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1.  Oral triazolam pretreatment for intravenous sedation. 
Anesthesia Progress  1993;40(4):117-121.
This double-blind, controlled clinical trial assessed the anxiety relief provided by oral triazolam given before intravenous sedation. Twenty-two healthy adults undergoing third-molar surgery with intravenous sedation were enrolled in this study. Subjects were randomly assigned to receive either 0.25 mg of triazolam p.o. or an identically appearing placebo 45 to 60 min before venipuncture. Immediately before test drug administration, subjects completed the Corah Anxiety Scale, a Visual Analog Scale (VAS) assessing state anxiety, and the Interval Scale of Anxiety Response (ISAR). The VAS and ISAR were repeated immediately before venipuncture. Intravenous sedation medications consisted of fentanyl, midazolam, and methohexital. At 24 hr, assessments of the venipuncture and global experience were obtained. Results indicated that the characteristics of the triazolam and placebo patients were similar at baseline. With triazolam pretreatment, both the VAS and ISAR scores decreased significantly. Dose requirements for conscious sedation medications were decreased in the triazolam group. Patients rated the venipuncture experience significantly less unpleasant when pretreated with triazolam, and global ratings of the overall surgical experience favored triazolam. An oral-intravenous combination sedation technique using 0.25 mg of triazolam may have a significant therapeutic advantage for outpatient oral surgery.
PMCID: PMC2148582  PMID: 7943920
2.  Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers 
Psychopharmacology  2009;206(1):141-154.
Rationale
Illicit gamma-hydroxybutyrate (GHB) has received attention as a “date rape drug” that produces robust amnesia; however, there is little experimental evidence in support of GHB’s amnestic effects.
Objectives
This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers.
Materials and methods
Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined.
Results
Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate.
Conclusions
Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers.
doi:10.1007/s00213-009-1589-1
PMCID: PMC2792587  PMID: 19543883
GHB; Xyrem; Human; Memory; Amnesia; Sexual assault
3.  Use of sevoflurane inhalation sedation for outpatient third molar surgery. 
Anesthesia Progress  1999;46(1):21-29.
This study attempted to determine if sevoflurane in oxygen inhaled via a nasal hood as a sole sedative agent would provide an appropriate level of deep sedation for outpatient third molar surgery. Twenty-four patients scheduled for third molar removal were randomly assigned to receive either nasal hood inhalation sevoflurane or an intravenous deep sedation using midazolam and fentanyl followed by a propofol infusion. In addition to measuring patient, surgeon, and dentist anesthesiologist subjective satisfaction with the technique, physiological parameters, amnesia, and psychomotor recovery were also assessed. No statistically significant difference was found between the sevoflurane and midazolam-fentanyl-propofol sedative groups in physiological parameters, degree of amnesia, reported quality of sedation, or patient willingness to again undergo a similar deep sedation. A trend toward earlier recovery in the sevoflurane group was identified. Sevoflurane can be successfully employed as a deep sedative rather than a general anesthetic for extraction of third molars in healthy subjects.
PMCID: PMC2148884  PMID: 10551056
4.  Comparative evaluation of midazolam and butorphanol as oral premedication in pediatric patients 
Background:
To compare oral midazolam (0.5 mg/kg) with oral butorphanol (0.2 mg/kg) as a premedication in 60 pediatric patients with regards to sedation, anxiolysis, rescue analgesic requirement, and recovery profile.
Materials and Methods:
In a double blinded study design, 60 pediatric patients belonging to ASA class I and II between the age group of 2–12 years scheduled for elective surgery were randomized to receive either oral midazolam (group I) or oral butorphanol (group II) 30 min before induction of anesthesia. The children were evaluated for levels of sedation and anxiety at the time of separation from the parents, venepuncture, and at the time of facemask application for induction of anesthesia. Rescue analgesic requirement, postoperative recovery, and complications were also recorded.
Results:
Butorphanol had better sedation potential than oral midazolam with comparable anxiolysis at the time of separation of children from their parents. Midazolam proved to be a better anxiolytic during venepuncture and facemask application. Butorphanol reduced need for supplemental analgesics perioperatively without an increase in side effects such as nausea, vomiting, or unpleasant postoperative recovery.
