Inpatient Hospice Palliative Care Unit and Palliative Consultation Service Enhance Comprehensive Quality of Life Outcomes in Terminally Ill Cancer Patients: A Prospective Longitudinal Study.

This study aimed to explore the effectiveness of an inpatient hospice palliative care unit (PCU) and palliative consultation service (PCS) on comprehensive quality of life outcome (CoQoLo) among terminally ill cancer patients. This was a prospective longitudinal study. Terminally ill cancer patients who met the inclusion criteria and received PCU or PCS in a northern Taiwanese medical center were recruited. The CoQoLo Inventory was used to measure CoQoLo level pre- and seven days following hospice care between August 2018 and October 2019. A total of 90 patients completed the study. No significant differences were found in CoQoLo levels between the PCU and PCS groups pre- and seven days following care. However, the CoQoLo level of patients significantly improved seven days following care in both PCU and PCS groups, compared with pre-hospice care. Patients' age, religious belief, marital status, closeness with family, palliative prognostic index (PPI), and symptom severity were significant concerning CoQoLo levels after adjusting for patients' baseline characteristics. PCU and PCS showed no difference in CoQoLo levels, but both of them can improve CoQoLo among terminally ill cancer patients. These patients could receive PCU or PCS to achieve a good CoQoLo at the end-of-life stage.

Visualizing Patterns of Medication Switching Among Major Depressive Patients with Various Stability and Difficulty to Treatments.

INTRODUCTION: Efforts have been made in assessing efficacy and tolerability to various antidepressants, but understanding personalized chances of stability to medication switching sequence is still inconclusive. This study aimed to identify naturalistic switching patterns of medication in stratifying MDD patients. METHODS: MDD patients were stratified based on treatment difficulty evaluated with the "Treatment Resistance to Antidepressants Evaluation Scale for Unipolar Depression" (TRADES). The duration of the time of diagnoses until the final switch to another class of antidepressants was used as prediction of unstable to drug therapy. ROC analysis was used to determine the cutoff values. A continuous temporal events function from the visual analytic tool was employed to perform patterns of switching between distinct pharmacological class such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). RESULTS: TRADES scores of 4.5 and not-switching times of 12.5 months were used as cutoff values to divide patients into four subgroups: stable/easy-to-treat (SE), unstable/easy-to-treat (UE), stable/difficult-to-treat (SD) and unstable/difficult-to-treat (UD). A total of 80% and 76.9% of patients initially treated with the SSRIs paroxetine or fluoxetine, respectively, were predicted to be stable to drug therapy. Approximately 70%, 44.8% and 41.4% of patients initially treated with the SNRIs fluvoxamine, sertraline and venlafaxine, respectively, were predicted to be UD, and 60% of patients using duloxetine were predicted to be stable to drug therapy. Analysis of the switching phenomenon showed that SSRIs were the first prescribed medications and mostly taken by the stable subgroups, and SNRIs were the preferentially chosen switching alternative. Medication switching patterns in unstable MDD patients are discussed. CONCLUSION: Paroxetine, fluoxetine and duloxetine users were mostly stable among MDD patients in Taiwan with various stability and difficulty to treatments. Although responsiveness to specific medication sequence is likely required for clinical application, the results provide a baseline for such studies.

Effects of Dispositional Resilience and Self-Efficacy on Practice in Advanced Care Planning of Terminally Ill Patients among Taiwanese Nurses: A Study Using Path Modeling.

This study aimed to expand on previous research elucidating the effects of dispositional resilience and self-efficacy on practice in advanced care planning (ACP) of terminally ill patients among Taiwanese nurses using path modeling. This cross-sectional study was conducted using cluster sampling. Data were collected using demographics, nurses' knowledge, attitude, and practice of ACP (KAP-ACP) inventory, Dispositional Resilience Scale, and General Self-Efficacy Scale. A total of 266 nurses from a tertiary medical center in northern Taiwan participated in this study in 2019. The results showed that gender and ward were significant K-ACP predictors among nurses. The ACP knowledge, ward, and experience of caring for terminally ill friends or relatives were significant A-ACP predictors, whereas ACP attitudes, dispositional resilience, self-efficacy, ward, and the frequency of caring for terminally ill patients were the key predictors of P-ACP. The path modeling showed that dispositional resilience; self-efficacy; medical, surgical, hematology and oncology wards; previous experience in caring for terminally ill friends or relatives; participating in the do-not-resuscitate signature; and the frequency of caring for terminally ill patients directly influenced ACP practices. We recommend that nurses enhance their dispositional resilience and self-efficacy, which may encourage them to appreciate the value of ACP practice of terminally ill patients and improve the quality of care.

