Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) depletes endogenous Vitamin C and generates oxidative stress in cardiac surgery. This study aimed to clarify whether Vitamin C supplementation reduces oxidant production and improves erythrocyte deformability in cardiac surgery with CPB. In a randomized and controlled design, 30 eligible patients undergoing cardiac surgery with hypothermic CPB were equally assigned to the Vitamin C group and control group. Subjects of the Vitamin C group and control group received an intravenous infusion of Vitamin C 20 mg·kg-1 and a placebo during rewarming period of CPB, respectively. We measured the plasma level of reactive oxygen species (ROS) and phosphorylation levels of non-muscle myosin IIA (NMIIA) in erythrocyte membrane, as an index of erythrocyte deformability, before and after CPB. Vitamin C supplementation attenuated the surge in plasma ROS after CPB, mean 1.661 ± standard deviation 0.801 folds in the Vitamin C group and 2.743 ± 1.802 in the control group. The tyrosine phosphorylation level of NMIIA after CPB was upregulated in the Vitamin C group compared to the control group, 2.159 ± 0.887 folds and 1.384 ± 0.445 (P = 0.0237). In addition, the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and focal adhesion kinase (FAK) in erythrocytes was concurrently enhanced in the Vitamin C group after CPB. The phosphorylation level of endothelial nitric oxide synthase in erythrocytes was significantly increased in the Vitamin C group (1.734 ± 0.371 folds) compared to control group (1.102 ± 0.249; P = 0.0061). Patients receiving Vitamin C had lower intraoperative blood loss and higher systemic vascular resistance after CPB compared to controls. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability via VASP/FAK signaling pathway in erythrocytes during CPB.

Glucose reduces the osmopressor response in connection with the tyrosine phosphorylation of focal adhesion kinase in red blood cells.

Glucose ingestion attenuates the water ingestion-induced increase in the total peripheral vascular resistance and orthostatic tolerance. We investigated the gastrointestinal physiology of glucose by examining the effect of glucose ingestion on the functional expression of focal adhesion kinase (FAK) in red blood cell (RBC) membrane. This study was performed in 24 young, healthy subjects. Blood samples were collected at 5 min before and 25 min and 50 min after an ingestion of 10% glucose water 500 mL, water 500 mL, or normal saline 500 mL. We determined glucose and osmolality in plasma, and phosphorylation of aquaporin 1 (AQP1), glucose transporter 1 (Glut1), and FAK in RBC membrane. Our results showed that glucose ingestion reduced the rise of peripheral vascular resistance after water ingestion and upregulated the serine phosphorylation of Glut1. It also lowered both the serine phosphorylation of FAK and tyrosine phosphorylation of AQP1, compared with the ingestion of either water or saline. In an ex vivo experiment, glucose activated the Glut1 receptor and subsequently reduced the expression of FAK compared with 0.8% saline alone. We concluded that glucose activates Glut1 and subsequently lowers the functional expression of FAK, a cytoskeleton protein of RBCs. The functional change in the RBC membrane proteins in connection with the attenuation of osmopressor response may elucidate the pathophysiology of glucose in postprandial hypotension.

Knowledge, Attitude and Practice Survey of Prescribing Opioids for Chronic Noncancer Pain in Taiwan-Comparison of Pain and Non-Pain Physicians.

