Superiority of split dose midazolam as conscious sedation for outpatient colonoscopy

AIM: To elucidate the efficacy and safety of a split dose of midazolam in combination with meperidine for colonoscopy. METHODS: Eighty subjects undergoing outpatient colonoscopy were randomly assigned to group A or B. Group A (n = 40) received a split dose of midazolam in combination with meperidine. Group B (n = 40) received a single dose of midazolam in combination with meperidine. Outcome measurements were level of sedation, duration of sedation and recovery, degree of pain and satisfaction, procedure-related memory, controllability, and adverse events. RESULTS: Group A had a lower frequency of significant hypoxemia (P = 0.043) and a higher sedation score on withdrawal of the endoscope from the descending colon than group B (P = 0.043). Group B recovered from sedation slightly sooner than group A (P < 0.002). Scores for pain and memory, except insertion-related memory, were lower in group A one week after colonoscopic examination (P = 0.018 and P < 0.030, respectively). Poor patient controllability was noted by the endoscopist and nurse in group B (P = 0.038 and P = 0.032, respectively). CONCLUSION: Split dose midazolam in combination with meperidine resulted in a safer, more equable sedation status during colonoscopic examination and a reduction in procedure-related pain and memory, but resulted in longer recovery time.

How to improve patient satisfaction during midazolam sedation for gastrointestinal endoscopy?

To determine the procedure-related factors that affect sedation satisfaction and to make a suggestion to improve it.METHODSWe prospectively enrolled a total of 456 patients who underwent outpatient endoscopy procedures with midazolam sedation between March 2014 and August 2014. All patients completed both pre- and post-endoscopy questionnaires about sedation expectations and satisfaction.RESULTSThe study cohort included 167 (36.6%) patients who underwent esophagogastroduodenoscopy (EGD), 167 (36.6%) who underwent colonoscopy, and 122 (26.8%) who underwent a combined procedure (EGD and colonoscopy). Over 80% of all patients were satisfied with sedation using midazolam. In univariate and multivariate analyses, total procedure time in the EGD group, younger age (≤ 50 years), and longer colonoscopy withdrawal time in the colonoscopy group were related to decreased satisfaction with sedation. However, in active monitoring and intervention group, there was no decrease in grade of satisfaction despite longer procedure time due to more procedures during colonoscopy. Younger age (≤ 50 years), longer inter-procedure time gap, and colonoscopy withdrawal time were related to decreased satisfaction in the combined EGD and colonoscopy group.CONCLUSIONMidazolam is still a safe and effective sedative for gastrointestinal endoscopy. Satisfaction with sedation depends on several factors including age (≤ 50 years) and procedure time duration. To improve patient satisfaction with sedation, active monitoring of sedation status by the endoscopist should be considered for patients who require long procedure time.

Voltammetric behavior of sedative drug midazolam at glassy carbon electrode in solubilized systems

Redox behavior of midazolam was studied at a glassy carbon electrode in various buffer systems,supporting electrolytes and pH using differential paise,square-wave and cyclic voltammetry.Based on its reduction behavior,a direct differential pulse voltammetric method has been developed and validated for the determination of midazolam in parenteral dosage.Three welldefined peaks were observed in 0.1％ SLS,Britton-Robinson (BR) buffer of pH 2.5.The effect of surfaetants like sodium lauryl sulfate (SLS),cetyl trimethyl ammonium bromide (CTAB) and Tween 20 was studied.Among these surfactants SLS showed significant enhancement in reduction peak.The cathodic peak currents were directly proportional to the concentration of midazolam with correlation coetfficient of 0.99.

Rhabdomyolysis after midazolam administration in a cirrhotic patient treated with atorvastatin

The administration of statins in patients with liver disease is not an absolute contraindication. Hepatotoxicity is a rare and often dose-related event and in the literature there are only a few described cases of fatal rhab-domyolysis in patients with chronic liver disease after statin administration. During treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors,the factors responsible for myopathy may either be related to the patient,or due to interactions with other medications that are metabolic substrates of the same isozymes and therefore able to increase blood statin concentration. The most important side effects consist of increased transaminase levels,abdominal pain or muscle weakness,increased serum levels of creatine kinase and rhabdomyolysis. In this article we report a case of fatal rhabdomyolysis with acute renal failure after gastric endoscopy,where midazolam was used as a sedation agent in a patient with chronic liver disease treated with a high dose of atorvastatin. Therefore,we suggest paying particular attention to the potential risks of associating atorvastatin and midazolam in patients with chronic liver disease who need to undergo gastric endoscopy.

