OBJECTIVES: To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (V_acetonitrile∶V_methanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring. RESULTS: The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively. CONCLUSIONS This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.
Chromatography, Liquid/methods* ; Tandem Mass Spectrometry ; Methanol ; Carbamazepine/analysis* ; Benzodiazepines/analysis* ; Solvents ; Chromatography, High Pressure Liquid ; Solid Phase Extraction

OBJECTIVES: To identify recent prescription patterns, as well as the demographic and clinical correlates of antidepressants (ADs) usage in schizophrenic patients. METHODS: A total of 297 patients diagnosed with schizophrenia enrolled at Seoul National Hospital in 2013. Brief Psychiatric Rating Scale (BPRS) was used to evaluate current psychiatric symptoms. Bivariate comparisons were used to assess the usage of concomitant psychotropics, demographic and clinical characteristics of ADs users compared with non-users. Multivariate analysis of covariance was performed consecutively. RESULTS: The rate of ADs usage was 26.3% and the most commonly used ADs were selective serotonin reuptake inhibitors. ADs users more often took benzodiazepine than ADs non-users (p=0.005), whereas there were no significant demographic and other clinical difference between the two groups. Regarding BPRS, somatic concern (p=0.022), anxiety (p=0.001) and depressive mood (p=0.009) scores were higher, and excitement (p=0.006) and hostility (p=0.04) scores were lower among ADs users compared to non-users, although there was no significant difference in the other scores of BPRS between the two groups. Moreover, among 5 components of BPRS, scores of affective symptoms (p < 0.001) were significantly higher, and scores of activation symptoms (p=0.014) were significantly lower in ADs users compared to non-users. CONCLUSION: This study suggests that the usage of ADs could be related to affective symptoms regardless of positive and negative symptoms of schizophrenia. Further studies are required in order to confirm the clinical correlates of ADs usage and the interactions between affective symptoms and psychotic symptoms.
Affective Symptoms ; Antidepressive Agents* ; Anxiety ; Benzodiazepines ; Brief Psychiatric Rating Scale ; Hostility ; Humans ; Multivariate Analysis ; Prescriptions* ; Schizophrenia* ; Seoul ; Serotonin Uptake Inhibitors

BACKGROUND: While the combination therapy of morphine and benzodiazepine has been recommended as a standard therapy for sedation and analgesia in patients with mechanical ventilation, morphine can suppress respiratory center, and also decrease blood pressure and bowel movement. Because ketamine has analgesic and sedative effects compatible to morphine without depression of the cardiovascular and respiratory systems in addition to the preservation of bowel activity, ketamine may substitute morphine. However, it has not well known such potential advantages of ketamine in patients with mechanical ventilation. METHODS: Thirty eight patients (male:female=30:8, age=62.6 +/- 11.7 years) with mechanical ventilation were randomized as ketamine and morphine group (n=21 vs. n=17). There was no significant differences in sex, age and APACHE III score at the initiation of mechanical ventilation (ketamine group, morphine group: 79.4 +/- 2.0, 82.0 +/- 20.6). The study duration was 24 h after drug administration and minimum dose, which maintains ventilator-patient synchrony or the status of Ramsay score 3, was used. Ramsay sedation score, hemodynamic variables, respiratory and arterial blood gas variables, and bowel sound were measured at every 4 h. Arterial blood gas analysis was checked at 0, 4, and 24 h. RESULTS: 1) There were no significant differences in Ramsay sedation score and other hemodynamic, respiratory, and arterial blood gas variables in each group. The dose of combined midazolam was not different between two groups (ketamine vs. morphine; 52.1 +/- 11.9 vs. 46.7 +/- 15.1 mg/d; p=0.23). 2) The cases with decreased mean arterial pressure over 25% of the baseline shortly after the drug administration less frequently observed in ketamine group, although the difference did not reach statistical significance (n=2, 9.5% vs. n=5, 29.4%; p=0.12). 3) Bowel movement reduction at 4 h after the drug administration was less in ketamine group (n=1, 4.8% vs. n=6, 35.3%, p=0.03). The difference was not observed at 8 h. 4) Cost of the drug for 24 h was more expensive in ketamine group (dose & cost; 688 506 mg/d & 25,891 7,743 won vs. 40 +/- 18 mg/d, 15,814 +/- 4,853 won; p<0.001). CONCLUSIONS: Considering the advantages in the hemodynamics and bowel movement, ketamine may substitute morphine for the sedation of patients with mechanical ventilation, if indicated.
Analgesia* ; APACHE ; Arterial Pressure ; Benzodiazepines ; Blood Gas Analysis ; Blood Pressure ; Depression ; Hemodynamics ; Humans ; Hypnotics and Sedatives ; Ketamine* ; Midazolam ; Morphine* ; Respiration, Artificial* ; Respiratory Center ; Respiratory System