BACKGROUND: Prescribing opioids for chronic noncancer pain (CNCP) has been strictly regulated in Taiwan. This study was undertaken to survey pain and non-pain related physicians' knowledge, attitudes, and practices regarding prescribing opioids for CNCP. METHODS: A questionnaire survey was conducted in this comparison study. All 66 physicians who were treating officially registered CNCP outpatients were visited and completed anonymous questionnaires. The other physicians (anesthesiologists, oncologists, and non-pain physicians) were surveyed by a mailed questionnaire. RESULTS: A total of 266 (75%) questionnaires were received from 355 board-certified physicians. More CNCP physicians (81.8%) and anesthesiologists (69.7%) had received prior CNCP-related training courses than had oncologists (21.2%) and non-pain physicians (10.3%). Varied proportions of physicians by type were unfamiliar with the Taiwan opioid regulations (16.7-86.8%) and would accordingly skip or reduce dosage of opioid prescriptions (27.3-73.5%). In addition, non-pain physicians had a significantly lower knowledge level, more negative attitudes, and greater hesitation about prescribing opioids compared to the pain-related physicians (P < 0.001). CNCP physicians who had received CNCP-related training courses had a higher knowledge score than did those not receiving training (P = 0.002). Overall, the leading barriers for prescribing opioids were inadequate knowledge of pain management (76%), physician reluctance (73%), and family reluctance (78%). CONCLUSION: There are substantial knowledge gaps, negative attitudes, and hesitation toward prescribing long-term opioids for CNCP patients by physicians in Taiwan, suggesting that efforts are needed to improve postgraduate education regarding adequate opioid management for CNCP.

Analgesic effects of repetitive transcranial magnetic stimulation on modified 2010 criteria-diagnosed fibromyalgia: Pilot study.

AIM: Fibromyalgia is often comorbid with depression, and less than half those patients achieve satisfactory improvement after adequate pharmacological intervention. The investigation of repetitive transcranial magnetic stimulation (rTMS) at left dorsolateral prefrontal cortex for modified-2010 American College of Rheumatology (ACR) fibromyalgia and major depressive disorder (MDD) is still in its infancy. METHODS: In this double-blind, randomized, sham-control study, subjects diagnosed with ACR-2010 fibromyalgia and DSM-IV-TR MDD were recruited and received either active or sham interventions for 2 weeks. Hamilton Depression Rating Scale (HDRS) and the 10-cm visual analogue pain scale were evaluated at baseline, week 1, and week 2. Multivariable generalized estimating equations analysis was performed for the association between depression and pain scores at each checkpoint. RESULTS: Twenty subjects were recruited. There was a significant difference over the 2 weeks between the rTMS and sham stimulation groups (P = 0.029), but subgroup analyses were further performed due to significant interaction of group and HDRS on pain outcomes (P = 0.020). The active group had significant improvement in pain at week 2 compared with week 1 (P = 0.021), but the control group did not have any improvement in pain (P = 0.585). Of the mild-moderate depression patients, the pain score in the active group was significantly lower than in the sham group at week 1 (P = 0.001) and at week 2 (P < 0.001). For the severe depression group, there was significantly lower pain over the 2 weeks in the active group (P = 0.045) but the sham group had significantly relapsing pain at week 2 (P < 0.001). CONCLUSION: Left prefrontal rTMS has an analgesic effect in modified-ACR 2010-defined fibromyalgia and MDD patients. Further investigation is required, however, in order to determine how to regulate the different rTMS treatment protocols according to individual baseline depression severity in patients with MDD and fibromyalgia.

Voluntary attendance of small-group brainstorming tutoring courses intensify new clerk's "excellence in clinical care": a pilot study.

