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.

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.

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.

Discrepant End-Tidal Concentrations of Sevoflurane at the Same A-Line Autoregressive Index Level during Induction of General Anesthesia: An Observational Study.

BACKGROUND: The A-Line Autoregressive Index (AAI), which is derived from auditory evoked potentials, has been used for determining anesthetic depth. This study verified the correlation between AAI values and the corresponding end-tidal concentrations of sevoflurane during general anesthesia induction. METHODS: Thirty young male adults undergoing elective minor orthopedic surgery were sequentially allocated to receive inspiratory 3%, 5%, or 6% sevoflurane for mask induction, followed by mechanical ventilation after tracheal intubation. The inspiratory, end-tidal and estimated jugular bulb concentrations of sevoflurane were recorded at three target AAI values: below 20, below 10, and at the start of burst suppression. RESULTS: The mean time to loss of consciousness in the 6% sevoflurane group was shorter than that in the 5% and 3% groups; however, the groups had comparable AAI values (range: 16-45). The 6% group had a higher end-tidal concentration (4.5% ± 0.2% vs. 3.8% ± 0.2%, p < 0.05) than did the 5% group, despite having the same target anesthetic levels by AAI score ≤10, whereas the estimated jugular bulb concentrations were comparable (1.9% vs. 1.9%) in both groups. CONCLUSIONS: Following mechanical ventilation with inspiratory 3%, 5%, or 6% sevoflurane, the end-tidal concentrations were discrepant at the same end points of AAI levels, despite similar estimated jugular bulb concentrations of sevoflurane. Thus, conventional alveolar concentration may overestimate anesthesia depth during rapid wash-in of sevoflurane.

Anesthesia services in Taiwan: A nationwide population-based study.

BACKGROUND: This study was conducted to provide an overview of anesthesia services in Taiwan from 2001 to 2010. METHODS: A retrospective population-based analysis was performed using data from Taiwan's National Health Insurance Research Database for the period 2001 to 2010. The results were stratified by patient sex, patient age, anesthesia type, and hospital setting. Categorical data are presented as totals and percentages. Linear regression was performed to analyze the anesthesia trends. RESULTS: The annual use of anesthesia increased continually from 964,440 instances in 2001 to 1,073,160 in 2010, totaling 10,076,600 cases with a total cost of 25.4 billion USD. The overwhelming majority (83.9%) of anesthesia cases was for anesthesia in an inpatient setting; general anesthesia accounted for 73.8% of anesthesia cases, and female patients outnumbered male patients (52.4% vs 47.6%). The average number of anesthesia cases was 44.2 per thousand of the population annually, but this percentage was much higher in elderly people (100.9 cases per thousand people annually). The annual number of anesthesia cases per thousand of the population increased from 104.4 in 2001 to 113.0 in 2010 in the oldest group (>80 years). By contrast, a considerable decline in use of anesthesia was discovered over the study period among those aged younger than 18 years. CONCLUSION: The use of anesthesia services in Taiwan has increased over the years. The relationships of age with anesthesia volume and cost were found to follow an inverse U-shaped pattern. Elderly people used anesthesia services more frequently. The planning of geriatric anesthesia services deserves attention, especially in continually aging societies such as Taiwan.

Evaluation of the pain intensity differences among hospitalized cancer patients based on a nursing information system.