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation.

Protein phosphorylation can induce signal transduction to change sperm motility patterns during sperm capacitation. However, changes in the phosphorylation of sperm proteins in mice are still incompletely understood. Here, capacitation-related phosphorylation in mouse sperms were firstly investigated by label-free quantitative (LFQ) phosphoproteomics coupled with bioinformatics analysis using ingenuity pathway analysis (IPA) methods such as canonical pathway, upstream regulator, and network analysis. Among 1632 phosphopeptides identified at serine, threonine, and tyrosine residues, 1050 novel phosphosites, corresponding to 402 proteins, were reported. Gene heatmaps for IPA canonical pathways showed a novel role for GSK-3 in GP6 signaling pathways associated with capacitation for 60 min. At the same time, the reduction of the abundant isoform-specific GSK-3α expression was shown by western blot (WB) while the LFQ pY of this isoform slightly decreased and then increased. The combined results from WB and LFQ methods explain the less inhibitory phosphorylation of GSK-3α during capacitation and also support the predicted increases in its activity. In addition, pAKAP4 increased at the Y156 site but decreased at the Y811 site in a capacitated state, even though IPA network analysis and WB analysis for overall pAKAP revealed upregulated trends. The potential roles of GSK-3 and AKAP4 in fertility are discussed.

The Effect of Practice toward Do-Not-Resuscitate among Taiwanese Nursing Staff Using Path Modeling.

This study aimed to elucidate the predictors and the effects of path modeling on the knowledge, attitude, and practice toward do-not-resuscitate (DNR) among the Taiwanese nursing staff. This study was a cross-sectional, descriptive design using stratified cluster sampling. We collected data on demographics, knowledge, attitude, and practice as measured by the DNR inventory (KAP-DNR), Mindful Attention Awareness Scale, General Self-Efficacy Scale, and Dispositional Resilience Scale. Participants were 194 nursing staff from a medical center in northern Taiwan in 2019. The results showed that participation in DNR signature and education related to palliative care were significant positive predictors of knowledge toward DNR. The DNR predictors toward attitude included DNR knowledge, mindfulness, self-efficacy, dispositional resilience, and religious belief of nurses. Generally, the critical predictors of DNR practice were DNR attitude, dispositional resilience, and male nurses. In path modeling, we identified that self-efficacy, dispositional resilience, master's degree, and religious belief directly influenced practice constituting DNR. Based on the findings of this study, we propose that nurses should improve their self-efficacy and dispositional resilience through training programs. Encouraging staff to undertake further education and have religious beliefs can enhance the practice of DNR and provide better end-of-life care.

Effectiveness of palliative care consultation service on caregiver burden over time between terminally ill cancer and non-cancer family caregivers.

PURPOSE: The responsibility of taking care of terminal patients is accepted as a role of family members in Taiwan. Only a few studies have focused on the effect of palliative care consultation service (PCCS) on caregiver burden between terminal cancer family caregivers (CFCs) and non-cancer family caregivers (NCFCs). Therefore, the purpose of this study is to address the effect of PCCS on caregiver burden between CFC and NCFC over time. METHODS: A prospective longitudinal study was conducted in a medical center in northern Taiwan from July to November 2017. The participants were both terminally ill cancer and non-cancer patients who were prepared to receive PCCS, as well as their family caregivers. Characteristics including family caregivers and terminal patients and Family Caregiver Burden Scale (FCBS) were recorded pre-, 7, and 14 days following PCCS. A generalized estimating equation model was used to analyze the change in the level of family caregiver burden (FCB) between CFC and NCFC. RESULTS: The study revealed that there were no statistically significant differences in FCB between CFC and NCFC 7 days and 14 days after PCCS (p > 0.05). However, FCB significantly decreased in both CFC and NCFC from pre-PCCS to 14 days after PCCS (ß = - 12.67, p = 0.013). PPI of patients was the key predictor of FCB over time following PCCS (ß = 1.14, p = 0.013). CONCLUSIONS: This study showed that PCCS can improve FCB in not only CFC but also NCFC. We suggest that PCCS should be used more widely in supporting family caregivers of terminally ill patients to reduce caregiver burden.