Conclusion:
Oral butorphanol is a better premedication than midazolam in children in view of its excellent sedative and analgesic properties. It does not increase side effects significantly.
doi:10.4103/0970-9185.92431
PMCID: PMC3275967  PMID: 22345942
Anxiolysis; oral midazolam; oral butorphanol; premedication; pediatric anesthesia; sedation
5.  Dose Effects of Triazolam and Scopolamine on Metamemory 
The present study compared the acute dose effects of the benzodiazepine triazolam and the anticholinergic scopolamine on metamemory (knowledge and awareness of one's own memory) in a two-phase paradigm designed to assess effects on both monitoring and control components of metamemory in both semantic (general knowledge) and episodic memory (cued recall) tasks. Placebo and two doses each of triazolam (0.125, 0.25 mg/70 kg, oral) and scopolamine (0.25, 0.50 mg/70 kg, subcutaneous) were administered to 80 healthy volunteers (16/group) in a double-blind, double-dummy, independent groups design. Both triazolam and scopolamine impaired episodic memory (quantity and accuracy) but not semantic memory. Results suggested that both drugs impaired monitoring as reflected in absolute accuracy measures (impaired calibration in the direction of overconfidence) and control sensitivity (the relationship between confidence and behavior). Overall, the results did not provide evidence for differences between triazolam and scopolamine in memory or metamemory. In addition to the clinical relevance of the observed effects, this study adds to the accumulating body of cognitive psychopharmacological research illustrating the usefulness of drug-induced amnesia as a vehicle to explore memory and metamemory.
doi:10.1037/a0018061
PMCID: PMC2846306  PMID: 20158291
6.  Hallucinations and Delirium in the Dental Office Following Triazolam Administration 
Anesthesia Progress  2005;52(1):17-20.
A rare and unusual case of hallucinations following triazolam administration is reported. A review of the literature suggests that hallucinations following triazolam are rare; this is the first report of such a reaction when triazolam was used for oral conscious sedation in dentistry. A discussion of dental implications follows with emphasis on complete medical history evaluation before administering oral sedatives. We conclude that the proper selection of oral sedation candidates, coupled with recognition and management of adverse events, is essential.
doi:10.2344/0003-3006(2005)52[17:HADITD]2.0.CO;2
PMCID: PMC2526214  PMID: 15859444
Triazolam; Hallucinations; Oral sedation
7.  Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans 
Drug and alcohol dependence  2012;128(3):206-213.
BACKGROUND
Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo.
METHODS
Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg /70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hours.
RESULTS
Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM.
CONCLUSION
The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse.
doi:10.1016/j.drugalcdep.2012.08.025
PMCID: PMC3562553  PMID: 22989498
Dextromethorphan; triazolam; cognitive; memory; Robitussin; Coricidin
8.  A Randomized Double-Blind Pilot Study to Compare Conscious Sedation Produced by Diazepam Against Sufentanil 
Anesthesia Progress  1987;34(4):137-141.
Intravenous sufentanil, an analog of fentanyl, was compared to diazepam for conscious sedation in ambulatory dental outpatients. Ten patients undergoing the surgical removal of impacted third molars served as subjects in a double-blind, within-subject, single crossover study. Sedation was achieved with a combination of 30% nitrous oxide/70% oxygen by nasal mask and either diazepam (0.05—0.15 mg/kg) or sufentanic (0.05—0.15 μg/kg) titrated to a clinical endpoint of altered speech and relaxation. Intraoperative physiologic monitoring, patients' and the oral surgeon's subjective estimates of efficacy and psychomotor recovery were used to compare the two treatments. Both patients (eight of 10) and surgeons (six of 10) preferred sufentanil sedation. No significant differences were noted between treatments for psychomotor recovery. These preliminary data in a small sample suggest that sufentanil produces adequate conscious sedation in dental outpatients and should be evaluated further with larger patient samples.
PMCID: PMC2186288  PMID: 2964215
9.  Anterograde Amnesia as a Possible Postoperative Complication of Midazolam as an Agent for Intravenous Conscious Sedation 
Anesthesia Progress  1988;35(4):160-162.
