Nasal Midazolam Research Articles

Oral Ketamine or Nasal Midazolam for Sedation in Pediatric Upper Gastrointestinal Endoscopy

Background: There is no agreement on the route of administration and the drug of choice for providing adequate sedation for pediatric invasive procedures. Objectives: We compared the utility, safety, and sedation effects of intranasal midazolam and oral ketamine. Materials & Methods: This double-blind clinical trial was performed on 100 children aged 2 to 14 years who were candidates for upper gastrointestinal (GI) endoscopy. Patients were randomly assigned to two groups: ketamine (4 mg/kg orally) and midazolam (0.1 mg/ kg intranasal). Sedation score, fear levels, children’s behavior at the time of separation from parents, and vital signs were recorded. Results: Higher systolic blood pressure was seen in children who received ketamine (P=0.012) and lower arterial oxygen saturation in the midazolam group (P=0.023). Also, the level of sedation showed no significant difference between the groups. Conclusion: Based on the results, administering oral ketamine or intranasal midazolam before endoscopy induced a similar sedation score in children. Also, both methods could be safe and non-invasive modalities for sedation.

Evaluation of the Efficacy of Nasal Sedation Midazolam Compared with Dexmedetomidine in the Management of Uncooperative Children with Down Syndrome during Dental Treatment.

Objective This study aimed to compare the intranasal administration of midazolam and dexmedetomidine in uncooperative children with Down syndrome. Materials and Methods The sample consisted of 20 children with Down syndrome aged 5 to 11 years who were divided equally into two groups: Group 1 (experimental) nasal dexmedetomidine and Group 2 (control) nasal midazolam. The efficacy of both the drugs was evaluated according to Ohio State University Behavioral Rating Scale (OSUBRS), University of Michigan scale (UMSS), and Houpt general behavior scale. Results Both substances have been effective in the management of children with Down syndrome. There were no statistically significant differences for Ohio State University Behavioral Rating Scale (OSUBRS) (P value = 0.631), University of Michigan scale (UMSS) (P value = 0.739), and Houpt general behavior scale (P value = 0.481). Conclusion Both midazolam and dexmedetomidine nasal can be used to sedate children with Down syndrome.

Peripheral nerve block for leg amputation in a high risk patientꓽ Case report

Introduction: Peripheral nerve blockages have many advantages which make them very useful in anaesthetic practice. The purpose of this presentation is to high light the effectiveness of peripheral nerve blocks in high risk patients. Methods and material: It is a case report and we use data from our clinic. A 68 year old male patient came to our hospital with osteomyelitis of his left foot. He has a medical history of hypertension, type 1 diabetes and coronary heart disease with acute myocardial infarction 25 days ago. According to the ASA classification was: IV E. Peripheral nerve block suggested to him which he accepted. We use posterior approach of the sciatic nerve in the iliac fossa. Ropivacaine 5 mg/mL (total 40 mL) was given. For nerve detection we use a 22 g needle 50 mm and a nerve stimulator. For the saphenous nerve 7 mL of Ropivacaine 5 mg/mL was given with subcutaneous infiltration from the tibial tuberosity to the posterior surface of the tibia. ECG, pulse oximetry, non –invasive blood pressure applied before the block until discharge from the operating theatre. O2 2 L via a nasal catheter and midazolam 2 mg was given to him. Results: Complete nerve block was achieved 20 minutes after the injection of the local anesthetic. The duration of the operation was 90 minutes. For the first 24 h postoperatively, the patient received only Paracetamol 1 gr/6 hours and his pain according to the Visual Analogue Scale was 0–2. Conclusion: In high risk patients peripheral nerve blocks are safe and alternative methods to general anesthesia or central nerve blocks. Minimal systemic effects, adequate analgesia in the immediate postoperative period, are some of their advantages.

