To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a comprehensive...To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a comprehensive behavioural training paradigm,relatively expensive apparatus and invasive surgical procedures.展开更多
Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MD...Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.Aims We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation,both anxious and non-anxious.Methods Fifty-four adolescents with anxious(n=33)and non-anxious(n=21)MDD received three infusions of esketamine 0.25mg/kg or active-placebo(midazolam 0.045 mg/kg)over 5 days,with routine inpatient care and treatment.Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Asberg Depression Rating Scale.Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion(day 6,primacy efficacy endpoint)and throughout the 4-week post-treatment(days 12,19 and 33).Results In subjects who received esketamine,a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6(72.7%vs 18.8%,p=0.015)and day 12(90.9%vs 43.8%,p=0.013),and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33(72.7%vs 26.7%,p=0.045).No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.Conclusions Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD;however,this benefit was temporary and was not maintained over time.展开更多
The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable ...The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable side effects to the patients. While not restricted to patients with chronic pain, these patients are often diagnosed with depression, presenting with symptoms such as poor mood, anhedonia, and altered cognitive processes. It is estimated that a substantial proportion of treated patients do not derive a substantive benefit from traditional pharmacological treatments for depression. The present study involved a retrospective review of cases, exploring the patient-reported satisfaction with and tolerability of a novel use of virtual reality (VR), coined KVR, as an adjunct to intravenous ketamine infusion therapies. Specifically, the ketamine-virtual reality protocol was employed as a potential adjunctive intervention for patients suffering from chronic pain and depression. Visual Analog Scores (VAS) associated with pain were significantly lower on the third than on the first assessment day. Montgomery-?sberg Depression Rating Scale (MADRS) scores improved following infusion and across days (i.e., sessions). Lastly, 2/3 of patients preferred the use of VR with their ketamine infusion. The results are considered in terms of implementing prospective studies to examine whether the combination therapies have a synergistic benefit and the nature and magnitude of clinically meaningful treatment effects, if any.展开更多
Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia...Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia has multiple benefits, including rapid, effective and titratable analgesic delivery. The aim of our study is to assess the efficacy and safety of intranasal analgesic-dose ketamine compared to multimodal analgesia in patients presenting with acute postoperative pain or headache after a spinal anaesthetic in the intensive care unit of obstetrics and gynaecology. Materials and Methods: This was a prospective descriptive study, with hospital Ethics Committee approval and written informed consent from study participants. We compared the effect of nebulized ketamine and multimodal analgesia postoperatively in 120 patients belonging to the physical status I - II of the American Society of Anesthesiologists, in the intensive care unit of obstetrics and gynaecology, at the Ibn Rochd University Hospital Center in Casablanca from June 2021 to June 2022. Results: We included 120 patients in our study divided into two groups of 60 patients: the average age was 35 years, with extremes ranging from 18 to 45 years, All patients were hospitalized for postoperative care: all women underwent locoregional anaesthesia with a standard dose according to the service protocol (10 mg of bupivacaine, 25γ of fentanyl, 100γ of morphine), where pain was the common denominator. Among these patients, 59 were admitted for management of postpartum haemorrhage, 43 for postoperative monitoring, 15 for post-spinal anaesthesia headache and 3 for pelviperitonitis. The results of the pain assessment 30 minutes after the ketamine nebulization were marked by a request for analgesia in 12 patients, which is 20% of group A, including 5 patients, whose visual analogue scale (VAS) on admission was between 5 and 7, and 7 patients whose VAS at admission was ≥8;all these patients received a second dose of ketamine by nebulization;the evaluation 30 min after the second dose was marked by a request for analgesia in 4 patients, which is 7% of Group A;in all these patients the VAS at admission was ≥8. Of the total number of patients of Group A, only 4 received morphine when they were requested for analgesia after the second dose of nebulized ketamine. Conclusion: The primary outcome of nebulized ketamine use is a significant reduction in VAS pain score. We believe that nebulized ketamine has a potential effect of reducing pain in the intensive care unit of obstetrics and gynaecology;this may be an additional analgesic modality for clinicians to provide rapid, effective and non-invasive pain relief.展开更多
<strong>Background</strong>: Inpatient subanaesthetic ketamine infusion for 5 days may improve pain and reduce oral opioid usage in patients with chronic pain. <strong>Objective</strong>: This ...<strong>Background</strong>: Inpatient subanaesthetic ketamine infusion for 5 days may improve pain and reduce oral opioid usage in patients with chronic pain. <strong>Objective</strong>: This study aims to investigate pain and psychological outcomes of ketamine parenteral infusion (0.1 - 0.35 mg/kg/h or maximum 24 mg/hour) for 5 days in patients with chronic refractory pain. The secondary objective is to explore any prognostic pain and psychological factors associated with the successful response to the ketamine treatment. <strong>Methodology</strong>: A prospective longitudinal study of a small cohort (N = 35) of patients with heterogenous chronic refractory pain conditions was conducted from one week to two months follow-up. <strong>Results</strong>: Pain Severity was significantly improved from mean 6.5 to 5.1 (t = 3.77, p < 0.001, d = 0.6) at 1-week and 5.9 (t = 2.14, p = 0.042, d = 0.4) at 2-month;Pain Interference from mean 7.0 to 5.1 (t = 4.99, p < 0.001, d = 0.9) at 1-week and 6.1 (t = 2.16, p = 0.041, d = 0.4) at 2-month;Pain Self-Efficacy Questionnaire (PSEQ) from mean 17 to 24 (t = <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>3.37, p = 0.002, d = <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>0.6) at 1-week and 23 (t =<span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>2.60, p = 0.016, d =<span style="white-space:nowrap;">−</span><span style="white-space:nowrap;"></span>0.5) at 2-month;Pain Catastrophizing (PCS) from 28 to 23 (t = 3.4, p = 0.002;d = 0.6) at 1-week and 21 (t = 2.45, p = 0.022, d = 0.5) at 2-month;Depression from mean 21 to 16 (t = 2.16, p = 0.038, d = 0.4) at 1-week and 16 (t = 3.53, p = 0.002, d = 0.7) at 2-month;and oral Morphine Equivalent Daily Dose (oMEDD) reduced from mean 191 mg/day on admission to 122 mg/day at 1-week (t = 2.38, p = 0.023;d = 0.4) and 93 mg/day at 2-month (t = 2.59, p = 0.016;d = 0.5). There was no significant difference between responders and non-responders on baseline psychological measures (t<sub>33</sub> < 1.19, p > 0.244) and pain classifications ( <img src="Edit_c68fc9e4-a875-4b79-b0cf-af146ed090fe.png" alt="" /> = 0.610, p = 0.894). <strong>Conclusion</strong>: Ketamine subanaesthetic dose infusion for 5 days was found to be effective in managing chronic refractory pain with significant opioid reduction and small improvements in all chronic pain outcomes, except anxiety, at 1-week and 2-month follow-up and with minimal severe adverse effects.展开更多
