Adverse Events Associated With Procedural Sedation in Pediatric Patients in the Emergency Department

Purpose:

To determine the agents used by emergency medicine (EM) physicians in pediatric procedural sedation and the associated adverse events (AEs) and to provide recommendations for optimizing drug therapy in pediatric patients.

Methods:

We conducted a prospective study at Stanford Hospital’s pediatric emergency department (ED) from April 2007 to April 2008 to determine the medications most frequently used in pediatric procedural sedation as well as their effectiveness and AEs. Patients, 18 years old or younger, who required procedural sedation in the pediatric ED were eligible for the study. The data collected included medical record number, sex, age, height, weight, procedure type and length, physician, and agents used. For each agent, the dose, route, time from administration to onset of sedation, duration of sedation, AEs, and sedation score were recorded. Use of supplemental oxygen and interventions during procedural sedation were also recorded.

Results:

We found that in a convenience sample of 196 children (202 procedures) receiving procedural sedation in a university-based ED, 8 different medications were used (ketamine, etomidate, fentanyl, hydromorphone, methohexital, midazolam, pentobarbital, and thiopental). Ketamine was the most frequently used medication (88%), regardless of the procedure. Only twice in the study was the medication that was initially used for procedural sedation changed completely. Fracture reduction was the most frequently performed procedure (41%), followed by laceration/suture repair (32%). There were no serious AEs reported.

Conclusion:

EM-trained physicians can safely perform pediatric procedural sedation in the ED. In the pediatric ED, the most common procedure requiring conscious sedation is fracture reduction, with ketamine as the preferred agent.     

Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting

Traditional first‐line therapy in the prehospital setting for the acutely agitated patient includes an antipsychotic in combination with a benzodiazepine. Recently, interest has grown regarding the use of ketamine in the prehospital setting as an attempt to overcome the limitations of the traditional medications and provide a more safe and effective therapy. This review provides an overview of the pharmacology of ketamine, evaluates the literature regarding ketamine use for prehospital agitation, and proposes an algorithm that may be used within the prehospital setting. A literature review was conducted to identify articles utilizing ketamine in the prehospital setting. The review was limited to English‐language articles identified in Embase (1988–June 2017) and the U.S. National Library of Medicine (1970–June 2017). References of all pertinent articles were also reviewed. Ten articles were identified including 418 patients receiving ketamine for agitation. The most commonly utilized route for administration was intramuscular (IM), with five of the seven IM administration studies using a ketamine dose of 5 mg/kg. Ketamine administered in this fashion was efficacious to achieve proper sedation during transport and did not require repeat dosing. Three studies applied a ketamine protocol to outline dosing and the management of ketamine adverse events. The most common adverse events identified were respiratory‐related events and hypersalivation. Ketamine has a role for agitation management in the prehospital setting; however, emergency personnel education and ketamine protocols should be utilized to aid in safe and effective pharmacotherapy and provide guidance on the management of adverse events. Future prospective comparative studies, with protocolized standard ketamine regimens, are needed to further delineate the role of ketamine in agitation management and identify accurate adverse event incidence rates.     

Prospective randomized trial evaluating ketamine for advanced endoscopic procedures in difficult to sedate patients

