Efficacy of oral midazolam prior to intravenous sedation for the removal of third molars.

The combination of oral and intravenous sedation has not been well investigated and this study examined the combination's effect on amnesia, anxiety, cardiovascular stability and recovery in a double blind, cross-over, placebo controlled trial. Patients were given 7.5 mg oral midazolam or placebo 1 h prior to intravenous midazolam and surgery. This investigation demonstrated significant anxiolysis, amnesia and patient preference for oral midazolam compared to placebo. There was no significant effect on cardiovascular stability, the intravenous dose of midazolam used or post-operative recovery. Low dose oral midazolam prior to intravenous sedation may be beneficial in very anxious patients, particularly if surgery is delayed.     

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.     

Factors associated with administration route when using midazolam for pediatric conscious sedation

Midazolam conscious sedation records of pediatric dental patients, one to six years of age, were reviewed retrospectively to: 1) examine the factors associated with the use of oral and nasal routes of administration and their effect on displayed behavior during dental treatment and 2) determine whether a child's compliance with oral administration is predictive of the intraoperative behavior displayed during dental treatment. Two hundred and fifty-seven conscious sedation records for 222 pediatric dental patients sedated with orally or nasally administered midazolam for dental treatment at the University of Florida were reviewed. Data collected included the patient's age, gender, route of administration, dose, compliance with oral administration, appointment type (planned vs. emergency), previous sedation experience with midazolam, operator vs. parent administration of the medication, use of papoose board and nitrous oxide/oxygen inhalation, types of procedures performed (restorations only, extractions only, or both), length of treatment rendered, and preoperative and intraoperative behavioral assessments of the child. The collected data were analyzed with Statview software using ANOVA and Chi-square analyses. There was a statistically significant difference (p < 0.001) between oral and nasal administration for the parameters of age, procedure length, appointment type, procedures performed, previous sedation experience and use of the papoose board and nitrous oxide/oxygen inhalation. While there was no statistically significant influence of chronological age on the preoperative Frankl behavior ratings, there was a statistically significant mean age difference with respect to the administrator of the medication (parent vs. operator), papoose board use, N2O/O2 use and previous sedation experience. Forty-five percent of the subjects were willing to accept oral administration of the medication, however, there was no statistically significant difference (p = 0.114) between the child's compliance to accept the medication and the intraoperative Frankl behavioral ratings displayed during dental treatment. In this review of midazolam conscious sedation records of pediatric dental patients. 1) route of administration was significantly influenced by several patient and procedural variables, resulting in different behavioral outcomes and 2) compliance with oral administration was not predictive of behavior displayed during treatment.     

Intensity and duration of amnesia from intravenous midazolam given for sedation

A clinical study was performed investigating the ability of intravenous midazolam to cause amnesia for visual, auditory and painful stimuli presented during surgical removal of third molars. Various stimuli were presented prior to and after administration of a sufficient quantity of midazolam to produce profound sedation. Recall was then tested immediately after, one day, and one week following the surgery. The study found that midazolam produces at least 20 minutes of profound amnesia for all stimuli in 93 +/- 6% of individuals. However, little correlation was found between the dose of midazolam and the duration of amnesia. Anesthesia literally means the loss of sensation. In the clinical dental situation, the principle sensation lost, when using either regional or general anesthesia, is pain perception. Although prevention of pain sensation is the primary reason patients request local anesthesia prior to invasive dental care, for many patients, control of pain only partially prepares them to receive dental care. These patients request the adjunctive use of sedation or general anesthesia, not for further pain control, but rather requiring periodontal or oral/maxillofacial surgery in which such factors as the sight and taste of blood, the noise of bone-cutting equipment, or the pressure placed on the jaws is not eliminated by local anesthetics. Although effective anxiolytic oral, inhalational, or parenteral agents have been available for several decades, patients still usually retain their memory of events occurring during their dental care, particularly anxiety-provoking events. This memory of the uncomfortable portions of dental care stimulates additional anxiety so that patients may procrastinate when dental care is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)     

