Comparison of various physiologic and psychomotor parameters in patients sedated with intravenous lorazepam, diazepam, or midazolam during oral surgery

Intravenously administered lorazepam (0.05 mg/kg), diazepam (0.25 mg/kg), and midazolam (0.1 mg/kg) were compared for sedation during oral surgery under local anesthesia. Sixty patients were randomly allocated into three groups in this double-blind, parallel study. The results from this trial show that all three drugs provide satisfactory sedation. Average mean arterial pressures, however, decreased significantly with midazolam and diazepam. Statistically significantly higher heart rates during the entire procedure were also found for lorazepam when compared with diazepam and midazolam. At the postblock stage, the midazolam group had respiratory rates that were significantly higher than those of the other two drug groups. Patients in the diazepam and midazolam groups took significantly longer to complete the pegboard test at the preblock stage than those in the lorzepam group. At 1, 1.5, and 2 hours after arrival in the recovery room, an inversion of groups took place, with the lorazepam group taking significantly longer for their tests than the other two groups. Significantly more improvement in anxiety levels was found at 10 minutes postdrug for the patients who had received diazepam and this tended to remain so on arrival in the recovery room. When compared with the other two groups, significantly more patients in the lorazepam group reported giddiness/dizziness and significantly more in the diazepam group reported pain on injection.     

Effects of intravenous midazolam and diazepam on patient response, percentage of oxygen saturation, and hemodynamic factors during periodontal surgery

BACKGROUND: The purpose of this double-masked study was to evaluate effects of intravenous sedation (IVS) using midazolam or diazepam during periodontal procedures on patient recall, psychomotor response, oxygen saturation, and hemodynamic factors. METHODS: Seventeen patients received either two or three scheduled periodontal surgeries under IVS with midazolam, diazepam, or placebo control. Patients were monitored throughout the procedure for hemodynamic variables, percent oxygen saturation, level of recall of common objects presented at baseline, and psychomotor function via the perceptual speed test (PST). RESULTS: Fifteen patients completed the study with average titrated dosages of 3.3 and 12.1 mg for midazolam and diazepam, respectively. Within the limitations of the study, there were few differences observed between the drugs with regard to hemodynamic variables, oxygen saturation, and overall percentage of objects recalled by patients sedated with either drug. However, midazolam was found to cause a greater incidence of amnesia lasting up to 30 minutes when compared to placebo. Patients on diazepam required an average of 15 minutes longer to recover accuracy as measured by the PST. CONCLUSIONS: The results suggest that diazepam and midazolam each may have advantages for IVS. In procedures lasting over 45 minutes, diazepam appears to be more clinically advantageous including a wider margin of safety during titration and gradual recovery. Midazolam may be used for shorter procedures for faster onset of action, predictable amnesic effects, and relatively rapid recovery.     

Midazolam, diazepam, and placebo as intravenous sedatives for dental surgery

This study was a comparison of the sedative and amnestic properties of midazolam and diazepam when administered for relief of patient discomfort during dental surgery. It was a double-blind placebo-controlled group study, which entailed the analysis of 60 patients randomly assigned to the three groups: midazolam, diazepam, and placebo. There were 20 patients in each group. Midazolam patients showed superior performance in the parameters of sedation and amnesia when compared to patients who were administered diazepam. Both groups showed better results than the placebo group, which had the best results with the Digit Symbol Substitution Test and the Trieger Test.     

The use of temazepam elixir in surgical dental sedation: a comparison with intravenous midazolam.

Out-patients attending for removal of at least one lower third molar were randomly allocated to treatment with temazepam elixir (n = 7) or intravenous midazolam (n = 8), as well as local analgesia. Patients were tested prior to drug administration and at the end of surgery. Both drugs increased heart rate and midazolam also decreased diastolic blood pressure. The two drugs caused significant, equal increases in ratings of sedation, but the reduction of anxiety was significant only for midazolam. There was significant amnesia for material presented after drug administration, as well as for dental events and this was significantly greater for midazolam. The effects of these drugs in dental patients were compared with those in normal volunteers treated in an identical manner, but without oral surgery. The drugs had similar significant cardiovascular and amnesic effects in the volunteers and the same effects on mood ratings, even though volunteers and patients differed in their pretreatment levels of anxiety and discontent. The dentist's ratings of the sedation and operating conditions were excellent in both cases. Thus temazepam elixir provided a useful sedative for oral surgery, avoiding the complications of intravenous administration. However, for equivalent levels of sedation, midazolam had greater anxiolytic and amnesic effects than temazepam.     