Background Adequate patient sedation is mandatory for advanced endoscopic procedures such as ERCP and EUS. Aim To evaluate the effectiveness and safety of ketamine in difficult to sedate patients undergoing advanced endoscopic procedures. Methods This was a prospective, randomized trial of all patients undergoing ERCP or EUS who were not adequately sedated despite administration of meperidine 50 mg, midazolam 5 mg and diazepam 5 mg. Patients during endoscopy were then randomized to receive either intravenous ketamine (20 mg) every 5 min or continue to receive standard sedation using meperidine and diazepam. Results Of 175 patients, 82 were randomized to receive ketamine and 93 standard sedatives. Compared with standard sedation, qualitative physician rating (P < 0.0001) and depth of sedation (P < 0.001) were superior in the ketamine group with shorter recovery times (P < 0.0001). Both patient discomfort and sedation‐related technical difficulty were significantly less among patients randomized to receive ketamine (P < 0.0001). More patients in the standard sedation group were crossed‐over to the ketamine group due to sedation failure (35.5 vs. 3.7%, P < 0.0001). Nine patients who received ketamine, developed adverse events that were managed conservatively. Conclusions Ketamine is a useful adjunct to conscious sedation in patients who are difficult to sedate. Its use results in better quality and depth of sedation with shorter recovery times than patients sedated using benzodiazepines and meperidine alone. Further prospective studies evaluating the effectiveness and safety of ketamine for endoscopic sedation are needed.     

The pharmacokinetics of ketamine following intramuscular injection to F344 rats

Ketamine is a glutamate N‐methyl‐D‐aspartate receptor antagonist that is a rapid‐acting dissociative anesthetic. It has been proposed as an adjuvant treatment along with other drugs (atropine, midazolam, pralidoxime) used in the current standard of care (SOC) for organophosphate and nerve agent exposures. Ketamine is a pharmaceutical agent that is readily available to most clinicians in emergency departments and possesses a broad therapeutic index with well‐characterized effects in humans. The objective of this study was to determine the pharmacokinetic profile of ketamine and its active metabolite, norketamine, in F344 rats following single or repeated intramuscular administrations of subanesthetic levels (7.5 mg/kg or 30 mg/kg) of ketamine with or without the SOC. Following administration, plasma and brain tissues were collected and analyzed using a liquid chromatography–mass spectrometry method to quantitate ketamine and norketamine. Following sample analysis, the pharmacokinetics were determined using non‐compartmental analysis. The addition of the current SOC had a minimal impact on the pharmacokinetics of ketamine following intramuscular administration and repeated dosing at 7.5 mg/kg every 90 minutes allows for sustained plasma concentrations above 100 ng/mL. The pharmacokinetics of ketamine with and without the SOC in rats supports further investigation of the efficacy of ketamine co‐administration with the SOC following nerve agent exposure in animal models.     

Combination ketamine and propofol for procedural sedation and analgesia

The combination of ketamine and propofol for procedural sedation and analgesia theoretically may be beneficial, with the rationale being that using lower doses of each agent may result in a reduction of the undesirable adverse effects of both agents while maintaining optimal conditions for performing procedures. To examine the current evidence for the efficacy and safety of ketamine and propofol in combination for procedural sedation and analgesia, we searched the MEDLINE (1966-March 2007), EMBASE (1980-March 2007), and Cochrane Database of Systematic Reviews (through the first quarter of 2007) databases for reports describing the use of ketamine and propofol in combination for procedural sedation and analgesia. Additional published reports were identified through a manual search of references from retrieved articles. Prospective, comparative, full-text reports of studies performed in humans that were published in English were reviewed for inclusion. Both authors independently evaluated all studies. Studies in adult and pediatric patients were included if they evaluated efficacy or safety end points. Eight clinical trials were included, seven of which compared a combination of propofol and ketamine with propofol monotherapy. In these trials, variable milligram:milligram ratios of propofol and ketamine were used, ranging from 10:1-2:1, and the optimum dose of these agents in combination is unclear. Combination propofol and ketamine has not demonstrated superior clinical efficacy compared with propofol alone for procedural sedation and analgesia. Conflicting data exist regarding reduced hemodynamic and respiratory complications in patients receiving the combination compared with propofol monotherapy. At higher doses, the addition of ketamine to propofol may incur more adverse effects. Compatibility data for the two agents combined in a syringe are limited. The available evidence does not support the use of a fixed-dose ketamine-propofol combination for procedural sedation and analgesia. Further research is needed to elucidate the role, if any, of this combination for procedural sedation and analgesia.     

