An observational study: The utility of perfusion index as a discharge criterion for pain assessment in the postanesthesia care unit

<div><p>Acute post-operative pain can remain untreated if patients cannot express themselves. The perfusion index (PI) may decrease when pain activates sympathetic tone and may increase after analgesics are administered. We evaluated if the perfusion index is a feasible indicator for objectively assessing pain relief in the postanesthesia care unit (PACU) and calculated the changes in PI measurements at the time of discharge from the PACU relative to baseline PI measurements to examine if the PI is a useful criterion for discharging patients from the postanesthesia care unit. This retrospective observational study enrolled female patients who were admitted for gynecological or general surgery. The patients received general anesthesia and were admitted to the postanesthesia care unit. The PI, visual analogue scale (VAS) score, heart rate, and blood pressure were recorded before and after administration of intravenous morphine. Changes in these parameters before and after analgesics were administered and the difference of these parameters between age and BMI subgroups were compared. The correlation between the PI and VAS score, ΔPI and ΔVAS, and %ΔPI and %ΔVAS were also evaluated. The percentage change in ΔPI (P9-T0/T0) of the patients at the time of discharge from the postanesthesia care unit relative to baseline PI measurements was calculated. Eighty patients were enrolled, and there were 123 instances during which analgesia was required. Heart rate, PI, and VAS score were significantly different before and after analgesics were administered (p < 0.0001). The difference of parameters between age and BMI subgroups were not significant. The correlation between the PI and VAS score, ΔPI and ΔVAS, and the percentage change in ΔPI and ΔVAS showed weak correlations in age, BMI subgroups, and all measurements. The baseline PI and the PI when arriving at and when being discharged from the postanesthesia care unit were significantly different (p < 0.01). The mean percentage change in Δ PI at the time of discharge from the PACU was 66.2%, and the 99% confidence interval was 12.2%~120.3%. The perfusion index was increased, and the VAS score was decreased significantly after analgesics were administered, but the correlation was weak in each subgroup. The VAS score is a subjective and psychometric parameter. The PI increased when partial pain relief was achieved after morphine was administered but did not reflect pain intensity or changes in the VAS score regardless of age or BMI. A percentage change in ΔPI at the time of discharge from the PACU relative to baseline PI measurements of greater than 12% can be used as a supplemental objective discharge criterion for pain assessment in the postanesthesia care unit.</p></div

Correlation between PI and VAS, ΔPI and ΔVAS, and percentage changes in ΔPI and ΔVAS in age or BMI subgroups and all measurement.

<p>Correlation between PI and VAS, ΔPI and ΔVAS, and percentage changes in ΔPI and ΔVAS in age or BMI subgroups and all measurement.</p

Demographic data.

<p>Demographic data.</p

Perfusion index changes at different time points.

<p>The perfusion index at the time of arrival to the postanesthesia care unit (PACU) was significantly different from the baseline PI. Differences in the PI between before and after the administration of analgesics also existed. There was no difference between the baseline PI and the PI at the time of discharge from the PACU.</p

Additional file 1: of Leading Comorbidity associated with 30-day post-anesthetic mortality in geriatric surgical patients in Taiwan: a retrospective study from the health insurance data

Original and operating code. We aggregated original codes into disease group to resemble clinical pre-anesthetic usage, and called it operating code. This process was conducted independently by three anesthesiologists. (DOCX 78 kb

The Molecular Basis for the Selectivity of Tadalafil toward Phosphodiesterase 5 and 6: A Modeling Study

Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalafil gives a high selectivity of 1020-fold against PDE6. Till now, their molecular mechanisms of selectivity of PDE5 versus PDE6 have remained unknown in the absence of the crystal structure of PDE6. In order to elucidate its isoform-selective inhibitory mechanism, a 3D model of PDE6 was constructed by homology modeling, and its interaction patterns with tadalafil plus sildenafil were exploited by molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations. The present work reveals that tadalafil exhibits a less negative predicted binding free energy of −35.21 kcal/mol with PDE6 compared with the value of −41.12 kcal/mol for PDE5, which suggests that tadalafil prefers PDE5 rather than PDE6 and confers a high selectivity for PDE5 versus PDE6. The binding free energy results for tadalafil were consistent with external bioassay studies (IC₅₀ = 5100 and 5 nM toward PDE6 and PDE5, respectively). Two important residues from the Q₂ pockets (Val782 and Leu804 in PDE5 and their corresponding Val738 and Met760 in PDE6) were further identified to account for the high selectivity of tadalafil for PDE5 versus PDE6. These findings have shed light on the continuous puzzle of why sildenafil (IC₅₀ = 74 and 6 nM toward PDE6 and PDE5, respectively) causes visual disorders because of its poor selectivity but tadalafil does not. In addition, the homology model of PDE6 can be used to design more potent and selective second-generation PDE5 inhibitors with less inhibitory potency against PDE6

