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.

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.

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.

Trends and characteristics of pethidine use in Taiwan: a six-year-long survey.

OBJECTIVES: To investigate the trends and characteristics of pethidine prescriptions and users in Taiwan from 2002 to 2007. METHOD: All pethidine users (n = 3,301,136) in Taiwan from 2002 to 2007 were linked to National Health Insurance claims to identify pethidine prescriptions. We examined the trends in pethidine user prevalence and the proportion of pethidine prescriptions according to health care characteristics. A logistic regression model was used to compare patient demographics and health care characteristics associated with pethidine prescriptions between 2002 and 2007. RESULTS: Despite the decline in the number of pethidine users and prescriptions over the six-year period, more than half a million people were prescribed pethidine annually. In fact, an increasing proportion of pethidine prescriptions were observed in clinics, outpatient settings, and patients who had both operations and cancer diagnoses. Pethidine prescriptions were mostly associated with a non-operation status without a cancer diagnosis (>60%). However, approximately 10% of the total pethidine prescriptions were found in patients with a cancer diagnosis but no operation. Compared to those in 2002, pethidine prescriptions in 2007 were more likely to be found in people 80 years or older, rural residents, patients from clinics, outpatient settings and operation patients with cancer diagnoses. CONCLUSIONS: A population-based survey in Taiwan demonstrated decreasing consumption of pethidine from 2002 to 2007; however, an increased proportion of prescriptions in certain health care settings was observed. In addition, 10% of the pethidine prescriptions were for cancer patients without operations. These cases need further evaluation for the determination of appropriate pethidine use.

Trends and characteristics of pethidine use in Taiwan: a six-year-long survey

OBJECTIVES: To investigate the trends and characteristics of pethidine prescriptions and users in Taiwan from 2002 to 2007. METHOD: All pethidine users (n = 3,301,136) in Taiwan from 2002 to 2007 were linked to National Health Insurance claims to identify pethidine prescriptions. We examined the trends in pethidine user prevalence and the proportion of pethidine prescriptions according to health care characteristics. A logistic regression model was used to compare patient demographics and health care characteristics associated with pethidine prescriptions between 2002 and 2007. RESULTS: Despite the decline in the number of pethidine users and prescriptions over the six-year period, more than half a million people were prescribed pethidine annually. In fact, an increasing proportion of pethidine prescriptions were observed in clinics, outpatient settings, and patients who had both operations and cancer diagnoses. Pethidine prescriptions were mostly associated with a non-operation status without a cancer diagnosis (>60%). However, approximately 10% of the total pethidine prescriptions were found in patients with a cancer diagnosis but no operation. Compared to those in 2002, pethidine prescriptions in 2007 were more likely to be found in people 80 years or older, rural residents, patients from clinics, outpatient settings and operation patients with cancer diagnoses. CONCLUSIONS: A population-based survey in Taiwan demonstrated decreasing consumption of pethidine from 2002 to 2007; however, an increased proportion of prescriptions in certain health care settings was observed. In addition, 10% of the pethidine prescriptions were for cancer patients without operations. These cases need further evaluation for the determination of appropriate pethidine use.

Pre-emptive intrathecal quinidine alleviates spinal nerve ligation-induced peripheral neuropathic pain.