Rectal sedation with diazepam or midazolam during extractions of traumatized primary incisors: a prospective, randomized, double-blind trial in Swedish children aged 1.5-3.5 years.

The aim of this study was to compare rectal sedation with diazepam and rectal sedation with midazolam with regard to sedative effect, treatment acceptance, and amnesia. Ninety children, 1.5-3.5 years of age, consecutively referred for extractions of traumatized primary incisors were randomly sedated with diazepam (0.7 mg/kg body weight) or midazolam (0.3 mg/kg body weight). The study design was randomized and double-blind. The level of sedation (state of mind) was assessed prior to and 10 and 60 min after administration of the drug by use of a behavioral scale (Wilton). The children's acceptance of procedures was assessed using another behavioral scale (Holst) during administration of the sedative, application of topical anesthesia, injection of a local anesthesia, and extraction. Amnesia was evaluated by the parents on the following day, with the child being asked standardized questions. Parental ratings of the child's and their own distress during and after treatment were made on a visual analog scale (VAS). No differences were found between the sedatives concerning level of sedation during treatment, acceptance of procedures, or amnesia. At discharge, 60 min after administration of the sedative, the children receiving diazepam were significantly more agitated (P=0.006). Parental rating on a VAS of the child's discomfort after treatment was significantly higher in the diazepam group (P=0.006). There was a tendency for children with poor acceptance of the rectal administration to display a more negative acceptance of the dental treatment. In conclusion, the present results, in combination with known pharmacological advantages, indicate that midazolam is preferable in outpatients when sedation is needed and amnesia is desirable.     

Benzodiazepine reversal with flumazenil--a review of the literature.

Benzodiazepines such as Valium (diazepam) or Versed (midazolam), as used in dental procedures for intravenous sedation, have been a boon to the profession. Yet in the event of sedation problems, no agent exists that consistently reverses all clinical effects of these drugs. This problem does not exist with narcotics, frequently employed in tandem with benzodiazepines, since an effective reversal agent, Narcan (naloxone hydrochloride), exists. It would be advantageous to effectively reverse benzodiazepines in cases of acute emergency with respiratory depression or paradoxical reactions, and to allow quick, full recovery after short dental procedures. None of the drugs currently available for benzodiazepine reversal, such as physostigmine, give consistent clinical results. The purpose of this paper is to discuss Flumazenil, a new specific benzodiazepine receptor antagonist, and its possible use for dental sedation procedures.     

Rectal sedation with diazepam or midazolam during extractions of traumatized primary incisors: a prospective,randomized, double-blind trial in Swedish children aged 1.5-3.5 years

The aim of this study was to compare rectal sedation with diazepam and rectal sedation with midazolam with regard to sedative effect, treatment acceptance, and amnesia. Ninety children, 1.5-3.5 years of age, consecutively referred for extractions of traumatized primary incisors were randomly sedated with diazepam (0.7 mg/kg body weight) or midazolam (0.3 mg/kg body weight). The study design was randomized and double-blind. The level of sedation (state of mind) was assessed prior to and 10 and 60 min after administration of the drug by use of a behavioral scale (Wilton). The children's acceptance of procedures was assessed using another behavioral scale (Holst) during administration of the sedative, application of topical anesthesia, injection of a local anesthesia, and extraction. Amnesia was evaluated by the parents on the following day, with the child being asked standardized questions. Parental ratings of the child's and their own distress during and after treatment were made on a visual analog scale (VAS). No differences were found between the sedatives concerning level of sedation during treatment, acceptance of procedures, or amnesia. At discharge, 60 min after administration of the sedative, the children receiving diazepam were significantly more agitated (P = 0.006). Parental rating on a VAS of the child's discomfort after treatment was significantly higher in the diazepam group (P = 0.006). There was a tendency for children with poor acceptance of the rectal administration to display a more negative acceptance of the dental treatment. In conclusion, the present results, in combination with known pharmacological advantages, indicate that midazolam is preferable in outpatients when sedation is needed and amnesia is desirable.     