BACKGROUND: Clerkship provides a unique way of transferring the knowledge and skills gathered during medical school's curriculum into real-ward clinical care environment. The annual program evaluation has indicated that the training of clerks in diagnostic and clinical reasoning skills needed to be enhanced. Recently, "clinical excellence" program have been promoted in our institution to augment the excellence in clinical care of new clerks. Current study aims to evaluate whether this pilot program improve the "clinical excellence" of new clerks. METHODS: In a pilot study, groups of new clerks in years 2013 and 2014 voluntarily attended either a small-group brainstorming course or a didactic classroom tutoring courses as part of their 3-month internal medicine clinical rotation block. A third group of new clerks did not join either of the above courses and this group served as the control group. Pre-block/post-block self-assessment and post-block 5-station mini-Objective Subjective Clinical Examinations (OSCEs) were used to evaluate the effectiveness of these two additional courses that trained diagnostic and clinical reasoning skills. RESULTS: Overtime, the percentages of new clerks that attended voluntarily either the small-group brainstorming or classroom tutoring courses were increased. Higher post-block self-assessed diagnostic and clinical reasoning skill scores were found among individuals who attended the small-group brainstorming courses compared to either the didactic group or the control group. In a corresponding manner, the small-group brainstorming group obtained higher summary OSCEdiag and OSCEreason scores than either the didactic group or control group. For all basic images/laboratory OSCE stations, the individual diagnostic skill (OSCEdiag) scores of the small-group brainstorming group were higher than those of the didactic group. By way of contrast, only the clinical reasoning skill (OSCEreason) scores of the basic electrocardiogram and complete blood count + biochemistry OSCE station of thesmall-group brainstorming group were higher than those of the didactic group. Among the small-group brainstorming group, clerks with higher cumulative learning hours (>30-h) had significant higher OSCEdiag and OSCEreason scores (>400) than those with less cumulative learning hours. CONCLUSION: Our pilot study provides a successful example of the use of a small-group tutoring courses for augmenting the diagnostic and clinical reasoning skills of new clerks. The positive results obtained during the initial 2-year long pilot "clinical excellence" program have encouraged the formal implementation of this course as part of the clerkship curriculum.

Long-term use of opioids in 210 officially registered patients with chronic noncancer pain in Taiwan: A cross-sectional study.

BACKGROUND/PURPOSE: Prescribing opioids for chronic noncancer pain has been strictly regulated for two decades in Taiwan. The aim of this study was to survey the patients' perspectives and potential drawbacks following long-term use of opioids. METHODS: An observational cross-sectional survey using the Taiwanese version of Brief Pain Inventory was conducted among outpatients with chronic noncancer pain registered by the Taiwan Food and Drug Administration. Patients were also asked about their sexual behavior, depression, opioid misuse behaviors, and use of complementary and alternative medicine. RESULTS: For 210 of 328 outpatients (64.0%), the median pain duration was 96 months and opioid treatment duration was 57 months. The median morphine equivalent dose was 150 mg/d, with 30.5% of patients exceeding the daily watchful dose, defined as 200 mg of morphine equivalent dose. Pain reduction after taking opioids was ∼50% in the past week. The top three diagnoses were chronic pancreatitis, spinal cord injury, and neuralgia. The leading side effects were constipation (46.7%), and decreased sexual desire (69.5%) and satisfaction (57.9%). Depression was currently diagnosed in 55.2% of patients. Twenty patients (9.5%) displayed at least one aberrant behavior in the past month. Only 76 (36.2%) patients had ever received nerve block procedures, and 118 (56.2%) tried complementary and alternative medicine. CONCLUSION: This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose.

Using a New Measurement to Evaluate Pain Relief Among Cancer Inpatients with Clinically Significant Pain Based on a Nursing Information System: A Three-Year Hospital-Based Study.

OBJECTIVE: Developing a new measurement index is the first step in evaluating pain relief outcomes. Although the percentage difference in pain intensity (%PID) is the most popular indicator, this indicator does not take into account the goal of pain relief. Therefore, the aims of this study were to develop a pain relief index (PRI) for outcome evaluation and to examine the index using demographic characteristics of cancer inpatients with clinically significant pain. DESIGN: Retrospective cohort study. SETTING: A national hospital. SUBJECTS: All cancer inpatients. METHODS: Pain intensity was assessed using a numerical rating scale, a faces pain scale or the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Tool. Using a nursing information system, a pain score database containing data from 2011 through 2013 was analyzed. RESULTS: Cancer patients representing 93,812 hospitalizations were considered in this study. We focused on cancer patients for whom the worst pain intensity (WPI) was ≥ 4 points. PRI values of -62.02% to -72.55% were observed in the WPI ≥ 7 and 4 ≤ WPI ≤ 6 groups. Significant (P < 0.05) effects on PRI values were observed among patients who were > 65 years old, those who were admitted to the medicine or gynecology and those who had a hospital stay > 30 days. CONCLUSION: This hospital-based study demonstrated that the PRI is an effective and valid measure for evaluating outcome data using an electronic nursing information system. We will further define the meaningful range of percentage difference in PRI from various perspectives.

