Pharmacoeconomic evaluation of flumazenil for routine outpatient EGD

BACKGROUND: Flumazenil is a benzodiazepine antagonist indicated for reversal of the sedative effects of benzodiazepines. Previous studies suggest that flumazenil may shorten recovery time after endoscopy, but there are few data on actual recovery room times and charges. METHODS: Fifty patients undergoing routine upper endoscopy were sedated with midazolam alone in the usual titrated manner. Patients were randomized in a double-blind fashion to receive either flumazenil or saline immediately after procedure. Assessments of responsiveness, speech, facial expression, and ptosis (Observer's Assessment of Alertness/Sedation [OAA/S] scale) were made before procedure, immediately after procedure and every 15 minutes thereafter. The patient was discharged from the recovery room when vital signs and OAA/S scale reached preprocedure levels. Recovery room times and charges were recorded. RESULTS: The flumazenil group demonstrated shorter recovery room times and recovery room charges than the placebo group (p < 0.001). The difference in recovery room charges was not statistically different when flumazenil charges were included (p = 0.09). CONCLUSIONS: The routine use of flumazenil after midazolam sedation for upper endoscopy significantly shortened recovery time and charges but did not statistically reduce overall charges.     

Combination of midazolam and flumazenil in upper gastrointestinal endoscopy, a doubleblind randomized study

We evaluated the clinical usefulness of flumazenil (formerly Ro15-1788), a benzodiazepine antagonist, in combination with midazolam in upper gastrointestinal endoscopy. Thirty outpatients were randomized into two groups: those receiving flumazenil and those receiving placebo after endoscopy. For sedation, only midazolam was used. Performances pre-sedation and post-sedation (at 30 and 60 min) were analyzed using the Trieger test, Number Connection test, and Digit Symbol test. Patients receiving flumazenil were fully alert and able to ambulate 5 min after injection with this medication. Performances at 30 min in the Trieger, Number Connection, and Digit Symbol tests were significantly better in the group receiving flumazenil, p less than 0.005, p less than 0.025, and p less than 0.01, respectively. No phlebitis, nausea, vomiting, or anxiety were noted. No resedation events were documented. We conclude that flumazenil can dramatically shorten the recovery period following sedation with midazolam in upper gastrointestinal endoscopy, and its use is not associated with major side effects.     

Flumazenil in children after esophagogastroduodenoscopy

OBJECTIVE: Our aim was to evaluate if the routine use of the benzodiazepine antagonist flumazenil would shorten postprocedure recovery times after esophagogastroduodenoscopy in pediatric patients receiving standard intravenous conscious sedation with the benzodiazepine diazepam in combination with meperidine. METHODS: Upper endoscopy was performed using intravenous conscious sedation with standardized doses of diazepam and meperidine on 29 children, age range 6-18 yr. Patients were randomized in a double-blind fashion to receive either intravenous normal saline (placebo) or 0.01 mg/kg (maximum, 1.0 mg) flumazenil within 5 min of procedure completion. Evaluation of the degree of sedation using a modified Observer' s Assessment of Alertness/Sedation Scale was performed presedation, immediately before reversal solution administration, and serially over 60 min after reversal solution injection. RESULTS: Fifteen patients received flumazenil and 14 received placebo; patient group composition did not vary significantly in age and weight. Fifty-four percent of flumazenil patients and 30% of control patients achieved full alertness within 10 min of reversal solution injection. However, this difference between groups was not significant (p > 0.45). Resedation or side effects directly attributable to flumazenil were not observed. CONCLUSIONS: A single postsedation dose of flumazenil is well-tolerated in children >6 yr old. However, its routine use after esophagogastroduodenoscopy is of questionable benefit in shortening recovery time in this age group.     