Anterograde amnesia is often considered to be a beneficial effect of intravenous conscious sedation. The recently introduced benzodiazepine, midazolam, has associated with its administration a significant anterograde amnesic period. In the case presented here, a healthy young female presented for third molar extraction under midazolam conscious sedation and local anesthesia. After uncomplicated removal of the teeth and clinically adequate recovery from sedation, it was noted that the patient had swallowed the postsurgical gauze packs. Efforts at recovery of the gauze packs were futile. Follow-up discussion with the patient revealed a complete lack of recall of all events occurring for up to an hour or more after the administration of intravenous midazolam. The need for written and oral postoperative instructions to both the patient and his/her escort is emphasized.
PMCID: PMC2167955  PMID: 3166354
10.  The efficacy and memory effects of oral triazolam premedication in highly anxious dental patients. 
Anesthesia Progress  1994;41(3):70-76.
Triazolam (0.375 or 0.50 mg) or placebo was administered orally to 31 highly anxious dental patients in a double-blind clinical trial 1 hr before treatment. The drug was safe and highly effective, in comparison to placebo, in reducing both anxious cognitions and disruptive movement during oral injections of local anesthetic and drilling. Episodic memory and implicit memory were both adversely affected by the active drug but not the placebo.
PMCID: PMC2148823  PMID: 8934963
11.  Substitution profile of Δ9-tetrahydrocannabinol, triazolam, hydromorphone and methylphenidate in humans discriminating Δ9-tetrahydrocannabinol 
Psychopharmacology  2008;203(2):241-250.
Rationale
Preclinical evidence suggests that non-cannabinoid neurotransmitter systems are involved in the behavioral and physiological effects of cannabinoids, but relatively little research has been conducted in humans.
Objectives
The aims of this study were to assess whether oral Δ9-tetrahydrocannabinol (Δ9- THC) would function as a discriminative stimulus in humans and to examine the substitution profile of drugs acting at opioid, GABA and dopamine systems.
Methods
Healthy subjects who reported moderate cannabis use were enrolled. Subjects learned to identify when they received oral 25 mg Δ9-THC or placebo under double-blind conditions. Once subjects acquired the discrimination (i.e., ≥ 80% drug-appropriate responding for four consecutive sessions), multiple doses of Δ9-THC, the GABAA positive modulator triazolam, the μ-opioid agonist hydromorphone and the dopamine reuptake inhibitor methylphenidate were tested to determine if they shared discriminative-stimulus effects with the training dose of Δ9-THC.
Results
Eight subjects (N=8) accurately discriminated Δ9-THC and completed the study. The training dose of Δ9-THC functioned as a discriminative-stimulus and produced prototypical subject-rated drug effects. All of the drugs tested produced significant effects on the self-report questionnaires, but only Δ9-THC substituted for the training dose.
Conclusion
These results suggest that the discriminative-stimulus effects of Δ9-THC in humans are not directly mediated through central neurotransmitter systems acted upon by the drugs tested in this study.
doi:10.1007/s00213-008-1393-3
PMCID: PMC2712322  PMID: 19018520
drug-discrimination; subjective effects; Δ9-THC; triazolam; hydromorphone; methylphenidate; marijuana; cannabis
12.  The reinforcing, self-reported, performance and physiological effects of Δ9-tetrahydrocannabinol, triazolam, hydromorphone and methylphenidate in cannabis users 
Behavioural pharmacology  2010;21(1):29-38.
The use of illicit prescription drugs is common in cannabis users; however, the effects of few psychoactive drugs have been characterized in this population. In the present study, Δ9-tetrahydrocannabinol (i.e., Δ9-THC), triazolam, hydromorphone and methylphenidate were administered to cannabis users (N=8). Subjects completed the Multiple-Choice Procedure to assess drug reinforcement, as well as self-report questionnaires and performance tasks; physiological assessments were also conducted. Only Δ9-THC increased the crossover point on the Multiple-Choice Procedure, but all of the drugs increased ratings on one or more “positive” drug-effect questionnaire items, as well as items specific for each drug. Triazolam produced the most robust performance impairment, except on a time reproduction task, which was impacted to a greater degree by Δ9-THC. Δ9-THC elevated heart rate and decreased temperature, triazolam increased heart rate, methylphenidate elevated all cardiovascular indices, and hydromorphone reduced respiration. The effects of the drugs tested in the present study were generally consistent with their known pharmacology, although minimal responses to hydromorphone were observed. Future research to directly compare the effects of different psychoactive drugs in cannabis users and non-users would be useful for identifying potential differences in drug effects as a function of use history.