Histopathologic effects of the single intramuscular injection of ketamine,atropine and midazolam in a rat model

Ketamine and atropine are often combined in a single syringe for im injection for pediatric conscious sedation; however, the effort of adding midazolam to this combination has not been studied. We investigated the single im injection of ketamine, atropine and midazolam (KAM) to determine if it causes histologic damage around the injection site in a rat model. Group 1 (n = 12) received a single in injection of ketamine, atropine and midazolam in the proportion given during pediatric conscious sedation. Group 2 (n = 12) received an equal volume of isotonic saline im. Group 3 (n = 5) received ketamine and atropine (KA), and a single rat (normal) received no injection. Four rats from each group were sacrificed at 1, 3 and 7 days post-injection, except group 3 KA rats were all sacrificed at 7 d. The injected limbs were harvested, fixed in formalin, decalcified in hydrochloric acid, cut, and mounted on slides. A pathologist examined the slides blinded to the slide label. On d 1 the injection sites of all groups had myocyte degeneration and necrosis with histiocytic infiltrates as well as perimysial edema and hemorrhage. These changes in varying degrees through d 3. By d 7 all histopathological processes had resolved in the saline injected rats and there was mild to no damage in the KA-injected rats. All rats that received KAM injections still had persistent pathologic changes 7 d post-injection. There was histologic evidence that ketamine, atropine and midazolam combination may lead to long-lasting, degenerative changes at the site of the im injection.     

Ketamine

There are two optical isomers of the 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone ketamine: S(+) ketamine and R(-) ketamine. Effects of this drug are mediated by N-methyl-d-aspartate (NMDA), opioid, muscarinic and different voltage-gated receptors. Clinically, the anaesthetic potency of the S(+)-isomer is approximately three to four times that of the R(-)-isomer, which is attributable to the higher affinity of the S(+)-isomer to the phencyclidine binding sites on the NMDA receptors. Ketamine is water- and lipid-soluble, allowing it to be administered conveniently via various routes and providing extensive distribution in the body. Ketamine metabolism is mediated by hepatic microsomal enzymes. It causes bronchodilation and stimulation of the sympathetic nervous system and cardiovascular system. In clinics, ketamine and particularly S(+)-ketamine are used for premedication, sedation, and induction and maintenance of general anaesthesia, which is than termed "dissociative anaesthesia". Ketamine and its S(+)-isomer are ideal anaesthetic agents for trauma victims, patients with hypovolemic and septic shock and patients with pulmonary diseases. Even subanaesthetic doses of this drug have analgesic effects, so ketamine is also recommended for post-operative analgesia and sedation. The combination of ketamine with midazolam or propofol can be extremely useful and safe for sedation and pain relief in intensive care patients, especially during sepsis and cardiovascular instability. In the treatment of chronic pain ketamine is effective as a potent analgesic or substitute together with other potent analgesics, whereby it can be added by different methods. There are some important patient side-effects, however, that limit its use, whereby psycho-mimetic side-effects are most common.     

Preparation of ketamine tablets for treatment of patients with neuropathic pain

Ketamine is known to have distinguished analgesic effects without anesthetic when administered in a low dose. Since ketamine is not commercially available except injection forms, we prepared ketamine tablets for the home-care medication of patients with neuropathic pain. The direct compression or wet granulation method was employed to form 150 mg of tablets containing 50 mg of ketamine. The latter method was superior to the former one in terms of content uniformity, weight variation and disintegration tests of the tablets. Ketamine contents in the tablet prepared by the wet granulation method were unchanged for 12 weeks under the conditions of 25 degrees C and 75% relative humidity (RH). The Cmax and AUC0-3 h values for ketamine after administration of the tablet were slightly smaller than those of the syrup in a healthy volunteer. However, analgesic effects of the tablet was similar to that of the syrup in a patient with neuropathic pain. And the tablet was also effective for another four patients with neuropathic pain. These results indicate that ketamine tablets are useful for the home-care medication of patients with neuropathic pain.     

