Objective To evaluate the safety and effectiveness of oral midazolam sedation combined nitrous oxide sedation for reducing dental fear in children.Methods Totally 77 children with a Frankl's Behavior Rating Scale score of 1 were included in this study,among whom 41 received a total of 78 person-times of oral midazolam sedation (0.50-0.75 mg·kg ) (midazolam group) and 36 children were treated with the combination of 0.4 mg/kg oral midazolam with 30%-40% nitrous oxide (totally 73 person-times)(combination group). At each visit,heart rate,arterial oxygen saturation,and treatments were recorded. The behaviors of children during the treatment were assessed by Frankl's Behavior Rating Scale,the completion of treatment was assessed by Houpt Scale,and the sedation status was assessed by Ramsay Scale. Telephone follow-up was performed to record the side effects 24 hours after treatment. Results The vital signs were stable among all the 77 subjects,with a Ramsay score of 2 or 3. In the midazolam group, the behaviors were cooperative in 52 person-times (66.7%) and not cooperative in 26 person-times (33.3%);the planned treatments were completed in 62 person-times (79.5%) and partially completed in 16 person-times(20.5%). In the combination group,the behaviors were cooperative in 56 person-times (76.7%) and not cooperative in 17 person-times (23.3%);64 person-times (87.7%) completed the planned treatments and 9 person-times (12.3%) partially completed the treatments. The success rates of sedation (χ =1.87,P= 0.17) and treatment (χ =1.83,P= 0.18) were not significantly different between these two groups. The median Frankl scale score was significantly higher in the combination group [3 (3,4)] than in the midazolam group [3 (2,4)] (Z=2.647,P=0.008]. The median score of Houpt scale in the combination group [5(4,6)] was also significantly higher than in midazolam group [5(3,5)] (Z=2.236,P=0.026]. In midazolam group,there were 7 person-times of dysphoria,3 person-times of diplopia,and 2 person-times of hiccough among 78 person-times;in the combination group,there were 5 person-times of dysphoria,5 person-times of diplopia,1 person-time of hiccough,and 2 person-times of vomit among 73 person-times of treatment. Thus,there was no significant difference in the incidence of side effects (15.4% vs.17.8%,χ =0.160,P=0.689). Logistic regression analysis showed that the success rate of treatment was not associated with sex (OR=1.704,P=0.174),dose (OR=1.289,P=0.516),and treatment types (OR=0.555,P=0.143). Children over 3 years old had a significantly high success rate than those under 3 years old (OR=3.372,P=0.011). Conclusions Oral midazolam is safe and effective for reducing dental fear in children. The combination of oral midazolam with 30%-40% nitrous oxide can improve the behaviors of children during the dental treatment,especially in children over 3 years old.
Administration, Oral ; Anesthesia, Dental ; Child ; Child, Preschool ; Conscious Sedation ; Cross-Over Studies ; Dental Anxiety ; Humans ; Hypnotics and Sedatives ; Midazolam ; therapeutic use ; Nitrous Oxide

OBJECTIVES: Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb–drug interactions and may modify the clinical safety profile of therapeutic drugs. METHODS: We investigated the potential herb–drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1ʹ-hydroxymidazolam (1ʹ-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg). RESULTS: It was found that the AUC of MDZ and 1ʹ-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein. CONCLUSIONS: The altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.
Absorption* ; Administration, Oral ; Animals ; Area Under Curve ; Cytochrome P-450 Enzyme System ; Far East ; Herb-Drug Interactions ; Herbal Medicine ; Hydrogen-Ion Concentration* ; Mice ; Midazolam* ; Oral Mucosal Absorption ; P-Glycoprotein ; Pharmacokinetics ; Plasma ; Stomach*

PURPOSETo evaluate midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in ICU.

