Injection Of Midazolam Research Articles

Homicides Using Muscle Relaxants, Opioids, and Anesthetic Drugs

Homicides Using Muscle Relaxants, Opioids, and Anesthetic Drugs

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Scapular manipulation for reduction of anterior shoulder dislocation without analgesia: Results of a prospective study

To the best of knowledge, this was the first study of scapular manipulation technique (SMT) in Asia. We conducted this prospective study to report our experiences of reducing anterior shoulder dislocation by SMT without analgesia in a large study group in Iran. Scapular manipulation technique was applied to 111 patients presenting with anterior shoulder dislocation to the ED of the largest teaching hospital in north-east of Iran between January 2009 and January 2010. Reduction was performed without medication and if unsuccessful, the second attempt was carried out with i.v. injection of midazolam. We also evaluated the pain experienced by the patients immediately after reduction attempt. The study consisted of 112 dislocations (one patient had bilateral dislocation). We achieved a success rate of 87.5% without medication at the first attempt and 97.3% overall. In total, 98.2% of dislocations were reduced in less than 1 min. The success rate was significantly lower in the presence of greater tuberosity fractures and also in late presentations (>6 h after trauma). We showed a success rate of 100% in recurrent dislocations. Some 81.1% of the patients reported no pain or mild pain. No complications were observed. The results of our study showed that SMT even without medication is a safe, rapid and relatively painless technique in reducing anterior shoulder dislocation in the ED that might reduce medical resource utilization and can be cost-effective.

Midazolam Inhibits Hippocampal Long-Term Potentiation and Learning through Dual Central and Peripheral Benzodiazepine Receptor Activation and Neurosteroidogenesis

Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity.

Central, but not basolateral, amygdala involvement in the anxiolytic-like effects of midazolam in rats in the elevated plus maze

The role of the amygdala in the mediation of fear and anxiety has been extensively investigated. However, how the amygdala functions during the organization of the anxiety-like behaviors generated in the elevated plus maze (EPM) is still under investigation. The basolateral (BLA) and the central (CeA) nuclei are the main input and output stations of the amygdala. In the present study, we ethopharmacologically analyzed the behavior of rats subjected to the EPM and the tissue content of the monoamines dopamine (DA) and serotonin (5-HT) and their metabolites in the nucleus accumbens (NAc), dorsal hippocampus (DH), and dorsal striatum (DS) of animals injected with saline or midazolam (20 and 30 nmol/0.2 µL) into the BLA or CeA. Injections of midazolam into the CeA, but not BLA, caused clear anxiolytic-like effects in the EPM. These treatments did not cause significant changes in 5-HT or DA contents in the NAc, DH, or DS of animals tested in the EPM. The data suggest that the anxiolytic-like effects of midazolam in the EPM also appear to rely on GABA-benzodiazepine mechanisms in the CeA, but not BLA, and do not appear to depend on 5-HT and DA mechanisms prevalent in limbic structures.

Cardiovascular effects of epidural morphine or ropivacaine in isoflurane-anaesthetised pigs during surgical devascularisation of the liver

The cardiovascular effects of non-abdominal and abdominal surgery during isoflurane anaesthesia (A-group) or isoflurane anaesthesia supplemented with either epidural ropivacaine (AR-group; 0.75 % solution, 0.2 ml/kg) or morphine (AM-group; 0.1 mg/kg diluted in saline to 0.2 ml/kg) were evaluated in 28 healthy pigs with a mean body weight of 30.3 kg SD +/- 4.1 during surgical devascularisation of the liver. Anaesthesia was induced with the intramuscular injection of midazolam (0.3 mg/kg) and ketamine (10 mg/kg). Anaesthesia was deepened with intravenous propofol to enable tracheal intubation and maintained with isoflurane on a circle rebreathing circuit. The vaporiser was set at 2.5% for the A-group and 1.5% for the AR- and AM-groups. Differences between treatment groups were not statistically significant (P > 0.05) for any of the variables. Differences between AM- and AR-groups were marginally significant heart rate (HR) (P = 0.06) and mean arterial blood pressure (MAP) (P = 0.08). Within treatment groups, differences for the A-group were statistically significant (P < 0.05) between non-abdominal and abdominal surgery for HR, systolic blood pressure, diastolic blood pressure (DIA) and MAP. Within the AM-group differences were statistically significant (P < 0.05) for DIA and MAE and within the AR group differences for all variables were not statistically significant (P > 0.05). It was concluded that in isoflurane-anaesthetised pigs, the epidural administration of ropivacaine decreased heart rate and improved arterial blood pressure during surgery.

