氯胺酮对体外循环患者磷酸二酯酶活性的影响

目的:探讨体外循环(CPB)期间静脉注射小剂量氯胺酮对外周血白细胞磷酸二酯酶(PDE)活性的影响。方法:30例择期行瓣膜置换术患者随机分为氯胺酮组和对照组,每组各15例,于麻醉诱导前、CPB开始后30min及CPB结束后1 h测定血白细胞的PDE活性。结果:两组PDE活性在CPB开始后30 min及CPB结束后1h时较术前均显著升高(P<0.05);但两组间比较,氯胺酮组明显低于对照组(P<0.05)。结论:CPB后人外周血白细胞PDE活性明显升高,小剂量氯胺酮具有抑制其升高的作用。     

异丙酚和氯胺酮麻醉在头面部肿瘤手术中的比较

目的研究异丙酚和氯胺酮麻醉在头面部手术中对血流动力学的影响和术后清醒度的比较。方法５０例病人，ＡＳＡ分级为Ⅰ－Ⅱ，随机分为两组，异丙酚麻醉组（Ｄ），氯胺酮麻醉组（Ｋ）。Ｄ组用异丙酚２．５ｍｇ．ｋｇ－１诱导，用Ｇｒａｅｓｂｙ－３４０泵注异丙酚４．５ｍｇ·ｋｇ－１·ｈ－１维持麻醉；ｋ组用氯胺酮２．０ｍｇ／ｋｇ－１诱导，静脉点滴氯胺酮３ｍｇ·ｋｇ－１·ｈ－１维持麻醉。观察麻醉前（Ｔ０）、注药后（Ｔ１）、插管后（Ｔ２）、手术时（Ｔ３）、拔管前（Ｔ４）５个时点的ＨＲ、ＢＰ的变化，同时观察术后病人清醒的情况，并比较组内的变化和组间的变化。结果两组均对血流动力学有影响，Ｋ组在注药后、插管后、拔管前血压明显升高、心率加快；而Ｄ组在相对时点的ＨＲ、ＢＰ变化比Ｋ组较轻。同时，Ｄ组术后比Ｋ组清醒明显快。结论异丙酚静脉麻醉在头面部肿瘤手术中比氯安酮麻醉更为安全。     

高效液相色谱法测定术前儿童口服复方氯胺酮的血药浓度

目的测定儿童口服复方氯胺酮的血药浓度并探讨血药浓度与药效学的关系。方法用高效液相方法测定用药后不同时点氯胺酮(KET)、咪达唑仑(MZ)、阿托品(AT)的血药浓度;观察药物显效时间、镇静止痛效果。结果KET的tmax=(30±15)min,Cmax=(633±121)ng·mL-1;MZ的tmax=(30±15)min,Cmax=(105±35)ng·mL-1。患儿服药(10±4)min,血中可测到KET、MZ的含量;(30±20)min达峰;未检测到AT。结论复方氯胺酮口服液起效时间与其血药浓度高峰期相近。     

