ABSTRACT SUMMARY:

ABSTRACT SUMMARY:

Intranasal Midazolam for Pediatric sedation

Contents Bibliography:

Title:

al-Rakaf, H., L. L. Bello, et al. (2001). “Intra-nasal midazolam in conscious sedation of young paediatric dental patients.” Int J Paediatr Dent 11(1): 33-40.

Lee-Kim, S. J., S. Fadavi, et al. (2004). "Nasal versus oral midazolam sedation for pediatric dental patients." J Dent Child (Chic) 71(2): 126-30.

Manani, G., M. F. Bazzato, et al. (2004). "Combined sedation with oral chlordemethyldiazepam and midazolam by nasal route in third molar surgery." Minerva Stomatol 53(5): 241-50.

Roelofse, J. A., E. A. Shipton, et al. (2004). "Intranasal sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in the pediatric population prior to undergoing multiple dental extractions under general anesthesia: a prospective, double-blind, randomized comparison." Anesth Prog 51(4): 114-21.

Bates, B. A., S. A. Schutzman, et al. (1994). “A comparison of intranasal sufentanil and midazolam to intramuscular meperidine, promethazine, and chlorpromazine for conscious sedation in children.” Ann Emerg Med 24(4): 646-51.

Davis, P. J., J. A. Tome, et al. (1995). “Preanesthetic medication with intranasal midazolam for brief pediatric surgical procedures. Effect on recovery and hospital discharge times.” Anesthesiology 82(1): 2-5.

Henry, R. J., N. Ruano, et al. (1998). “A pharmacokinetic study of midazolam in dogs: nasal drop vs. atomizer administration.” Pediatr Dent 20(5): 321-6.

Louon, A. and V. G. Reddy (1994). “Nasal midazolam and ketamine for paediatric sedation during computerised tomography.” Acta Anaesthesiol Scand 38(3): 259-61.

Malinovsky, J. M., C. Populaire, et al. (1995). “Premedication with midazolam in children. Effect of intranasal, rectal and oral routes on plasma midazolam concentrations.” Anaesthesia 50(4): 351-4.

Theroux, M. C., D. W. West, et al. (1993). “Efficacy of intranasal midazolam in facilitating suturing of lacerations in preschool children in the emergency department.” Pediatrics 91(3): 624-7.

Yealy, D. M., J. H. Ellis, et al. (1992). “Intranasal midazolam as a sedative for children during laceration repair.” Am J Emerg Med 10(6): 584-7.

Zedie, N., D. W. Amory, et al. (1996). “Comparison of intranasal midazolam and sufentanil premedication in pediatric outpatients.” Clin Pharmacol Ther 59(3): 341-8.

al-Rakaf, H., L. L. Bello, et al. (2001). “Intra-nasal midazolam in conscious sedation of young paediatric dental patients.” Int J Paediatr Dent 11(1): 33-40.

OBJECTIVES: To compare the effects of 3 different doses of intra-nasal midazolam in the conscious sedation of young paediatric dental patients and to compare the effectiveness of the sedation in the fasting and non-fasting child. DESIGN: Double blind random controlled trial. SAMPLE AND METHODS: Thirty-eight uncooperative young children aged 2-5 years (mean age 4.02 years) were randomly assigned to one of 3 groups. The groups and the doses of midazolam administered intra-nasally were A: 0.3 mg/kg, B: 0.4 mg/kg, and C: 0.5 mg/kg body weight. Each child in each group had two visits for restorative treatment: one without food (fasting) and the other with soft drink and light food (non-fasting) before treatment. Child behaviour and sedative effects were evaluated using the scoring system of Houpt. The vital signs were monitored continuously using a pulse oximeter and Dinamap machine. RESULTS: There was rapid onset of sedation with the maximal effect between 8 and 15 minutes. This sedation lasted for 25-40 minutes in Groups A and B and for 60 minutes in Group C. Conscious sedation and dental treatment were achieved in 79%, 96% and 100% of the children in Groups A, B and C, respectively. Consistently higher Houpt scores were seen in Groups B and C, with statistically significant differences between Groups A and C, and B and C (Tukey's range test, P < 0.05). There were no significant differences in the general behaviour of the child, the onset and the duration of sedation between the fasting and the non-fasting child (nonparametric ANOVA P > 0.05). All the vital signs were within normal physiological limits and there were no significant adverse effects either with or without fasting. CONCLUSIONS: All 3 doses of intranasal midazolam were effective in modifying the behaviour of the uncooperative child patient to accept dental treatment. This was irrespective of fasting.

Lee-Kim, S. J., S. Fadavi, et al. (2004). "Nasal versus oral midazolam sedation for pediatric dental patients." J Dent Child (Chic) 71(2): 126-30.