Evaluating the absolute difference in pain intensity and the percentage difference in pain intensity could facilitate an understanding of pain reduction among cancer patients during repeated hospitalizations. Examinations of the absolute differences in pain intensity and the percentage differences in pain intensity according to the worst pain intensity and last evaluated pain intensity before discharge are lacking. The aim of this study was to evaluate the absolute and percentage difference in pain intensities among cancer patients with moderate or severe pain from their 1st to 18th hospitalizations from 2011-2013. A population-based retrospective cohort study was conducted. Pain intensity was assessed using scales and was recorded in a nursing information system. The absolute and percentage difference in pain intensities were examined via the one-sample Kolmogorov-Smirnov test, and group differences in moderate or severe pain were evaluated with the Mann-Whitney U test. For moderate pain patients, the mean absolute difference in pain intensity was 1.52, and the percentage difference in pain intensity was 29.0%; both these values were significant. More significant changes in the absolute and percentage difference in pain intensities were associated with severe pain patients. Both the average absolute difference in pain intensity (3.09) and the percentage difference in pain intensity (38.5%) in patients with severe pain were significantly higher than the average absolute difference in pain intensity (1.52) and the percentage difference in pain intensity (29.0%) in patients with moderate pain. Cancer patients with moderate and severe pain experienced pain reductions of approximately 30% and 40%, respectively. Early pain management intervention in patients with severe pain is necessary to achieve an obvious analgesic effect, and the formula of the percentage difference in pain intensity should be incorporated into the nursing information system to alert clinicians for early detection of the effectiveness of cancer pain management.

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.

The Osmopressor-Induced Angiopoietin-1 Secretion in Plasma and Subsequent Activation of the Tie-2/Akt/eNOS Signaling Pathway in Red Blood Cell.

BACKGROUND: Water ingestion induces the osmopressor response, which typically presents as increased total peripheral vascular resistance in young healthy subjects. A previous study has suggested that the RBC membrane receptor is involved in osmopressor stress. Recent studies have indicated nitric oxide synthase phosphorylation in RBCs. However, the main process in signaling pathway activation to elicit such a response is unknown. Herein, we hypothesized that hypo-osmotic stress following water ingestion modulates the eNOS/NO pathway, thereby alternating vascular resistance. METHODS: We included 24 young, healthy subjects. Physiological parameters and blood samples were collected at 5 minutes before and 25 and 50 minutes after 50 ml water, 500 ml water, or 500 ml normal saline ingestion. A human receptor tyrosine kinase (RTK) phosphorylation antibody array was used to simultaneously detect and monitor the biological activation pathways in RBCs. RESULTS: Of the 71 RTKs assayed during the osmopressor response, several RTKs were significantly upregulated, including Tie-2 and Tie-1. Plasma angiopoietin-1 levels significantly increased at 25 minutes after 500 ml water ingestion compared to those at baseline. Simultaneous phosphorylation of Tie-2, Akt, and eNOS in RBCs occurred. RBCs in vitro were stimulated with angiopoietin-1, Tie-2, or 0.8% saline and showed significant increase in Tie-2, Akt, and eNOS phosphorylation upon angiopoietin-1 treatment and enhanced activation upon cotreatment of angiopoietin-1 and 0.8% saline. CONCLUSIONS: The hypo-osmotic stimulus of water ingestion increases angiopoietin-1 secretion and subsequently activates the Tie-2/Akt/eNOS signaling pathway in RBCs, thereby revealing a novel biological mechanism simultaneously occurring with the osmopressor response.

Isoflurane compared with fentanyl-midazolam-based anesthesia in patients undergoing heart transplantation: A retrospective cohort study.

Inhalation anesthetics provide myocardial protection for cardiac surgery. This study was undertaken to compare the perioperative effects between isoflurane and fentanyl-midazolam-based anesthesia for heart transplantation. A retrospective cohort study was conducted by reviewing the medical records of heart transplantation in a single medical center from 1990 to 2013. Patients receiving isoflurane or fentanyl-midazolam-based anesthesia were included. Those with preoperative severe pulmonary, hepatic, or renal comorbidities were excluded. The perioperative variables and postoperative short-term outcomes were analyzed, including blood glucose levels, urine output, inotropic use, time to extubation, and length of stay in the intensive care units. After reviewing 112 heart transplantations, 18 recipients with fentanyl-midazolam-based anesthesia, and 29 receiving isoflurane anesthesia with minimal low-flow technique were analyzed. After cessation of cardiopulmonary bypass, recipients with isoflurane anesthesia had a significantly lower mean level and a less increase of blood glucose, as compared with those receiving fentanyl-based anesthesia. In addition, there was less use of dobutamine upon arriving the intensive care unit and a shorter time to extubation after isoflurane anesthesia. Compared with fentanyl-midazolam-based anesthesia, isoflurane minimal low-flow anesthesia maintained better perioperative homeostasis of blood glucose levels, less postoperative use of inotropics, and early extubation time among heart-transplant recipients without severe comorbidities.