N-乙酰半胱氨酸和氯胺酮联用对脑缺血再灌注损伤的影响

目的:研究巯基供体物质N 乙酰半胱氨酸(NAC)和非竞争性NMDA受体拮抗剂氯胺酮(KT)联用对小鼠脑缺血再灌注损伤的影响。方法:雄性ICR小鼠,随机分为假手术组、生理盐水组(0 .0 1L·g- 1)、氯胺酮组(15mg·kg- 1)、N 乙酰半胱氨酸组(75mg·kg- 1)和联合组(KT 15mg·kg- 1 NAC75mg·kg- 1)。参照蒋晓帆等建立的方法,制备局灶性短暂性脑缺血再灌注模型(tMCAO) ,再灌注后6、2 4h测定神经行为缺陷评分,处死TTC染色测定脑梗死面积百分比;制备不完全性脑缺血再灌注模型(2 VO) ,在再灌注0 .5、2和6h时取全脑制成10 %匀浆,比色法测定MDA含量、SOD和GSH Px活力。结果:(1)短暂性局灶性脑缺血再灌注后6、2 4h ,各组小鼠脑组织均有不同程度梗死灶、神经行为缺陷明显,与生理盐水组比较,药物联合组可显著改善缺血再灌注小鼠的神经行为缺陷(均为P <0 .0 1) ,减少脑梗死面积百分比(均为P <0 .0 1) ,药物单用对以上指标有轻度的改善作用(P >0 .0 5 )。(2 )联合用药可明显改善脑细胞损伤。(3)与假手术组比较,不完全性全脑缺血再灌注损伤0 .5、2和6h后,生理盐水组小鼠MDA含量显著升高(均为P <0 .0 1) ,SOD活性(均为P <0 .0 1)和GSH Px活性均显著降低(均为P <0 .0 1)。与生理盐水组比较,联合组可显著地降低缺血再灌注小鼠脑组织     

Sedation with intravenous ketamine and midazolam for painful procedures in children

BACKGROUND: Children often require relief of pain and anxiety when undergoing painful procedures. The purpose of this study is to evaluate the effectiveness and safety of painful pediatric procedures performed by pediatric intensivist, using the combination of intravenous ketamine and midazolam for sedation and analgesia. METHODS: The records of the patients who received intravenous ketamine-midazolam combination for painful procedures in the pediatric sedation unit of a university hospital over a 3 year period were retrospectively reviewed to determine indications, dosing, assessment of the level of sedation, adverse events, and recovery time for each procedural sedation and analgesia. RESULTS: A total of 227 children aged 4 months to 18 years were admitted to the pediatric sedation unit for a total of 356 procedures. The indications for procedural sedation and analgesia included bone marrow aspiration or biopsy (50.8%), central venous catheter insertion (27%), and others (22%). A total of 46 adverse events (12.9%) were observed. These adverse events included SpO2 below 85% without apnea (n = 14), apnea (n = 3), transient stridor (n = 2), hypertension and tachycardia (n = 8), hypersalivation (n = 6), vomiting (n = 5), hallucinatory emergence reaction (n = 4), and rash (n = 4). There were no adverse outcomes attributable to ketamine and midazolam combination. CONCLUSION: Skilled pediatric intensivists can safely and effectively administer ketamine and midazolam to facilitate painful procedures outside the operating room setting.     

鞘内注射哌唑嗪对氯胺酮抗伤害作用的影响

目的　探讨脊髓α1 受体和氯胺酮(Ket, 37. 5mg·kg-1,ip)抗伤害作用的关系。方法　用热水甩尾法观察大鼠鞘内预先注射α1 受体拮抗剂哌唑嗪(Pra, 10, 30μg)对Ket抗伤害作用的影响。并用c fos基因免疫组织化学技术,观察Ket对痛刺激诱发的大鼠脊髓c- fos表达的调节作用及鞘内预先注射Pra(30μg)对Ket调节作用的影响。结果　鞘内单独注射各剂量Pra对动物痛阈均无明显影响(P>0 .05), 鞘内预注Pra(10μg)对Ket抗伤害作用无明显影响(P>0 .05)。而鞘内预注Pra(30μg)则可明显减弱Ket抗伤害作用(P<0 .05)。痛刺激前给予Ket明显减少背角各层Fos免疫阳性神经元的数量(P<0 .05),Ket对痛刺激诱发的脊髓ⅠⅣ层c fos表达的抑制作用可被鞘内预注Pra所减弱(P<0 .05)。结论　脊髓α1 受体参与Ket抗伤害作用。     

Effect of Ketamine Added to Ropivacaine in Nerve Block for Postoperative Pain Management in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Trial