PURPOSE: The purpose of this study was to evaluate and compare intranasal (IN) and oral (PO) midazolam for effect on behavior, time of onset, maximum working time, efficacy, and safety for patients requiring dental care. METHODS: Forty anxious subjects (20 IN, 20 PO, Frankl Scale 3 and 4, ages 2-6 years, ASA I and II) were sedated randomly with either IN (0.3 mg/kg) or PO (0.7 mg/kg) midazolam. The dental procedure under sedation was videotaped and rated by a blinded and calibrated evaluator using Houpt's behavior rating scale. RESULTS: There was no statistical difference for overall behavior (F3,27 = 0.407; P = .749). The planned contrasts showed significant interactions between time and route (IN vs PO) between 25 and 30 minutes after starting sedation. The time of onset (P = .000) and the working time (P = .007) were significantly different between IN and PO midazolam. There were no statistically significant differences in vital signs (O2 sat, HR, RR, BP) between PO and IN (P = .595). IN subjects showed more movement and less sleep toward the end of the dental procedures, and faster onset time but shorter working time than PO. Vital signs were stable throughout the procedures with no significant differences. CONCLUSIONS: Mean onset time was approximately 3 times faster with IN administration compared to PO administration. Mean working time was approximately 10 minutes longer with PO administration than it was with IN administration. Overall behavior under PO and IN was similar. However, more movement and less sleep were shown in subjects under IN than those under PO toward the end of the dental session. All vital signs were stable throughout the procedures and showed no significant differences between PO and IN administration.

Manani, G., M. F. Bazzato, et al. (2004). "Combined sedation with oral chlordemethyldiazepam and midazolam by nasal route in third molar surgery." Minerva Stomatol 53(5): 241-50.

AIM: This study was performed to evaluate the effects on the cardiocirculatory system, on perioperative anxiety and compliance of sedation with 2 benzodiazepines, chlordemethyldiazepam (CDDZ) a long acting oral drug for presedation and midazolam, a short acting drug, administered by nasal route to induce intraoperative sedation. METHODS: Fifty randomized patients undergoing third molar extraction at the Dental Clinic, University of Padua, were preoperatively evaluated. Anxiety was evaluated through a visual, analogue, scale (VAS) of 10 cm, a questionnaire of adjectives called interval scale of anxiety response (ISAR) and the Newman test was applied to evaluate the changes in psychomotor functions. All patients were treated with 1 ml of oral CDDZ for presedation and midazolam by the nasal route for intraoperative sedation at doses of 1 mg in Group 1 (25 patients) and 2 mg in Group 2 (25 patients). In all patients preoperative cardiocirculatory parameters were evaluated and in the first 20 min after the beginning of intervention. At the end of intervention the Newman test was reapplied, anxiety and postoperative cardiocirculatory data were reevaluated and the quality of the intervention judged in an interview made 1 week after the intervention (quality of the sedation technique, perioperative pain intensity, assumption of analgesic drugs, swelling, amnesia etc. after intervention). RESULTS: The treatment with 1 mg CDDZ + 2 mg midazolam by nasal route is the best association to slightly attenuate intra- and postoperative cardiocirculatory response, anxiety and to improve the quality of the treatment without interfering on the psychomotor response of patients at the time of the discharge. CONCLUSION: To conclude, the sedative technique employed is easily applied by the dentist, and is safe, efficacious and well tolerated by patients.

This article details a double-blind, randomized study evaluating the efficacy and safety of intranasal sufentanil and intranasal midazolam (S/M) when compared with intranasal ketamine and intranasal midazolam (K/M) for sedation and analgesia in pediatric patients undergoing dental surgery. Fifty healthy ASA status 1 children aged 5-7 years, weighing 15-20 kg, and having 6 or more teeth extracted, were randomly allocated to 2 groups of 25 patients each (n = 50). In the S/M group, 25 children received intranasal sufentanil 20 microg, and intranasal midazolam 0.3 mg/kg 20 minutes before the induction of anesthesia. In the K/M group, 25 children received intranasal ketamine 5 mg/kg and intranasal midazolam 0.3 mg/kg 20 minutes before the induction of anesthesia. Sevoflurane in nitrous oxide and oxygen was used for induction and maintenance of anesthesia. This study demonstrated the safety and efficacy of both methods with ease of administration, combined with a rapid onset of action. Both groups were equally sedated. A smooth mask induction of anesthesia was experienced in the majority of children. Effective postoperative analgesia for multiple dental extractions was provided. The intranasal administration of drugs for sedation and analgesia has some promising features in preschool children undergoing multiple dental extractions.