Awakening arterial blood and end-tidal concentrations of isoflurane in female surgical patients.

Delayed extubation occurs after isoflurane anesthesia, especially following prolonged surgical duration. We aimed to determine the arterial blood concentrations of isoflurane and the correlation with end-tidal concentrations for predicting emergence from general anesthesia.Thirty-four American Society of Anesthesiologists physical status class I-II gynecologic patients were included. General anesthesia was maintained with a fixed 2% inspiratory isoflurane in 6 L/minute oxygen, which was discontinued after surgery. One milliliter of arterial blood was obtained for the determination of isoflurane concentration by gas chromatography at 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuation, in addition to the time of eye opening to verbal command, defined as awakening. Inspiratory and end-tidal concentrations were simultaneously detected by an infrared analyzer.The mean awakening arterial blood concentration of isoflurane was 0.20%, which was lower than the simultaneous end-tidal concentration 0.23%. The differences between arterial and end-tidal concentrations during emergence fell into an acceptable range (±1.96 standard deviation). After receiving a mean time of 108-minute general anesthesia, the time to eye opening after discontinuing isoflurane was 18.5 minutes (range 11-30, median 18 minutes), without statistical significance with anesthesia duration (P = 0.078) and body mass index (P = 0.170).We demonstrated the awakening arterial blood concentration of isoflurane in female patients as 0.20%. With well-assisted ventilation, the end-tidal concentration could be an indicator for the arterial blood concentration to predict emergence from shorter duration of isoflurane anesthesia.

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.

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.

Trends in Clinically Significant Pain Prevalence Among Hospitalized Cancer Patients at an Academic Hospital in Taiwan: A Retrospective Cohort Study.

Clinically significant pain (CSP) is one of the most common complaints among cancer patients during repeated hospitalizations, and the prevalence ranges from 24% to 86%. This study aimed to characterize the trends in CSP among cancer patients and examine the differences in the prevalence of CSP across repeated hospitalizations. A hospital-based, retrospective cohort study was conducted at an academic hospital. Patient-reported pain intensity was assessed and recorded in a nursing information system. We examined the differences in the prevalence of worst pain intensity (WPI) and last evaluated pain intensity (LPI) of ≥ 4 or ≥ 7 points among cancer inpatients from the 1st to the 18th hospitalization. Linear mixed models were used to determine the significant difference in the WPI and LPI (≥ 4 or ≥ 7 points) at each hospitalization. We examined 88,133 pain scores from the 1st to the 18th hospitalization among cancer patients. The prevalence of the 4 CSP types showed a trend toward a reduction from the 1st to the 18th hospitalization. There was a robust reduction in the CSP prevalence from the 1st to the 5th hospitalization, except in the case of LPI ≥ 7 points. The prevalence of a WPI ≥ 4 points was significantly higher (0.240-fold increase) during the 1st hospitalization than during the 5th hospitalization. For the 2nd, 3rd, and 4th hospitalizations, there was a significantly higher prevalence of a WPI ≥ 4 points compared with the 5th hospitalization. We also observed significant reductions in the prevalence of a WPI ≥ 7 points during the 1st to the 4th hospitalizations, an LPI ≥ 4 points during the 1st to the 3rd hospitalizations, and an LPI ≥ 7 points during the 1st to the 2nd hospitalization. Although the prevalence of the 4 CSP types decreased gradually, it is impossible to state the causative factors on the basis of this observational and descriptive study. The next step will examine the factors that determine the CSP prevalence among cancer patients. However, based on these positive findings, we can provide feedback to nurses, physicians, and pharmacists to empower them to be more committed to pain management.

