A comparison of midazolam and diazepam for intravenous sedation in dentistry

In a randomised cross-over trial, midazolam, a new water soluble benzodiazepine was compared with the conventional diazepam preparation (Valium) in 34 patients aged 16-45 years who were undergoing outpatient conservation dentistry. Midazolam hydrochloride (0.17 mg/kg) was virtually free of venous complications and showed advantages over diazepam (0.32 mg/kg) in providing a faster onset of action, higher incidence of amnesia and more rapid recovery. Midazolam produced a higher incidence of respiratory side effects hiccough (17.6% compared with 2.9%), brief apnoea following induction (11.8% compared with 5.8%), and airway obstruction during maintenance (8.8% compared with 0%). These may be related to the greater potency of midazolam as suggested by the smaller total dose required. Cardiovascular changes and operating conditions were similar.     

Studies of midazolam, diazepam and thiopentone on respiratory and cardiovascular function during induction anesthesia

In this study, the effects of midazolam (M), diazepam (D) and thiopentone (T) on respiratory and cardiovascular systems were compared. The patients were randomly divided into 6 groups, besides minute ventilatory volume (MV), onset of induction and cardiovascular changes were also observed. Induction was performed by a bolus injection of one of the following: midazolam (0.3 mg/kg), diazepam (0.3 mg/kg) or thiopentone (5 mg/kg). Five minutes later, 5 micrograms/kg fentanyl and 1.5-2.0 mg/kg succinylcholine were administered. The results showed that: (1) Inhibitory effect on MV was not prominent and similar after use of midazolam and diazepam but was remarkable after thiopental; (2) As for the onset, midazolam was faster than diazepam but slower than thiopentone; (3) Hemodynamic changes of midazolam, diazepam and thiopentone were similar, however during intubation, cardiovascular response was the least in midazolam, diazepam the intermediate and thiopentone the most significant. We conclude that midazolam is a water-soluble, safe and effective inductive anesthetic with its short eliminated half-life period, and much lesser venous irritation, and it is certainly superior to both diazepam and thiopentone.     

A comparison of midazolam and diazepam for induction of anaesthesia in high-risk patients

Fifty ASA Class III patients were divided randomly into two equal groups for induction of anaesthesia with diazepam 0.25 mg/kg, or midazolam 0.15 mg/kg. All subjects were premedicated with a narcotic and monitored by ECG, radial arterial catheter and a spirometer for measurement of minute ventilation. The QF interval (time period from the Q wave of the ECG to the foot of the radial artery pulse), mean arterial pressure, heart rate and minute ventilation were recorded before, during and immediately after the induction of anaesthesia. Although mean arterial pressure fell slightly (6%) following midazolam, all other cardiovascular variables were stable in both groups. Minute ventilation was depressed to 70% of control by both drugs and nearly one-half the diazepam patients complained of pain on injection compared with only one midazolam patient. These data suggest that midazolam is a reasonable alternative to diazepam for induction of anaesthesia in the high-risk patient.     

The effects of low-dose midazolam for induction of high-dose fentanyl anesthesia for coronary artery bypass graft

A small dose of midazolam 0.06 mg/kg or diazepam 0.15 mg/kg was used for induction of high-dose fentanyl (50 μg/kg) anesthesia in patients undergoing coronary artery bypass grafting operation. Hemodynamic variables were measured 5 min after the injection of midazolam or diazepam, after the end of the fentanyl infusion, and following endotracheal intubation. Midazolam and diazepam caused a slight but significant decrease in mean arterial pressure (−9.8%) and −11.8%), respectively) and a further significant depression was observed in the diazepam group but not in the midazolam group after fentanyl. Although the cardiac index was maintained in patients who received madazolam, a significant decrease was observed in the diazepam group (−28.5%) after administration of fentanyl. Heart rate was decreased in the diazepam group but not in the midazolam group. Therefore, a small dose of midazolam may be a suitable induction agent for high-dose fentanyl anesthesia in patients with coronary artery disease.     

Rectal administration of midazolam versus diazepam for preanesthetic sedation in children

Sixty children were included in the trial. Each subject received midazolam 0.4 mg/kg body weight of diazepam 0.75 mg/kg body weight rectally in a double-blind randomized order. The degree of sedation of the children was assessed on arrival in the operating unit and during the induction of anesthesia. Adequate sedation on arrival in the operating unit and during induction of anesthesia was obtained in 84% and 67%, respectively, following administration of midazolam compared with 80% and 70% in the diazepam group. No side effects were noted. It is concluded that rectally administered midazolam 0.4 mg/kg is comparable to diazepam 0.75 mg/kg with respect to preanesthetic sedation in children.     

