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Ketamine
Kinds of Ketamine Terms modified by Ketamine Selected AbstractsELECTROPHYSIOLOGICAL EFFECTS OF KETAMINE ON HUMAN ATRIAL MYOCYTES AT THERAPEUTICALLY RELEVANT CONCENTRATIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2008Chun-Yu Deng SUMMARY 1Ketamine is widely used for the induction of anaesthesia in high-risk patients with cardiovascular instability or severe hypovolaemia. However, the ionic mechanisms involved in the effects of ketamine at therapeutically relevant concentrations in human cardiac myocytes are unclear. The present study was designed to investigate the effects of ketamine on L-type Ca2+ (ICa), transient outward K+ (Ito), ultra-rapid delayed rectifier K+ (IKur) and inward rectifier potassium (IK1) currents, as well as on action potentials, in human isolated atrial myocytes. 2Atrial myocytes were isolated enzymatically from specimens of human atrial appendage obtained from patients undergoing coronary artery bypass grafting. The action potential and membrane currents were recorded in both current- and voltage-clamp modes using the patch-clamp technique. 3Ketamine inhibited ICa with an IC50 of 1.8 µmol/L. In addition, 10 µmol/L ketamine decreased the ICa peak current at +10 mV from 5.1 ± 0.3 to 2.1 ± 0.4 pA/pF (P < 0.01), but did not change the threshold potential, peak current potential and reverse potential. 4Ketamine had no effect on Ito, IKur or IK1, but it reversibly shortened the duration of the action potential in human atrial myocytes. 5In conclusion, ketamine, at a clinically relevant concentration, shortens the action potential duration of the human atrial myocytes, probably by inhibiting ICa. [source] Enantioselective analysis of ketamine and its metabolites in equine plasma and urine by CE with multiple isomer sulfated ,-CDELECTROPHORESIS, Issue 15 2007Regula Theurillat Abstract CE with multiple isomer sulfated ,-CD as the chiral selector was assessed for the simultaneous analysis of the enantiomers of ketamine and metabolites in extracts of equine plasma and urine. Different lots of the commercial chiral selector provided significant changes in enantiomeric ketamine separability, a fact that can be related to the manufacturing variability. A mixture of two lots was found to provide high-resolution separations and interference-free detection of the enantiomers of ketamine, norketamine, dehydronorketamine, and an incompletely identified hydroxylated metabolite of norketamine in liquid/liquid extracts of the two body fluids. Ketamine, norketamine, and dehydronorketamine could be unambiguously identified via HPLC fractionation of urinary extracts and using LC-MS and LC-MS/MS with 1,mmu mass discrimination. The CE assay was used to characterize the stereoselectivity of the compounds' enantiomers in the samples of five ponies anesthetized with isoflurane in oxygen and treated with intravenous continuous infusion of racemic ketamine. The concentrations of the ketamine enantiomers in plasma are equal, whereas the urinary amount of R -ketamine is larger than that of S -ketamine. Plasma and urine contain higher S - than R -norketamine levels and the mean S -/R -enantiomer ratios of dehydronorketamine in plasma and urine are lower than unity and similar. [source] What is the nature of the emergence phenomenon when using intravenous or intramuscular ketamine for paediatric procedural sedation?EMERGENCY MEDICINE AUSTRALASIA, Issue 4 2009Greg Treston Abstract Objective: Ketamine has become the drug most favoured by emergency physicians for sedation of children in the ED. Some emergency physicians do not use ketamine for paediatric procedural sedation (PPS) because of concern about emergence delirium on recovery. The present study set out to determine the true incidence and nature of this phenomenon. Methods: Prospective data relating to any emergence agitation, crying, hallucinations, dreams, altered perceptions, delirium and necessary interventions were recorded in consecutive cases of ketamine PPS from March 2002 to June 2007, and analysed. Standard inclusion and exclusion criteria for the use of ketamine were followed. Results: A total of 745 prospective data collection records were available for analysis over the 5 year period. Of all, 93 (12.5%) children cried on awakening when recovering from PPS, 291 (39%) experienced pleasant altered perceptions and 16 (2.1%) experienced what was called ,emergence delirium'. None required any active treatment and all except one settled within 20 min. There was no evidence of an increased rate of nightmares on telephone follow up in the weeks post procedure. Conclusion: The belief that ketamine, in the doses used for ED PPS, causes frequent emergence delirium is flawed. A pleasant emergence phenomenon is common, but is not distressing for the child, and has no long-term (up to 30 days) negative sequelae. Rarely, there is anxiety or distress on awakening from ketamine sedation, which settles spontaneously. This should not deter emergency physicians from using ketamine for PPS. [source] A Combination of Midazolam and Ketamine for Procedural Sedation and Analgesia in Adult Emergency Department PatientsACADEMIC EMERGENCY MEDICINE, Issue 3 2000Carl R. Chudnofsky MD Abstract Objective: To describe the clinical characteristics of a combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department (ED) patients. Methods: This was a prospective, observational trial, conducted in the ED of an urban level II trauma center. Patients , 18 years of age requiring procedural sedation and analgesia were eligible, and enrolled patients received 0.07 mg/kg of intravenous midazolam followed by 2 mg/kg of intravenous ketamine. Vital signs were recorded at regular intervals. The adequacy of sedation, adverse effects, patient satisfaction, and time to reach discharge alertness were determined. Descriptive statistics were calculated using statistical analysis software. Results: Seventy-seven patients were enrolled. Three were excluded due to protocol violations, three due to lack of documentation, and one due to subcutaneous infiltration of ketamine, leaving 70 patients for analysis. The average age was 31 years, and 41 (59%) were female. Indications for procedural sedation and analgesia included abscess incision and drainage (66%), fracture/joint reduction (26%), and other (8%). The mean dose of