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.     

Continuous transcutaneous O2 and CO2 monitoring during conscious sedation for oral surgery

Continuous transcutaneous oxygen and carbon dioxide monitoring during conscious sedation using diazepam, fentanyl, and methohexital indicates that hypoxia occurs in all patients maintained on room air; 36% of the patients maintained on room air showed a decrease in transcutaneous oxygen of greater than 20 mg Hg. Although the use of supplemental O2 prevented hypoxia, the combination of diazepam, fentanyl, and methohexital depressed all of the patient's carbon dioxide chemoreceptors, resulting in a rise in carbon dioxide in the oxygen-supplemented patients as well as in the patients who were maintained on room air. The need for supplemental oxygen in patients sedated with diazepam, fentanyl, and methohexital is clearly established.     

Prolonged recovery after intravenous diazepam

Prolonged recovery from intravenous diazepam after the day of administration has been examined in 2,468 consecutive patients who underwent oral surgery and general dentistry. Patients ranged in age from 2 to 94 years and received a mean diazepam dose of 19 mg, either by itself or with small amounts of methohexital sodium. Recovery was assessed by use of a questionnaire, and the answers were related to sexual gender, age, weight, dosage, procedure, duration, level of apprehension, and results of the sedation.     

Human cardiorespiratory and analgesic effects of intravenous diazepam and local anesthesia.

The only clinically detectable cardiovascular changes after intravenous diazepam administration are a moderate fall in systolic blood pressure and a rise in pulse rate. But it will produce significant cardiovascular changes, principally the lowering of total peripheral resistance and stroke volume. The drug has a long history of safety but is not totally innocuous. It is suggested that if diazepam is used in combination with methohexital, consideration should be given to the additive effects on total peripheral resistance.     

Monitored anesthesia care for dental implant surgery: analysis of effectiveness and complications

The optimal method of providing safe and effective sedation for outpatients undergoing lengthy dental operations is unclear. We provided monitored anesthesia care (conscious sedation) for 102 consecutive dental implant procedures, using intravenous midazolam and fentanyl as primary pharmacologic agents. Midazolam was administered by multiple, intermittent injection or via continuous infusion. The dose of midazolam required for the induction of sedation ranged from 3.4 +/- 1.6 mg to 4.0 +/- 2.0 mg. Maintenance of adequate sedation required a mean midazolam administration rate of 4.0 +/- 2.1 mg/h to 5.1 +/- 2.1 mg/h, and a mean fentanyl administration rate of 54 +/- 29 mcg/h to 60 +/- 27 mcg/h. Continuous monitoring allowed for rapid detection and treatment of 40 separate hemodynamic and respiratory problems. There was no evidence of patient injury, and all patients returned home on the day of surgery. A post-operative telephone survey revealed that 65% of patients had complete amnesia for operative events, 96% were satisfied with monitored anesthesia care, and 94% would desire a similar anesthetic technique for future procedures.     

Cardiorespiratory effects of a balanced anesthetic technique in outpatient general anesthesia.

Detailed measures have been made of the cardiorespiratory effects of a balanced general anesthetic technique on ten young patients undergoing oral surgery. The combination of fentanyl, diazepam, and atropine followed by N2O/O2 and methohexital resulted in a respiratory hyperoxic state throughout surgery and there was no evidence of hypercardia at any anesthesia stage. Cardiovascular stability was judged to be generally superior to that reported for techniques that have relied on methohexital without premedication. This balanced general anesthetic technique offers the oral surgeon-anesthetist a safe, effective, and practical alternative to techniques that rely on more potent anesthetic gases.     

A comparison of chloral hydrate and diazepam sedation in young children

The purpose of this study was to compare a high and low dose of diazepam with chloral hydrate in the sedation of young children. Thirty healthy children between the ages of 20 and 48 months, with a mean age of 33.5 months, participated in the study. All children exhibited negative behavior during a screening visit and required at least two restorative appointments with the use of sedation. A dose of either 0.3 mg/kg or 0.6 mg/kg of diazepam at one visit and 50 mg/kg of chloral hydrate at another visit was administered in a double-blind manner. All children were restrained in a Papoose Board with auxiliary head restraint and received 50% nitrous oxide/oxygen during treatment. The degree of sleep, body movement, crying, pulse rate, respiratory rate, and blood oxygen saturation were monitored before and during the operative procedures. Vital signs remained essentially unchanged during treatment, except for transitory elevations of the pulse during periods of stimulation. There were no statistically significant differences among the three drug regimens with regard to movement and crying. Significantly more patients who received chloral hydrate were asleep than when either dose of diazepam was given during the first 60 min of treatment. The only side effect found was vomiting in one patient with both chloral hydrate and diazepam. It is concluded that the sedative effects of chloral hydrate and diazepam are similar when young children are sedated for dental treatment. The use of diazepam might be more advantageous because chloral hydrate produces more sleep during the first hour of treatment.     