Constructing a bilingual website with validated database for Herb and Western medicine interactions using Ginseng, Ginkgo and Dong Quai as examples.

BACKGROUND: Concerns have been raised regarding the efficacy and safety resulting from the potential interactions of herbs with Western medications due to the use of both herbs and Western medicine by the general public. Information obtained from the web must be critically evaluated prior to its use in making decisions. DESCRIPTION: This study aimed to construct an herb-drug interaction (HDI) website (https://drug-herb-interaction.netlify.com) with a critically reviewed database. Node.js was used to store the database by running JavaScript. Vue.js is a front-end framework used for web interface development. A total of 135 sets of information related to the interactions of ginseng, ginkgo and dong quai with Western medicine from the literature identified in Medline were collected, followed by critical reviews to prepare nineteen items of information for each HDI monograph. A total of 80 sets of validated HDIs met all criteria and were further assessed at the individual reliability level (likely, possible, and unevaluable) and labeled with the "interaction" item. This query system of the website can be operated in both the Chinese and English languages to obtain all monographs on HDIs in the database, including bilingual interaction data. The database of HDI monographs can be updated by simply uploading a new version of the information Excel file. The designed "smart search" module, in addition to the "single search", is convenient for requesting multiple searches. Among the "likely" interactions (n = 26), 50% show negative HDIs. Ten of these can increase the effect of the Western drug, and the others (n = 3) imply that the HDI can be beneficial. CONCLUSIONS: The current study provides a website platform and 80 sets of validated bilingual HDIs involving ginseng, ginkgo and dong quai in an online database. A search of HDI monographs related to these three herbs can be performed with this bilingual, easy-to-use query website, which is feasible for professionals and the general public. The identified reliability level for each HDI may assist readers' decisions regarding whether taking Western medications concomitant with one of three herbal medicinal foods is safe or whether caution is required due to potentially serious outcomes.

Long-Term Effectiveness of Two Educational Methods on Knowledge, Attitude, and Practice Toward Palliative Care Consultation Services Among Nursing Staff: A Longitudinal Follow-Up Study.

This experimental study investigated long-term effectiveness of two educational methods on knowledge, attitude, and practice (KAP) about palliative care consultation services (PCCS) among nurses, recruited from a medical center located in Northern Taiwan in 2015, using a stratified cluster sampling method, with 88 participants in multimedia (experimental) and 92 in traditional paper education (control) group. Data were collected using KAP-PCCS questionnaire before education, immediately after, and 3rd and 6th month after education. Results showed that both K-PCCSI and P-PCCSI significantly increased immediately after, and at the 3rd month after education for the experimental group; the K-PCCSI remained significantly higher for the experimental group at the 6th month. The highest increase in scores for both K-PCCSI and P-PCCSI was observed at the 3rd month. There was no significant change in A-PCCS in both groups after follow-up periods, when compared before education. Therefore, using multimedia every 3 months to continue strengthening their knowledge may increase the referrals of terminal patients to PCCS.

Path modeling of knowledge, attitude and practice toward palliative care consultation service among Taiwanese nursing staff: a cross-sectional study.