Propofol vs midazolam sedation for elective endoscopy in patients with cirrhosis:A systematic review and meta-analysis of randomized controlled trials

BACKGROUND Patients with cirrhosis frequently require sedation for elective endoscopic procedures.Several sedation protocols are available,but choosing an appropriate sedative in patients with cirrhosis is challenging.AIM To conduct a systematic review and meta-analysis to compare propofol and midazolam for sedation in patients with cirrhosis during elective endoscopic procedures in an attempt to understand the best approach.METHODS This systematic review and meta-analysis was conducted using the PRISMA guidelines.Electronic searches were performed using MEDLINE,EMBASE,Central Cochrane,LILACS databases.Only randomized control trials(RCTs)were included.The outcomes studied were procedure time,recovery time,discharge time,and adverse events(bradycardia,hypotension,and hypoxemia).The risk of bias assessment was performed using the Revised Cochrane Risk-of-Bias tool for randomized trials(RoB-2).Quality of evidence was evaluated by GRADEpro.The meta-analysis was performed using Review Manager.RESULTS The search yielded 3,576 records.Out of these,8 RCTs with a total of 596 patients(302 in the propofol group and 294 in the midazolam group)were included for the final analysis.Procedure time was similar between midazolam and propofol groups(MD:0.25,95%CI:-0.64 to 1.13,P=0.59).Recovery time(MD:-8.19,95%CI:-10.59 to-5.79,P<0.00001).and discharge time were significantly less in the propofol group(MD:-12.98,95%CI:-18.46 to-7.50,P<0.00001).Adverse events were similar in both groups(RD:0.02,95%CI:0-0.04,P=0.58).Moreover,no significant difference was found for bradycardia(RD:0.03,95%CI:-0.01 to 0.07,P=0.16),hypotension(RD:0.03,95%CI:-0.01 to 0.07,P=0.17),and hypoxemia(RD:0.00,95%CI:-0.04 to 0.04,P=0.93).Five studies had low risk of bias,two demonstrated some concerns,and one presented high risk.The quality of the evidence was very low for procedure time,recovery time,and adverse events;while low for discharge time.CONCLUSION This systematic review and meta-analysis based on RCTs show that propofol has shorter recovery and patient discharge time as compared to midazolam with a similar rate of adverse events.These results suggest that propofol should be the preferred agent for sedation in patients with cirrhosis.

BLOOD PRESSURE CHANGES OF ELDERLY HYPERTENSIVE PATIENTS DURING DENTAL EXTRACTION UNDER SEDATION WITH CONTINUOUS INTRAVENOUS INFUSION OF MIDAZOLAM

Objective To evaluate the changes in blood pressure (BP) of elderly hypertensive patients having dental extraction under sedation with continuous intravenous infusion of midazolam. Methods One hundred elderly hypertensive patients undergoing dental extraction were recruited for this single-blind, randomized, controlled study. Patients in intervention group (n=50) were given midazolam dissolved in glucose solution and patients in control group (n=50) were given glucose solution only with communication technique. Systolic BP (SBP) and diastolic BP (DBP) were recorded in five time points. Results Under basal conditions, intervention group did not show significant difference in BP compared with control group. Before sedation, mean values of SBP and DBP (especially SBP) significantly increased compared with basal conditions in both groups (P<0.05). During dental extraction sessions, mean values of BP in intervention group significantly decreased than control group (P<0.05), but coefficient of variation did show significant difference in both groups. Conclusion Continuous intravenous infusion of midazolam has been proved to be very successful in controlling BP of elderly patients having dental extraction.