Objective:To investigate the effects of propofol and ketamine on the cognitive function and immune function in young rats.Method:A total of 80 young rats were randomly divided into four groups:Control group,ketamine g...Objective:To investigate the effects of propofol and ketamine on the cognitive function and immune function in young rats.Method:A total of 80 young rats were randomly divided into four groups:Control group,ketamine group(experimental group A),propofol group(experimental group B),ketamine and propofol group(experimental group Q.All rats had continuous injection for three times,serum IL-2,IL-4 and II.-10 and whole brain IL-I P level,hippocampal neuronal apoptosis level were measured.The cognitive ability in rats was tested by water maze.Results:Water maze test showed on the 1st d,the maze test latency of the control group,the experimental group B and the experimental group C water were decreased gradually;Compared with the control group after 3 days,the latency of the experimental group A,experimental group B and experimental group C were all decreased,the crossing circle times were also reduced.Hippocampal neuron apoptosis were(2.3±1.7)%,(14.7±6.9)%,(4.2±3.3)%,(10.2±4.8r%in control group,experimental group A,experimental group B and experimental group C,respectively.The neurons apoptosis of experimental group A was significantly increased.The serum IL-4 and 1L-10 of the experimental group A,experimental group B and experimental group C after anesthesia were significantly higher than the control group.The whole brain IL-1β of the experimental group A,experimental group B and experimental group C were significantly lower than the control group.Conclusions:Propofol can reduce anesthesia effect of ketamine on the cognitive function and immune function in the young rats.展开更多
Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapopto...Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when activated.Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour intervals.At 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated p66ShcA.We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours.The same procedure was performed on a different group of rats.At the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water maze.Latency to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was similar.These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period.This may have contributed to the deficit in spatial learning and memory that persisted into adulthood.The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval No.A13.008) on January 22,2013.展开更多
Objective: To discuss the neuron-protective effect and possible mechanism of subanesthestic-dosage ketamine on Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Methods: A total of 3...Objective: To discuss the neuron-protective effect and possible mechanism of subanesthestic-dosage ketamine on Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Methods: A total of 30 mice were divided equally into three groups, model control group(MC group), ketamine treatment group(KT group), and blank control group(BC group), respectively.The Parkinson's disease mice of MC group and KT groups were established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(20 mg/kg/d), while mice in KT group were treated by intraperitoneal injection of subanesthestic-dosage ketamine(8 mg/kg).Differences on behaviors and the number of nigra dopaminergic neurons of mice in each group were compared through the behavioral test and tyrosine hydroxylase immunohistochemistry experiments after the treatments.Furthermore, Western blot was used to test the expression of autophagy-related gene LC3-Ⅱ, Beclin1, Parkin, PINK1,and mTOR.Results: Compared with the BC group, the neuroethology scores were lower and the amount of TH positive cells were less both in MC and MT groups; In KT group, the neuroethology scores were higher and the amount of tyrosine hydroxylase positive cells were significantly more than that in MC group(P < 0.05).Moreover, expression levels of autophagy-related proteins LC3-II, Beclin1, Parkin, and PINK1 were higher, while the mTOR expression level was lower than that in MC group.Conclusions: The subanesthestic-dosage ketamine has some protective effects on the coordinating ability of movement and cognitive ability of Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.This is probably due to that the autophagy activity of cells is activated by subanesthestic-dosage ketamine and that the neurons are protected.展开更多
OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neur...OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.展开更多
Ketamine, a rapid-acting antidepressant drug, has been used to treat major depressive disorder and bipolar disorder(BD). Recent studies have shown that ketamine may increase the potential risk of treatment-induced man...Ketamine, a rapid-acting antidepressant drug, has been used to treat major depressive disorder and bipolar disorder(BD). Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in patients. Ketamine has also been applied to establish animal models of mania. At present, however, the underlying mechanism is still unclear. In the current study, we found that chronic lithium exposure attenuated ketamine-induced mania-like behavior and c-Fos expression in the medial prefrontal cortex(mPFC) of adult male mice. Transcriptome sequencing was performed to determine the effect of lithium administration on the transcriptome of the PFC in ketamine-treated mice, showing inactivation of the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Pharmacological inhibition of AKT signaling by MK2206(40 mg/kg), a selective AKT inhibitor, reversed ketamine-induced mania.Furthermore, selective knockdown of AKT via AAVAKT-sh RNA-EGFP in the mPFC also reversed ketamine-induced mania-like behavior. Importantly,pharmacological activation of AKT signaling by SC79(40 mg/kg), an AKT activator, contributed to mania in low-dose ketamine-treated mice. Inhibition of PI3K signaling by LY294002(25 mg/kg), a specific PI3K inhibitor, reversed the mania-like behavior in ketamine-treated mice. However, pharmacological inhibition of mammalian target of rapamycin(mTOR)signaling with rapamycin(10 mg/kg), a specific mTOR inhibitor, had no effect on ketamine-induced mania-like behavior. These results suggest that chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway, which may be a novel target for the development of BD treatment.展开更多
