Sihai Zhu

Comparison of restrictive and liberal transfusion strategy on postoperative delirium in aged patients following total hip replacement: A preliminary study

Few studies have examined the association between perioperative blood transfusion and postoperative delirium (POD) in aged patients undergoing total hip replacement surgery. In this prospective study, 186 patients older than 65 years undergoing elective unilateral total hip replacement surgery were enrolled. Of those, 94 patients were randomly assigned to the restrictive strategy transfusion strategy group, in which red blood cells were transfused in order to maintain 10.0 g/dL>hemoglobin≧8.0 g/dL. Ninety-two patients were randomly assigned to the liberal transfusion strategy group, in which red blood cells were transfused in order to maintain hemoglobin≧10.0 g/dL. POD was diagnosed by confusion assessment method. The baseline characteristics of patients, the length of hospital stay, the incidence of POD, myocardial infarction, stroke, wound infection, pulmonary embolism, and the transfusion volume were recorded. No difference was observed in the baseline characteristics, the length of hospital stay, and the incidence of POD, myocardial infarction, stroke, wound infection, and pulmonary embolism between the two groups (P>0.05). The proportion of patients transfused with red blood cell and frozen plasma was decreased in the restrictive transfusion group compared with the liberal transfusion group (P<0.05). In conclusion, restrictive transfusion does not influence the incidence of POD but reduces blood transfusion. Thus, restrictive transfusion may serve as an effective and safe strategy for aged patients following total hip replacement.

Pre-administration of curcumin prevents neonatal sevoflurane exposure-induced neurobehavioral abnormalities in mice.

Sevoflurane, a commonly used inhaled anesthetic, can induce neuronal apoptosis in the developing rodent brain and correlate with functional neurological impairment later in life. However, the mechanisms underlying these deleterious effects of sevoflurane remain unclear and no effective treatment is currently available. Herein, the authors investigated whether curcumin can prevent the sevoflurane anesthesia-induced cognitive impairment in mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane 2h daily for 3 consecutive days and were treated with curcumin at the dose of 20 mg/kg or vehicle 30 min before the sevoflurane anesthesia from postnatal days 6 (P6) to P8. Cognitive functions were evaluated by open field, Morris water maze, and fear conditioning tests on P61, P63-69, and P77-78, respectively. In another separate experiment, mice were killed on day P8 or P78, and the brain tissues were harvested and then subjected to biochemistry studies. Our results showed that repeated neonatal sevoflurane exposure led to significant cognitive impairment later in life, which was associated with increased neuronal apoptosis, neuroinflammation, oxidative nitrosative stress, and decreased memory related proteins. By contrast, pre-administration of curcumin ameliorated early neuronal apoptosis, neuroinflammation, oxidative nitrosative stress, memory related proteins, and later cognitive dysfunction. In conclusion, our data suggested that curcumin pre-administration can prevent the sevoflurane exposure-induced cognitive impairment later in life, which may be partly attributed to its ability to attenuate the neural apoptosis, inflammation, and oxidative nitrosative stress in mouse brain.

Association between perioperative blood transfusion and early postoperative cognitive dysfunction in aged patients following total hip replacement surgery

Abstract Introduction. Accumulating evidence suggests that enhanced inflammatory responses contribute to the pathogenesis of postoperative cognitive dysfunction (POCD). Blood transfusion can trigger an enhancement of acute inflammatory responses. Therefore, we hypothesized that perioperative blood transfusion is associated with a higher risk of POCD in aged patients following total hip replacement surgery. Material and methods. Patients older than 65 years undergoing elective total hip replacement surgery were enrolled from October 2011 to December 2012. Neurocognitive tests were evaluated at baseline and at 7 d after surgery by a Mini-Mental State Test. Multivariate logistic regression analysis was used to determine risk factors associated with POCD. Results. Fifty-six patients (27.3%) developed POCD 7 d postoperatively. Patients who developed POCD were older, had a lower education level and preoperative hemoglobin concentration, had more blood loss, and had a lower body weight (p < 0.05). Patients with POCD were more likely to receive red blood cells (RBCs) transfusion (51.8% versus 31.5%; p < 0.05). A multivariable logistic regression model identified older age, lower education level, and perioperative blood transfusion of more than 3 units as independent risk factors for POCD 7 d postoperatively. Conclusion. Our data suggested that perioperative blood transfusion of more than 3 units of RBCs is an independent risk factor for POCD in aged patients following total hip replacement surgery.