Appetitive nature of drug cues <Emphasis Type="Italic">re</Emphasis>-confirmed with physiological measures and the potential role of stage of change

Rationale A growing number of investigators are studying ketamine effects in healthy human subjects, but concerns remain about its safety as a research tool. Therefore, it is timely to revisit the safety of subanesthetic doses of ketamine in experimental psychopharmacology studies. Objective To report on the safety of laboratory studies with subanesthetic doses of ketamine in healthy humans using an existing dataset. Materials and methods Medically healthy subjects with no personal or familial Axis I psychotic spectrum disorders were administered subanesthetic doses of ketamine by intravenous infusion in a series of clinical investigations from 1989 to 2005. The safety of ketamine administration was monitored in these subjects. Results Four hundred and fifty subjects received at least one dose of active ketamine. Eight hundred and thirty three active ketamine and 621 placebo infusions were administered. Ten adverse mental status events were documented in nine subjects/infusions that were deemed related to ketamine administration (2% of subjects, 1.45% of infusions). All but one adverse reaction resolved by the end of the test session. The side effects in the remaining individual were no longer clinically significant within 4 days of the test session. No residual sequelae were observed. Conclusion Ketamine administration at subanesthetic doses appears to present an acceptable level of risk for carefully screened populations of healthy human subjects in the context of clinical research programs that intensively monitor subjects throughout their study participation. Other members of the Yale Ketamine Study Group are listed in the Acknowledgements.     

Optimizing dosage of ketamine and xylazine in murine echocardiography

1. Ketamine and xylazine (KX) mixture is the most commonly used anaesthetic drug during echocardiography in mice to induce sedation and immobility. Nevertheless, the doses of KX reported in the literature vary substantially with associated significant difference in cardiac function. To explore the optimal KX dosage and observation time for murine echocardiography, we compared the effects of various KX combinations on echocardiographic measurement. 2. Mice were anaesthetized with ketamine (50 or 100 mg/kg) and xylazine (0-10 mg/kg). Echocardiography was performed 5, 10, 20 and 40 min after induction of anaesthesia. Also, cardiac function was assessed in mice with and without pressure-overload induced left ventricle (LV) hypertrophy and dysfunction, either under anaesthesia with KX or whilst conscious. 3. Ketamine at 100 mg/kg alone or together with xylazine at 0.1 mg/kg was associated with a high and stable heart rate (HR), a high fractional shortening (FS) and produced the least effect on LV inner dimension at end of diastole (LVIDd). Ketamine and xylazine at 100 and 10 mg/kg, respectively, produced a lower and stable FS, but with a low and unstable HR. All other combinations resulted in depressed and unstable cardiac function during this period. 4. The dose-dependent suppression of FS by xylazine was counteracted partly by ketamine. 5. Although in the chronic pressure-overload model LV hypertrophy can be detected accurately in both the anaesthetized or conscious state, systolic dysfunction was masked partially by higher doses of xylazine (2.5 or 10 mg/kg) combined with ketamine at 100 mg/kg. 6. With KX anaesthesia, both the dose of xylazine and the anaesthetic duration are critical in achieving an ideal condition for murine echocardiography. Ketamine at 100 mg/kg alone produces acceptable anaesthesia, stable cardiac function with a minimal depressant effect and is therefore recommended if single-dose anaesthetic is to be used.     

Effects of ketamine on the peripheral autonomic nervous system of the rat.