Intra Nasal Midazolam vs. Rectal Diazepam in Management of Acute Seizures in Pediatrics, Considering the Antiepileptic Drugs Monitoring

Immediate management of children's epilepsy is essential before the patient arrives to the hospital. The purpose of this study was to compare the efficacy of intranasal midazolam vs. rectal diazepam in the management of acute pediatric seizures. In this cross-sectional study, 68 patients having acute seizure were evaluated for response to treatment after receiving intra-nasal midazolam (34 patients) or rectal diazepam (34 patients). Patents were assessed by physicians at the arrival to emergency department for history taking and examination. Blood samples were assessed for valproate, phenobarbital and phenytoin levels in serum to determine previous use of antiepileptic drugs. Seizure duration and response time to treatment were evaluated along with health care utilization and were compared between study groups, by the statistical package for the social sciences software. Mean age of study participants, sex disturbance, age at onset of a seizure, type of seizure and prehospital time had not any significant differences between two groups (p>0.05). The mean response time to diazepam was 8.0±4.9 min and 6.3±2.2 min for midazolam; which had a significant difference between groups (0.001). Linear regression of serum antiepileptic drug levels in association of response time in each group was not significant in all case (p>0.05), expect the lamotrigine serum level in midazolam group (p=0.029). Intranasal midazolam was seen to have a better effect than rectal diazepam in the management and treatment of acute seizures in children; while antiepileptic drugs monitoring want helpful in assessing the absolute effect.

A prospective randomised double blinded comparative study between nasal atomized dexmedetomidine and midazolam as premedicants in paediatric adenotonsillectomy

Adenotonsillectomy is one of the most common ambulatory surgeries in the pediatric population. Fear and anxiety at parental separation is one of the important challenges to the anesthesiologist in spite of improvements in the drug armamentarium, seen in 40-60% children. The gold standard of premedication is Midazolam, which is effective by all routes, intravenous, intramuscular, oral, submucosal and nasal.1,2 Nasal Midazolam is commercially available, each puff delivering 0.5mg. Nasal route is now being popular because it is non-invasive, easy and has rich blood supply which ensures a faster absorption and faster onset of action. Besides, it bypasses the hepatic metabolism, so bioavailability is improved from 40-60% in oral route to about 82% in nasal route. The search for ideal premedicant continues3 and Dexmedetomidine, alpha-2 agonist, is the new kid in town. It is effective by all routes including nasal.3 But, so far only studies with nasal instillation of Dexmedetomidine, is available, especially in children. Syed et al. in 2019 has used atomized form of Dexmedetomidine in adults for minor orofacial procedures. Hence we decided to compare nasal atomized Dexmedetomidine and Midazolam using atomization devices like LMA MAD NASAL and INSED ATOMISER because atomization helps to break down particle to 30-100microns, hence absorption would be quicker with minimum or no side effects.

Treatment of Seizures in Children and Adults in the Emergency Medical System of the City of Zurich, Switzerland - Midazolam vs. Diazepam - A Retrospective Analysis.

Seizures count to critical situations emergency medical systems (EMS) are confronted with. Evaluation of a modified treatment algorithm (MTAS-EMS) using diazepam and midazolam due to a supply bottleneck of iv lorazepam in 2012. Retrospective study where data from patients treated for seizures by the EMS of the city of Zurich were analyzed. Effectiveness of the MTAS-EMS and i.v. diazepam in children and adults was compared with respect of cessation of seizure without recurrence over the period until arrival at the hospital. The chi-square and Fisher's exact test were used to compare categorical data. The Student's t-test and Mann Whitney test were used to compare numerical data. p-values < 0.05 are considered significant. Of 584 documented missions, 165 treated patients (126 adults and 39 children) were included. 115 patients (80 adults and 35 children) were treated according the MTAS-EMS. Cessation of seizure was achieved in 85% of the adults and in 97% of the children, if all options of the MTAS-EMS were used. The first dose of nasal midazolam was more successful in children compared to adults (p = 0.012). In adults, the single dose of i.v. diazepam terminated the seizure in 98% (p = 0.001) compared to 57% for the single dose of iv and 64% for nasal midazolam. The treatment success of the MTAS-EMS is high. However, in adults the single dose of i.v. diazepam is as successful as the completely used MTAS-EMS and seems to be superior to the single dose iv and nasal midazolam.

Comparative Analysis of Intravenous Midazolam with Nasal Spray for Conscious Sedation in Minor Oral and Maxillofacial Surgeries.

