Anesthetic Induction With Etomidate in Cardiac Surgical Patients: A PRISMA-Compliant Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aimed to systematically review the effects of etomidate (ETM) during anesthetic induction on patients undergoing cardiac surgery. DESIGN: Systematic review and meta-analysis. SETTING: Operating room. PARTICIPANTS: Patients undergoing cardiac surgery. INTERVENTIONS: ETM or control drugs. MEASUREMENTS AND MAIN RESULTS: PubMed, Cochrane Library, OVID, and EMBASE were searched through August 31, 2020. Primary outcomes included hemodynamic profiles and stress responses. Secondary outcomes included morbidity, mortality, and postoperative recovery. For continuous/dichotomous variables, treatment effects were calculated as weighted mean difference (WMD)/odds ratio (OR) and 95% confidence interval (CI). A database search yielded 18 randomized controlled trials including 1,241 patients. The present meta-analysis demonstrated that ETM-anesthetized patients had lower heart rates (WMD, -3.31; 95% CI -5.43 to -1.19; p = 0.002), higher blood pressures (systolic blood pressure: WMD, 12.02; 95% CI 6.24 to 17.80; p < 0.0001; diastolic blood pressure: WMD, 5.23; 95% CI 2.39 to 8.08; p = 0.0003; mean arterial pressure (MAP): WMD, 8.64; 95% CI 5.85 to 11.43; p < 0.00001), less requirement for vasopressor (OR, 0.26; 95% CI 0.15 to 0.44; p < 0.00001), and more nitroglycerin usage (OR, 14.89; 95% CI 4.92 to 45.08; p < 0.00001) during anesthetic induction. Current meta-analysis also demonstrated that single-dose ETM lowered cortisol levels transiently and did not have a significant effect on endogenous norepinephrine and epinephrine levels and was not associated with increased postoperative inotrope and/or vasopressor requirement. Additionally, the meta-analysis suggested that ETM anesthesia was associated with neither increased mortality nor morbidity, except a higher incidence of transient adrenal insufficiency in ETM recipients. CONCLUSION: The present meta-analysis suggested that single-dose ETM during anesthetic induction could be associated with more stable hemodynamics, transient and reversible lower cortisol levels, and a higher adrenal insufficiency incidence, but not worse outcomes in cardiac surgical patients.

Penehyclidine Hydrochloride Premedication Is Not Associated with Increased Incidence of Post-Operative Cognitive Dysfunction or Delirium:A Systemic Review and Meta-Analysis.

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 (OR) and 95% confidential interval (CI). 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% CI. Statistical significance was defined as P<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 (OR=0.97; 95% CI: 0.58-1.64; P=0.92), scopolamine group (OR=0.78; 95% CI: 0.48-1.27; P=0.32) and atropine group (OR=1.20; 95% CI: 0.86-1.67; P=0.29). The incidence of POD in PHC group was comparable to that in saline group (OR=1.53; 95% CI: 0.81-2.90; P=0.19) and scopolamine group (OR=0.53; 95% CI: 0.06-4.56; P=0.56), but higher than that in atropine group (OR=4.49; 95% CI: 1.34-15.01; P=0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.

Ulinastatin reduces postoperative bleeding and red blood cell transfusion in patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Ulinastatin is a type of glycoprotein and a nonspecific wide-spectrum protease inhibitor like antifibrinolytic agent aprotinin. Whether Ulinastatin has similar beneficial effects on blood conservation in cardiac surgical patients as aprotinin remains undetermined. Therefore, a systematic review and meta-analysis were performed to evaluate the effects of Ulinastatin on perioperative bleeding and transfusion in patients who underwent cardiac surgery. METHODS: Electronic databases were searched to identify all clinical trials comparing Ulinastatin with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Primary outcomes included perioperative blood loss, blood transfusion, postoperative re-exploration for bleeding. Secondary outcomes include perioperative hemoglobin level, platelet counts and functions, coagulation tests, inflammatory cytokines level, and so on. For continuous variables, treatment effects were calculated as weighted mean difference (WMD) and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Statistical significance was defined as P < .05. RESULTS: Our search yielded 21 studies including 1310 patients, and 617 patients were allocated into Ulinastatin group and 693 into Control (placebo/blank) group. There was no significant difference in intraoperative bleeding volume, postoperative re-exploration for bleeding incidence, intraoperative red blood cell transfusion units, postoperative fresh frozen plasma transfusion volumes and platelet concentrates transfusion units between the 2 groups (all P > .05). Ulinastatin reduces postoperative bleeding (WMD = -0.73, 95% CI: -1.17 to -0.28, P = .001) and red blood cell (RBC) transfusion (WMD = -0.70, 95% CI: -1.26 to -0.14, P = .01), inhibits hyperfibrinolysis as manifested by lower level of postoperative D-dimer (WMD = -0.87, 95% CI: -1.34 to -0.39, P = .0003). CONCLUSION: This meta-analysis has found some evidence showing that Ulinastatin reduces postoperative bleeding and RBC transfusion in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Ulinastatin.

