Application of quantitative pharmacology in vaccine research and development: overview and prospect / 中国临床药理学与治疗学

This article introduces the mechanism including antigen presentation, adjuvant, lymphatic system and the characteristics of vaccine, and then summarizes the key applications of core pharmacometrics approaches including QSP, PK/PD, dose response analysis, MBMA, in dose-response, preclinical and clinical translation, and correlation between biomarkers and efficacy of vaccines. It is expected that the successful application of model informed drug development can promote model informed vaccine development so that pharmacometrics makes its due contributions to the development of safer, more effective and more controllable vaccine products.

Data Mining and Systems Pharmacology to Elucidate Effectiveness and Mechanisms of Chinese Medicine in Treating Primary Liver Cancer / 中国结合医学杂志

OBJECTIVE@#To identify specific Chinese medicines (CM) that may benefit patients with primary liver cancer (PLC), and to explore the mechanism of action of these medicines.@*METHODS@#In this retrospective, singlecenter study, prescription information from PLC patients was used in combination with Traditional Chinese Medicine Inheritance Supports System to identify the specific core drugs. A system pharmacology approach was employed to explore the mechanism of action of these medicines.@*RESULTS@#Taking CM more than 6 months was significantly associated with improved survival outcomes. In total, 77 putative targets and 116 bioactive ingredients of the core drugs were identified and included in the analysis (P<0.05). A total of 1,036 gene ontology terms were found to be enriched in PLC. A total of 75 pathways identified from Kyoto Encyclopedia of Genes and Genomes were also enriched in this disease, including fluid shear stress, interleukin-17 signaling, signaling between advanced glycan end products and their receptors, cellular senescence, tumor necrosis factor signaling, p53 signaling, cell cycle signaling, steroid hormone biosynthesis, T-helper 17 cell differentiation, and metabolism of xenobiotics by cytochrome. Docking studies suggested that the ingredients in the core drugs exert therapeutic effects in PLC by modulating c-Jun and interleukin-6.@*CONCLUSIONS@#Receiving CM for 6 months or more improves survival for the patients with PLC. The core drugs that really benefit for PLC patients likely regulates the tumor microenvironment and tumor itself.

Mechanisms of Chinese medical formula Fangji Huangqi Decoction as an effective treatment of nephrotic syndrome based on systems pharmacology / 中草药·英文版

Objective: With the development of the society, the number of people who catch the nephrotic syndrome (NS) is going up roughly. As we all know, traditional Chinese medicine (TCM), especially Fangji Huangqi Decoction (FHD), has a long history with good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated. Methods: In this study, TCMSP platform was employed to screen active compounds of each herb of Fangji Huangqi Decoction combined with literatures. Furthermore, PharmMapper and SEA were used to predict and screen the active targets of FHD, and the HOME-NCBI-GENE, GeneCards and OMIM database were used to screen the active targets of NS. The GO and KEGG pathways involved in the targets were analyzed by ClueGO. Finally, contribution index was used to screen the active ingredients of FHD in the treatment of NS. Results: After drug-likeness (DL) and bioavailability (OB) filtering, 43 compounds were selected from FHD, interacting with 85 NS-related targets. Systematic analysis of the constructed networks revealed that it was mainly involved in PI3K-Akt signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway and TNF signaling pathway. The contribution index of every active ingredient also indicated five compounds, including astragaloside IV, quercetin, glycyrrhizic acid, glycyrrhizin and fangchinoline. Conclusions: These results have successfully predicted the pharmacodynamic material basis and the mechanism efficiency of FHD in the treatment of NS.

Mechanism of Dipsaci Radix in treatment of osteoporosis based on systematic pharmacology / 中草药