Aim:The aim of the current study was to evaluate the efficacy of nasal spray midazolam by collating it with conventional intravenous midazolam for conscious sedation in minor oral surgeries.Materials and Methods:Sixty patients were selected randomly and divided into two groups: group A for intranasal midazolam atomized spray (n = 30) and group B for intravenous midazolam (n = 30). Physiological parameters, anxiety score, sedation rating, patient’s cooperation score, and retrograde and anterograde amnesia were recorded for each patient during preoperative, intraoperative, and postoperative period. Final evaluation of safety and efficacy in the nasal and intravenous routes of midazolam drug during minor oral surgery was compared.Results:In this study, both intranasal and intravenous groups showed decrease in systolic blood pressure and diastolic blood pressure intraoperatively but within physiological limits and increase in the average pulse rates in both the groups. The average oxygen saturation levels were maintained to normal range in both the groups. The average respiratory rate decreased in both intranasal and intravenous groups during surgical procedure. The preoperative to postoperative anxiety scores were decreased significantly in the both groups and there was no significant difference in pre- to postoperative anxiety scores between the groups.Conclusion:Both intravenous and intranasal administration of midazolam showed better patient cooperation, satisfaction, and clinical effectiveness. Intranasal midazolam spray is effective in the reduction of subjective stress, reliable anxiolysis while preserving protective reflexes.

Nasal midazolam vs ketamine for neonatal intubation in the delivery room: a randomised trial

ObjectiveTo compare the effectiveness of sedation by intranasal administration of midazolam (nMDZ) or ketamine (nKTM) for neonatal intubation.DesignA multicentre, prospective, randomised, double-blind study.SettingDelivery rooms at four tertiary perinatal centres in...

Buccal and nasal midazolam cost effective for paediatric SE

Buccal and nasal midazolam cost effective for paediatric SE

Nonintravenous rescue medications for pediatric status epilepticus: A cost-effectiveness analysis.

To quantify the cost-effectiveness of rescue medications for pediatric status epilepticus: rectal diazepam, nasal midazolam, buccal midazolam, intramuscular midazolam, and nasal lorazepam. Decision analysis model populated with effectiveness data from the literature and cost data from publicly available market prices. The primary outcome was cost per seizure stopped ($/SS). One-way sensitivity analyses and second-order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters. The most cost-effective rescue medication was buccal midazolam (incremental cost-effectiveness ratio ([ICER]: $13.16/SS) followed by nasal midazolam (ICER: $38.19/SS). Nasal lorazepam (ICER: -$3.8/SS), intramuscular midazolam (ICER: -$64/SS), and rectal diazepam (ICER: -$2,246.21/SS) are never more cost-effective than the other options at any willingness to pay. One-way sensitivity analysis showed the following: (1) at its current effectiveness, rectal diazepam would become the most cost-effective option only if its cost was $6 or less, and (2) at its current cost, rectal diazepam would become the most cost-effective option only if effectiveness was higher than 0.89 (and only with very high willingness to pay of $2,859/SS to $31,447/SS). Second-order Monte Carlo simulations showed the following: (1) nasal midazolam and intramuscular midazolam were the more effective options; (2) the more cost-effective option was buccal midazolam for a willingness to pay from $14/SS to $41/SS and nasal midazolam for a willingness to pay above $41/SS; (3) cost-effectiveness overlapped for buccal midazolam, nasal lorazepam, intramuscular midazolam, and nasal midazolam; and (4) rectal diazepam was not cost-effective at any willingness to pay, and this conclusion remained extremely robust to wide variations of the input parameters. For pediatric status epilepticus, buccal midazolam and nasal midazolam are the most cost-effective nonintravenous rescue medications in the United States. Rectal diazepam is not a cost-effective alternative, and this conclusion remains extremely robust to wide variations of the input parameters.

Safety and Efficacy of 3 Pediatric Midazolam Moderate Sedation Regimens.

Our aim was to characterize effectiveness and complications in children receiving oral midazolam alone, nasal midazolam alone, or oral midazolam with other sedatives. Children received oral midazolam alone, nasal midazolam, or oral midazolam in combination with other sedative medications. All subjects received a presedation history and physical examination and were sedated per protocol by any of 28 resident providers under attending supervision. Sedations were rated for success and complications by clinicians. Postoperative complications were assessed by trained staff up to 48 hours postoperatively. Seven hundred and one encounters, completed over 24 months, yielded 650 usable sedations. The majority of children were healthy (469; 68.2%) and 86% (532) weighed between 10 and 25 kg. Sedations were deemed successful in about 80% of cases. Planned treatment was completed in over 85% of encounters. Oral midazolam alone yielded the best behavior. Physical assessment factors of behavior and age were correlated (P = .035) with effectiveness. Hiccups and a positive medical history were significantly related (P = .049). Side effects of either nausea/vomiting, dysphoria, or hiccups occurred in less than 10% of cases. All 3 regimens were effective with minimal postoperative complications.