Intravenous loading of nitroglycerin during rewarming of cardiopulmonary bypass improves metabolic homeostasis in cardiac surgery: a retrospective analysis.

PURPOSE: The aim of the study was to evaluate the effects of high-dose nitroglycerine (NTG) on glucose metabolism, tissue oxygenation and postoperative recovery in cardiac surgical patients. METHODS: Cardiac surgical patients in the retrospective survey were classified into two groups based on the NTG regimen. NTG group had intravenous loading of NTG (infusion rate 10-20 mg/h with total dose of ≥0.5 mg/kg) starting at rewarming of cardiopulmonary bypass (CPB) (n = 101), and control group had no intravenous loading of NTG (n = 151). Data for intraoperative plasma glucose and lactate levels, and regular insulin consumption were collected. Propensity score methodology was utilized to adjust for potential confounders. RESULTS: After adjustment for propensity score, the plasma glucose was significantly lower in the NTG group during (161 ± 39 versus 179 ± 45 mg/dl, p = 0.005) and after CPB (167 ± 41 versus 184 ± 48 mg/dl, p = 0.012). Total consumption of regular insulin was significantly lower in the NTG group, median 8 (range 0-50) versus 13 (0-90) international units, p = 0.005. There was a trend towards statistical significance in a lower incidence of hyperlactatemia (>2.2 mmol/l) in the NTG group during CPB, 21/100 (21 %) versus 40/132 (30.3 %), p = 0.065. The mixed venous oxygen saturation in the intensive care unit was higher in the NTG group, 65 ± 9 versus 62 ± 11 %, p = 0.056. CONCLUSIONS: Intravenous loading of NTG during and after CPB is safe and effective for attenuating the hyperglycemic response and reduce the incidence of hyperlactatemia during cardiac surgery with CPB.

Factors associated with Taiwan anesthesiologists' intention to leave anesthesia practice.

BACKGROUND/PURPOSE: Anesthesiologists in Taiwan had the heaviest workload compared with other Taiwanese specialists. In a previous study, anesthesia-related mortality was >12 times the rate reported in the USA, UK, and Japan. Nine percent of Taiwanese anesthesiologists left their jobs to work as general practitioners in clinics. This study aims to assess the current working conditions of anesthesiologists in Taiwan and their satisfaction with their occupation, and to identify the factors associated with the intentions of anesthesiologists in Taiwan to leave anesthesia practice. METHODS: A self-reported questionnaire was completed by 474 attending anesthesiologists in Taiwan. The Chi-square test was used for categorical variables and the t test for continuous variables. Multivariate logistic regression was conducted to identify the factors significantly associated with the willingness of anesthesiologists to continue in anesthesiology. RESULTS: The sample anesthesiologists worked 59.9 hours/week, however a reasonable length of time to work is 49.6 hours/week. They simultaneously covered four operating rooms daily, but three rooms is considered reasonable. Surprisingly, 54.9% of them expressed their unwillingness to practice clinical anesthesia. Those anesthesiologists dissatisfied with their overall working conditions had a substantially increased odds ratio (6.96) of deterring continuing to practice in anesthesia. Furthermore, an inability to take care of the family and a low salary significantly decreased the willingness to practice in anesthesia (odds ratio: 0.42 and 0.38, respectively). CONCLUSION: Unfavorable working conditions were considered to lower the satisfaction of anesthesiologists in Taiwan. In particular, an inability to take care of the family and a low salary were major factors in deterring anesthesiologists in Taiwan from continuing in anesthesia.