Safe and effective sedation in endoscopic submucosal dissection for early gastric cancer: a randomized comparison between propofol continuous infusion and intermittent midazolam injection

Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) generally takes longer to perform than conventional endoscopy and usually requires moderate/deep sedation with close surveillance for patient safety. The aim of this study was to compare the safety profiles and recovery scores propofol continuous infusion and intermittent midazolam (MDZ) injection as sedation for ESD. Sixty EGC patients scheduled for ESDs between August and November 2008 were included in this prospective study and randomly divided into a propofol (P-group, 28 patients) and an MDZ (M-group, 32 patients) group using an odd-even system. The P-group received a 0.8 mg/kg induction dose and a 3 mg/kg/h maintenance dose of 1% propofol using an infusion pump. All patients received 15 mg pentazocine at the start of the ESD and at 60-min intervals thereafter. We recorded and analyzed blood pressure, oxygen saturation and heart rate during and following the procedure and evaluated post-anesthetic recovery scores (PARS) and subsequent alertness scores. The propofol maintenance and total dose amounts were (mean +/- standard deviation) 3.7 +/- 0.6 mg/kg/h and 395 +/- 202 mg, respectively. The mean total dose of MDZ was 10.3 +/- 4.5 mg. There were no cases of de-saturation <90% or hypotension <80 mmHg in either group. Alertness scores 15 and 60 min after the procedures were significantly higher in the P-group (4.9/4.9) than in the M-group (4.6/4.5; p < 0.05). The mean PARS 15 and 30 min after the ESDs were significantly higher in the P-group (9.6/9.9) than in the M-group (8.6/9.2; p < 0.01). Based on our results, the ESDs for EGC performed under sedation using propofol continuous infusion were as safe as those performed using intermittent MDZ injection. Propofol-treated patients had a quicker recovery profile than those treated with MDZ. We therefore recommend the use of continuous propofol sedation for ESD, but sedation guidelines for the use of propofol are necessary.

High rates of midazolam injection among drug users in Bangkok, Thailand

BackgroundReports from Thailand suggest that a growing number of people who inject drugs (IDU) are now injecting midazolam, a legal benzodiazepine with potent amnestic and ventilatory depressant effects. We therefore sought to examine midazolam injection among a community-recruited sample of Thai IDU.MethodsWe examined the prevalence and correlates of midazolam injection among 252 IDU participating in the Mitsampan Community Research Project, Bangkok, using multivariate logistic regression. We also examined the use of midazolam in combination with other drugs.Results252 IDU participated in this study, including 66 (26.2%) women. In total, 170 (67.5%) participants reported ever having injected midazolam, and 144 (57.1%) reported daily midazolam injection in the past six months. In multivariate analyses, a history of midazolam injection was independently associated with using drugs in combination (adjusted odds ratio [AOR] = 5.86; 95% confidence interval [CI]: 2.96-11.60), younger age (AOR = 0.43; 95%CI: 0.22-0.83), having a history of methadone treatment (AOR = 3.12, 95%CI: 1.55-6.90), and binge drug use (AOR = 2.25, 95%CI: 1.09-4.63). The drugs most commonly used in combination with midazolam were heroin (72.3%) and yaba (methamphetamine) (30.5%).ConclusionWe observed a high rate of midazolam injection among Thai IDU. Midazolam injection was strongly associated with polysubstance use and binge drug use, and was most commonly used in combination with both opiates and methamphetamines. Our findings suggest that midazolam injection has become increasingly common within Thailand. Evidence-based approaches for reducing harms associated with midazolam injection are needed.

Mice Treated With a Benzodiazepine Had an Improved Survival Rate Following Pseudomonas aeruginosa Infection