Conscious Sedation in Minor Oral Surgery with Midazolam IV Versus Nasal Spray a Comparative Study

Aim: The purpose of this study was to assess the effectiveness of nasal spray midazolam by comparing it with conventional intravenous midazolam conscious sedation in minor oral surgical procedures. Objective: To assess the safety and effectiveness of the midazolam nasal spray in comparison to its IV midazolam. Patients and methods: Total forty number of patients were selected, and they were divided in to two groups. Group A for intra nasal midazolam atomized spray (n=20) and Group B for intravenous midazolam (n=20). Physiological parameters, anxiety score, sedation rating, patient’s cooperation score, retrograde and anterograde amnesia were recorded for each patient during preoperative, intra operative and postoperative period. Final evaluation of safety and efficacy in the nasal and intravenous routes of midazolam drug during minor oral surgery were compared. Results: In the present study both intranasal and intravenous groups showed decrease in SBP and DBP intra operatively but in physiological limits and increase in the average pulse rates in the both groups. The average oxygen saturation levels were maintained to normal range in both the groups. The average respiratory rate decreased in the both intranasal and intravenous groups during surgical procedure. The preoperative to postoperative anxiety scores were decreased significantly in the both groups and there was no significant difference in pre to postoperative anxiety scores in between the groups. Conclusion: Both intravenous and intranasal routes of administration of midazolam showed patient cooperation, satisfaction and clinical effectiveness. Intranasal route of midazolam spray is effective in reduction of subjective stress feelings, reliable anxiolysis while preserving protective reflexes.

A comparison of intranasal ketamine and intranasal midazolam for pediatric premedication

Aims and Objectives:The aim of our study is to compare the efficacy and side-effects of Ketamine and Midazolam administered nasally for the pediatric premedication.Materials and Methods:We studied 100 American Society of Anesthesiology I and II children aged from 1 to 10 years undergoing various surgical procedures. Totally, 50 children were evaluated for nasal ketamine (using 50 mg/ml vials) at the dose of 5 mg/kg and the other 50 received nasal midazolam 0.2 mg/kg, before induction in operation theater each patient was observed for onset of sedation, degree of sedation, emotional status being recorded with a five point sedation scale, response to venipuncture and acceptance of mask, whether readily, with persuasion or refuse.Results:The two groups were homogenous. Midazolam showed a statistically significant early onset of sedation (10.76 ± 2.0352 vs. 16.42 ± 2.0696 min). There were no significant differences in venipuncture score, sedation scale at 20 min, acceptance of mask and oxygen saturation throughout the study. Significant tachycardia and ‘secretions were observed in the ketamine group intra operatively. Postoperatively emergence (8% vs. 0%) and secretions (28% vs. 4%) were significant in the ketamine group. Nausea and vomiting occurred in l6% versus 10% for midazolam and ketamine group.Conclusions:Both midazolam and ketamine nasally are an effective pediatric premedication. Midazolam has an early onset of sedation and is associated with fewer side-effects.

Are febrile seizures an indication for intermittent benzodiazepine treatment, and if so, in which cases?

