Different Doses Of Midazolam Research Articles

Comparative assessment of different doses of midazolam to prevent etomidate-induced myoclonus – A randomized, double-blind, placebo-controlled trial

Background: Etomidate is a popular induction agent, due to its several advantages for example, an extremely stable hemodynamic profile with no effects on sympathetic nervous system and baroreceptors, minimal effect on respiration and also prevents histamine release in healthy patients or in those with reactive airway disease. It, however, may be associated with myoclonus whose incidence has been reported as 50%–80% in nonpremedicated patients. Ideally, a pretreatment drug for preventing myoclonic movements should be short acting, not have significant effects on respiration and hemodynamics, and not prolong recovery from anesthesia. Midazolam has been used as a pretreatment to attenuate myoclonus in different doses with varied results, but the optimal dose has not been established. The present study was planned to compare the effect of three doses of midazolam, i.e., 0.015 mg/kg, 0.03 mg/kg, and 0.05 mg/kg in preventing etomidate-induced myoclonus.Materials and Methods: This study comprised 164 American Society of Anesthesiologists I/II consenting patients between 18 and 60 years. They were randomly divided into four groups after which pretreatment with normal saline in group M0, midazolam 0.015 mg/kg in group M0.015, 0.03 mg/kg in group M0.03, and 0.05 mg/kg in group M0.05 was administered. The primary outcome was the incidence of myoclonus after etomidate. The secondary outcome measures included severity of myoclonus and changes in hemodynamic parameters. One-way analysis of variance with Bonferroni's correction was used to compare quantitative data. Chi-square test was applied for qualitative data. Further, as there were four groups with multiple comparisons, Bonferroni's correction was applied and P < 0.01 was considered statistically significant.Results: We observed a significant reduction in the incidence of myoclonus of group M0.015 as compared to group M0 (P < 0.001). A significant reduction in severity of myoclonus was observed in all the three midazolam groups compared to the control group (P < 0.001) without any significance among the patients receiving different doses of midazolam.Conclusion: We recommend using midazolam pretreatment in a dose of 0.015 mg/kg for prevention of etomidate-induced myoclonus.

Comparison of pre-extubation propofol and midazolam to prevent emergence agitation in children—a prospective randomized study

BackgroundEmergence delirium is one of the most common and troublesome complications seen after inhalational anesthesia, with an estimated 20–80% incidence rate. It can lead to an increase in mortality, morbidity, and hospital stay, which indirectly reflects a major economic burden. The aim of our study is to compare the effect of propofol and two different doses of midazolam to prevent emergence agitation in children given 5 min before extubation. Seventy-five ASA (American Society of Anesthesiologists) Physical Status I–II patients aged 2–14 years who were scheduled for elective surgeries under general anesthesia were included in the study. Patients in the study groups were randomized into three groups 25 in each group; group P (propofol of 0.5 mg/kg iv), group ML (midazolam low dose of 0.03 mg/kg iv), and group M (midazolam of 0.05 mg/kg iv) given 5 min before extubation. The primary objective was to study the effect of propofol and two different doses of midazolam for the prevention of emergence agitation in children. The secondary objective was to observe the complications like bronchospasm, laryngospasm, persistent cough, and desaturation in pediatric patients.ResultsThe time taken for emergence from anesthesia after surgery in the propofol group was 5.11 ± 1.223 min and in the group midazolam low dose and midazolam time taken was 8.53 ± 2.326 min and 12.45 ± 2.145 min, respectively, and was found to be statistically significant. The incidence of delirium observed with a Cole score of >3 was seen in 14 (56%) patients in group P, 7 (28%), and 6 (24%) patients of groups ML and M, respectively.ConclusionsMidazolam in low doses given before extubation is effective in preventing the emergence delirium during the postoperative period in pediatric patients without delay in recovery during general anesthesia.