Prenylated Coumarins: Natural Phosphodiesterase‑4 Inhibitors from <i>Toddalia asiatica</i>

Bioassay-guided fractionation of the ethanolic extract of the roots of <i>Toddalia asiatica</i> led to the isolation of seven new prenylated coumarins (<b>1</b>–<b>7</b>) and 14 known analogues (<b>8</b>–<b>21</b>). The structures of <b>1</b>–<b>7</b> were elucidated by spectroscopic analysis, and their absolute configurations were determined by combined chemical methods and chiral separation analysis. Compounds <b>1</b>–<b>5</b>, named toddalin A, 3‴-<i>O</i>-demethyltoddalin A, and toddalins B–D, represent an unusual group of phenylpropenoic acid-coupled prenylated coumarins. Compounds <b>1</b>–<b>21</b> and four modified analogues, <b>10a</b>, <b>11a</b>, <b>13a</b>, and <b>17a</b>, were screened by using tritium-labeled adenosine 3′,5′-cyclic monophosphate ([³H]-cAMP) as substrate for their inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds <b>3</b>, <b>8</b>, <b>10</b>, <b>10a</b>, <b>11</b>, <b>11a</b>, <b>12</b>, <b>13</b>, <b>17</b>, and <b>21</b> exhibited inhibition with IC₅₀ values less than 10 μM. Toddacoumalone (<b>8</b>), the most active compound (IC₅₀ = 0.14 μM), was more active than the positive control, rolipram (IC₅₀ = 0.59 μM). In addition, the structure–activity relationship and possible inhibitory mechanism of the active compounds are also discussed

Selaginpulvilins A–D, New Phosphodiesterase‑4 Inhibitors with an Unprecedented Skeleton from <i>Selaginella pulvinata</i>

Selaginpulvilins A–D (<b>1</b>–<b>4</b>), four new phenols with an unprecedented 9,9-diphenyl-1-(phenylethynyl)-9<i>H</i>-fluorene skeleton, together with four known selaginellins (<b>5</b>–<b>8</b>) were isolated from <i>Selaginella pulvinata</i>. Their structures were elucidated by spectroscopic analysis and chemical correlation. The structure of <b>1</b> was confirmed by single-crystal X-ray diffraction. Compounds <b>1</b>–<b>8</b> exhibited remarkable inhibitory activities (IC₅₀ values in the range of 0.11–5.13 μM) against phosphodiesterase-4 (PDE4), a drug target for the treatment of asthma and chronic obstructive pulmonary disease

Bioactive triterpenoids from the leaves of <i>Eriobotrya japonica</i> as the natural PDE4 inhibitors

<p>The ethanolic extract of the leaves of <i>Eriobotrya japonica</i> exhibited inhibitory activity against phosphodiesterase-4D (PDE4D), which is a therapeutic target of inflammatory disease. Subsequent bioassay-guided fractionation led to the isolation of a new triterpene (<b>1</b>), together with seven known triterpenoids, methyl corosolate (<b>2</b>), ursolic acid (<b>3</b>), oleanolic acid (<b>4</b>), methyl maslinate (<b>5</b>), <i>α</i>-amyin (<b>6</b>), 3<i>β</i>,19<i>α</i>,23-trihydroxy-urs-12-ene (<b>7</b>) and uvaol (<b>8</b>). The structure of compound <b>1</b> was established as 3<i>β</i>-hydroxyl-21<i>β</i>-acetoxyl-urs-12-en-28-carboxylate on the basis of interpretation of its 1D and 2D NMR and HR-ESI-MS spectroscopic data. The bioassay results verified compounds <b>2</b>, <b>3</b> and <b>8</b> inhibited PDE4D2 effectively with the IC₅₀ values of 3.06, 2.18 and 5.17 μM, respectively, which may provide a novel mechanism for the anti-inflammatory activity of the leaves of <i>E.</i> <i>japonica.</i></p

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis

<div><p>The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired <i>t</i>-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SR_IVR) and E/ SR_IVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SR_IVR and decreases in E/ SR_IVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SR_IVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.</p></div