Oral midazolam is an effective premedication for children having day-stay anaesthesia.

The effect of oral premedication was studied in a double-blind, randomised trial of 200 children undergoing day-stay anaesthesia. Midazolam 0.25 mg/kg, midazolam 0.5 mg/kg, diazepam 0.5 mg/kg or a placebo was given orally one hour prior to anaesthesia. Patient state was assessed at nine stages, from administration of the premedication up to and including induction of anaesthesia, using a four-point behavioural scale. Patient state was also assessed postoperatively in the recovery area and the day-stay ward. There was no difference between the four groups until induction of anaesthesia. At this stage 82% of children were either asleep or awake and calm. Patients who received midazolam 0.5 mg/kg were more likely to be asleep or awake and calm at induction rather than other groups (P = 0.05). Children receiving midazolam 0.5 mg/kg or diazepam 0.5 mg/kg slept longest in the post anaesthetic recovery room (P less than 0.005), and spent most time there (P less than .005). There was no difference between groups in the length of time spent in the day-stay ward or in the number of overnight admissions. The study shows that a high proportion of unsedated children are calm at induction of anaesthesia and that oral midazolam is an effective premedication in children for day-stay anaesthesia.     

Total intravenous versus inhalational anaesthesia for colonoscopy: a prospective study of clinical recovery and psychomotor function

A randomized, prospective study was conducted on 69 patients comparing recovery after two different anaesthetic techniques for ambulatory colonoscopy. Thirty-five patients received an intravenous fentanyl (1 microg/kg), midazolam (0.05 to 0. 075 mg/kg) and propofol (10 to 20 mg boluses as required) combination. 34 patients received sevoflurane in 67% nitrous oxide. Drug administration was titrated to clinical signs. At baseline and 30, 60, 90 and 120 minutes after the procedure patient performance on a comprehensive battery of psychomotor tests was recorded. Emergence times were noted. Depth of sedation was assessed at 5 minute intervals for 30 minutes after the end of the procedure. Emergence times were faster in the fentanyl/midazolam/propofol group by 2.2 minutes. A lower sedation score was detected at 20 minutes in the sevoflurane/nitrous oxide group. Psychomotor impairment was of a greater magnitude and more prolonged by 30 to 90 minutes in the fentanyl/midazolam/propofol group. It is concluded that a sevoflurane/nitrous oxide anaesthetic has a suitable recovery profile for ambulatory colonoscopy and results in faster recovery of cognitive function compared with a fentanyl, midazolam and propofol combination.     

Oral midazolam in children: effect of time and adjunctive therapy.

The purpose of this study was to determine the influence of timing and concomitant administration of atropine and/or meperidine on the perioperative effects of oral midazolam in children. In 154 healthy children, 1-8 yr old, we studied six oral preanesthetic medication regimens according to a randomized, double-blind protocol. Group A (placebo) received 5 mL of apple juice. The other five groups received medication with apple juice to a total volume of 5 mL, 20-60 min before induction of anesthesia. Group B received atropine (0.02 mg/kg); group C received midazolam (0.5 mg/kg); group D received midazolam (0.5 mg/kg) and atropine (0.02 mg/kg); group E received meperidine (1.5 mg/kg) and atropine (0.02 mg/kg); and group F received meperidine (1.5 mg/kg), atropine (0.02 mg/kg), and midazolam (0.5 mg/kg). The sedative effect of midazolam was maximal 30 min after oral administration. Ninety-five percent of the children who were separated from their parents within 45 min after oral midazolam administration (with or without atropine) had satisfactory separation scores (vs 66% of those separated after 45 min; P less than 0.02). Midazolam-treated patients were more cooperative with a mask induction of anesthesia compared with non-midazolam-treated children (83% vs 56%). Neither atropine nor meperidine appeared to significantly improve the effectiveness of oral midazolam. No preoperative changes in heart rate, respiratory rate, or hemoglobin oxygen saturation were noted in any of the treatment groups. Finally, oral midazolam did not prolong recovery even after outpatient procedures lasting less than 30 min. In conclusion, midazolam (0.5 mg/kg) given orally 30-45 min before induction of anesthesia is safe and effective without delaying recovery after ambulatory surgery.     