AIM To determine if ketamine sedation is a safe and cost effective way of treating displaced paediatric radial and ulna fractures in the emergency department. METHODS Following an agreed interdepartmental protocol, fr...AIM To determine if ketamine sedation is a safe and cost effective way of treating displaced paediatric radial and ulna fractures in the emergency department. METHODS Following an agreed interdepartmental protocol, fractures of the radius and ulna(moderately to severely displaced) in children between the age of 2 and 16 years old, presenting within a specified 4 mo period, were manipulated in our paediatric emergency department. Verbal and written consent was obtained prior to procedural sedation to ensure parents were informed and satisfied to have ketamine. A single attempt at manipulation was performed. Pre and postmanipulation radiographs were requested and assessed to ensure adequacy of reduction. Parental satisfaction surveys were collected after the procedure to assess the perceived quality of treatment. After closed reduction and cast immobilisation, patients were then followed-up in the paediatric outpatient fracture clinic and functional outcomes measured prospectively. A cost analysis compared to more formal manipulation under a general anaesthetic was also undertaken.RESULTS During the 4 mo period of study, 10 closed, moderate to severely displaced fractures were identified and treated in the paediatric emergency department using our ketamine sedation protocol. These included fractures of the growth plate(3), fractures of both radius and ulna(6) and a single isolated proximal radius fracture. The mean time from administration of ketamine until completion of the moulded plaster was 20 min. The mean time interval from sedation to full recovery was 74 min. We had no cases of unacceptable fracture reduction and no patients required any further manipulation, either in fracture clinic or under a more formal general anaesthetic. There were no serious adverse events in relation to the use of ketamine. Parents, patients and clinicians reported extremely favourable outcomes using this technique. Furthermore, compared to using a manipulation under general anaesthesia, each case performed under ketamine sedation was associated with a saving of ￡1470, the overall study saving being ￡14700. CONCLUSION Ketamine procedural sedation in the paediatric population is a safe and cost effective method for the treatment of displaced fractures of the radius and ulna, with high parent satisfaction rates.展开更多
Objective:To investigate the effects of propofol and ketamine on seizure duration,hemodynamics,and recovery of electroconvulsive therapy(ECT).Methods:This prospective randomized trial included patients who had undergo...Objective:To investigate the effects of propofol and ketamine on seizure duration,hemodynamics,and recovery of electroconvulsive therapy(ECT).Methods:This prospective randomized trial included patients who had undergone ECT under anesthesia.Patients received injection of propofol 1.5 mg/kg i.v.(the propofol group)or ketamine 0.8-1.2 mg/kg i.v.(the ketamine group)during ECT.Seizure duration,hemodynamics,and recovery were recorded and compared between the two groups.Results:This trial included 44 patinets with 22 patients receiving propofol and 22 patients receiving ketamine.The total dose of propofol and ketamine was(105.68±25.27)mg and(81.36±24.55)mg,respectively.The motor seizure and electroencephalogram seizure duration were prolonged in the ketamine group(P<0.001).The hemodynamics at the admission of the two groups were comparable(P>0.05);however,the mean systolic blood pressure during the procedure was significantly higher in the ketamine group(P=0.04).Besides,spontaneous eye-opening in the ketamine group took longer than that of the propofol group(P=0.001).Conclusion:Both propofol and ketamine are safe as anesthetic agents for modified ECT,and ketamine provides a longer seizure duration without hemodynamic instability or any significant complication.展开更多
BACKGROUND:Pain in the emergency department(ED)is common but undertreated.The objective of this study was to examine the efficacy and safety of intranasal(IN)ketamine used as an analgesic for patients with acute injur...BACKGROUND:Pain in the emergency department(ED)is common but undertreated.The objective of this study was to examine the efficacy and safety of intranasal(IN)ketamine used as an analgesic for patients with acute injury with moderate to severe pain.METHODS:This study was a cross sectional,observational study of patients more than 8 years old experiencing moderate to severe pain[visual analog score(VAS)>50 mm].The initial dose of IN ketamine was 0.7 mg/kg with an additional dose of 0.3 mg/kg if VAS was more than 50 mm after 15minutes.Pain scores and vital signs were recorded at 0,15,30 and 60 minutes.Side-effects,sedation level and patient's satisfaction were also recorded.The primary outcome was the number of patients achieving≥20 mm reductions in VAS at 15 minutes.Other secondary outcome measures were median reduction in VAS at 15,30 and 60 minutes,changes of vital signs,adverse events,satisfaction of patients,and need for additional ketamine.RESULTS:Thirty-four patients with a median age of 29.5 years(IQR 17.5–38)were enrolled,and they had an initial median VAS of 80 mm(IQR 67–90).The VAS decreased more than 20 mm at15 minutes in 27(80%)patients.The reduction of VAS from baseline to 40 mm(IQR 20–40),20 mm(IQR 14–20)and 20 mm(IQR 10–20)respectively at 15,30 and 60 minutes(P<0.001).No critical changes of vital signs were noted and adverse effects were mild and transient.CONCLUSION:This study showed that IN ketamine is an analgesic choice for patients with acute injury in moderate to severe pain in an overcrowded and resource limited ED.展开更多
Major depressive disorder(MDD)is a common,serious,debilitating condition affecting 350 million people worldwide,which remains to be unsatisfactorily treated with 53%of patients still complaining of symptoms after comp...Major depressive disorder(MDD)is a common,serious,debilitating condition affecting 350 million people worldwide,which remains to be unsatisfactorily treated with 53%of patients still complaining of symptoms after completing their courses with the correct dosage.Ketamine,which was approved by the Food and Drug Administration in 2019,is a potential treatment option for those recalcitrant cases.The mechanism of ketamine is not fully understood,but as type it is classified as an N-methyl-D-aspartate(NMDA)glutamate receptor antagonist,and can be given intravenously,intranasally and orally.It is used to treat treatment-resistant depression,depression associated with suicidal ideation,mood and anxiety disorders and depressions associated with either type of bipolar disorder.Although ketamine is considered relatively safe,several side effects have been reported with the major ones being psychiatric in the form of worsening mood,anxiety and agitation;psychotomimetic in the form of dissociation,perceptual disturbance and abnormal sensations;cardiovascular in the form of increased blood pressure and increased heart rate;and neurological in the form of headache and dizziness.Ketamine is still not approved worldwide for usage in patients with treatment-resistant MDD,but if it is approved sometime in the future with relatively fewer side effects,it is expected to significantly save millions of dollars spent yearly on patients with treatment-resistant depression and that will lift this major burden off the shoulders of healthcare professionals.This study was designed to measure the effects of ketamine,an NMDA receptor antagonist,on patients with treatment-resistant MDD and to analyse the concept that makes it different and relatively safer than other major antidepressants like selective serotonin reuptake inhibitors,monoamine oxidase inhibitors and TCAs(tricyclic antidepressants).展开更多