doi:10.1097/FBP.0b013e32833470d7
PMCID: PMC2903043  PMID: 19949319
marijuana; multiple-choice procedure; subjective effects; time reproduction; repeated acquisition task; digit-symbol-substitution task; cardiovascular; respiration; temperature; human
13.  Comparing single and cumulative dosing procedures in human triazolam discriminators. 
This study evaluated a cumulative dosing procedure for drug discrimination with human participants. Four participants learned to discriminate triazolam (0.35 mg/70 kg) from placebo. A crossover design was used to compare the results under a single dosing procedure with results obtained under a cumulative dosing procedure. Under the single dosing procedure, a dose of triazolam (0, 0.05, 0.15, or 0.35 mg/70 kg) or secobarbital (0, 25, 75, or 175 mg/70 kg) was administered 45 min before assessment. Determining each dose-effect curve thus required four sessions. Under the cumulative dosing procedure, four doses of triazolam (0, 0.05, 0.10, and 0.20 mg/70 kg) or secobarbital (0, 25, 50, and 100 mg/70 kg) were administered approximately 55 min apart, producing a complete dose-effect curve in one four-trial session. Regardless of procedure, triazolam and secobarbital produced discriminative stimulus and self-reported effects similar to previous single dosing studies in humans. Shifts to the right in cumulative dose-effect curves compared to single dose-effect curves occurred on several self-report measures. When qualitative stimulus functions rather than quantitative functions are of interest, application of cumulative dosing may increase efficiency in human drug discrimination.
doi:10.1901/jeab.1999.71-417
PMCID: PMC1284713  PMID: 10344022
14.  Aminophylline Fails to Reverse Conscious Sedation with Midazolam in Dentistry 
Anesthesia Progress  1986;33(3):152-154.
A double blind, randomized crossover study investigated whether aminophylline reverses the conscious sedation with midazolam in dentistry to result in quicker clinical recovery than when midazolam is used alone. Twenty-five patients between 17-30 years of age (ASA Grade 1) were sedated with midazolam for bilateral third molar extractions, one side being operated on one visit. Aminophylline or normal saline was given at the end of the surgical procedure on one visit and the alternative during the second visit. No significant difference in recovery was noted with either solution, suggesting that aminophylline does not produce significant reversal of sedation to achieve quicker clinical recovery. The majority of patients preferred to be alert following the operation while some (N = 5) wished to be drowsy, indicating the necessity to question the patient as to preference before deciding to administer a reversal agent.
PMCID: PMC2175479  PMID: 2943194
15.  Comparison of Propofol-Remifentanil Versus Propofol-Ketamine Deep Sedation for Third Molar Surgery 
Anesthesia Progress  2012;59(3):107-117.
This study aimed to compare continuous intravenous infusion combinations of propofol-remifentanil and propofol-ketamine for deep sedation for surgical extraction of all 4 third molars. In a prospective, randomized, double-blinded controlled study, participants received 1 of 2 sedative combinations for deep sedation for the surgery. Both groups initially received midazolam 0.03 mg/kg for baseline sedation. The control group then received a combination of propofol-remifentanil in a ratio of 10 mg propofol to 5 μg of remifentanil per milliliter, and the experimental group received a combination of propofol-ketamine in a ratio of 10 mg of propofol to 2.5 mg of ketamine per milliliter; both were given at an initial propofol infusion rate of 100 μg/kg/min. Each group received an induction loading bolus of 500 μg/kg of the assigned propofol combination along with the appropriate continuous infusion combination . Measured outcomes included emergence and recovery times, various sedation parameters, hemodynamic and respiratory stability, patient and surgeon satisfaction, postoperative course, and associated drug costs. Thirty-seven participants were enrolled in the study. Both groups demonstrated similar sedation parameters and hemodynamic and respiratory stability; however, the ketamine group had prolonged emergence (13.6 ± 6.6 versus 7.1 ± 3.7 minutes, P = .0009) and recovery (42.9 ± 18.7 versus 24.7 ± 7.6 minutes, P = .0004) times. The prolonged recovery profile of continuously infused propofol-ketamine may limit its effectiveness as an alternative to propofol-remifentanil for deep sedation for third molar extraction and perhaps other short oral surgical procedures, especially in the ambulatory dental setting.
