Objective: To estimate the consumption level of four drugs in Beijing using wastewater-based epidemiology (WBE). Methods: The primary sludge from one large wastewater treatment plants (WWTPs) was collected in Beijing from July 2020 to February 2021. The concentrations of codeine, methadone, ketamine and morphine in the sludge were detected through solid-phase extraction-liquid chromatography-tandem mass spectrometry. The consumption, prevalence and number of users of four drugs were estimated by using the WBE approach. Results: Among 416 sludge samples, codeine had the highest detection rate (82.93%, n=345) with a concentration [M (Q₁, Q₃)] of 0.40 (0.22-0.8) ng·g^-1, and morphine had the lowest detection rate (28.37%,n=118) with a concentration [M (Q₁, Q₃)] of 0.13 (0.09, 0.17) ng·g^-1. There was no significant difference in the consumption of the four drugs on working days and weekends (all P values>0.05). Drug consumption was significantly higher in winter than that in summer and autumn (all P values <0.05). The consumption [M (Q₁, Q₃)] of codeine, methadone, ketamine and morphine in winter was 24.9 (15.58, 38.6), 9.39 (4.57, 26.72), 9.84 (5.18, 19.45) and 5.67 (3.57, 13.77) μg·inhabitant^-1·day^-1, respectively. For these drugs, there was an upward trend in the average drug consumption during summer, autumn and winter (the Z values of the trend test were 3.23, 3.16, 2.19, and 3.32, respectively and all P values<0.05). The prevalence [M (Q₁, Q₃)] of codeine, methadone, ketamine and morphine were 0.0056% (0.003 4%, 0.009 2%), 0.0148% (0.009 6%, 0.026 7%),0.0333% (0.0210%, 0.0710%) and 0.0072% (0.003 8%, 0.011 7%), respectively. The estimated number of drug users [M (Q₁, Q₃)] was 918 (549, 1 511), 2 429 (1 578, 4 383), 5 451 (3 444, 11 642) and 1 173 (626, 1 925),respectively. Conclusion: Codeine, methadone, ketamine and morphine have been detected in the sludge of WWTPs in Beijing, and the consumption level of these drugs varies in different seasons.
Humans ; Beijing ; Wastewater-Based Epidemiological Monitoring ; Sewage/analysis* ; Wastewater ; Ketamine/analysis* ; Codeine/analysis* ; Methadone/analysis* ; Water Pollutants, Chemical/analysis*

Gamma band oscillation (GBO) and sensory gating (SG) are associated with many cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal cortex (PFC). However, the time-courses of the effects of different doses of ketamine on GBO power and SG are poorly understood. Studies have indicated that GBO power and SG have a common substrate for their generation and abnormalities. In this study, we found that (1) ketamine administration increased GBO power in the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were significantly correlated in awake rats. These results indicate a relationship between mechanisms underlying auditory SG and GBO power.
Acoustic Stimulation ; Analysis of Variance ; Animals ; Dose-Response Relationship, Drug ; Electroencephalography ; Excitatory Amino Acid Antagonists ; pharmacology ; Gamma Rhythm ; drug effects ; Ketamine ; pharmacology ; Male ; Prefrontal Cortex ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sensory Gating ; drug effects ; Sleep Stages ; drug effects ; Statistics as Topic ; Time Factors ; Wakefulness ; drug effects

OBJECTIVETo study the effects of ketamine combined with penehyclidine hydrochloride on the learning and memory abilities and the expression of synaptophysin in the hippocampus CA3 region in the brain of neonatal rats.

METHODSEighty seven-day-old Sprague-Dawly rats were randomly intraperitoneally injected with 50 mg/kg of ketamine (K group), 2 mg/kg of penehyclidine hydrochloride (P group), 50 mg/kg of ketamine plus 2 mg/kg penehyclidine hydrochloride (PK group) or normal saline (control group). The rats were trained and tested in a Morris water maze 14 days after administration. The immunhistochemical method was used to ascertain the expression of synaptophysin in the hippocampus CA3 region 24 hrs, 14 days and 28 days after administration.

RESULTSIn the Morris water maze training, the rats in the PK group performed worst, followed by the K group. The rats from the P and NS groups performed well. Compared with the NS group, the expression of synaptophysin in the K and the PK groups decreased significantly 24 hrs and 14 days after administration (p<0.05). The PK group had lower synaptophysin expression than the K group 24 hrs and 14 days after administration (p<0.05). Up to 28 days after administration, the synaptophysin expression increased in all of the four groups and there were no significant differences between groups.