Midazolam and diazepam in ketamine anaesthesia

Midazolam 0.07 mg/kg was compared with diazepam 0.12 mg/kg intravenously as an adjuvant to ketamine anaesthesia in healthy patients undergoing minor gynaecological operations of less than 15 minutes duration. The occurrence of induction and emergence sequelae, and patient acceptance of the technique was assessed by means of a questionnaire. The incidence of unpleasant dreams was 6.7% with midazolam and 26.7% with diazepam. There was no significant difference in any other sequelae. Overall patient acceptance was high at 96.7%.     

Effects of diazepam and midazolam on baroreflex control of heart rate and on sympathetic activity in humans

The effects of induction of anesthesia with diazepam and midazolam on baroreflex control of heart rate and on plasma levels of catecholamines were investigated in this study. Group 1 subjects (n = 10) received diazepam, 0.4 mg/kg. Group 2 subjects (n = 10) received midazolam, 0.3 mg/kg. Baroreflex function was assessed using a pressor test (phenylephrine). In addition, samples for subsequent determination of plasma norepinephrine and epinephrine levels and plasma diazepam or midazolam concentrations were collected before and 5, 10, and 15 min after intravenous drug administration. The pressor baroreflex slope declined significantly after diazepam or midazolam administration with the maximal changes (-45 and -43%, respectively) observed when plasma diazepam or midazolam concentrations were the highest. Norepinephrine plasma concentrations decreased at each measurement with both drugs. In contrast, epinephrine concentration decreased only after midazolam. The authors conclude that diazepam or midazolam used for induction of anesthesia results in a transient depression of baroreflex function and a sustained decrease of sympathetic tone. This study also indicates that the depression of arterial baroreflex heart rate responses under diazepam or midazolam anesthesia are less pronounced than the depression of baroreflex responses reported by other investigators with potent inhalational anesthetics. However, this disruptive effect of diazepam and midazolam on sympathetic control of circulation might induce a limited ability to compensate for hemodynamic alterations related to hypovolemia.     

Sedation and recovery of psychomotor function after intravenous administration of various doses of midazolam and diazepam.

A placebo-controlled, double-blind, crossover trial in 11 healthy male volunteers compared clinical sedation and psychomotor function after intravenous injection of midazolam (0.05, 0.1, or 0.15 mg/kg), diazepam (0.15 or 0.3 mg/kg), or placebo (saline). The depth of sedation was estimated at 5-10-min intervals during the first hour after injection. A comprehensive battery of psychomotor tests was used to collect objective data of psychomotor performance before drug injection and 1, 3, 5, and 7 h after injection. Midazolam (0.15 mg/kg) produced the highest scores of sedation and most impairment of psychomotor performance. In most tests, the maximal psychomotor effects seen after 0.3 mg/kg of diazepam did not reach those of 0.1 mg/kg of midazolam. Although the strongest psychomotor effects were induced by midazolam, these effects disappeared sooner than those of diazepam. By 5 h after injection, 0.3 mg/kg of diazepam showed the highest scores of psychomotor impairment. The authors conclude that at least four times as much diazepam as midazolam is needed to produce equally severe psychomotor impairment. That the residual effects of midazolam terminate sooner than those of diazepam probably accounts for the occasional underestimation of the potency of midazolam in clinical practice.     

A comparison of midazolam and diazepam for sedation during locoregional anesthesia

Midazolam is a recently introduced benzodiazepine with a half life of 1-4 hours. Midazolam (0.15 mg/kg) has been compared with diazepam (0.2 mg/kg) for sedation during locoregional anesthesia in 60 premedicated patients. No difference among the two groups for heart rate, bloodpressure, respiratory rate and incidence, and duration of apnoea was noticed after an i.v. bolus administration. The recovery time was equal in both groups. Midazolam was significantly less painful at injection. The sedation pattern between both groups is only different at 60 minutes, where more better sedated patients are seen in the midazolam group. Except the pain at injection and a better sedation pattern after 60 min. the differences in the other parameters are only borderline.     