Mild sedation before transesophageal echo induces significant hemodynamic and respiratory depression

AIMS: Midazolam is often used for conscious sedation before transesophageal echo (TEE) studies. It is not clear to what extent midazolam administration or the insertion of the TEE probe itself is responsible for the respiratory and hemodynamic depression during TEE examinations. We compared the performance of TEE with versus without midazolam to elucidate the effects of each. METHODS: Patients were given the choice of having midazolam prior to their TEE. Thirty-one patients preferred to have sedation (Sed+) and 31 others declined sedation (Sed-). Both groups had SaO(2) and blood pressure measured before the study, following sedation (in Sed+) and at the end of the TEE study. RESULTS: Increase in HR was greater in Sed+ than in Sed- (12 +/- 19% vs 6 +/- 11%, both P < 0.05). There was a greater decrease in saturation of O(2) in Sed+ than in Sed- (3 +/- 3% vs 2 +/- 3%, both P < 0.05). Systolic blood pressure (SBP) increased in Sed- by 6 +/- 11% (P< 0.05) but dropped in Sed+ immediately after sedation (16 +/- 8%, P < 0.000001). Diastolic blood pressure decreased in Sed+ after sedation by 11 +/- 9% (P < 0.05). CONCLUSIONS: Midazolam sedation before TEE examinations causes more prominent tachycardia and depression of SaO(2)than insertion of the TEE probe alone. It also causes a substantial drop in SBP. Midazolam should be offered only to hemodynamically stable patients without preceding respiratory depression.     

Clinical evaluation of the short half-life injectable benzodiazepine midazolam, and of the specific antagonist flumazenil in upper digestive tract endoscopy.

In a first step, midazolam 0.1 mg/kg, midazolam 0.05 mg/kg and diazepam 0.15 mg/kg administered intravenously were blindly evaluated as a sedating preparation in 3 groups of each 30 patients undergoing gastroscopy. Although amnesia is better with midazolam 0.1 mg/kg, the induced sedation is protracted, which is not to be wished in ambulatory patients. On the other side, diazepam 0.15 mg/kg was locally less well tolerated. Taking into consideration the efficacy and the general and local tolerance, the dose of midazolam 0.05 mg/kg seems the best compromise. In a second step, the specific benzodiazepine antagonist flumazenil was blindly evaluated at two intravenous doses, 1 mg and 0.5 mg, against placebo for reversal of midazolam (0.1 mg/kg) induced sedation in gastroscopy patients. 1 mg of flumazenil (and to a lesser degree 0.5 mg) suppresses the sedation and amnesia induced by midazolam and normalizes attention and sensori-motor functions. However a certain degree of resedation can reappear 45-60 min. after the administration of flumazenil. Though this phenomenon did not alter the tests measuring attention and sensorimotor functions and the recovery of memory (contrary to placebo), it incites to be cautious when the drug is given to ambulatory patients.     

Impact of flumazenil on recovery after outpatient endoscopy: a placebo-controlled trial

BACKGROUND: Flumazenil is an imidazobenzodiazepine that blocks the central effects of benzodiazepines by competitive interaction at the receptor level. In this study we assessed the impact of flumazenil use on postsedation observation time in outpatients undergoing endoscopy. METHODS: Sixty outpatients received midazolam for conscious sedation and were randomized after endoscopy to receive intravenous flumazenil (0.1 mg/mL) or placebo until awake or a total of 10 mL was given. All patients were assessed using various psychomotor and cognitive tests at baseline and at 5, 15, 30, 45 and 60 minutes after flumazenil or placebo was administered. RESULTS: The two groups were similar in age, gender, midazolam dose (mg/kg), vital signs, and baseline parameters. The average dose of flumazenil given was 0.41 mg. Sedation scores returned to presedation levels earlier in the flumazenil group, with significant differences compared to placebo at 5 minutes (84.6% vs. 24.2%), 15 minutes (88. 5% vs. 57.6%) and 30 minutes (96.2% vs. 66.7%). Other parameters tested were not significantly different for patients receiving placebo compared to those given flumazenil. Sedation scores returned to baseline earlier than other psychomotor and cognitive tests in both groups. Flumazenil reduced the mean observation time from 23.5 minutes to 8.3 minutes (p < 0.0005), a difference of 15.2 minutes (64.7%) based on sedation score. CONCLUSIONS: Flumazenil significantly reduces postsedation observation time. Actual cost savings will vary depending on staff and facility capacity, patient volume, flumazenil cost, and unit cost of observation time.     