Objective To explore the possible mechanism of Dipsaci Radix in the treatment of osteoporosis based on systems pharmacology method. Methods The drug components of Dipsaci Radix were obtained from TCMSP database to screen active ingredients and predict target protein. The target protein of osteoporosis was searched in the TTD and CTD database in order to build Drug-Target protein-Disease interaction Network. Then, the analysis on the role of core target protein pathways were performed by DAVID tool. The protein interaction network of primary signal pathways was built in String database. Results Seven active ingredients of Dipsaci Radix and their 63 target proteins were obtained, 118 targets of osteoporosis were selected, and 118 cross-acting proteins between Dipsaci Radix and osteoporosis were obtained. Then 24 signaling pathways related to cell proliferation and differentiation and immune function were enriched, wherein PI3K-AKT signaling pathway contained the largest number of related genes. String database analysis showed that AKT1, MAPK1, and MAPK3 protein appeared frequently in signal pathways. Conclusion Dipsaci Radix may affect the PI3K-AKT signaling pathway mainly through AKT1, MAPK1, and MAPK3 for the treatment of osteoporosis. This study provides a new idea for the further mechanism study on the treatment of osteoporosis of Dipsaci Radix.

In Silico System Pharmacology for the Potential Bioactive Ingredients Contained in Xingnaojing Injection () and Its Material Basis for Sepsis Treatment / 中国结合医学杂志

OBJECTIVE@#To elucidate the action mechanism of Xingnaojing Injection (, XNJI) for sepsis, and to target screen the potential bioactive ingredients.@*METHODS@#An integrated protocol that combines in silico target screen (molecular docking) and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target (C-T) interaction network. The XNJI's bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-lipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction.@*RESULTS@#Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment.@*CONCLUSIONS@#The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.

System pharmacology-based study on mechanism of Polygala Radix in the treatment of Alzheimer's disease / 药学学报

This study was designed to investigate the molecular mechanism and potential active constituents of Polygala Radix in the treatment of Alzheimer's disease with multiple data bases combined with literature mining to build Polygala Radix chemical composition database. A novel analysis tool Pharmmapper was used to obtain the main active ingredient and potential target of Polygala Radix. By extensive data profiling, the Polygala Radix was found to contain 111 chemical constituents. Among them, a total of 10 active molecules included 3 xanthone, 1 saponins, 3 oligosaccharide esters, and 3 other classes were related to 13 Alzheimer's disease-related targets. Two of the core targets were beta-secretase 1 and glycogen synthase kinase-3 beta. Use the GO analysis and KEGG to explore the molecular mechanism of Polygala Radix in treatment of Alzheimer's disease, which has 3 signaling pathways, and the most important signaling pathway is the cell death signaling pathway. The active constituents of Polygala Radix could control the formation of Aβ and the apoptosis of cells through the interaction with multiple targets, and control the treatment of Alzheimer's disease.

Effect of Intravenous Clonidine-Fentanyl on Prevention of Postepidural Shivering / 대한마취과학회지

BACKGROUND: The purpose of this study was to evaluate the efficacy of intravenous clonidine-fentanyl to prevent postepidural shivering in patients undergoing an elective orthopedic surgery. METHODS: Forty ASA class 1 or 2 patients who received epidural anesthesia for an orthopedic surgery were allocated randomly to two groups. 10 min before epidural anesthesia group 1 received intravenous clonidine 2.0ng/kg and group 2 received clonidine 1.0ng/kg and fentanyl 1.0ng/kg shivering was determined objectively by observing involuntary muscle activity. Mean arterial pressure, heart rate and sedation score were measured at 5 minute intervals during the first 30 minutes following epidural anesthesia. RESULTS: There were no significant differences between the two groups in the occurrence of shivering, hemodynamic changes and sedation score. CONCLUSIONS: Intravenous clonidine 2.0ng/kg and the combination of clonidine 1.0ng/kg and fentanyl 1.0ng/kg were not significantly different in occurrence of postepidural shivering. Therefore, a combination of small doses of intravenous clonidine and fentanyl may be safe and useful to reduce postepidural shivering.

The Effect of Epidural Phenylephrine on Hypotension Induced by Epidural Anesthesia for Cesarean Delivery / 대한마취과학회지