Effects of intravenous administration of propofol and midazolam on pentylenetetrazole kindled seizures in rats

To date, studies examining the proconvulsants or anticonvulsants in chronic epileptic models in rat are rare. Propofol has conflicting reports regarding the pro- or anti-convulsant effects on chronic seizures. Midazolam is considered another anesthetic option that used in combination with propofol and has documented anticonvulsant properties. The present study was undertaken to examine the effects of intravenous administration of various doses of propofol, in comparison to midazolam, on seizures activity in chronically epileptic rats, using PTZ seizures kindled model. Kindling in control and experimental rats was induced by intraperitoneal sub - convulsive dose of PTZ (35 mg/kg) every alternate day. After each injection of PTZ, rats were monitored for 30 minutes for behavioral seizures occurrence. Seizure scores were rated according to Racin scale. Once kindled, animals were treated with different doses of midazolam or propofol prior to PTZ challenge and were subsequently observed. The present study showed that, propofol or midazolam intravenous administration suppressed PTZ seizures in kindled rats and led to a significant, dose dependent decrease of behavioral seizures score and increased the percent inhibition of PTZ kindled seizures stage. The ED50 of propofol for percent inhibition of PTZ kindled seizures stage was 5.36 mg/kg, whereas the ED50 of midazolam was 1.85 mg/kg, suggesting that the anticonvulsant effects of midazolam against PTZ kindled seizures are more profound. In conclusion, the current study showed that propofol protected against PTZ kindled seizures and provided further evidence for its anticonvulsant effects reported in other chronic animal seizures, namely amygdala-kindled convulsions in rats.

Comparison of Caudal Tramadol with different doses of Midazolam addon for Postoperative analgesia in Children Undergoing Inguinoscrotal Operations

Background: Safe and effective postoperative analgesic modalities have remained a subject of contemporary clinical research, particularly in children. The present study aimed at comparing the effectiveness of pain relief in children undergoing inguinoscrotal surgery with caudal tramadol alone and in combination with different doses of midazolam.&#x0D; Methods: Ninety children of either sex, aged one year to fifteen years, undergoing inguinoscrotalsurgical procedures under general anesthesia were recruited in a randomized double blinded fashion to receive one of the three study medications through caudal route. Group T (n= 30) received injectiontramadol 2mg/kg in a volume of 0.5ml/kg up to a maximum volume of 20ml, while group TM (n= 30)and TM/2 (n= 30) received additional midazolam 50mcg/kg and 25mcg/kg respectively. The study medications were administered immediately after induction of anesthesia. Postoperative analgesia was measured using a modified Hannallah 10 points Pediatric Objective Pain Scale described by Hannallah and colleagues. Pain score of ≤ 4 was considered effective analgesia. Duration of analgesia was defined as the time between caudal injection to the first need of analgesia.&#x0D; Results: The duration of analgesia in group TM (1145±281.41 min) and TM/2 (1012.67±260.68 min)was significantly longer than that in group T (690.83±215.7 min) (p&lt;0.005). The sedation score was the highest in group TM and the least in group T. Nausea vomiting was the commonest side effect in all the three groups without any significant differences in the incidences between the groups.&#x0D; Conclusion: Addition of midazolam to tramadol for caudal administration in children undergoinginguinoscrotal operations produces significantly longer duration of postoperative analgesia than produced by epidural administration of tramadol alone.

A comparative study of analgesic efficacy of intrathecal bupivacain(0.5) heavy with different doses of midazolam(1mg and 2mg) as adjuvant in patients undergoing elective lower limb surgeries

A comparative study of analgesic efficacy of intrathecal bupivacain(0.5) heavy with different doses of midazolam(1mg and 2mg) as adjuvant in patients undergoing elective lower limb surgeries

The efficacy of different doses of Midazolam added to Lidocaine for upper extremity Bier block on the sensory and motor block characteristics and postoperative pain.