Double-blind controlled trial of flumazenil in patients who underwent upper gastrointestinal endoscopy

The antisedative effect of flumazenil, a benzodiazepine antagonist, was studied in a double-blind placebo controlled trial in 61 patients who underwent upper gastrointestinal endoscopy and sedation with benzodiazepines. The efficacy of flumazenil in reversing the effect of both benzodiazepines, diazepam and midazolam, was significantly higher than placebo (p less than 0.0001). The effect of flumazenil was prompt and was clearly noticed at the first assessment, 5 min after its administration. In none of the patients was a relapse of the sedative effect of the benzodiazepines noticed. The administration of flumazenil was free of major side effects. Flumazenil administration permits an earlier discharge of patients following endoscopy. Its availability in the endoscopy suite may improve the outcome of serious but rare side effects related to benzodiazepines.     

Delayed Flumazenil Injection after Endoscopic Sedation Increases Patient Satisfaction Compared with Immediate Flumazenil Injection

Background/Aims

Flumazenil was administered after the completion of endoscopy under sedation to reduce recovery time and increase patient safety. We evaluated patient satisfaction after endoscopy under sedation according to the timing of a postprocedural flumazenil injection.

Methods

In total, 200 subjects undergoing concurrent colonoscopy and upper endoscopy while sedated with midazolam and meperidine were enrolled in our investigation. We randomly administered 0.3 mg of flumazenil either immediately or 15 minutes after the endoscopic procedure. A postprocedural questionnaire and next day telephone interview were conducted to assess patient satisfaction.

Results

Flumazenil injection timing did not affect the time spent in the recovery room when comparing the two groups of patients. However, the subjects in the 15 minutes injection group were more satisfied with undergoing endoscopy under sedation than the patients in the immediate injection group according to the postprocedural survey (p=0.019). However, no difference in overall satisfaction, memory, or willingness to undergo a future endoscopy was observed between the two groups when the telephone survey was conducted on the following day.

Conclusions

This study demonstrated that a delayed flumazenil injection after endoscopic sedation increased patient satisfaction without prolonging recovery time, even though the benefit of the delayed flumazenil injection did not persist into the following day.     

Antagonizing the effect of midazolam by flumazenil in gastroscopy: results of a randomized double blind study

The action and side effects of the benzodiazepine antagonist Flumazenil were evaluated and compared with placebo in a double blind parallel group randomized trial involving 40 patients having upper gastrointestinal endoscopy under Midazolam premedication. Flumazenil reversed the hypnotic effect of midazolam within a few minutes. The patients were alert, cooperative, oriented and had recall of events after endoscopy. The effects were better than placebo concerning alertness for up to 30 minutes after administration whereas drowsiness remained almost stable after placebo. Time to reach full alertness was shorter after Flumazenil compared with placebo (42 vs 62 minutes). There were no significant side effects. Flumazenil allows effective reversal of midazolam premedication after upper gastrointestinal endoscopy.     

Is routine sedation or topical pharyngeal anesthesia beneficial during upper endoscopy?