Background The use of ketamine in electroconvulsive therapy(ECT)has been examined in the treatment of major depressive disorder(MDD);however,there has been no systematic review and meta-analysis of related randomised ...Background The use of ketamine in electroconvulsive therapy(ECT)has been examined in the treatment of major depressive disorder(MDD);however,there has been no systematic review and meta-analysis of related randomised controlled trials(RCTs).Aim To examine the efficacy and safety of ketamine augmentation of ECT in MDD treatment.Methods Two reviewers searched Chinese(China National Knowledge Infrastructure and Wanfang)and English(PubMed,PsycINFO,Embase and Cochrane Library)databases from their inception to 23 July 2019.The included studies'bias risk was evaluated using the Cochrane risk of bias assessment tool.The primary outcome of this metaanalysis was improved d印ressive symptoms at day 1 after a single ECT treatment session.Data were pooled to calculate the standardised mean difference and risk ratio with their 95%CIs using RevMan V.5.3.We used the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach to assess the whole quality of evidence.Results Four RCTs(n=239)compared ketamine alone or ketamine plus propofol(n=149)versus propofol alone(n=90)in patients with MDD who underwent a single ECT session.Three RCTs were considered as unclear risk with respect to random sequence generation using the Cochrane risk of bias.Compared with propofol alone,ketamine alone and the combination of ketamine and propofol had greater efficacy in the treatment of depressive symptoms at days 1,3 and 7 after a single ECT session.Moreover,compared with propofol alone,ketamine alone and the combination of ketamine and propofol were significantly associated with increased seizure duration and seizure energy index.Compared with propofol,ketamine alone was significantly associated with increased opening-eye time.Based on the GRADE approach,the evidence level of primary and secondary outcomes ranged from very low(26.7%,4/15)to‘low'(73.3%,11/15).Conclusion Compared with propofol,there were very low or low evidence levels showing that ketamine alone and the combination of ketamine and propofol appeared to rapidly improve depressive symptoms of patients with MDD undergoing a single ECT session.There is a need for highquality RCTs.展开更多
Background: Anesthetic agents are commonly utilized in the handling of non‐human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to...Background: Anesthetic agents are commonly utilized in the handling of non‐human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to describe the effect of age and dissociative anesthetics (ketamine and tiletamine), and their combinations with acepromazine, xylazine and zolazepam, on the physiological and blood biochemical parameters in Macaca mulatta. Methods: Eighty male Macaca mulatta were divided into four experimental groups depending on the anesthetic mixture applied. Each group of 20 males was divided into five sub‐groups according to age. Physiological parameters were recorded every five minutes during a 30‐minute period. A blood sample was drawn to analyze blood biochemistry. Results: Statistical analyses revealed significant differences in the physiological parameters between the ketamine‐acepromazine and ketamine‐xylazine groups compared to the control group. The analysis of blood biochemistry found significant differences by age and by anesthetic mixture among all groups. Conclusion: These findings contribute to standardizing this animal model in biological research.展开更多
Objective: To compare acute and long-term postoperative pain and side effects in patients undergoing mastectomy for breast cancer under general anesthesia induced with ketamine or thiamylal. Methods: Twenty four ASA p...Objective: To compare acute and long-term postoperative pain and side effects in patients undergoing mastectomy for breast cancer under general anesthesia induced with ketamine or thiamylal. Methods: Twenty four ASA physical status I-III patients undergoing mastectomy were randomly assigned to one of two groups. Ketamine group received intravenous ketamine, 1 mg/kg, and thiamylal group received intravenous thiamylal, 4 mg/kg, at the induction of general anesthesia. Anesthesia was maintained with sevoflurane, N2O and fentanyl. The intensity of pain was assessed by using visual analog scale (VAS) 3 and 16 hr and 2, 3 and 4 weeks after surgery. Postoperative side effects, including nausea, vomiting and hallucination were also recorded. Results: At 16 hr after surgery, VAS in ketamine group was significantly lower than that in thiamylal group. However, there were no statistically significant differences between the two groups in the VAS at 3 hr and 2, 3 and 4 weeks after surgery. There were no differences in the incidence of side effects such as nausea, vomiting and hallucination between the two groups. Conclusion: Intravenous ketamine at the induction of anesthesia could reduce acute postoperative pain but not long-term pain after mastectomy.展开更多
Background: Emergence agitation (EA) after sevoflurane anesthesia is common in children. When rapid intravenous induction of general anesthesia is indicated in a brief procedure, the induction agent can reduce the inc...Background: Emergence agitation (EA) after sevoflurane anesthesia is common in children. When rapid intravenous induction of general anesthesia is indicated in a brief procedure, the induction agent can reduce the incidence of EA after sevoflurane anesthesia. The aim of this study was to compare the efficacy of intravenous induction with ketamine and propofol for reducing EA in children after short sevoflurane anesthesia. Methods: Children aged 2 to 6 years who were scheduled to undergo inguinal hernia repair were randomly divided into 3 groups to receive 2 mg/kg ketamine iv, 3 mg/kg propofol iv, or inspired concentration of 8% sevoflurane for induction of anesthesia. After a laryngeal mask airway (LMA) insertion, a caudal block was performed in all children. Anesthesia was maintained with 1.5% sevoflurane and 65% nitrous oxide in oxygen with spontaneous ventilation. The recovery characteristics were recorded and EA were evaluated by using the Pediatric Anesthesia Emergence Delirium (PAED) scale. Results: One hundred and twenty children were enrolled and randomized to treatment. Children who received ketamine induction had higher incidence of EA than those who received propofol (42% vs 16%, P < 0.05) and showed delayed recovery (32 ± 9 min) as compared with those who received propofol or sevoflurane (22 ± 8 min and 20 ± 7 min, respectively, P < 0.05). The mean peak PAED score was significantly lower in children who received propofol induction (6.8 ± 4.0, P < 0.05) than ketamine (11.8 ± 4.1) or sevoflurane (11.6 ± 3.8). Conclusions: Intravenous induction with ketamine does not prevent the incidence of EA and delays recovery. Induction with propofol improves the quality of recovery by reducing the incidence of EA and provides a safe and early recovery.展开更多
Background: This study compares the effect of dexmedetomidine versus Ketamine for the prevention of emergence agitation in children undergoing general anaesthesia. Method: 75 Children are randomly allocated into three...Background: This study compares the effect of dexmedetomidine versus Ketamine for the prevention of emergence agitation in children undergoing general anaesthesia. Method: 75 Children are randomly allocated into three groups. Group C: Were assigned to receive normal saline. Group K: Were assigned to receive Ketamine 0.25 mg/kg. Group D: assigned to receive 0.25 ug /kg of dexmedetomidine, before the end of surgery. Results: There was no statistically significant difference in demographic data and intraoperative parameters between the three groups. But as regards to time to discharge, there was a significant difference between group C, group K and group D (group C = 39.96 ± 2.84, group K = 37.28 ± 3.80, group D = 35.08 ± 3.36 and P value = 0.0002). FLACC scale was low after extubation, before leaving the operating room and on arrival to PACU (small FLACC scale in group K, D than group C). PAED scoreless in Group K and Group D than Group C (postoperative, at 10 minutes, 20 min, 30 min). Conclusion: Ketamine and dexmedetomidine reduced the incidence and severity of emergence delirium effectively when compared to normal saline, and the effects of dexmedetomidine being much superior to Ketamine.展开更多
基金This study was financially supported by the National Natural Science Foundation of China(81822017,82171493,52003021)the Lingang Laboratory(LG-QS-202203-10)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20181715).
