-
Revista Medica de Chile Feb 2021Benzodiazepines are used for perioperative conscious sedation. However, its use may be associated with paradoxical reactions. The known risk factors for these reactions...
BACKGROUND
Benzodiazepines are used for perioperative conscious sedation. However, its use may be associated with paradoxical reactions. The known risk factors for these reactions are age, alcohol and drug abuse and psychiatric disorders.
AIM
To assess the incidence and impact of risk factors of paradoxical reactions to midazolam.
MATERIAL AND METHODS
Cross sectional study of 218 patients aged 50 ± 16 years (51% women) scheduled for elective surgical procedures under regional anesthesia and midazolam sedation. The paradoxical reactions were classified according to their severity in three categories.
RESULTS
The incidence of paradoxical reactions to midazolam was 8.3% (95% confidence interval (CI) 5.0-12.7). All were mild and only 28% of the affected patients required pharmacological treatment, none of them flumazenil. A multivariable logistic regression model showed that the variables independently associated with a paradoxical reaction to midazolam were the use of psychoactive medications (Odds Ratio (OR) = 3.4 [1.1-11], p = 0.04, and the dose of midazolam (OR 1.35 [1.03-1.78], p = 0.03.
CONCLUSIONS
The incidence of paradoxical reactions to midazolam was 8,3% and all were mild. Their risk factors are the use of psychoactive medications and the use of higher doses of midazolam.
Topics: Conscious Sedation; Cross-Sectional Studies; Female; Flumazenil; Humans; Hypnotics and Sedatives; Male; Midazolam
PubMed: 34479268
DOI: 10.4067/s0034-98872021000200237 -
JPMA. the Journal of the Pakistan... Feb 2021To compare the efficacy of intravenous midazolam and diazepam in the management of status epilepticus seizures in children.
OBJECTIVE
To compare the efficacy of intravenous midazolam and diazepam in the management of status epilepticus seizures in children.
METHODS
The comparative study was conducted in the paediatric neurological emergency unit of The Children's Hospital and the Institute of Child Health, Multan, Pakistan, from December 15, 2018, to May 14, 2019, and comprised paediatric patients of status epilepticus seizures which were divided into Diazepam and Midazolam groups. Data was analysed using Graph-Pad Prism 5.
RESULTS
Of the 164 patients, 82(50%) were in each of the two groups. There was no significant difference between the groups in terms of weight, age, residence area of patients and mean duration of seizures (p>0.05). Status epilepticus seizures subsided after intravenous midazolam administration in 77(93.90%) cases, while success in the diazepam group 64(78.05%) (p<0.05). Mean time taken by midazolam to halt seizures was significantly shorter than diazepam (p<0.05) and less cases of treatment failure were observed with intravenous midazolam (p<0.05). Somnolence was observed after diazepam administration in 47(57.3%) cases (p=0.0001).
CONCLUSION
Intravenous midazolam was found to be superior in efficacy than intravenous diazepam in controlling status epilepticus seizures.
Topics: Anticonvulsants; Child; Diazepam; Humans; Midazolam; Pakistan; Status Epilepticus
PubMed: 33941951
DOI: 10.47391/JPMA.843 -
Journal of Chromatography. B,... Nov 2017Pharmacokinetic, pharmacodynamic and pharmacogenomic studies of midazolam are currently being performed in critically ill children to find suitable dose regimens....
Development and validation of a sensitive assay for analysis of midazolam, free and conjugated 1-hydroxymidazolam and 4-hydroxymidazolam in pediatric plasma: Application to Pediatric Pharmacokinetic Study.
