ABSTRACT
Objective Post-operative cognitive dysfunction (POCD) and post-operative delirium (POD) are two common post-operative cerebral complications. The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride (PHC) on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients. Primary outcomes of interest included the incidences of POCD and POD; the secondary outcomes of interest included peri-operative mini-mental state examination (MMSE) scores. Two authors independently extracted peri-operative data, including patients' baseline characteristics, surgical variables, and outcome data. For dichotomous data (POCD and POD occurrence), treatment effects were calculated as odds ratio () and 95% confidential interval (). Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. For continuous variables (MMSE scores), treatment effects were calculated as weighted mean difference (WMD) and 95% . Statistical significance was defined as <0.05.Results Our search yielded 33 studies including 4017 patients. Meta-analysis showed that, the incidence of POCD in PHC group was comparable to that in saline group (=0.97; 95% : 0.58-1.64; =0.92), scopolamine group (=0.78; 95% : 0.48-1.27; =0.32) and atropine group (=1.20; 95% : 0.86-1.67; =0.29). The incidence of POD in PHC group was comparable to that in saline group (=1.53; 95% : 0.81-2.90; =0.19) and scopolamine group (=0.53; 95% : 0.06-4.56; =0.56), but higher than that in atropine group (=4.49; 95% : 1.34-15.01; =0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.
ABSTRACT
<p><b>BACKGROUND</b>It has been proved that sevoflurane postconditioning (SpostC) could protect the heart against myocardial ischemia/reperfusion injury, however, there has been few research focused on the electrophysiological effects of SpostC. The objective of the study was to investigate the effects of SpostC on action potential duration (APD) and L-type calcium current (I(Ca, L)) in isolated cardiomyocytes.</p><p><b>METHODS</b>Langendorff perfused SD rat hearts were randomly assigned to one of the time control (TC), ischemia/reperfusion (I/R, 25 minutes of ischemia followed by 30 minutes of reperfusion), and SpostC (postconditioned with 3% sevoflurane) groups. At the end of reperfusion, epicardial myocytes were dissociated enzymatically for patch clamp studies.</p><p><b>RESULTS</b>Sevoflurane directly prolonged APD and decreased peak I(Ca, L) densities in epicardial myocytes of the TC group (P < 0.05). I/R injury shortened APD and decreased peak I(Ca, L) densities in epicardial myocytes of the I/R group (P < 0.05). SpostC prolonged APD and increased peak I(Ca, L) densities in epicardial myocytes exposed to I/R injury (P < 0.05). SpostC decreased intracellular reactive oxygen species (ROS) levels, reduced the incidence of ventricular tachycardia and ventricular fibrillation, and decreased reperfusion arrhythmia scores compared with the I/R group (all P < 0.05).</p><p><b>CONCLUSIONS</b>SpostC attenuates APD shortening and I(Ca, L) suppression induced by I/R injury. The regulation of APD and I(Ca, L) by SpostC might be related with intracellular ROS modulation, which contributes to the alleviation of reperfusion ventricular arrhythmia.</p>
Subject(s)
Animals , Rats , Action Potentials , Calcium , Metabolism , Electrocardiography , Methyl Ethers , Therapeutic Uses , Patch-Clamp Techniques , Pericardium , Metabolism , Reactive Oxygen Species , Metabolism , Reperfusion Injury , Drug Therapy , MetabolismABSTRACT
<p><b>BACKGROUND</b>Studies suggested that anesthetics administered upon the early reperfusion or "anesthetic postconditioning" could protect post-ischemic hearts against myocardial ischemia reperfusion injury (MIRI). However, the mechanism responsible for such protection was not well-elucidated. We investigated the cardioprotection induced by sevoflurane postconditioning (SpostC) in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase 1 and 2 (ERK 1/2), mitochondrial K(ATP) channels (mitoK(ATP)) and mitochondrial permeability transition pore (mPTP), by selectively inhibiting PI3K, ERK 1/2, mitoK(ATP), with LY294002 (LY), PD98059 (PD), 5-hydroxydecanoate (5-HD) and by directly opening of mPTP with atractyloside (ATR), respectively.