BACKGROUND: Upper endoscopy is an invasive procedure. However, the benefits of routinely administered sedative medication or topical pharyngeal anesthesic are controversial. The aim of this study was to clarify their effects on patient tolerance and difficulty of upper endoscopy. METHODS: A total of 252 patients scheduled for diagnostic upper endoscopy were randomly assigned to 4 groups: (1) sedation with midazolam and placebo pharyngeal spray (midazolam group), (2) placebo sedation and lidocaine pharyngeal spray (lidocaine group), (3) placebo sedation and placebo pharyngeal spray (placebo group), and (4) no intravenous cannula/pharyngeal spray (control group). The endoscopist and the patient assessed the procedure immediately after the examination. Another questionnaire was sent to the patients 2 weeks later. RESULTS: Patients in the midazolam group rated the examination easier and less uncomfortable compared with those in the other groups. The differences were especially evident in the questionnaires completed 2 weeks after the examination ( p < 0.001). Lidocaine did not significantly improve patient tolerance. However, endoscopists found the procedure easier in patients in the lidocaine group compared with the midazolam ( p < 0.01) and control groups ( p < 0.01) but not the placebo group. CONCLUSIONS: Routine administration of midazolam for sedation increased patient tolerance for upper endoscopy. However, endoscopists found intubation to be more difficult in sedated vs. non-sedated patients. Topical pharyngeal anesthesia did not enhance patient tolerance, but it did make upper endoscopy technically easier compared with endoscopy in patients sedated with midazolam without topical pharyngeal anesthesia, and in patients who had no sedation or pharyngeal anesthesia, but not in patients who received placebo sedation and placebo pharyngeal anesthesia.     

Midazolam sedation for upper gastrointestinal endoscopy: comparison between the states of patients in partial and complete amnesia

BACKGROUND/AIMS: The amnesia produced by anesthesia is advantageous for unpleasant procedures like gastroscopy, and midazolam is one of the most commonly used anesthesias for endoscopy. However the proper use of midazolam from the viewpoint of complete amnesia has been discussed very little. METHODOLOGY: One hundred and thirty-three unselected patients about to undergo upper gastrointestinal endoscopy were premedicated with sufficient intravenous midazolam to cause enough sedation so that no response was evoked when calling their name. Pulse, arterial pressure, arterial oxygen saturation and the physical signs of patients were recorded continuously during the procedures. After the study, patients were given 0.25 mg of flumazenil and asked if they could recall the procedures. Those who could recall even part of the procedure were not regarded as achieving complete amnesia. The efficacy of the sedative was judged by the appearance of complete amnesia. RESULTS: From our regression analysis complete amnesia was achieved in 75.9% of the total patients. The differences of the blood pressure fall, pulse rate increase and arterial oxygen saturation fall between the patients with complete and partial amnesia were minute and did not cause serious complications. Regression analysis revealed the most important factors for the complete amnesia to be midazolam dose per body weight and habitual hypnotic use. CONCLUSIONS: There are no obvious disadvantages to producing complete amnesia with midazolam for upper gastrointestinal endoscopy. Habitual hypnotic use along with midazolam dose per body weight is the most influencing factor for that purpose.     

Diazepam versus midazolam (versed) in outpatient colonoscopy: a double-blind randomized study

Midazolam is a new parenteral benzodiazepine premedication for endoscopy. Consecutive patients were randomized to receive either intravenous midazolam or diazepam as premedication for outpatient total colonoscopy by one endoscopist. Fifty-five patients received diazepam (0.15 mg/kg) and 50 received midazolam (0.07 mg/kg). Both patient and endoscopist were blind to the study drug used. The two groups were similar with respect to age, sex, and indication for colonoscopy. Patients were rated by the endoscopist for degree of cooperation, sedation, and pain during examination. There was significantly more oversedation in the midazolam group than in the diazepam group (p less than 0.05). Immediate procedure recall was less in midazolam patients (p less than 0.005), but on repeat interview the next day there was no difference between the two groups concerning recall of the endoscopy. There was no significant difference between the two groups in the incidence of arm pain. We conclude that in a clinical setting, midazolam does not appear to offer any significant advantage over diazepam, except for cost. Midazolam carries an increased risk of oversedation when it is administered on a milligram per kilogram basis and should instead be titrated individually.     