METHODSThis randomized, prospective study was conducted in Tianjin Third Central Hospital, China. Using a sealed-envelope method, the patients were randomly divided into 2 groups (40 patients per group). Each patient of group A received an initial loading dose of midazolam at 0.3-3mg/kg·h 24 h before extubation, followed by an infusion of dexmedetomidine at a rate of 0.2-1 μg/kg·h until extubation. Each patient of group B received midazolam at a dose of 0.3-3 mg/kg·h until extubation. The dose of sedation was regulated according to RASS sedative scores maintaining in the range of -2-1. All patients were continuously monitored for 60 min after extubation. During the course, heart rate (HR), mean artery pressure (MAP), extubation time, adverse reactions, ICU stay, and hospital stay were observed and recorded continuously at the following time points: 24 h before extubation (T1), 12 h before extubation (T2), extubation (T3), 30 min after extubation (T4), 60 min after extubation (T5).

RESULTSBoth groups reached the goal of sedation needed for ICU patients. Dexmedetomidine was associated with a significant increase in extubation quality compared with midazolam, reflected in the prevalence of delirium after extubation (20% (8/40) vs 45% (18/40)), respectively (p= 0.017). There were no clinically significant decreases in HR and MAP after infusing dexmedetomidine or midazolam. In the group A, HR was not significantly increased after extubation; however, in the group B, HR was significantly increased compared with the preextubation values (p < 0.05). HR was significantly higher in the group B compared with the group A at 30 and 60 min after extubation (both, p <0.05). Compared with preextubation values, MAP was significantly increased at extubation in the group B (p < 0.05) and MAP was significantly higher at T3, T4, T5 in the group B than group A (p < 0.05). There was a significant difference in extubation time ((3.0 ± 1.5) d vs (4.3 ± 2.2) d, p < 0.05), ICU stay ((5.4 ± 2.1) d vs (8.0 ± 1.4) d, p < 0.05), hospital stay ((10.1 ± 3.0) d vs (15.3 ± 2.6) d, p <0.05) between group A and B.

CONCLUSIONMidazolam sequential with dexmedetomidine can reach the goal of sedation for ICU agitated patients, meanwhile it can maintain the respiratory and circulation parameters and reduce adverse reactions.

Adult ; Aged ; Critical Care ; methods ; Delirium ; drug therapy ; etiology ; Dexmedetomidine ; administration & dosage ; Female ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Intensive Care Units ; Length of Stay ; Male ; Midazolam ; administration & dosage ; Middle Aged ; Prognosis ; Prospective Studies ; Respiration, Artificial ; adverse effects ; methods ; Risk Assessment ; Statistics, Nonparametric ; Treatment Outcome ; Ventilator Weaning ; adverse effects ; psychology

Dentists often sedate patients in order to reduce their dental phobia and stress during dental treatment. Sedatives are administered through various routes such as oral, inhalation, and intravenous routes. Intravenous administration has the advantage of rapid onset of action, predictable duration of action, and easy titration. Typically, midazolam, propofol or dexmedetomidine are used as intravenous sedatives. Administration of these sedatives via infusion by using a syringe pump is more effective and successful than infusing them as a bolus. However, during intravenous infusion of sedatives or opioids using a syringe pump, fatal accidents may occur due to the clinician's carelessness. To prevent such risks, smart syringe pumps have been introduced clinically. They allow clinicians to perform effective sedation by using a computer to control the dose of the drug being infused. To ensure patient safety, various alarm features along with a drug library, which provides drug information and prevents excessive infusion by limiting the dose, have been added to smart pumps. In addition, programmed infusion systems and target-controlled infusion systems have also been developed to enable effective administration of sedatives. Patient-controlled infusion, which allows a patient to control his/her level of sedation through self-infusion, has also been developed. Safer and more successful sedation may be achieved by fully utilizing these new features of the smart pump.
Administration, Intravenous ; Analgesics, Opioid ; Dental Anxiety ; Dentists ; Dexmedetomidine ; Humans ; Hypnotics and Sedatives ; Infusion Pumps ; Infusions, Intravenous ; Inhalation ; Midazolam ; Patient Safety ; Propofol ; Syringes*

BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is an uncomfortable procedure that requires adequate sedation for its successful conduction. We investigated the efficacy and safety of the combined use of intravenous midazolam and propofol for sedation during ERCP. METHODS: A retrospective review of patient records from a single tertiary care hospital was performed. Ninety-four patients undergoing ERCP received one of the two medication regimens, which was administered by a nurse under the supervision of a gastroenterologist. Patients in the midazolam (M) group (n=44) received only intravenous midazolam, which was titrated to achieve deep sedation. Patients in the midazolam pulse propofol (MP) group (n=50) initially received an intravenous combination of midazolam and propofol, and then propofol was titrated to achieve deep sedation. RESULTS: The time to the initial sedation was shorter in the MP group than in the M group (1.13 minutes vs. 1.84 minutes, respectively; p<0.001). The recovery time was faster in the MP group than in the M group (p=0.031). There were no significant differences between the two groups with respect to frequency of adverse events, pain experienced by the patient, patient discomfort, degree of amnesia, and gag reflex. Patient cooperation, rated by the endoscopist as excellent, was greater in the MP group than in the M group (p=0.046). CONCLUSIONS: The combined use of intravenous midazolam and propofol for sedation during ERCP is more effective than midazolam alone. There is no difference in the safety of the procedure.
Amnesia ; Cholangiopancreatography, Endoscopic Retrograde* ; Conscious Sedation ; Deep Sedation ; Humans ; Midazolam* ; Organization and Administration ; Patient Compliance ; Propofol* ; Reflex ; Retrospective Studies ; Tertiary Healthcare

This case report describes a life-threatening anaphylaxis to fentanyl during radiofrequency ablation (RFA). A 50-year-old woman with hepatocellular carcinoma was admitted for RFA. She denied any history of adverse drug reactions or past adverse anesthetic reaction. Physical examination, vital signs, any laboratory findings were all within normal limits. Ten minutes after intravenous administration of 50 mcg of fentanyl before starting RFA, she developed generalized erythema and sudden onset of bronchospasm followed by respiratory arrest. Cardiopulmonary resuscitation (CPR) commenced with 100% oxygen and intravenous administration of epinephrine 1 mg. After 5 minutes of CPR, she had the return of spontaneous circulation. Chest X-ray revealed pulmonary edema which resolved over two days. She recovered completely and was discharged home. After six weeks, intradermal tests performed with fentanyl, remifentanyl, midazolam, and profopol. Among those, only fentanyl induced positive skin response. Fentanyl induced anaphylaxis was diagnosed for this case, and fentanyl was avoided in the subsequent general anesthesia for liver transplantation. This case suggested that fentanyl could induce anaphylaxis combined with uncommon comorbidities like pulmonary edema.
Administration, Intravenous ; Anaphylaxis ; Anesthesia, General ; Bronchial Spasm ; Carcinoma, Hepatocellular ; Cardiopulmonary Resuscitation ; Comorbidity ; Drug Toxicity ; Epinephrine ; Erythema ; Female ; Fentanyl ; Humans ; Intradermal Tests ; Liver Transplantation ; Midazolam ; Middle Aged ; Oxygen ; Physical Examination ; Pulmonary Edema ; Skin ; Skin Tests ; Thorax ; Vital Signs

Adolescent ; Adult ; Analgesics ; administration & dosage ; Anesthetics, Intravenous ; administration & dosage ; Flurbiprofen ; administration & dosage ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Midazolam ; administration & dosage ; Middle Aged ; Molar, Third ; Pain Measurement ; Pain, Postoperative ; prevention & control ; Patient Satisfaction ; Preoperative Care ; Prospective Studies ; Tooth Extraction ; Young Adult

OBJECTIVETo observe the effectiveness of conscious sedation with midazolam, propofol and sufentanil for patients in plastic surgery.

METHODS81 patients, scheduled for plastic surgery, were randomly selected to receive conscious sedation with midazolam 0.05 mg x kg(-1) and sufentanil 0.1 microg x kg(-1) intravenously, following by a continuous infusion of midazolam-propofol-sufentanil combination (midazolam 5 mg + propofol 200 mg + sufentanil 10 microg, a total of 23 ml). The initial infusion rate was 0.2 ml x kg(-1) x h(-1), and was adjusted (in 20% of initial infusion rate increment) to maintain OAA/S score as 11 during the operation. The patients' vital signs, discomfort and level of sedation were evaluated at 5 to 10 min intervals until the end of the surgery. The complications (i. e. anoxemia, apnea, restlessness, nausea and vomiting), anesthesia duration and drug consumption were recorded. The drug infusion was discontinued at 5 - 10 min before the end of the surgical procedure. On the first postoperative day, patients were asked to rate their satisfaction with the anesthetic management and whether they would choose to receive the same anesthetic technique if necessary in the future.