Psychological stress has a high incidence after burn injury, therefore, anxiolytic drugs are often prescribed. Unfortunately, to date, no burn study has investigated the effects of anxiolytic drugs on the ability to fight infection. This study was undertaken to determine if psychological stress, anxiety-modulating drugs, or both, alter survival following an infection. On day 0, 7-week-old male C57Bl/6 mice either received a 15% full-thickness flame burn or were sham treated (anesthesia and shaved), whereas controls received no treatment. Mice received midazolam (1 mg/kg intraperitoneally) or saline daily and were stressed by exposure to rat in a guinea pig cage or placed in an empty cage for 1 hour a day, beginning on postburn day 1. For the survival experiments, mice either received bacteria after 2 or 8 consecutive days of predator exposure and drug treatment, which continued daily for 7 days after inoculation. In a separate set of experiments, after eight daily injections of midazolam, mice were given lipopolysaccharide, bacteria, or saline and were killed 12 hours later. Mice that received midazolam had improved survival rates when compared with their saline-treated counterparts, and the protective effect was more significant the more days they received the drug. For most of the cytokines, the bacteria-induced increase was significantly attenuated by midazolam as was the amount of bacteria in the liver. The protective effect seems to be independent of the drug's anxiolytic activity as there were no significant differences in survival between the predator-stressed and the nonstressed mice. The mechanisms responsible for the protective effect remain to be elucidated.

Expanding the reach of harm reduction in Thailand: Experiences with a drug user-run drop-in centre

Background Despite an ongoing epidemic of HIV among Thai people who inject drugs (IDU), Thailand has failed to implement essential harm reduction programmes. In response, a drug user-led harm reduction centre opened in 2004 in an effort to expand reduction programming in Thailand. Methods We examined experiences with the Mitsampan Harm Reduction Centre (MSHRC) among IDU participating in the Mitsampan Community Research Project (Bangkok). Multivariate logistic regression was used to identify factors associated with MSHRC use. We also examined services used at and barriers to the MSHRC. Results 252 IDU participated in this study, including 66 (26.2%) females. In total, 74 (29.3%) participants had accessed the MSHRC. In multivariate analyses, MSHRC use was positively associated with difficulty accessing syringes (Adjusted Odds Ratio [AOR] = 4.05; 95% Confidence Interval [CI]: 1.67–9.80), midazolam injection (AOR = 3.25; 95%CI: 1.58–6.71), having greater than primary school education (AOR = 1.88; 95%CI: 1.01–3.52), and was negatively associated with female gender (AOR = 0.20; 95%CI: 0.08–0.50). Forms of support most commonly accessed included: syringe distribution (100%), food and a place to rest (83.8%), HIV education (75.7%), and safer injecting education (66.2%). The primary reason given for not having accessed the MSHRC was “didn’t know it existed.” Conclusion The MSHRC is expanding the scope of harm reduction in Thailand by reaching IDU, including those who report difficulty accessing sterile syringes, and by providing various forms of support. In order to maximise its benefits, efforts should be made to increase awareness of the MSHRC, in particular among women.

The anterior cingulate cortex is a target structure for the anxiolytic-like effects of benzodiazepines assessed by repeated exposure to the elevated plus maze and Fos immunoreactivity

Prior experience with the elevated plus maze (EPM) increases the avoidance of rodents to the open arms and impairs the anxiolytic-like effects of benzodiazepines on the traditional behaviors evaluated upon re-exposure to the maze, a phenomenon known as one-trial tolerance. Risk assessment behaviors are also sensitive to benzodiazepines. During re-exposure to the maze, these behaviors reinstate the information-processing initiated during the first experience, and the detection of danger generates stronger open-arm avoidance. The present study investigated whether the benzodiazepine midazolam alters risk assessment behaviors and Fos protein distribution associated with test and retest sessions in the EPM. Naive or maze-experienced Wistar rats received either saline or midazolam (0.5 mg/kg i.p.) and were subjected to the EPM. Midazolam caused the usual effects on exploratory behavior, increasing exploratory activity of naive rats in the open arms and producing no effects on these conventional measures in rats re-exposed to the maze. Risk assessment behaviors, however, were sensitive to the benzodiazepine during both sessions, indicating anxiolytic-like effects of the drug in both conditions. Fos immunohistochemistry showed that midazolam injections were associated with a distinct pattern of action when administered before the test or retest session, and the anterior cingulate cortex, area 1 (Cg1), was the only structure targeted by the benzodiazepine in both situations. Bilateral infusions of midazolam into the Cg1 replicated the behavioral effects of the drug injected systemically, suggesting that this area is critically involved in the anxiolytic-like effects of benzodiazepines, although the behavioral strategy adopted by the animals appears to depend on the previous knowledge of the threatening environment.