BACKGROUND: The Taiwanese government has promoted palliative care consultation services (PCCS) to support terminally ill patients in acute ward settings to receive palliative care since 2005. Such an intervention can enhance the quality of life and dignity of terminally ill patients. However, research focusing on the relationship between the knowledge, attitude and practice of a PCCS using path modelling in nursing staff is limited. Therefore, the aim of this study was to elucidate the effect of path modeling on the knowledge, attitude and practice toward PCCS in Taiwanese nursing staff. METHODS: This was a cross-sectional, descriptive study design using convenience sampling. Data collected included demographics, knowledge, attitude and practice as measured by the PCCS inventory (KAP-PCCSI). Two hundred and eighty-four nursing staff from a medical center in northern Taiwan participated in the study in 2013. We performed descriptive statistics, regression analysis, and path modeling using SPSS 19.0 and set p < 0.05 as the statistical significance threshold. RESULTS: The results showed that the identical factor significantly associated with knowledge, attitude, and practice toward PCCS among nurses was the frequency of contact with PCCS. In addition, higher level of knowledge toward PCCS was associated with working in haematology and oncology wards, and participation in education related to palliative care. A more positive attitude toward PCCS was associated with working in a haematology and oncology ward, and experience of friends or relatives dying. Higher level of practice toward PCCS was associated with nurses who participated in education related to palliative care. In the path modeling, we found that holders of a master's degree indirectly positive affected practice toward PCCS. Possession of a bachelor degree or above, being single, working within a haematology and oncology ward, and frequency of contact with PCCS positively affected practice toward PCCS. CONCLUSIONS: Based on this study, it is proposed that consultation with PCCS has a positive impact on the care of terminally ill patients. Encouragement of staff to undertake further education can improve the practice of ward staff providing palliative care.

Trimucrin, an Arg-Gly-Asp containing disintegrin, attenuates myocardial ischemia-reperfusion injury in murine by inhibiting platelet function.

Trimucrin, a novel small-mass Arg-Gly-Asp (RGD)-containing disintegrin, has been demonstrated to possess anti-platelet and anti-inflammatory effect through blockade of platelet αIIbß3 and phagocyte αvß3 integrin. In this study, we found that the platelet-rich plasma prepared from trimucrin-treated rats platelet aggregation was diminished in response to adenosine diphosphate (ADP). We tried to determine whether trimucrin is cardioprotective in rats subjected to myocardial ischemia-reperfusion (I-R) injury. The left anterior descending coronary artery of anesthetized rats was subjected to 1h occlusion and 3h reperfusion. The animals received intravenous trimucrin or saline, and the severities of I-R-induced arrhythmia and infarction were compared. Trimucrin significantly reduced I-R-induced arrhythmias and reduced mortality, as well as infarct volume, troponin-I levels, creatine kinase, and lactate dehydrogenase activity in carotid blood compared with vehicle-treated animals during the same period. Trimucrin also improved cardiac function and survival rates after I-R injury. In addition, trimucrin concentration-dependently inhibited platelet adhesion on collagen- and fibrinogen-coated surfaces without affecting platelet counts. Trimucrin also significantly reduced neutrophil infiltration into heart tissues after I-R compared with controls. Furthermore, trimucrin treatment caused significant downregulation of Bax, Caspase-3 apoptotic proteins and upregulation of anti-apoptotic Bcl-2 protein. These results demonstrate that trimucrin exerts cardioprotective property against myocardial I-R injury mediated through antiplatele, anti-inflammatory, anti-apoptotic mechanism, as well as improvements in cardiac function.

The disintegrin, trimucrin, suppresses LPS-induced activation of phagocytes primarily through blockade of NF-κB and MAPK activation.

