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PubMed1994

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Dental↗

PubMed1990

[Total intravenous anesthesia with continuous infusion of midazolam--study on plasma levels of midazolam and catecholamines].

Total intravenous anesthesia was performed with continuous infusion of midazolam and bolus injection of fentanyl. A bolus injection of midazolam 0.3 mg.kg-1 was followed by an infusion regimen with an initial infusion rate of 0.68 mg.kg-1.hr-1 for 15 min followed by a maintenance infusion of 0.125 mg.kg-1.hr-1 and infusion was stopped at about 30 min before the end of operation. Fentanyl and pancuronium were injected as required. Nicardipine was given for intraoperative hypertension. Plasma concentrations of epinephrine and norepinephrine decreased significantly at 10 min after induction, but increased significantly during operation. Therefore, this anesthetic method was considered not to be so deep. Plasma concentrations of midazolam were higher than 200 ng.ml-1 during operation. After discontinuation of midazolam infusion, its concentration decreased quickly, and the elimination half life of midazolam was 1.675 +/- 0.2807 hr. The value was not so large as we had anticipated. Total intravenous anesthesia with continuous infusion of midazolam and bolus injection of fentanyl is thought to produce light anesthesia. Plasma concentration of midazolam decreased quickly.

Adult↗

PubMed1996

Efficacy and safety of combined meperidine and midazolam for EGD sedation compared with midazolam alone.

BACKGROUND/AIMS: Safety concerns have been raised about the use of the combination of an opioid and benzodiazepine for esophagogastroduodenoscopy (EGD) sedation, a common practice of American gastroenterologists. If we could show that patients in American practice settings satisfactorily tolerate EGD with midazolam alone, as is commonly done in Europe, it would provide impetus for American gastroenterologists to change practice habits. METHODS: We performed a randomized, double-blind trial to determine whether meperidine, used in addition to midazolam, improved patient tolerance to EGD compared with the use of midazolam alone in our academic practice setting. Safety parameters were also examined. One hundred twenty adult patients undergoing diagnostic EGD were randomized to receive either 50 mg of meperidine (group I) or 1 mg of midazolam (group II). Patients were then given additional midazolam in incremental doses at the discretion of the attending gastroenterologist to induce a state of conscious sedation. RESULTS: Including the study drug, patients in group I received an average of 1.8 mg less of midazolam compared with group II (mean total midazolam dose, 3.8 mg vs 5.6 mg; p = 0.037). Patients in group I showed improved tolerance for EGD compared with those in group II in terms of a physician rating of "poor" for the overall adequacy of sedation (7 vs 20%, p = 0.033), the need for supplemental narcotics or droperidol during the procedure (7 vs 20%, p = 0.033), the need for additional medication during intubation of the esophagus (12 vs 25%, p = 0.06), the need for a faculty member to accomplish esophageal intubation (7 vs 20%, p = 0.051), the presence of retching, which interfered with the procedure (21 vs 39%, p = 0.046), and premature termination of the exam (0 vs 7%, p = 0.055). No difference was seen in the degree of amnesia, in the willingness of patients to undergo another EGD in the future, or in cardiorespiratory parameters. CONCLUSIONS: In our academic practice setting, 50 mg of meperidine given i.v. at the start of the procedure improved the ability of our patients to tolerate EGD from the endoscopists' standpoint. We found no difference in cardiorespiratory parameters between the groups.

Adolescent↗

PubMed1993

Differential sensitivity to midazolam discriminative-stimulus effects following self-administered versus response-independent midazolam.

Interactions between the discriminative and reinforcing effects of midazolam were studied in two baboons trained to discriminate midazolam (0.32 mg/kg, IV) from saline. The midazolam generalization gradient determined after the baboons were permitted to self-administer midazolam (IV) was shifted to the left of that determined before self-administration. In contrast, the midazolam generalization gradient determined after the same doses of midazolam were delivered response-independently, but in the same order and with the same temporal pattern as during self-administration, was shifted to the right of that determined just before the response-independent phase. These data suggest that sensitivity to the discriminative-stimulus effects of a drug can be modulated by behavioral experience with that drug.

Animals↗

PubMed2000

Auditory and electroencephalographic effects of midazolam and alpha-hydroxy-midazolam in healthy subjects.