Objective:This study was designed to evaluate the effect of different doses of midazolam on anesthesia and analgesia quality when added to lidocaine during the intravenous regional anesthesia (IVRA).Methods:One hundred and forty patients underwent hand surgery were randomly allocated into four groups to receive 3 mg/kg lidocaine 2% diluted with saline to a total volume of 40 mL in the control Group L-C (n = 35), 30 μg/kg midazolam plus 3 mg/kg lidocaine 2% diluted with saline to a total volume of 40 mL in the midazolam Group L-M1 (n = 35), 40 μg/kg midazolam plus 3 mg/kg 2% lidocaine diluted with saline to a total volume of 40 mL in the midazolam Group L-M2 (n = 35), and 50 μg/kg midazolam plus 3 mg/kg lidocaine 2% diluted with saline to a total volume of 40 mL in the midazolam Group L-M3 (n = 35). Sensory and motor block and recovery times, tourniquet pain, intra-operative analgesic requirement, and visual analog scale (VAS) scores were recorded.Findings:Onset time of sensory and motor block in L-M3 Group was shorter than the L-M2 and L-M1 and L-C Groups (P < 0.001). Furthermore, prolonged sensory (P = 0.005) and motor recovery time (P = 0.001) in L-M3 were longer than the other groups. Intra-operative VAS score and intra-operative fentanyl consumption in L-M3 were lower than the other groups (P < 0.001). The numbers of patients needed to pethidine in Group L-M3 were significantly less compared with the other groups (P = 0.035). VAS scores were significantly lower in Group L-M3 in different time intervals in the postoperative period compared with the other groups (P < 0.001).Conclusion:Addition of 50 μg/kg midazolam for IVRA (Group L-M3) enhanced intra-operative analgesia and improved anesthesia quality better than other groups receiving lower midazolam doses as well as a control group.

Comparison of dexmedetomidine and three different doses of midazolam in preoperative sedation

Background:This study was conducted to compare the efficacy and effects of dexmedetomidine and midazolam in preoperative sedation.Materials and Methods:A total of 125 patients in American Society of Anaesthesiologists (ASA) I-II were divided into three groups: Group I (n = 40) for controls, Group II (n = 40) for Dexmedetomidine (1 μg/kg), and group III was the midazolam group (n = 45). Group III was further divided into three subgroups according to the doses of midazolam: Group IIIA (n = 15) received 0.02 mg/kg, group IIIB (n = 15) received 0.04 mg/kg, and group IIIC (n = 15) received 0.06 mg/kg of midazolam. Drugs were infused over a 10-minute period with appropriate monitoring. Ramsay and visual analog scores, for sedation and anxiety, respectively, and mean arterial pressure, heart rate, and SpO2 measurement, including respiratory rates were recorded, every 5 minutes for 30 minutes following infusion.Results:There was marked sedation and a decrease in anxiety in groups II and IIIC (P < 0.01). Mean arterial pressure (MAP) and heart rate (HR) decreased significantly in group II (P < 0.01 and P < 0.05, respectively), but there was no associated hypotension (MAP <60 mm Hg) or bradycardia (HR <50 bpm) (P < 0.05). Respiratory rates and SpO2 values decreased in groups II, IIIA, IIIB, and IIIC. The differences in respiratory rates were not significant (P > 0.05); however, decrease in SpO2 was significant in group IIIC (P < 0.01).Conclusions:Dexmedetomidine was as effective as higher doses of midazolam in sedation. The hemodynamic and respiratory effects were minimal. Although dexmedetomidine caused significant decrease in the blood pressure and heart rate, it probably just normalized increased levels caused by preoperative stress.

Effect of epidural midazolam on the epidural analgesia with sufentanil after gynecological operation