In addition to antiplatelet activity, disintegrin, a small-mass RGD-containing polypeptide, has been shown to exert anti-inflammatory effects but the mechanism involved remains unclear. In this study, we report that trimucrin, a disintegrin from the venom of Trimeresurus mucrosquamatus, inhibits lipopolysaccharide (LPS)-induced stimulation of THP-1 and RAW 264.7 cells. We also investigate the underlying mechanism. Trimucrin decreased the release of proinflammatory cytokines including tumor necrosis factor α (TNFα), interleukin-6 (IL-6), nitric oxide, and reactive oxygen species (ROS), and inhibited the adhesion and migration of LPS-activated phagocytes. Trimucrin significantly blocked the expression of nuclear factor kappaB (NF-κB)-related downstream inducible enzymes such as inducible nitric oxide synthase (iNOS) and COX-2. In addition, its anti-inflammatory effect was associated with the decreased mitogen-activated protein kinase (MAPK) phosphorylation. Furthermore, trimucrin concentration dependently inhibited LPS-induced phosphorylation of focal adhesion kinase (FAK), PI3K, and Akt. Trimucrin also reversed the DNA-binding activity of NF-κB by suppressing the LPS-induced nuclear translocation of p65 and the cytosolic IκB release. Flow cytometric analyses showed that trimucrin bound to cells in a concentration-dependent manner. The anti-αVß3 mAb also specifically decreased the binding of fluorescein isothiocyanate (FITC)-conjugated trimucrin. Binding assays demonstrated that integrin αVß3 was the binding site for trimucrin on THP-1 and RAW 264.7 cells. In conclusion, we showed that trimucrin decreases the inflammatory reaction through the attenuation of iNOS expression and nitric oxide (NO) production by blocking MAP kinase and the NF-κB activation in LPS-stimulated THP-1 and RAW 264.7 cells.

Discotic liquid crystals as novel corrosion-resistant coatings.

A discotic liquid crystal (DLC), HBC-C12, coating was successfully applied to improve the corrosion resistance of an iron surface. The iron surface with the DLC-coating exhibited improved corrosion resistance in various environments, including exposure to air and solutions with different pH values. To the best of our knowledge, studies regarding corrosion protection using DLCs have never been reported.

Agreement of cardiac output measurement between pulse contour analysis and thermodilution in various body positions: a porcine study.

BACKGROUND: We elucidated the effects of various body positions on the agreement of cardiac output (CO) measurement between pulse contour analysis with the PiCCO monitor and thermodilution with pulmonary artery catheterization. METHODS: Fifteen anesthetized and mechanically ventilated pigs (40 ± 2 kg) were sequentially placed in various positions to facilitate simultaneous CO measurement. Between-methods agreement was assessed using the Bland-Altman method. Trending ability was assessed using Pearson product-moment correlation coefficient analysis. RESULTS: In supine, reverse Trendelenburg, Trendelenburg, and left lateral decubitus (lateral) positions, CO measured by these two methods was comparable (4.9 ± 1.5 versus 4.6 ± 1.6 L/min, 4.6 ± 2.2 versus 4.8 ± 1.8 L/min, 5.1 ± 2.1 versus 4.9 ± 2.1 L/min, and 5.4 ± 1.8 versus 5.0 ± 1.6 L/min; all P > 0.05). Mean bias between methods and limits of agreement (percentage error) were 0.3 ± 2.9 L/min (61%), -0.3 ± 3.3 L/min (71%), 0.1 ± 4.1 L/min (77%), and 0.5 ± 3.7 L/min (71%). Directional changes of paired CO revealed 66% (reverse Trendelenburg), 57% (Trendelenburg), and 66% (lateral) concordance. The correlation coefficient (r(2)) was 0.199, 0.127, and 0.108. For paired CO ≤6 L/min, mean bias between methods and limits of agreement (percentage error) were 0.2 ± 1.0 L/min (25%), -0.1 ± 1.0 L/min (28%), 0.2 ± 1.1 L/min (29%), and 0.5 ± 0.9 L/min (23%). Directional changes of paired CO revealed 84% (reverse Trendelenburg), 76% (Trendelenburg), and 65% (lateral) concordance. The correlation coefficient (r2) was 0.583, 0.626, and 0.213. CONCLUSIONS: The mean CO measured by pulse contour analysis and thermodilution did not agree well in various body positions. Moreover, the measurements tended to trend differently in response to positional changes. For paired CO ≤6 L/min, however, the between-methods agreement and the trending ability improved significantly.

Electroacupuncture analgesia, stress responses, and variations in sensitivity in rats anesthetized with different sub-MAC anesthetics.