</p><p><b>METHODS</b>Isolated rat hearts were randomly assigned to one of the 12 groups (n = 15): Time control (continuous perfusion), ISCH (30 minutes of ischemia followed by 60 minutes of reperfusion alone), SpostC (3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia), ISCH + LY, ISCH + PD, ISCH + ATR, ISCH + 5-HD and ISCH + dimethyl sulfoxide (DMSO) groups (LY, PD, ATR, 5-HD and DMSO (the vehicle) was administered respectively during the first 15 minutes of reperfusion following test ischemia), SpostC + LY, SpostC + PD, SpostC + ATR and SpostC + 5-HD groups (LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively). Hemodynamics was compared within and between groups. Infarction size was determined at the end of experiments using triphenyltetrazolium chloride (TTC) staining. Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) released from necrotic myocardium, were compared among TC, ISCH and SpostC groups. To investigate the relationships between RISK and mPTP implicated in SpostC, NAD(+) content in myocardium, a marker of mPTP opening, was compared among some experimental groups (TC, ISCH, ISCH + LY, ISCH + PD, ISCH + DMSO, SpostC, SpostC + LY, SpostC + PD). To further investigate whether the anti-apoptotic mechanism is implicated in SpostC-induced cardioprotection and its association with mitochondria, TUNEL staining was performed in some experimental groups (TC, ISCH, ISCH + 5-HD, ISCH + ATR, ISCH + DMSO, SpostC, SpostC + 5-HD, SpostC + ATR).</p><p><b>RESULTS</b>When compared with unprotected hearts subjected to 30 minutes of ischemia, exposure to 3% sevoflurane for 15 minutes during early reperfusion significantly improved functional recovery, decreased myocardial infarct size, decreased LDH, CK-MB and cTnI release, and decreased cardiomyocyte apoptosis (P < 0.05). However, such cardioprotective effects of hemodynamic recovery and infarct size reduction by sevoflurane was completely abolished by any one of LY294002, PD98059, atractyloside and 5-hydroxydecanoate (P < 0.05). Additionally, either LY294002 or PD98059 could reverse the inhibitory effect of SpostC over mPTP opening upon reperfusion (P < 0.05). Both atractyloside and 5-hydroxydecanoate could abrogate the anti-apoptotic effects of SpostC (P < 0.05).</p><p><b>CONCLUSION</b>These findings demonstrate that PI3K, ERK 1/2, mitoK(ATP) and mPTP are key players in sevoflurane postconditioning induced cardioprotective mechanisms in isolated rat hearts subjected to MIRI.</p>
Subject(s)
Animals , Male , Rats , Anesthetics, Inhalation , Therapeutic Uses , Apoptosis , Heart , Methyl Ethers , Therapeutic Uses , Random Allocation , Rats, Sprague-Dawley , Reperfusion InjuryABSTRACT
<p><b>OBJECTIVE</b>To identify the predictors of prolonged intensive care unit (ICU) stay in patients undergoing aortic arch replacement.</p><p><b>METHODS</b>The clinical data of 173 consecutive patients undergoing aortic arch replacement requiring deep hypothermic circulatory arrest plus antegrade selective cerebral perfusion were reviewed retrospectively. Patients who had undergone one-stage total or subtotal aortic replacement were excluded. Data collected from records were used to identify univariate and multivariate predictors for prolonged ICU stay, which was defined as longer than 5 days in ICU postoperatively.</p><p><b>RESULTS</b>Patients aged (45.4 +/- 10. 6) years and male accounted for 76.3%. The incidence of prolonged ICU stay was 22.0%. The incidences of postoperative stroke and acute renal failure were 6.4% and 4.6%, respectively. The in-hospital mortality rate was 2.9%. Univariate predictors for prolonged ICU stay included body mass index, preoperative serum creatinine level, emergent surgery, coronary artery bypass grafting at the same time, cardiopulmonary bypass time, myocardial ischemic time, and occurrence of postoperative stroke and/or acute renal failure. Multivariable modeling identified that emergent surgery (odds ratio [95% confidence interval] -3.1 [1.3, 7.6]), cardiopulmonary bypass time longer than 180 min (3.3 [1.4, 8.1]), postoperative stroke (6.9 [1.1, 43.1]) and acute renal failure (14.5 [1.3, 161.6]) were the independent predictors for prolonged ICU stay.</p><p><b>CONCLUSIONS</b>The incidence of prolonged ICU stay is high after aortic arch replacement. Patients with identified multivariate predictors carry a higher risk of prolonged ICU stay and may benefit from enhanced perioperative protection of brain and kidney.</p>