doi:10.2344/12-00001.1
PMCID: PMC3468288  PMID: 23050750
Propofol; Ketamine; Remifentanil; Deep sedation; TIVA
16.  Effect of two Different Concentrations of Propofol and Ketamine Combinations (Ketofol) in Pediatric Patients under Lumbar Puncture or Bone Marrow Aspiration 
Background
Ketamine is an anesthetic drug that is importantly analgesic without respiratory depression. Ketamine increases blood pressure and heart rate. Propofol is an anesthetic drug with good sedation, rapid recovery, but it causes respiratory depression, low heart rate and low blood pressure. Combination of Ketamine and Propofol provides sedation, analgesia and rapid recovery with hemodynamic stability and minimal respiratory depression. The aim of this study was to compare two different combinations of these two drugs to reach necessary sedation scale for the Lp or BMA in pediatric with ALL.
Materials and Methods
This randomized, double blinded study was designed to compare the quality of sedation and side effects of intravenous Ketofol on 60 patients of both gender. Patients received titrated injection of a solution containing combination of one part of Ketamine and two parts of Propofol (1:2) (group I) or one part of Ketamine and three parts of Propofol (1:3) (group II) to reach almost near 5 sedation level (using Ramsay Sedation Scale). Respiratory and hemodynamic profiles, amount of drug injected and side effects were recorded.
Results
These drug combinations were used on 60 children with a median age of 6.2 years. In this study, recovery time and hallucination was significantly high in group I, but in both groups hemodynamic were stable, amnesia was enough, and there was no respiratory depression.
Conclusion
Lower doses of Ketamine in these combinations have lower psycho mimetic side effects, and shorter recovery time.
PMCID: PMC3915440  PMID: 24575262
Ketamine; Propofol; Spinal Puncture; Pediatrics
17.  Comparison between the recovery time of alfentanil and fentanyl in balanced propofol sedation for gastrointestinal and colonoscopy: a prospective, randomized study 
BMC Gastroenterology  2012;12:164.
Background
There is increasing interest in balanced propofol sedation (BPS) titrated to moderate sedation (conscious sedation) for endoscopic procedures. However, few controlled studies on BPS targeted to deep sedation for diagnostic endoscopy were found. Alfentanil, a rapid and short-acting synthetic analog of fentanyl, appears to offer clinically significant advantages over fentanyl during outpatient anesthesia.
It is reasonable to hypothesize that low dose of alfentanil used in BPS might also result in more rapid recovery as compared with fentanyl.
Methods
A prospective, randomized and double-blinded clinical trial of alfentanil, midazolam and propofol versus fentanyl, midazolam and propofol in 272 outpatients undergoing diagnostic esophagogastroduodenal endoscopy (EGD) and colonoscopy for health examination were enrolled. Randomization was achieved by using the computer-generated random sequence. Each combination regimen was titrated to deep sedation. The recovery time, patient satisfaction, safety and the efficacy and cost benefit between groups were compared.
Results
260 participants were analyzed, 129 in alfentanil group and 131 in fentanyl group. There is no significant difference in sex, age, body weight, BMI and ASA distribution between two groups. Also, there is no significant difference in recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between two groups. Though deep sedation was targeted, all cardiopulmonary complications were minor and transient (10.8%, 28/260). No serious adverse events including the use of flumazenil, assisted ventilation, permanent injury or death, and temporary or permanent interruption of procedure were found in both groups. However, fentanyl is New Taiwan Dollar (NT$) 103 (approximate US$ 4) cheaper than alfentanil, leading to a significant difference in total cost between two groups.