Differential pharmacology of drugs used for intravenous pre-medication

The differential effects of drugs used for intravenous pre-medication are reviewed using the results of controlled clinical trials in dental outpatients. The evaluation of clinical success requires experimental control of factors which can confound both the therapeutic and evaluation processes. The evaluation of drugs which are given primarily to alleviate anxiety requires that this effect be assessed by the patient's self-report rather than by the clinician's estimate of drug effect based on external manifestations. The results of the studies reviewed suggest that intravenous diazepam accomplishes the therapeutic objectives of anxiety relief, decreased pain perception, and amnesia. The addition of a narcotic, while reducing the diazepam dose, does not result in any greater effect, but does improve patient cooperation. It is concluded that diazepam, administered to clinical end-point, accomplishes most of the goals of intravenous pre-medication with minimal potential for adverse effects. The use of additional agents may improve patient cooperation, but this possible advantage must be weighed against the potential for increased systemic effects.     

Respiratory effects of fentanyl, diazepam, and methohexital sedation.

The respiratory depressant effects of fentanyl, diazepam, and methohexital were studied in 18 patients who were breathing room air. Two patients had 70% oxygen supplementation administered by a nasal inhaler. Varying degrees of hypoxia occurred when the narcotic was given but hypoxia was not seen in patients who received diazepam alone. The hypoxic changes may be attributed to various physiological responses and can probably be prevented with administration of adequate oxygen.     

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.     

Intravenous or rectal diazepam for outpatient sedation in minor oral surgery

In a randomized cross-over study on sedation in outpatient oral surgery, intravenous and rectal administration of diazepam were compared. The mean dose for intravenous diazepam was 0.22 mg X kg-1 (range 0.15-0.38) and for rectal diazepam 0.58 mg X kg-1 (range 0.50-0.71). The determining factors for the patients' preference for sedation method, apprehension, effect produced by the sedative, recovery from sedation and the postoperative course were studied. The patients preferred the session in which they experienced stronger effect, regardless of the route of administration. Patient preference for sedation method did not differ when optimal dose regimens were used, and a preset dose of 10 mg rectal diazepam did not produce the desired effect. Apprehension was significantly higher prior to and during the first operation than the second operation, and all patients recovered from sedation within 2 1/2 hours after the administration.     

Comparing the safety, efficacy and recovery of intranasal midazolam vs. oral chloral hydrate and promethazine.

PURPOSE: The purpose of this study was to compare the safety, efficacy and recovery time of intranasal midazolam spray administered using an atomizer to orally administered chloral hydrate and promethazine for the sedation of pediatric dental patients. METHODS: A randomized double-blind crossover study design was utilized in which 31 patients (mean age 41.8 months, range 26-58 months) underwent two restorative dental appointments. At one appointment, subjects received 0.2 mg/kg intranasal midazolam; at the other appointment subjects received 62.5 mg/kg chloral hydrate with 12.5 mg promethazine. Administered at each appointment was 25%-50% N(2)0/0(2). Physiologic parameters (heart rate, blood pressure, respiratory rate, oxygen saturation) and behavior assessments (crying, movement, sleep) using the Houpt Sedation Rating Scale were recorded at baseline and every five minutes during treatment. Overall behavior was assessed at baseline and at the end of treatment. Following treatment, a modified Vancouver Recovery Scale was used to determine the length of time it took each subject to meet established discharge criteria. RESULTS: There were no clinically significant differences in physiologic parameters, however a statistically significant decrease in systolic and diastolic blood pressure was observed in patients sedated with chloral hydrate/promethazine. There were no significant differences in behavior between groups. Patients sedated with intranasal midazolam slept less and recovered quicker than patients sedated with oral chloral hydrate/promethazine. CONCLUSIONS: Intranasal midazolam administered using an atomizer is as safe (as assessed by physiologic parameters) and effective (as assessed by behavior ratings) as oral chloral hydrate/promethazine for conscious sedation of pediatric dental patients.     