Febrile seizures occur in ∼4% of children. After a first febrile seizure, the risk of recurrence is ∼40%, but excellent studies document that febrile seizures do not cause brain damage or deficits in cognition or behaviour. The risk of subsequent epilepsy is 2-4%. Prolonged febrile seizures are of concern because a child may later develop mesial temporal sclerosis and intractable epilepsy in rare cases. Most prolonged febrile seizures represent the first febrile seizure and cannot be anticipated. A first prolonged febrile seizure does not increase the risk of recurrence, but if there is a recurrence, it is more likely to be prolonged. Prevention of recurrent febrile seizures is difficult. Antipyretics are ineffective. Daily AED treatment is not often justified. Intermittent oral diazepam at the time of illness is not very successful and has significant side effects. The most optimistic study found that the number of subjects required to treat in order to prevent one recurrence was 14. Intermittent clobazam has fewer side effects than diazepam and may be somewhat effective. Rescue benzodiazepines given outside health care facilities may be effective in selected patients to prevent prolonged recurrences, although this has not been proven with rectal diazepam which has been more extensively studied than buccal or nasal midazolam. Currently, we suggest that, for children with febrile seizures, candidates for consideration for rescue benzodiazepines are those with a prolonged febrile seizure or poor access to medical care. It is possible that the use of a rescue benzodiazepine may alleviate severe parental anxiety, but this remains to be established.

Comparative Evaluation of Oral Transmucosal Fentanyl Citrate and Nasal Transmucosal Midazolam Spray as Premedication in Children

Context: Premedication is an integral part of anaesthetic management. An ideal premedicant drug is anxiolytic, analgesic, sedative and amnestic. It should fulfill the aims of premedication, be safe for the patient and be easily administered. Aims: To evaluate and compare the efficacy of oral transmucosal fentanyl citrate lollipop and intranasal midazolam spray as a premedication in children by a non-invasive route and to evaluate post-operative sedation score. Settings and design: Our study was conducted in Government Medical College, Jammu, J&K. It was a comparative clinical trial done in 3 groups (40 subjects in each). The study was approved by the Ethical committee of the Institute. Methods and material: Children aged 5 to 10 years undergoing surgery in general anaesthesia were included in our study. Informed written consent was obtained from the parents of each child before adding the child in the study. Statistical analysis used: Data was collected on 120 children. Variables were reported as mean and standard deviation. The difference in mean values across the groups was assessed by One-Way Analysis of Variance (ANOVA). Statistical significance of qualitative variables was assessed with the use of chi-square test. Intergroup comparisons were made post-hoc by Bonferroni’s t-test. Results: Children who were given oral transmucosal fentanyl citrate (15 μgm/kg) were better sedated in the preoperative period, had less apprehension at venipuncture, had better mask acceptance, were calmer at emergence and post-operative period, as compared to those who were given nasal transmucosal midazolam spray (0.2 mg/kg) or nasal saline spray. Conclusions: It was concluded that oral transmucosal fentanyl citrate, in the dose of 15 μg/kg, is superior to nasal transmucosal midazolam spray (0.2 mg/kg) in providing preoperative sedation, decreasing anxiety at the time of placement of anaesthesia mask and intravenous cannulation and lowering the level of agitation at emergence.

Comparison of nasal Midazolam with Ketamine versus nasal Midazolam as a premedication in children

Background:This study was done to compare effects of intranasal midazolam and intranasal midazolam with ketamine for premedication of children aged 1-12 yrs undergoing intermediate and major surgeries.Aims:Midazolam and Ketamine have already been used as premedicants in children. Our aim was to find out advantage of combination of midazolam with ketamine over midazolam by nasal route.Methods:Sixty children of age group 1-12 yrs of American Society of Anesthesiologists (ASA) grade 1 and 2 were selected. Group A- midazolam (0.2 mg/kg), Group B- midazolam (0.15 mg/kg + ketamine 1 mg/kg). Both groups received drug intranasally 30 min before surgery in recovery room with monitored anesthesia care. Onset of sedation, sedation score, emotional reaction, intravenous cannula acceptance, and mask acceptance were studied.Statistical Analysis:Unpaired t test and chi square test.Results:Sedation score, anxiolysis, attitude, reaction to intravenous cannulation, face mask acceptance, and emotional reaction were significantly better in midazolam with ketamine group. Intra operatively, in both groups, pulse rate, oxygen saturation, and respiratory rate had no significant difference; also, post operatively, no significant difference was observed in above parameters, post operative analgesia was significantly better in midazolam with ketamine group.Conclusions:Intra nasal premedication allows rapid and predictable sedation in children. Midazolam as well as combination of Midazolam with ketamine gives good level of sedation and comfort. But quality of sedation, analgesia, and comfort is significantly better in midazolam with ketamine group. No significant side effects were observed in both groups.