BACKGROUND: Hypotension can occur after high level of epidural anesthesia. Like ephedrine, epidural phenylephrine is known to reduce the incidence of hypotension induced by the epidural administration of lidocaine. The purpose of this study was to determine whether combining epidural phenylephrine can reduce the incidence of hypotension in epidural anesthesia. METHODS: Ninety-two patients undergoing a cesarean section were divided into three groups. Patients assigned to three groups received 20-25 ml of lidocaine containing fentanyl 50 microgram with one of three doses of phenylephrine; 0 microgram (Group 1), 100 microgram (Group 2), or 200 microgram (Group 3), injected via the lumber epidural catheter. The mean blood pressure and heart rate were recorded every 10 min for 1 h after injection and were compared among the groups. Pinprick testing was performed to determine the highest level of sensory block and the time to two-segment regression. Also, the incidence of hypotension and ephedrine required were investigated. RESULTS: The incidence of hypotension was 37%, 28%, and 40% in Group 1-3, respectively. The time to two-segment regression was 94.7 +/- 21.6 in group 1, 100.8 +/- 20.1 min in Group 2, compared to 118.2 +/- 26.3 min in Group 3. CONCLSIONS: We found that epidural phenylephrine significantly prolonged the duration of epidural anesthesia, but it was ineffective for preventing hypotension induced by lidocaine epidural anesthesia.

Effects of Intracoronary Epinephrine on Coronary Blood Flow, Oxidative Metabolism and Mechanical Function in Normal and Stunned Myocardium in Dogs / 대한마취과학회지

BACKGROUND: Epinephrine is frequently administered during cardiac surgery. The vascular response to epinephrine might be altered by ischemia and reperfusion, since altered vascular control has been demonstrated even after a short period of ischemia. To test the hypothesis, the effects of epinephrine on regional myocardial contractility, coronary blood flow (CBF) and myocardial oxygen consumption (MVO2) were investigated before and after ischemia in an open-chest canine myocardium. METHODS: Fifteen dogs were acutely instrumented under enflurane anesthesia to measure aortic and left ventricular pressures, pulmonary and left anterior descending (LAD) blood flows via Doppler flowmeter, and subendocardial segment length in the region supplied by LAD. Incremental doses of epinephrine (4, 10, 20, 30 ng/mL of LAD flow) were infused directly into LAD before (normal) and after a 15 min of LAD occlusion and subsequent 30 min-reperfusion (stunned). Segment shortening (%SS), as an index of regional myocardial contractility was evaluated. Simultaneous arterial and coronary venous contents of oxygen and lactate were measured during epinephrine (0.0, 4, 10, and 30 ng/mL) infusion. Effectiveness of metabolic vasodilation was determined from oxygen extraction ratio (EO2). RESULTS: Epinephrine infusions before ischemia resulted in dose-dependent increases in %SS and MVO2. These changes were accompanied by excessive increases in CBF, resulting in decreased EO2. After the ischemia and reperfusion, %SS was depressed and lactate extraction (Elac) was reduced, but similar mechanical responses to epinephrine were observed. However, in the stunned myocardium, CBF increased in parallel with increases in MVO2, resulting in unaltered EO2. Epinephrine infusion further decreased Elac dose-dependently in stunned myocardium. Heart rate and left ventricular systolic and diastolic pressures were little but similarly affected during epinephrine infusions before and after myocardial ischemia. CONCLUSIONS: The results suggest that epinephrine exerts positive inotropic effects in both normal and stunned myocardium, and that epinephrine causes direct coronary vasodilation in normal myocardium, but this effect is abolished in stunned myocardium in dogs. It is also suggested that epinephrine infusion depresses Elac dose-dependently in stunned myocardium.

The Effect of Norepinephrine on Blood Pressure and Blood Flow of the Brachial and Femoral Arteries / 대한마취과학회지

BACKGROUND: Arterial pressure is the most commonly utilized guideline for the management of critically ill patients. However, the site of arterial pressure monitoring can impact the observed pressure. In patients undergoing cardiac surgery, peripheral arterial pressure can underestimate central aortic pressure and vasodilators magnify this phenomenon. There was also a large discrepancy between radial and femoral artery pressure in endotoxemic patients treated with vasopressors or hypothermic patients. We evaluated the effect of the continuous infusion of norepinephrine, the most commonly used vasopressor, on pressure and blood flow in both the brachial and femoral artery in dogs in normal condition. METHODS: Both the brachial and femoral arteries were cannulated for pressure monitoring and the other side arteries were exposed for the measurement of blood flow in 10 dogs. Two doses of norepinephrine (NE), 0.05 microgram/kg/min and 0.1 microgram/kg/min, were infused for 10 minutes each in sequence. Hemodynamic variables and blood flow were measured before the infusion of NE, and immediately after the infusion of the two doses of NE. RESULTS: NE increased both brachial and femoral arterial pressures with no difference between the two pressures. NE decreased blood flow in both brachial and femoral arteries even though cardiac output was maintained constantly which means NE caused the redistribution of blood flow. CONCLUSIONS: Unlike endotoxemic shock conditions or hypothermic vasoconstriction, NE didn't show different effects on pressure monitoring sites regardless of their diameter in normal condition. NE increased blood pressure and decreased blood flow in the same degree in both the brachial and femoral artery.