Persistent zinc depletion in the mossy fiber terminals in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy

Zinc is released in synaptic vesicles with glutamate, and modulates glutamatergic neurotransmission. In brain, the highest amount of zinc, detected by Timm staining, is in the mossy fiber (MF) system in the hippocampus. In the intrahippocampal kainate (KA) mouse model of mesial temporal lobe epilepsy, which is elicited by intrahippocampal KA, prominent MF sprouting develops rapidly within 2 weeks post-KA. However, the intensity of Timm staining is reduced gradually thereafter. The present study is designed to determine the mechanisms underlying this reduction of Timm staining. The changes in Timm staining, and VGluT1, Synapsin-1, and zinc transporter 3 (ZnT3) immunoreactivity (IR) were examined from 4-56 days post-KA. An analysis of glutamate release in the KA-injected hippocampus was conducted by microdialysis before and during the continuous injection of midazolam (MDZ). At 56 days post-KA, Timm staining disappeared completely, whereas VGluT-1-, Synapsin-1-, and ZnT3-IR were increased in the sprouted MF boutons. However, when the seizures were suppressed by a continuous perfusion of MDZ, the glutamate release in the hippocampus decreased and Timm staining was recovered. This study showed that the reduction of Timm staining is the result of decreased zinc content but not the loss of MF itself. The reduction is the result of the enhanced release of zinc relative to storage, and it should facilitate the glutamate excitation that might be related to the epileptogenesis and rapid advancement of the morphologic changes in this model.

Drug use patterns among Thai illicit drug injectors amidst increased police presence

Thailand has traditionally pursued an aggressive enforcement-based anti-illicit drug policy in an effort to make the country "drug-free." In light of this ongoing approach, we sought to assess impacts of enforcement on drug use behaviors among a cohort of injection drug users (IDU) in Thailand. We examined drug use patterns among IDU participating in a cross-sectional study conducted in Bangkok (n = 252). Participants were asked to provide data regarding patterns of drug use in the previous six months, including types of drugs consumed, method of consumption, frequency of use, and weekly income spent on drugs. We also conducted bivariate analyses to identify a possible effect of a reported increase in police presence on measures of drug use and related risk behaviors among study participants. One hundred fifty-five (61.5%) individuals reported injection heroin use and 132 (52.4%) individuals reported injection midazolam use at least daily in the past six months. Additionally, 86 (34.1%) individuals reported at least daily injection Yaba and Ice (i.e., methamphetamine) use. Participants in our study reported high levels of illicit drug use, including the injection of both illicit and licit drugs. In bivariate analyses, no association between increased police presence and drug use behaviors was observed. These findings demonstrate high ongoing rates of drug injecting in Thailand despite reports of increased levels of strict enforcement and enforcement-related violence, and raise questions regarding the merits of this approach.

Forced-air warming effectively prevents midazolam-induced core hypothermia in volunteers

Midazolam is a commonly used sedative and anaesthetic adjuvant and the agent is known to decrease core temperature by core-to-periphery redistribution of heat. We tested the hypothesis that forced-air warming could effectively prevent midazolam-induced hypothermia. Six healthy male volunteers were studied over 3 days. On the first day, the volunteers were alert during a 30 min control period with forced-air warming. On the second day, after the volunteers were vasoconstricted, 75 microg kg(-1) midazolam was injected intramuscularly and they were covered with a cotton blanket. On the third day, after the volunteers were vasoconstricted, 75 microg kg(-1) midazolam was again administered and they were given forced-air warming. Tympanic temperature was measured as the core temperature. Four adhesive skin-surface probes with thermocouples were fixed on the chest, upper right arm, lateral calf and thigh, and both mean skin and body temperatures were calculated. Fingertip perfusion was evaluated using forearm minus fingertip and calf minus toe skin-surface temperature gradients. Thirty minutes after the intramuscular injection of midazolam, the level of sedation in volunteers was measured by a blinded observer according to the alertness/sedation scale. Core temperature significantly decreased by midazolam premedication in a time-dependent manner. Although forced-air warming did not prevent the midazolam-induced transient decrease in core temperature, it increased the temperature to the control level thereafter. We conclude that forced-air warming can effectively prevent midazolam-induced redistribution hypothermia.