AIMS: Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in six healthy volunteers in a randomized, double-blind, three-way cross-over study. METHODS: Acoustically evoked short (SLP) and middle (MLP) latency potentials, transitory evoked otoacoustic emissions (TEOAE), and EEG power spectra were analysed after short i. v. injections of placebo, or 0.15 mg kg-1 midazolam, or alpha-hydroxy-midazolam, respectively. RESULTS: All subjects fell asleep during the 4 min infusion of active drug. SLP showed a significant transient increase of Jewett wave V 10 min after injection for midazolam and alpha-hydroxy-midazolam while the latency of wave I was unchanged. Both benzodiazepines induced a marked and long-lasting MLP amplitude decrease for 240 min with slow recovery over the following 360 min. No changes of TEOAE were observed. In agreement with earlier reports, increases in EEG beta activity and decreases in alpha activity were observed after administration of either drug. CONCLUSIONS: Systemically administered benzodiazepines modulate the auditory pathway above the level of the cochlea. While SLP changes were closely associated with sedation and high plasma benzodiazepine concentrations, MLP effects persisted for hours after sedation even at low benzodiazepine plasma levels. Evoked potentials may therefore be more sensitive than EEG as a tool to monitor benzodiazepine effects.

Adult↗

PubMed2002

A comparison of two different doses of ketamine with midazolam and midazolam alone as oral preanaesthetic medication on recovery after sevoflurane anaesthesia in children.

BACKGROUND: This investigation prospectively evaluated the effect of oral premedication of two different doses of ketamine with midazolam and midazolam alone on the recovery of children after sevoflurane anaesthesia. METHODS: In a randomized, double-blind study, 79 children (aged 1-8 years, ASA physical status I or II) were assigned to receive one of three premedications in a volume of 0.5 ml x kg(-1): group 1 received midazolam 0.5 mg x kg(-1) (MD); group 2 received midazolam 0.5 mg x kg(-1) with ketamine 1.8 mg x kg(-1) (MK-1); and group 3 received midazolam 0.5 mg x kg(-1) with ketamine 3 mg x kg(-1) (MK-2). The reactions of the children during administration were noted. Anaesthesia was induced by facemask with incremental sevoflurane administration. All children received alfentanil (15 micro g x kg(-1)). Tracheal intubation was facilitated by mivacurium (0.2 mg x kg(-1)). Anaesthesia was maintained with sevoflurane and an additional dose of alfentanil, if necessary. During recovery, the time interval between discontinuation of anaesthesia and arousal (spontaneous ventilation, extubation) were recorded. RESULTS: Emergence (spontaneous ventilation, extubation) and recovery times (discharge, Aldrete score=9) did not differ significantly between groups (P=0.24, P=0.59 and P=0.145, respectively). CONCLUSIONS: The combination of midazolam and ketamine as oral preanaesthetic medication did not significantly affect the recovery time of children after sevoflurane anaesthesia.

Administration, Oral↗

PubMed2003

Midazolam premedication in children: a comparison of two oral dosage formulations on sedation score and plasma midazolam levels.

We compared two available oral formulations of midazolam with respect to sedation score and plasma midazolam levels in pediatric surgical patients 2-10 yr old. The commercially available oral syrup was compared with a mixture of the IV midazolam preparation in Syrpalta syrup at an equivalent concentration of 2 mg/mL. ASA status I-II patients were randomly assigned to receive 0.5 mg/kg of either the commercial syrup (Group 1) or the prepared mixture (Group 2) as anesthetic premedication. Observer's Assessment of Alertness/Sedation scores were obtained by a blinded observer at 15 and 30 min after drug administration. Plasma midazolam levels were acquired exactly 45, 60, and 90 min after administration. Group 2 patients had a significantly lower median Observer's Assessment of Alertness/Sedation score (Group 1, 17; Group 2, 15) at 30 min (P < 0.03) and significantly higher mean plasma midazolam levels at all three acquisition times (mean +/- SD) (45 min: 63.1 +/- 23.9 ng/mL, Group 2; 43.4 +/- 19.6 ng/mL, Group 1; 60 min: 45.8 +/- 18.2 ng/mL, Group 2; 30.8 +/- 17.9 ng/mL, Group 1; 90 min: 28.9 +/- 12.6 ng/mL, Group 2; 21.0 +/- 8.9 ng/mL, Group 1) (P < 0.02). We conclude that IV midazolam mixed in Syrpalta syrup yields more reliable sedation and correspondingly higher plasma levels than an equivalent dose of the commercially formulated and marketed preparation.