Current status of anesthesia residency in Taiwan: a questionnaire survey.

PURPOSE: There are 26 teaching hospitals in Taiwan that provide anesthesia residency training programs (one program per hospital), and only an average of 40 medical graduates are accepted for residency training per year. The aim of this study is to understand how this situation affects the learning and working conditions of anesthesia residents in Taiwan. METHODS: A self-structured survey was mailed to all 178 anesthesia residents receiving training in Taiwan in April 20, 2012. Survey questions included resident characteristics, working and learning conditions, satisfaction with resident training programs, and reasons for choosing anesthesiology as a career. In addition to descriptive statistics, linear regression was used to test correlation between working conditions and satisfaction with training programs. RESULTS: The survey was completed by 136 residents. Although the residents' expected optimal working time was 54.1 ± 12.2 h per week, their actual working time was an average of 64.0 ± 15.7 h per week. In addition, the workload included managing 4.2 ± 1.3 operating rooms simultaneously. The ratio of working vs. learning time was 2.2 ± 1.1. Less than 40 % of the residents were satisfied with their training in critical care and pain management. Anesthesia residents with heavier workloads and higher ratios of work vs. learning time had significantly lower satisfaction with their training programs, especially with training environments (R (2) = 0.169). General interest in anesthesiology and related work (66.1 %) was the main factor in choosing anesthesia as their career. CONCLUSIONS: Anesthesia residents in Taiwan are treated as an integral part of hospital manpower. This may limit the effectiveness of their learning and cause dissatisfaction with their training environment. To improve the current status, anesthesia residents should perform anesthesia in one operating room at a time and some of the anesthesia training hospitals should be suggested for removal.

Commonly used excipients modulate UDP-glucuronosyltransferase 2b7 activity to improve nalbuphine oral bioavailability in humans.

PURPOSE: Nalbuphine (NAL) is a potent opioid analgesic, but can only be administered by injection. The major aim of this study was to develop an oral NAL formulation employing known excipients as UDP-glucuronosyltransferase 2B7 (UGT2B7) inhibitors to improve its oral bioavailability. METHODS: Twenty commonly used pharmaceutical excipients were screened in vitro by using liver microsomes to identify inhibitors of UGT2B7, the major NAL metabolic enzyme. Tween 20 and PEG 400 were potent UGT2B7 inhibitors and both were co-administered (Tween-PEG) with NAL to rats and humans for pharmacokinetic and/or pharmacodynamic analyses. RESULTS: In animal studies, oral Tween-PEG (4 mg/kg of each) significantly increased the area under the plasma NAL concentration-time curve (AUC) and the maximal plasma concentration (Cmax) by 4- and 5-fold, respectively. The results of the pharmacodynamic analysis were in agreement with those of the pharmacokinetic analysis, and showed that Tween-PEG significantly enhanced the analgesic effects of orally administered NAL. In humans, oral Tween-PEG (240 mg of each) also increased NAL Cmax 2.5-fold, and AUC by 1.6-fold. CONCLUSIONS: Tween-PEG successfully improved oral NAL bioavailability and could formulate a useful oral dosage form for patient's convenience.

Pharmacokinetics of sevoflurane elimination from respiratory gas and blood after coronary artery bypass grafting surgery.

