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.

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.

Matrix Metalloproteinase-9 Production following Cardiopulmonary Bypass Was Not Associated with Pulmonary Dysfunction after Cardiac Surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) causes release of matrix metalloproteinase- (MMP-) 9, contributing to pulmonary infiltration and dysfunction. The aims were to investigate MMP-9 production and associated perioperative variables and oxygenation following CPB. METHODS: Thirty patients undergoing elective cardiac surgery were included. Arterial blood was sampled at 6 sequential points (before anesthesia induction, before CPB and at 2, 4, 6, and 24 h after beginning CPB) for plasma MMP-9 concentrations by ELISA. The perioperative laboratory data and variables, including bypass time, PaO2/FiO2, and extubation time, were also recorded. RESULTS: The plasma MMP-9 concentrations significantly elevated at 2-6 h after beginning CPB (P < 0.001) and returned to the preanesthesia level at 24 h (P = 0.23), with predominant neutrophil counts after surgery (P < 0.001). The plasma MMP-9 levels at 4 and 6 h were not correlated with prolonged CPB time and displayed no association with postoperative PaO2/FiO2, regardless of reduced ratio from preoperative 342.9 ± 81.2 to postoperative 207.3 ± 121.3 mmHg (P < 0.001). CONCLUSION: Elective cardiac surgery with CPB induced short-term elevation of plasma MMP-9 concentrations within 24 hours, however, without significant correlation with CPB time and postoperative pulmonary dysfunction, despite predominantly increased neutrophils and reduced oxygenation.

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.

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.

Association of general anesthesia exposure with risk of postoperative delirium in patients receiving transcatheter aortic valve replacement: a meta-analysis and systematic review.

The aim of this meta-analysis was to assess the association of general anesthesia (GA) exposure with the risk of POD in this patient population. Databases including Medline, EMBASE, Cochrane library, and Google Scholar were searched from inception to December 2022. Analysis of 17 studies published between 2015 and 2021 involving 10,678 individuals revealed an association of GA exposure with an elevated risk of POD [odd ratio (OR) = 1.846, 95% CI 1.329 to 2.563, p = 0.0003, I2 = 68.4%, 10,678 patients]. Subgroup analysis of the diagnostic methods also demonstrated a positive correlation between GA exposure and POD risk when validated methods were used for POD diagnosis (OR = 2.199, 95% CI 1.46 to 3.31, p = 0.0002). Meta-regression analyses showed no significant impact of age, male proportion, and sample size on the correlation between GA and the risk of POD. The reported overall incidence of POD from the included studies regardless of the type of anesthesia was between 0.8 and 27%. Our meta-analysis showed a pooled incidence of 10.3% (95% CI 7% to 15%). This meta-analysis suggested an association of general anesthesia with an elevated risk of postoperative delirium, implying the necessity of implementing appropriate prophylactic strategies against this complication when general anesthesia was used in this clinical setting.

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.

Cerebral Oximetry-Monitored Nitroglycerin Infusion and Tissue Perfusion during Rewarming of Cardiopulmonary Bypass in Cardiac Surgery: A Prospective Randomized Trial.

BACKGROUND: Nitroglycerin facilitates microcirculation and oxygen delivery through vasodilation. The purpose of this study was to clarify the effects of nitroglycerin-induced vasodilation and potential hypotension on tissue perfusion under cerebral oximetry monitoring during rewarming in cardiopulmonary bypass. METHODS: Elective cardiac surgical patients were randomly assigned to either a nitroglycerin group (n = 32) with an intravenous infusion of 1-5 mcg/kg/min or a control group (n = 31) with 0-0.1 mcg/kg/min infusion, since the initiation of rewarming. Perioperative arterial blood gas data were collected in addition to hemodynamic variables, cerebral oximetry values, urine output, and postoperative outcomes. RESULTS: Nearly one-fifth (6/32) of patients in the nitroglycerin group experienced transient (≤5 min) profound hypotension (mean arterial blood pressure ≤40 mmHg) after the initiation of infusion. There were no significant differences between groups in terms of perioperative levels of cerebral oximetry, cardiac index, plasma glucose, lactate, bicarbonate, base excess, or post-bypass activated coagulation time. In the nitroglycerin group, urine output was nonsignificantly higher during cardiopulmonary bypass (p = 0.099) and within 8 h after surgery (p = 0.157). Perioperative transfused blood products, postoperative inotropic doses, extubation time, and intensive care unit stay were comparable for the two groups. CONCLUSIONS: Initiation of intravenous nitroglycerin infusion (at 1-5 mcg/kg/min) during rewarming in hypothermic cardiopulmonary bypass resulted in transient profound hypotension in one-fifth of patients and did not improve perioperative cerebral oxygenation, tissue perfusion, and coagulation in cardiac surgery.