Micellar liquid chromatography (MLC) is a reversed phase liquid chromatography with mobile phases containing surfactant above its critical micellar concentration (CMC). The basic mechanism and advantages of MLC in physicochemical analysis were reviewed, and its applications in analysis of drugs, barbiturates, benzodiazepines were chiefly introduced in this paper. MLC is a potential method to toxicological analysis due to strong selectivity, wide application scope and easy biological samples, etc.
Analgesics, Opioid/analysis* ; Barbiturates/chemistry* ; Benzodiazepines/chemistry* ; Chromatography, Liquid/methods* ; Humans ; Hypnotics and Sedatives/chemistry* ; Micelles ; Reproducibility of Results ; Sensitivity and Specificity ; Solvents/chemistry* ; Surface-Active Agents/chemistry*

A new benzodiazepine derivative, Rohypnol (Ro 5-4200), was used for management of general anesthesia with nitrous oxide, narcotics and muscle relaxants to evaluate the effect on the cardiovascular and respiratory system in 35 surgical patients. In each patient, we observed the blood pressure, pulse rate, minute volume and arterial blood gas analysis and also local effects, postoperative recovery state and amnesia. The results are as follows; 1) Induction dosage of Rohypnol was not constant as other benzodiazepines. 2) Rohypnol showed a little effect an the cardiovascular system. 3) The effects of Rohypnol on the respiratory system were negligible but slight depression was seen. 4) If respiration became shallower or apnea occured during induction with Rohypnol, it was preferred to use assisted or controlled ventilation with 100% oxygen. 5) It was thought better to give oxygen through a nasal catheter for prevention of decreased PaO2 in recovery room. 6) When we used the non-depolarizing muscular relaxants instead of S.C.C. for intubation, we observed that a significantly decreased amount of relaxant was needed for maintenance of general anesthesia.
Amnesia ; Anesthesia, General ; Apnea ; Balanced Anesthesia* ; Benzodiazepines ; Blood Gas Analysis ; Blood Pressure ; Cardiovascular System ; Catheters ; Depression ; Flunitrazepam* ; Heart Rate ; Humans ; Intubation ; Narcotics ; Nitrous Oxide ; Oxygen ; Recovery Room ; Respiration ; Respiratory System ; Ventilation

OBJECTIVETo evaluate the effect of neonatal perioperative anesthetic exposure in complex cardiac surgery on neurodevelopmental outcomes in preschool children.

METHODSGeneral clinical data and data concerning anesthetic exposure were collected from 89 infants undergoing complex cardiac surgery at Sichuan People' Hospital. The cohort was followed for neurodevelopment till preschool age (48-72 months) and assessed with Wechsler Preschool and Primary Scale of Intelligence-III, Beery-Buktenica Developmental Test of Visual Motor Integration (VMI-V), and General Adaptive Composite (GAC) of the Adaptive Behavior Assessment System-II.

RESULTSSeventy-one children were enrolled into the final analysis. Multiple linear regression found days on benzodiazepines (beta;=-0.49, P=0.005) and cumulative dose of benzodiazepines (β=-0.10, P=0.023) were associated with the full-scale IQ in these preschool children. Days on benzodiazepines (beta;=-0.39, P=0.009) and on chloral hydrate (beta;=-1.19, P=0.020) were associated with lower performance intelligence quotient (PIQ) at the preschool age. Cumulative dose of benzodiazepine exposure (beta;=-0.008, P=0.012) was associated with lower VMI scores. No correlations of other sedation/analgesia variables were found with the full-scale IQ, PIQ, Verbal IQ, VMI, or GAC scores.

CONCLUSIONWe found a significant association of days on benzodiazepines, cumulative dose of benzodiazepines, and days on chloral hydrate in neonatal cardiac surgery with neurodevelopmental outcomes at the preschool age, suggesting the need of minimizing anesthetic exposure during a neonatal cardiac surgery to improve the children's neurodevelopmental outcomes.

Anesthetics ; administration & dosage ; adverse effects ; Benzodiazepines ; administration & dosage ; adverse effects ; Cardiac Surgical Procedures ; Child ; Child Development ; drug effects ; Child, Preschool ; Chloral Hydrate ; administration & dosage ; adverse effects ; Humans ; Infant, Newborn ; Linear Models ; Multivariate Analysis ; Perioperative Period