Arterial blood and end-tidal concentrations of sevoflurane during the emergence from anesthesia in gynecologic patients.

OBJECTIVE: The end-tidal concentration of inhalation anesthetics is a clinical indicator for predicting the emergence from anesthesia. This study was conducted to assess the relationship between arterial blood and end-tidal sevoflurane concentrations during emergence. METHODS: Thirty-two female American Society of Anesthesiologists physical status I-II patients receiving general anesthesia for elective gynecologic surgery were included. A fixed dose of 3.5% inspiratory sevoflurane in 6 L min-1 oxygen was maintained until the end of surgery. At 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuing sevoflurane, as well as at the time of eye opening by verbal command, defined as awakening, 1 ml arterial blood was obtained to measure its sevoflurane concentration by gas chromatography. Simultaneous inspiratory and end-tidal concentrations of sevoflurane were detected by an infrared analyzer and tested by Bland-Altman agreement analysis. RESULTS: The arterial blood concentrations of sevoflurane were similar to the simultaneous end-tidal concentrations during emergence: 0.36% (0.10) and 0.36% (0.08) sevoflurane at awakening, respectively. The mean time from discontinuing sevoflurane to eye opening was 15.8 minutes (SD 2.9, range 10-26) and was significantly correlated with the duration of anesthesia (52-192 minutes) (P = 0.006) but not with the body mass index or total fentanyl dose. CONCLUSION: The mean awakening arterial blood concentration of sevoflurane was 0.36%. The time to awakening was prolonged in accordance with the anesthetic duration within 3 hours. With well-assisted ventilation during emergence, the sevoflurane end-tidal concentration was nearly equal to its arterial blood concentration, which could be a feasible predictor for awakening.

Arterial blood and end-tidal concentrations of sevoflurane during the emergence from anesthesia in gynecologic patients

OBJECTIVE: The end-tidal concentration of inhalation anesthetics is a clinical indicator for predicting the emergence from anesthesia. This study was conducted to assess the relationship between arterial blood and end-tidal sevoflurane concentrations during emergence. METHODS: Thirty-two female American Society of Anesthesiologists physical status I-II patients receiving general anesthesia for elective gynecologic surgery were included. A fixed dose of 3.5% inspiratory sevoflurane in 6 L min-1 oxygen was maintained until the end of surgery. At 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuing sevoflurane, as well as at the time of eye opening by verbal command, defined as awakening, 1 ml arterial blood was obtained to measure its sevoflurane concentration by gas chromatography. Simultaneous inspiratory and end-tidal concentrations of sevoflurane were detected by an infrared analyzer and tested by Bland-Altman agreement analysis. RESULTS: The arterial blood concentrations of sevoflurane were similar to the simultaneous end-tidal concentrations during emergence: 0.36% (0.10) and 0.36% (0.08) sevoflurane at awakening, respectively. The mean time from discontinuing sevoflurane to eye opening was 15.8 minutes (SD 2.9, range 10-26) and was significantly correlated with the duration of anesthesia (52-192 minutes) (P = 0.006) but not with the body mass index or total fentanyl dose. CONCLUSION: The mean awakening arterial blood concentration of sevoflurane was 0.36%. The time to awakening was prolonged in accordance with the anesthetic duration within 3 hours. With well-assisted ventilation during emergence, the sevoflurane end-tidal concentration was nearly equal to its arterial blood concentration, which could be a feasible predictor for awakening. .

Anesthetic premedication: new horizons of an old practice.