PurposeNerve blocks are commonly used as a part of multimodal pain relief. It was previously shown that ketamine could enhance the analgesic effect of local anesthetics in nerve blocks. A literature review on adding ketamine to local anesthetics for ameliorating analgesia revealed inconsistencies in analgesic efficiency and safety. This prospective, randomized, double-blind trial was performed to evaluate the antinociceptive effect of mixing ketamine with local anesthetics in a combined femoral and sciatic nerve block (CFSNB) during anterior cruciate ligament (ACL) reconstruction.MethodsSeventy-six patients undergoing preoperative ultrasound-guided CFSNB in ACL reconstruction were enrolled. Patients were randomly assigned to 3 groups: Group RNK received perineural administration of 40-mg ketamine plus 0.375% ropivacaine in 40-mL volume; Group RIK received 40 mL of 0.375% ropivacaine, as well as IV ketamine 40 mg; and Group R received 40 mL of 0.375% ropivacaine. Pain scores were recorded. AUC was calculated based on the pain scores at different times. Duration of CFSNB, postoperative analgesic demand, time to first analgesic demand, and adverse events were also examined.FindingsPerineural ketamine decreased pain scores 20 and 24 h' postoperatively, as well as lowered AUC values (all, P = 0.001). Group RNK had a prolonged time to first analgesic request (P = 0.014), inhibited rebound pain (P = 0.001), and increased satisfactory score at 48 h’ postsurgery (P = 0.001). Perineural ketamine prolonged the duration of sensory block (P = 0.001) with no effect on early mobilization. There were no significant differences between Group R and Group RIK in terms of postoperative pain scores, AUC of different time intervals (P = 0.832 or more), and time to first rescue analgesics (P = 0.585). Compared with the 2 other groups, IV ketamine had a higher incidence of hallucination after operations.ImplicationsPerineural ketamine added to the ropivacaine-enhanced analgesic efficacy of CFSNB with less rebound pain compared with the IV ketamine and control groups. IV ketamine had no effect in potentiating analgesia when a conventional multimodal approach was used in the study. Chinese Clinical Trial Registry: ChiCTR1900023867.     

Molecular mechanisms for the antidepressant-like effects of a low-dose ketamine treatment in a DFP-based rat model for Gulf War Illness

Exposure to organophosphates (OP) during the First Gulf War is among one of the factors for Gulf War Illness (GWI) development in veterans and it has been challenging to treat GWI symptoms with existing therapies. Ketamine produces a rapid-onset and sustained antidepressant response, but there is no evidence whether ketamine treatment is effective for GWI depression. Repeated, low-dose exposure to diisopropyl fluorophosphate (DFP) mimic Gulf War related OP exposures and produces a chronic depressive state in rats. In this study, DFP-exposed rats treated with ketamine (10 mg/kg, i.p.) exhibited antidepressant-like effect on the Forced Swim Test at 1-h. This effect persisted at 24-h post ketamine, a time-point by which it is eliminated from the brain suggesting involvement of mechanisms that affect long-term synaptic plasticity. Western blot analysis showed significantly lower Brain-Derived Neurotrophic Factor (BDNF) levels in DFP rat brains. Ketamine produced a nonsignificant increase in BDNF expression at 1-h but produced a larger, significant (2.2-fold) increase at 24-h in DFP rats. We previously reported chronic hippocampal calcium elevations ([Ca²⁺]_i) in DFP rats. Ketamine-treated DFP rats exhibited significantly lower [Ca²⁺]_i at 1-h but not at 24-h. Interestingly, treatment with ANA-12, a TrkB-BDNF receptor antagonist, in DFP rats blunted ketamine’s antidepressant-like effect at 24-h but not at 1-h. These experiments suggest that in a rat model of DFP-induced depression, inhibition of the NMDAR-Ca²⁺ contributes to the rapid-onset antidepressant effects of ketamine while the antidepressant actions that persisted at 24-h post ketamine administration involve upregulation of BDNF signaling.     

Ketamine for chronic pain: risks and benefits

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.