The Effect of Thoracic Epidural Block on the Defibrillation Threshold and Neuroendocrine Responses in Dogs / 대한마취과학회지

BACKGROUND: Epidural block is known to block sympathetic efferent nerve fiber, resulting in the decrease of catecholamine. We examined the effects of thoracic epidural block on DFT, neuroendocrine responses and hemodynamic changes in dogs. METHODS: Twenty one dogs were divided into three groups. The control group (N = 7) was anesthesized with only alpha-chloralose for general anesthesia, and a high thoracic epidural (T; N = 7) while the thoracolumbar epidural groups (TL; N = 7) were put under general anesthesia with high thoracic or thoracolumbar epidural blocks, respectively. The DFT was determined at 30 mins after surgical manipulation in the control group and at 10 mins after the epidural blocks in the two epidural groups. Four hemodynamic variables, catecholamine, cAMP and lactate were measured at 30 mins after the surgical manipulation (resting period), at 10 mins after epidural blocks and after defibrillation. RESULTS: 1) The DFT levels were significantly higher in the T (6.4 +/- 2.2 J) and TL groups (11.2 +/- 9.3 J) than in the control group (3.2 +/- 1.6 J)(P < 0.05). In the TL group, epinephrine-induced second DFT was lower (3.0 +/- 1.5 J) than the first DFT (11.2 +/- 9.3 J)(P < 0.05). 2) Catecholamine levels and hemodynamic variables including heart rate, mean arterial pressure, and cardiac output significantly decreased in the TL group compared with the control group after epidural block and defibrillation (P < 0.05). The DFT showed a significant correlation with plasma epinephrine levels after the epidural block (r = 0.56, P < 0.05). CONCLUSIONS: Our results show, an increase in transmyocardial DFT by the epidural block which may be caused by a decrease in catecholamine, especially epinephrine.

The Effects of Ephedrine and Prehydration on the Cardiovascular Response during Spinal Anesthesia / 대한마취과학회지

BACKGROUND: This study was designed to compare the efficacy of an ephedrine intramuscular injection with crystalloid or colloid administration for the prevention of cardiovascular change during spinal anesthesia undergoing Transurethral Resection of Prostate (TURP). METHODS: Eighty ASA I-II patients scheduled for TURP under spinal anesthesia were randomly allocated to receive non of the vasopressors or fluids (control group), 40 mg of i.m. ephedrine (ephedrine group), 15 ml/kg of i.v. lactated Ringer'solution (crystalloid group), and 8 ml/kg of i.v. pentastarch(colloid group). 12 mg of 0.5% hyperbaric tetracaine was injected through a 24 gauge Quinke needle at the L4-5 interspace in all patients. All patients were placed in the supine position and blood pressure (BP) and heart rate were recorded at 1-min intervals for 10 min, 2-min intervals for the next 10 min and subsequently at 5-min intervals. The sensory level was determined by pin prick test using 27 gauge needle. RESULTS: In the ephedrine group, systolic blood pressure was significantly greater than the other groups between 1 and 40 min after spinal anesthesia. (p<0.05) The changes in diastolic BP, mean BP and heart rate in the all groups were similar. CONCLUSION: The result of intramuscular injection of ephedrine may be more effective than crystalloid or colloid adminstration for the prophylaxis of hypotension during spinal anesthesia undergoing TURP.