Limited sampling strategy in rats to predict the inhibited activities of hepatic CYP3A

The present study was undertaken in order to evaluate feasibility of a limited sampling strategy (LSS) to predict the systemic clearance of midazolam (MDZ), which is a hepatic CYP3A activity phenotyping probe. Groups of rats pretreated with or without serial doses of ketoconazole, which is a selective inhibitor on CYP3A, were used as training set. Linear regression analysis and a Jack-knife validation procedure were performed based on plasma MDZ concentrations at specific time points after sublingual vein injection of MDZ to establish the most informative LSS equations for accurately estimating the clearance of MDZ. Another group of rats in the same setting was used as the validation set to confirm the individual values of estimated clearance (Clest) that were derived from the predictive equations developed in the training set. LSS that were derived from one, two or three sampling times, namely 90 min, 60-90 min, 30-60-90 min and 30-60-120 min, gave the best correlation and acceptable errors between the values of observed clearance (Clobs) and Clest and were chosen to evaluate hepatic CYP3A activity. Our results supported the hypothesis that using limited plasma sampling is simpler than the usual method of estimating CYP3A phenotyping by predicting the systemic clearance of MDZ when the hepatic activity of CYP3A is reduced in the rat. This experimental design offers opportunities to reduce animal use in the study of drug metabolism.

Does remifentanil shorten ventilator maintenance, midozolam prolong it, or both alter its duration?

Dear Sir: Rozendaal et al. [1] should not have concluded that the shortened ventilator weaning time associated with remifentanil use was because of the characteristics of this medication, without considering at least one other possible cause. Cortisol deficiency is present in 30–50% of patients receiving mechanical ventilation in some series [2, 3], and in them has been associated with more than a doubling of weaning time [2] and striking increases in mortality [3]. Acute and prolonged administration of benzodiazepines strongly inhibits cortisol production [4], with a single injection of midazolam at a dose of 0.07 mg/kg sometimes prominently inhibiting cortisol formation for more than a week [5]. Multiple studies suggest that benzodiazepine-induced lowering of cortisol levels may be enhanced by concurrent use of opioids and propofol, but cortisol levels during the use of remifentanil and propofol have not been investigated. In order to examine the possible effect of medications in each of their study arms on the duration of required mechanical ventilation, any cortisol levels measured in their patients, any administration of corticosteroid therapy to them, relationships between these values and the duration of mechanical ventilation, and withdrawal of patients from the study for any reason, including death, would help to clarify any contributions by remifentanil to the duration of ventilator support and other aspects of patient care.

Midazolam-Related Drug Interactions

To identify clinically significant drug interactions and potentially related adverse drug events associated with the use of midazolam. Retrospective data analysis was performed at a single tertiary Brazilian Teaching Hospital from an electronic database derived from the Hospital's computerized physician order entry system over 1 year. Records from patients who received injectable midazolam within a period of 24 hours before flumazenil use were selected. Patients' orders were checked for the presence of clinically significant drug interactions and for the inclusion and discontinuation of potential trigger medications for adverse drug events related to midazolam. A total of 7431 patients were exposed to midazolam, representing 28% of all patients admitted to the hospital. Twenty-six (0.35%) patients received flumazenil within 24 hours after midazolam, corresponding to more than one third of the orders for flumazenil. Clinically significant drug interactions were observed in prescriptions of drugs preceding the use of flumazenil for 23 (88%) of these patients. The most prevalent group of drug interactions were related to the prescription of central nervous system depressants (22 cases), mainly opiate agonists. Analysis of inclusion and discontinuation of drugs demonstrated that the first order for opiates preceded the use of flumazenil in 31% of the cases and, except for tramadol, all opiates were discontinued after its administration, highlighting the potential of these drugs to act as triggers for adverse drug events. Midazolam-related drug interactions are not infrequent and may conduce to serious adverse drug events, including hypotension, respiratory depression, and arrest. Efforts directed toward monitoring interactions and preventing injuries from midazolam use are expected to have a substantial impact on patient safety concerning the use of midazolam.

Evaluation of Soft Palate Changes Using Sleep Videofluoroscopy in Patients With Obstructive Sleep Apnea

To quantitatively evaluate the changes in the soft palate (SP) by sleep videofluoroscopy (SVF). Retrospective analysis. Academic tertiary referral center. A total of 63 consecutive patients with snoring or sleep apnea (53 with obstructive sleep apnea [OSA] and 10 simple snorers). All the subjects underwent SVF and nocturnal polysomnography. Sleep videofluoroscopy was performed before and after sleep induction by intravenous injection of low-dose midazolam (2 mg per person) and was recorded during 3 kinds of events: awake, normoxygenation sleep, and desaturation sleep events. Changes in SP length and the angle between inspiratory and expiratory efforts in each group were evaluated according to sleep events; changes in the SP was assessed according to obstruction sites and severity of OSA. Desaturation sleep events were detected in all patients with OSA but not in simple snorers. In awake events, inspiratory efforts increased the length and angle of the SP in patients with OSA but not in simple snorers. Elongation and angulation were greatest during desaturation sleep events and least during awake events. In normoxygenation events, changes in the SP were significantly larger in patients with OSA than in simple snorers (P < .01 for SP length; P = .03 for SP angle). Elongation of the SP was the biggest in SP-type obstruction. Sleep videofluoroscopy quantitatively showed that the SP was considerably elongated and angulated in patients with OSA even in an awake state. It is an easy way to measure the SP changes and may be a useful technique to differentiate OSA from simple snoring with short examination time.