CONCLUSIONSKetamine combined with penehyclidine hydrochloride may inhibit more significantly learning and memory abilities and the synaptophysin expression in the hippocampus CA3 region than ketamine alone in neonatal rats. Penehyclidine hydrochloride alone has no effect on learning and memory abilities and the synaptophysin expression. The synaptophysin expression may increase to a normal level by training and with increasing age.

Animals ; Animals, Newborn ; Cholinergic Antagonists ; pharmacology ; Drug Therapy, Combination ; Excitatory Amino Acid Antagonists ; pharmacology ; Hippocampus ; chemistry ; drug effects ; Ketamine ; pharmacology ; Maze Learning ; drug effects ; Memory ; drug effects ; Quinuclidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; physiology ; Synaptophysin ; analysis

We replaced anesthesia of operations, which has done under local or general anesthesia, by MAC(monitored anesthesia care) with various patient's monitoring devices such as BIS(bispectral index). From April 2003 to March 2004, 48 cases of operations were done in MAC with supplemental equipments. Induction, maintenance of anesthesia was performed by propofol and midazolam. Pain control was done by fentanyl and ketamine. For monitoring the depth of anesthesia in real time, and BIS scale was checked and was maintained in 40-60. All anesthesias were done by the anesthesiologist that was communicated with operator for information between patient's status and operation procedures. All operations and anesthesias progressed with stability and safety, and there was no major postoperative complication. Because BIS was relatively accurate device, there was no over dose of anesthetic agents, which was induced by patient's uncertain pain complain under sedation and no anxiety of operator, that was raised by no responsive patient. BIS made possible that operation under MAC was effective and safe, operator perform it with non-stress condition and followed by good surgical result.
Anesthesia* ; Anesthesia, General ; Anesthesia, Intravenous ; Anesthetics ; Anxiety ; Conscious Sedation* ; Fentanyl ; Humans ; Ketamine ; Midazolam ; Postoperative Complications ; Propofol ; Spectrum Analysis ; Surgery, Plastic*

BACKGROUND: The problem of psychological complications (trauma) by intraoperative awareness is a well discussed issue recently. The bispectral index (BIS) is reported to be closely related to the sedation and consciousness of anesthetics. This study was to observe the effects of ketamine injection and enflurane inhalation on the BIS, Apgar score of the neonate and blood gas analysis of umbilical cord artery and vein with general anesthesia for a Cesarean section. METHODS: The subjects of the study were 30 pregnant women who received a Cesarean section with general anesthesia. Before the delivery enflurane 1.0% inhalation group (group 1, n = 10), ketamine 20 mg injected group (group 2) and both ketamine 20 mg injected and enflurane 1.0% inhalation group (group 3) were assessed by BIS, blood pressure, heart rate, induction-delivery time, Apgar score of the neonate at 1, 5 minutes and blood gas analysis of the umbilical artery and vein. RESULTS: The BIS of all groups was over 70 after tracheal intubation and the ketamine injected group (group 2) was higher than the enflurane inhalation group (group 1) from 2 minutes after tracheal intubation. The BIS of the both ketamine 20 mg injected and enflurane 1.0% inhalation group (group 3) was lower than the ketamine injected group (group 2), 4 minutes after tracheal intubation. The Apgar score of neonates and blood gas analysis of the umbilical cord artery and vein had no significant differences between these groups. CONCLUSIONS: In the anesthetics injected before delivery in a cesarean section under general anesthetics, a small dose of ketamine can increase the BIS while a small dose of ketamine with 1.0% enflurane inhalation decreases the BIS, but in all groups the BIS was over 70 which can cause intraoperative awareness. Thus to avoid this problem, more studies are needed on the methods of anesthesia and multifactorial approaches to increase the utility of BIS monitoring.
Anesthesia ; Anesthesia, General* ; Anesthetics ; Anesthetics, General ; Apgar Score ; Arteries ; Blood Gas Analysis ; Blood Pressure ; Cesarean Section* ; Consciousness ; Enflurane ; Female ; Heart Rate ; Humans ; Infant, Newborn ; Inhalation ; Intraoperative Awareness ; Intubation ; Ketamine ; Pregnancy ; Pregnant Women ; Umbilical Arteries ; Umbilical Cord ; Veins