文摘To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a comprehensive behavioural training paradigm,relatively expensive apparatus and invasive surgical procedures.
基金funded by Guangzhou Science and Technology Planning Project of Guangdong(202103000032)Science and Technology Plan Project of Guangdong Province(2019B030316001)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2019A1515011366,2022A1515011567)National Natural Science Foundation of China(81801343).
文摘Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.Aims We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation,both anxious and non-anxious.Methods Fifty-four adolescents with anxious(n=33)and non-anxious(n=21)MDD received three infusions of esketamine 0.25mg/kg or active-placebo(midazolam 0.045 mg/kg)over 5 days,with routine inpatient care and treatment.Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Asberg Depression Rating Scale.Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion(day 6,primacy efficacy endpoint)and throughout the 4-week post-treatment(days 12,19 and 33).Results In subjects who received esketamine,a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6(72.7%vs 18.8%,p=0.015)and day 12(90.9%vs 43.8%,p=0.013),and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33(72.7%vs 26.7%,p=0.045).No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.Conclusions Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD;however,this benefit was temporary and was not maintained over time.
文摘The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable side effects to the patients. While not restricted to patients with chronic pain, these patients are often diagnosed with depression, presenting with symptoms such as poor mood, anhedonia, and altered cognitive processes. It is estimated that a substantial proportion of treated patients do not derive a substantive benefit from traditional pharmacological treatments for depression. The present study involved a retrospective review of cases, exploring the patient-reported satisfaction with and tolerability of a novel use of virtual reality (VR), coined KVR, as an adjunct to intravenous ketamine infusion therapies. Specifically, the ketamine-virtual reality protocol was employed as a potential adjunctive intervention for patients suffering from chronic pain and depression. Visual Analog Scores (VAS) associated with pain were significantly lower on the third than on the first assessment day. Montgomery-?sberg Depression Rating Scale (MADRS) scores improved following infusion and across days (i.e., sessions). Lastly, 2/3 of patients preferred the use of VR with their ketamine infusion. The results are considered in terms of implementing prospective studies to examine whether the combination therapies have a synergistic benefit and the nature and magnitude of clinically meaningful treatment effects, if any.
文摘Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia has multiple benefits, including rapid, effective and titratable analgesic delivery. The aim of our study is to assess the efficacy and safety of intranasal analgesic-dose ketamine compared to multimodal analgesia in patients presenting with acute postoperative pain or headache after a spinal anaesthetic in the intensive care unit of obstetrics and gynaecology. Materials and Methods: This was a prospective descriptive study, with hospital Ethics Committee approval and written informed consent from study participants. We compared the effect of nebulized ketamine and multimodal analgesia postoperatively in 120 patients belonging to the physical status I - II of the American Society of Anesthesiologists, in the intensive care unit of obstetrics and gynaecology, at the Ibn Rochd University Hospital Center in Casablanca from June 2021 to June 2022. Results: We included 120 patients in our study divided into two groups of 60 patients: the average age was 35 years, with extremes ranging from 18 to 45 years, All patients were hospitalized for postoperative care: all women underwent locoregional anaesthesia with a standard dose according to the service protocol (10 mg of bupivacaine, 25γ of fentanyl, 100γ of morphine), where pain was the common denominator. Among these patients, 59 were admitted for management of postpartum haemorrhage, 43 for postoperative monitoring, 15 for post-spinal anaesthesia headache and 3 for pelviperitonitis. The results of the pain assessment 30 minutes after the ketamine nebulization were marked by a request for analgesia in 12 patients, which is 20% of group A, including 5 patients, whose visual analogue scale (VAS) on admission was between 5 and 7, and 7 patients whose VAS at admission was ≥8;all these patients received a second dose of ketamine by nebulization;the evaluation 30 min after the second dose was marked by a request for analgesia in 4 patients, which is 7% of Group A;in all these patients the VAS at admission was ≥8. Of the total number of patients of Group A, only 4 received morphine when they were requested for analgesia after the second dose of nebulized ketamine. Conclusion: The primary outcome of nebulized ketamine use is a significant reduction in VAS pain score. We believe that nebulized ketamine has a potential effect of reducing pain in the intensive care unit of obstetrics and gynaecology;this may be an additional analgesic modality for clinicians to provide rapid, effective and non-invasive pain relief.
文摘<strong>Background</strong>: Inpatient subanaesthetic ketamine infusion for 5 days may improve pain and reduce oral opioid usage in patients with chronic pain. <strong>Objective</strong>: This study aims to investigate pain and psychological outcomes of ketamine parenteral infusion (0.1 - 0.35 mg/kg/h or maximum 24 mg/hour) for 5 days in patients with chronic refractory pain. The secondary objective is to explore any prognostic pain and psychological factors associated with the successful response to the ketamine treatment. <strong>Methodology</strong>: A prospective longitudinal study of a small cohort (N = 35) of patients with heterogenous chronic refractory pain conditions was conducted from one week to two months follow-up. <strong>Results</strong>: Pain Severity was significantly improved from mean 6.5 to 5.1 (t = 3.77, p < 0.001, d = 0.6) at 1-week and 5.9 (t = 2.14, p = 0.042, d = 0.4) at 2-month;Pain Interference from mean 7.0 to 5.1 (t = 4.99, p < 0.001, d = 0.9) at 1-week and 6.1 (t = 2.16, p = 0.041, d = 0.4) at 2-month;Pain Self-Efficacy Questionnaire (PSEQ) from mean 17 to 24 (t = <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>3.37, p = 0.002, d = <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>0.6) at 1-week and 23 (t =<span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>2.60, p = 0.016, d =<span style="white-space:nowrap;">−</span><span style="white-space:nowrap;"></span>0.5) at 2-month;Pain Catastrophizing (PCS) from 28 to 23 (t = 3.4, p = 0.002;d = 0.6) at 1-week and 21 (t = 2.45, p = 0.022, d = 0.5) at 2-month;Depression from mean 21 to 16 (t = 2.16, p = 0.038, d = 0.4) at 1-week and 16 (t = 3.53, p = 0.002, d = 0.7) at 2-month;and oral Morphine Equivalent Daily Dose (oMEDD) reduced from mean 191 mg/day on admission to 122 mg/day at 1-week (t = 2.38, p = 0.023;d = 0.4) and 93 mg/day at 2-month (t = 2.59, p = 0.016;d = 0.5). There was no significant difference between responders and non-responders on baseline psychological measures (t<sub>33</sub> < 1.19, p > 0.244) and pain classifications ( <img src="Edit_c68fc9e4-a875-4b79-b0cf-af146ed090fe.png" alt="" /> = 0.610, p = 0.894). <strong>Conclusion</strong>: Ketamine subanaesthetic dose infusion for 5 days was found to be effective in managing chronic refractory pain with significant opioid reduction and small improvements in all chronic pain outcomes, except anxiety, at 1-week and 2-month follow-up and with minimal severe adverse effects.