midazolam was 5.6 ± 1.4 mg and the mean dose of ketamine was 159 ± 42 mg. The mean time to achieve discharge criteria was 64 ± 24 minutes. Fivepatients experienced mild emergence reactions, but there were no episodes of hallucinations, delirium, or other serious emergence reactions. Eighteen (25%) patients recalled dreaming while sedated; twelve (17%) were described as pleasant, two (3%) unpleasant, three (4%) both pleasant and unpleasant, and one (1%) neither pleasant nor unpleasant. There were four (6%) cases of respiratory compromise, two (3%) episodes of emesis, and one (1%) case of myoclonia. All of these were transient and did not result in a change in the patient's disposition. Only one (1%) patient indicated that she was not satisfied with the sedation regimen. Conclusions: The combination of midazolam and ketamine provides effective procedural sedation and analgesia in adult ED patients, and appears to be safe. [source] Ketamine reduce left ventricular systolic and diastolic function in patients with ischaemic heart diseaseACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2010C.-J. JAKOBSEN Objective: Ketamine may be followed by a general increase in haemodynamics and oxygen consumption, which may be of concern in patients with ischaemic heart disease. The purpose of this study was to evaluate the effect of ketamine on left ventricular (LV) systolic and diastolic function by different modalities of echocardiography and tissue Doppler imaging in patients with ischaemic heart disease. Methods and Results: Prospective observational study of 11 patients acting as own control based on echocardiographic imaging before and after bolus ketamine 0.5 mg/kg. Simpson's 2 D-volumetric method was used to quantify left ventricular volume and ejection fraction. General global LV deformation was assessed by Speckle tracking ultrasound, systolic LV longitudinal displacement was assessed by Tissue Tracking score index and the diastolic function was evaluated from changes in early-(E') and atrial (A') peak velocities during diastole. Average heart rate (34%) and blood pressure (35%) increased significantly after ketamine (P<0.0001). Mean tissue tracking score index decreased from 11.2±2.3 to 8.3±2.6 (P=0.005) and Global Speckle tracking 2D strain from 17.7±2.7 to 13.7±3.6 (P=0.0014) indicating a decrease in LV global systolic function. The E'/A' ratio decreased from 1.11±0.43 to 0.81±0.46 (P=0.044) indicating impaired relaxation. Conclusion: Different modalities of echocardiography in combination with tissue Doppler indicate both diminished systolic and diastolic function after ketamine administration in patients with ischaemic heart disease. [source] Scandinavian clinical practice guidelines on general anaesthesia for emergency situationsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2010A. G. JENSEN Emergency patients need special considerations and the number and severity of complications from general anaesthesia can be higher than during scheduled procedures. Guidelines are therefore needed. The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine appointed a working group to develop guidelines based on literature searches to assess evidence, and a consensus meeting was held. Consensus opinion was used in the many topics where high-grade evidence was unavailable. The recommendations include the following: anaesthesia for emergency patients should be given by, or under very close supervision by, experienced anaesthesiologists. Problems with the airway and the circulation must be anticipated. The risk of aspiration must be judged for each patient. Pre-operative gastric emptying is rarely indicated. For pre-oxygenation, either tidal volume breathing for 3 min or eight deep breaths over 60 s and oxygen flow 10 l/min should be used. Pre-oxygenation in the obese patients should be performed in the head-up position. The use of cricoid pressure is not considered mandatory, but can be used on individual judgement. The hypnotic drug has a minor influence on intubation conditions, and should be chosen on other grounds. Ketamine should be considered in haemodynamically compromised patients. Opioids may be used to reduce the stress response following intubation. For optimal intubation conditions, succinylcholine 1,1.5 mg/kg is preferred. Outside the operation room, rapid sequence intubation is also considered the safest method. For all patients, precautions to avoid aspiration and other complications must also be considered at the end of anaesthesia. [source] Ketamine attenuates post-operative cognitive dysfunction after cardiac surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009J. A. HUDETZ Background: Post-operative cognitive dysfunction (POCD) commonly occurs after cardiac surgery. Ketamine exerts neuroprotective effects after cerebral ischemia by anti-excitotoxic and anti-inflammatory mechanisms. We hypothesized that ketamine attenuates POCD in patients undergoing cardiac surgery concomitant with an anti-inflammatory effect. Methods: Patients randomly received placebo (0.9% saline; n=26) or an i.v. bolus of ketamine (0.5 mg/kg; n=26) during anesthetic induction. Anesthesia was maintained with isoflurane and fentanyl. A nonsurgical group (n=26) was also included as control. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery or a 1-week waiting period for the nonsurgical controls. Serum C-reactive protein (CRP) concentrations were determined before surgery and on the first post-operative day. Results: Baseline neurocognitive and depression scores were similar in the placebo, ketamine, and nonsurgical control groups. Cognitive performance after surgery decreased by at least 2 SDs (z -score of 1.96) in 21 patients in the placebo group and only in seven patients in the ketamine group compared with the nonsurgical controls (P<0.001, Fisher's exact test). Cognitive performance was also significantly different between the placebo- and the ketamine-treated groups based on all z -scores (P<0.001, Mann,Whitney U -test). Pre-operative CRP concentrations were similar (P<0.33, Mann,Whitney U -test) in the placebo- and ketamine-treated groups. The post-operative CRP concentration was significantly (P<0.01, Mann,Whitney U -test) lower in the ketamine-treated than in the placebo-treated group. Conclusions: Ketamine attenuates POCD 1 week after cardiac surgery and this effect may be related to the