The effects of ketamine (2-(o-chlorophenyl) 2-methylaminocyclohexanone) (2-50 mg/kg) on the responses of the pithed rat arterial pressure, anococcygeus muscle and colon to selective stimulation of the spinal autonomic outflows were examined. Ketamine depressed the vasopressor response produced by stimulation of the lumbar sympathetic outflow in a dose-dependent manner but did not significantly affect the pressor response to intravenous noradrenaline (NA) administration. Ketamine depressed the motor responses of the anococcygeus to stimulation of the pre-ganglionic lumbar sympathetic outflow or to stimulation of post-ganglionic fibres in the sacral region in a dose-dependent manner, the response to preganglionic stimulation being relatively more sensitive to such depression. The anococcygeus response to NA was significantly potentiated with doses of ketamine of 20 mg/kg and 50 mg/kg. Ketamine depressed the motor response of the smooth muscle of the colon to stimulation of the sacral parasympathetic outflow in a dose-dependent manner and at lower doses than were required to produce an equivalent depression of the sympathetic responses in the other tissues. A comparison was made of the effects of ketamine and cocaine on the motor responses of the anococcygeus muscle in vitro to NA, carbachol and field stimulation. Both ketamine and cocaine produced a non-specific depression of all responses at high doses whereas cocaine but not ketamine produced a large potentiation of NA and motor nerve responses at lower doses. The results are discussed in relation to the hypothesis that ketamine might elevate blood pressure in conscious animals and man by potentiating vascular adrenergic responses.     

Ketamine Induces Toxicity in Human Neurons Differentiated from Embryonic Stem Cells via Mitochondrial Apoptosis Pathway

Ketamine is widely used for anesthesia in pediatric patients. Growing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models. Our understanding of anesthesia neurotoxicity in humans is currently limited by difficulties in obtaining neurons and performing developmental toxicity studies in fetal and pediatric populations. It may be possible to overcome these challenges by obtaining neurons from human embryonic stem cells (hESCs) in vitro. hESCs are able to replicate indefinitely and differentiate into every cell type. In this study, we investigated the toxic effect of ketamine on neurons differentiated from hESCs. Two-week-old neurons were treated with different doses and durations of ketamine with or without the reactive oxygen species (ROS) scavenger, Trolox. Cell viability, ultrastructure, mitochondrial membrane potential (ΔΨm), cytochrome c distribution within cells, apoptosis, and ROS production were evaluated. Here we show that ketamine induced ultrastructural abnormalities and dose- and timedependently caused cell death. In addition, ketamine decreased ΔΨm and increased cytochrome c release from mitochondria. Ketamine also increased ROS production and induced differential expression of oxidative stress-related genes. Specifically, abnormal ultrastructural and ΔΨm changes occurred earlier than cell death in the ketamine-induced toxicity process. Furthermore, Trolox significantly decreased ROS generation and attenuated cell death caused by ketamine in a dose-dependent manner. In conclusion, this study illustrates that ketamine time- and dose-dependently induces human neurotoxicity at supraclinical concentrations via ROS-mediated mitochondrial apoptosis pathway and that these side effects can be prevented by the antioxidant agent Trolox. Thus, hESC-derived neurons might provide a promising tool for studying anesthetic-induced developmental neurotoxicity and prevention strategies.     

Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation

The ability to deliver safe and effective moderate sedation is crucial to the ability to perform invasive procedures. Sedative drugs should have a quick onset of action, provide rapid and clear-headed recovery, and be easy to administer and monitor. A number of drugs have been demonstrated to provide effective sedation for outpatient procedures but since each agent has its own limitations, a thorough knowledge of the available drugs is required to choose the appropriate drug, dose and/or combination regimen for individual patients. Midazolam, propofol, ketamine and sevoflurane are the most frequently used agents, and all have a quick onset of action and rapid recovery. The primary drawback of midazolam is the potential for accumulation of the drug, which can result in prolonged sedation and a hangover effect. The anaesthetics propofol and sevoflurane have recently been used for sedation in procedures of short duration. Although effective, these agents require monitored anaesthesia care. Ketamine is an effective agent, particularly in children, but there is concern regarding emergence reactions. AQUAVAN injection (fospropofol disodium), a phosphorylated prodrug of propofol, is an investigational agent possessing a unique and distinct pharmacokinetic and pharmacodynamic profile. Compared with propofol emulsion, AQUAVAN is associated with a slightly longer time to peak effect and a more prolonged pharmacodynamic effect. Advances in the delivery of sedation, including the development of new sedative agents, have the potential to further improve the provision of moderate sedation for a variety of invasive procedures.     