Objective To evaluate the effect of different doses of midazolam administered epidurally on the epidural analgesia with sufentanil after gynecologic operation. Methods One hundred and twenty ASA patients aged 30-50 yr with body weight index<30 kg/m2 undergoing abdominal gynecological operation under epidnral anesthesia received continuous epidnral infusion of sufentanil for 48 h (a loading dose of 10 ml of sufentanil+continuous infiusion at 2 ml/h) after operation. The patients were randomly allocated to one of 4 groups (n=30each):group Ⅰcontrol (C) received epidural sufentanil only; group Ⅱ, Ⅲ , Ⅳ received epidural sufentanil +epidural midazolam 0.025 mg/kg (M1), 0.050 mg/kg (M2) and 0.075 mg/kg (M3) respectively. Epidural catheter was placed at L1.2 or L2.3 interspace. The severity of postoperative pain was assessed with an 100 cm VAS score. Adequate analgesia was defined as VAS score of ≤ 30 cm. Echo of epidural sufentanil was determined by up-and-down sequential technique. The initial sufentanil concentration was 1 μg/ml. Each time the concentration of epidural sufentanil increased/decreased by 20% of the previous concentration. The level of sedation was evaluated with Ramsay sedation score (1=fully awake, 6=asleep, unresponsive to verbal stimulus). The side effects were also recorded. Results The EC50 of sufentanil and 95% confidence interval were 0.87 ('0.79-0.96),0.82(0.74-60.90), 0.67 (0.61-0.74) and 0.63 (0.56-0.71) μg/ml respectively in group C, group M1, M2 and M3. EC50 was significantly lower in group M2 and M3 than in group C. The Ramsay sedation score was in the order of group M3 group M2 group M1 and group C (P<0.05). The incidences of over-sedation and respiratory depression were significantly higher in group M3 than in other 3 groups. Conclusion Epidural midazolam 0.050-0.075 mg/kg can enhance the analgesic effect of epidural sufentanil after gynecological operation. Key words: Sufentanil; Midazolam; Dose-response relationship, drug; Analgesia, epidural; Gynecologic surgical procedures

The Antinociceptive Effects of Midazolam on Three Different Types of Nociception in Mice

Antinociceptive effects of systemically administered midazolam remain controversial. The present study was performed to investigate its antinociceptive effects on different types of nociception in mice. Four different doses of midazolam (1, 3, 10, and 30 mg/kg) were administered intraperitoneally (i.p.). Saline was used as a control. The hot plate test, tail pressure test, acetic acid writhing test, the running wheel test, and the balance beam test were performed following the drug administration. In the hot plate test and tail pressure test, i.p. midazolam produced significant antinociceptive effects with the 50% effective dose (ED50) of 3.46 mg/kg [confidence interval (CI), 1.99 – 6.01 mg/kg] and 3.52 mg/kg (CI, 2.77 – 4.47 mg/kg), respectively. In the acetic acid writhing test, i.p. midazolam also produced significant antinociceptive effects. In the running wheel test, no mice stopped running after saline or midazolam at 1, 3, or 10 mg/kg, but all mice stopped running 30 and 45 min after i.p. administration of midazolam at 30 mg/kg. In the balance beam test, 30 min after i.p. administration of saline or midazolam at 1, 3, and 10 mg/kg, all mice were able to stay on the beam for 90 s, none of them could with midazolam at 30 mg/kg. In conclusion, systemically administered midazolam had antinociceptive effects on acute thermal, acute mechanical, and acute inflammatory-induced nociception in mice. The antinociceptive potency of midazolam was the same for both acute thermal-induced nociception and mechanical-induced nociception.

Midazolam for patients undergoing upper gastrointestinal endoscopy: A prospective, single‐blind and randomized study to determine the appropriate amount and time of initiation of endoscopy