anti-inflammatory action of the drug. [source] Dose-dependent effect of S(+) ketamine on post-ischemic endogenous neurogenesis in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2009U. WINKELHEIDE Background: Ketamine is a non-competitive antagonist at N -methyl- d -aspartate (NMDA) receptors and reduces neuronal injury after cerebral ischemia by blocking the excitotoxic effects of glutamate. However, cerebral regeneration by means of endogenous neurogenesis may be impaired with blockade of NMDA receptors. The effects of S(+) ketamine on post-ischemic neurogenesis are unknown and investigated in this study. Methods: Thirty-two male Sprague,Dawley rats were randomly assigned to the following treatment groups with intravenous S(+) ketamine anesthesia: S(+) ketamine 0.75 mg/kg/min with or without cerebral ischemia and S(+) ketamine 1.0 mg/kg/min with or without cerebral ischemia. Eight non-anesthetized, non-ischemic animals were investigated as naïve controls. Forebrain ischemia was induced by bilateral common carotid artery occlusion in combination with hemorrhagic hypotension. 5-bromo-2-deoxyuridine (BrdU) was injected intraperitoneally for seven consecutive post-operative days. BrdU-positive neurons in the dentate gyrus and histopathological damage of the hippocampus were analyzed after 28 days. Results: The number of new neurons was not affected by S(+) ketamine in the absence of cerebral ischemia. The ischemia-induced increase in neurogenesis was reduced by high-dose S(+) ketamine. Cell death of ischemic animals did not vary between low- and high-dose S(+) ketamine. Conclusion: While low concentrations of S(+) ketamine allow an ischemia-induced increase in the number of new neurons, high S(+) ketamine concentrations block the post-ischemic increase in newly generated neurons. This effect is irrespective of the extent of other histopathological damage and in line with studies showing that NMDA receptor antagonists like MK-801 inhibit neurogenesis after cerebral ischemia. [source] Pre-hospital use of ketamine in paediatric traumaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2009P. P. BREDMOSE Objectives: To describe the use of ketamine in children by a pre-hospital physician-based service. Methods: A five and a half year retrospective database review of all patients aged <16 years who were attended by London's Helicopter Emergency Medical Service and given ketamine. Results: One hundred and sixty-four children met the inclusion criteria. The median age was 10 years (range 0,15 years). One hundred and four (63%) had a Glasgow Coma Scale (GCS) of 15 and 153 (93%) had a GCS>8 before administration of ketamine. Patients received from 2 to 150 mg ketamine IV (mean=1.0 mg/kg) and 112 (68%) received concomitant midazolam (0.5,18 mg, mean=0.1 mg/kg). One hundred and forty-one (86%) received ketamine intravenously and 23 (14%) intramuscularly. Only 12 patients (7%) were trapped. The most common mechanisms of injury in those who received ketamine were road traffic collisions, burns and falls. Conclusion: The safe delivery of adequate analgesia and appropriate sedation is a priority in paediatric pre-hospital care. Ketamine was predominantly used in awake non-trapped patients with blunt trauma for procedural sedation and analgesia. Detailed database searches did not demonstrate loss of airway, oxygen desaturation or clinically significant emergence reactions after ketamine administration. This study failed to demonstrate any major side effects of the drug and reassured us that the safety profile of the drug in this environment is likely to be satisfactory. The use of ketamine in trapped children was rare. [source] A Prospective Case Series of Pediatric Procedural Sedation and Analgesia in the Emergency Department Using Single-syringe Ketamine,Propofol Combination (Ketofol)ACADEMIC EMERGENCY MEDICINE, Issue 2 2010Gary Andolfatto MD Abstract Objectives:, This study evaluated the effectiveness, recovery time, and adverse event profile of intravenous (IV) ketofol (mixed 1:1 ketamine,propofol) for emergency department (ED) procedural sedation and analgesia (PSA) in children. Methods:, Prospective data were collected on all PSA events in a trauma-receiving, community teaching hospital over a 3.5-year period, from which data on all patients under 21 years of age were studied. Patients receiving a single-syringe 1:1 mixture of 10 mg/mL ketamine and 10 mg/mL propofol (ketofol) were analyzed. Patients received ketofol in titrated aliquots at the discretion of the treating physician. Effectiveness, recovery time, caregiver and patient satisfaction, drug doses, physiologic data, and adverse events were recorded. Results:, Ketofol PSA was performed in 219 patients with a median age of 13 years (range = 1 to 20 years; interquartile range [IQR] = 8 to 16 years) for primarily orthopedic procedures. The median dose of medication administered was 0.8 mg/kg each of ketamine and propofol (range = 0.2 to 3.0 mg/kg; IQR = 0.7 to 1.0 mg/kg). Sedation was effective in all patients. Three patients (1.4%; 95% confidence interval [CI] = 0.0% to 3.0%) had airway events requiring intervention, of which one (0.4%; 95% CI = 0.0% to 1.2%) required positive pressure ventilation. Two patients (0.9%; 95% CI = 0.0% to 2.2%) had unpleasant emergence requiring treatment. All other adverse events were minor. Median recovery time was 14 minutes (range = 3 to 41 minutes; IQR = 11 to 18 minutes). Median staff satisfaction was 10 on a 1-to-10 scale. Conclusions:, Pediatric PSA using ketofol is highly effective. Recovery times were short; adverse events were few; and patients, caregivers, and staff were highly satisfied. ACADEMIC EMERGENCY MEDICINE 2010; 17:194,201 © 2010 by the Society for Academic Emergency Medicine [source] Glycine Receptors Contribute to Hypnosis Induced by EthanolALCOHOLISM, Issue 6 2009Jiang H. Ye Background:, Glycine is a major inhibitory neurotransmitter in the adult central nervous system (CNS), and its receptors (GlyRs) are well known for their effects in the spinal cord and the lower brainstem. Accumulating evidence indicates that GlyRs are more widely distributed in the CNS, including many supraspinal regions. Previous in vitro studies have demonstrated that ethanol potentiates the function of these brain GlyRs, yet the behavioral role of the brain GlyRs has not been well explored. Methods:, Experiments were