Midazolam dose is associated with recurrence of paradoxical reactions during endoscopy

BACKGROUND Midazolam is commonly used for sedation during gastrointestinal procedures.However,some patients experience paradoxical reactions characterized by excessive movement or excitement.AIM To investigate the rate of recurrence of paradoxical reactions to midazolam during an upper endoscopy.METHODS We retrospectively reviewed 122152 sedative endoscopies among a total of 58553 patients at the Seoul National University Hospital,Healthcare System Gangnam Center,from July 2013 to December 2018.Among them,361 patients with a history of paradoxical reaction during sedative upper endoscopy were enrolled.The characteristics of patients in the recurrent and non-recurrent groups were compared via multivariable analysis using logistic regression.RESULTS Paradoxical reactions occurred in 0.86%(1054/122152)of endoscopies,and in 1.51%(888/58553)of patients.Among the 361 subjects with previous paradoxical reactions in sedative endoscopies,111(30.7%)experienced further paradoxical reactions.Univariable analysis revealed that the total midazolam dose used was higher in the recurrent group(6.74±2.58 mg)than in the non-recurrent group(5.49±2.04 mg;P<0.0001).Patients were administered a lower dose of midazolam than previous doses:1 mg less in the recurrent group and 2 mg less in the non-recurrent group.Multivariable analysis showed that the midazolam dose difference was an independent risk factor for recurrent paradoxical reaction(odds ratio:1.213,95%CI:1.099-1.338,P=0.0001).CONCLUSION The rate of recurrence of paradoxical reactions is significantly associated with midazolam dosage.The dose of midazolam administered to patients with previous paradoxical reactions should be less than that previously used.

Effect of midazolam on the proliferation of neural stem cells isolated from rat hippocampus

In many recent studies, the inhibitory transmitter gamma-aminobutyric acid has been shown to modulate the proliferation, differentiation and survival of neural stem cells. Most general anesthetics are partial or allosteric gamma-aminobutyric acid A receptor agonists, suggesting that general anesthetics could alter the behavior of neural stem cells. The neuroprotective efficacy of general anesthetics has been recognized for decades, but their effects on the proliferation of neural stem cells have received little attention. This study investigated the potential effect of midazolam, an extensively used general anesthetic and allosteric gamma-aminobutyric acid A receptor agonist, on the proliferation of neural stem cells in vitro and preliminarily explored the underlying mechanism. The proliferation of neural stem cells was tested using both Cell Counting Kit 8 and bromodeoxyuridine incorporation experiments. Cell distribution analysis was performed to describe changes in the cell cycle distribution in response to midazolam. Calcium imaging was employed to explore the molecular signaling pathways activated by midazolam. Midazolam （30-90 IJM） decreased the proliferation of neural stem cells in vitro. Pretreatment with the gamma-aminobutyric acid A receptor antagonist bicuculline or Na-K-2CI cotransport inhibitor furosemide partially rescued this inhibition. In addition, midazolam triggered a calcium influx into neural stem cells. The suppressive effect of midazolam on the proliferation of neural stem cells can be partly attributed to the activation of gamma-aminobutyric acid A receptor. The calcium influx triggered by midazolam may be a trigger factor leading to further downstream events.

Comparison of sedative effectiveness of thiopental versus midazolam in reduction of shoulder dislocation

BACKGROUND: Various sedative drugs have been proposed to control anxiety and agitation in shoulder dislocation, but none of them has been diagnosed as the best sedative and relaxant agent. The study aimed to compare the sedative effectiveness of thiopental versus midazolam in reduction of shoulder dislocation.METHODS: A randomized double-blind controlled trail was performed in 80 patients with shoulder dislocation recruited from the emergency department. Ten patients were excluded and 70 patients were enrolled in the study. Case group received intravenous thiopental 2 mg/kg+2 μg/kg fentanyl while control group received intravenous midazolam 0.1 mg/kg+2 μg/kg fentanyl. Number of times, patients and physician's satisfaction, difficulty of procedure, degree of muscle relaxation, time of sedation and complete recovery, number of patients with apnea episode, O2 saturation, patient's pain score and adverse events were all recorded.RESULTS: Muscular tone had significant difference between the two groups(P-value=0.014) and thiopental was more muscle relaxant than midazolam. Replacement of shoulder dislocation in thiopental group was easier than midazolam group(P-value=0.043). There was no need to use multiple methods of reduction in either group. Before drug infusion the mean±SD VAS scores were 8.37±2.21 in the midazolam group(A) and 8.94±1.78 in the thiopental group(B); mean difference 0.57, 95% CI= –0.38 to 1.52. After completion of the procedure, the mean±SD VAS scores in group(A) and(B) were 3.20±1.30 vs. 3.65±1.30; mean difference –0.45, 95% CI= –1.07 to 0.16.CONCLUSION: Thiopental might be more effective and relaxant than midazolam for reduction of shoulder dislocation.