Midazolam and Fat-Emulsion Diazepam as Intramuscular Premedication A Double-Blind Clinical Trial

Sixty female patients were given, in random order, under double-blind conditions, either midazolam or fat-emulsion diazepam, intramuscularly, as premedication, 1 h before general anaesthesia. The dose of midazolam used was 0.13 mg/kg and that of diazepam 0.17 mg/kg. The degree of sedation, mood of the patient, and time at which onset of effect was perceptible were assessed before induction of anaesthesia, together with skin temperature and concentrations of midazolam or diazepam in plasma. Patients were interviewed postoperatively to discover their subjective evaluation of the premedication and to assess its amnesic effects. Midazolam was significantly superior (P less than 0.05) to diazepam as regards sedation. There were no differences in effects on mood of the patients between the two groups. Sixteen patients in the diazepam group and four in the midazolam group had no perception of onset of effect. The difference is significant (P less than 0.01). The skin temperature was, on average, 2 degrees C higher in the midazolam group than in the diazepam group (P less than 0.005). The mean plasma concentration was 67.8 +/- 24.5 micrograms/l in the midazolam group and 44.8 +/- 25.7 micrograms/l in the diazepam group. In only two cases was the concentration of diazepam above 100 micrograms/l (arbitrarily defined as the minimum sedative concentration). Subjective evaluation of efficacy significantly (P less than 0.002) favoured midazolam. Local pain was evident in two patients in the diazepam group, and three patients experienced nausea immediately after administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic changes during induction of anaesthesia with midazolam and diazepam (Valium) in patients undergoing coronary artery bypass surgery

Midazolam 0.3 mg/kg and diazepam 0.5 mg/kg were used for induction of anaesthesia in two groups of 10 patients each undergoing coronary artery bypass surgery. Haemodynamic variables were measured during induction of anaesthesia, after pancuronium and following tracheal intubation. Haemodynamic indices were derived from these measurements using standard formulae. The induction of anaesthesia with midazolam produced a slight but significant increase in heart rate. There was a significant fall in systemic arterial pressure and pulmonary artery pressure following both drugs. Despite the fall in systemic arterial pressure, the cardiac index was maintained in patients who received midazolam. The cardio-stimulatory effect of laryngoscopy and tracheal intubation was not prevented by either of the benzodiazepines and morphine in the dosage used. Midazolam is a suitable alternative to diazepam as part of an intravenous induction regimen in patients with ischaemic heart disease.     

Benzodiazepines and neuromuscular blocking drugs in patients

The interaction between four benzodiazepines (diazepam, lorazepam, lormetazepam and midazolam) and two nondepolarizing neuromuscular blocking drugs (vecuronium and atracurium) was investigated in 113 patients during general anaesthesia. Neuromuscular function was monitored by recording the mechanical twitch tension of the adductor pollicis muscle of the thumb in response to ulnar nerve stimulation with single supramaximal stimuli of 0.2 ms at 0.1 Hz. In the first group of patients a benzodiazepine (diazepam 20 mg, lorazepam 5 mg, lormetazepam 2 mg or midazolam 15 mg), was injected i.v. 15 min before a single bolus of vecuronium 45 micrograms kg-1. In the second group of patients suxamethonium 1 mg kg-1 was given for endotracheal intubation, and 30 min later the patients received atracurium 200 micrograms kg-1. Fifteen min before injection of atracurium one of the same benzodiazepines as in the first group was injected i.v. Comparisons were made with control patients receiving thiopentone. Neither benzodiazepine caused significant potentiation of neuromuscular blocking agents in comparison with control. With midazolam, however, the duration to 25% and to 75% recovery of the twitch height after vecuronium was significantly longer than with diazepam. The time to 25% recovery of the twitch height after atracurium was significantly longer in patients receiving midazolam than in those receiving diazepam. The recovery index was not influenced by the four benzodiazepines.     

Rectal administration of midazolam as an adjuvant in the premedication of infants

In a randomized, double-blind study of premedication in 69 infants aged between 13 and 48 months the effects of 0.82 mg/kg midazolam or diazepam rectally plus 2.0 mg/kg ketamine i.m., or the administration of 2.4 mg/kg ketamine i.m. alone was studied. A satisfying result of 94.1% following the premedication with midazolam/ketamine, of 82.9% with diazepam/ketamine and of 81.3% with ketamine alone was observed. Premedication with midazolam/ketamine was the best one in the review of vigilance, agitation, and behaviour of defence against the mask at the beginning of anaesthesia. The amnestic action of midazolam extinguished the infants' memory of the i.m.-injection. The dose of midazolam/ketamine is suitable as an effective and positive method for premedication of infants within 20 min.     