Oral Midazolam Premedication for Children Undergoing General Anaesthesia for Dental Care

Objectives. To assess the efficacy and safety of injectable midazolam administered orally in 3 different doses in children undergoing complete dental rehabilitation under GA. Subjects and Methods. 60 children aged 2–6 years were enrolled in the study. The children were randomly assigned to one of 3 groups and received orally 0.5, 0.75, or 1.0 mg/kg of injectable midazolam mixed with apple juice 30 minutes before separation from parents. The following measurements were assessed: patient's acceptance of the medication, reaction to separation from parents, sedation scores, and recovery conditions. Results. More children were comfortable with parent separation in the group that received the 1.0 mg/kg dose (90%) compared to the group that received the 0.75 mg/kg dose (75%) and the group that received the 0.5 mg/kg dose (55%). The number of children who had desirable sedation was similar in the 0.75 mg/kg and 1.0 mg/kg dose groups. Twenty five percent of the children in the group that received the 0.5 mg/kg dose did not allow venepuncture before induction of GA, and induction of GA was poor for 20% of the children in this group. An increasing number of children scored excellent in terms of ease of venepuncture in 0.75 mg/kg dose group (10%) and in the 1.0 mg/kg dose group (20%) and in terms of induction of GA, 25% and 35%, respectively. Recovery of spontaneous ventilation and extubation was delayed by over 15 minutes in 2 children in the 1.0 mg/kg dose group. Conclusion. The dose of 0.75 mg/kg of injectable midazolam given orally as premedication is acceptable, effective, and safe.

Prospective clinical trial of magnetic-anchor–guided endoscopic submucosal dissection for large early gastric cancer (with videos)

The treatment of early gastric cancer (EGC) by endoscopic submucosal dissection (ESD) has been rapidly gaining popularity in Japan. However, the procedure needs a high quality of skill. To facilitate complicated ESD by using a single working-channel gastroscope ("one-hand surgery method"), the magnetic-anchor-guided ESD (MAG-ESD) controlled by an extracorporeal electromagnet was reported to be successful in a porcine model. The purpose of this prospective clinical trial was to evaluate the feasibility of MAG-ESD for large EGC located on the gastric body in human beings. Prospective clinical trial at a single center. National Cancer Center Hospital, Tokyo, Japan. From January 2005 to May 2006, 25 patients with EGC >20 mm in diameter, located in the gastric body, and intestinal-type histology were enrolled. Patients with a cardiac pacemaker, advanced malignancy in other organs, severe cardiac and/or pulmonary diseases, and uncontrolled hypertension and/or diabetes mellitus were excluded from this study. Similar to a standard ESD, the MAG-ESD procedure was performed with the patient under conscious sedation by intravenous injection of midazolam (3-5 mg) and pentazocine (15 mg). Unfavorable events and other intraoperative complications caused by the magnetic anchor or the magnetic force were recorded and evaluated. Two GI endoscopists (T.G., I.O.) assessed whether the magnetic anchor facilitated gastric ESD according to 2 criteria: "supportive" and "not supportive." The en bloc resection rate, complications, total operation time, bleeding, perforation, and recurrence rate were also evaluated. The total operation time was measured from insertion to withdrawal of the endoscope, including the retrieving of the magnetic anchor or anchors. All tumors were resected en bloc, without any perforations or severe uncontrollable bleeding. All magnetic anchors were safely retrieved. Two endoscopists assessed that the MAG system was supportive in 23 patients. None of the patients experienced physiologic and mental abnormalities as a result of long-term magnetic-field exposure. During a median follow-up of 20 months (15-32 months), neither delayed adverse effects nor allergies caused by the stainless steel of the magnetic anchor were observed. MAG-ESD is a feasible and safe method that allowed an excellent visualization by suitable tissue tension and facilitated gastric ESD in patients with EGC. The system should be miniaturized to make it applicable in daily clinical practice.