Programmable Pump for Intrathecal Morphine Delivery to Cisterna Magna: Clinical Implications in Novel Management of Refractory Pain Above Middle Thoracic Vertebrae Level Utilizing a Prospective Trial Protocol and Review.

BACKGROUND: The cisterna Intrathecal Drug Delivery system (IDDS) with morphine has proven to be effective in treating refractory cancer pain above the middle thoracic vertebrae level in some countries. However, it has not been fully investigated in others. We designed the current project to investigate the efficacy and safety of cisterna IDDS for pain relief in refractory pain above the middle thoracic vertebrae level in advanced cancer patients. METHODS: This study protocol allows for eligible cancer patients to receive the cisterna IDDS operation. Pain intensity (Visual Analogue scale, VAS), quality of life (36-Item Short-Form Health Survey, SF-36), and depression (Self-Rating Depression scale, SDS) are assessed along with side effects in the postoperative follow-up visits. Recent literature suggests a potential role for cisterna IDDS morphine delivery for refractory pain states above the middle thoracic level. CONCLUSION: The results of this study may provide further evidence that cisterna IDDS of morphine can serve as an effective and safe pain relief strategy for refractory pain above the middle thoracic vertebrae level in advanced cancer patients.

Intrathecal Morphine Delivery at Cisterna Magna to Control Refractory Cancer-Related Pain: A Prospective Cohort Study.

Background: For patients suffering from primary or metastatic cancer above the middle thoracic vertebrae, refractory pain management still remains a great challenge. Theoretically, inserting a catheter tip into the cisterna magna may be a promising solution. However, at present, there have been no reliable data regarding this novel technique. We therefore investigated the efficacy and safety of an advanced approach for pain relief in a specific population. Methods: Thirty participants from two hospitals received the intrathecal deliveries of opioid to either one of two sites: cisterna magna (n = 15) or lower thoracic region (n = 15). Pain relief (visual analogue scale, VAS), quality of life (short form (36) health survey, SF-36) as well as depression (self-rating depression scale, SDS) were assessed in the follow-up visits and compared between the two groups. Results: Patients receiving intrathecal morphine delivery to cisterna magna achieved greater pain improvement indicated as significant decrease of VAS scores at day 1 and 7, and achieved better improvement in physical function (day 7 and 30), role physical (day 7 and 30), body pain (day 7, 30 and 90), general health (day 7, 30 and 90), vitality (day 7, 30 and 90), social function (day 90), role emotional (day 7 and 90), mental health (day 7, 30 and 90) and SDS (day 1 and 7). Conclusions: Intrathecal morphine delivery to cisterna magna might be an effective and safe technique for patients suffering from cancer at the middle thoracic vertebrae or above to control refractory pain. Trial registration: No. ChiCTR-ONN-17010681.

Potential Beneficial Effects of Probiotics on Human Migraine Headache: A Literature Review.

BACKGROUND: Recent studies have shown that migraine headache is often associated with concomitant gastrointestinal diseases. There is a higher prevalence of headaches in patients with gastrointestinal disorders. These associations between migraine and gastrointestinal disorders suggest a potential link to a bidirectional modulation of gut microbiota and brain function. The underlying working mechanistic links between migraine and gastrointestinal diseases may include increased intestinal epithelial permeability and inflammation. OBJECTIVE: This review presents an overview of the relationship between gut microbiota and brain function, especially with regard to migraine headache. STUDY DESIGN: Literature review. SETTING: Anesthesia and Operation Center, Department of Anesthesiology, Chinese PLA General Hospital. METHODS: The present investigation included a PubMed search using the following terms: migraine headache, gut microbiota, brain function, and probiotics. RESULTS: In this literature review, we mainly discussed the relationship between gut microbiota and brain function, especially with regard to migraine headache. The potential effects of probiotics supplement on migraine headache were also included. LIMITATIONS: There is limited evidence from clinical studies of the positive effects of probiotics in patients with migraine headache. Large-scale randomized, placebo-controlled clinical trials are warranted to evaluate the clinical efficacy and safety of probiotics in patients with migraine headache. CONCLUSIONS: Similar to migraine headache, disorders of the brain involving depression and anxiety have been demonstrated to be associated with increased gut permeability. An improvement in gut microbiota and reduction of inflammation can have positive effects on strengthening gut and brain function. Moreover, it can be inferred that probiotics may have a beneficial effect on the frequency and severity of migraine headache attacks. Large-scale randomized, placebo-controlled studies are warranted in the future to evaluate the clinical efficacy and safety of probiotics in patients with migraine headache.Key words: Migraine headache, gut microbiota, brain function, probiotics.