The impact of intra-abdominal pressure on the stroke volume variation and plethysmographic variability index in patients undergoing laparoscopic cholecystectomy

The purpose of the present study was to evaluate the effect of increasing intra-abdominal pressure (IAP) on stroke volume variation (SVV) and plethysmographic variability index (PVI) in patients undergoing laparoscopic cholecystectomy. PVI examined by Masimo Radical 7 pulse oximeter and SVV determined using FloTrac/Vigileo were monitored simultaneously in forty-five patients undergoing laparoscopic cholecystectomy (LC). Mean arterial blood pressure (MAP), heart rate (HR), cardiac index (CI), perfusion index (PI), airway pressures (P), SVV, and PVI were also recorded at the following predetermined time: 5 min after endotracheal intubation (T1), 5 min after pneumoperitoneum at 5 mmHg (T2), 5 min after pneumoperitoneum at 10 mmHg (T3), 5 min after pneumoperitoneum at 15 mmHg (T4), and 5 min after the termination of pneumoperitoneum (T5). Forty-five patients with a total of 225 pairs of measurements were included in the analysis. Compared with the values at T1, both SVV and PVI showed significant progressive increases as the IAP was adjusted from 5 to 10, 15 mmHg at T2, T3, and T4, respectively. No significant difference was found when the pneumoperitoneum was terminated at T5. Further regressive analysis indicated strong relationships between SVV and IAP (r = 0.8118, p < 0.001), PVI and IAP(r = 0.8876, p < 0.001) respectively. Both PVI and SVV showed rapid and IAP correlative changes with increasing intra-abdominal pressure in patients undergoing laparoscopic cholecystectomy.

Endomorphins and ohmefentanyl in the inhibition of immunosuppressant function in rat peritoneal macrophages: An experimental in vitro study.

BACKGROUND The potential immunosuppressant effects of opioids might have clinical implications. The effects of endomorphins (EMs) and ohmefentanyl (OMF) on cultured rat peritoneal macrophages remain unclear. OBJECTIVE The aim of this study was to investigate the immunosuppressant effects of EMs and OMF on cultured rat peritoneal macrophages in vitro. METHODS Purified rat peritoneal macrophages, from healthy adult male Sprague-Dawley rats, were cultured with EM-1 (EM-1 group), EM-2 (EM-2 group), OMF (OMF group), and saline (saline group). We measured the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-β in supernatant when macrophages were cultured with 10(-6) mol/L of EM-1, EM-2, OMF, or saline for 0, 6, 12, and 24 hours (time-effect relationship) or with 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L of these substances for 24 hours (concentration-effect relationship). We also determined the phagocytic and bactericidal activities of macrophages using isotope markers when macrophages were cultured with 10(-6) mol/L of EM-1, EM-2, OMF, or saline for 24 hours. RESULTS Compared with the saline group, TNF-α concentration decreased significantly in the OMF, EM-2, and EM-1 groups at 12 hours (P < 0.05, P < 0.05, and P < 0.01, respectively) and at 24 hours (P < 0.05, P < 0.01, and P < 0.01, respectively). Compared with the saline group, IL-1β concentration decreased signifcantly in the OMF, EM-2, and EM-1 groups at 12 hours (P < 0.05, P < 0.05, and P < 0.01, respectively) and at 24 hours (P < 0.05, P < 0.01, and P < 0.01, respectively). Decreased TNF-α and IL-1β concentrations were observed in the supernatant at 24 hours when cultured with 10(-8), 10(-7), and 10(-6) mol/L in the OMF and EM-2 groups (all, P < 0.05) and in the EM-1 group (all, P < 0.01). Compared with the saline group, macrophage phagocytic activity (all, P < 0.05) and macrophage bactericidal activity (all, P < 0.01) were significantly lower in the 3 experimental groups compared with the saline group. CONCLUSION In this in vitro experiment, EM-1, EM-2, and OMF inhibited the immunosuppressant function of cultured rat peritoneal macrophages, including decreasing TNF-α and IL-1β concentrations and phagocytic and bactericidal activities.