Conclusions
This randomized, double-blinded clinical trial showed that there is no significant difference in the recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between the two most common sedation regimens for EGD and colonoscopy in our hospital. However, fentanyl is NT$103 (US$ 4) cheaper than alfentanil in each case.
Trial registration
Institutional Review Board of Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry (ChiCTR-TRC-12002575)
doi:10.1186/1471-230X-12-164
PMCID: PMC3607964  PMID: 23170921
Balanced propofol sedation; Alfentanil; Fentanyl; Deep sedation; Diagnostic endoscopy; Cost benefit
18.  Dose effects of triazolam and alcohol on cognitive performance in healthy volunteers 
Benzodiazepines and alcohol are widely used psychoactive substances that have performance-impairing effects. Research suggests that the impairment profiles for benzodiazepines and alcohol differ, though few cognitive psychopharmacological studies have directly compared these drugs. This double-blind, double-dummy, placebo-controlled, repeated measures study directly compared the acute dose effects of triazolam (0.125 mg, 0.25 mg/70 kg) and alcohol (0.40 g, 0.80 g/kg) in 20 social drinkers. At doses that produced comparable psychomotor impairment, triazolam was more likely to impair several objective measures of cognitive performance (e.g., episodic memory, divided attention) and to slow performance across several measures. However, only alcohol impaired accuracy on the digit symbol substitution and semantic memory tasks. In addition to objective measures, both drugs impaired awareness of performance impairments (i.e., metacognition) such that participants over-estimated impairment, and the magnitude of this effect was generally larger for alcohol. Only triazolam impaired other measures of metacognition (e.g., error detection on a choice reaction time task). Future research might examine the clinical implications of the performance impairments reported here given the widespread use of benzodiazepines and alcohol.
doi:10.1037/a0018407
PMCID: PMC2847582  PMID: 20158290
Performance; Cognition; Benzodiazepines; Triazolam; Alcohol
19.  Cognitive effects of intramuscular ketamine and oral triazolam in healthy volunteers 
Psychopharmacology  2012;226(1):53-63.
Rationale
Several studies have documented impairments in memory processes as a result of ketamine administration; however, few studies have compared the profile of cognitive effects of ketamine to other drugs.
Objectives
The aim of this study was to compare the cognitive effects of ketamine with those of triazolam in healthy volunteers.
Methods
Doses of ketamine (0.2, 0.4 mg/kg intramuscular (i.m.)), triazolam (0.2, 0.4 mg/70 kg p.o.), and double-dummy placebos were administered to 20 volunteers under repeated measures, counterbalanced, double-blind conditions. Peak physiological, psychomotor, subjective, and cognitive effects were examined.
Results
Ketamine impaired balance when balance was assessed early in the task order, whereas triazolam impaired psychomotor coordination and divided attention irrespective of task order. Triazolam also tended to produce greater effects on working memory and episodic memory tasks than ketamine at doses that produced lower subjective effects and higher estimates of performance.
Conclusions
Ketamine produces less cognitive impairment than triazolam at doses that produced greater subjective effects. Thus ketamine does not produce the underestimation of cognitive impairment typically seen with triazolam.
doi:10.1007/s00213-012-2883-x
PMCID: PMC3572303  PMID: 23096769
Ketamine; Triazolam; Cognitive; Memory; Psychomotor; Metacognition
20.  A comparison of midazolam and clonidine as an oral premedication in pediatric patients 
Background:
To compare oral midazolam (0.5 mg/kg) versus oral clonidine (4 μg/kg) as a premedication in pediatric patients aged between 2-12 years with regard to sedation and anxiolysis.
Methods:
Sixty pediatric patients belonging to the American Society of Anesthesiologists class I and II between the age group of 2-12 years scheduled for elective surgery were randomly allocated to receive either oral midazolam (group I) 30 min before induction or oral clonidine (group II) 90 min before induction of anesthesia. The children were evaluated for levels of sedation and anxiety at the time of separation from the parents, venepuncture, and at the time of mask application for induction of anesthesia.