Ampicillin concentrations in human serum, gingiva, mandibular bone, dental follicle, and dental pulp following a single oral dose of talampicillin

Eighty-one patients who underwent the extraction of impacted mandibular third molars in the nonfasting state were given a single oral dose of talampicillin (500 mg) preoperatively. Specimens of venous blood (n = 132), gingiva (n = 70), mandibular bone (n = 78), dental follicle (n = 63), and dental pulp (n = 59) were obtained during the operation and assayed for ampicillin content. The mean peak concentrations in serum (9.64 micrograms/ml), gingiva (4.72 micrograms/mg), mandibular bone (1.77 micrograms/ml), dental follicle (3.46 micrograms/ml), and dental pulp (5.53 micrograms/mg) all occurred at approximately 150 minutes after administration of talampicillin. The ratios of the corresponding serum concentration to the peak concentrations in the various oral tissues when both were plotted as drug concentration curves were: gingiva, 0.50; mandibular bone, 0.16; dental follicle, 0.34; and dental pulp, 0.52. Talampicillin was absorbed well by the intestine, and sufficient concentrations of the resulting metabolite, ampicillin, were found in oral tissues.     

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.     

Continuous infusion of methohexital and alfentanil hydrochloride for general anesthesia in outpatient third molar surgery

Three anesthetic techniques were compared in this study: 1) Intermittent Brevital boluses supplemented with fentanyl and midazolam all titrated to patient movement, 2) constant infusion of Brevital supplemented with fentanyl and midazolam all delivered in calculated mg/kg doses based on total body weight, and 3) constant infusion of methohexital (Brevital) and alfentanil (Alfenta) supplemented by midazolam (Versed), droperidol, and glycopyrolate (Robinul) delivered in calculated mg/kg doses based on lean body mass. Nitrous oxide was delivered in all cases via nasal mask in a 30% to 50% concentration. The mean total dose of Brevital in group 1 (intermittent Brevital bolus) was 0.17 mg/kg/min (SD = 0.07), group 2 (Brevital infusion) was 0.23 mg/kg/min (SD = 0.06), and group 3 (alfentanil/Brevital infusion) was 0.12 mg/kg/min (SD = 0.07). Mean total dose of alfentanil in group 3 equaled 1.58 mcg/kg/min (SD = 0.73). In group 1, 94% of the patients experienced moderate to severe movement intraoperatively. Twenty-three percent of the patients in group 2, and only 7% of group 3 exhibited moderate to severe movement. Emergence in group 3 averaged 4.5 minutes (SD = 1.6). Three patients (7%) in group 3 had postoperative nausea. Additional subjective findings in group 3 included easier airway maintenance during administration of the anesthetic, lack of unpleasant emergence phenomena such as crying, and prompt readiness for discharge. It was concluded that continuous alfentanil and Brevital infusion satisfied the objectives of safety, stability, predictability, and rapid recovery, while improving operating conditions (less patient movement) when compared with more traditional anesthetic techniques.     

The effects of midazolam on pediatric patients with asthma

PURPOSE: This study was performed to evaluate the safety and efficacy of midazolam in asthmatic patients undergoing dental treatment. METHODS: Twenty-four children, aged 19 to 65 months, with a diagnosis of mild to moderate asthma were given an oral dose of 0.5 mg/kg of midazolam. Oxygen saturation, respiratory rate, and pulse rate were monitored before, during, immediately after, and 30 minutes following dental treatment. The child's asthma score was also determined before and after treatment. The dental operator assessed the overall sedation outcome immediately after treatment. RESULTS: Twenty-three of the 24 subjects had asthma scores of "0" before and after treatment. During dental treatment, 2 patients had oxygen saturations of 94% at one point during treatment. However, oxygen saturation increased when the patient's head and neck were repositioned. Twenty-three of the 24 subjects had oxygen saturations above 95% at 30 minutes following treatment. Pulse rates and respiratory rates exhibited transitory increases, linked to when the child was stimulated. Statistical analysis was conducted from within subjects repeated measures via ANOVA and with a general linear model approach. No statistically significant differences occurred in oxygen saturation and respiratory rate. However, significant differences did occur in pulse rate between 5 and 10 minutes (mean difference=10+/-3.84) and between 10 and 15 minutes (mean difference=19+/-5.50), as expected. No statistically significant differences occurred in asthma score before and after treatment. Twelve subjects were assessed to have excellent behavior, 5 subjects were satisfactory, and 7 subjects were unsatisfactory. No treatment was aborted. CONCLUSIONS: With adherence to the AAPD's sedation guidelines, midazolam at a dose of 0.5 mg/kg is a safe and effective mean for sedation of patients with mild to moderate asthma.     