The Effects of Ephedrine and Prehydration on the Cardiovascular Response during Spinal Anesthesia / 대한마취과학회지

BACKGROUND: This study was designed to compare the efficacy of an ephedrine intramuscular injection with crystalloid or colloid administration for the prevention of cardiovascular change during spinal anesthesia undergoing Transurethral Resection of Prostate (TURP). METHODS: Eighty ASA I-II patients scheduled for TURP under spinal anesthesia were randomly allocated to receive non of the vasopressors or fluids (control group), 40 mg of i.m. ephedrine (ephedrine group), 15 ml/kg of i.v. lactated Ringer'solution (crystalloid group), and 8 ml/kg of i.v. pentastarch(colloid group). 12 mg of 0.5% hyperbaric tetracaine was injected through a 24 gauge Quinke needle at the L4-5 interspace in all patients. All patients were placed in the supine position and blood pressure (BP) and heart rate were recorded at 1-min intervals for 10 min, 2-min intervals for the next 10 min and subsequently at 5-min intervals. The sensory level was determined by pin prick test using 27 gauge needle. RESULTS: In the ephedrine group, systolic blood pressure was significantly greater than the other groups between 1 and 40 min after spinal anesthesia. (p<0.05) The changes in diastolic BP, mean BP and heart rate in the all groups were similar. CONCLUSION: The result of intramuscular injection of ephedrine may be more effective than crystalloid or colloid adminstration for the prophylaxis of hypotension during spinal anesthesia undergoing TURP.

Efficacy of an Epidural Test Dose with Intravenous Isoproterenol in Enflurane-Anesthetized Adults / 대한마취과학회지

BACKGROUND: The efficacy of an epidural test dose for detecting inadvertent intravascular injection during general anesthesia with volatile anesthetics has not been clearly determined. The object of this study is to evaluate the efficacy of a simulated intravenous isoproterenol test dose in adult patients anesthetized with O2-N2O-enflurane. METHODS: Forty-five healthy adult patients were anesthetized with 1 vol% enflurane and nitrous oxide after endotracheal intubation and were randomized to one of three groups according to the dose of isoproterenol. Isoproterenol 1, 2 and 3 microgram groups (n = 15 each) received 3 ml of 2% lidocaine with 1, 2 and 3 microgram isoproterenol IV respectively, to simulate an intravascularly administered test dose. HR and systolic blood pressure were measured at 20-s intervals for 4 min after injection. RESULTS: Mean maximal heart rate increases were 15 8, 21 8, and 27 10 bpm (mean SD) in the isoproterenol 1, 2 and 3 microgram groups, respectively. Isoproterenol 3 microgram produced 100% sensitivity in the modified (> or = 10 bpm increase) HR criteria and 67% sensitivity in the conventional (> or = 20 bpm increase) HR criteria. CONCLUSIONS: To determine whether an epidural catheter may be in a blood vessel, various vasoactive drugs are often administered. The epidural test dose containing 3 microgram isoproterenol might be a reliable marker for intravascular injection based on the modified HR criterion.

Efficacy of an Epidural Test Dose with Intravenous Isoproterenol in Enflurane-Anesthetized Adults / 대한마취과학회지

BACKGROUND: The efficacy of an epidural test dose for detecting inadvertent intravascular injection during general anesthesia with volatile anesthetics has not been clearly determined. The object of this study is to evaluate the efficacy of a simulated intravenous isoproterenol test dose in adult patients anesthetized with O2-N2O-enflurane. METHODS: Forty-five healthy adult patients were anesthetized with 1 vol% enflurane and nitrous oxide after endotracheal intubation and were randomized to one of three groups according to the dose of isoproterenol. Isoproterenol 1, 2 and 3 microgram groups (n = 15 each) received 3 ml of 2% lidocaine with 1, 2 and 3 microgram isoproterenol IV respectively, to simulate an intravascularly administered test dose. HR and systolic blood pressure were measured at 20-s intervals for 4 min after injection. RESULTS: Mean maximal heart rate increases were 15 8, 21 8, and 27 10 bpm (mean SD) in the isoproterenol 1, 2 and 3 microgram groups, respectively. Isoproterenol 3 microgram produced 100% sensitivity in the modified (> or = 10 bpm increase) HR criteria and 67% sensitivity in the conventional (> or = 20 bpm increase) HR criteria. CONCLUSIONS: To determine whether an epidural catheter may be in a blood vessel, various vasoactive drugs are often administered. The epidural test dose containing 3 microgram isoproterenol might be a reliable marker for intravascular injection based on the modified HR criterion.