The use of anesthetics to stabilize animals for the purpose of electroacupuncture (EA) analgesic studies can be problematic because of the interference of differential physiological responses to EA and pain. In this study, EA-induced physiological profiles were surveyed under a sub-minimal alveolar concentration (sub-MAC) of two different anesthetics in a previously proposed minimal stress model. First, to select an adequate concentration, compliance with EA and tail-flick stimulation was evaluated under various concentrations of halothane and isoflurane. Second, using the chosen concentrations, low- (4-Hz) and high-frequency (100-Hz) EA were conducted on the right hind limb. The EA effects of the two gases were compared by tail-flick latency (TFL), hemodynamic variables, and individual variations in analgesic sensitivity. The optimal concentrations for halothane and isoflurane were 0.5% and 0.75%, respectively. TFLs were stable under these anesthetic levels, but rats under 0.75% isoflurane had better compliance than those under 0.5% halothane. EA inhibited TFLs with distinct analgesic patterns when comparing high- and low-frequency EA, but TFL suppression did not differ between the two gases. Heart rate and blood pressure showed temporal and differential responses to low- vs. high-frequency EA, but were comparable between groups under the two anesthetics. The ratios of EA non-responders in the isoflurane and halothane groups were 32.4% and 26.7%, respectively, without statistical difference. We concluded that sub-MAC halothane and isoflurane provide optimal conditions for the study of EA-induced analgesia in rats. In this model, 0.75% isoflurane appears to be a better choice than 0.5% halothane in terms of EA compliance.

Resiniferatoxin combined with antidepressants preferentially prolongs sensory/nociceptive block in rat sciatic nerve.

BACKGROUND: Current techniques of peripheral nerve block have major limitations, including lack of differentiation between motor and sensory fibers and potential toxicity of local anesthetics. Recent studies have suggested that a nociceptive-selective nerve block can be achieved via a transient receptor potential vanilloid type 1 activator (capsaicin) along with local anesthetics. We hypothesized that the combination of potent transient receptor potential vanilloid type 1 agonist resiniferatoxin (RTX) and selected antidepressants (amitriptyline, doxepin, and fluoxetine, also potent sodium channel blockers) would produce prolonged and predominantly sensory nerve block. METHODS: Rats were anesthetized with isoflurane, and 0.2 mL of amitriptyline, doxepin, or fluoxetine was deposited next to the surgically exposed sciatic nerves (n = 8 per group). Some animals received a second injection containing RTX (n = 8 per group). The effect of nerve block was assessed by neurobehavioral tests of the motor function (extensor postural thrust) and the nocifensive reaction (mechanical pinch). RESULTS: A single application of RTX produced nociceptive-selective sciatic nerve block, whereas antidepressants produced nociceptive and motor block. The combined administration of RTX and antidepressant resulted in a predominantly nociceptive nerve block. Compared with antidepressants or RTX alone, the combination prolonged the nociceptive nerve block more than the motor block. CONCLUSIONS: The combined application of RTX and antidepressants produced a markedly prolonged nociceptive peripheral nerve block in rat sciatic nerves compared with either agent alone. However, the 2-drug regimen also elicited prolonged blockade of the motor function, although disproportionately less compared with the nociceptive modality, suggesting the existence of nontransient receptor potential vanilloid type 1-mediated mechanisms. The mechanisms through which RTX affects nociceptive signal transduction/transmission have yet to be fully elucidated.

Calcium chloride prolongs the effects of lidocaine and bupivacaine in rat sciatic nerve.

