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      Preliminary Intraoperative Validation of the Nociception Level Index

      1 , 1 , 1 , 1

      Anesthesiology

      Ovid Technologies (Wolters Kluwer Health)

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          Abstract

          Background

          The nociception level (NoL) index is an index of nociception based on nonlinear combination of heart rate, heart rate variability, photoplethysmograph wave amplitude, skin conductance, skin conductance fluctuations, and their time derivatives. The authors evaluated the abilities of the NoL index and other measures of nociception to discriminate between noxious and nonnoxious stimuli, to progressively respond to graded stimuli, and to respond to opioid administration.

          Methods

          Intraoperative NoL was compared to heart rate, pulse plethysmograph amplitude, noninvasive blood pressure, and the surgical pleth index around five specific stimuli: tetanic stimulation with and without fentanyl analgesia, intubation, first incision/trocar insertion, and a nonnoxious period. The response around first incision was analyzed at two target plasma concentrations of remifentanil.

          Results

          In 58 patients, the NoL index responded progressively to increased stimulus intensity and remained unchanged in response to nonnoxious stimuli. Compared to other accepted measures of nociception, the NoL index better discriminated noxious from nonnoxious stimuli with an area under the curve of 0.93 (95% CI, 0.89 to 0.97) and a sensitivity of 87% at a specificity of 84%. The NoL index was the only measure that reliably reflected two different analgesic concentrations of remifentanil during initial skin incision or trocar insertion.

          Conclusions

          The NoL index changes proportionately with patients’ response to various clinical and experimental noxious stimuli and discriminates noxious from nonnoxious stimuli with high sensitivity and specificity. The NoL index also responds progressively to increasing stimuli intensity and is appropriately blunted by analgesic administration. The NoL index was superior to other compared measures and appears to accurately characterize nociception during general anesthesia.

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          Most cited references 24

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            Inflammation in atherosclerosis.

             Peter Libby (2002)
            Abundant data link hypercholesterolaemia to atherogenesis. However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation. Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis, and malfunction of inflammatory mediators mutes atheroma formation in mice. Moreover, inflammatory pathways promote thrombosis, a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes. The new appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies. Identifying the triggers for inflammation and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.
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              Increased surgical stress promotes tumor metastasis.

              Although it is well-known that excessive surgical stress augments the growth of residual cancer and metastasis, whether surgical stress is increased according to the degree of surgical manipulation and can consequently lead to the enhancement of cancer metastasis has not been thoroughly examined. Moreover, the molecules associated with response for stress-enhanced metastasis have not been well-analyzed. The aim of this study was to examine whether cancer metastasis is enhanced with an increase of surgical stress with an experimental lung metastasis model and to analyze the related molecules responsible for stress-enhanced metastasis. Colon 26-L5 carcinoma cells (1.5 x 10(4)/mouse) were injected intravenously into 6-week-old female BALB/c mice (Japan SLC, Hamamatsu, Japan). Two hours later, the mice were divided into 5 groups: untreated controls (the C group); mice given anesthesia only (the A group); mice given anesthesia and laparotomy (the AL group); mice given anesthesia, laparotomy, and appendectomy (the ALAp group); and mice given anesthesia, laparotomy, appendectomy, and left hepatic lobectomy (the ALApH group). The anesthesia procedures were the same in all groups (intraperitoneal administration of 0.8 mg/mouse sodium pentobarbital). In the AL, ALAp, and ALApH groups, a 3-cm long laparotomy was performed, and the time of the whole operation was just 5 minutes. All mice were killed 14 days after the procedures, and the number of lung metastases on the lung surface was counted manually. At the same time, BALB/c mice without tumor burden were given the same 5 kinds of surgical stress, and the messenger RNA expression of various metastasis-related molecules in the lung was measured with reverse transcriptase-polymerase chain reaction at 6, 24, and 48 hours after surgical stress. We also examined the effect of ONO-4817 (an inhibitor of matrix metalloproteinases ([MPs]) on lung metastasis in the mice with the 5 kinds of surgical stress. The numbers of lung metastases on the lung surface and the messenger RNA expression of MMP-9, membrane type IBMMP, and urokinase-type plasminogen activator at 24 hours after surgery were enhanced in proportion to the degree of surgical stress. Moreover, ONO-4817 significantly inhibited lung metastasis. These results strongly suggest that increased surgical stress augments cancer metastasis via surgical stress-induced expression of proteinases in the target organ of metastasis.
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                Author and article information

                Journal
                Anesthesiology
                Ovid Technologies (Wolters Kluwer Health)
                0003-3022
                July 01 2016
                July 01 2016
                : 125
                : 1
                : 193-203
                Affiliations
                [1 ]From the Department of Anesthesiology, Rambam Medical Centre, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel (R.E.); Department of Anesthesiology, Rambam Medical Centre, Haifa, Israel (V.R., Y.D.); and Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio (D.I.S.).
                Article
                10.1097/ALN.0000000000001130
                27171828
                © 2016

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