基金supported by Youth Innovation Fund of The First Affiliated Hospital of Zhengzhou University(2012-2015)National Natural Science Foundation(81200909)
文摘Objective:To investigate the effects of propofol and ketamine on the cognitive function and immune function in young rats.Method:A total of 80 young rats were randomly divided into four groups:Control group,ketamine group(experimental group A),propofol group(experimental group B),ketamine and propofol group(experimental group Q.All rats had continuous injection for three times,serum IL-2,IL-4 and II.-10 and whole brain IL-I P level,hippocampal neuronal apoptosis level were measured.The cognitive ability in rats was tested by water maze.Results:Water maze test showed on the 1st d,the maze test latency of the control group,the experimental group B and the experimental group C water were decreased gradually;Compared with the control group after 3 days,the latency of the experimental group A,experimental group B and experimental group C were all decreased,the crossing circle times were also reduced.Hippocampal neuron apoptosis were(2.3±1.7)%,(14.7±6.9)%,(4.2±3.3)%,(10.2±4.8r%in control group,experimental group A,experimental group B and experimental group C,respectively.The neurons apoptosis of experimental group A was significantly increased.The serum IL-4 and 1L-10 of the experimental group A,experimental group B and experimental group C after anesthesia were significantly higher than the control group.The whole brain IL-1β of the experimental group A,experimental group B and experimental group C were significantly lower than the control group.Conclusions:Propofol can reduce anesthesia effect of ketamine on the cognitive function and immune function in the young rats.
基金supported by the National Natural Science Foundation of China,No.81200851(to DL)the National Institutes of Health of the USA,No.NS 040723(to QL)
文摘Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when activated.Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour intervals.At 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated p66ShcA.We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours.The same procedure was performed on a different group of rats.At the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water maze.Latency to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was similar.These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period.This may have contributed to the deficit in spatial learning and memory that persisted into adulthood.The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval No.A13.008) on January 22,2013.
基金supported by National Natural Science Foundation of China(No.81600940)the Science of Technology project of Henan,China(No.142102310246)
文摘Objective: To discuss the neuron-protective effect and possible mechanism of subanesthestic-dosage ketamine on Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Methods: A total of 30 mice were divided equally into three groups, model control group(MC group), ketamine treatment group(KT group), and blank control group(BC group), respectively.The Parkinson's disease mice of MC group and KT groups were established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(20 mg/kg/d), while mice in KT group were treated by intraperitoneal injection of subanesthestic-dosage ketamine(8 mg/kg).Differences on behaviors and the number of nigra dopaminergic neurons of mice in each group were compared through the behavioral test and tyrosine hydroxylase immunohistochemistry experiments after the treatments.Furthermore, Western blot was used to test the expression of autophagy-related gene LC3-Ⅱ, Beclin1, Parkin, PINK1,and mTOR.Results: Compared with the BC group, the neuroethology scores were lower and the amount of TH positive cells were less both in MC and MT groups; In KT group, the neuroethology scores were higher and the amount of tyrosine hydroxylase positive cells were significantly more than that in MC group(P < 0.05).Moreover, expression levels of autophagy-related proteins LC3-II, Beclin1, Parkin, and PINK1 were higher, while the mTOR expression level was lower than that in MC group.Conclusions: The subanesthestic-dosage ketamine has some protective effects on the coordinating ability of movement and cognitive ability of Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.This is probably due to that the autophagy activity of cells is activated by subanesthestic-dosage ketamine and that the neurons are protected.
文摘OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.
基金supported by the Key Project of the National Natural Science Foundation of China(81920108018 to T.L.and P.S.)Ministry of Science and Technology of the People’s Republic of China(2022ZD0205200)+4 种基金Natural Science Foundation of Sichuan Province(2022NSFSC1607)Key R&D Program of Zhejiang(2022C03096 to T.L.)Special Foundation for Brain Research from Science and Technology Program of Guangdong(2018B030334001)Project for Hangzhou Medical Disciplines of Excellence&Key Project for Hangzhou Medical Disciplines。
文摘Ketamine, a rapid-acting antidepressant drug, has been used to treat major depressive disorder and bipolar disorder(BD). Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in patients. Ketamine has also been applied to establish animal models of mania. At present, however, the underlying mechanism is still unclear. In the current study, we found that chronic lithium exposure attenuated ketamine-induced mania-like behavior and c-Fos expression in the medial prefrontal cortex(mPFC) of adult male mice. Transcriptome sequencing was performed to determine the effect of lithium administration on the transcriptome of the PFC in ketamine-treated mice, showing inactivation of the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Pharmacological inhibition of AKT signaling by MK2206(40 mg/kg), a selective AKT inhibitor, reversed ketamine-induced mania.Furthermore, selective knockdown of AKT via AAVAKT-sh RNA-EGFP in the mPFC also reversed ketamine-induced mania-like behavior. Importantly,pharmacological activation of AKT signaling by SC79(40 mg/kg), an AKT activator, contributed to mania in low-dose ketamine-treated mice. Inhibition of PI3K signaling by LY294002(25 mg/kg), a specific PI3K inhibitor, reversed the mania-like behavior in ketamine-treated mice. However, pharmacological inhibition of mammalian target of rapamycin(mTOR)signaling with rapamycin(10 mg/kg), a specific mTOR inhibitor, had no effect on ketamine-induced mania-like behavior. These results suggest that chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway, which may be a novel target for the development of BD treatment.