conducted in rats. The loss of righting reflex (LORR) was used as a marker of the hypnotic state. We compared the LORR induced by systematic administration of ethanol and of ketamine in the absence and presence of the selective glycine receptor antagonist strychnine. Ketamine is a general anesthetic that does not affect GlyRs. Results:, Systemically administered (by intraperitoneal injection) ethanol and ketamine dose-dependently induced LORR in rats. Furthermore, systemically administered (by subcutaneous injection) strychnine dose-dependently reduced the percentage of rats exhibiting LORR induced by ethanol, increased the onset time, and decreased the duration of LORR. Strychnine had no effect, however, on the LORR induced by ketamine. Conclusions:, Given that hypnosis is caused by neuronal depression in upper brain areas, we therefore conclude that brain GlyRs contribute at least in part to the hypnosis induced by ethanol. [source] Comparison of the effect of ketamine added to bupivacaine and ropivacaine, on stress hormone levels and the duration of caudal analgesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2005M. Akbas Background:, The aim of this study was to compare bupivacaine 0.25% and ropivacaine 0.2%, singly and in combination with ketamine, for caudal administration in children. Duration of analgesia, the need for other analgesics and the stress response were measured. Methods:, Eighty children were ramdomized into four groups of twenty. The bupivacaine group received bupivacaine 0.25% and the ketamine/bupivacaine group received bupivacaine 0.25% plus 0.5 mg/kg ketamine. The ropivacaine group received ropivacaine 0.2%, and the ketamine/ropivacaine group received ropivacaine 0.2% plus 0.5 mg/kg ketamine. The duration of analgesia and analgesic requirements were recorded for each group, as were peri-operative and post-operative concentrations of the stress hormones insulin, glucose and cortisol. Results:, Ketamine, added to either bupivacaine or ropivacaine for caudal analgesia, gave a longer duration of analgesia (P < 0.05) than bupivacaine or ropivacaine alone. In all groups, blood insulin concentration was increased, and cortisol concentration reduced. Glucose concentration was significantly increased in all groups (P < 0.05). Conclusions:, Ketamine can safely be added to ropivacaine 0.2% or bupivacaine 0.25% for caudal anesthesia in order to prolong duration of analgesia and reduce the need for additional analgesics. Stress hormone levels are partially attenuated. [source] The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2004A. Kvarnström Background:, Pain following spinal cord injury (SCI) is a therapeutic challenge. Only a few treatments have been assessed in randomized, controlled trials. The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury. We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments resulted in changes of sensibility. Methods:, Ten patients with spinal cord injury and neuropathic pain below the level of injury were included. The analgesic effect of ketamine 0.4 mg kg,1 and lidocaine 2.5 mg kg,1 was investigated. Saline was used as placebo. The drugs were infused over 40 min. A randomized, double-blind, three-period, three-treatment, cross-over design was used. Systemic plasma concentrations of ketamine and lidocaine were assessed. Pain rating was performed using a visual analogue scale (VAS). Sensory function was assessed with a combination of traditional sensory tests and quantitative measurement of temperature thresholds. Results:, Response to treatment, defined as 50% reduction in VAS-score during infusion, was recorded in 5/10 in the ketamine, 1/10 in the lidocaine and 0/10 in the placebo groups. Neither ketamine nor lidocaine changed temperature thresholds or assessments of mechanical; dynamic and static sensibility. Nor could these sensory assessments predict response to treatment in this setting. Lidocaine and particularly ketamine were associated with frequent side-effects. Conclusion:, Ketamine but not lidocaine showed a significant analgesic effect in patients with neuropathic pain after spinal cord injury. The pain relief was not associated with altered temperature thresholds or other changes of sensory function. [source] Complete Recovery From Intractable Complex Regional Pain Syndrome, CRPS-Type I, Following Anesthetic Ketamine and MidazolamPAIN PRACTICE, Issue 2 2007Ralph-Thomas Kiefer MD Abstract Objective: To describe the treatment of an intractable complex regional pain syndrome I (CRPS-I) patient with anesthetic doses of ketamine supplemented with midazolam. Methods: A patient presented with a rapidly progressing contiguous spread of CRPS from a severe ligamentous wrist injury. Standard pharmacological and interventional therapy successively failed to halt the spread of CRPS from the wrist to the entire right arm. Her pain was unmanageable with all standard therapy. As a last treatment option, the patient was transferred to the intensive care unit and treated on a compassionate care basis with anesthetic doses of ketamine in gradually increasing (3,5 mg/kg/h) doses in conjunction with midazolam over a period of 5 days. Results: On the second day of the ketamine and midazolam infusion, edema, and discoloration began to resolve and increased spontaneous movement was noted. On day 6, symptoms completely resolved and infusions were tapered. The patient emerged from anesthesia completely free of pain and associated CRPS signs and symptoms. The patient has maintained this complete remission from CRPS for 8 years now. Conclusions: In a patient with severe spreading and refractory CRPS, a complete and long-term remission from CRPS has been obtained utilizing ketamine and midazolam in anesthetic doses. This intensive care procedure has very serious risks but no severe complications occurred. The psychiatric side effects of ketamine were successfully managed with the concomitant use of midazolam and resolved within 1 month of treatment. This case report illustrates the effectiveness and safety of high-dose ketamine in a patient with generalized, refractory CRPS. [source] Review article: Intravenous vs intramuscular ketamine for pediatric procedural sedation by emergency medicine specialists: a reviewPEDIATRIC ANESTHESIA, Issue 9 2010CONOR DEASY MB, FCEM, MRCS A & E ED Summary Ketamine is a general anesthetic agent widely used for