BACKGROUND AND OBJECTIVES: Elevated extracellular calcium ion has been shown to shift the voltage dependence of Na+- and K+-ion channels rightward, making the nerve less excitable. We hypothesized that calcium chloride (CaCl2) when used as an adjuvant prolongs and intensifies the block by local anesthetics (LAs). We investigated the effects of LAs combined with calcium in rat sciatic nerve blockade and in cultured rat GH3 cells expressing Na+ channels. Furthermore, we tested for histologic changes due to CaCl2. METHODS: We anesthetized rats with sevoflurane, exposed the sciatic nerves, and injected 0.2 mL of 1% lidocaine or 0.1% bupivacaine, alone or coadministered with 0.625%, 1.25%, 2.5%, or 5% CaCl2 (n = 8-10 per group). We assessed the complete-block time and complete-recovery time of proprioception, motor function, and nocifensive reaction. To elucidate the mechanism of nerve block, we performed electrophysiology experiments in cultured rat GH3 cells. Sciatic nerves were harvested at day 7 and stained with hemotoxylin/eosin. RESULTS: The addition of CaCl2 overall prolonged the duration of blockade by lidocaine or bupivacaine. Adding 10 mM CaCl2 to 300 microM lidocaine caused a right shift of the steady-state Na+-channel inactivation curve, indicating that the CaCl2 reduced the potency of lidocaine. Rat sciatic nerves treated with 1% lidocaine coadministered with 5% CaCl2 showed microscopic signs of neurotoxicity. CONCLUSIONS: The mechanism of prolonged nerve block of CaCl2 coadministered with LAs seems to be a raised threshold for nerve excitation. Major histopathologic changes at higher concentrations of CaCl2 are evident, and therefore, clinical application as an adjuvant to LAs seems unlikely.

Premedication with mirtazapine reduces preoperative anxiety and postoperative nausea and vomiting.

BACKGROUND: Mirtazapine is a new antidepressant that blocks 5-HT2 and 5-HT3 receptors. With this receptor profile, it is possible that mirtazapine could provide both anxiolysis and efficacy for postoperative nausea and vomiting (PONV). We therefore tested the hypothesis that premedication with mirtazapine can reduce preoperative anxiety and PONV. METHODS: Eighty female patients with at least two PONV risk factors scheduled for gynecological surgery were enrolled. Dexamethasone 8 mg was given before induction of anesthesia and patients were randomly assigned to group M + D (mirtazapine plus dexamethasone) or group dexamethasone. An oral disintegrating mirtazapine 30 mg or placebo tablet was given 1 h before surgery. Preoperative anxiety level was assessed by a visual analog scale (VAS) before mirtazapine administration and 1 h thereafter. General anesthesia was induced with 1% propofol at the rate of 200 mL/h (until loss of consciousness) and was then maintained with sevoflurane in oxygen and air. An auditory evoked potentials index monitor was used to titrate sevoflurane. The incidence of PONV, the use of rescue antiemetic, complete response, postoperative Ramsay Sedation Scores, and VAS pain scores were assessed 1, 2, and 24 h after surgery and compared. RESULTS: The VAS anxiety scale was lower in group M + D after mirtazapine administration. There were no differences in the induction dose of propofol, the concentrations of sevoflurane during anesthesia, and recovery times between the two groups. The incidence of complete response to PONV over 0-24 h was lower in group M + D (80% vs 50%, P < 0.01). CONCLUSIONS: Premedication with mirtazapine 30 mg reduces the level of preoperative anxiety and the risk of PONV in moderate and high-risk female patients.

Changes of regional cerebral oxygen saturation during spinal anesthesia.

BACKGROUND: During spinal anesthesia, hemodynamic status is routinely monitored, but this may not give an accurate assessment of cerebral oxygenation. Cerebral oximetry, facilitated by using a near-infrared spectroscope, is a way of estimating regional cerebral oxygen saturation (SrO2). We designed this prospective clinical study to determine whether the changes in mean arterial pressure (MAP) and heart rate (HR) could predict changes in SrO2 during spinal anesthesia. METHODS: The study sample available for analysis included 45 patients, ASA class I to II, who were scheduled for elective ureteroscopic surgery requiring spinal anesthesia. Spinal anesthesia was performed with 12 mg 0.5% hyperbaric bupivacaine injected intrathecally via L3-4 or L4-5 interspace. MAP, HR, oxygen saturation by pulse oximeter, and SrO2 by near-infrared spectroscope were recorded every 2 min throughout the procedure. RESULTS: SrO2 was tested by the Shapiro-Wilk test and the results departed from the multivariate normal distribution. The method of generalized estimating equations (GEE) was then used to estimate the model. The output of the GEE analysis for the time-lag model showed that there were relationships between SrO2 and two predictors (MAP and HR) with the correction of the baseline values. All the parameters were significant at a level of 5%. The effects of the decreases of MAP and HR on SrO2 lasted continuously for at least 6 min. CONCLUSIONS: Based on the time-lag pattern between two predictors (MAP and HR) and SrO2 during spinal anesthesia, we ventured to conclude that a change in MAP or HR caused a significant decrease in SrO2. Since no patient developed any neurologic complication perioperatively, further study must be performed to elucidate the clinical importance of our findings.