A randomized, double-blind study of the use of droperidol for conscious sedation during therapeutic endoscopy in difficult to sedate patients

BACKGROUND: Droperidol has been used in combination with narcotics and benzodiazepines to achieve conscious sedation. We performed a randomized, double-blind, study of droperidol in patients at risk for difficult sedation scheduled for therapeutic endoscopy. METHODS: Patients with regular ethanol, narcotic, or benzodiazepine usage, suspected sphincter of Oddi dysfunction, or a history of difficult sedation were eligible for the study. Patients were randomized to receive either droperidol or placebo along with midazolam and meperidine as preprocedure sedation. Time to achieve sedation, interruptions due to undersedation, medication dosages, recovery time, and subjective assessments of sedation were recorded. RESULTS: One hundred one patients were randomized. The droperidol group had significantly fewer procedure interruptions and observer ratings of difficulty with sedation and required significantly less midazolam (23%) and meperidine (16%) than the placebo group. There were no significant differences in time to achieve sedation, incomplete procedures, procedure length, recovery room time, or complications. There were significantly higher observer ratings of the quality of sedation for patients who received droperidol. CONCLUSIONS: Droperidol is a useful adjunct to conscious sedation in patients who are difficult to sedate. Its use results in significantly fewer interruptions due to poor sedation and improved sedation ratings compared with sedation using midazolam and meperidine alone.     

Risk of sedation for diagnostic esophagogastroduodenoscopy in obstructive sleep apnea patients

AIM: To investigate whether patients with obstructive sleep apnea (OSA) are at risk of sedation-related complications during diagnostic esophagogastroduodenoscopy (EGD). METHODS: A prospective study was performed in consecutive patients with OSA, who were confirmed with full-night polysomnography between July 2010 and April 2011. The occurrence of cardiopulmonary complications related to sedation during diagnostic EGD was compared between OSA and control groups. RESULTS: During the study period, 31 patients with OSA and 65 controls were enrolled. Compared with the control group, a higher dosage of midazolam was administered (P = 0.000) and a higher proportion of deep sedation was performed (P = 0.024) in the OSA group. However, all adverse events, including sedation fail-ure, paradoxical responses, snoring or apnea, hypoxia, hypotension, oxygen or flumazenil administration, and other adverse events were not different between the two groups (all P > 0.1). Patients with OSA were not predisposed to hypoxia with multivariate logistic regression analysis (P = 0.068). CONCLUSION: In patients with OSA, this limited sized study did not disclose an increased risk of cardiopulmonary complications during diagnostic EGD under sedation.     

Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial

STUDY OBJECTIVES: To determine whether sedation with propofol would lead to shorter times to tracheal extubation and ICU length of stay than sedation with midazolam. DESIGN: Multicenter, randomized, open label. SETTING: Four academic tertiary-care ICUs in Canada. PATIENTS: Critically ill patients requiring continuous sedation while receiving mechanical ventilation. INTERVENTIONS: Random allocation by predicted requirement for mechanical ventilation (short sedation stratum, < 24 h; medium sedation stratum, > or = 24 and < 72 h; and long sedation stratum, > or = 72 h) to sedation regimens utilizing propofol or midazolam. MEASUREMENTS AND RESULTS: Using an intention-to-treat analysis, patients randomized to receive propofol in the short sedation stratum (propofol, 21 patients; midazolam, 26 patients) and the long sedation stratum (propofol, 4 patients; midazolam, 10 patients) were extubated earlier (short sedation stratum: propofol, 5.6 h; midazolam, 11.9 h; long sedation stratum: propofol, 8.4 h; midazolam, 46.8 h; p < 0.05). Pooled results showed that patients treated with propofol (n = 46) were extubated earlier than those treated with midazolam (n = 53) (6.7 vs 24.7 h, respectively; p < 0.05) following discontinuation of the sedation but were not discharged from ICU earlier (94.0 vs 63.7 h, respectively; p = 0.26). Propofol-treated patients spent a larger percentage of time at the target Ramsay sedation level than midazolam-treated patients (60.2% vs 44.0%, respectively; p < 0.05). Using a treatment-received analysis, propofol sedation either did not differ from midazolam sedation in time to tracheal extubation or ICU discharge (sedation duration, < 24 h) or was associated with earlier tracheal extubation but longer time to ICU discharge (sedation duration, > or = 24 h, < 72 h, or > or = 72 h). CONCLUSIONS: The use of propofol sedation allowed for more rapid tracheal extubation than when midazolam sedation was employed. This did not result in earlier ICU discharge.     