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

Ketamine is well known for its analgesic, bronchodilating and sympathetic stimulating effect. Hence, it has been widely used for induction of patients with hypotension or asthma and also for analgesic and sedating purposes in the ICU. We presented a 62 year old female patient with ventilator support in septic shock with refractory asthma whom we managed successfully with continuous intravenous infusion of ketamine postoperatively in the ICU. The patient had a history of asthma but had been asymptomatic recently and was scheduled for an emergent explo-laparotomy under the diagnosis of acute panperitonitis. Before the induction of anesthesia, the patient was in septic shock but no wheezing could be auscultated. After the induction of general anesthesia and endotracheal intubation, wheezing was apparent in both lung fields with a high peak inspiratory pressure. Inotropics, vasopressors and bronchodilators were promptly instituted without any improvement of asthma and the patient had to be transferred to the ICU with intubated after the operation. Clinical symptoms of asthma continued throughout the first day despite using bronchodilators under mechanical ventilation but, after starting the IV infusion of ketamine, there were decrease in the peak inspiratory pressure and wheezing with a subsequent improvement in the arterial blood gas analysis findings. We could also achieve considerable analgesic and sedating effect without any decrease in the blood pressure. The patient's general physical status improved and weaning with extubation was successfully done on the 21st day and was transferred to the general ward on the 28th day.
Anesthesia ; Anesthesia, General ; Anesthetics ; Asthma ; Blood Gas Analysis ; Blood Pressure ; Bronchodilator Agents ; Diagnosis ; Female ; Humans ; Hypotension ; Infusions, Intravenous ; Critical Care ; Intubation, Intratracheal ; Ketamine* ; Lung ; Middle Aged ; Patients' Rooms ; Respiration, Artificial ; Respiratory Sounds ; Shock, Septic* ; Status Asthmaticus* ; Ventilators, Mechanical ; Weaning

BACKGROUND: The use of ketamine as the sole anesthetic induces marked central sympathetic stimulation, causing an increase of heart rate and blood pressure. alpha2-receptor agonist has been demonstrated to attenuate many of these undesirable effects when used as a premedicant. Brimonidine is a new and highly selective alpha2-receptor agonist, and rauwolscine is a selective alpha2-receptor antagonist with little affinity for imidazoline receptors. Using power spectral analysis of heart rate variability, this study examines the effect of brimonidine premedication during ketamine anesthesia on the changes in the autonomic nervous system. METHODS: From 57 Sprague-Dawley rats, 12 rats were anesthetized by urethane (U Group, 1.5 g/kg), 18 rats by ketamine (K Group, 100 mg/kg, 2 mg/kg/min continuous infusion) intraperitoneal injection after saline premedication. Brimonidine (BK Group, 30 microgram/kg, n=15), brimonidine with rauwolscine (BRK Group, 30 microgram/kg, 20 mg/kg, n=12) were adminstered as a premedicant before induction of ketamine anesthesia. ECG signals were recorded for 5 min after a period of 10 min of anesthetic stabilization. Power spectal analysis of the data was computed, using short-time Fourier transform. The spectral peaks within each measurement were calculated; a low frequency area (0.04~1.0 Hz), a high frequency area (1.0~5.0 Hz), and a total frequency area (0.04~5.0 Hz) were measured. RESULTS: The results documented that the K Group showed sympathetic activation as compared with the U Group (p<0.001). The BK Group showed sympathetic depression compared with the K and BRK Groups (p<0.001). There were no significant differences in sympatho-vagal balance between the K and BRK Groups. CONCLUSIONS: These results suggest that premedication with brimonidine is effective in attenuating the sympathetic stimulatory effect of ketamine.
Anesthesia* ; Animals ; Autonomic Nervous System ; Blood Pressure ; Depression ; Electrocardiography ; Fourier Analysis ; Heart Rate ; Imidazoline Receptors ; Injections, Intraperitoneal ; Ketamine* ; Premedication* ; Rats ; Rats, Sprague-Dawley ; Sympathetic Nervous System* ; Urethane ; Yohimbine ; Brimonidine Tartrate