Administration, Oral↗

PubMed2005

Comparison of a combination of midazolam and diazepam and midazolam alone as oral premedication on preanesthetic and emergence condition in children.

BACKGROUND: Preanesthetic anxiety and emergence agitation are major challenges for anesthesiologists in pediatric anesthesia. Thus, midazolam has been used as premedication for children. However, midazolam alone is not effective for emergence agitation. The present study tested the effect of a combination of midazolam and diazepam on the preanesthetic condition and emergence behavior in children. METHODS: Forty-two children were allocated to one of three groups: the NoPre group received no premedication; the Mi group received midazolam 0.5 mg kg(-1) orally; and the Mi + Di group received midazolam 0.25 mg kg(-1) and diazepam 0.25 mg kg(-1) orally. When anesthesia was induced with 7% sevoflurane in 100% oxygen, qualities of mask induction and sedation were rated. Anesthesia was maintained with sevoflurane (3-5%) in 100% oxygen. During emergence from anesthesia, the score of the child's emergence behavior was rated. RESULTS: Children in the Mi and Mi + Di groups were more sedated than those in the NoPre group. A combination of midazolam and diazepam provided a better quality of mask induction, when compared with no premedication. Also, the children in the Mi + Di group were less agitated than those in the other groups during the emergence. CONCLUSION: Children in the Mi + Di group were significantly more sedated at induction of anesthesia and less agitated during emergence from anesthesia.

Adenoidectomy↗

PubMed2003

Possibility of influence of midazolam sedation on the diagnosis of brain death: concentrations of active metabolites after cessation of midazolam.

Midazolam and its active metabolites have a depressant effect on respiration and consciousness level, and therefore their effects should be considered in all patients for whom brain death testing is contemplated. The concentrations of midazolam and its active metabolites were measured in critically ill patients on a ventilator during and after continuous intravenous infusion of midazolam. Three days after cessation of midazolam infusion, the concentrations of midazolam and 1-hydroxymidazolam decreased to below the therapeutic range (100-1000 ng/ml) in all patients, although the concentrations of 1-hydroxymidazolam glucuronide remained extremely high in a patient who showed deteriorating renal function. The concentrations of 1-hydroxymidazolam glucuronide (19,497-29,761 ng/ml) were measured in this patient. When it is impossible to confirm factors consistent with irreversible brain death, such as the lack of cerebral blood flow, until 3 days after cessation of midazolam infusion, monitoring of the concentration of these substances should be carried out in all patients in whom suspicion exists prior to the evaluation of brain death. It is particularly imperative that monitoring of the 1-hydroxymidazolam glucuronide concentration be carried out in patients with poor renal function.

Adult↗

PubMed2002

A randomized, clinical trial of oral midazolam plus placebo versus oral midazolam plus oral transmucosal fentanyl for sedation during laceration repair.

OBJECTIVE: To determine whether a combination of oral transmucosal fentanyl (Fentanyl Oralet, Abbott Laboratories, North Chicago, IL) plus oral midazolam has an acceptable safety profile and is more effective than oral midazolam alone for sedation during laceration repair in a pediatric emergency department (ED). METHODS: Randomized, double-blind, placebo-controlled, clinical trial. Patients between 2 and 8 years of age who weighed >10 kg and presented to the ED with a laceration in need of repair under sedation were eligible for inclusion. All patients received oral midazolam (0.5 mg/kg; maximum dose 10 mg) and either fentanyl (5-10 microg/kg) or placebo in oralet form. Data collected every 5 minutes included the following: heart rate, oxygen saturation, respiratory rate, pain as measured on a Children's Hospital of Eastern Ontario Pain Score (CHEOPS) scale (range: 4-13), and an activity scale (range: 1-5). Effectiveness of sedation was measured by CHEOPS and activity scores compared between the treatment groups. RESULTS: Fifty-one patients were randomized to receive oral midazolam plus fentanyl (N = 28) or oral midazolam plus placebo (N = 23). Age, weight, gender, or baseline pain and activity scores did not differ between the 2 groups. Seven patients in the fentanyl group vomited compared with 0 patients in the placebo group. Three patients in the fentanyl group and no patients in the placebo group had brief oxygen saturation below 93% on room air. The mean pain score within 5 minutes of the start of the procedure did not differ between the 2 groups (fentanyl group, 9.4 versus placebo group, 8.8). Mean activity scores within 5 minutes of the start of the procedure were also similar (fentanyl group, 4.3 versus placebo group, 4.3). CONCLUSIONS: The addition of oral transmucosal fentanyl to oral midazolam did not improve pain or activity scores in pediatric patients given sedation for laceration repair. Patients who received Fentanyl Oralet suffered significantly more side effects despite the relatively low doses administered in this study. Oral transmucosal fentanyl should not be used for procedural sedation in the ED.