Comparison of midazolam with or without fentanyl for conscious sedation and hemodynamics in coronary angiography

OBJECTIVE: To compare the hemodynamic and sedative effects of midazolam - with or without fentanyl combination - with placebo in coronary angiography. DESIGN: Prospective, double-blind, randomized study. SETTING: University medical centre. PATIENTS: All patients undergoing coronary angiography. INTERVENTIONS: Demographic data, hemodynamic variables, sedation and anxiety scores, amnesia, patient and cardiologist satisfaction, and adverse effects were evaluated and compared among coronary angiography patients taking midazolam, midazolam and fentanyl, or placebo before the procedure. MAIN RESULTS: Ninety patients scheduled for coronary angiography were randomly assigned into three groups: a midazolam-placebo group (group MP), a midazolam-fentanyl group (group MF) and a placebo group (group P). Hemodynamic stability was better in each sedation group (groups MP and MF) than in group P. Sedation scores, anxiolysis, and patient and cardiologist satisfaction were not different between the sedation groups. CONCLUSIONS: Both techniques of conscious sedation - midazolam and midazolam with fentanyl - are satisfactory for coronary angiography where hemodynamic stability and patient cooperation are required. In such procedures, local anesthesia without sedation may lead to hypertension and increase overall morbidity.     

Is routinely given conscious sedation of benefit during colonoscopy?

BACKGROUND: Sedative drugs are generally given to patients undergoing colonoscopy. However, the benefit of routinely administered conscious sedation for colonoscopy has not been studied in adequately controlled trials. METHODS: We randomly assigned 180 patients scheduled for diagnostic colonoscopy into 3 groups: (1) sedation with intravenous midazolam (midazolam group); (2) sedation with intravenous saline (placebo group); and (3) no intravenous cannula (control group). The endoscopist assessed the procedure immediately after the examination. The patients completed a questionnaire before leaving the endoscopy unit. Another questionnaire was sent to the patients 2 weeks after the examination. Answers were mainly given on a 100 mm visual analog scale. RESULTS: Shortly after the procedure, the patients in the midazolam group rated the examination less difficult than those in the placebo group (30 vs. 40 mm; p < 0.05; visual analog scale, 0 to 100 mm: 0 = not at all, 100 = extremely). However, no significant difference was found between midazolam and control groups (30 vs. 36 mm, respectively). Otherwise, there were no differences between the three groups with respect to the patients' or endoscopists' assessments or the examination time. CONCLUSIONS: Routinely administered sedation does not markedly increase patient tolerance or make colonoscopy technically easier.     