The health and psycho-social consequences of ketamine use

Ketamine is a non-competitive NMDA receptor antagonist that acts as a dissociative anaesthetic with analgesic and amnestic properties. Ketamine has broad areas of application and is a rapidly acting, relatively safe analgesic and anaesthetic agent, particularly for children and is widely used in veterinary practice. Ketamine can induce schizophrenic-like symptoms in healthy adults and schizophrenic patients. It has a wide margin of safety and there are very few cases of pure ketamine overdose recorded, with the majority of deaths due to the dangerous activities or contexts of its use. Information on ketamine is not routinely collected in population surveys and morbidity and mortality data collections. Levels of use in the general population, however, appear to be very low with higher levels in groups with access to the drug, medical and veterinarian professionals, and party drug users. There are a number of potential ketamine effects that may be seen as adverse or harmful, with growing evidence of the physical and psychological symptoms of ketamine dependence among recreational ketamine users. A withdrawal syndrome, including psychotic features, is beginning to be described. The use of ketamine with other neurotoxic drugs, such as alcohol, should be avoided. Increased rates of high risk sexual and injecting behaviours in association with ketamine use, however, have been reported by gay men and marginalised youth in the US. In conclusion, ketamine does not appear to currently pose a significant public health risk, however, at the individual level the usual harm minimisation strategies should be observed.     

Ketamine-induced neurotoxicity and changes in gene expression in the developing rat brain

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used for analgesia and anesthesia in obstetric and pediatric practice. Recent reports indicate that ketamine causes neuronal cell death in developing rodents and nonhuman primates. The present study assessed the potential dose- and time-dependent neurotoxic effects and associated changes in gene expression after ketamine administration to postnatal day 7 (PND-7) rat pups. Pups were exposed to ketamine subcutaneously at doses of 5, 10, or 20 mg/kg, in one, three or six injections respectively. Control animals received the same volume of saline at the same time points. The animals were sacrificed 6 h after the last ketamine or saline administration and brain tissues were collected for RNA isolation and histochemical examination. Six injections of 20 mg/kg ketamine significantly increased neuronal cell death in frontal cortex, while lower doses and fewer injections did not show significant effects. The ketamine induced cell death seemed to be apoptotic in nature. In situ hybridization demonstrated that NMDA receptor NR1 subunit expression was dramatically increased in the frontal cortex of ketamine treated rats. Microarray analysis revealed altered expression of apoptotic relevant genes and increased NMDA receptor gene expression in brains from ketamine treated animals. Quantitative RT-PCR confirmed the microarray results. These data suggest that repeated exposures to high doses of ketamine can cause compensatory up-regulation of NMDA receptors and subsequently trigger apoptosis in developing neurons.     

L-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

Ketamine, an antagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptors, is a pediatric anesthetic. Ketamine has been shown to be neurotoxic and cardiotoxic in mammals. Here, we show that after 2 h of exposure, 5 mM ketamine significantly reduced heart rate in 26 h old zebrafish embryos. In 52 h old embryos, 1 mM ketamine was effective after 2 h and 0.5 mM ketamine at 20 h of exposure. Ketamine also induced significant reductions in activated MAPK (ERK) levels. Treatment of the embryos with the ERK inhibitor, PD 98059, also significantly reduced heart rate whereas the p38/SAPK inhibitor, SB203580, was ineffective. Ketamine is known to inhibit lipolysis and a decrease of ATP content in the heart. Co-treatment with l-carnitine that enhances fatty acid metabolism effectively rescued ketamine-induced attenuated heart rate and ERK activity. These findings demonstrate that l-carnitine counteracts ketamine's negative effects on heart rate and ERK activity in zebrafish embryos.     