Safety of applying midazolam-ketamine-propofol sedation combination under the supervision of endoscopy nurse with patient-controlled analgesia pump in colonoscopy

AIM To compare the results of midazolam-ketaminepropofol sedation performed by an endoscopy nurse and anaesthetist during colonoscopy in terms of patient satisfaction and safety.METHODS American Statistical Association(ASA) Ⅰ-Ⅱ 60 patients who underwent colonoscopy under sedation were randomly divided into two groups: sedation under the supervision of an anaesthetist(SSA) and sedation under the supervision of an endoscopy nurse(SSEN). Both groups were initially administered 1 mg midazolam, 50 mg ketamine and 30-50 mg propofol. Continuation of sedation was performed by the anaesthetist in the SSAgroup and the nurse with a patient-controlled analgesia(PCA) pump in the SSEN group. The total propofol consumption, procedure duration, recovery times, pain using the visual analogue scale(VAS) and satisfaction score of the patients, and side effects were recorded. In addition, the patients were asked whether they remembered the procedure and whether they would prefer the same method in the case of re-endoscopy.RESULTS Total propofol consumption in the SSEN group was significantly higher(P < 0.05) than that in the SSA group. When the groups were compared in terms of VAS score, recovery time, patient satisfaction, recall of the procedure, re-preference for the same method in case of re-endoscopy, and side effects, there were no significant differences(P > 0.05) between the two groups. No long-term required intervention side effects were observed in either group.CONCLUSION Colonoscopy sedation in ASA Ⅰ-Ⅱ patients can be safely performed by an endoscopy nurse using PCA pump with the incidence of side effects and patient satisfaction levels similar to sedation under anaesthetist supervision.

EVALUATION OF ORAL MIDAZOLAM AS CONSCIOUS SEDATION FOR PEDIATRIC PATIENTS IN ORAL RESTORATION

Objective To evaluate the effect of midazolam alone on sedation in young children for dental restorative care. Methods Forty children, aged 5 to 10 years with a mean age of 7.3 years, participated in this study. Twenty-one patients were assigned to intervention group received 0. 5 mg/kg of oral midazolam 20 minutes prior to the beginning of dental treatment, and 19 patients in control group received placebo liquid 20 minutes before treatment. All patients received painless local anesthetic injection and were restrained with children＇s board and bands. Blood pressure （ BP）, heart rate （HR）, oxygen saturation, treatment compliance scores of the Ramsay scale, the Briekopf and Butmer scale, Frankl scale, and the Houpt scale were recorded. Each procedure was taped and all the data were evaluated every 5 minutes by an anesthetist or experienced dentist who was unaware of the drug given to the child. Results HR in intervention group （82. 5 ± 5.1 bpm） was much lower than that in control group （95.2 ± 8.9 bpm; F=31.20, P 〈0. 001 ）. Intervention group had a significantly lower systolic BP level （94.8±5.6 mmHg） than control group （98.5±5.5 mm Hg; F=4. 34, P =0. 04）, but the diastolic BP （63.0 ± 3.5 mm Hg） was not significantly lower than control group （ 65.5 ± 4. 8 mm Hg; F = 3.31, P = 0. 07 ）. Children in intervention group showed more compliance. The patients＇ scores of the Ramsay scale, Briekopf and Buttner scale, Frankl scale, and Houpt scale in intervention group （ 1.37 ± 0. 96, 1.37 ± 0. 83, 1.32 ± 0. 67, and 2. 32 ± 1.49, respectively） were significantly lower than those in control group （3.71 ± 1.23, 2.71 ± 0. 96, 2.71 ± 0. 90, and 4.71 ± 1.19 ; F = 44. 66, 22. 36, 30.39,and 31.88,respectively,all P〈0.001） Conclusions Oral midazolam alone is safe and produces effective sedation for the dental treatment of young children. Oral midazolam application should be generally preferred because it is more easily accepted by pediatric patients.