Adjuvants, Anesthesia↗

PubMed1984

Clinical comparison of midazolam hydrochloride and midazolam maleate for anesthesia induction.

The current study was undertaken to determine whether the same doses (mg/kg) of 5 mg/ml of midazolam hydrochloride and 2.5 mg/ml of midazolam maleate are required for the induction of anesthesia. Midazolam hydrochloride and midazolam maleate were compared in a prospective double-blind fashion, in which both cardiopulmonary and sedative effects were measured in 12 patients who required repeated anesthesia for serial gynecologic radium insertions. The results showed no significant differences in clinical activity between midazolam maleate and the newer preparation, midazolam hydrochloride. Time of onset, recovery time, lack of venous irritation, and stability of cardiopulmonary variables when using the hydrochloride were essentially the same with the maleate.

Adult↗

PubMed1995

150 mg fluconazole does not substantially increase the effects of 10 mg midazolam or the plasma midazolam concentrations in healthy subjects.

Fluconazole, an azole antifungal agent, moderately inhibits the CYP3A-mediated metabolism of midazolam in vitro. We therefore studied whether such an interaction takes place in vivo following oral administration of these drugs, given as relevant double blinded doses in capsule form. In study I parallel groups of healthy subjects received oral midazolam 10 mg (MID 10) or 15 mg (MID 15), placebo, or MID 10 mg + 150 mg fluconazole (FLU) given 2 h earlier. Objective and subjective performance tests were made before, and 30 and 90 min after the intake of midazolam. MID 10 and MID 15 moderately impaired performance on digit symbol substitution, letter cancellation and flicker fusion tests, and visual analogue scales revealed mild sedation. FLU + MID 10 had similar or slightly stronger effects than MID 10; it differed from MID 10 in that it lowered the flicker fusion threshold and produced subjective slowness and overall impairment. In study II 5 subjects received MID 10 after placebo, after FLU, and after 750 mg erythromycin (ERY) at 1-week intervals, following a crossover and double-blinded study design. Blood was sampled before MID intake and 30, 60 and 90 min after it, and performance was measured. FLU and ERY increased the effect of MID on flicker fusion and letter cancellation performances, and increased the HPLC-assayed plasma midazolam (ERY + 100%, FLU + 50%) in comparison to that measured after MID ingested alone. When the concentrations of midazolam together with its active metabolite alpha-OH-midazolam were assayed by radioreceptor technique the increases caused by ERY and FLU were less and compatible with the pharmacodynamic data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2001

The comparison of midazolam and topical lidocaine spray versus the combination of midazolam, meperidine, and topical lidocaine spray to sedate patients for upper endoscopy.

BACKGROUND: Whether an opiate-benzodiazepine combination is superior to benzodiazepine alone for sedation in upper endoscopy is controversial. The purpose of this study was to compare the effectiveness of intravenous midazolam alone versus the combination of intravenous midazolam and intravenous meperidine for the sedation of patients undergoing upper endoscopy. METHODS: One hundred seven patients scheduled for outpatient diagnostic esophagogastroduodenoscopy were randomly assigned to receive 50 mg intravenous meperidine (53 of 107) or placebo (54 of 107). All patients received topical lidocaine spray and as much midazolam as the endoscopist thought the patient needed. Patients and endoscopists were blinded as to assignment. Data collected included intubation time (seconds), procedure time (minutes), pulse, blood pressure, complications, and the need for reversal agents. The endoscopist evaluated the quality of sedation immediately after the procedure (1 = excellent, 2 = good, 3 = fair, and 4 = poor). The patient evaluated the procedure the next day by phone (1 = no discomfort or did not remember, 2 = slightly uncomfortable, 3 = extremely uncomfortable, and 4 = unacceptable). Patients were also asked whether they would agree to another esophagogastroduodenoscopy if their doctor thought it was medically necessary. RESULTS: The intubation time, procedure time and blood pressure were not significantly different between the 2 groups. In comparing the meperidine group versus placebo group, the highest pulse (82.3 vs. 93.7, p = 0.0010), lowest pulse (67.2 vs. 72.3, p = 0.0194) and amount of midazolam used (4.0 vs. 4.8 mg, p = 0.0185 or 0.53 vs. 0.67 mg/kg, p = 0.0083) were significantly different by using a t test analysis. Patient evaluations comparing meperidine versus placebo showed responses of 1 (52 vs. 49), 2 (1 vs. 3), 3 (0 vs. 2) and 4 (0 vs. 0), which were not significantly different. The endoscopists'evaluation comparing meperidine versus placebo gave responses of excellent (44 vs. 27), good (6 vs. 22), fair (3 vs. 5) and poor (0 vs. 0), which were highly significantly different (p < 0.001) by using chi-square statistical techniques. CONCLUSION: The addition of meperidine to midazolam in sedating patients undergoing upper endoscopy adds no benefit from the patient viewpoint, whereas endoscopists favored the use of both medications.