Clinical uses of dexmedetomidine in pediatric patients

Dexmedetomidine is being used off-label as an adjunctive agent for sedation and analgesia in pediatric patients in the critical care unit and for sedation during non-invasive procedures in radiology. It also has a potential role as part of anesthesia care to prevent emergence delirium and postanesthesia shivering. Dexmedetomidine is currently approved by the US FDA for sedation only in adults undergoing mechanical ventilation for <24 hours. Pediatric experiences in the literature are in the form of small studies and case reports. In patients sedated for mechanical ventilation and/or opioid/benzodiazepine withdrawal, the loading dose ranged from 0.5 to 1 microg/kg and was usually administered over 10 minutes, although not all patients received loading doses. This patient group also received a continuous infusion at rates ranging from 0.2 to 2 microg/kg/h, with higher rates used in burn patients and those with withdrawal following > or =24 hours of opioid/benzodiazepine infusion. The dexmedetomidine dosage used for anesthesia and sedation during non-invasive procedures, such as radiologic studies, ranged from a loading dose of 1-2 microg/kg followed by a continuous infusion at 0.5-1.14 microg/kg/h, with most patients spontaneously breathing. For invasive procedures, such as awake craniotomy or cardiac catheterization, dosage ranged from a loading dose of 0.15 to 1 microg/kg followed by a continuous infusion at 0.1-2 microg/kg/h. Adverse hemodynamic and respiratory effects were minimal; the agent was well tolerated in most patients. The efficacy of dexmedetomidine varied depending on the clinical situation: efficacy was greatest during non-invasive procedures, such as magnetic resonance imaging (MRI), and lowest during invasive procedures, such as cardiac catheterization. Dexmedetomidine may be useful in pediatric patients for sedation in a variety of clinical situations. The literature suggests potential use of dexmedetomidine as an adjunctive agent to other sedatives during mechanical ventilation and opioid/benzodiazepine withdrawal. In addition, because of its minimal respiratory effects, dexmedetomidine has also been used as a single agent for sedation during non-invasive procedures such as MRI. However, additional studies in pediatric patients are warranted to further evaluate its safety and efficacy in all age ranges.     

Cytoskeleton interruption in human hepatoma HepG2 cells induced by ketamine occurs possibly through suppression of calcium mobilization and mitochondrial function

Ketamine is an intravenous anesthetic agent often used for inducing and maintaining anesthesia. Cytoskeletons contribute to the regulation of hepatocyte activity of drug biotransformation. In this study, we attempted to evaluate the effects of ketamine on F-actin and microtubular cytoskeletons in human hepatoma HepG2 cells and its possible molecular mechanisms. Exposure of HepG2 cells to ketamine at 相似文献   

Opioid mechanisms of some behavioral effects of ketamine

The effect of naloxone on the duration of sleep and on analgesia produced by ketamine, and on the development of tolerance and cross-tolerance with morphine to ketamine analgesic effects were investigated in mice. Ketamine produced a dose-dependent analgesia. Naloxone (4 mg/kg) significantly inhibited the analgesic effects of ketamine (40 mg/kg), but (given in a dose of 2 mg/kg) did not affect the duration of ketamine sleep. Chronic administration of ketamine (160 mg/kg twice daily for 7 days) resulted in a gradual shortening of ketamine sleep and in the development of tolerance to the analgesic action of ketamine. There also developed cross-tolerance between analgesic effects of morphine and ketamine. Ketamine (20 mg/kg) significantly inhibited symptoms of morphine abstinence produced in morphine-pelleted mice by naloxone administration or by pellet removal. The results suggest that at least some elements of the mechanism of action of ketamine and morphine may be common and related to the endogenous opioid system.