Comparison of impact of adjuvant treatment of midazolam, fentanyl, and magnesium sulfate with intrathecal bupivacaine on block characteristics and postoperative analgesia in knee arthroplasty: A randomized clinical trial

Objective:To compare the efficacy of midazolam,fentanyl,and magnesium sulfate as adjuvants to intrathecal bupivacaine on both block characteristics and postoperative analgesia in knee arthroplasty.Methods:This randomized double-blind clinical trial recruited spinal anesthesia patients of the American Society of Anesthesiologists classⅠorⅡ,who needed knee arthroplasty.Patients were stratified into three intervention groups,including the midazolam group,the fentanyl group,and the magnesium sulfate group,and the patients were administered with midazolam,fentanyl,and magnesium sulfate,respectively.Hemodynamic parameters,sensory and motor block,and pain score(Visual Analogue Scale)were measured and compared among the three groups.Results:A total of 105 patients were included in this study with 35 patients in each group.There was no statistically significant difference in terms of oxygen saturation,mean blood pressure,duration of surgery,and postoperative complications,including nausea,vomiting,bradycardia,dizziness,and hypotension,as well as the time of opioid administration among the three groups(P>0.05).Statistically significant differences were found in terms of heart rate at 15,30,45,60,75,and 105 min after beginning of operation among the three groups,which was lower in the midazolam group(P<0.05).The midazolam group showed a shorter time to achieve sensory block after spinal anesthesia,sensory block to T8 or higher and sensory block to T12 and L1(P<0.05).Besides,the three groups showed significantly differences in terms of onset of motor block after spinal anesthesia and time to achieve motor block to T8 or higher or Bromage score 3(P=0.001).No significant difference was noted in pain scores among the three groups(P>0.05).Conclusion:Midazolam resulted in a shorter time to achieve sensory and motor block to T8 or higher,the onset of motor block and sensory block after spinal anesthesia,and time to achieve sensory block to T12 and L1,and the pain scores were not significantly different among the groups.Thus,midazolam can be highly underlined,if a shorter onset of sensory and motor blocks is targeted.[Funded by the research deputy of Arak University of Medical Sciences(No.99258);fa.irct.ir number,IRCT20141209020258N164].

Effect of oral premedication of midazolam, ketamine, and dexmedetomidine on pediatric sedation and ease of parental separation in anesthesia induction for elective surgery: A randomized clinical trial

Objective:To compare effect of midazolam,dexmedetomidine,and ketamine as oral premedication on pediatric sedation and ease of parental separation anxiety in anesthesia induction.Methods:This multicenter,prospective,randomized,double-blind,clinical trial focused on a pediatric population aged 2-7 years(n=153)with the American Society of AnesthesiologistsⅠ-Ⅱwho required elective surgery.The patients were stratified into three intervention groups:midazolam,ketamine,and dexmedetomidine.Hemodynamic parameters(blood pressure,heart rate,and oxygen saturation)every 5 min until induction of anesthesia along with non-hemodynamic factors,comprised of sedation score before the administration and at the time of being separated from the parents,as well as parental separation anxiety scale,acceptance of anesthesia induction,and side effects were recorded and compared.Results:No statistically significant difference in oxygen saturation,heart rate,blood pressure,duration of surgery,time to achieve an Aldrete score of 9-10,or sedation score was noted in the study groups.More patients in the dexmedetomidine and midazolam groups could better ease parental separation anxiety than the ketamine group(P=0.001).Moreover,fewer patients accept anesthesia induction(P=0.001)and more had side effects in the ketamine group(P=0.047).Conclusions:Our findings indicate that compared to the ketamine group,dexmedetomidine and midazolam are better in easing parental separation anxiety and accepting induction of anesthesia with fewer side effects.Dexmedetomidine and midazolam may be considered better choices.However,the final choice hinges on the patient's specific physical condition and the anesthesiologist's preference.Clinical registarion:This study is registered in the Iranian Registry Clinical Trial center with the clinical trial code of IRCT20211007052693N1.

A COMPARISON OF THE EFFECTS OF THE PROPOFOL VERSUS MIDAZOLAM DURING TOTAL INTRAVENOUS ANESTHESIA FOR GYNECOLOGICAL SURGERY PROCEDURES

The effects of propofol and midazolam as an intravenous anesthetic were compared in 40 ASA Ⅰ-Ⅱ patients undergoing gynecological surgery during total intravenous anesthesia (TIVA). They were divided into propofol group (Pn= 20) and midazolam group (Mn= 20) randomly. The anesthesia was designed for each group respectively. Here, we discuss the experimental method and the results, which indicate that propofol is not only an effective anesthetic but also has more rapid and head-clear recovery properties than midazolam.