Magnesium sulfate diminishes the effects of amide local anesthetics in rat sciatic-nerve block.

BACKGROUND AND OBJECTIVES: Magnesium sulfate (MgSO(4)) is well known as an antagonist of N-methyl-d-aspartate receptors and was used for intrathecal analgesia a century ago. However, the effects of MgSO(4) combined with local anesthetics (LAs) on peripheral nerves are unclear. We tested the hypothesis that MgSO(4) could be used as an adjuvant to prolong and intensify conduction block by amide-type LAs in a rat sciatic-nerve block model. Further, the mechanism of possible synergy between LAs and MgSO(4) was investigated in whole-cell mode patch-clamp experiments. METHODS: Sciatic nerves were exposed to 2%/73.9 mM lidocaine, 0.25%/7.7 mM bupivacaine, and 0.5%/15.4 mM ropivacaine, with or without addition of 1.25%, 2.5%, or 5% MgSO(4)/50.7 mM, and nerve block characteristics were assessed. To elucidate the LA-MgSO(4) interaction, voltage-dependent inactivation curves were determined in cultured rat GH(3) cells that expressed neuronal Na(+) channels. RESULTS: Unexpectedly, the addition of MgSO(4) overall significantly shortened the duration of block by lidocaine, bupivacaine, and ropivacaine. The steady-state inactivation of Na(+) channels in the presence of 300 muM lidocaine was almost unchanged by the addition of 10 mM MgSO(4), indicating that MgSO(4) does not affect the potency of lidocaine toward the inactivated Na(+) channel. CONCLUSIONS: MgSO(4) coadministered with amide-type LAs shortened the duration of sciatic-nerve block in rats. Therefore, it does not seem to be useful as an adjuvant for peripheral-nerve block. The mechanism of this observed antagonism is unclear but appears to be independent of the action of LAs and MgSO(4) at the LA receptor within the Na(+) channel.

Mitigation of direct neurotoxic effects of lidocaine and amitriptyline by inhibition of p38 mitogen-activated protein kinase in vitro and in vivo.

BACKGROUND: Local anesthetic-induced direct neurotoxicity (paresthesia, failure to regain normal sensory and motor function) is a potentially devastating complication of regional anesthesia. Local anesthetics activate the p38 mitogen-activated protein kinase (MAPK) system, which is involved in apoptotic cell death. The authors therefore investigated in vitro (cultured primary sensory neurons) and in vivo (sciatic nerve block model) the potential neuroprotective effect of the p38 MAPK inhibitor SB203580 administered together with a clinical (lidocaine) or investigational (amitriptyline) local anesthetic. METHODS: Cell survival and mitochondrial depolarization as marker of apoptotic cell death was assessed in rat dorsal root ganglia incubated with lidocaine or amitriptyline either with or without the addition of SB203580. Similarly, in a sciatic nerve block model, the authors assessed wallerian degeneration by light microscopy to detect a potential mitigating effect of MAPK inhibition. RESULTS: Lidocaine at 40 mm/approximately 1% and amitriptyline at 100 microm reduce neuron count, but coincubation with the p38 MAPK inhibitor SB203580 at 10 mum significantly reduces cytotoxicity and the number of neurons exhibiting mitochondrial depolarization. Also, wallerian degeneration and demyelination induced by lidocaine (600 mm/approximately 15%) and amitriptyline (10 mm/approximately 0.3%) seem to be mitigated by SB203580. CONCLUSIONS: The cytotoxic effect of lidocaine and amitriptyline in cultured dorsal root ganglia cells and the nerve degeneration in the rat sciatic nerve model seem, at least in part, to be mediated by apoptosis but seem efficiently blocked by an inhibitor of p38 MAPK, making it conceivable that coinjection might be useful in preventing local anesthetic-induced neurotoxicity.