STUDY OBJECTIVE: To compare intranasal sufentanil and midazolam (IN-SM) with intramuscular meperidine, promethazine, and chlorpromazine (IM-MPC) for sedation in children. DESIGN: Single-blind, randomized, controlled study. SETTING: Urban children's emergency department. PARTICIPANTS: A convenience sample of children aged 1 to 4 years requiring suturing. INTERVENTIONS: IN-SM or IM-MPC. RESULTS: Vital signs, O2 saturation, and anxiety and pain scores were recorded. A 6-point scale was used to assess response to medication, and a 12-point recovery score was used to determine readiness for discharge. Both groups were similar in age and sex distribution. There were no significant adverse effects in either group. Patients tolerated the IN regimen better than the IM regimen. Behavioral scores were lower during repair than at baseline within each group; however, they were not different between groups. Time to discharge was longer and recovery scores were lower (worse) among the IM-MPC group. CONCLUSION: IN-SM is as effective as IM-MPC for sedation in children.

BACKGROUND: The perfect preanesthesia medication and its ideal route of administration are still debated, but for pediatric surgical patients undergoing brief procedures, preanesthesia medication is frequently omitted because of the concern that it will prolong the child's recovery from anesthesia. The effects of nasally administered midazolam on anesthetic recovery and hospital discharge times were determined in 88 ASA physical status 1 and 2 ambulatory surgical patients undergoing a brief surgical procedure. METHODS: Using a randomized, double-blind, placebo-controlled design, 88 ambulatory surgical patients 10-36 months of age undergoing myringotomy and tube insertion were entered into the study. All patients were randomly assigned to one of three medication groups. One group received 0.2 mg/kg intranasal midazolam; a second group received 0.3 mg/kg intranasal midazolam; and the third group received intranasal saline drops. All patients were anesthetized with nitrous oxide, oxygen, and halothane administered via mask. The duration of anesthesia lasted between 9 and 10 min. After preanesthetic medication, the children were evaluated for ease of separation and induction of anesthesia. In addition, the time from when the anesthetic was discontinued until the child recovered from anesthesia and the time the child was discharged home were recorded by a nurse observer blinded to the patient grouping. RESULTS: Children receiving midazolam had smoother, calmer parent-child separation and anesthesia induction scores, and their anesthesia recovery times and hospital discharge times were the same as those receiving placebo. CONCLUSIONS: For children undergoing brief surgical procedures, nasal midazolam provides satisfactory anxiolysis without delaying anesthesia recovery and hospital discharge.

Henry, R. J., N. Ruano, et al. (1998). “A pharmacokinetic study of midazolam in dogs: nasal drop vs. atomizer administration.” Pediatr Dent 20(5): 321-6.

PURPOSE: The purpose of this investigation was to compare the pharmacokinetics of midazolam following intravenous, intranasal drop, and nasal-atomizer administration in beagle dogs. METHODS: Six animals weighing 9-13 kg were used in a repeated-measure design, group assignment based on route of drug administration. Midazolam (1.5 mg/kg) was administered with the delivery route based on group assignment. Blood samples were obtained at baseline and at 1, 3, 5, 7, 10, 15, 20, 30, and 45 min after administration. Cerebrospinal fluid samples (CSF) were obtained at 5 and 10 min after administration. Plasma and CSF concentrations of midazolam were determined by electron-capture gas-liquid chromatography. RESULTS: Comparison between groups and over time demonstrated that both nasal routes resulted in significantly higher CSF concentrations relative to corresponding plasma levels, and that nasal-atomizer administration produced significantly higher CSF concentrations compared to the drop approach.

Louon, A. and V. G. Reddy (1994). “Nasal midazolam and ketamine for paediatric sedation during computerised tomography.” Acta Anaesthesiol Scand 38(3): 259-61.

We have studied the sedation achieved with a mixture of midazolam (0.56 mg/kg-1) and ketamine (5 mg/kg-1) administered nasally in 30 children weighing less than 16 kg undergoing computerised tomography. Assessment was two fold using a visual analogue scale; the radiologist/radiographer rated the exam from "failed examination" to "perfect working conditions" while the anesthetist's assessment ranged from "poor sedation" to "perfect sedation with clinical well being". This new method proved to be effective alone in 83% of the cases and there were no complications. The rapid onset obtained after intranasal midazolam and ketamine offers advantages over orally or rectally administered drugs. The absence of respiratory depression and oxygen desaturation suggests that this technique is safe and efficient in the CT room with its particular working conditions.

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.

Theroux, M. C., D. W. West, et al. (1993). “Efficacy of intranasal midazolam in facilitating suturing of lacerations in preschool children in the emergency department.” Pediatrics 91(3): 624-7.