Midazolam is currently the most used sedative agent in endoscopy. The present study was designed to examine the appropriate dose of midazolam, time of initiation of endoscopy after midazolam infusion, and to prove the necessity of flumazenil as an antidote. One hundred and eighty patients undergoing diagnostic gastroscopy were assigned three different amounts of intravenous midazolam in prospective, single-blinded and randomized setting as follows: (i) group I 0.03 mg/kg midazolam; (ii) group II 0.06 mg/kg midazolam; and (iii) group III 0.09 mg/kg midazolam. Endoscopy was initiated 30, 60 and 90 s after infusion of midazolam within each group. After endoscopy, patients were divided into two groups, one receiving flumazenil and one placebo in a double-blind fashion. The ease of the procedure, the conscious sedative state, the paradoxical response, the level of satisfaction and anterograde amnesia were assessed using a 100 mm visual analog scale. The endoscopist's assessments were not changed by the different doses of midazolam; however, significant differences were observed in the paradoxical responses (P < 0.05). The level of satisfaction with endoscopy was notably different between group I and the other two groups (P < 0.05). Amnesia was boosted according with increasing doses of midazolam (P < 0.05). The time until discharge after endoscopy was significantly different between group III and the other two groups (P < 0.05) and the discharge time was reduced in the flumazenil subgroup compared with the placebo subgroup in group III (P < 0.05). Group II (0.06 mg/kg) reported good levels of satisfaction, fewer paradoxical responses and short discharge time without any side-effects. Comparing the time of initiation of endoscopy (at 30, 60 and 90 s after midazolam) in each group, there were no significant differences in the level of satisfaction, conscious sedative state and amnesia. Midazolam should be administered at a dose of 0.06 mg/kg and the endoscopy should be initiated 30 s after midazolam injection for appropriate effects without any side-effects. Flumazenil is not necessary, except in the case of the use of a high dose (above 0.09 mg/kg) of midazolam.

Clinical effects of adding different doses of midazolam to epidural 0.5% bupivacaine

Clinical effects of adding different doses of midazolam to epidural 0.5% bupivacaine

Clinical effects of adding different doses of midazolam to epidural 0.5% bupivacaine

Clinical effects of adding different doses of midazolam to epidural 0.5% bupivacaine

Phenotyping CYP3A using midazolam in cancer and noncancer Asian patients.

To investigate CYP3A activity in cancer and noncancer Asian patients using midazolam and to reveal possible alternative traits for phenotyping CYP3A. Intravenous midazolam 2.5 mg or 2.5-8 mg was administered to 27 cancer and 24 noncancer patients, respectively. Plasma was sampled at 0, 0.25, 0.5, 1, 1.5, 2, 3.5 and 5 h after intravenous ultrashort, 30 s infusion. Plasma midazolam and 1'-hydroxymidazolam concentrations were determined using GCMS. The disposition of midazolam and 1'-hydroxymidazolam in these patients was compared. Midazolam clearance was correlated with dose-normalized plasma midazolam concentrations (concentration/per dose). Clearance (CL) and steady state volume of distribution (Vss) of midazolam (mean +/- SD, 95% confidence level) in cancer (424 +/- 155, 61.3 ml min(-1); 1.21 +/- 0.46, 0.18 l kg(-1)) and noncancer (407 +/- 135, 57.1 ml min(-1); 1.15 +/- 0.33, 0.155 l kg(-1)) patients, respectively, were not different and comparable with published data. Clearance variability was 4-5 fold in both groups. Midazolam clearance correlated significantly with all plasma concentration/per dose at and after the 1-h time point, with a minimum correlation coefficient of r = 0.752, P < 0.001. CYP3A activities determined with different doses of midazolam in cancer and noncancer Asian patients showed variability of 4-5-fold and were not different between groups. One to two-fold plasma midazolam concentrations per dose may be feasible as a simple alternative phenotypic trait for hepatic CYP3A activity determination.

Effect of midazolam on propofol-induced positive affective state assessed by place conditioning in rats.

The effect of either midazolam or the combination of midazolam and propofol on the affective state was assessed in rats at subanesthetic doses and at recovery from anesthesia. The putative drug(s)-induced affective states were repeatedly paired with one of two distinguishable compartments of an experimental cage, whereas the vehicle(s)-induced effect was repeatedly paired with the other compartment. During a subsequent choice test for one compartment over the other, the rats' preference for the drug(s)-paired compartment over the vehicle(s)-paired compartment is indicative of a pleasant state induced by the drug(s). In experiment 1, rats were conditioned with different doses of midazolam either at subanesthetic states or at recovery from anesthesia. In experiment 2, groups of rats were conditioned with different combinations of midazolam and propofol either at subanesthetic states or at recovery from anesthesia induced jointly by midazolam (10 mg/kg) and propofol (60 mg/kg). Experiment 3 was conducted in the same way as experiment 2, except that midazolam was paired with both compartments. In addition, these groups were tested not only in an undrugged state but also in a drugged (with midazolam) state. In experiment 1, rats exhibited a place preference for the environment previously associated with midazolam, at subanesthetic and anesthetic doses. Experiment 2 showed that a propofol-induced place preference was found to be dose-dependently suppressed by midazolam. Experiment 3 replicated the findings of experiment 2 and extended them to the mechanism by which midazolam blocked a propofol-induced place preference. Midazolam administered before propofol blocked the expression of a propofol-induced pleasant state.