盐酸咪达唑仑镇静药在阻生智齿拔除术中应用的临床观察

目的观察马来酸咪达唑仑（midazolam HCl）静脉输注提高下颌阻生智齿拔除时患者舒适度的效果。方法50例双侧下颌阻生智齿拔除难度基本相同的患者，采用自身对照设计，一侧采用盐酸咪达唑仑低流量（平均流量0．042±0．010mg·kg^-1）静脉输入，另一侧空白对照。结果试验组焦虑视觉模拟量表（visual analogue scale，VAS）平均得分21．4±12．2mm，疼痛VAS平均得分（6．92±9．50）mm，与对照组（35．9±18．2）mm；（16．4±12．4mm）比较，差异有统计学意义（P=0．000；P=0．000）。结论在拔除阻生智齿时，对轻度恐惧的患者应用盐酸咪达唑仑镇静，可以显著提高患者的舒适度。     

Sedation in uncooperative children undergoing dental procedures: a comparative evaluation of midazolam, propofol and ketamine

Dentists usually face a common problem dealing with pediatric patients due to their high levels of anxiety and fear, associated with dental procedures. Such children are usually managed by various pharmacological methods. The efficacy and safety of conscious sedation, using intravenous short acting group of drugs (midazolam, propofol and ketamine) in uncooperative children, requiring oral rehabilitation was thus evaluated in this study. A total of 30 uncooperative children, aged 3-6 years, belonging to ASA I, II category formed the study group. The efficacy of the three group of drugs was evaluated on the basis of the onset of sedation, duration of action, side effects encountered, and the overall cooperative behavior of the child throughout the course of the procedure, after obtaining parental consent. Results showed that propofol was highly effective in terms of onset of sedation, although increased body movements and crying, pain on injection and intermittent cough was observed as the main side effects of the drug. Midazolam showed the longest duration of action, but was not very effective in terms of treatment completion due to increased movements and crying. Maximum cooperation during the procedure was obtained with ketamine and no adverse effects were encountered. We preferred ketamine from the results of our study and recommended future evaluation of ketamine in combination with other sedatives.     

Cognitive properties of sedation agents: comparison of the effects of nitrous oxide and midazolam on memory and mood

OBJECTIVES: To compare the effects of nitrous oxide and midazolam on cognition and mood. DESIGN: A three-way, counterbalanced, cross-over study, using patients receiving conscious sedation for routine dental treatment. METHODS: On each of three separate visits, patients performed a computerised test battery to determine baseline cognitive performance. Then, following administration of either midazolam, nitrous oxide, or no drug, patients re-performed the test battery. Finally, patients completed visual analogue scales assessing their subjective mood state. RESULTS: Relative to baseline performance, midazolam administration produced significantly slower reaction times compared with nitrous oxide and no-drug conditions. Furthermore, patients receiving midazolam were impaired in accuracy relative to the other conditions on many of the cognitive tasks, particularly those assessing the recall of information. Patient performance in nitrous oxide and control conditions did not significantly differ. These results could not be explained by differences in mood between the conditions, as subjective mood ratings during midazolam or nitrous oxide administration were very similar. CONCLUSIONS: It is important for clinicians to be aware that peri-operative recall of information is reduced in patients who have undergone midazolam sedation. This is an advantage for patients who are anxious, and do not wish to be aware of the operative treatment being performed. However, as the cognitive impairment is enduring, an adult escort and written post-operative instructions should be mandatory for midazolam sedation patients. In contrast, the use of nitrous oxide sedation does not significantly impair higher cognitive tasks and thus patients receiving nitrous oxide sedation can resume normal activities in the post-operative period.     

The effectiveness of flurazepam as night sedation prior to the removal of third molars

Anxiety prior to dental treatment is a well-recognized problem. Although oral sedation has been recommended the night before appointments to reduce this anxiety, there are no well-controlled studies to support this claim. The present double-blind cross-over study investigated the effect of 30 mg of flurazepam taken the night before the removal of impacted third molars. Preoperative anxiety, visuomotor performance and sleep patterns were investigated in 20 adult patients with similarly impacted third molars. While preoperative flurazepam led to a statistically significant improvement in sleep patterns, there was no reduction in pre-operative anxiety on the morning of surgery. In addition, the flurazepam-treated group demonstrated significantly impaired visuo-motor performance 60 min after intravenous sedation compared to this group where intravenous sedation was used only preceded by placebo. Patients had a significant preference for flurazepam over placebo as a night-time sedative.     