Results:
After premedication, the percentage of children who were sedated and calm increased in both the groups. The overall level of sedation was better in the children in the clonidine group, but children in the midazolam group had a greater degree of anxiolysis at times of venepuncture and mask application. In addition, midazolam did not cause significant changes in hemodynamics unlike clonidine where a significant fall in blood pressure was noted, after premedication, but preinduction.
Conclusion:
We conclude that under the conditions of the study, oral midazolam is superior to clonidine as an anxiolytic in pediatric population. Clonidine with its sedative action especially at the time of separation from parents along with its other perioperative benefits cannot be discounted.
doi:10.4103/1658-354X.93045
PMCID: PMC3299128  PMID: 22412769
Anxiolysis; oral clonidine; oral midazolam; pediatric anesthesia; premedication; sedation
21.  Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration 
Objectives To investigate the effectiveness of non-benzodiazepine hypnotics (Z drugs) and associated placebo responses in adults and to evaluate potential moderators of effectiveness in a dataset used to approve these drugs.
Design Systematic review and meta-analysis.
Data source US Food and Drug Administration (FDA).
Study selection Randomised double blind parallel placebo controlled trials of currently approved Z drugs (eszopiclone, zaleplon, and zolpidem).
Data extraction Change score from baseline to post-test for drug and placebo groups; drug efficacy analysed as the difference of both change scores. Weighted raw and standardised mean differences with their confidence intervals under random effects assumptions for polysomnographic and subjective sleep latency, as primary outcomes. Secondary outcomes included waking after sleep onset, number of awakenings, total sleep time, sleep efficiency, and subjective sleep quality. Weighted least square regression analysis was used to explain heterogeneity of drug effects.
Data synthesis 13 studies containing 65 separate drug-placebo comparisons by type of outcome, type of drug, and dose were included. Studies included 4378 participants from different countries and varying drug doses, lengths of treatment, and study years. Z drugs showed significant, albeit small, improvements (reductions) in our primary outcomes: polysomnographic sleep latency (weighted standardised mean difference, 95% confidence interval −0.57 to −0.16) and subjective sleep latency (−0.33, −0.62 to −0.04) compared with placebo. Analyses of weighted mean raw differences showed that Z drugs decreased polysomnographic sleep latency by 22 minutes (−33 to −11 minutes) compared with placebo. Although no significant effects were found in secondary outcomes, there were insufficient studies reporting these outcomes to allow firm conclusions. Moderator analyses indicated that sleep latency was more likely to be reduced in studies published earlier, with larger drug doses, with longer duration of treatment, with a greater proportion of younger and/or female patients, and with zolpidem.
Conclusion Compared with placebo, Z drugs produce slight improvements in subjective and polysomnographic sleep latency, especially with larger doses and regardless of type of drug. Although the drug effect and the placebo response were rather small and of questionable clinical importance, the two together produced to a reasonably large clinical response.
doi:10.1136/bmj.e8343
PMCID: PMC3544552  PMID: 23248080
22.  Quality of life following third molar removal under conscious sedation 
Aim: The aim of this study was to assess quality of life (QoL) and degree of satisfaction among outpatients subjected to surgical extraction of all four third molars under conscious sedation. A second objective was to describe the evolution of self-reported pain measured in a visual analogue scale (VAS) in the 7 days after extraction. Study design: Fifty patients received a questionnaire assessing social isolation, working isolation, eating and speaking ability, diet modifications, sleep impairment, changes in physical appearance, discomfort at suture removal and overall satisfaction at days 4 and 7 after surgery. Pain was recorded by patients on a 100-mm pain visual analogue scale (VAS) every day after extraction until day 7. Results: Thirty-nine patients fulfilled correctly the questionnaire. Postoperative pain values suffered small fluctuations until day 5 (range: 23 to 33 mm in a 100-mm VAS), when dicreased significantly. A positive association was observed between difficult ranked surgeries and higher postoperative pain levels. The average number of days for which the patient stopped working was 4.9. Conclusion: The removal of all third molars in a single appointment causes an important deterioration of the patient’s QoL during the first postoperative week, especially due to local pain and eating discomfort.