文摘AIM To determine if ketamine sedation is a safe and cost effective way of treating displaced paediatric radial and ulna fractures in the emergency department. METHODS Following an agreed interdepartmental protocol, fractures of the radius and ulna(moderately to severely displaced) in children between the age of 2 and 16 years old, presenting within a specified 4 mo period, were manipulated in our paediatric emergency department. Verbal and written consent was obtained prior to procedural sedation to ensure parents were informed and satisfied to have ketamine. A single attempt at manipulation was performed. Pre and postmanipulation radiographs were requested and assessed to ensure adequacy of reduction. Parental satisfaction surveys were collected after the procedure to assess the perceived quality of treatment. After closed reduction and cast immobilisation, patients were then followed-up in the paediatric outpatient fracture clinic and functional outcomes measured prospectively. A cost analysis compared to more formal manipulation under a general anaesthetic was also undertaken.RESULTS During the 4 mo period of study, 10 closed, moderate to severely displaced fractures were identified and treated in the paediatric emergency department using our ketamine sedation protocol. These included fractures of the growth plate(3), fractures of both radius and ulna(6) and a single isolated proximal radius fracture. The mean time from administration of ketamine until completion of the moulded plaster was 20 min. The mean time interval from sedation to full recovery was 74 min. We had no cases of unacceptable fracture reduction and no patients required any further manipulation, either in fracture clinic or under a more formal general anaesthetic. There were no serious adverse events in relation to the use of ketamine. Parents, patients and clinicians reported extremely favourable outcomes using this technique. Furthermore, compared to using a manipulation under general anaesthesia, each case performed under ketamine sedation was associated with a saving of ￡1470, the overall study saving being ￡14700. CONCLUSION Ketamine procedural sedation in the paediatric population is a safe and cost effective method for the treatment of displaced fractures of the radius and ulna, with high parent satisfaction rates.
文摘Objective:To investigate the effects of propofol and ketamine on seizure duration,hemodynamics,and recovery of electroconvulsive therapy(ECT).Methods:This prospective randomized trial included patients who had undergone ECT under anesthesia.Patients received injection of propofol 1.5 mg/kg i.v.(the propofol group)or ketamine 0.8-1.2 mg/kg i.v.(the ketamine group)during ECT.Seizure duration,hemodynamics,and recovery were recorded and compared between the two groups.Results:This trial included 44 patinets with 22 patients receiving propofol and 22 patients receiving ketamine.The total dose of propofol and ketamine was(105.68±25.27)mg and(81.36±24.55)mg,respectively.The motor seizure and electroencephalogram seizure duration were prolonged in the ketamine group(P<0.001).The hemodynamics at the admission of the two groups were comparable(P>0.05);however,the mean systolic blood pressure during the procedure was significantly higher in the ketamine group(P=0.04).Besides,spontaneous eye-opening in the ketamine group took longer than that of the propofol group(P=0.001).Conclusion:Both propofol and ketamine are safe as anesthetic agents for modified ECT,and ketamine provides a longer seizure duration without hemodynamic instability or any significant complication.
文摘BACKGROUND:Pain in the emergency department(ED)is common but undertreated.The objective of this study was to examine the efficacy and safety of intranasal(IN)ketamine used as an analgesic for patients with acute injury with moderate to severe pain.METHODS:This study was a cross sectional,observational study of patients more than 8 years old experiencing moderate to severe pain[visual analog score(VAS)>50 mm].The initial dose of IN ketamine was 0.7 mg/kg with an additional dose of 0.3 mg/kg if VAS was more than 50 mm after 15minutes.Pain scores and vital signs were recorded at 0,15,30 and 60 minutes.Side-effects,sedation level and patient's satisfaction were also recorded.The primary outcome was the number of patients achieving≥20 mm reductions in VAS at 15 minutes.Other secondary outcome measures were median reduction in VAS at 15,30 and 60 minutes,changes of vital signs,adverse events,satisfaction of patients,and need for additional ketamine.RESULTS:Thirty-four patients with a median age of 29.5 years(IQR 17.5–38)were enrolled,and they had an initial median VAS of 80 mm(IQR 67–90).The VAS decreased more than 20 mm at15 minutes in 27(80%)patients.The reduction of VAS from baseline to 40 mm(IQR 20–40),20 mm(IQR 14–20)and 20 mm(IQR 10–20)respectively at 15,30 and 60 minutes(P<0.001).No critical changes of vital signs were noted and adverse effects were mild and transient.CONCLUSION:This study showed that IN ketamine is an analgesic choice for patients with acute injury in moderate to severe pain in an overcrowded and resource limited ED.
文摘Major depressive disorder(MDD)is a common,serious,debilitating condition affecting 350 million people worldwide,which remains to be unsatisfactorily treated with 53%of patients still complaining of symptoms after completing their courses with the correct dosage.Ketamine,which was approved by the Food and Drug Administration in 2019,is a potential treatment option for those recalcitrant cases.The mechanism of ketamine is not fully understood,but as type it is classified as an N-methyl-D-aspartate(NMDA)glutamate receptor antagonist,and can be given intravenously,intranasally and orally.It is used to treat treatment-resistant depression,depression associated with suicidal ideation,mood and anxiety disorders and depressions associated with either type of bipolar disorder.Although ketamine is considered relatively safe,several side effects have been reported with the major ones being psychiatric in the form of worsening mood,anxiety and agitation;psychotomimetic in the form of dissociation,perceptual disturbance and abnormal sensations;cardiovascular in the form of increased blood pressure and increased heart rate;and neurological in the form of headache and dizziness.Ketamine is still not approved worldwide for usage in patients with treatment-resistant MDD,but if it is approved sometime in the future with relatively fewer side effects,it is expected to significantly save millions of dollars spent yearly on patients with treatment-resistant depression and that will lift this major burden off the shoulders of healthcare professionals.This study was designed to measure the effects of ketamine,an NMDA receptor antagonist,on patients with treatment-resistant MDD and to analyse the concept that makes it different and relatively safer than other major antidepressants like selective serotonin reuptake inhibitors,monoamine oxidase inhibitors and TCAs(tricyclic antidepressants).