Efficacy of a Simulated Epidural Test Dose in Isoflurane-Anesthetized Adults / 대한마취과학회지

BACKGROUND: An epidural test dose containing epinephrine may be incomplete marker of incidental intravenous injection or migration of the epidural catheter in adult patients under general anesthesia. This study tests the hypothesis that the efficacy of simulated epidural test doses in anesthetized adult can be used to predict the adequacy of correct catheter placement. METHODS: Seventy-five healthy adult patients were randomly assigned to inject intravenously one of 5 solutions, either 2% lidocaine 3ml and epinephrine 15 microgram(Group E15, n=15) or epinephrine 20 microgram (Group E20. n=15) or isoproterenol 3microgram (Group I3, n=15) or isoproterenol 5microgram (Group I5, n=15) and 0.9% saline(Group NS, n=15), which was anesthetized with isoflurane and nitrous oxide. After the injection, a blinded observer recorded systolic blood pressure(SBP) and heart rate(HR) every 30seconds for 4minutes and the changes were analyzed. RESULTS: Although none in the saline group developed a HR increase> or20bpm, 6, 10, 12 and 15 patients elicited positive reponses in group E15, I3, E20, and I5(40%, 67%, 80% and 100% sensitivities), respectively. Meanwhile, none in the saline group developed a SBP increase> or15mmHg and 11, 1, 14 and 4 patients elicited positive reponses in E15, I3, E20, and I5(73%, 7%, 93% and 27% sensitivities), respectively. CONCLUSIONS: We conclude that under isoflurane anesthesia, (a) epinephrine 15 microgram or isoproterenol 3microgram is not reliable marker for incidental intravenous injection or migration of the epidural catheter, (b) epinephrine 20 microgram is applicable on SBP criterion and, (c) isoproterenol 5 microgram is applicable on HR criterion.

Effects of Induced Hypotension with Labetalol on Blood Loss and Blood Pressure in Maxillofacial Surgical Patients / 대한마취과학회지

BACKGROUND: The worst problem in anesthetic management of maxillofacial surgery is bleeding from bone cutting site. Induced hypotension reduces bleeding and minimizes the need for blood transfusion. This study was performed to evaluate the effects of induced hypotension with labetalol on blood loss and blood pressure in maxillofacial surgical patients. METHODS: Twenty-four adult patients, either sex, ASA physical status I or II, undergoing orthognathic surgery were randomly selected and divided into two groups; one group was administered 20 mg of labetalol and the other group was not. Anesthetic maintenance was consisted of O2-N2O-enflurane (2~2.5 vol%). Then 20 mg of labetalol was given intravenously at skin incision time in the labetalol group. Hemodynamic variables were recorded before induction of anesthesia, at the beginning of the labetalol infusion and at 10 min, 20 min, 30 min, 60 min and 90 min after the infusion. Blood loss determined by measuring the weight of the sponges and by measuring the volume of blood in suction-trap bottle. RESULTS: There was no significant difference in preoperative hemoglobin and postoperative hemoglobin between two groups. The amount of blood loss in the labetalol group (408 +/- 202 ml) was less than those in the control group (450 +/- 255 ml), but statistically not significant. The blood pressure was significantly decreased in the labetalol group than those of the control group at 20 minutes after the labetalol infusion. CONCLUSIONS: Labetalol is a useful agent for inducing hypotension. But 20 mg of labetalol was insufficient to decrease the blood loss. So I think the more amount of labetalol required to reduce the blood loss.

Effects of Propofol in Combination with Ephedrine on the Hemodynamic Effects during Anesthesia Induction / 대한마취과학회지