A clinical investigation of the relationship between different sedation depths and the restlessness after using midazolam as an adjuvant during regional anesthesia

Objective： To investigate the relationship between different sedation depth and the restlessness after using midazolam as an adjuvant during regional anesthesia. Methods ： One hundred and fifty patients undergoing regional anesthesia were randomly divided into three groups. In group A, the patients were sedated at the level of OAA/S IV with midazolam during regional anesthesia. In group B and C, the sedation depths were kept at the levels of Ⅲ and Ⅱrespectively. The changes of BP, HR and SpO2 were recorded before and after midazolam. The rate of restlessness was also evaluated. Results： Blood pressures decreased in certain degree at 5 and 10 min after midazolam compared with those before in all three groups. BP decreased over 20% of the baseline in 4 cases in group A, in 5 cases in group B, and in 5 cases in group C. There was no significant difference in BP dropping among three groups. Compared with group B and C SpO2 dropped significantly at 3 and 5 rain after midazolam in group C, in which SpO2 was less than 93% in 8 cases. The restlessness rate in group C was 22%, which was significantly higher than those in group A （2% ,P〈0.01） and group B（4% ,P〈0.05）. Conclusion： The sedation depth is related to the rate of restlessness when midazolam is used as an adjuvant during regional anesthesia. It is suggested that the appropriate sedation depth for the patients under regional anesthesia is OAA/S Ⅲ.

Intranasal Delivery of Two Benzodiazepines, Midazolam and Diazepam, by a Microemulsion System

Nasal application of benzodiazepines might be an alternative to intravenous administration in acute clinical situations such as seizures emergencies. However, irritation and pain as well as symptoms like teary eyes, dizziness, discomfort, nasal drainage and bad taste usually accompany subject received midazolam and diazepam via the nasal route. The purpose of this study was to evaluate the use of a new alcohol-free microemulsion system as a carrier for diazepam or midazolam given intranasally. Midazolam (base) or diazepam was solubilized in the microemulsion to obtain a high drug concentration of 25 mg/g (2.5% by weight), to provide 2.5 mg drug in 100 μl spray (d ≈ 1.00 g/ml). The nasal absorption of both drugs from the same microemulsion formulation (containing 20% aqueous phase) was found to be fairly rapid after administration of 0.4 mg/kg to rabbits. The absolute bioavailability of diazepam after intranasal administration using this formulation was 33.45% ± 12.36% and the tmax was 18.33 ± 23.09 min, which was twice longer than the tmax obtained after midazolam administration, 9.25 ± 6.75 min. The pharmacokinetic parameters of midazolam in W/O (20% water) microemulsion and their comparison with midazolam in O/W (50% water) microemulsion have shown that both formulations resulted in a relatively short time to reach the peak plasma level (tmax), that is, 9.25 ± 6.75 min and 6.75 ± 5.67 min, respectively. However, the peak plasma levels (Cmax) and the absolute bioavailability (FA) of midazolam were significantly higher after administration of the W/O formulation than those obtained after application of O/W formulation, i.e., 46.62 ± 17.38 μg/ml vs. 15.44 ± 4.00 μg/ml, and 35.19% ± 11.83% vs. 19.83% ± 16.32%, respectively. Our results suggest that the new microemulsion system may be useful for getting rapid-onset of midazolam and diazepam following intranasal administration, resulting in reasonable peak plasma levels and bioavailability, but most importantly, providing a high measure of tolerability and comfort.

The Addition of Midazolam Reduces the Incidence of Early Postoperative Nausea and Vomiting in Short Time Gynecological Procedures

Background: If untreated, one third of patients who undergo surgery develop postoperative nausea and/or vomiting (PONV). The prevention of postoperative nausea and vomiting can improve satisfaction among vulnerable patients. We hypothesized that preoperative anxiety may increase the incidence of PONV. The objective was to assess whether administration of a benzodiazepine prior to surgery would reduce the incidence of PONV. Methods: 130 women (ASA I and II) scheduled to undergo dilatation and curettage comprised the study group. The women were allocated randomly to two study groups according to the type of anesthesia administered (with and without midazolam). Results: Sixty-eight women received midazolam and 62 did not. Patients treated with midazolam were feeling more comfortable (“friendliness”, p = 0.005 and “elation”, p = 0.01) and had less postoperative fatigue (p = 0.04) than non-midazolam-treated group. Patients treated with midazolam had significantly fewer emetic episodes during the first 4 hours after surgery than those without midazolam (0.1 ± 0.2 vs 0.3 ± 0.6, respectively, p = 0.003). Conclusions: Midazolam reduces the incidence of PONV and improves patient’s comfort. We suggest that midazolam has to be routinely included in the anesthesia protocol for short-term gynecological procedures (dilatation and curettage).