Administration, Topical↗

PubMed2003

Single bolus of midazolam versus bolus midazolam plus meperidine for colonoscopy: a prospective, randomized, double-blind trial.

BACKGROUND: The aim of this study was to determine whether a single bolus of meperidine in addition to midazolam improves patient tolerance during colonoscopy. METHODS: Consecutive patients undergoing outpatient colonoscopy were randomly assigned in double-blind fashion to receive a single rapid intravenous bolus of 5 mg of midazolam and placebo (Group A, n = 125) or 5 mg midazolam plus 50 mg meperidine (Group B, n = 128). Tolerance (4-point scale: 1 excellent, 4 unbearable), pain (4-point scale: 1 none, 4 severe) and willingness to undergo another colonoscopy were assessed 24 to 48 hours later in a telephone interview conducted by an independent observer blinded to the regimen of sedative medication. RESULTS: Significantly more patients in Group A reported moderate or severe pain (28% vs. 9%; p < 0.001), poor or unbearable tolerance (18% vs. 6%; p < 0.01) and unwillingness to undergo colonoscopy again in the future (14% vs. 5%; p < 0.05). By multivariate analysis, randomization to the midazolam group and younger age were the only variables independently associated with the risk of reporting at least one of these outcomes. Recovery time, frequency of oxygen desaturation, and need for supplemental oxygen were not significantly different between the 2 groups. CONCLUSIONS: The addition of a single bolus of meperidine to midazolam improves patient tolerance and lessens pain during colonoscopy without significantly increasing the frequency of side effects or prolonging recovery time.

Analgesics, Opioid↗

PubMed1995

A comparison of sedation techniques for outpatient rhinoplasty: midazolam versus midazolam plus ketamine.

A total of 859 patients presenting for outpatient rhinoplasty were divided into two groups that received intravenous sedation of midazolam 0.1 mg/kg either with or without ketamine 0.4 to 0.5 mg/kg immediately prior to conduct of the local anesthetic injections and surgery. Additional midazolam was given intraoperatively as needed. No patient received narcotic either as premedication or intraoperatively. Patients were evaluated by the surgeon on their response to the injections and surgery, and patients were given a questionnaire 1 week postoperatively to examine their response to and recall of the procedure. Scoring by both the surgeon and patients revealed that the great majority of patients in both groups had adequate "sedation." Patients from both groups related a high degree of satisfaction (> 90 percent) with the technique of sedation. The differences between the two study groups achieved statistical significance only on 4 of the 12 parameters investigated. Those who had received only midazolam were less likely to vocalize during the surgery or to experience the procedure as being of undue duration. Those who had also received ketamine had a lesser chance of remembering the local anesthetic injections (11.1 versus 19.8 percent) and a lesser likelihood of being dissatisfied with their surgical experience (3.3 versus 7.4 percent). In conclusion, the use of an opioid-free sedative technique of intravenous midazolam was highly successful in meeting the needs of both patients and surgeons. The addition of a single preblock dose of intravenous ketamine to intravenous midazolam sedation for rhinoplasty does not improve intraoperative conditions for the surgeon in terms of patient behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Premedication with midazolam in children. Effect of intranasal, rectal and oral routes on plasma midazolam concentrations.