Prescription Opioid Use among Patients with Chronic Noncancer Pain before and after the COVID-19 Outbreak in Taiwan: A Multicenter Prospective Observational Study.

BACKGROUND: The COVID-19 outbreak disrupted medical access for patients receiving chronic opioid therapy. This study investigated their prescription opioid dosages before and after the 2020 outbreak in Taiwan. METHODS: A prospective questionnaire survey was conducted among registered outpatients receiving long-term opioids before July 2019 in Taiwan. The questionnaire included items from the Taiwanese Brief Pain Inventory and quality of life assessment. Follow-up surveys in outpatient departments through October 2020 were conducted to collect opioid prescription data. RESULTS: After a mean of 531 days, the questionnaire responses of 103 of the initial 117 respondents were reviewed. Daily opioid doses decreased for 31 respondents (30.1%), remained roughly equivalent (defined as ±2.5%) for 27 (26.2%), and increased for 45 (43.7%) after the first wave of the pandemic. The use of strong opioids and nonopioid medications did not significantly differ among the three groups, but less fentanyl patch use was noted in the decreased-dose group after the outbreak. More than 70% of the patients received daily high-dose opioids (≥90 morphine milligram equivalents); moreover, 60% reported constipation. No deaths due to opioid overdose occurred during the study period. CONCLUSIONS: The COVID-19 outbreak in 2020 did not interrupt access to long-term opioid prescriptions for most registered patients with chronic pain in Taiwan. Less fentanyl patch use was observed in participants whose opioid dose was tapering.

Extracorporeal Life Support and Temporary CentriMag Ventricular Assist Device to Salvage Cardiogenic-Shock Patients Suffering from Prolonged Cardiopulmonary Resuscitation.

Background: The extracorporeal life support (ECLS) and temporary bilateral ventricular assist device (t-BiVAD) are commonly applied in patients with cardiogenic shock. Prolonged cardiopulmonary resuscitation (CPR) has poor prognosis. Herein, we report our findings on a combined ECLS and t-BiVAD approach to salvage cardiogenic-shock patients with CPR for more than one hour. Methods: Fifty-nine patients with prolonged CPR and rescued by ECLS and subsequent t-BiVAD were retrospectively collected between January 2015 and December 2019. Primary diagnoses included ischemic, dilated cardiomyopathy, acute myocardial infarction, post-cardiotomy syndrome, and fulminant myocarditis. The mean LVEF was 16.9% ± 6.56% before t-BiVAD. The median ECLS-to-VAD interval is 26 h. Results: A total of 26 patients (44%) survived to weaning, including 13 (22%) bridged to recovery, and 13 (22%) bridged to transplantation. Survivors to discharge demonstrated better systemic perfusion and hemodynamics than non-survivors. The CentriMag-related complications included bleeding (n = 22, 37.2%), thromboembolism (n = 5, 8.4%), and infection (n = 4, 6.7%). The risk factors of mortality included Glasgow Coma Scale (Motor + Eye) ≤ 5, and lactate ≥ 8 mmol/L at POD-1, persistent ventricular rhythm or asystole, and total bilirubin ≥ 6 mg/dL at POD-3. Mortality factors included septic shock (n = 11, 18.6%), central failure (n = 10, 16.9%), and multiple organ failure (n = 12, 20.3%). Conclusions: Combined ECLS and t-BiVAD could be a salvage treatment for patients with severe cardiogenic shock, especially for those already having prolonged CPR. This combination can correct organ malperfusion and allow sufficient time to bridge patients to recovery and heart transplantation, especially in Asia, where donation rates are low, as well as intracorporeal VAD or total artificial heart being seldom available.