Sufentanil-midazolam anesthesia for coronary artery surgery

The combination of benzodiazepines and high-dose narcotics has been reported to produce hypotension in patients undergoing coronary artery surgery. This study was performed to evaluate the cardiovascular effects of lower doses of the narcotic sufentanil administered with the benzodiazepine midazolam. Thirty adult patients with good ventricular function undergoing elective coronary revascularization received sufentanil, 2.5 μg/kg, and midazolam, 0.1 mg/kg, followed by infusions of sufentanil; 0.7 to 1.5 μg/kg/h, and midazolam, 0.07 to 0.15 mg/kg/h. Overall, stable hemodynamics were achieved before and after cardiopulmonary bypass (CPB). Patients who were not receiving preoperative β-adrenergic blockade (n = 15) had increases from baseline heart rate and rate-pressure product after sternotomy, during aortic dissection, and after CPB that were not clinically significant. Five patients developed hypertension (increases greater than 20% over the baseline value), which was controlled with additional sufentanil or a vasodilator. Hypertension requiring vasodilator therapy did not occur in patients taking β-adrenergic blockers. Blood pressure decreases exceeding 20% of the baseline value did not occur. Two of 15 patients receiving β-blockers, versus 3 of 15 not receiving β-blockers, developed ischemic electrocardiographic changes before CPB (NS): one of these patients without β-blockade had a postoperative myocardial infarction. The results of this study show that the infusion of low doses of sufentanil with midazolam provides a hemodynamically safe and stable anesthetic for coronary artery surgery and avoids the hypotension seen when a high-dose narcotic is combined with a benzodiazepine.     

Does midazolam alter the clinical effects of intravenous ketamine sedation in children? A double-blind, randomized, controlled, emergency department trial

STUDY OBJECTIVE: This study was conducted to investigate the frequency and severity of adverse effects, specifically emergence phenomena, experienced by patients receiving intravenous ketamine with or without midazolam for sedation in a pediatric emergency department. METHODS: Patients aged 4.5 months to 16 years receiving ketamine sedation were prospectively enrolled in a double-blind, randomized, controlled study at a university-affiliated children's hospital-pediatric ED. All patients received ketamine (1 mg/kg) and glycopyrrolate (5 microgram/kg) intravenously. Patients were randomly assigned to receive midazolam (0.1 mg/kg) intravenously or no midazolam. Total time of sedation, sedation efficacy, and adverse effects were recorded. Adverse effects were compared between patients receiving ketamine versus those who received ketamine and midazolam. Additional comparisons were made based on age and number of ketamine doses administered. RESULTS: Two hundred sixty-six patients were studied; 129 received ketamine and 137 patients received ketamine and midazolam. Time of sedation and efficacy of sedation were equivalent between groups. Overall, adverse effects with ketamine sedation included respiratory events (12 [4.5%]), vomiting (50 [18.7%]), emergence phenomena in the pediatric ED (71 [26.7%]), and emergence phenomena at home (60 [22.4%]). Significant emergence phenomena in the pediatric ED (ie, nightmares, hallucinations, and severe agitation) occurred in 7.1% of the ketamine group and in 6.2% of the ketamine-midazolam group, a rate difference of 0.8 (95% confidence interval [CI] -5.3 to 7.0). The addition of midazolam led to an increased incidence of oxygen desaturation events (ketamine 1.6% versus ketamine-midazolam 7.3%; rate difference -5.7, 95% CI -10.6 to -0.9) but a decreased incidence of vomiting (ketamine 19.4%, ketamine-midazolam 9.6%, rate difference 9.8, 95% CI 1.4 to 18.2). The incidence of emergence phenomena and significant emergence phenomena was not affected by the addition of midazolam. However, the addition of midazolam was associated with more agitation in the pediatric ED in children 10 years or older (ketamine 5.7% versus ketamine-midazolam 35.7%; rate difference -30.0, 95% CI -10.7 to -49.3). Age breakdown further showed 6.3% (95% CI 0.9 to 11.6) more episodes of oxygen desaturation in the ketamine-midazolam group in children younger than 10 years, and 12.1% (95% CI 1.5 to 22.6) more vomiting episodes in the ketamine group in children younger than 10 years. CONCLUSION: Ketamine and combined ketamine and midazolam provided equally effective sedation. The addition of midazolam did not alter the incidence of emergence phenomena. Vomiting occurred more frequently in the ketamine only group, whereas oxygen desaturation occurred more frequently in the ketamine-midazolam group. These findings were more pronounced in patients younger than 10 years. Parental and physician satisfaction remained high for all patients receiving intravenous ketamine sedation.