Comparing efficacy and safety of four intravenous sedation regimens in dental outpatients.

BACKGROUND: Management of patients' fear and anxiety during dental treatment is a primary concern of dental practitioners. Pharmacological strategies used in outpatient dental settings must be both safe and effective. Regimens of intravenously administered sedative drugs were evaluated in a collaborative, multicenter study of outpatients undergoing removal of impacted third molars. METHODS: A total of 997 patients randomly received one of five treatments: placebo; midazolam administered to a clinical endpoint of conscious sedation (mean dose, 8.6 milligrams); midazolam plus additional midazolam as needed during the procedure (mean total dose, 12.2 mg); fentanyl (1.4 micrograms/kilogram) plus midazolam to achieve the same endpoint of conscious sedation (mean dose, 5.7 mg); or fentanyl (1.4 (micrograms/kg), midazolam (mean dose, 5.8 mg) and methohexital as needed during the procedure (mean dose, 61.0 mg). RESULTS: Each drug regimen reduced anxiety during surgery in comparison with placebo, with the combination of midazolam, fentanyl and methohexital resulting in significantly less anxiety in comparison with the other treatment groups. Pain reports by patients during surgery also were reduced significantly by the combination of fentanyl, midazolam and methohexital. Patients' global evaluations of the efficacy of sedation ranked midazolam with supplemental midazolam and the combination of fentanyl, midazolam and methohexital as significantly more efficacious than the other two drug regiments. The authors noted transient respiratory depression in patients in the two opioid-treated groups, but no other physiological changes were detected. CONCLUSIONS: These data provide evidence that the drugs and doses evaluated resulted in therapeutic benefit to dental outpatients, with minimal incidence of potentially serious adverse effects. CLINICAL IMPLICATIONS: The results of this large-scale study provide assurance to both the public and the dental profession of the safety of parenteral sedation with these drugs and combinations of these drugs when titrated slowly in the recommended doses by appropriately trained dentists.     

Butorphanol/diazepam compared to meperidine/diazepam for sedation in oral maxillofacial surgery: a double-blind evaluation

Butorphanol and meperidine, each combined with titrated diazepam, 10 to 20 mg, were compared in a randomized, double-blind trial for their sedative-analgesic effects. The fifty patients underwent multiple dental extractions under local anesthesia and sedation in an outpatient clinic. Butorphanol was significantly superior to meperidine with respect to the diazepam dose required to achieve the target level of sedation, the total diazepam dose administered, the clinical level of sedation, the surgeon's overall evaluations of effectiveness and of sedation level, and several patient evaluation parameters measured at discharge from the recovery room and at follow-up interview. All study drugs were well tolerated. Butorphanol offers clinical advantages over meperidine when combined with diazepam for sedation analgesia in outpatient oral surgery.     

Arterial blood gas levels after midazolam or diazepam administered with or without fentanyl as an intravenous sedative for outpatient surgical procedures

The purpose of this study was to compare arterial blood gas measurements made during the baseline, initial sedation, maintenance, and recovery periods in patients sedated with midazolam and saline (MS), midazolam and fentanyl (MF), diazepam and saline (DS), and diazepam and fentanyl (DF). During induction both the MF and the DF groups had significantly lower average PO2, pH, and O2 saturations and significantly higher PCO2 values than either the MS or the DS group. While the differences were not as great, the same was also true during the maintenance phase of the procedure. During recovery, patients receiving MF had lower average PO2, pH, and O2 saturation and higher PCO2 values than the MS or the DF group. Patients receiving MF had significantly lower average PO2, pH, and O2 saturation levels and significantly higher average PCO2 levels during all three postsurgical periods than at baseline. Patients receiving DF had significantly lower average PO2, pH, and O2 saturation levels and significantly higher Pco2 levels during both induction and maintenance than at baseline.     

