Intraoperative Continuous Norepinephrine Infusion Combined with Restrictive Deferred Hydration Significantly Reduces the Need for Blood Transfusion in Patients Undergoing Open Radical Cystectomy: Results of a Prospective Randomised Trial

Background

Open radical cystectomy (ORC) is associated with substantial blood loss and a high incidence of perioperative blood transfusions. Strategies to reduce blood loss and blood transfusion are warranted.

Objective

To determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringer's maleate solution can reduce blood loss and the need for blood transfusion.

Design, setting, and participants

This was a double-blind, randomised, parallel-group, single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion (UD). Exclusion criteria were severe hepatic or renal dysfunction, congestive heart failure, and contraindications to epidural analgesia.

Intervention

Patients were randomly allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour until the bladder was removed, then to 3 ml/kg per hour of Ringer's maleate solution (norepinephrine/low-volume group) or 6 ml/kg per hour of Ringer's maleate solution throughout surgery (control group).

Outcome measurements and statistical analysis

Intraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed. Data were analysed using nonparametric statistical models.

Results and limitations

Total median blood loss was 800 ml (range: 300–1700) in the norepinephrine/low-volume group versus 1200 ml (range: 400–2800) in the control group (p < 0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%) required an average of 1.8 U (±0.8) of packed red blood cells (PRBCs). In the control group, 50 of 83 patients (60%) required an average of 2.9 U (±2.1) of PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI], 0.38–0.77; p = 0.0006). The absolute reduction in transfusion rate throughout hospitalisation was 28% (95% CI, 12–45). In this study, surgery was performed by three high-volume surgeons using a standardised technique, so whether these significant results are reproducible in other centres needs to be shown.

Conclusions

Continuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss, the rate of blood transfusions, and the number of PRBC units required per patient undergoing ORC with UD.     

Effects of Milrinone continuous intravenous infusion on global cerebral oxygenation and cerebral vasospasm after cerebral aneurysm surgical clipping

BackgroundCerebral vasospasm (CVS) is a disabling disease with high morbidity and mortality risk. Milrinone (phosphodiesterase III inhibitor) has inotropic and vasodilator effects, noninvasive transcranial cerebral oximetry (rSO2%) useful in estimating the effect of triple-H therapy preventive measures against CVS.ObjectiveThe objective of the study is to clarify the value of the use of Milrinone continuous IV infusion as a cerebral vasodilator in post-clipping spasm prevention during the period of maximum vasospasm incidence, guided by noninvasive rSO2%.MethodsPost-clipping all patients extubated in the operative room, shifted to Neurosurgical ICU, and fully monitored. Then, in the period from 4th till the 11th day post-clipping, they were divided into two groups 15 patients each: Group 1: control group, given Norepinephrine continuous IV infusion alone in a dose ranges from 0.05 to 0.2 μg/kg/min. Group 2: given Norepinephrine continuous IV infusion 0.05–0.2 μg/kg/min, Plus Milrinone starting with 50 μg/kg bolus dose, followed by IV infusion at a rate of [0.5–0.75 μg/kg/min]. IMAP, ICP and CPP, GCS, Norepinephrine dose, rSO2%, were recorded every 6 h for the next 168 h. Any attack of cerebral vascular spasm recorded as number and % in each group as an incident.ResultsMBP, rSO2%, ICP, CPP, Norepinephrine Infusion dose, and GCS were significantly increased in Group (2) in comparison with Group (1) mostly during the period of the study. CVS occurrence was significantly lower in group (2), i.e., (20%) cases compared to (46.6%) in group (1).ConclusionsMilrinone improved significantly the global cerebral oxygenation and reduced the incidence of cerebral vasospasm during the dangerous period of cerebral spasm after cerebral aneurysm clipping.     

Antagonistic influences of dibutyryl cyclic AMP and dibutyryl cyclic GMP on the beating rate of cultured mouse myocardial cells.

Cultured myocardial cells obtained from neonatal mouse ventricles beat spontaneously and rhythmically. Norepinephrine and dibutyryl cyclic AMP accelerated the rate of spontaneous beating. Dibutyryl cyclic GMP slightly decreased the rate of spontaneous beating. The acceleration of the beating rate of cultured myocardial cells by norepinephrine or dibutyryl cyclic AMP was counteracted by dibutyryl cyclic GMP. Preincubation of cultured myocardial cells with dibutyryl cyclic GMP prevented the positive chronotropic effect of dibutyryl cyclic AMP.     