PURPOSE: Sevoflurane, with a relative low blood-gas partition coefficient, is an ideal anesthetic to achieve rapid offset and recovery from general anesthesia. This study will determine the profiles of four concentration-time curves to characterize the pharmacokinetics of sevoflurane elimination. METHODS: Eight patients (aged 54-76 years) undergoing coronary arterial bypass grafting surgery were enrolled in this study. At the end of surgery, anesthetic gas and blood were sampled 20 min before and after stopping sevoflurane administration, with prior maintenance of a fixed 5% inspired sevoflurane (CIsev) in 6 L/min oxygen flow for 60 min before the cessation of sevoflurane administration for the subsequent 20 min elimination. An infrared analyzer was used to determine both CIsev and end-tidal sevoflurane (CEsev). The sevoflurane concentrations in the internal jugular-bulb (Jsev), arterial (Asev) and pulmonary arterial blood (PAsev) were analyzed by gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. RESULTS: A bi-exponential decay function was the best fit for the CEsev,Jsev, Asev, and PAsev time curves. There were two distinct components, the initial 5-min fast or distribution phase and the subsequent 15-min slow or elimination phase. Before cessation of the sevoflurane supplement, the step-down concentration of sevoflurane was listed in the following order: CIsev > CEsev > Asev ≧ Jsev > PAsev. During the elimination phase, the fastest decay occurred in CEsev, followed by Jsev, Asev and PAsev. Therefore, a reverse step-down pattern was observed (PAsev > Asev ≧ Jsev > CEsev) after 20 min. The ratio of Asev to CEsev was 89% at baseline before stopping sevoflurane administration, but the ratio of Asev to CEsev increased to 128% at the twentieth min of the sevoflurane elimination phase. CONCLUSIONS: During elimination, the initial washout of sevoflurane from the functional residual capacity of the lungs was reflected in the fast component of the CEsev, Jsev, Asev, and PAsev time curves. In contrast, the slow component was dominated by the tangible effects of the physiological membrane barriers, such as the alveoli-pulmonary capillary and blood-brain barriers.

Pharmacokinetics of desflurane uptake and disposition in piglets.

Introduction: Many respiratory but few arterial blood pharmacokinetics of desflurane uptake and disposition have been investigated. We explored the pharmacokinetic parameters in piglets by comparing inspiratory, end-tidal, arterial blood, and mixed venous blood concentrations of desflurane. Methods: Seven piglets were administered inspiratory 6% desflurane by inhalation over 2 h, followed by a 2-h disposition phase. Inspiratory and end-tidal concentrations were detected using an infrared analyzer. Femoral arterial blood and pulmonary artery mixed venous blood were sampled to determine desflurane concentrations by gas chromatography at 1, 3, 5, 10, 20, 30, 40, 50, 60, 80, 100, and 120 min during each uptake and disposition phase. Respiratory and hemodynamic parameters were measured simultaneously. Body uptake and disposition rates were calculated by multiplying the difference between the arterial and pulmonary artery blood concentrations by the cardiac output. Results: The rates of desflurane body uptake increased considerably in the initial 5 min (79.8 ml.min-1) and then declined slowly until 120 min (27.0 ml.min-1). Similar characteristics of washout were noted during the subsequent disposition phase. Concentration-time curves of end-tidal, arterial, and pulmonary artery blood concentrations fitted well to zero-order input and first-order disposition kinetics. Arterial and pulmonary artery blood concentrations were best fitted using a two-compartment model. After 2 h, only 21.9% of the desflurane administered had been eliminated from the body. Conclusion: Under a fixed inspiratory concentration, desflurane body uptake in piglets corresponded to constant zero-order infusion, and the 2-h disposition pattern followed first-order kinetics and best fitted to a two-compartment model.

Salivary alpha-amylase as a biomarker for the osmopressor response in healthy adults.

Water ingestion induces a sympathetically mediated increase in blood pressure in dysautonomic patients and the elderly, but not consistently in young healthy subjects. The aim of study was to determine the extent of the pressor response and changes of sympathetic activity biomarker salivary alpha-amylase (sAA) after water ingestion in young healthy subjects. Compared with ingestion of 50 mL of water, the blood pressure, total peripheral resistance and sAA significantly increased and the plasma osmolality decreased 25 min after drinking 500 mL of water. The results confirm the osmopressor response in young subjects and suggest that sAA may be used as a non-invasive marker of sympathetic activity in future studies.