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.

Knowledge, attitude, and barriers regarding prescribing long-term opioids among Taiwan physicians treating officially registered patients with chronic noncancer pain.

BACKGROUND: Prescribing opioids for patients with chronic noncancer pain (CNCP) remains controversial. This study surveyed Taiwanese physicians who were clinically treating CNCP outpatients with long-term opioids. METHODS: Anonymous questionnaires investigating the clinical practices, opioid knowledge, attitude, and barriers regarding the prescription of long-term opioids were delivered to 66 physicians treating CNCP outpatients who were officially registered and monitored by the Taiwan Food and Drug Administration in 2011. RESULTS: All 66 (100%) physicians responded to the survey, comprising 41 (62%) board-certified pain specialists and 25 (38%) nonpain board-certified physicians. Pain specialists treated a greater number of CNCP outpatients and attended more CNCP training courses than nonpain board-certified physicians (97.6% vs. 56.0%, p < 0.001). Most of pain specialists stated that they were familiar with the Taiwan's narcotic regulations for CNCP patients (92.7% vs. 68.0%, p = 0.015). In addition, pain specialists were less likely to skip or reduce the dosage and duration of opioid prescriptions (22.0% vs. 36.0%, p < 0.001). By contrast, nonpain board-certified physicians had significantly less knowledge and a more negative attitude toward opioid prescription. The major perceived barriers were physician's reluctance to prescribe opioids (78% vs. 92%) and an inadequate knowledge of pain management (73% vs. 84%) among all physicians. CONCLUSION: Among the Taiwanese physicians treating the officially registered CNCP patients, nonpain board-certified physicians had fewer patients, less knowledge, and an increased negative attitude toward long-term opioid prescriptions. Better education on chronic pain management is needed for improvement of clinical practice.

Gender Differences in Depression and Sex Hormones among Patients Receiving Long-Term Opioid Treatment for Chronic Noncancer Pain in Taiwan-A Multicenter Cross-Sectional Study.

BACKGROUND: Long-term use of opioids for chronic noncancer pain is associated with sex hormone disturbances. The interferences with sex hormones, sexual function, and depression were investigated in patients with chronic noncancer pain. METHODS: A cross-sectional multicenter survey was conducted on 170 officially registered outpatients receiving long-term opioid treatment in nine medical centers in Taiwan between October 2018 and July 2019. Serum sex hormone levels were examined after the collection of self-administered questionnaires containing the Taiwanese version of the Brief Pain Inventory, depressive status, and sexual function interference. RESULTS: Among 117 (68.8%) questionnaire responses from 170 enrolled outpatients, 38 women and 62 men completed the sex hormone tests, among whom only 23 (23%) had previously received blood hormone tests. Low serum total testosterone levels were detected in 34 (89.5%) women (<30 ng/dL) and 31 (50%) men (<300 ng/dL). Over 60% of women and men reported reduced sexual desire and function despite a nearly 50% reduction in pain intensity and daily function interference over the previous week after opioid treatment. Women generally had higher risks of a depression diagnosis (p = 0.034) and severe depressive symptoms (p = 0.003) and nonsignificantly lower opioid treatment duration (median 81 vs. 120 months) and morphine milligram equivalent (median 134 vs. 165 mg/day) compared with men. CONCLUSIONS: This survey demonstrated the high prevalence of depression diagnosis, low sex hormone levels, and reduced sexual function among Taiwanese patients with chronic noncancer pain receiving prolonged opioid therapy. Regular hypogonadal screenings are recommended for further management.

Can hypertonic saline influence platelet P selectin expression and platelet-leukocyte aggregation?