Comparison of a combination of midazolam and diazepam and midazolam alone as oral premedication on preanesthetic and emergence condition in children

BACKGROUND: Preanesthetic anxiety and emergence agitation are major challenges for anesthesiologists in pediatric anesthesia. Thus, midazolam has been used as premedication for children. However, midazolam alone is not effective for emergence agitation. The present study tested the effect of a combination of midazolam and diazepam on the preanesthetic condition and emergence behavior in children. METHODS: Forty-two children were allocated to one of three groups: the NoPre group received no premedication; the Mi group received midazolam 0.5 mg kg(-1) orally; and the Mi + Di group received midazolam 0.25 mg kg(-1) and diazepam 0.25 mg kg(-1) orally. When anesthesia was induced with 7% sevoflurane in 100% oxygen, qualities of mask induction and sedation were rated. Anesthesia was maintained with sevoflurane (3-5%) in 100% oxygen. During emergence from anesthesia, the score of the child's emergence behavior was rated. RESULTS: Children in the Mi and Mi + Di groups were more sedated than those in the NoPre group. A combination of midazolam and diazepam provided a better quality of mask induction, when compared with no premedication. Also, the children in the Mi + Di group were less agitated than those in the other groups during the emergence. CONCLUSION: Children in the Mi + Di group were significantly more sedated at induction of anesthesia and less agitated during emergence from anesthesia.     

Comparison of propofol induction with thiopentone or methohexitone in short outpatient general anaesthesia

The per- and post-operative characteristics of three different i.v. anaesthetic induction agents were studied double-blindly in 75 patients admitted for outpatient gynaecological dilatation and curettage. All the patients were premedicated with midazolam 0.1 mg/kg i.m. Induction started with alfentanil 0.015 mg/kg i.v. 60 s before either: propofol 2.2 mg/kg i.v., or thiopentone 4.0 mg/kg i.v., or methohexitone 2.0 mg/kg i.v. All the patients received 66% nitrous oxide in oxygen. The propofol patients were significantly better relaxed and had a higher incidence of hypotension during the procedure. The methohexitone patients had higher pulse rates and a higher frequency of hiccups during the procedure. Propofol induction resulted in a faster awakening of the patients and a better recovery function compared with methohexitone for the first 15 min and compared with thiopentone for the first 240 min after the procedure. Postoperative side-effects were less frequent in the thiopentone group, and minor abdominal pain was significantly more frequent in the propofol group. There was no significant difference between the groups for any variable after 240 min postoperatively.     

Oral ketamine or midazolam or low dose combination for premedication in children

This randomized controlled trial was designed to evaluate whether the combination of low dose oral midazolam (0.25 mg/kg) and low dose oral ketamine (3 mg/kg) provides better premedication than oral midazolam (0.5 mg/kg) or oral ketamine (6 mg/kg). Seventy-eight children of ASA physical status I or II scheduled for elective ophthalmic surgery were randomly divided into three groups and given premedication in the holding area 30 minutes before surgery. Two subjects from each group vomited the medication and were excluded, leaving 72 subjects for further analysis. The onset of sedation was earlier in the combination group than the other two groups. At 10 minutes after premedication 12.5% in the combination group had an acceptable sedation score compared with none in the other two groups. After 20 minutes 54% in the combination group had an acceptable sedation score, 21% in the midazolam group and 16% in the ketamine group (P<0.05). There were no significant differences in the parental separation score, response to induction and emergence score. The mean time for best parental separation score was significantly less in the combination group (19+/-8 min) than either the midazolam (28+/-7) or ketamine (29+/-7 min) groups (P<0.05). Recovery was earlier in the combination group, as the time required to reach a modified Aldrete score of 10 was significantly less in the combination group (22+/-5 min) than in the oral midazolam (36+/-11 min) or ketamine (38+/-8 min) groups. The incidence of excessive salivation was significantly higher in the ketamine alone group (P<0.05). In conclusion, the combination of oral ketamine (3 mg/kg) and midazolam (0.25 mg/kg) has minimal side effects and gives a faster onset and more rapid recovery than ketamine 6 mg/kg or midazolam 0.5 mg/kg for premedication in children.     

Midazolam in conservative dentistry

In a double-blind trial, 50 patients were randomly allocated to receive up to 0.29 mg/kg diazepam (Valium 5 mg/ml) or 0.14 mg/kg of midazolam (midazolam hydrochloride 5 mg/ml) intravenously at a first session of conservative dentistry, the alternative being administered at the second session. Good operating conditions were reported under each sedative and no important physiological differences were observed. Most patients failed to return to 'street fitness' 30 minutes after either session of treatment. Previous reports of reduced incidence of venous thrombophlebitis with midazolam were not convincingly confirmed in this trial, but data quality was poor. For about half the patients, the amnesic effect was stronger following midazolam.