Reversal of midazolam sedation with flumazenil following conservative dentistry

The purpose of this double-blind randomized study was to assess recovery of mental function following reversal of midazolam-induced sedation with the specific antagonist flumazenil (R015-1788) or placebo following conservative dental procedures. Recovery was assessed using choice reaction time and critical flicker fusion threshold, both objective tests of psychomotor function; linear analogue sedation scores and simple memory tests. Assessments were repeated up to 3 h after administration of flumazenil or placebo to discover whether recovery was sustained or whether resedation occurred due to the short duration of action of flumazenil. Flumazenil in doses from 0.5 to 1.0 mg rapidly reversed the sedative and amnesic effects of a mean dose of 8.2 mg of midazolam without apparent evidence of subsequent resedation. Since recovery of mental function in the control group had ordinarily occurred 45 min after administration of placebo, routine reversal of midazolam sedation with flumazenil cannot be justified. Nevertheless, in cases of undue sedation persisting after dental treatment, flumazenil may be used with minimal risk of resedation occurring.     

口服与肌注咪达唑仑镇静治疗儿童牙科焦虑症的临床疗效对比

目的:评估咪达唑仑口服或肌注两种不同给药方法对牙科焦虑症患儿牙科治疗时的镇静效果。方法:将2020年1月~2020年7月于深圳市儿童医院口腔科接受咪达唑仑镇静下牙齿治疗的90例患儿随机分为两组,每组45例。肌注组给予肌注咪达唑仑(0.2 mg/kg),口服组给予口服咪达唑仑(0.6 mg/kg,单次最大剂量20.0 mg)。采用Ramssay量表评估患儿镇静情况,Frankl量表评估患儿治疗依从性,Houpt量表评估患儿治疗完成情况。同时记录药物起效时间、患儿治疗过程中的心率、血氧饱和度、术中及术后不良反应情况等。结果:肌注组起效时间(13.0±2.0)min明显短于口服组(15.6±1.8)min,差异有统计学意义(t=6.489,P<0.05)。两组的Ramssay量表评分中位分值(Z=-1.089,P=0.276),Frankl量表评分中位分值(Z=-0.0863,P=0.388)及Houpt量表评分中位分值(Z=-1.854,P=0.064)差异无统计学意义(P>0.05),评分分布相似。两组患儿的镇静成功率(χ^2=0.178,P>0.05)及治疗成功率(χ^2=3.103,P>0.05)差异无统计学意义(P>0.05)。两组不良反应发生率差异无统计学意义(χ^2=0.080,P>0.05)。结论:口服或肌注咪达唑仑镇静效果相似,是治疗牙科焦虑症患儿的安全有效的镇静方法,但肌注组的镇静起效更快。     

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.     

Intravenous sedation and patient response to minor oral surgery--experience of 408 cases

This article presents the results of a patient questionnaire on response to minor oral surgery carried out under local anaesthetic and intravenous sedation. The predominantly favourable response of the respondents leads the author to suggest the use of IV sedation as a means of reducing patient anxiety, and so increasing dental attendance.     

Temperament and acceptance of dental treatment under sedation in preschool children

The major aim of the study was to investigate whether differences concerning acceptance of dental treatment and amnesia after rectal sedation with midazolam can be explained by temperament traits in the child. Fifty children (1.5 4.0 years), consecutively referred for dental extractions because of dental trauma or caries, were sedated with midazolam 0.3 mg kg(-1) rectally. Level of sedation (state of mind) was assessed according to Wilton before and 10 min after administration of the sedative. The children's acceptance of procedures during the oral examination, the administration of the sedative, and the dental treatment were assessed according to Holst. Acceptance of an injection of local anesthesia and tooth extraction was dichotomized as satisfactory (n = 26) or unsatisfactory (n = 24). The parent assessed temperament using the Emotionality Activity Sociability (EAS) Scale of Child Temperament. Amnesia was evaluated by the parent on the following day. The relation between temperament and outcome variables was analyzed using a multiple logistic regression analysis. Children regarded as shy by the parent were at significantly greater risk of unsatisfactory acceptance of the dental treatment (P< 0.05). High scores of negative emotionality were significantly related to less amnesia (P < 0.05). We conclude that parental ratings of their child's temperament are valuable in predicting a child's acceptance of dental treatment under sedation.     