OBJECTIVES: Part of platelet function involves aggregation and activation. Activation leads to platelet P selectin expression and platelet-leukocyte aggregation. Hypertonic saline inhibits platelet aggregation, although the effects of hypertonic saline on platelet activation are not known. We evaluated the effects of hypertonic saline on platelet activation as measured by platelet P selectin expression and platelet-leukocyte aggregation. METHODS: Blood samples from healthy volunteers (n = 6) were treated in vitro with various solutions including 23.5%, 7.5%, 3%, and 0.9% saline; Ringer's solution; 5% dextrose in water; and 10% hydroxyethyl starch. Blood was diluted with each type of solution to 2.5%, 5%, 10%, 20%, and 30% (vol/vol) dilution. All blood samples were activated with adenosine diphosphate (20 micromol/L), stained with fluorochrome-conjugated antibodies, and analyzed by flow cytometry to measure platelet P selectin expression and platelet-leukocyte aggregation. RESULTS: The 23.5% saline solution reduced P selectin expression at 20% and 30% dilutions and platelet-leukocyte aggregation at 10%, 20%, and 30% dilutions. The 7.5% solution saline had no effect on P selectin expression and significantly inhibited platelet-leukocyte aggregation only at 30% dilution. Other solutions had no effect on platelet P selectin expression or platelet-leukocyte aggregation. CONCLUSIONS: Our data suggest that hypertonic saline does not affect platelet P selectin expression or platelet-leukocyte aggregation at therapeutic plasma concentrations but that an inhibitory effect occurs at supratherapeutic doses. Dilutions of other solutions caused the least disturbance of platelet activation.

Chronic opioid therapy in patients with chronic noncancer pain in Taiwan.

PURPOSE: Our aim was to analyze the physiopsychosocial variables in patients with long-term opioid therapy for chronic noncancer pain (CNCP) in Taiwan. METHODS: Patients registered in the database of the National Bureau of Controlled Drugs (NBCD), Taiwan, were interviewed and completed questionnaires on pain assessment and interference in quality of life, using the Taiwanese version of the Brief Pain Inventory, and questionnaires on depressive status, using the Chinese version of the Beck Depression Inventory-II; in addition, they completed questionnaires on the adverse effects of the opioid therapy and the use of complementary and alternative medicine. RESULTS: Of 114 patients registered at the NBCD, Taiwan, in August 2001, 61 completed the interviewing procedures and questionnaires. The durations of pain and opioid administration were 93.6 ± 84.3 months (range, 10-480, median 72) and 54.2 ± 57.6 months (range, 6-240, median 30), respectively. Significantly reduced pain intensity (range, 8.8 ± 2.0 to 3.2 ± 2.5) and pain-induced interference with general activity (8.2 ± 2.6 to 3.5 ± 2.5), in addition to improvements in mood, walking ability, normal work, relationships with other people, sleep, and enjoyment of life, indicated remarkably improved quality of life after chronic opioid therapy. The major adverse effects of the opioids were constipation (48%), dry mouth (30%), and nausea and vomiting (21%). Almost half of the patients reported decreases in sexual desire and capability. Up to 60% of the patients received alternative medicine, including acupuncture and herbal drugs. Despite the improved quality of life, 31 of the 61 patients stated that they had moderate or severe depression. CONCLUSIONS: The long-term use of opioids provided significant improvement of pain relief and quality of life in these patients with CNCP; this therapy is a good solution if other modalities are not effective or useful.

Effects of changes in alveolar ventilation on isoflurane arterial blood concentration and its uptake into the human body.

We investigated whether minute alveolar ventilation affects isoflurane concentration in arterial blood and uptake of isoflurane into the body. Thirty female patients scheduled to undergo elective gynecological surgery were randomly assigned to one of three groups: i.e. hyperventilation, normal ventilation and hypoventilation. Inspiratory (CIiso) and end-tidal (CEiso) concentrations of isoflurane were measured by infrared analysis, and arterial blood isoflurane concentration (Aiso) was analyzed by gas chromatography. Cardiac index was measured by Doppler ultrasonography. The body uptake of isoflurane was determined by multiplying alveolar ventilation by the gradient of CIiso-CEiso. Aiso was highest in the hyperventilation group (significant), followed by the normal ventilation and hypoventilation groups, during the 40-min study. During the first 10 min of the study, the slope of the Aiso-over-time curve was highest in the hyperventilation group, followed by the normal ventilation group and the hypoventilation group. During the second half of the study (20-40 min), the slope Aiso-over-time curve did not differ among the three groups. Changes in ventilation affected the concentration of isoflurane in arterial blood but did not significantly alter the uptake of it during the last 20 min of the study. The change of alveolar ventilation altered the speed of functional residual capacity wash-in by isoflurane, which was the integral factor influencing Aiso and body uptake of isoflurane.