Key words:Third molar removal, quality of life, sedation.
doi:10.4317/medoral.17677
PMCID: PMC3505722  PMID: 22926461
23.  The effects of preoperative anxiety on intravenous sedation. 
Anesthesia Progress  2004;51(2):46-51.
Anxiety is known to cause feelings of uneasiness, tension, and nervousness, and previous studies have noted that anxiety and its effects may have an effect on out-patient sedation for patients undergoing surgical procedures. In this study, we assess the effects of anxiety on 25 outpatients undergoing intravenous sedation for third molar extraction. Before the procedure, subjects completed the State-Trait Anxiety Inventory, and intraoperative patient movement was assessed using a subjective scale. We found that patients with a high level of preoperative anxiety had a greater degree of average intraoperative movement (P = .037) and also required a greater amount of propofol to maintain a clinically acceptable level of sedation (P = .0273) when compared with patients with less preoperative anxiety. Increased state anxiety and trait anxiety serve as predictors for an increased total dose requirement of propofol to maintain an acceptable level of sedation (r2 = 0.285, P = .0060, and r2 = 0.233, P = .0146, respectively). An increased level of trait anxiety was also a predictor of an increased degree of average intraoperative movement (r2 = 0.342, P = .0022). Patients who exhibit a high level of preoperative anxiety require a greater total dose of propofol to achieve and maintain a clinically acceptable level of sedation and are more prone to unwanted movement while under sedation.
PMCID: PMC2007471  PMID: 15366317
24.  Anxiety in Children Undergoing VCUG: Sedation or No Sedation? 
Advances in Urology  2008;2008:498614.
Background. Voiding cystourethrograms are distressing for children and parents. Nonpharmacological methods reduce distress. Pharmacological interventions for VCUG focus on sedation as well as analgesia, anxiolysis, and amnesia. Sedation has cost, time, and safety issues. Which agents and route should we use? Are we sure that sedation does not influence the ability to diagnose vesicoureteric reflux? Methods. Literature search of Medline, EMBASE, and the Cochrane Database. Review of comparative studies found. Results. Seven comparative studies including two randomised controlled trials were reviewed. Midazolam given orally (0.5-0.6 mg/kg) or intranasally (0.2 mg/kg) is effective with no apparent effect on voiding dynamics. Insufficient evidence to recommend other sedating agents was found. Deeper sedating agents may interfere with voiding dynamics. Conclusion. Midazolam reduces the VCUG distress, causes amnesia, and does not appear to interfere with voiding dynamics. Midazolam combined with simple analgesia is an effective method to reduce distress to children undergoing VCUG.
doi:10.1155/2008/498614
PMCID: PMC2443423  PMID: 18615194
25.  Flumazenil Reversal of Sublingual Triazolam: A Randomized Clinical Trial 
Background
Incremental sublingual triazolam has emerged as a popular sedation technique. Nevertheless, little research has evaluated the technique’s safety or efficacy. Given its popularity, an easily administered rescue strategy is needed.
Methods
We conducted an RCT to investigate how intraoral submucosal flumazenil (0.2 mg) attenuates CNS depression produced by incremental sublingual dosing of triazolam (3 doses of 0.25 mg over 90 minutes) in 14 adult subjects. Outcomes were assessed with the Observer Assessment of Alertness/Sedation (OAA/S) scale, BIS and physiological monitoring.
Results
OAA/S and BIS scores increased after flumazenil injection at the 30-minute observation point, but were not sustained. Six hours after the initial dose of triazolam (4 hours after flumazenil or placebo challenge), all could be discharged.
Conclusions
Deep sedation from sequential triazolam is incompletely reversed by a single intraoral injection. Reversal did not persist: discharge was at 360 minutes.
Clinical Implications
A single intraoral injection of flumazenil at 0.2 mg cannot be used to immediately rescue oversedation with triazolam. A larger dose might be effective. Reversal for discharging the patient early is neither appropriate nor safe.
PMCID: PMC2754714  PMID: 19411525
flumazenil; triazolam; sedation/sublingual; behavior/drug effects; dental anxiety/drug therapy; conscious sedation; patient safety

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