丙泊酚和异氟醚麻醉对舌癌围术期患者细胞因子反应的影响

目的比较丙泊酚和异氟醚麻醉对舌鳞癌围术期患者炎性和抗炎性细胞因子反应的影响。方法选择24例拟行舌鳞癌根治手术的患者,随机分为丙泊酚组（ P组）和异氟醚组（ I组）。P组手术中麻醉维持采用丙泊酚5～8 mg·kg-1·h-1;I组麻醉维持采用异氟醚,维持呼气末浓度为体积分数0.6%。于麻醉诱导前（ T0）、手术结束时（ T1）、术后24（h T2）和术后48（h T3）分别采集外周静脉血,用酶联免疫吸附法检测血清白细胞介素（ IL）- 6和IL- 10水平,并记录4个观测点的平均动脉压和直肠温度。结果两组患者T1、T2和T3时的IL- 6、IL- 10质量浓度均较术前明显增加（ P<0.05）,均于T1点达到峰值,术后24 h开始回落;I组IL- 6质量浓度在T1点时高于P组（ P<0.01）,而IL- 10质量浓度在T1、T2点时低于P组（ P<0.05）。两组患者的平均动脉压和直肠温度在4个观测点均无统计学差异（ P>0.05）。结论丙泊酚全静脉麻醉对舌癌根治术术后炎症反应比异氟醚轻,对预防严重并发症具有潜在的治疗意义。     

An RCT pilot study to test the effects of intravenous midazolam as a conscious sedation technique for anxious children requiring dental treatment--an alternative to general anaesthesia

AIM: To add to the evidence base for acceptable and effective paediatric conscious sedation techniques in dental primary care. OBJECTIVES: To compare three conscious sedation techniques for primary care as an alternative to dental general anaesthesia (DGA) in children. To assess the feasibility and practicality of running the trial in general dental practice. To form the basis for sample size calculations and assess scales of measurement. DESIGN: Single centre, randomised control trial (RCT). SETTING: Queensway Anxiety Management Clinic (QAMC). A primary care based general and referral dental practice for the management of anxious patients. SUBJECTS, MATERIALS AND METHODS: Sixty five children too anxious for management with relative analgesia, requiring invasive dental procedure for which dental general anaesthesia (DGA) will be required if an alternative cannot be found. INTERVENTIONS: Group 1 (n = 20) - A combination of inhaled medical air and titrated intravenous midazolam. Group 2 (n = 22) - A combination of inhaled 40% nitrous oxide in oxygen and titrated intravenous midazolam. Group 3 (n = 23) - A combination of an inhaled mixture of 0.3% sevoflurane and 40% nitrous oxide in oxygen with titrated intravenous midazolam. MAIN OUTCOME MEASURES: Successful completion of the intended dental treatment with a child who is co-operative and responsive to verbal commands. RESULTS: Fifty per cent (ten children) successfully completed treatment in Group 1, 73% (16 children) in Group 2 and 83% (19 children) in Group 3. This difference was not significant at a 5% level (chi(2) = 5.53, df = 2, P = 0.07) Of the total of 20 failures, eight children in Group 1 and one child in Group 2 were successfully treated with the addition of sevoflurane and nitrous oxide in oxygen. Only two children required referral to a hospital setting for DGA and the remaining nine children were managed with an alternative conscious sedation technique. CONCLUSION: This pilot shows that intravenous midazolam especially in combination with the addition of inhaled nitrous oxide or sevoflurane and nitrous oxide were promising safe and effective techniques, sufficient to justify progression to a definitive RCT with appropriate methods.     

Oral clonidine pre-treatment and diazepam/meperidine sedation

Clonidine has recently been used as a pre-operative medication and sedative/anxiolytic drug. Its extended duration of action makes it suitable for longer procedures. In this randomized, crossover, placebo-controlled clinical trial, we characterized the effects of oral clonidine pre-treatment on intravenous diazepam/meperidine sedation using the bi-spectral index (BIS) in 13 participants. Clonidine significantly increased the numbers of BIS-depressed readings and percent memory loss during sedation, while reducing total diazepam and post-operative analgesic dosages by 44% and 55%, respectively. Systolic, diastolic, and mean arterial blood pressures, as well as pulse rates, were reduced. Respiratory rate, oxygen saturation, end-tidal CO(2), and recovery from sedation were unchanged. Participants, surgeons, and sedationists preferred clonidine over the placebo. Clonidine pre-treatment increased and prolonged sedation and amnesia and stabilized vital signs while significantly decreasing diazepam and post-operative analgesic usage. These results suggest that pre-operative clonidine administration could be a useful supplement to intravenous sedation for dental procedures of long duration.     

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.