pediatric procedural sedation outside the operating theater by nonanesthesiologists. In a setting where efficacy and safety of the agent are paramount, there are conflicting recommendations in terms of optimal mode of parenteral administration, as well as optimal dosage and need for the coadministration of adjunctive agents to decrease side effects. We investigated existing evidence to determine whether ketamine should be best administered intravenously or intramuscularly. This analysis was made difficult by limited direct comparisons of both modes of parenteral administration and a lack of consistent definitions for key outcomes such as ,effectiveness,',adverse events,',hypoxia,',ease of completion of the procedure,' and ,satisfaction' across studies that have evaluated ketamine. Based on large data sets, the safety and efficacy of both modes of administration are broadly similar. Although data on head to head comparisons of intravenous and intramuscular ketamine is limited, based on our analysis, we conclude that the trends indicate ketamine is ideally administered intravenously. [source] Sedation with ketamine and low-dose midazolam for short-term procedures requiring pharyngeal manipulation in young childrenPEDIATRIC ANESTHESIA, Issue 1 2008HELENA NOVAK MD Summary Background:, Pediatric intestinal biopsy procedures including considerable transpharyngeal manipulation of a wire-guided metal capsule require adequate sedation or anesthesia. This retrospective cohort study was designed to evaluate intravenous sedation with ketamine and low-dose midazolam in young children undergoing these procedures before and also after discharge from the hospital. Methods:, A total of 244 biopsy procedures in 217 children under the age of 16 years were evaluated. All anesthesia records were reviewed according to a defined study protocol and in 145 cases the parents were also interviewed by telephone to obtain further information on possible adverse effects before and after discharge. Results:, Ketamine and low-dose midazolam were carefully titrated by an experienced anesthesia team at an approximate dose ratio of 40 : 1 (total doses 2.3 and 0.05 mg·kg,1) in continuously monitored spontaneously breathing children. Possibly associated problems before discharge were salivation (5.7%), vomiting (4.9%), oxygen desaturation (3.3%), laryngospasm (2.5%) and rash (1.2%) according to the patient records and blurred vision (27%), nausea and vomiting (19%), vertigo (13%) and hallucinations or nightmares (3.5%) according to telephone interviews. Few, mild and transient problems remained after discharge from the hospital. Conclusions:, Careful titration of ketamine and low-dose midazolam provides adequate sedation for nonsurgical pediatric short-term procedures also requiring considerable pharyngeal manipulation, particularly considering the low number of serious airway problems such as laryngospasm. The high incidence of late postoperative problems suggests that prospective studies should be designed for long-term follow-up of young children subjected to sedation or anesthesia. [source] Letter to the Editor: Ketamine and spinal instrumentation by Alain BorgeatPEDIATRIC ANESTHESIA, Issue 12 2007Article first published online: 1 NOV 200 No abstract is available for this article. [source] Ketamine and spinal instrumentationPEDIATRIC ANESTHESIA, Issue 11 2007Alain Borgeat No abstract is available for this article. [source] Anaesthesia in haemodynamically compromised emergency patients: does ketamine represent the best choice of induction agent?ANAESTHESIA, Issue 5 2009C. Morris Summary In rapid sequence induction of anaesthesia in the emergency setting in shocked or hypotensive patients (e.g. ruptured abdominal aortic aneurysm, polytrauma or septic shock), prior resuscitation is often suboptimal and comorbidities (particularly cardiovascular) may be extensive. The induction agents with the most favourable pharmacological properties conferring haemodynamic stability appear to be ketamine and etomidate. However, etomidate has been withdrawn from use in some countries and impairs steroidogenesis. Ketamine has been traditionally contra-indicated in the presence of brain injury, but we argue in this review that any adverse effects of the drug on intracranial pressure or cerebral blood flow are in fact attenuated or reversed by controlled ventilation, subsequent anaesthesia and the greater general haemodynamic stability conferred by the drug. Ketamine represents a very rational choice for rapid sequence induction in haemodynamically compromised patients. [source] Ketamine or alfentanil administration prior to propofol anaesthesia: the effects on ProSealÔ laryngeal mask airway insertion conditions and haemodynamic changes in childrenANAESTHESIA, Issue 3 2009Z. Begec Summary This study was designed to compare the effects of ketamine and alfentanil administered prior to induction of anaesthesia with propofol, on the haemodynamic changes and ProSeal laryngeal mask airway® (PLMA) insertion conditions in children. Eighty children, aged between 3,132 months, were randomly allocated to receive either alfentanil 20 ,g.kg,1 (alfentanil group) or ketamine 0.5 mg.kg,1 (ketamine group) before induction of anaesthesia. Ninety seconds following the administration of propofol 4 mg.kg,1, a PLMA was inserted. In the ketamine group, heart rate and mean arterial pressure were higher during the study period compared with the alfentanil group (p < 0.05). The time for the return of spontaneous ventilation was prolonged in the alfentanil group (p = 0.004). In conclusion, we found that the administration of ketamine 0.5 mg.kg,1 with propofol 4 mg.kg,1 preserved haemodynamic stability, and reduced the time to the return of spontaneous ventilation, compared with alfentanil 20 ,g.kg,1 during PLMA placement. In addition, the conditions for insertion of the PLMA with ketamine were similar to those found with alfentanil. [source] Ketamine for emergency anaesthesia at very high altitude (4243 m above sea-level),ANAESTHESIA, Issue 9 2007M. P. W. Grocott Summary A 22-year-old woman presenting with postpartum haemorrhagic shock at 4243 m altitude required anaesthesia to identify and treat the source of bleeding. Slow intravenous administration of ketamine (0.5 mg.kg,1) resulted in deep anaesthesia and apnoea requiring hand ventilation for 5 min. Haemodynamic stability