Comparison of oxycodone and morphine on the proliferation, apoptosis and expression of related molecules in the A549 human lung adenocarcinoma cell line

The present study aimed to compare the effects of oxycodone and morphine hydrochloride on the proliferation, apoptosis and migration of A549 lung cancer cells. A549 human lung cancer cells were cultured in vitro and treated with oxycodone or morphine at various concentrations (10, 20 and 40 µg/ml). Cell migration was determined using a wound healing assay, whereas apoptosis was detected using flow cytometry. Reverse transcription quantitative-polymerase chain reaction was performed in order to assess the apoptosis-related gene expression levels, including p53, B-cell lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax). The levels of vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) were detected using enzyme-linked immunosorbent assays. The expression levels of intercellular cell adhesion molecule (ICAM)-1 were determined by immunofluorescence. In the present study, oxycodone and morphine induced apoptosis in A549 lung cancer cells with similar potency; however, >20 µg/ml oxycodone was more effective at inhibiting cell proliferation (P<0.05) and migration (P<0.05), as compared with morphine at the same concentration. Oxycodone induced a dose-dependent increase in the expression levels of p53 and Bax apoptosis-related genes, whereas it decreased the gene expression levels of Bcl-2. Furthermore, oxycodone decreased, whereas morphine increased, the expression levels of ICAM-1 in a concentration-dependent manner. In addition, at 40 µg/ml, the expression levels of VEGF and uPA in the morphine group were significantly higher than those demonstrated in the oxycodone group (P<0.05). In conclusion, oxycodone was more effective in inhibiting the proliferation and migration of A549 lung cancer cells, as compared with morphine.

Tolerance and dependence of edomorphin-1 in rats and possible mechanisms

Abstract Objective To observe the tolerance and the dependence of endomorphin-1(EM-1) in rats and the possible mechanisms. Methods Sixty Sprague-Dawley rats were randomly allocated into saline, acute EM-1-treated and chronic EM-1-treated groups. The rats were intracerebroventricularly injected with saline, acute EM-110 μg/kg 30 min prior to sacrifice, and chronic EM-1 by daily administration at 8:00 A.M. and 15:00 P.M. from 10 μg/kg on the 1st day to 50 μg/kg on the 9th day, respectively. In chronic EM-1-treated group, the median antinociceptive dose(AD50) and the catatonic median effective dose(ED50) were determined by the improved Dixon±s method. Natural withdrawl test was used to assess the dependence of EM-1. Maximal binding capacity(Bmax) and dissociation constant(Kd) of 3H-DAMGO, binding to mu-opioid receptor(MOR) in brain tissue, was measured by Scatchard analysis. Gene expression of MOR was measured by reverse transcription-polymerase chain reaction(RT-PCR). Results Tolerance of the antinociceptic and catatonic effects on the 3rd day(3.1-fold and 1.9-fold) and the 9th day(28.4-fold and 8.5-fold) were observed in chronic EM-1-treated group(P 0.05).AD50, ED50, Bmax, Kd and gene expression of MOR were recorded. Conclusion EM-1 possesses the tolerance and the dependence. After a long-term treatment, EM-1 down regulates the binding capacity and mRNA of MOR, which somewhat accounts for the dependence.