Comparative study of oral and trans nasal midazolam as a sedative premedication in paediatric patients

Background: Premedication in pediatric patient before induction of anaesthesia is of vital importance. Midazolam is a benzodiazepine which produces anxiolytic, amnestic, hypnotic and skeletal muscle relaxant effects. Objectives: To evaluate the safety, acceptability, level of sedation and ease of administration of midazolam by using oral and trans nasal route as a sedative premedication in paediatric patient. Materials and Methods: Sixty paediatric patients of ASA grade I or II, aged 2-10 years, undergoing elective surgery were randomly divided into two groups. Group I received oral syrup midazolam 0.5mg/kg and Group II received nasal spray midazolam 0.25mg/kg. Demographic profile, response to drug administration, level of sedation, separation from parents, venipuncture, induction and postoperative recovery scores were noted and statistically analyzed. Results: The study shows that children receiving oral midazolam has better acceptability (group I, 76.66%) than when administered through intranasal route (group II, 53.33%). Sedation score were better at 20 min. in intranasal group (3.06 versus 2.96) than oral group. Post anesthesia recovery scores were similar in both groups. Conclusion: On the basis of our study, we concluded that oral syrup midazolam has better acceptability while intranasal spray midazolam has slightly faster onset without prolonging recovery from anesthesia.

Intubation in the delivery room: Experience with nasal midazolam

BackgroundNeonates are often intubated in the delivery room (DR) without anesthesia because vascular access is impossible. AimsTo assess neonatal comfort and adverse events after use of nasal midazolam (nMDZ) for intubation in the DR. Study designProspective data collection over 6months on the intubation of neonates with respiratory distress requiring tracheal instillation of surfactant. SubjectsTwenty-seven neonates with median (Q25–75) gestational age and birthweight of, respectively, 29 (27–33)weeks and 1270 (817–1942)g received a 0.1mg/kg dose of nMDZ, and intubation was performed at the onset of tonus resolution or apnea. Outcome measuresComfort was assessed with a scale of hetero-pain assessment and electrical skin conductance monitoring. Continuous pulse oximetry was recorded in the first postnatal hour, with oscillometric blood pressure measurement every 10min. ResultsSeventy percent of the patients required a single dose, with intubation performed 4.8 (3–9)min after administration. Combined electro-clinical assessment found adequate comfort during the procedure in 68% of neonates. Mean blood pressure decreased from 39 (34–44)mmHg before to 31 (25–33)mmHg 1h following nMDZ (p=0.011). ConclusionnMDZ provided rapid and effective sedation to intubate neonates in the DR but potentially exposed them to hypotension, thus requiring close hemodynamic monitoring.

Oral chloral hydrate vs. intranasal midazolam for sedation during computerized tomography

We conducted this single blind randomized clinical trial to compare the efficacy and safety of oral chloral hydrate and intranasal midazolam for induction of sedation for computerized tomography scan of brain in children. Participants aged 1-10 years (n=60) were randomized to receive 100 mg/kg chloral hydrate orally with intra nasal normal saline OR intranasal midazolam 0.2 mg/kg with oral normal saline. Adequate sedation (Ramsay sedation score of four) was obtained and CT scan completed successfully in 76.7% of chloral hydrate group and in 40% of midazolam group (P=0.004). No significant difference was seen for side effects frequency between the two drugs (10% in chloral hydrate, 3.3% in midazolam group; P=0.34). We conclude that oral chloral hydrate can be considered as a safe and effective drug for sedation in children undergoing CT scan of brain.

Successful use of ketamin combined with remifentanil in two patients with epidermolysis bullosa

Epidermolysis Bullosa (EB) is characterized by the presence of extremely fragile skin and painful blister formations in the skin. We present the anesthetic management of 15-years-old, twin sisters with EB during the syndactyly operation. Premedication was done with 0.5 mg/kg nasal midazolam. Anesthesia induction was performed with sevoflurane without touching the facial masks to the skin. After intravenous 2 mgkg-1 ketamine and 50 μg fentanyl, anesthesia was maintained by intravenous 1 mg/kg/hr ketamine and 0.1 μg/kg/min remifentanil. We injected 2 mg intravenous morfin for postoperative pain control. Ketamine with remifentanil seems to be effective, simple, and safe for airway management and practical way to provide general anesthesia and analgesia of EB.