Comparison of the effectiveness of oral diazepam and midazolam for the sedation of autistic patients during dental treatment

PURPOSE: This study was undertaken to compare the effectiveness of oral diazepam and midazolam in sedating autistic patients during dental treatment. METHODS: The treatment regimen consisted of nitrous oxide/oxygen inhalation in conjunction with oral administration of either diazepam 0.3 mg/kg or midazolam 0.5 mg/kg in a cross-over design study of 13 subjects aged 5.8 to 14.7 years. A drug was classified as being effective when over 70% of the patients taking the drug were judged as "success" in all 3 behavioral criteria: (1) sleeping; (2) body movement; and (3) crying behaviors. The study was observed by an independent clinician with an intraexaminer reliability of 88%. RESULTS: For sleeping behavior, midazolam was found to be significantly more effective than diazepam as the duration of stimulation increased (P<.05). For the movement and crying behaviors, midazolam also proved to be significantly more effective from the start of treatment through the 35- and 40-min markers, respectively (P<.05). For the remainder of treatment, however, there was no statistically significant difference in these behaviors between the trials (P>.05). Diazepam and midazolam were rated as 77% and 100% successful, according to the overall behavior evaluation criteria (P=.02). CONCLUSIONS: Both diazepam and midazolam were shown to be effective sedative agents, successfully and safely used to sedate autistic patients for dental treatment. Midazolam was significantly more effective than diazepam in those portions of the procedure with increased stimulation.     

A comparison of midazolam with and without nalbuphine for intravenous sedation

The introduction of nalbuphine to intravenous sedation with midazolam added little to the quality of sedation for short operative procedures. There was a greater tendency for patients who received nalbuphine and midazolam to sleep in the afternoon after treatment compared with those who received only midazolam. Significantly more patients had nausea and vomiting in the midazolam/nalbuphine group than did patients in the midazolam-only group.     

A comparative evaluation of oral midazolam with other sedatives as premedication in pediatric dentistry

The purpose of present study was to evaluate the safety and efficacy of orally administered midazolam in children as a sedative agent and to compare it with two other older agents, triclofos and promethazine. The study was conducted on ninety child patients requiring some short dental procedure. All the patients were with a good physical status (ASA-I). The ages ranged between 3 and 9 years. The patients were randomized into three study groups: Group 1, midazolam, Group II, triclofos and Group III, promethazine, on the basis of the drugs to be administered. After administration of drugs in each group, the effects were evaluated in terms of onset of action, sedative effect, ease of treatment completion, recovery time and postoperative amnesia. Midazolam was found to be the best drug among the three to produce conscious sedation in children.     

右美托咪定与几种镇静药物在口腔门诊手术中镇静效果的meta分析

目的:采用meta分析,比较右美托咪定与咪达唑仑、氯胺酮和安慰剂在口腔门诊手术中的镇静效果。方法:计算机检索PubMed、Embase、Cochrane Library、Web of Science,检索时间从建库至2017年10月。收集口腔门诊手术中比较右美托咪定与咪达唑仑、氯胺酮或安慰剂镇静效果的随机对照试验（RCT）。采用Cochrane协作网系统评价法评价纳入文献质量,采用RevMan5.3软件对收集的患者资料进行meta分析。结果:共纳入12篇RCT、678例患者。Meta分析结果显示,右美托咪定组儿童的镇静评分低于生理盐水组(SMD=-1.73,95%CI:-2.70~-0.77,P=0.0004);右美托咪定组成人的镇静评分也低于生理盐水组(SMD=-2.23,95%CI:-4.39~-0.08,P=0.04);右美托咪定组儿童的镇静满意度与氯胺酮组无显著差异（RR=1.14,95%CI：1.00~1.30,P=0.05）;右美托咪定组儿童的镇静满意度优于咪达唑仑组（RR=1.38,95%CI：1.15~1.67,P=0.0006）;右美托咪定组成人的镇静满意度与咪达唑仑组无显著差异（RR=1.42,95%CI：0.86~2.33,P=0.17）;并且右美托咪定组儿童的行为满意度优于氯胺酮组（RR=1.19,95%CI：1.03~1.36,P=0.01）,也优于咪达唑仑组（RR=1.28,95%CI：1.07~1.54,P=0.008）。结论:与其他镇静药物相比,右美托咪定用于口腔门诊手术适度镇静可能是一种更好的选择。     