was maintained throughout the procedure. Haemostasis was achieved following uterine packing and suture of a second-degree vaginal tear and small cervical tear. Confusion and visual hallucinations occurred upon awakening but recovery was otherwise uneventful. Ketamine can be used for emergency anaesthesia in a wilderness environment over 4000 m but it is probable that the benefits outweigh the risks only where life or limb are acutely threatened. Careful titration of the administered dose is strongly advised, particularly in patients where hypovolaemia and/or hypoxaemia are present. The availability of airway management equipment and the skills to use them may significantly reduce the risks associated with anaesthetic administration at very high altitude. [source] Pediatric Procedural Sedation with Ketamine: Time to Discharge after Intramuscular versus Intravenous AdministrationACADEMIC EMERGENCY MEDICINE, Issue 2 2009Preeti Ramaswamy MBBS Abstract Objectives:, Ketamine is an attractive agent for pediatric procedural sedation. There are limited data on time to discharge comparing intramuscular (IM) vs. intravenous (IV) ketamine. The authors set out to determine whether IM or IV ketamine leads to quicker discharge from the emergency department (ED) and how side effect profiles compare. Methods:, All patients who had received ketamine IM or IV at a tertiary children's hospital ED during the 3-year study period (2004,2007) were identified. Prospective sedation registry data, retrospective medical records, and administrative data were reviewed for drug dosages, use of additional agents, time of drug administration to discharge, total ED time (triage to discharge), and adverse events. A subgroup analysis for patients requiring five or fewer sutures (short suture group) was performed. Results:, A total of 229 patients were enrolled (60% male) with median age of 2.8 years (IQR =1.8,4.3 years) and median weight of 15.7 kg (range = 8.7,74 kg). Ketamine was most frequently employed for laceration repair (80%) and foreign body removal (9%). Overall, 48% received ketamine IM and 52% received it IV. In the short-suture subgroup, 52% received ketamine IM, while 48% received it IV. Multivariate linear regression analysis determined time from drug administration to patient discharge as 21 minutes shorter for IV compared with IM administration, adjusted for age and number of additional doses (R2 = ,0.35; 95% CI = ,0.5 to ,0.19; p < 0.001). Total time in the ED (triage to discharge) comparing IV versus IM administration, adjusting for age and gender and number of additional doses, was not significantly different (p = 0.16). In the short-suture subgroup, time to discharge from administration was also shorter in the IV ketamine group (R2 = ,0.454; 95%CI = ,0.66 to ,0.25; p < 0.001) but similar for total time in ED (p = 0.16). Overall, adverse events occurred in 35% (95% CI = 27% to 45%) of the IM group and 20% (95% CI = 13% to 28%) of the IV group (p = 0.01). Only one patient required brief bag-mask ventilation. Conclusions:, In this institution, time from drug injection to discharge was shorter in the IV compared to IM ketamine group, both overall and for the short-suture group. However, time from triage to discharge was similar. [source] Chronic Administration of Ketamine Elicits Antidepressant-Like Effects in Rats without Affecting Hippocampal Brain-Derived Neurotrophic Factor Protein LevelsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008Lêda S. Garcia The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine- and ketamine-treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders. [source] Subdissociative-dose Ketamine versus Fentanyl for Analgesia during Propofol Procedural Sedation: A Randomized Clinical TrialACADEMIC EMERGENCY MEDICINE, Issue 10 2008David W. Messenger MD Abstract Objectives:, The authors sought to compare the safety and efficacy of subdissociative-dose ketamine versus fentanyl as adjunct analgesics for emergency department (ED) procedural sedation and analgesia (PSA) with propofol. Methods:, This double-blind, randomized trial enrolled American Society of Anesthesiology (ASA) Class I or II ED patients, aged 14,65 years, requiring PSA for orthopedic reduction or abscess drainage. Subjects received 0.3 mg/kg ketamine or 1.5 ,g/kg fentanyl intravenously (IV), followed by IV propofol titrated to deep sedation. Supplemental oxygen was not routinely administered. The primary outcomes were the frequency and severity of cardiorespiratory events and interventions, rated using a composite intrasedation event rating scale. Secondary outcomes included the frequency of specific scale component events, propofol doses required to achieve and maintain sedation, times to sedation and recovery, and physician and patient satisfaction. Results:, Sixty-three patients were enrolled. Of patients who received fentanyl, 26/31 (83.9%) had an intrasedation event versus 15/32 (46.9%) of those who received ketamine. Events prospectively rated as moderate or severe were seen in 16/31 (51.6%) of fentanyl subjects versus 7/32 (21.9%) of ketamine subjects. Patients receiving fentanyl had 5.1 (95% confidence interval [CI] = 1.9 to 13.6; p < 0.001) times the odds of having a more serious intrasedation event rating than patients receiving ketamine. There were no significant differences in secondary outcomes, apart from higher propofol doses in the ketamine arm. Conclusions:, Subdissociative-dose ketamine is safer than fentanyl for ED PSA with propofol and appears to have similar efficacy. [source] Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant ,7 and ,4,2 neuronal nicotinic acetylcholine receptors in Xenopus oocytesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Kristen M Coates Ketamine is a dissociative anaesthetic that is formulated as Ketalar, which contains the preservative benzethonium chloride (BCl). We have studied the effects of pure racemic ketamine, the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the ,7 subunit or ,4 and ,2 subunits expressed in Xenopus laevis oocytes. Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human ,7 and ,4,2 nAChRs, with IC50 values of 20 and 50 ,M respectively. Inhibition of the ,7 nAChRs occurred within a clinically relevant concentration range, while inhibition of the ,4,2 nAChR was observed only at higher concentrations. The Ketalar formulation inhibited nAChR function more effectively than was expected given its ketamine concentration. The surprising increased inhibitory potency of Ketalar compared with pure ketamine appeared to be due to the activity of BCl, which inhibited both ,7 (IC50 value of 122 nM) and ,4,2 (IC50 value of 49 nM) nAChRs at concentrations present in the clinical formulation of Ketalar. Ketamine is a noncompetitive inhibitor at both the ,7 and ,4,2 nAChR. In contrast, BCl causes a parallel shift in the ACh dose-response curve at the ,7 nAChR suggesting competitive inhibition. Ketamine causes both voltage-dependent and use-dependent inhibition, only in the ,4,2 nAChR. Since ,7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this receptor subtype may play a role in the profound analgesia, amnesia, immobility and/or autonomic modulation produced by this anaesthetic. British Journal of Pharmacology (2001) 134, 871,879; doi:10.1038/sj.bjp.0704315 [source] Stimulation of DNA synthesis, activation of mitogen-activated protein kinase ERK2 and nuclear accumulation of c-fos in human aortic smooth muscle cells by ketamineCELL PROLIFERATION, Issue 3 2002V. Boulom Proliferation of vascular smooth muscle cells is known to be regulated by autocrine and paracrine stimuli, including extracellular matrix, reactive oxygen species, lipids, and biomechanical forces. The effect of many pharmacological agents to which smooth muscle cells may be exposed, however, is widely unexplored. Ketamine, an intravenous anaesthetic and a phencyclidine derivative, regulates diverse intracellular signalling pathways in smooth muscle cells, several of which are known to affect cell proliferation. The effect of ketamine on proliferative response of smooth muscle cells, however, is not determined. We tested the hypothesis that ketamine may regulate proliferation of smooth muscle cells, and investigated the effects of pharmacological doses of ketamine on their proliferative capacity by measuring DNA synthesis and activation of mitogen-activated protein (MAP) kinase signalling pathway in human aortic smooth muscle cells. DNA synthesis, as determined by incorporation of 3H-thymidine into DNA, was enhanced by 73% (P < 0.0001) and 130% (P < 0.0001) with 10 and 100 µm ketamine, respectively. Ketamine-induced DNA synthesis was dependent on de novo protein synthesis, as it was abolished by an inhibitor of protein synthesis, cycloheximide. A synthetic inhibitor of MAP kinase pathway, PD98059, decreased 50% (P < 0.0001) of ketamine-induced DNA synthesis, suggesting that the activation of MAP kinase pathway was partially responsible for ketamine-induced effects. Consistently, in-gel kinase assay and in vitro kinase assay of cell lysates showed ketamine-induced MAP kinase activation and expression of ERK2 (extracellular signal-regulated kinase) in smooth muscle cells. This effect of ketamine was not dependent on de novo protein synthesis. Immunofluorescent light microscopy showed ketamine-induced nuclear accumulation of c-fos, a downstream effect of MAP kinase activation, in smooth muscle cells. In conclusion, these data support the hypothesis of the study and demonstrate that ketamine, by stimulating DNA synthesis in human aortic smooth muscle cells, may have an impact on proliferative capacity of these cells. The present results also demonstrate that ketamine induces the activation of MAP kinase pathway and nuclear accumulation of transcription factor c-fos in smooth muscle cells. They further demonstrate that the activation of MAP kinases is partially responsible for ketamine-induced DNA synthesis in human aortic smooth muscle cells. Together, these findings suggest that ketamine may play a role as a pharmacological regulator of mechanisms involved in proliferation of smooth muscle cells. [source] Randomized Clinical Trial of Propofol Versus Ketamine for Procedural Sedation in the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 6 2010James R. Miner MD Abstract Objectives:, The objective was to compare the occurrence of respiratory depression, adverse events, and recovery duration of propofol versus ketamine for use in procedural sedation in the emergency department (ED). Methods:, This was a randomized nonblinded prospective clinical trial of adult patients undergoing procedural sedation for painful procedures in the ED. Patients with pain before the procedure were treated with intravenous (IV) morphine sulfate until their pain was adequately treated at least 20 minutes before starting the procedure. Patients were randomized to receive either propofol 1 mg/kg IV followed by 0.5 mg/kg every 3 minutes as needed or ketamine 1.0 mg/kg IV followed by 0.5 mg/kg every 3 minutes as needed. Doses, vital signs, nasal end-tidal CO2 (ETCO2), and pulse oximetry were recorded. Subclinical respiratory depression was defined as a change in ETCO2 of >10 mm Hg, an oxygen saturation of <92% at any time, or an absent ETCO2 waveform at any time. Clinical interventions related to respiratory depression were noted during the procedure, including the addition of or increase in the flow rate of supplemental oxygen, the use of a bag-valve mask apparatus, airway repositioning, or stimulation to induce breathing. After the procedure, patients were asked if they experienced pain during the procedure and had recall of the procedure. Physicians were asked to describe any adverse events or the occurrence of recovery agitation. Results:, One-hundred patients were enrolled; 97 underwent sedation and were included in the analysis. Fifty patients received propofol and 47 received ketamine. Subclinical respiratory depression was seen in 20 of 50 patients in the propofol group and 30 of 47 patients in the ketamine group (p = 0.019, effect size 22.8%; 95% CI = 4.0% to 43.6%). Clinical interventions related to respiratory depression were used in 26 of 50 propofol patients and 19 of 47 ketamine patients (p = 0.253, effect size = ,13.7%; 95% CI = ,33.8% to 6.4%). The median times of the procedures were 11 minutes (range = 4 to 33 minutes) for the ketamine group versus 10 minutes (range = 5 to 33 minutes) for the propofol group (p = 0.256). The median time to return to baseline mental status after the procedure was completed was 14 minutes (range = 2 to 47 minutes) for the ketamine group and 5 minutes (range = 1 to 32 minutes) for the propofol group (p < 0.001). Pain during the procedure was