Pharmacokinetic, pharmacodynamic and pharmacogenomic studies of midazolam are currently being performed in critically ill children to find suitable dose regimens. Sensitive assays using small volumes of plasma are necessary to determine the concentrations of midazolam and its respective metabolites in pediatric studies. Midazolam is metabolized to hydroxylated midazolam isomers, which are present as free as well as the corresponding glucuronide conjugates. A high-performance liquid chromatographic method with tandem mass spectrometry has been developed and validated for the quantification of midazolam, and free and total 1-hydroxymidazolam and 4-hydroxymidazolam metabolites in small volumes of plasma. Cleanup consisted of 96-well μ-elution solid phase extraction (SPE). The analytes were separated by gradient elution using a C analytical column with a total run time of 5min. Multiple reaction monitoring was employed using precursor to product ion transitions of m/z 326.2→291.3 for midazolam, m/z 342.1→203.0 for 1-hydroxymidazolam, m/z 342.1→325.1 for 4-hydroxymidazolam and m/z 330.2→295.3 for H-midazolam (internal standard). Since authentic hydroxymidazolamglucuronide standards are not available, samples were hydrolyzed with β-glucuronidase under optimized conditions. Assay conditions were modified and optimized to provide appropriate recovery and stability because 4-hydroxymidazolam was very acid sensitive. Standard curves were linear from 0.5 to 1000ng/mL for all three analytes. Intra- and inter day accuracy and precision for quality control samples (2, 20, 200 and 800ng/mL) were within 85-115% and 15% (coefficient of variation), respectively. Stability in plasma and extracts were sufficient under assay conditions. Plasma samples were processed and analyzed for midazolam, and free 1-hydroxymidazolam and 4-hydroxymidazolam metabolites. Plasma samples that were hydrolyzed with β-glucuronidase were processed and analyzed for midazolam, and total 1-hydroxymidazolam and 4-hydroxymidazolam metabolites under the same assay conditions. The difference in concentration between the total and free hydroxymidazolam metabolites provided an estimate of conjugated hydroxymidazolam metabolites. The combination of 96-well μ-elution SPE and LC-MS/MS allows reliable quantification of midazolam and its metabolites in small volumes of plasma for pediatric patients. This assay is currently being successfully utilized for analysis of samples from ongoing clinical trials.
Topics: Child; Chromatography, High Pressure Liquid; Drug Stability; Female; Humans; Limit of Detection; Linear Models; Male; Midazolam; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 28978489
DOI: 10.1016/j.jchromb.2017.09.030 -
Drug Design, Development and Therapy 2020To compare the efficacy of dexmedetomidine and midazolam in the prevention of postoperative nausea and vomiting (PONV) caused by hemabate in postpartum hemorrhage during... (Comparative Study)
Comparative Study Randomized Controlled Trial
A Comparison of Dexmedetomidine and Midazolam for the Prevention of Postoperative Nausea and Vomiting Caused by Hemabate in Cesarean Delivery: A Randomized Controlled Trial.
OBJECTIVE
To compare the efficacy of dexmedetomidine and midazolam in the prevention of postoperative nausea and vomiting (PONV) caused by hemabate in postpartum hemorrhage during cesarean delivery.
METHODS
One hundred and five parturients with American Society of Anesthesiology (ASA) physical status I and II, aged 20-40 years, undergoing elective cesarean delivery under epidural anesthesia were randomly allocated into dexmedetomidine group (group D, n=35), midazolam group (group M, n=35) and control group (group C, n=35). Patients received an intrauterine injection of 250 μg hemabate and continuous intravenous infusion of 5 units oxytocin immediately following the delivery of the infant. At the same time, patients in group D received 1μg/kg intravenous dexmedetomidine, group M received 0.02 mg/kg intravenous midazolam and group C received 20 mL intravenous saline. Parameters such as the PONV, other adverse reactions (chest distress, flush, etc.) caused by hemabate, patient satisfaction, the sedation (OAA/S) scores, and the hemodynamic parameters were recorded in both groups.
RESULTS
The PONV incidence in group D and group M was significantly lower compared with group C (6%, 17%, and 71% for group D, group M, and group C, respectively, P<0.05). The sedation (OAA/S) scores in group D and group M was significantly higher compared with group C (1.62±0.28, 1.75±0.31, and 1.00±0.00 for group D, group M, and group C, respectively, P<0.05). The patient satisfaction in group D and group M was significantly higher compared with group C (94%, 69%, and 46% for group D, group M, and group C, respectively, P<0.05). Furthermore, there were more patients satisfied with group D than group M (94% vs.69%, P<0.05).