Effect of submucosal midazolam on behavior and physiologic response when combined with oral chloral hydrate and nitrous oxide sedation

PURPOSE: This study was designed to examine the efficacy and safety of submucosal (SM) midazolam and oral chloral hydrate (CH) when used for pediatric conscious sedation in a clinical dental environment. METHODS: Twenty children ages 32 to 63 months participated in this institutionally approved study. Selection criteria included good health (ASA I), 2 to 5 years of age, uncooperative behavior, and the need for multiple restorative visits. In a double-blind crossover design, patients were randomly assigned to receive either oral CH (50 mg/kg) and SM midazolam (0.2 mg/kg), or oral CH (50 mg/kg) and SM saline placebo on their first sedation visit. On the second sedation visit, the patient received the opposite drug regimen than the first visit. Nitrous oxide (50%) was used during each sedation visit. Behavior response was rated as quiet (Q), crying (C), movement (M), or struggling (S) every 2.5 minutes through 40 minutes of operative procedures. Sedations were monitored using a capnograph, pulse oximeter, an automated blood pressure cuff, and precordial stethoscope. Respiratory rate (RR), heart rate (HR), and blood pressure (BP) were evaluated for each procedure. Data was analyzed using ANOVA and multinomial repeated-measures logistic regression. RESULTS: Analysis showed a significant difference in behavior during sedation across drug regimen (chi-square = 55.6, df = 3, P < .0001). Patients given SM midazolam in addition to oral CH showed increased Q rating and decreased C, M, and S ratings. RR, BP, and HR for both groups remained within the normal values for 2- to 5-year-olds. CONCLUSIONS: SM midazolam improved the quality of sedation without compromising safety. Quiet behavior was increased and struggling behavior was decreased. In addition, mean HR, RR, and BP analysis did not deviate from the norm for this age group.     

Rectal ketamine and midazolam for premedication in pediatric dentistry

Rectally administered midazolam (0.30 mg/kg) and ketamine (5 mg/kg) were compared for preanesthetic medication in children undergoing dental extractions. Sixty patients between the ages 2 and 9 years were randomly allocated to three groups in this double-blind study. In one group of patients who received ketamine rectally, intravenous midazolam (0.05 mg/kg) also was administered immediately after induction of anesthesia. The results from this trial show that 30 minutes after rectal administration of the two drugs, good anxiolysis, sedation, and cooperation were obtained in most patients. Although midazolam appeared to be marginally more efficacious than ketamine in the majority of assessments made and seemed to have less adverse effects, no statistically significant differences could be shown. Ketamine showed a slight decrease and midazolam a slight increase in average blood pressures after premedication. These blood pressure differences were, however, considered to be of little clinical importance.     

Conscious sedation by rectal administration of midazolam or midazolam plus ketamine as alternatives to general anesthesia for dental treatment of uncooperative children

The trial included 24 children (aged 2–7 yr) referred for dental treatment under general anesthesia, since conventional behavioral management methods had failed to achieve treatment acceptance. As an alternative, they received, on two separate occasions with "identical" dental treatment, conscious sedation by rectal administration of either midazolam (0.3 mg/kg body weight (bwt)) or midazolam (0.3 mg/kg bwt) plus ketamine (1.0 mg/kg bwt). This allowed a double-blind, crossover design. The aims were to assess conscious sedation, combined with local anesthesia, as an alternative to general anesthesia, and further to evaluate the effects obtained by addition of a low dose of ketamine to rectally administered midazolam. The feasibility of dental treatment was rated as excellent or good for 16 of the 24 children when premedicated with midazolam, and for 18 of the 24 children when ketamine was added to midazolam. At least some treatment could be given to all children. Verbal contact was maintained with all children throughout both treatment sessions. The children were significantly less anxious when they arrived for the second session. Amnesia and drowsiness were significantly increased when ketamine was added to midazolam. The combination also tended to be more efficient in relief of anxiety and prevention of pain, but there were large variations in the children's responses to the drugs. Midazolam significantly reduced the blood oxygen level, but not with ketamine added. For most children, both regimens proved to be appropriate as alternatives to general anesthesia. From a pharmacologic point of view, the combination of midazolam and ketamine appears to be reasonable because 1) both drugs have sedative and amnestic properties, 2) ketamine adds an analgesic component, 3) midazolam counteracts the psychic side-effects of ketamine, and 4) ketamine counteracts the depressive effects of midazolam on vital body functions (respiration and circulation).     