We report a study performed to compare the time and plasma drug concentrations necessary to achieve a similar state of sedation after midazolam premedication given by various routes in children of 2-5 years old. Children were randomly allocated to one of three groups to receive midazolam 0.2 mg.kg-1 given intranasally, 0.5 mg.kg-1 given orally or 0.3 mg.kg-1 given rectally. Sedation was measured regularly until venepuncture was possible in a cooperative child. At this time, a first blood sample was taken to measure plasma concentration, followed by another 10 min later. Anaesthesia consisted of intravenous propofol supplemented with regional analgesia. At recovery from anaesthesia, a third blood sample was taken. Adequate sedation occurred sooner (7.7, SD 2.4 min) with intranasal than oral (12.5, SD 4.9 min) or rectal (16.3, SD 4.2 min) midazolam. The initial blood levels were lower when the drug was given by the alimentary routes despite higher doses (146, SD 51 ng.ml-1 in 11.5, SD 3.9 min; 104, SD 34 ng.ml-1 in 21 +/- 6 min; and 93, SD 63 ng.ml-1 in 23.1, SD 3.5 min for the intra nasal, rectal and oral routes respectively). Duration of surgical procedures, and of propofol infusion, and recovery from anaesthesia was similar for the three groups. The only problem arose in a 30-month-old boy in the intranasal group who developed respiratory depression with a plasma midazolam concentration of 169 ng.ml-1. Intranasal midazolam is an excellent alternative for rapid premedication provided that respiratory monitoring is used.

Administration, Intranasal↗

PubMed2001

Intravenous ketamine plus midazolam is superior to intranasal midazolam for emergency paediatric procedural sedation.

OBJECTIVES: This study compared intranasal midazolam (INM) with a combination of intravenous ketamine and intravenous midazolam (IVKM) for sedation of children requiring minor procedures in the emergency department. METHOD: A single blinded randomised clinical trial was conducted in the emergency department of a major urban paediatric hospital. Subjects requiring sedation for minor procedures were randomised to receive either INM (0.4 mg/kg) or intravenous ketamine (1 mg/kg) plus intravenous midazolam (0.1 mg/kg). Physiological variables and two independent measures of sedation (Sedation Score and Visual Analogue Sedation Scale) were recorded before sedation and at regular intervals during the procedure and recovery period. Times to adequate level of sedation and to discharge were compared. RESULTS: Fifty three patients were enrolled over a 10 month period. Sedation was sufficient to complete the procedures in all children receiving IVKM and in 24 of the 26 receiving INM. Onset of sedation was an average of 5.3 minutes quicker with IVKM than with INM (95%CI 3.2, 7.4 minutes, p<0.001). Children given INM were discharged an average of 19 minutes earlier than those given IVKM (95%CI 4, 33 minutes, p=0.02). Mean Sedation Scores and Visual Analogue Sedation Scale scores for the 30 minutes after drug administration were significantly better in children given IVKM compared with INM (2.4 and 1.8 versus 3.5 and 3.8, respectively). Both doctors and parents were more satisfied with sedation by intravenous ketamine and midazolam. CONCLUSIONS: Intravenous ketamine plus midazolam used in an appropriate setting by experienced personnel provides an excellent means of achieving sedation suitable for most non-painful minor procedures for children in the emergency department. This combination is superior to INM in terms of speed of onset and consistency of effect. INM delivered via aerosol spray has a more variable effect but may still be adequate for the completion of many of these procedures.

Administration, Intranasal↗

PubMed1994

Cardiopulmonary effects of medetomidine-midazolam and medetomidine-midazolam- atipamezole in laboratory pigs.

The cardiopulmonary effects of medetomidine (40 micrograms/kg)-midazolam (0.2 mg/kg) and medetomidine (40 micrograms/kg)-midazolam (0.2 mg/kg)-atipamezole (160 micrograms/kg) were evaluated in laboratory pigs. The intramuscular administration of medetomidine-midazolam caused a pressor response, characterized by a rapid increase in arterial and pulmonary arterial pressure mediated mainly through systemic and pulmonary vasoconstriction. These pressures decreased after reaching a peak 5 to 10 min after the administration of sedatives, but maintained higher values than the base-line. However, all these changes caused by medetomidine-midazolam were within the physiological fluctuation. In addition, this combination did not induce bradycardia, subsequent hypotension or a significant decrease in cardiac output, which were generally observed with alpha 2-adrenoceptor agonists, and caused fewer changes in the respiratory system. The administration of atipamezole resulted in a marked transient decrease in vascular resistance, and caused a decrease in blood pressure and increases in cardiac output and heart rate. However, these changes were relatively small and sustained for a short time. Thus the combination of medetomidine-midazolam and atipamezole have minimal cardiopulmonary effects and might be used safely in laboratory pigs.

Adrenergic alpha-Agonists↗