CONCLUSION
Intravenous dexmedetomidine (1 μg/kg) and midazolam (0.02 mg/kg) were equally effective in preventing PONV introduced by hemabate and dexmedetomidine is superior to midazolam in patient satisfaction.
Topics: Adult; Cesarean Section; Dexmedetomidine; Female; Humans; Injections, Intravenous; Midazolam; Postoperative Nausea and Vomiting; Postpartum Hemorrhage; Pregnancy; Young Adult
PubMed: 32546975
DOI: 10.2147/DDDT.S251525 -
American Journal of Veterinary Research Dec 2018OBJECTIVE To compare sedation in cockatiels (Nymphicus hollandicus) after intranasal administration of midazolam and midazolam-butorphanol. ANIMALS 9 healthy adult...
OBJECTIVE To compare sedation in cockatiels (Nymphicus hollandicus) after intranasal administration of midazolam and midazolam-butorphanol. ANIMALS 9 healthy adult cockatiels. PROCEDURES A randomized, controlled, blinded, complete crossover study was conducted. Birds were assigned to 3 treatment groups. Midazolam (3 mg/kg), midazolam-butorphanol (3 mg/kg for each drug), or sterile saline (0.9% NaCl) solution (control treatment) was administered intranasally. Sedation quality was assessed at 3 time points by use of eye and body position; response to visual, auditory, and tactile stimulation; and response during manual restraint on the basis of eye position and struggling intensity. To evaluate attenuation of the manual restraint-induced stress response, heart rate, respiratory rate, and cloacal temperature were measured over a 15-minute period. Treatments were repeated after a minimum washout period of 7 days. RESULTS Median onset of first sedation effects was 85 seconds (range, 60 to 120 seconds) for midazolam and 90 seconds (range, 45 to 180 seconds) for midazolam-butorphanol. Midazolam-butorphanol resulted in significantly less vigorous struggling during restraint than did midazolam or the control treatment. Heart rate did not differ significantly among treatments. The stress-induced increase in respiratory rate was significantly attenuated by midazolam and midazolam-butorphanol, whereas the increase in cloacal temperature was not attenuated by midazolam or midazolam-butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE Intranasal administration of midazolam and midazolam-butorphanol resulted in a rapid onset of sedation in cockatiels. Midazolam-butorphanol resulted in deeper sedation in both restrained and unrestrained birds than did midazolam alone. Midazolam and midazolam-butorphanol both provided safe and effective sedation in cockatiels.
Topics: Administration, Intranasal; Anesthesia; Animals; Butorphanol; Cockatoos; Cross-Over Studies; Female; Heart Rate; Hypnotics and Sedatives; Male; Midazolam; Respiratory Rate; Single-Blind Method
PubMed: 30457900
DOI: 10.2460/ajvr.79.12.1246 -
Epilepsia Open Jun 2023The neurosteroid allopregnanolone (ALLO) is under investigation as a treatment for benzodiazepine-refractory status epilepticus (SE). Here, we assess the cardiopulmonary...
The neurosteroid allopregnanolone (ALLO) is under investigation as a treatment for benzodiazepine-refractory status epilepticus (SE). Here, we assess the cardiopulmonary safety of intravenous ALLO by itself and after a clinically recommended dose of midazolam (MDZ) in two healthy adult beagles. Each dog received ALLO (1 mg/kg, IV), and after a washout period of 2 weeks, each dog was dosed with MDZ (0.2 mg/kg, IV) followed 10 minutes later by ALLO. Behavioral state, vital signs, arterial blood gases, blood chemistries, and plasma ALLO concentrations were monitored for up to 6 hours after dosing. The dogs appeared sleepy but were fully responsive after both treatments. No depression of mean arterial pressure or respiratory rate was noted. Blood gas measurements failed to show evidence of drug-induced acute respiratory acidosis. Estimated maximum plasma ALLO concentrations were in the range of 1500 to 3000 ng/ml. The results indicate that intravenous ALLO can be used safely to treat benzodiazepine-refractory SE, even when administered shortly after a benzodiazepine.