reported by 3 of 50 patients in the propofol group and 1 of 47 patients in the ketamine group (effect size = ,3.9%, 95% confidence interval [CI] = ,11.9 to 4.1). Recall of some part of the procedure was reported by 4 of 50 patients in the propofol group and 6 of 47 patients in the ketamine group (effect size = 4.8%, 95% CI = ,7.6% to 17.1%). Forty-eight of 50 procedures were successful in the propofol group and 43 of 47 in the ketamine group (p = 0.357, effect size = 0.3%; 95% CI = ,7.8% to 8.4%). Recovery agitation was reported in 4 of 50 in the propofol group and 17 of 47 in the ketamine group (effect size = 28.2%, 95% CI = 12.4% to 43.9%). Conclusions:, This study detected a higher rate of subclinical respiratory depression in patients in the ketamine group than the propofol group. There was no difference in the rate of clinical interventions related to respiratory depression, pain, or recall of the procedure between the groups. Recovery agitation was seen more frequently in patients receiving ketamine than in those receiving propofol. The time to regain baseline mental status was longer in the ketamine group than the propofol group. This study suggests that the use of either ketamine or propofol is safe and effective for procedural sedation in the ED. ACADEMIC EMERGENCY MEDICINE 2010; 17:604,611 © 2010 by the Society for Academic Emergency Medicine [source] Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal studyADDICTION, Issue 1 2010Celia J. A. Morgan ABSTRACT Background ,Recreational' use of ketamine is spreading rapidly among young people. In healthy individuals an acute dose of the N-methyl D-aspartate (NMDA) receptor antagonist ketamine induces marked psychosis-like effects and cognitive impairments, but little is known about the long-term effects of the drug. Aims To evaluate the long-term neuropsychiatric or cognitive consequences. Methods A total of 150 individuals were assessed, 30 in each of five groups: frequent ketamine users, infrequent ketamine users, abstinent users, polydrug controls and non-users of illicit drugs. Twelve months later, 80% of these individuals were re-tested. Results Cognitive deficits were mainly observed only in frequent users. In this group, increasing ketamine use over the year was correlated with decreasing performance on spatial working memory and pattern recognition memory tasks. Assessments of psychological wellbeing showed greater dissociative symptoms in frequent users and a dose,response effect on delusional symptoms, with frequent users scoring higher than infrequent, abstinent users and non-users, respectively. Both frequent and abstinent using groups showed increased depression scores over the 12 months. Conclusions These findings imply that heavy use of ketamine is harmful to aspects of both cognitive function and psychological wellbeing. Health education campaigns need to raise awareness among young people and clinicians about these negative consequences of ketamine use. [source] Enantioselective analysis of ketamine and its metabolites in equine plasma and urine by CE with multiple isomer sulfated ,-CDELECTROPHORESIS, Issue 15 2007Regula Theurillat Abstract CE with multiple isomer sulfated ,-CD as the chiral selector was assessed for the simultaneous analysis of the enantiomers of ketamine and metabolites in extracts of equine plasma and urine. Different lots of the commercial chiral selector provided significant changes in enantiomeric ketamine separability, a fact that can be related to the manufacturing variability. A mixture of two lots was found to provide high-resolution separations and interference-free detection of the enantiomers of ketamine, norketamine, dehydronorketamine, and an incompletely identified hydroxylated metabolite of norketamine in liquid/liquid extracts of the two body fluids. Ketamine, norketamine, and dehydronorketamine could be unambiguously identified via HPLC fractionation of urinary extracts and using LC-MS and LC-MS/MS with 1,mmu mass discrimination. The CE assay was used to characterize the stereoselectivity of the compounds' enantiomers in the samples of five ponies anesthetized with isoflurane in oxygen and treated with intravenous continuous infusion of racemic ketamine. The concentrations of the ketamine enantiomers in plasma are equal, whereas the urinary amount of R -ketamine is larger than that of S -ketamine. Plasma and urine contain higher S - than R -norketamine levels and the mean S -/R -enantiomer ratios of dehydronorketamine in plasma and urine are lower than unity and similar. [source] What is the nature of the emergence phenomenon when using intravenous or intramuscular ketamine for paediatric procedural sedation?EMERGENCY MEDICINE AUSTRALASIA, Issue 4 2009Greg Treston Abstract Objective: Ketamine has become the drug most favoured by emergency physicians for sedation of children in the ED. Some emergency physicians do not use ketamine for paediatric procedural sedation (PPS) because of concern about emergence delirium on recovery. The present study set out to determine the true incidence and nature of this phenomenon. Methods: Prospective data relating to any emergence agitation, crying, hallucinations, dreams, altered perceptions, delirium and necessary interventions were recorded in consecutive cases of ketamine PPS from March 2002 to June 2007, and analysed. Standard inclusion and exclusion criteria for the use of ketamine were followed. Results: A total of 745 prospective data collection records were available for analysis over the 5 year period. Of all, 93 (12.5%) children cried on awakening when recovering from PPS, 291 (39%) experienced pleasant altered perceptions and 16 (2.1%) experienced what was called ,emergence delirium'. None required any active treatment and all except one settled within 20 min. There was no evidence of an increased rate of nightmares on telephone follow up in the weeks post procedure. Conclusion: The belief that ketamine, in the doses used for ED PPS, causes frequent emergence delirium is flawed. A pleasant emergence phenomenon is common, but is not distressing for the child, and has no long-term (up to 30 days) negative sequelae. Rarely, there is anxiety or distress on awakening from ketamine sedation, which settles spontaneously. This should not deter emergency physicians from using ketamine for PPS. 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