文摘Background The use of ketamine in electroconvulsive therapy(ECT)has been examined in the treatment of major depressive disorder(MDD);however,there has been no systematic review and meta-analysis of related randomised controlled trials(RCTs).Aim To examine the efficacy and safety of ketamine augmentation of ECT in MDD treatment.Methods Two reviewers searched Chinese(China National Knowledge Infrastructure and Wanfang)and English(PubMed,PsycINFO,Embase and Cochrane Library)databases from their inception to 23 July 2019.The included studies'bias risk was evaluated using the Cochrane risk of bias assessment tool.The primary outcome of this metaanalysis was improved d印ressive symptoms at day 1 after a single ECT treatment session.Data were pooled to calculate the standardised mean difference and risk ratio with their 95%CIs using RevMan V.5.3.We used the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach to assess the whole quality of evidence.Results Four RCTs(n=239)compared ketamine alone or ketamine plus propofol(n=149)versus propofol alone(n=90)in patients with MDD who underwent a single ECT session.Three RCTs were considered as unclear risk with respect to random sequence generation using the Cochrane risk of bias.Compared with propofol alone,ketamine alone and the combination of ketamine and propofol had greater efficacy in the treatment of depressive symptoms at days 1,3 and 7 after a single ECT session.Moreover,compared with propofol alone,ketamine alone and the combination of ketamine and propofol were significantly associated with increased seizure duration and seizure energy index.Compared with propofol,ketamine alone was significantly associated with increased opening-eye time.Based on the GRADE approach,the evidence level of primary and secondary outcomes ranged from very low(26.7%,4/15)to‘low'(73.3%,11/15).Conclusion Compared with propofol,there were very low or low evidence levels showing that ketamine alone and the combination of ketamine and propofol appeared to rapidly improve depressive symptoms of patients with MDD undergoing a single ECT session.There is a need for highquality RCTs.
文摘Background: Anesthetic agents are commonly utilized in the handling of non‐human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to describe the effect of age and dissociative anesthetics (ketamine and tiletamine), and their combinations with acepromazine, xylazine and zolazepam, on the physiological and blood biochemical parameters in Macaca mulatta. Methods: Eighty male Macaca mulatta were divided into four experimental groups depending on the anesthetic mixture applied. Each group of 20 males was divided into five sub‐groups according to age. Physiological parameters were recorded every five minutes during a 30‐minute period. A blood sample was drawn to analyze blood biochemistry. Results: Statistical analyses revealed significant differences in the physiological parameters between the ketamine‐acepromazine and ketamine‐xylazine groups compared to the control group. The analysis of blood biochemistry found significant differences by age and by anesthetic mixture among all groups. Conclusion: These findings contribute to standardizing this animal model in biological research.
文摘Objective: To compare acute and long-term postoperative pain and side effects in patients undergoing mastectomy for breast cancer under general anesthesia induced with ketamine or thiamylal. Methods: Twenty four ASA physical status I-III patients undergoing mastectomy were randomly assigned to one of two groups. Ketamine group received intravenous ketamine, 1 mg/kg, and thiamylal group received intravenous thiamylal, 4 mg/kg, at the induction of general anesthesia. Anesthesia was maintained with sevoflurane, N2O and fentanyl. The intensity of pain was assessed by using visual analog scale (VAS) 3 and 16 hr and 2, 3 and 4 weeks after surgery. Postoperative side effects, including nausea, vomiting and hallucination were also recorded. Results: At 16 hr after surgery, VAS in ketamine group was significantly lower than that in thiamylal group. However, there were no statistically significant differences between the two groups in the VAS at 3 hr and 2, 3 and 4 weeks after surgery. There were no differences in the incidence of side effects such as nausea, vomiting and hallucination between the two groups. Conclusion: Intravenous ketamine at the induction of anesthesia could reduce acute postoperative pain but not long-term pain after mastectomy.
文摘Background: Emergence agitation (EA) after sevoflurane anesthesia is common in children. When rapid intravenous induction of general anesthesia is indicated in a brief procedure, the induction agent can reduce the incidence of EA after sevoflurane anesthesia. The aim of this study was to compare the efficacy of intravenous induction with ketamine and propofol for reducing EA in children after short sevoflurane anesthesia. Methods: Children aged 2 to 6 years who were scheduled to undergo inguinal hernia repair were randomly divided into 3 groups to receive 2 mg/kg ketamine iv, 3 mg/kg propofol iv, or inspired concentration of 8% sevoflurane for induction of anesthesia. After a laryngeal mask airway (LMA) insertion, a caudal block was performed in all children. Anesthesia was maintained with 1.5% sevoflurane and 65% nitrous oxide in oxygen with spontaneous ventilation. The recovery characteristics were recorded and EA were evaluated by using the Pediatric Anesthesia Emergence Delirium (PAED) scale. Results: One hundred and twenty children were enrolled and randomized to treatment. Children who received ketamine induction had higher incidence of EA than those who received propofol (42% vs 16%, P < 0.05) and showed delayed recovery (32 ± 9 min) as compared with those who received propofol or sevoflurane (22 ± 8 min and 20 ± 7 min, respectively, P < 0.05). The mean peak PAED score was significantly lower in children who received propofol induction (6.8 ± 4.0, P < 0.05) than ketamine (11.8 ± 4.1) or sevoflurane (11.6 ± 3.8). Conclusions: Intravenous induction with ketamine does not prevent the incidence of EA and delays recovery. Induction with propofol improves the quality of recovery by reducing the incidence of EA and provides a safe and early recovery.
文摘Background: This study compares the effect of dexmedetomidine versus Ketamine for the prevention of emergence agitation in children undergoing general anaesthesia. Method: 75 Children are randomly allocated into three groups. Group C: Were assigned to receive normal saline. Group K: Were assigned to receive Ketamine 0.25 mg/kg. Group D: assigned to receive 0.25 ug /kg of dexmedetomidine, before the end of surgery. Results: There was no statistically significant difference in demographic data and intraoperative parameters between the three groups. But as regards to time to discharge, there was a significant difference between group C, group K and group D (group C = 39.96 ± 2.84, group K = 37.28 ± 3.80, group D = 35.08 ± 3.36 and P value = 0.0002). FLACC scale was low after extubation, before leaving the operating room and on arrival to PACU (small FLACC scale in group K, D than group C). PAED scoreless in Group K and Group D than Group C (postoperative, at 10 minutes, 20 min, 30 min). Conclusion: Ketamine and dexmedetomidine reduced the incidence and severity of emergence delirium effectively when compared to normal saline, and the effects of dexmedetomidine being much superior to Ketamine.