The practice of anesthetic premedication embarked upon soon after ether and chloroform were introduced as general anesthetics in the middle of the 19(th) century. By applying opioids and anticholinergics before surgery, the surgical patients could achieve a less anxious state, and more importantly, they would acquire a smoother course during the tedious and dangerous induction stage. Premedication with opioids and anticholinergics was not a routine practice in the 20(th) century when intravenous anesthetics were primarily used as induction agents that significantly shorten the induction time. The current practice of anesthetic premedication has evolved into a generalized scheme that incorporates several aspects of patient care: decreasing preoperative anxiety, dampening intraoperative noxious stimulus and its associated neuroendocrinological changes, and minimizing postoperative adverse effects of anesthesia and surgery. Rational use of premedication in modern anesthesia practice should be justified by individual needs, the types of surgery, and the anesthetic agents and techniques used. In this article, we will provide our readers with updated information about premedication of surgical patients with a focus on the recent application of second generation serotonin type 3 antagonist, antidepressants, and anticonvulsants.

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.

Clearance of meperidine and its metabolite normeperidine in hemodialysis patients with chronic noncancer pain.

CONTEXT: Normeperidine accumulates in patients with impaired renal function and may cause central neurotoxicity. However, some uremic patients still undergo meperidine treatment for chronic pain. OBJECTIVES: To prevent normeperidine side effects and complications, we investigated the clearance rate and extraction ratio of meperidine and normeperidine in hemodialysis patients with chronic pain. METHODS: Three hemodialysis patients, with diagnoses of chronic pancreatitis, chronic back pain, and intractable intra-abdominal pain, received long-term (more than six months) administration of meperidine for chronic noncancer pain. During regular hemodialysis, 72 blood samples in total were collected from the afferent port, efferent port, and ultradiafiltrate port at eight time points. The plasma concentrations of meperidine and normeperidine were determined by high-performance liquid chromatography. RESULTS: The prehemodialysis plasma concentrations of meperidine and normeperidine were 2963 ± 315 and 2369 ± 1974 ng/mL, which declined to 591 ± 109 and 853 ± 765 ng/mL, with 80% and 65% reduction, respectively. The plasma clearance and extraction ratios of meperidine were 22.7 ± 9.8 mL/minute and 10.1 ± 5.6% and for normeperidine 26.0 ± 11.4 mL/minute and 10.8 ± 2.5%, respectively. CONCLUSION: Hemodialysis can efficiently remove meperidine and its active metabolite, normeperidine, in uremic patients receiving long-term meperidine therapy for chronic noncancer pain.

Duration effect of desflurane anesthesia and its awakening time and arterial concentration in gynecologic patients.

OBJECTIVES: To determine the awakening arterial blood concentration of desflurane and its relationship with the end-tidal concentration during emergence from various durations of general anesthesia. METHOD: In total, 42 American Society of Anesthesiologists physical status class I-II female patients undergoing elective gynecologic surgery were enrolled. General anesthesia was maintained with fixed 6% inspiratory desflurane in 6 l min-1 oxygen until shutoff of the vaporizer at the end of surgery. One milliliter of arterial blood was obtained for desflurane concentration determination by gas chromatography at 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after the discontinuation of desflurane and at the time of eye opening upon verbal command, defined as awakening. Concentrations of inspiratory and end-tidal desflurane were simultaneously detected by an infrared analyzer. RESULTS: The mean arterial blood concentration of desflurane was 1.20% at awakening, which correlated with the awakening end-tidal concentration of 0.96%. The mean time from the discontinuation of desflurane to eye opening was 5.2 minutes (SD = 1.6, range 3-10), which was not associated with the duration of anesthesia (60-256 minutes), total fentanyl dose, or body mass index (BMI). CONCLUSIONS: The mean awakening arterial blood concentration of desflurane was 1.20%. The time to awakening was independent of anesthetic duration within four hours. Using well-assisted ventilation, the end-tidal concentration of desflurane was proven to represent the arterial blood concentration during elimination and could be a clinically feasible predictor of emergence from general anesthesia.