Topics: Dogs; Animals; Midazolam; Pregnanolone; Status Epilepticus; Administration, Intravenous
PubMed: 36919379
DOI: 10.1002/epi4.12723 -
Journal of Pain and Symptom Management Mar 2002Significant distress is experienced by patients, families, and caregivers when a symptom or disorder, such as an agitated delirium, becomes an intractable, or a...
Significant distress is experienced by patients, families, and caregivers when a symptom or disorder, such as an agitated delirium, becomes an intractable, or a catastrophic event, such as irreversible stridor. When palliative sedation is indicated for these patients, midazolam is usually the preferred drug. In some cases, however, midazolam fails to provide adequate sedation. Two cases are presented to illustrate this phenomenon and explore the possible mechanisms underlying this lack of response. These mechanisms appear to be multifaceted. The heterogeneity of the GABA(A) receptor complex and the alterations that this complex can undergo functionally can explain, to some degree, the diversity of the physiological and pharmacological outcomes. Other factors responsible for the diversity in response may include concomitant medications, age, concurrent disease, overall health status, alcohol use, liver disease, renal disease, smoking and hormonal status. Evidence-based guidelines on alternative treatment options should midazolam fail are required. In the interim, a lower threshold for adding an alternative drug, such as phenobarbital, or substituting midazolam with another drug, such as propofol, should be considered in these circumstances.
Topics: Humans; Hypnotics and Sedatives; Male; Midazolam; Middle Aged; Respiratory Sounds; Treatment Failure
PubMed: 11888723
DOI: 10.1016/s0885-3924(01)00412-2 -
Anesthesiology Nov 1990More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical...
More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical procedures. We investigated the respiratory effects of midazolam (0.05 mg.kg-1) and fentanyl (2.0 micrograms.kg-1) in volunteers. The incidence of hypoxemia (oxyhemoglobin saturation less than 90%) and apnea (no spontaneous respiratory effort for 15 s) and the ventilatory response to carbon dioxide were evaluated. Midazolam alone produced no significant respiratory effects. Fentanyl alone produced hypoxemia in half of the subjects and significant depression of the ventilatory response to CO2, but did not produce apnea. Midazolam and fentanyl in combination significantly increased the incidence of hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects), but did not depress the ventilatory response to CO2 more than did fentanyl alone. Adverse reactions linked to midazolam and reported to the Department of Health and Human Services highlight apnea- and hypoxia-related problems as among the most frequent adverse reactions. Seventy-eight per cent of the deaths associated with midazolam were respiratory in nature, and in 57% an opioid had also been administered. All but three of the deaths associated with the use of midazolam occurred in patients unattended by anesthesia personnel. We conclude that combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea. Adequate precautions, including monitoring of patient oxygenation with pulse oximetry, the administration of supplemental oxygen, and the availability of persons skilled in airway management are recommended when benzodiazepines are administered in combination with opioids.
Topics: Adolescent; Adult; Apnea; Carbon Dioxide; Conscious Sedation; Drug Interactions; Drug Therapy, Combination; Fentanyl; Humans; Hypoxia; Male; Midazolam; Respiration
PubMed: 2122773
DOI: 10.1097/00000542-199011000-00005 -
American Journal of Veterinary Research Sep 2022To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and...
A randomized clinical trial on effects of alfaxalone combined with medetomidine and midazolam in preventing stress-related neurohormonal and metabolic responses of isoflurane-anesthetized cats undergoing surgery.
OBJECTIVE
To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and metabolic changes in isoflurane-anesthetized cats undergoing ovariohysterectomy or castration.
ANIMALS
72 client-owned mixed-breed cats undergoing ovariohysterectomy or castration between October 4, 2018, and January 10, 2020.