Effects of Leached Amylose and Amylopectin in Rice Cooking Liquidon Texture and Structure of Cooked Rice

ABSTRACT Effects of leached amylose (AM) and amylopectin (AP) on textural and morphological properties of cooked rice were investigated separately by replacing cooking liquid with AM and AP separated from pouring cooking liquid. The pouring of cooking water reduced the hardness (from 28.45 to 19.42N) and stickiness (from 1.74 to 1.19N·s) significantly. However, the addition of AM and AP enhanced the hardness (27.63N) and stickiness (1.71N·s).Scanning electron microscopy show that the leached short-chain AM entered the surface hollows in the cooked rice after water evaporation. Meanwhile, the Long-chain AM cross-linked to formed a three-dimensional network structures, which covered on the filled hollows. This distribution led to a harder texture of cooked rice. The leached AP absorbed water and swelledto form masses. Atthe gelatinization temperature,theAPmassesagglomeratedtoformafilmlayer,whichcoveredtheunevenstructure, the thicker and smoother film contributed to the sticky texture.

The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration.

One promising strategy to prevent the chronicity of post-operative pain (POP) is to attenuate acute POP during the early phase by efficacious medications with fewer side effects. Duloxetine, one of the serotonin (5-HT)-norepinephrine (NE) reuptake inhibitors (SNRI), is used to treat a wide range of acute and chronic pain. However, its effect on POP has not been investigated. In the present study, we investigated the anti-hypersensitivity effect of duloxetine using a rat model of POP. The possible involvement of spinal 5-HT2A and α2-noradrenergic receptors were also evaluated by using antagonists for 5-HT2A (ketanserin) or α2-noradrenergic receptors (idazoxan). Finally, with the method of in vivo microdialysis, the increase in spinal NA and 5-HT levels after intraperitoneal (i.p.) delivery of duloxetine were investigated. The results showed that intrathecal (i.t.) or i.p. delivery of duloxetine produced an anti-hyperalgesic effect in a dose-dependent manner. The anti-hypersensitivity effect of duloxetine was partly attenuated by pretreatment with ketanserin or idazoxane. Microdialysis study revealed that 5-HT and NA concentrations at the spinal dorsal horn were increased, peaking at 30min after i.p. injection of 20mg/kg duloxetine. These findings indicate that duloxetine inhibits POP by increasing spinal NA and 5-HT levels and activating spinal 5-HT2A or α2-noradrenergic receptors.

Synergistic analgesia of duloxetine and celecoxib in the mouse formalin test: a combination analysis.

Duloxetine, a serotonin and noradrenaline reuptake inhibitor, and celecoxib, a non-steroidal anti-inflammatory drug, are commonly used analgesics for persistent pain, however with moderate gastrointestinal side effects or analgesia tolerance. One promising analgesic strategy is to give a combined prescription, allowing the maximal or equal efficacy with fewer side effects. In the current study, the efficacy and side effects of combined administration of duloxetine and celecoxib were tested in the mouse formalin pain model. The subcutaneous (s.c.) injection of formalin into the left hindpaw induced significant somatic and emotional pain evaluated by the biphasic spontaneous flinching of the injected hindpaw and interphase ultrasonic vocalizations (USVs) during the 1 h after formalin injection, respectively. Pretreatment with intraperitoneal (i.p.) injection of duloxetine or celecoxib at 1 h before formalin injection induced the dose-dependent inhibition on the second but not first phase pain responses. Combined administration of duloxetine and celecoxib showed significant analgesia for the second phase pain responses. Combination analgesia on the first phase was observed only with higher dose combination. A statistical difference between the theoretical and experimental ED50 for the second phase pain responses was observed, which indicated synergistic interaction of the two drugs. Concerning the emotional pain responses revealed with USVs, we assumed that the antinociceptive effects were almost completely derived from duloxetine, since celecoxib was ineffective when administered alone or reduced the dosage of duloxetine when given in combination. Based on the above findings, acute concomitant administration of duloxetine and celecoxib showed synergism on the somatic pain behavior but not emotional pain behaviors.

Treatment of functional chest pain with antidepressants: a meta-analysis.