Hemocoagulase reduces postoperative bleeding and blood transfusion in cardiac surgical patients: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Hemocoagulase is isolated and purified from snake venoms. Hemocoagulase agents have been widely used in the prevention and treatment of surgical bleeding. A systematic review was performed to evaluate the effects of hemocoagulase on postoperative bleeding and transfusion in patients who underwent cardiac surgery. METHODS: Electronic databases were searched to identify all clinical trials comparing hemocoagulase with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Two authors independently extracted perioperative data and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. Sensitivity analyses were done by examining the influence of statistical model and individual trial on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P < .05. RESULTS: Our search yielded 12 studies including 900 patients, and 510 patients were allocated into hemocoagulase group and 390 into control group. Meta-analysis suggested that, hemocoagulase-treated patients had less bleeding volume, reduced red blood cells and fresh frozen plasma transfusion, and higher hemoglobin level than those of controlled patients postoperatively. Meta-analysis also showed that, hemocoagulase did not influence intraoperative heparin or protamine dosages and postoperative platelet counts. Meta-analysis demonstrated that, hemocoagulase-treated patients had significantly shorter postoperative prothrombin time, activated partial thromboplastin time, and thrombin time, higher fibrinogen level and similar D-dimer level when compared to control patients. CONCLUSION: This meta-analysis has found some evidence showing that hemocoagulase reduces postoperative bleeding, and blood transfusion requirement in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Hemocoagulase.

Restoration of autophagic flux in myocardial tissues is required for cardioprotection of sevoflurane postconditioning in rats.

AIM: Sevoflurane postconditioning (SpostC) has been shown to protect the heart from ischemia-reperfusion (I/R) injury. In this study, we examined whether SpostC affected autophagic flux in myocardial tissues that contributed to its cardioprotective effects in rats following acute I/R injury. METHODS: SD rats underwent 30 min of left anterior descending coronary artery ligation followed by 120 min of reperfusion. The rats were subjected to inhalation of 2.4% (v/v) sevoflurane during the first 5 min of reperfusion, and chloroquine (10 mg/kg, ip) was injected 1 h before I/R. Myocardial infarct size was estimated using TTC staining. Autophagosomes in myocardial tissues were detected under TEM. Expression of LC3B-II, beclin-1, p62/SQSTM1, cathepsin B, caspase-3 and cleaved PARP was assessed using Western blot analysis. Plasma cardiac troponin I was measured using ELISA. Cardiomyocyte apoptosis was evaluated with TUNEL staining. RESULTS: I/R procedure produced severe myocardium infarct and apoptosis accompanied by markedly increased number of autophagosomes, as well as increased levels of LC3B-II, beclin-1 and p62 in myocardial tissues. SpostC significantly reduced infarct size, attenuated myocardial apoptosis, restored intact autophagic flux and improved the lysosomal function in myocardial tissues. Administration of chloroquine that blocked autophagic flux abrogated the cardioprotective effects of SpostC. CONCLUSION: SpostC exerts its cardioprotective effects in rats following I/R injury via restoring autophagic flux in myocardial tissues.

Sevoflurane postconditioning alleviates action potential duration shortening and L-type calcium current suppression induced by ischemia/reperfusion injury in rat epicardial myocytes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Sevoflurane postconditioning attenuates reperfusion-induced ventricular arrhythmias in isolated rat hearts exposed to ischemia/reperfusion injury.

Sevoflurane postconditioning has been proven to protect the hearts against ischemia/reperfusion injury, manifested mainly by improved cardiac function, reduced myocardial specific biomarker release, and decreased infarct size. This study is to observe the effects of sevoflurane postconditioning on reperfusion-induced ventricular arrhythmias and reactive oxygen species generation in Langendorff perfused rat hearts. Compared with the unprotected hearts subjected to 25 min of global ischemia followed by 30 min of reperfusion, exposure of 3% sevoflurane during the first 15 min of reperfusion significantly improved cardiac function, reduced cardiac troponin I release, decreased infarct size and attenuated reperfusion-induced ventricular arrhythmia. Further analysis on arrhythmia during the 30 min of reperfusion showed that, sevoflurane postconditioning decreased both the duration and incidence of ventricular tachycardia and ventricular fibrillation. In the meantime, intracellular malondialdehyde and reactive oxygen species levels were also reduced. These above results demonstrate that sevoflurane postconditioning protects the hearts against ischemia/reperfusion injury and attenuates reperfusion-induced arrhythmia, which may be associated with the regulation of lipid peroxidation and reactive oxygen species generation.

Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Attenuation of ischemia-reperfusion injury by sevoflurane postconditioning involves protein kinase B and glycogen synthase kinase 3 beta activation in isolated rat hearts.

Volatile anesthetic ischemic postconditioning reduces infarct size following ischemia/reperfusion. Whether phosphorylation of protein kinase B (PKB/Akt) and glycogen synthase kinase 3 beta (GSK3ß) is causal for cardioprotection by postconditioning is controversial. We therefore investigated the impact of PKB/Akt and GSK3ß in isolated perfused rat hearts subjected to 40 min of ischemia followed by 1 h of reperfusion. 2.0% sevoflurane (1.0 minimum alveolar concentration) was administered at the onset of reperfusion in 15 min as postconditioning. Western blot analysis was used to determine phosphorylation of PKB/Akt and its downstream target GSK3ß after 1 h of reperfusion. Mitochondrial and cytosolic content of cytochrome C checked by western blot served as a marker for mitochondrial permeability transition pore opening. Sevoflurane postconditioning significantly improved functional cardiac recovery and decreased infarct size in isolated rat hearts. Compared with unprotected hearts, sevoflurane postconditioning-induced phosphorylation of PKB/Akt and GSK3ß were significantly increased. Increase of cytochrome C in mitochondria and decrease of it in cytosol is significant when compared with unprotected ones which have reversal effects on cytochrome C. The current study presents evidence that sevoflurane-induced cardioprotection at the onset of reperfusion are partly through activation of PKB/Akt and GSK3ß.

[Predictors of prolonged intensive care unit stay in patients undergoing aortic arch replacement].

OBJECTIVE: To identify the predictors of prolonged intensive care unit (ICU) stay in patients undergoing aortic arch replacement. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.