has been done on studying the effects of NMDA antagonists on the post-LTP cascade of events implicated in consolidation as measured by administering the drug after the initial learning experience.Objective The purpose of this experiment was to examine the effect of ketamine on mental status and to identify NMDA antagonist-induced memory deficits by comparing the recall performance of items presented both immediately before and during ketamine infusion.Methods Thirteen normal controls received a 60-min infusion of ketamine in a randomized double-blind, cross-over design. Mental status was evaluated with the Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale. The first 12-item word list was presented immediately before infusion, and two lists were subsequently presented during the infusion. Verbal memory performance was assessed by measuring the delayed cued recall of each list 30 min after its presentation.Results At the beginning, subjects experienced perceptual and reality distortion symptoms, followed later by mild subjective effects. Ketamine significantly reduced the delayed recall of words presented immediately before, but not during, drug infusion. Ketamine-induced decrements in verbal recall correlated significantly with plasma ketamine levels.Conclusion This study characterizes the behavioral effects associated with ketamine and suggests that ketamine decreases verbal memory performance by interfering with early consolidation processes.     

Impaired visuospatial divided attention in the spontaneously hypertensive rat

The magnitude of an acoustic startle response can be reduced by a weak stimulus presented immediately before the startle-eliciting noise. This phenomenon has been termed prepulse inhibition of the startle reaction (PPI). Previous studies indicated that the primary neural pathways mediating PPI belong to the brain stem and that the inferior colliculus (IC) was crucial. Its destruction reduced PPI. Stimulations applied to brain areas may be as deleterious as lesions. Therefore, we looked for the possibility of a brain stimulation applied to the IC during a PPI test to reduce also PPI. Rats were implanted with chronic electrodes, their tips being aimed at the IC. They were located within or close to the inter-colliculus nucleus. A train of stimulations was applied and PPI was tested alternately during and between periods of stimulation. As the most common method used to attenuate PPI consists in administrating drugs, for example ketamine, we also tested the effect of this drug. Another drug was also tested, diazepam, since it alters the functioning of the IC without any known effect on PPI. This allowed a comparative analysis of the neurobiological and the pharmacological effects. It appeared that the stimulation decreased PPI quantitatively as much as ketamine (6 mg/kg) without an effect of the basic startle reaction. These effects did not interfere with each other. Diazepam (1 mg/kg) did not modify PPI, neither under stimulation nor per se. Only for a very high dose (4 mg/kg), a sedative and myo-relaxant one the basic startle and PPI were altered.     

Dialogues on complex analgesic strategies for difficult pain syndromes

Although the use of oral analgesics for the control of cancer pain has been demonstrated to be successful in most patients, some patients will fail to respond to pharmacological therapy or will suffer unacceptable adverse effects. Experience is accumulating that when adverse effects prevail with oral opioid administration, the analgesic response may be improved by changing the drug and/or the route of administration. Switching to an alternative opioid may further improve the balance between analgesia and adverse effects Despite optimal systemic opioid treatment, in some complicated circumstances it is necessary to find different solutions, including the neuraxial administration of multiple drugs with different characteristics, which are difficult to manage. Three case reports illustrate how complex could be the analgesic approach using multiple analgesic regimens and different routes of administration to effectively manage complex pain syndromes commonly defined as unresponsive.     

Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose–response study

Rationale Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist that has medical indications but is also used as a recreational drug. Previous research has found persisting cognitive and psychotogenic effects of ketamine in chronic abusers of this drug 3 days after an acute dose.Objective The present study aimed to investigate the effects of ketamine on two processes related to drug abuse, response inhibition and reinforcement, and to examine whether an acute dose of ketamine produced residual cognitive effects in healthy volunteers.Methods Fifty-four healthy volunteers were given an 80-min infusion of one of two doses (0.4, 0.8 mg kg^–1) of ketamine or placebo. Subjects completed a battery of tests at three time points: pre-infusion, during the infusion and 3 days later at follow-up. The battery consisted of tests of episodic and semantic memory, schizophrenic-like and dissociative symptoms, response inhibition and measures of subjective effects, including mood, bodily symptoms and enjoyment of and desire for the drug.Results Ketamine acutely impaired response inhibition and had related biphasic effects on the subjective reinforcing effects of the drug. Ketamine also acutely impaired episodic but not semantic memory and increased schizophrenic-like and dissociative symptoms. No residual cognitive effects were observed 3 days following an acute dose.Conclusions The lack of residual effects in healthy volunteers on day 3 indicates that impairments found on day 3 in ketamine abusers are chronic effects. The abuse of ketamine may be related to its capacity both to reinforce and to decrease response inhibition.     