Simultaneous determination of nalbuphine and its prodrug sebacoly dinalbuphine ester in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in humans.

A rapid, simple, sensitive and selective ultraperformance liquid chromatography-tandem spectrometry (UPLC-MS/MS) method for the determination of nalbuphine and its prodrug sebacoly dinalbuphine ester (SDE) was developed and validated in human plasma. The sample pretreatment involves basification and iterative liquid-liquid extraction with ethyl-ether-dichloromethane (7:3, v/v) solution, followed by LC separation and positive electrospray ionization (ESI) API-3000 mass spectrometry detection. The chromatography was on a Waters Acquity UPLC BEH HILIC column (2.1 × 100 mm, 1.7 µm). The mobile phase was composed of acetonitrile and water (83:17, v/v) that contained 0.2% formic acid and 4 mm ammonium formate at a flow rate of 0.25 mL/min. Ethylmorphine and naloxine were selected as the SDE and nalbuphine internal standard (IS), respectively. The calibration curve for both was linear over the range from 0.05 to 20 ng/mL, with correlation coefficients ≥0.995. The lower limit of quantification was set at 0.05 ng/mL. The intra- and inter-day precision values for nalbuphine and SDE were acceptable as per FDA guidelines. The method was applied successfully to determine nalbuphine concentration in human plasma samples obtained from four Taiwanese volunteers receiving intramuscularly administration of sebacoyl dinalbuphine ester. The method is sensitive, selective and directly applicable to human pharmacokinetic studies involving nalbuphine.

Pharmacokinetics of desflurane elimination from respiratory gas and blood during the 20 minutes after cardiac surgery.

BACKGROUND/PURPOSE: Desflurane, with a low blood-gas partition coefficient, is an ideal anesthetic to achieve rapid offset and recovery from general anesthesia. Investigation of desflurane elimination from blood and respiratory gas should provide useful information with respect to a patient's recovery from anesthesia. Therefore, this study is designed to characterize the pharmacokinetics of desflurane elimination after cardiac surgery. METHODS: Sixteen patients undergoing coronary artery bypass graft surgery were enrolled. At the end of surgery, multiple gas and blood samples were taken in the 20 minutes before and after stopping desflurane administration, with prior maintenance of a fixed 7% inspired desflurane in 6 L/minute oxygen flow for 60 minutes before the cessation. The blood desflurane concentrations, including internal jugular-bulb blood (Jdes), arterial blood (Ades) and pulmonary arterial blood (PAdes) were analyzed using gas chromatography. The inspiratory desflurane concentration (CIdes) and end-tidal desflurane (CEdes) were measured with an infrared analyzer, and cardiac output was measured using an Opti-Q pulmonary artery catheter. RESULTS: Before cessation of desflurane administration, the inspiratory desflurane concentration (CIdes) was relatively higher than end-tidal (CEdes), arterial (Ades), internal jugular-bulb blood (Jdes), and pulmonary (PAdes) concentrations in sequence (CIdes > CEdes > Ades≈ Jdes > PAdes). During the elimination phase, rapid decay occurred in CEdes, followed by Jdes, Ades and PAdes. Twenty minutes after stopping desflurane administration, the desflurane concentrations were: PAdes > Ades≈ Jdes > CEdes. The decay curves of desflurane concentrations demonstrated two distinct elimination components: an initial, fast 5-minute component followed by a slow 15-minute component. CONCLUSION: Desflurane is eliminated fastest from the lungs, as indicated by CEdes, compared to elimination from circulating blood. The initial, rapid 5-minute desflurane washout reflected the diluting effect of functional residual capacity of the lungs.

Hyperventilation accelerates rise in arterial blood concentrations of sevoflurane in gynecologic patients.