Benzodiazepine Site Pharmacokinetic/Pharmacodynamic Quantification in Man: Direct Measurement of Drug Occupancy and Effects on the Human Brain In Vivo

To date, the study of the relationship between drug occupancy and action in the brain has had to rely on the use of either animal models or of indirect kinetic measures in man, e.g. serum concentrations of unbound drug (as a measure of “free” drug in brain). We describe the first set of experiments which directly measure agonist-induced changes in both pharmacodynamic effects and pharmacokinetic parameters simultaneously and which demonstrate the feasibility of these studies in man. Five healthy volunteers each had two PET scans using [11C]flumazenil (a radiolabelled benzodiazepine site antagonist) as part of a study investigating kinetic models and the relationship between occupancy and effect of benzodiazepine site ligands. In both studies the [11C]flumazenil was displaced from the brain by an infusion of midazolam administered i.v. 30 min into the scan. In one study a higher dose of midazolam was administered than in the other (range 12.5–50 μg/kg). Time-activity curves of the concentration of radioligand were derived in 17 different brain regions using a stereotactic automatic method of region selection. We demonstrated that there are significant differences in an index of occupancy, induced by the two different doses of midazolam, both across brain regions and within subjects. There was a significant correlation between measured occupancy index change and pharmacodynamic effects as measured by the peak change in beta1 spectral power observed on EEG. There was no significant correlation between dose administered and EEG changes; plasma concentrations of midazolam were correlated with the occupancy index and with the EEG measures. In addition, we have demonstrated that a non-regional total index of brain occupancy can be obtained by analysing the non-tomographic data obtained with the PET scanner (total radioactivity counts head curve) and that this index shows significant correlations both with the dose administered and with the pharmacodynamic measure. This last finding validates the use of other non-tomographic counting techniques (Malizia et al., 1995a) where an index of displacement can be obtained after the administration of less than 1% of the dose of radiation needed for a PET study. These studies are likely to be useful in human psychopharmacology, in particular in the assessment of tolerance and of putative changes in benzodiazepine sensitivity in anxiety disorders. The same principles can be applied to other ligand studies and will be useful to validate current PK/PD models. Copyright © 1996 Elsevier Science Ltd

Respiratory Depressant Effects of Different Doses of Midazolam and Lack of Reversal with Naloxone-A Double-Blind Randomized Study

Conflicting data concerning the ventilatory effects of benzodiazepines may be caused by the large variability in investigational conditions. Respiratory effects of three different intravenous doses of midazolam (0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg) and placebo were measured in a double-blind and randomized fashion in eight healthy volunteers. The respiratory variables were analyzed by means of a noninvasive method, thereby avoiding interferences associated with the stimulating effects of mouthpiece and nose clip. After injection of midazolam, tidal volume decreased by 40% with the three doses and respiratory frequency increased to the same extent, minute ventilation remained constant. Only the largest dose of the drug produced a significant decrease (P less than 0.05) in O2 saturation that was related to the longer duration of apnea. Intravenous naloxone (0.015 mg/kg) injected 5 min after midazolam did not change any measured respiratory or hemodynamic variable. We conclude that the respiratory effects of midazolam are poorly dose related and not reversed by naloxone. The observed compensatory increase in respiratory frequency which is not noted in other studies, is probably related to the noninvasive measurement technique used.