PROCEDURES
For each type of surgery, cats were assigned to 1 of 6 premedication protocols groups, with 6 cats/group: physiologic saline (0.9% NaCl) solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IV); physiologic saline solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IM); medetomidine (50 μg/kg, IM) and alfaxalone (5 mg/kg, IV); medetomidine (50 μg/kg, IM) and alfaxalone (5 mg/kg, IM); midazolam (0.5 mg/kg, IM), medetomidine (50 μg/kg, IM), and alfaxalone (5 mg/kg, IV); or midazolam (0.5 mg/kg, IM), medetomidine (50 μg/kg, IM), and alfaxalone (5 mg/kg, IM). Venous blood was taken before pretreatment, pre- and postoperatively during anesthesia with isoflurane and oxygen, and during early and complete recovery.
RESULTS
Compared with baseline concentrations, plasma adrenaline and noradrenaline concentrations decreased during anesthesia in cats premedicated with alfaxalone alone and in combination with medetomidine. The combination of medetomidine, midazolam, and alfaxalone prevented an excessive increase in catecholamines during anesthesia and surgery in cats. Postoperative plasma cortisol concentration after ovariohysterectomy was lower for cats premedicated with the combination of medetomidine and alfaxalone or the combination of medetomidine, midazolam, and alfaxalone, compared with cats premedicated with alfaxalone alone. Cats treated with combinations that included medetomidine and midazolam had hyperglycemia during anesthesia. Cats treated with medetomidine or medetomidine and midazolam in combination with alfaxalone, compared with alfaxalone alone, had lower concentrations of nonesterified fatty acids during anesthesia. Behavioral recovery scores were lower (better) for cats that received medetomidine in addition to alfaxalone, compared with alfaxalone alone.
CLINICAL RELEVANCE
Results indicated that pretreatments with medetomidine and alfaxalone or with medetomidine, midazolam, and alfaxalone were useful for preventing stress-related hormonal and metabolic responses, other than hyperglycemia, during isoflurane anesthesia and surgery in cats.
Topics: Cats; Animals; Medetomidine; Midazolam; Isoflurane; Pregnanediones; Hyperglycemia; Anesthetics, Combined; Cat Diseases
PubMed: 36103386
DOI: 10.2460/ajvr.22.03.0041 -
Annals of Palliative Medicine Aug 2021Bronchoscopic examination including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is well established for lung cancer diagnosis and...
BACKGROUND
Bronchoscopic examination including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is well established for lung cancer diagnosis and staging. Sedation using fentanyl and midazolam is recommended during bronchoscopic examinations. Meanwhile, inadvertent oversedation is a clinical problem. The objective of this research was to estimate the frequency of apnea episodes by end-tidal capnography under fentanyl and midazolam sedation during bronchoscopy.
METHODS
Eighty-five patients were enrolled retrospectively between August 2017 and March 2018 at Okayama Medical Center. Apnea was defined as the cessation of airflow for more than 10 seconds. We reviewed medical records, including capnographic data, by cap-ONE YG-227T (NIHON KOHDEN, Tokyo, Japan) during flexible bronchoscopy under fentanyl and midazolam sedation.
RESULTS
Patients received 49.4±20.6 µg of fentanyl [mean ± standard deviation (SD)] and 4.35±2.0 mg of midazolam (mean ± SD). The patients included 52 males and 33 females; the median age was 71 (range, 31-88) years were enrolled. Apnea episodes were recorded (median duration 18 seconds) in 85 patients (100%). Prolonged apnea episodes with more than 30 seconds occurred in 56 patients (65.8%). Furthermore, the median time was 32 (range, 5-102) seconds whose delay between the onset of an apnea episode and decline in the SpO2 level of ≥4% from baseline.
CONCLUSIONS
End-tidal capnography, cap-ONE YG-227T was effective for detecting the occurrence of apnea in patients undergoing a bronchoscopic examination under fentanyl and midazolam sedation. Monitoring might be useful for preventing inadvertent oversedation.
Topics: Aged; Bronchoscopy; Conscious Sedation; Female; Fentanyl; Humans; Male; Midazolam; Retrospective Studies
PubMed: 34379981
DOI: 10.21037/apm-21-1009