BACKGROUND: This study was aimed to elucidate the effect of ketamine anesthesia on circulatory response to hemorrhage in rats by power spectral analysis of heart rate and blood pressure variability. METHODS: Nineteen male Sprague-Dawley rats weighing 290~475 g were divided into ketamine (100 mg/kg, im)-anesthetized(K, n=10) and conscious(C, n=9) groups. Hemorrhage was induced with a withdrawal pump from the femoral artery at 3 ml/kg/min for 5 min. Arterial pressure was measured with a pressure transducer connected to the contralateral femoral artery for 5 min before, during and after hemorrhage. The blood pressure signal digitized at 500 Hz through a data acquisition system was analyzed with fast Fourier transform algorithm to yield power spectra of sytolic(SP) and diastolic(DP) blood pressure and instantaneous heart rate(HR). Powers of very low frequency(VLF, 0.02~0.26 Hz), low frequency (LF, 0.26~0.75 Hz) and high frequency(HF, 0.75~5.00 Hz) band were expressed as percent of total power. RESULTS: Before hemorrhage blood pressure was higher in K(152.4+/-3.7/99.9+/-4.9 mmHg) than in C(143.3+/-5.7/95.5+/-4.1 mmHg) rats, but was changed by hemorrhage in both groups. Before hemorrhage HR in K and C rats were 361.4+/-17.5 and 363.4+/-18.5 beats/min . HR were significantly increased to 403.2+/-20.3 and 396.2+/-18.9 beats/min during and after hemorrhage in K rats, and increased to 409.1+/-20.9 beats/min during hemorrhage in C rats. Before hemorrhage total powers of blood pressure and HR variability were higher in K than in C rats. During hemorrhage, total powers of blood pressure and heart rate variability tended to increase in both groups. Before hemorrhage, percent powers of systolic pressure variability of HF and VLF were higher in K than in C rats and LF was lower in K than in C rats. During hemorrhage, K group showed no significant changes but C group showed significant changes. Before hemorrhage, percent powers of diastolic pressure variability of VLF was higher in Kthan in C rats, and HF and LF were lower in K than in C rats. During and after hemorrhage, K group showed no significant changes, but C group showed significant decrease in LF and increase in VLF. Before hemorrhage, percent powers of heart rate variability of K rats showed higher HF and VLF, and lower LF than C rats. During and after hemorrhage HF and VLF of both groups showed no significant changes except significant increase in VLF after hemorrhage in C rats, but LF of both groups showed significant decrease. CONCLUSIONS: It was concluded that autonomic activity, especially cardiac sympathetic activity, was increased in response to hemorrhage in K rats. Ketamine anesthesia stimulated overall autonomic activity, especially sympathetic activity and vasomotor tone. In C rats hormonal factor contributed to blood pressure and heart rate variability during hemorrhage.
Anesthesia ; Animals ; Arterial Pressure ; Blood Pressure* ; Femoral Artery ; Fourier Analysis ; Heart Rate* ; Heart* ; Hemorrhage* ; Humans ; Ketamine ; Male ; Rats* ; Rats, Sprague-Dawley ; Transducers, Pressure

BACKGROUND: Serious pulmonary complications after lung surgery increase morbidity and mortality in perioperative period. Ketamine hydrochloride produces strong analgesic effect in spite of the psychomimetic effects. Intravenous anesthesia with ketamine was performed in lung surgery of patients with decreased pulmonary function and compared with inhalation anesthesia with enflurane. METHODS: Sixty patients, scheduled for elective lung surgery, were randomly assigned to two groups. Patients received either enflurane (Group 1, n=30) or ketamine (Group 2, n=30) as main anesthetic drug. Blood pressure and heart rate were compared in preinduction, postinduction, postintubation, postincision, intraoperative period (30 minutes, 60 minutes) and recovery room between groups, and in each group. Arterial blood gas analysis was compared in preoperative period, intraoperative period and recovery room between groups. Postoperative psychological complications evaluated in group 2. RESULTS: Blood pressure and heart rate were significantly different in postinduction, postintubation and recovery room between groups. PaO2 in group 2 was higher than in group 1 during intraoperative period and recovery room. Postoperative psychological complications occured in 4 patients (13%) in group 2. CONCLUSIONS: Ketamine affords advantage over enflurane anesthesia in terms of PaO2 during intraoperative period and recovery room in lung surgery of patients with decreased pulmonary function.
Anesthesia ; Anesthesia, Inhalation* ; Anesthesia, Intravenous* ; Blood Gas Analysis ; Blood Pressure ; Enflurane* ; Heart Rate ; Humans ; Inhalation* ; Intraoperative Period ; Ketamine* ; Lung* ; Mortality ; Perioperative Period ; Preoperative Period ; Recovery Room