Midazolam conscious sedation in a large Danish municipal dental service for children and adolescents

Objective.  The aim of this study was to describe the introduction and the first six years use of midazolam for conscious sedation in a municipal dental service in Denmark.
Methods.  In 1998, all dentists were introduced to midazolam conscious sedation. A sedation chart was filled in for each session, and parents' assessment was obtained. In 2004, all clinical materials were collected.
Results.  Six hundred and eighty sessions were performed; 63.7% of the children were between 2 and 6 years of age; 88.5% belonged to American Society of Anesthesiologists grade 1; 74.8% of the sedations performed used the oral route of administration. Restorations were performed during 60.3% of the sessions, and extractions during 38.4%. Complications during the sessions were rare, the most frequent being double vision (6.1%), hiccups (2.7%), and paradoxical reaction (2.0%). Using Wilton's sedation scale, 42.9% were calm and 27.7% were agitated during treatment, whereas after treatment 61.7% were calm; 80.4% of the parents were very positive towards this sedation method.
Conclusion.  Sedation with midazolam for dental treatment of children with dental fear and anxiety is a feasible and an efficient method with a low rate of complications. It can probably reduce the need for dental treatment under general anaesthesia.     

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.     

咪达唑仑作为口腔颌面外科麻醉前用药的探讨

目的研究咪达唑仑用于口腔颌面外科麻醉前用药的效果。方法60例患者随机等分为Ⅰ、Ⅱ、Ⅲ组,麻醉前30min分别肌肉注射咪达唑仑0.06mg/kg、地西泮0.12mg/kg、苯巴比妥钠3mg/kg,观察镇静和抗焦虑作用、对循环和呼吸的影响以及不良反应。结果Ⅰ组用药后5min始出现BIS明显下降、Ramsay镇静评分明显增大,用药后30min时AVAT和SAI数值明显降低(P<0.05),Ⅱ组和Ⅲ组无明显改变;3组的循环和呼吸功能无明显变化,也未见明显不良反应。结论咪达唑仑作为麻醉前用药,镇静和抗焦虑作用确切,无明显不良反应,值得推广应用。     

Evaluation of sedation failure in the outpatient oral and maxillofacial surgery clinic.

PURPOSE: Our goal was to report on the incidence of sedation failures in our outpatient oral surgery clinic. Sedation failure is the inability to complete a procedure under intravenous sedation. There is very little in the oral surgery literature on this subject. MATERIALS AND METHODS: Proper Institutional Review Board approval was obtained from the appropriate governing body for this project. The medical records of 539 intravenous sedation patients treated at the Oral and Maxillofacial Surgery Clinic at our institution were retrospectively evaluated to determine the incidence of failed sedation. Patients sedated with midazolam and fentanyl were placed in group A. There were 323 patients in group A. We placed patients sedated with midazolam, fentanyl and methohexital into group B. There were 216 patients in group B. The gender, medical history, type of procedure being performed, amount of drug given, and the patient's vital signs throughout the procedure were recorded. RESULTS: There were 9 failed sedations with a rate of 1.6% (9/539); 3 in group B (1%) and 6 in group A (2%). Five of our failures were undergoing multiple tooth extractions. Two of the failures were undergoing surgical removal of impacted third molars. Two patients underwent mandibular fracture reduction. Failure was attributed to increased agitation and combativeness, uncontrolled hypertension, tachycardia and desaturation. CONCLUSION: The mandible fracture population and multiple teeth extraction patients had higher rates of failure than other groups. This may be the result of procedure length, type of procedure, or a preoperative anxiety and attitude toward treatment expressed by the patient making sedation unpredictable. Level of training and experience of the practitioner may contribute to sedation failure. These results allow us to develop a prospective study protocol of outpatient sedation and to quantify more detailed information about preoperative anxiety, medical status, and social history than we had available during our chart review. More specific conclusions may help us determine if certain patient populations are at a higher risk for failed sedations.