Propofol for pediatric radiotherapy

Objective : Pediatric radiotherapy is a day care procedure. In children, anaesthesia is necessary to prevent movement during the therapy. Traditionally intramuscular ketamine is used for these procedure because of its inherent safety in a child who used to be left alone in the cobalt room.Methods : This study was designed to explore the efficacy of propofol and ketamine in pediatric radiotherapy in nineteen children. The inclusion criteria was a child fasting for six hours with no fever or URTI in the past week. A child coming to the radiotherapy (RT) unit without an intravenous cannula was given intramuscular ketamine 10 mg/kg and taken for the procedure. Before the child recovered from anaesthesia an intravenous cannula, 20–22G, Vasofix was inserted for subsequent sittings of RT. The child coming with an intravenous cannula was given propofol 2.5 mg/kg with xylocaine (0.1 mg/kg) without adrenaline. The parameters recorded were pulse rate, oxygen saturation and respiratory rate-baseline to every 30 seconds till five minutes. Onset time, recovery time, oral feeding time and any untoward effects like nausea, vomiting, nystagmus were also noted.Result: The drug was graded on a scale of 0–10 according to parental acceptability where 0 is the worst and 10 is the best acceptability. The mean (±SD) of all the measured parameters were calculated and compared between the two groups.Conclusion : Propofol was associated with faster onset, better recovery, early oral feeding time, no nausea and vomiting and better parental acceptability. There was no hypotension, bradycardia and oxygen saturation at 60 seconds, which was betwen 94–95%, was easily treatable with supplementation of oxygen by face mask     

Low dose ketamine increases prepulse inhibition in healthy men

The N-methyl-D-aspartate (NMDA) antagonist, ketamine, produces neurobehavioural symptoms that mimic aspects of schizophrenia. Prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating, is decreased in chronically ill, medicated schizophrenic patients and in animals treated acutely with NMDA antagonists. We tested the hypothesis that ketamine would produce psychotic symptoms and reduce PPI in healthy humans. Twenty male volunteers received placebo and ketamine in a within-subject, double-blind, cross-over design with 0.23 mg/kg ketamine hydrochloride or saline as a loading dose, followed by 0.5 mg/kg ketamine or saline over 45 min. Prepulse to pulse intervals were 30 ms and 120 ms. The Brief Psychiatric Rating Scale (BPRS) and the Clinician Administered Dissociative States Scale (CADSS) were administered. Ketamine produced a significant increase in PPI and significantly reduced startle magnitude, but did not alter habituation. Ketamine produced significant increases in BPRS and CADSS scores, with symptoms mimicking the negative and disorganisation symptoms of psychosis. In contrast to effects in rodents, this low dose of ketamine produced an increase in PPI despite producing psychopathological symptoms consistent with the NMDA psychosis model. These findings suggest that the cognitive and PPI changes of NMDA antagonists are not consistently linked at a phenomenological or neurochemical level.     

Antinociceptive interactions of ketamine with morphine or methadone in mononeuropathic rats

To study the antinociceptive synergy resulting from the combination of opioid receptor agonists and N-methyl-D-aspartate (NMDA) receptor antagonists on neuropathic pain, an isobolographic analysis of equianalgesic combinations of ketamine with methadone or morphine was performed in rats with mononeuropathy produced by placing four constrictive ligatures around the common sciatic nerve. Two weeks later, the antinociceptive effect of subcutaneous administration of the drugs alone or combined was evaluated by using the paw pressure test. Drugs and their combinations produced dose-dependent antinociception. Combinations produced synergy of a supra-additive nature in the neuropathic paw, but only additive antinociception in the normal paw. The ketamine/methadone combination was more effective to produce antinociception in the neuropathic paw than was the ketamine/morphine association, as revealed by the lower ED25. The results indicate supra-additive synergy between NMDA receptor antagonists and opioids, especially methadone, to produce antinociception in experimental neuropathy.