OBJECTIVES: Quinidine, a class I anti-arrhythmic agent, is a sodium channel blocker that is more potent than lidocaine and mexiletine. This study tested pre-emptive intrathecal quinidine to attenuate neuropathic pain induced by lumbar spinal nerve ligation (SNL). METHODS: Ninety-six adult male Sprague-Dawley rats were grouped equally (n=24 per group) as follows: group S (sham), removal of transverse process only; group L, SNL; group Q35, SNL pretreated with intrathecal quinidine 35 mM (50 µl); group Q70, SNL pretreated with intrathecal quinidine 70 mM (50 µl). Neuropathic pain was measured by thermal hyperalgesia and mechanical allodynia. Other measurements included dys-regulation of sodium channel Nav1.3 in dorsal root ganglion (DRG) and spinal microglia activation in spinal dorsal horn. KEY FINDINGS: Spinal nerve ligation induced abnormal mechanical allodynia and thermal hyperalgesia, up-regulated Nav1.3 in DRG, and activated microglia in spinal cord. Group Q70 showed attenuated thermal hyperalgesia (P<0.001) and mechanical allodynia (P<0.05) on postoperative day 5 (POD5) but not on POD7, reversed up-regulated expression of Nav1.3 on POD3 and POD7 in DRG and significantly attenuated microglia activation on POD7 (P=0.032) in spinal cord. CONCLUSIONS: Pretreatment with intrathecal quinidine 70 mM before SNL attenuates nerve ligation-induced neuropathic pain. The duration of the effect is 5 days.

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.

In vitro and in vivo evaluation of the metabolism and pharmacokinetics of sebacoyl dinalbuphine.

A diester prodrug of nalbuphine, sebacoyl dinalbuphine (SDN), and its long-acting formulation are currently being developed to prolong the duration of nalbuphine. A comparative in vitro hydrolysis study was conducted for SDN in rat, rabbit, dog, and human blood. Both SDN and nalbuphine in blood or plasma were measured by high-performance liquid chromatography. The hydrolysis rates of SDN in blood were ranked as follows: rat > rabbit > human > dog. The rapid formation of nalbuphine in the blood accounted for almost 100% of the prodrug, which supported the contention that nalbuphine is the major metabolite after SDN hydrolysis. The hydrolysis profiles of SDN were similar both in plasma and in red blood cells when compared in the blood. In vitro release results of SDN long-acting formulation showed that the rate-limited step of SDN hydrolysis to nalbuphine in blood is the penetration of SDN from oil into the blood. After intravenous administration of SDN in sesame oil into rats, nalbuphine quickly appeared in plasma and, thereafter, exhibited monoexponential decay. Pharmaceutical dosage forms affecting the drug disposition kinetics were demonstrated after intravenous administration. The AUC of nalbuphine was significantly higher and clearance was significantly lower, without changes in the t(1/2) of nalbuphine after intravenous dosing of SDN in sesame oil when compared with that of intravenous dosing with nalbuphine HCl in rats. Overall, these results suggest that SDN fulfilled the original pro-soft drug design in which the prodrug can rapidly metabolize to nalbuphine, and no other unexpected compounds were apparent in the blood.

Low-dose dexamethasone ameliorates circulatory failure and renal dysfunction in conscious rats with endotoxemia.

Corticosteroids have long been proposed as a therapeutic adjuvant in septic renal dysfunction because of their anti-inflammatory properties and favorable results from animal experiments. However, some reports suggested the potential for harm associated with the administration of early high-dose corticosteroids in patients with severe sepsis and septic shock. Thus, we examined the effects of low-dose dexamethasone (0.01 and 0.1 mg/kg) on hemodynamics and renal function in conscious rats with endotoxemia. Intravenous injection of rats with endotoxin (E. coli lipopolysaccharide, LPS, 1 mg/kg) caused hypotension, vascular hyporeactivity, and tachycardia as well as renal dysfunction. Circulatory failure and renal dysfunction caused by LPS were significantly attenuated in the dexamethasone 0.1 mg/kg-treated group. The nitric oxide (NO) production in plasma and renal tissue and the iNOS protein expression in the kidney were suppressed by cotreatment of LPS rats with dexamethasone, 0.1 mg/kg. Light microscopy showed that 0.1 mg/kg dexamethasone reduced marked infiltration of neutrophils in renal tissues from LPS rats. Moreover, the survival rate at 18 h was significantly increased in the dexamethasone 0.1 mg/kg-treated group when compared with the LPS group. These results suggest that the beneficial effects of low-dose dexamethasone (0.1 mg/kg) in conscious rats with endotoxic shock are associated with amelioration of circulatory failure and renal dysfunction, and this is attributed to inhibition of NO production.