BIS monitoring during midazolam and midazolam-ketamine conscious intravenous sedation for oral surgery

OBJECTIVE: The purpose of this study was to determine whether the bispectral index scale (BIS) would provide added benefit to established methods of monitoring conscious sedation with midazolam (M group) or midazolam supplemented with ketamine (MK group). STUDY DESIGN: BIS was prospectively and blindly examined in 22 patients receiving outpatient oral surgery with conscious sedation supplemented with local anesthesia. RESULTS: The average midazolam dose in the midazolam group over the treatment period was 0.01 mg/kg/h, and the average midazolam plus ketamine dose was 0.01 and 0.05 mg/kg/h, respectively. Mean BIS values throughout the sedation study period were 90 for the midazolam group and 94 for the midazolam plus ketamine group. The addition of ketamine did not lower BIS. BIS values did not alter significantly over time except for an expected transient drop after the midazolam bolus induction. CONCLUSION: BIS levels remained close to baseline levels, suggesting that BIS would not provided any additional benefit to currently established methods of monitoring patient consciousness during conscious sedation for oral surgery.     

Conscious sedation with propofol

The study was designed to assess the suitability of propofol for conscious sedation. Thirty-one patients undergoing bilateral third molar surgery were randomly given either propofol or midazolam for sedation as an adjunct to local anaesthesia at the first visit, and the alternative at the second visit. Propofol, like midazolam, produced reliable sedation, good operating conditions, stable vital signs and profound amnesia, with minimum intra-operative and post-operative adverse effects. Furthermore, most patients were willing to undergo either sedation procedure again. The advantages of propofol over midazolam were the ease with which the degree of sedation could be altered and the quick recovery. Its disadvantages were pain during injection, increased talkativeness, the extra equipment needed, and cost.     

A sedation technique for implant and periodontal surgery

OBJECTIVE: Evaluation of a sedation technique which involved titrating intravenous midazolam to an 'ideal' sedation end point, followed by a continuous infusion of propofol. This technique might be a satisfactory alternative to general anaesthesia for implant surgery in anxious patients or when procedures exceed 60-min duration. MATERIAL AND METHODS: 20 patients were treated on 23 occasions. A 2-mg bolus of midazolam was injected intravenously followed after 90 s by 1 mg increments until the patient was adequately sedated. 30 min after this induction with midazolam, a propofol infusion was started at a rate which varied between 0-300 mg/h (0-30 ml/h). The actual infusion rate was adjusted in order to maintain the optimum sedation level which had been achieved using midazolam. The quality of sedation was assessed using Ellis and Sedation scores. RESULTS: Midazolam dosage varied between 5 and 14 mg. The initial propofol infusion rate was 200 mg/h (20 ml/h) for 21 of the 23 implant surgery treatments. CONCLUSION: The sedation technique described takes advantage of the differing pharmacokinetic properties of midazolam and propofol. Initial sedation was achieved using midazolam, this was then maintained using a variable propofol infusion. The shorter distribution and elimination half-lifes of the latter drug made matching the level of sedation to the patient's needs easier and also provided good short-term recovery.     

A comparison of midazolam and midazolam with remifentanil for patient-controlled sedation during operations on third molars