PURPOSE: We investigated whether ventilation volumes affected arterial blood sevoflurane concentration (A (sev)) and its uptake into the body during general anesthesia. METHODS: Thirty female patients undergoing elective gynecologic surgery were randomly allocated into three groups: hyperventilation, normal ventilation, and hypoventilation. Inspiratory (CI(sev)) and end-tidal ((sev)) sevoflurane concentrations were routinely measured by infrared analysis, and A (sev) were analyzed by gas chromatography for 40 min after intubation. Cardiac index and total peripheral vascular resistance were measured with a Finometer. RESULTS: During the first 10 min after sevoflurane administration, A (sev) in the hyperventilation group was the highest and differed significantly from those in the normal ventilation group, followed by those in the hypoventilation group. In addition, hyperventilation significantly increased the slope of A (sev) over time in the first 5 min, but there were no differences in slopes in the 5-10, 10-20, and 20-40 min periods, which indicates no difference in sevoflurane bodily uptake among the three groups after 5 min. CONCLUSION: Hyperventilation accelerated the rate of A (sev) increase immediately after sevoflurane administration, which was time dependent with respect to different alveolar ventilation levels.

Preoperative Use and Discontinuation of Traditional Chinese Herbal Medicine and Dietary Supplements in Taiwan: A Cross-Sectional Questionnaire Survey.

Traditional Chinese herbal medicine has widespread use in Taiwan. This cross-sectional questionnaire survey investigates the preoperative use and discontinuation of Chinese herbal medicine and dietary supplements among Taiwanese patients. We obtained the types, frequency, and sources of Chinese herbal remedies and supplements used. Among 1428 presurgical patients, 727 (50.9%) and 977 (68.4%) reported the use of traditional Chinese herbal medicine and supplements in the past one month, respectively. Only 17.5% of the 727 patients stated discontinuation of herbal remedies 4.7 ± 5.1 (1-24) days before the surgery, and 36.2% took traditional Chinese herbal medicine with concomitant physician-prescribed Western medicine for their underlying diseases. The most commonly used Chinese herbs are goji berry (Lycium barbarum) (62.9%) and Si-Shen-Tang (48.1%) in single and compound forms, respectively. The presurgical use of traditional Chinese herbal medicine was common in patients undergoing gynecologic (68.6%) surgery or diagnosed with asthma (60.8%). Women and those with a high household income had a greater tendency to use herbal remedies. This study demonstrates the high proportion of the presurgical use of Chinese herbal remedies and supplements along with physician-prescribed Western medicine in Taiwan. Surgeons and anesthesiologists should be aware of the potential adverse effects of drug-herb interaction for Chinese patients.

Water ingestion reduces skin blood flow through sympathetic vasoconstriction.

OBJECTIVE: Water ingestion induces a pressor effect in patients with efferent baroreflex impairment and a mild pressor effect in elderly healthy subjects. However, water raised the total peripheral vascular resistance (TPR) without a prominent change in blood pressure in young healthy subjects. We try to investigate whether water elicits a cardiovascular response via regulating regional skin blood flow (SkBF) in young healthy subjects. METHODS: In a randomized, controlled, crossover fashion, 15 healthy male subjects (19-27 years old) ingested either 500 (water session) or 50 ml of water (control). The heart rate, blood pressure, cardiac index, and TPR were measured using a Task Force Monitor. A laser Doppler velocimeter was used to determine the change in the SkBF at the left thenar eminence. Plasma catecholamines and their metabolites were also measured. RESULTS: At 25 min after ingestion of 500 ml water, the cardiac index and SkBF significantly decreased compared to control. In contrast, the TPR significantly increased after ingestion of 500 ml water. Plasma dihydroxyphenylalanine significantly increased at 25 min after water. INTERPRETATION: Water ingestion decreases the cardiac index to compensate for the increase in the TPR, leading to no net change in blood pressure in young healthy subjects. This study suggests that water decreases the SkBF, a mechanism that might account partly for the nature of osmopressor response to water in young healthy subjects.