Development and Validation of a Method to Quantify Midazolam in a New Oral Formulation for Pediatric Use

Aim: To develop an HPLC method to quantify midazolam in a new oral formulation for pediatric use. Methods: The stability of the new formulation was evaluated at different storage conditions and a preliminary assay of relative bioavailability was carried out in healthy volunteers. Results: The method of quantification was linear in the range of 5 to 60 μg·mL-1. The midazolam amount in the formulation remained stable for 90 days at 4 and 40℃ (in the dark) while at 25℃ was stable only for 14 days (exposed to light). Discussion: The relative bioavailability assay suggests that our preparation of midazolam in white chocolate reaches plasma levels similar to those induced by the apple juice formulation. Conclusion: This new white chocolate formulation masks the unpleasing flavour and has a more attractive presentation to the paediatric patient, which may be useful for children sedation and to ease its management by health carers.

Midazolam Impairs Learning and Memory Ability Through ERK/CREB Signaling Pathway and Oxidative Damage of Hippocampus in Rats

This study aimed to elucidate whether midazolam affected the learning and memory of rats through the extracellular signal-regulated kinase(ERK)/cyclic adenosine monophosphate response element-binding(CREB)signaling pathway and hippocampal oxidative damage.Overall 120 Wistar rats were randomly assigned to four groups,including one control and three midazolam-exposed groups(20,60 and 150 mg•kg^(-1)).After an intraperitoneal injection of midazolam/physiological saline for both 1 h(n=15)and 24 h(n=15),10 rats(five came from 1 h,and the remaining five came from 24 h)were randomly selected from each group for the Morris water maze test.The hippocampus tissue samples were harvested for the assessment of superoxide dismutase(SOD)and catalase(CAT)activities as well as glutathione peroxidase(GPx),malonyl dialdehyde(MDA),nitric oxide(NO)and inducible nitric oxide synthase(iNOS)levels.The remaining 80 rats were euthanized,and the hippocampal tissue was isolated.The expressions of ERK1,ERK2 and CREB mRNA were tested using RT-qPCR.The protein expressions of p-ERK1/2 and p-CREB were tested using Western blotting.The Morris water maze tests indicated that midazolam-treated rats have weaker learning and memory ability compared to the control rats.Midazolam increased MDA,NO,iNOS and CAT,and decreased GPx and SOD activities compared to the control group.The expression levels of ERK1/2 and CREB in the hippocampus of rats in the midazolam treatment groups were significantly lower compared to the control group at 1 h after intraperitoneal injection of midazolam,and in a dose-dependent relationship but returning it to normal levels at 24 h after midazolam intraperitoneal injection.Therefore,it was concluded that the learning and memory impairment of midazolam might be associated with the down-regulation of the ERK/CREB signaling pathway and oxidative damage in rat hippocampus.

Influence of Acetaminophen on Pharmacokinetics and Pharmacodynamics of Midazolam in Healthy Volunteers

Background: Midazolam and acetaminophen are often co-administered in anesthesia practice. Both are metabolized by CYP 3A4 enzyme in the liver, and hence compete for the enzyme sites. This might lead to reduced metabolic breakdown and enhanced pharmacodynamic effects of midazolam in the presence of acetaminophen. Methods: The present study was undertaken to test this hypothesis. After IRB approval from Mount Sinai Medical Center, 15 healthy volunteers were used for 2 tests. For the first test, they were randomly assigned to receive oral doses of either midazolam 0.3 mg/kg in cherry syrup (Protocol A), or midazolam 0.3 mg/kg plus cherry flavored acetaminophen 15 mg/kg (Protocol B). At set intervals from 0 to 480 min, the blood levels of midazolam and the subjects pulse rate, mean arterial pressure, respiratory rate, BIS index, and OAA/S scores were determined. After 2 weeks, the same subjects underwent the second test;they received the other medication protocol. Results: Acetaminophen slightly, but not significantly, increased the half life of blood midazolam, and the depressive effects of midazolam on the clinical signs of the subjects. Conclusion: These results lead us to conclude that there is no need to reduce the doses of midazolam when used in combination with acetaminophen.