BACKGROUND: Recurrent Functional Chest pain (FCP) with normal coronary anatomy and no detectable gastroenterological and respiratory causes is a common problem that sometimes leads to excess use of medical care. OBJECTIVE: The purpose of this meta-analysis is to investigate the efficacy of antidepressant treatments for FCP. SETTINGS: MEDLINE, PsycINFO, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to July 2011. Randomized controlled trials (RCTs) that tested any type of antidepressants for FCP with normal coronary anatomy were analyzed. Diagnoses included non-specific chest pain, noncardiac chest pain, atypical chest pain, syndrome X, or chest pain with normal coronary anatomy. METHODS: Two authors independently extracted data. Effects were summarized using standardized mean differences (SMDs), weighed mean differences (WMD), or odds ratio (OR) by suitable effects model. RESULTS: Seven RCTs (median duration, 5 weeks; range, 3 - 16 weeks) involving 319 participants were included. There was strong evidence for an association of antidepressants with reduction in pain (SMD -1.26; 95% confidence interval [CI], -2.34 to -0.19) and psychological symptoms (SMD -0.87; 95% CI, -1.67 to - 0.08) as well as increased side effects (OR 0.34; 95% CI, 0.15 to 0.78). Current analysis did not support the association of antidepressants with improved health related quality of life (WMD 2.00; 95% CI, - 2.54 to - 6.65). LIMITATIONS: Demographics, co-morbidities of study participants and the amount of co-medication were not reported, these possible sources of heterogeneity could not be examined. CONCLUSIONS: Antidepressant medications are associated with improvements in pain and psychological symptoms. The effects of factors including psychiatric co-morbidity, gender, age, ethnic group, and treating period on the outcomes should be checked further.

Can bispectral index or auditory evoked potential index predict implicit memory during propofol-induced sedation?

BACKGROUND: Some patients still suffer from implicit memory of intraoperative events under adequate depth of anaesthesia. The elimination of implicit memory should be a necessary aim of clinical general anaesthesia. However, implicit memory cannot be tested during anaesthesia yet. We propose bispectral index (BIS) and auditory evoked potential index (AEPI), as predictors of implicit memory during anaesthesia. METHODS: Thirty-six patients were equally divided into 3 groups according to the Observer's Assessment of Alertness/Sedation Score: A, level 3; B, level 2; and C, level 1. Every patient was given the first auditory stimulus before sedation. Then every patient received the second auditory stimulus after the target level of sedation had been reached. BIS and AEPI were monitored before and after the second auditory stimulus presentation. Four hours later, the inclusion test and exclusion test were performed on the ward using process dissociation procedure and the scores of implicit memory estimated. RESULTS: In groups A and B but not C, implicit memory estimates were statistically greater than zero (P < 0.05). The implicit memory scores in group A did not differ significantly from those in group B (P > 0.05). Implicit memory scores correlated with BIS and AEPI (P < 0.01). The area under ROC curve is BIS > AEPI. The 95% cutoff points of BIS and AEPI for predicting implicit memory are 47 and 28, respectively. CONCLUSIONS: Implicit memory does not disappear until the depth of sedation increases to level 1 of OAA/S score. Implicit memory scores correlate well with BIS and AEPI during sedation. BIS is a better index for predicting implicit memory than AEPI during propofol induced sedation.

Investigation and analysis of incidence of awareness in patients undergoing cardiac surgery in Beijing, China.

BACKGROUND: Awareness under general anesthesia is a serious complication which leads to psychiatric disorders. The incidence of awareness in patients undergoing cardiac surgery has been reported in as many as 1.5% - 23% in foreign countries. But so far, medical literature about awareness during cardiac surgery is still rare in China. Therefore, we investigated the incidence of awareness in patients undergoing different kinds of cardiac surgery, the phases when awareness occurred and the effect of cardiopulmonary bypass on the incidence of awareness in coronary artery bypass grafting in Beijing. METHODS: Patients' recall of awareness during cardiac surgery was assessed. One hundred patients undergoing coronary artery bypass grafting (CABG) in Chaoyang Hospital, Beijing, one hundred patients undergoing CABG and one hundred patients undergoing valve replacement or septal defect repair in Fuwai Hospital, Beijing, were interviewed 3-6 days after surgery. Every report about patients on recall of awareness was recorded. An independent research team, blinded to patients' surgery and anesthesia, assessed every report of awareness. RESULTS: The incidence of awareness of patients received CABG under cardiopulmonary bypass (CPB), off -pump CABG, septal repair or valve replacement under CPB was 4.7% (5 of 106 cases), 9.6% (9 of 94 cases) and 4% (4 of 100 cases), respectively. CPB did not greatly affect the incidence of awareness during the period of CABG (P > 0.05). The incidence of awareness of patients who received CABG under CPB did not increase significantly, in comparison with that of patients who received septal repair or valve replacement under CPB in Fuwai Hospital (P > 0.05). Awareness easily occurred before bypass grafting or CPB. CONCLUSIONS: Awareness mainly occurs before bypass grafting or CPB in cardiac surgery. Most cases with awareness have auditory perceptions. CPB is not a main factor which affects the incidence of awareness of CABG. Surgical types do not affect the incidence of awareness of patients under CPB.