RESULTSThe OAA/S score decreased from 20.0 +/- 0 to 11.9 +/- 2.6 after midazolam and sufentanil IV (P < 0.05), and was maintained as 10.5-11.1 during the procedure. At the end of the procedure, the OAA/S score returned to 16.0 +/- 2.2, which was also lower significantly compared with baseline value (P < 0.05). The induction of sedation produced a significant decrease in SBP and DBP (P < 0.05) and no significant changes in heart rate (P > 0.05). At the end of the procedure, SBP, DBP and HR returned to the baseline value. The anoxemia happened in 11 cases, apnea in 5 cases and restlessness in 2. No nausea and vomiting occurred. The anesthesia duration and consumption of midazolam, propofol and sufentanil were (101.1 +/- 42.5) min, (8.4 +/- 3.7) mg, (189.1 +/- 88.7) mg and (18.2 +/- 5.6) microg respectively. In an interview on the first postoperative day, 96% (78/ 81) of the patients were satisfied with their anesthesia and were willing to receive the same anesthetic technique if necessary in the future.

CONCLUSIONConscious sedation with midazolam, propofol and sufentanil is an effective anesthetic technique for patients in plastic surgery.

Adolescent ; Adult ; Conscious Sedation ; methods ; Female ; Humans ; Male ; Midazolam ; administration & dosage ; Middle Aged ; Propofol ; administration & dosage ; Sufentanil ; administration & dosage ; Surgery, Plastic ; Young Adult

Opioids are widely used as painkillers and anesthetics. Though we use opioids to relieve pain, these drugs can induce mood elevation, dependency, and withdrawal symptoms. This is why opioids are controlled-substances. Most physicians think that some substances should be controlled if they have opioid-like pharmacological properties, especially a long duration, preservation of respiration, and dependency. It is noteworthy that short-acting substances, such as midazolam and thiopental, are included in controlled substances. Their abuse is very dangerous because they frequently induce severe respiratory depression due to a narrow therapeutic window. Teaching point of this article is that designation of a new drug as a controlled substance requires scientific evidence of its link to dependency and/or withdrawal symptoms. However, this does not require abusers' convenience (long duration) or safety (maintenance of respiration). The authors present the addiction and abuse patterns of propofol as an reasons for the Korean Food and Drug Administration to designate propofol as a controlled substance. As a future study, an animal and/or a clinical model for dependency is needed to identify addictive substances. Though several neurotransmitters and their loci in the central nervous system have been studied, the precise mechanism for addiction is unknown. Also, it should be recognized that the potential for drug addiction and abuse could be masked in the early marketing period of a new drug. Physicians should monitor patients' responses carefully when they deal with the drug.
Aluminum Hydroxide ; Analgesics, Opioid ; Anesthetics ; Animals ; Carbonates ; Central Nervous System ; Controlled Substances ; Dependency (Psychology) ; Drug and Narcotic Control ; Marketing ; Masks ; Midazolam ; Neurotransmitter Agents ; Organothiophosphorus Compounds ; Propofol ; Respiration ; Respiratory Insufficiency ; Substance Withdrawal Syndrome ; Substance-Related Disorders ; Thiopental ; United States Food and Drug Administration

Anesthetics, Intravenous ; administration & dosage ; pharmacology ; Animals ; Animals, Newborn ; Cerebral Cortex ; cytology ; metabolism ; Drug Synergism ; Female ; Fentanyl ; administration & dosage ; pharmacology ; Male ; Midazolam ; administration & dosage ; pharmacology ; Neurons ; metabolism ; Patch-Clamp Techniques ; Primary Cell Culture ; Rats ; Rats, Sprague-Dawley ; Voltage-Gated Sodium Channels ; drug effects