Sedating children safely and effectively for minor laceration repair is a well-recognized clinical problem. A randomized, double-blind, and controlled study was conducted to evaluate the efficacy of intranasal midazolam for reducing stress during the suturing of lacerations in preschool children. Fifty-nine children with simple lacerations that required suturing were randomly assigned to one of three groups. Group 1 received intranasal midazolam, 0.4 mg/kg, prior to suturing. Group 2 received an equivalent volume of normal saline intranasally prior to suturing as a placebo. Group 3 was the control group and received no intervention prior to suturing. Heart rate, respiratory rate, blood pressure, and pulse oximetry were monitored at 5-minute intervals throughout the procedure. Subjective variables were also measured at 5-minute intervals and included a cry score, a motion score, and a struggle score. Parent satisfaction was measured via a short telephone interview the following day. There were no significant differences in outcome between the placebo group and the control group. Their results were pooled and compared with the results for the midazolam group. The midazolam group showed significant reductions for mean heart rate, maximum heart rate, and maximum systolic blood pressure when compared with the placebo/control group. Scores for two of the three subjective variables, cry and struggle, were significantly reduced for the midazolam group. The papoose board was considered unnecessary in retrospect for more than half of patients in the midazolam group compared with only one fifth of patients in the placebo/control group.

Yealy, D. M., J. H. Ellis, et al. (1992). “Intranasal midazolam as a sedative for children during laceration repair.” Am J Emerg Med 10(6): 584-7.

We performed a retrospective chart review to determine the onset, duration, safety, and clinical sedative effects of 0.2 to 0.5 mg/kg intranasal midazolam in young children during laceration repair. Of 408 children treated for lacerations during an 8-month period, 42 (10%) received intranasal midazolam. Documentation was adequate for detailed analysis in 40 cases. Data are reported as mean +/- standard deviation and the frequency with 95% confidence limit (CL) estimates. The mean age of the study population was 32 +/- 9 months (range 12 months to 6 years), and the mean body mass was 14.5 +/- 3 kg. Topical or injected local anesthesia was used in 37 cases. Overall, 73% (CL 56% to 85%) of the children achieved adequate sedation. However, those receiving 0.2 to 0.29 mg/kg had adequate sedation in only 27% (CL 6% to 60%) of the cases compared with 80% (CL 52% to 95%) and 100% (CL 79% to 100%) when 0.3 to 0.39 and 0.4 to 0.5 mg/kg respectively were administered. When achieved, sedation occurred within 12 +/- 4 minutes, recovery occurred at 41 +/- 9 minutes, and discharge occurred at 56 +/- 11 minutes. No vomiting or clinically significant oxygen desaturation (defined as a drop of > 4% or to < 91%) was observed. We conclude that intranasal midazolam is a safe and effective sedative for laceration repair under local anesthesia in preschool-aged children. We recommend a dose of 0.3 to 0.5 mg/kg, with treatment failure less likely after 0.4 to 0.5 mg/kg compared with less than 0.3 mg/kg.

Zedie, N., D. W. Amory, et al. (1996). “Comparison of intranasal midazolam and sufentanil premedication in pediatric outpatients.” Clin Pharmacol Ther 59(3): 341-8.

BACKGROUND: Intranasally administered midazolam was compared with sufentanil as a premedicant for 60 patients, aged 1/2 to 6 years, undergoing outpatient surgery of 2 hours or less. METHODS: Thirty minutes before anesthetic induction (halothane in 50% nitrous oxide/oxygen), patients were randomly assigned to receive either intranasal midazolam (0.2 mg/kg) or sufentanil (2 microg/kg). A "blinded" observer evaluated preoperative emotional state, response to premedication, induction, and emergence from anesthesia and side effects. RESULTS: Children who had not previously cried were more likely to cry when midazolam was administered compared with sufentanil (71% versus 20%, p = 0.0031). Of 31 midazolam patients, 20 experienced nasal irritation. Approximately 15 to 20 minutes after drug administration, most patients in both groups could be comfortably separated from their parents. The sufentanil group appeared to be more sedated and more cooperative during induction of anesthesia. Vital signs and oxygen saturation did not change significantly with either medication before or after surgery, although two sufentanil patients had a moderate reduction in ventilatory compliance after anesthetic induction. Sufentanil was associated with more nausea and vomiting than midazolam (34% versus 6%, p < 0.02). CONCLUSION: Both intranasal midazolam and sufentanil provide rapid, safe, and effective sedation in small children before anesthesia for ambulatory surgery. Sufentanil provided somewhat better conditions for induction and emergence. Midazolam causes more nasal irritation during instillation, and sufentanil causes more postoperative nausea and vomiting. Both drugs enabled patients to be separated from their parents with a minimum of distress. Patients in the midazolam group were discharged approximately 40 minutes earlier (p <0.005).