Our aim was to compare patients' satisfaction and cooperation, and clinical efficacy, of midazolam alone, and midazolam and remifentanil for patient-controlled sedation during removal of third molars. Forty patients, American Society of Anesthesiologists grades I and II, admitted for extraction of impacted mandibular third molars were included in this randomised, prospective study. They were given an intravenous bolus of midazolam 0.03 mg/kg and then allowed to use patient-controlled sedation. In the midazolam group, 2 ml of 0.5 mg/ml midazolam was given automatically. In the midazolam-remifentanil group, 2 ml of 0.5 mg/ml midazolam and 12.5 microg/ml remifentanil were given in the same manner. The lockout period was 5 min. Vital signs and oxygen saturation were recorded. Patients' and surgeons' satisfaction, and the patients' degree of amnesia about the local anaesthetic, drilling, removal of the tooth, and pain during extraction were also assessed. There were no significant differences between systolic and diastolic blood pressures during sedation, but heart rate after 30 min in the combined group was significantly lower than in the midazolam group (p<0.05). Surgeons described the midazolam group as excellent in 9 and good in 11. In the combined group, satisfaction was excellent in 11, good in 7, and satisfactory or unacceptable in 1 of each. Immediately postoperatively, 19 patients in each group ranked their satisfaction as excellent and 1 as good. Twenty-four hours later it was unchanged in the midazolam group, while 15 patients in the other group thought it was excellent, 3 good, and 2 poor. Patient-controlled analgesia with midazolam or midazolam and remifentanil is safe and reliable during extraction of third molars.     

Outcomes of moderate sedation in paediatric dental patients

Background: The aim of this study was to evaluate the outcomes of moderate sedation with nitrous oxide/oxygen (N₂O/O₂) alone or combined with different dosages and administration routes of midazolam in uncooperative paediatric dental patients using the Bispectral Index System (BIS). Methods: This one‐year clinical study examined first‐visit moderate sedation performed in 240 healthy children aged 4–6 years. Subjects were randomly divided into four groups according to drug, route and dosage, as follows: Group 1 – 0.20 mg/kg midazolam (40 mg/ml) delivered intranasally; Group 2 – 0.75 mg/kg midazolam (15 mg/3 ml) delivered orally; Group 3 – 0.50 mg/kg midazolam (15 mg/3 ml) delivered orally. All children in these three groups also received inhalation sedation with 50%–50% N₂O/O₂, whereas children in Group 4 received inhalation sedation with 50%–50% N₂O/O₂ only. The outcome of sedation was evaluated as either ‘successful’, ‘failed’ or ‘not accepted’. Results: The highest success rate was found in Group 1 (0.20 mg/kg intranasally, 87%), followed by Group 2 (0.75 mg/kg orally, 79%). The overall mean success rate for all groups was 73%. Conclusions: Moderate sedation can be successfully used in the clinical management of paediatric dental patients, with both intranasal and oral sedation using midazolam in conjunction with nitrous oxide found to be effective methods.     

A study of the effectiveness of oral midazolam sedation for orthodontic extraction of permanent teeth in children: a prospective,randomised, controlled,crossover trial

OBJECTIVES: To assess the safety, effectiveness and acceptability of o:ral midazolam sedation for orthodontic extraction of permanent teeth in children. DESIGN: A prospective, randomised, controlled, crossover trial. METHODS: A total of 26 children aged 10-16 (ASA I), referred for orthodontic extraction of premolar or canine teeth under sedation, were included in the study. Each child required two treatment sessions for the extraction of equivalent teeth on opposite sides of the mouth. Each subject was sedated with either ora midazolam (0.5 mg/kg) or nitrous oxide and oxygen (30%/70%) at the first visit and the alternative form at the second visit. At each visit two teeth were extracted, one upper and one lower. Heart rate, arterial oxygen saturation, respiration rate, sedation and behavioural scores were recorded every five minutes. Overall behaviour, patient acceptance and patient satisfaction were recorded at the end of treatment. RESULTS: Of the 26 children included in the study there were 12 males and 14 females. The mean age was 12.5 years. The mean heart rate and respiratory rate for both groups were similar and within acceptable clinical limits. The lowest mean arterial oxygen saturation levels for nitrous oxide and midazolam sedation were 97.7% and 95.0% respectively. Although midazolam caused greater oxygen desaturation, the range (91%-100%) was within safe limits for conscious sedation. The mean level of sedation was greater in the midazolam group compared with the nitrous oxide group and all but one case completed treatment. A total of 23 patients (88%) said they would be prepared to have ora midazolam sedation again and 17 (65%) actually preferred oral midazolam to nitrous oxide sedation. CONCLUSION: Oral midazolam (0.5mg/kg) appears to be a safe and acceptable form of sedation for 10-16 year old paediatric dental patients.