BACKGROUND: Propofol is a useful induction agent, but it can cause hypotention and bradycardia. Meanwhile, ephedrine has alpha-vasoconstriction and beta-cardiac stimulant effect. The purpose of this study was to assess the hemodynamic effects of adding various doses of ephedrine to propofol to obtund adverse hemodynamic response and to determine the optimal dose. METHODS: Unpremedicated 120 ASA physical status I adult patients (20~50yrs) scheduled for elective surgery were randomly allocated into four groups according to the doses of ephedrine added to propofol (1%, 20 ml). Group 1 (control group) was given propofol alone and 10, 15 and 20 mg of ephedrine was added to propofol in Group 2, 3 and 4, respectively (n=30 for each group). Propofol was loaded at 150 ml/hr using a syringe pump and no response to verbal command was ascertained as the end-point of induction. Vital signs and SpO2 were checked every 1 min during the induction period. RESULTS: In group 1, there was a significant decrease in both systolic and diastolic pressure prior to intubation. Group 2 and 3 showed relatively stable hemodynamic changes and significant systolic or diastolic changes occured only in the pre or post 1 min periods of intubation. But, in pulse rate, group 3 showed significant change 1 and 2 min after intubation, in contrary to group 2. Group 4 showed significant changes in systolic and diastolic pressure 1 and 2 min after intubation, and in pulse rate throughout the postintubation period. CONCLUSIONS: Ephedrine 10mg may be safely employed to reduce the hemodynamic changes during induction preiod with propofol.

Continuous Epidural Clonidine for Analgesia after Cesarean Section / 대한마취과학회지

BACKGROUND: Clonidine, an 2-adrenergic agonist, shows the analgesic effect and potentiates the analgesic effect of opioid. However, when it is injected with bolus technique, it reveals the short duration of inadequate analgesia and induces hypotension, bradycardia or sedation. We examined the analgesic and side effects of clonidine administered by continuous epidural infusion over 24 hrs, following epidural morphine injection. METHODS: Sixty parturients, scheduled for elective cesarean section under epidural anesthesia were randomly allocated into three groups. They received an infusion of saline alone (group 1, n= 20), clonidine 20 g/hr (group 2, n= 20), or 40 g/hr (group 3, n= 20) respectively, following epidural morphine 3 mg injection at the end of operation. The total doses and number of request for supplemental analgesic, blood pressure, heart rate, and degree of sedation were measured during 24 hrs. RESULTS: There were significant differences in pain relief between clonidine groups and group 1. The total doses and number of patient's request for supplemental analgesic in clonidine groups, compared to group 1 were significantly decreased (p<0.05), but no significant differences between the two clonidine groups. The diastolic pressure of group 3 was significantly lower than that of group 1 over 24 hrs, and that of group 2 at 18 hr, 24 hr (p<0.05). However, there was no severe hypotension, bradycardia or sedation in the three groups. CONCLUSION: Clonidine administered by continuous epidural infusion over 24 hrs enhances the analgesic effect of epidural morphine, and the infusion of clonidine with 20 g/hr rather than 40 g/hr shows minimal changes of blood pressure. Therefore, administration of epidural clonidine (20 g/hr) following epidural morphine may be considered as a regimen for pain management after cesarean section.

Clinical Anaylsis of Anesthetic Dosage and Use of Ephedrine in Epidural Anesthesia for Cesarean Section / 대한마취과학회지

BACKGROUND: Hypotension occurs frequently after epidural anesthesia. Intravenous fluid or vasopressors are among treatment methods to many suggested causes. This study was undertaken retrospectively to determine if the age, weight and height of parturients are related to the local anesthetic dosage in epidural anesthesia for the cesarean section, and if the dosage of local anesthetic influence the change of blood pressure and the requirement of fluid or epherine. METHODS: Sixty-nine parturients were studied by reviewing patients' anesthetic records. During lumbar epidural anesthesia to T4 sensory level, all patients were monitored with mean arterial blood pressure, and prevented from hypotension by administration of Ringer's lactated solution. But if hypotension has been sustained in spite of rapid fluid loading, intermittent ephedrine was injected. We studied the correlation of local anesthetic dosage, decrement of mean blood pressure and total required intravenous fluid volume, and difference of these variables between cases using ephedrine and not using. RESULTS: The volume of local anesthetic to achieve a T4 sensory level was 21.20 3.81ml, which did not correlate with age, weight and height, and did not influence the decrease of mean blood pressure and the volume of administered fluid. But the patients (n=30) who needed ephedrine were adminstered significantly larger dose of the local anesthetic and showed more decrease in the mean blood pressure than those (n=39) who did not. CONCLUSIONS: The dose requirement of local anesthetic during epidural anesthesia for the cesarean section is not determined by the age, weight and height of parturients. But when larger dose of local anesthetic is administered, the patients seem to be more hypotensive and need ephedrine as well as intravenous fluid administration.