去甲肾上腺素对肝星状细胞增殖和凋亡的影响

目的探讨交感神经递质去甲肾上腺素（NE）对HSC细胞株（CSFC）增殖和凋亡的影响。方法体外培养CFSC,分为以下6组：（1）空白对照组,为单纯CFSC培养;（2）交感兴奋（NE）组;（3）交感抑制（酚妥拉明＋普萘洛尔）组;（4）α肾上腺素受体（AR）阻滞（酚妥拉明）组;（5）β1AR阻滞（CGP20712A）组;（6）β2AR阻滞（ICI118551）组。MTT法测定细胞增殖;TUNEL法观察CFSC凋亡状况;流式细胞仪检测细胞凋亡率;倒置相差显微镜观察细胞形态学变化。结果MTT法显示,NE对CFSC具有明显的促增殖作用,加入α-AR、β1AR、β2AR阻滞剂后细胞增殖均受到明显抑制。NE作用于CFSC 24h,TUNEL法显示CFSC的凋亡率显著低于对照组（6.60%±3.05%与12.60%±4.76%,P〈0.05）;加入AR阻滞剂后CFSC凋亡率升高,其中α-AR和β2AR阻滞剂作用最显著。同时,流式细胞仪显示加入NE后CFSC凋亡率也显著降低（2.29%±0.22%与3.06%±0.57%,P〈0.05）;与TUNEL结果一致。NE对细胞形态没有明显影响。结论交感神经递质NE对体外活化的CFSC具有促增殖作用,并且可以抑制CFSC的凋亡,可能主要通过α受体和β2体起作用。     

一次力竭运动小鼠中枢单胺类神经递质的代谢特点

目的：探讨力竭运动中枢单胺类神经递质的代谢变化特点,以期为运动疲劳的中枢机制提供一定实验室依据。方法：4月龄C57/BL小鼠,随机分为安静对照组（SC组）和一次性游泳力竭组（SE组）。力竭游泳即刻取材（皮层、下丘脑、纹状体、海马、脑干和小脑）六个脑区,高功率微波灭活脑组织相关酶类;HPLC测定去甲肾上腺素（NE）、多巴胺（DA）及其代谢产物多巴克（DOPAC）、5羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）含量。结果：力竭时皮层、海马和脑干NE含量较安静时明显增加（P〈0.05）,而下丘脑、纹状体和小脑NE含量有降低趋势。海马、脑干组织DA含量力竭时极显著增加（P〈0.01）,皮层、纹状体区仅有增加趋势,而下丘脑DA含量较安静时有降低趋势;DA的代谢产物DOPAC仅在脑干有明显增加。各脑区力竭时5-HT均较安静时明显增加（P〈0.05）,其代谢产物5-HIAA在皮层、下丘脑及小脑也增加显著（P〈0.05）。结论：运动至力竭过程中各脑区单胺类神经元激活程度不相同,其中5-HT和NE可以作为中枢皮层疲劳的一个标志。     

Effects of terlipressin on microcirculation of small bowel mesentery in rats with endotoxic shock

Background

Septic shock is still related to unacceptably high morbidity and mortality. Microcirculatory alteration has been demonstrated to be one important reason associated with this evolution. Vasoactive drugs are often used to restore adequate arterial pressure and tissue perfusion in septic shock. To define the roles of different drugs, the effects of terlipressin (TP) on the microcirculation of small bowel mesentery in rats with endotoxic shock were evaluated and compared with those of norepinephrine (NE).

Methods

Twenty-five adult male Wistar rats were randomized to the control (n = 5), TP (n = 10), and NE (n = 10) groups. After endotoxic shock was induced by intravenous lipopolysaccharide administration for 30 min, rats in the NE and TP groups were infused with saline 5 mL/kg/h and simultaneously given NE 4 μg/kg/min or TP 8 μg/kg/h. The mean arterial pressure, heart rate, blood gas analysis, and microvascular blood flow images of small bowel mesentery were recorded.

Results

After fluid resuscitation and vasopressor infusion, the mean arterial pressure was restored to the baseline values in the NE and TP groups. In the TP group, the heart rate was significantly lower compared with the NE group (P = 0.013). The proportion of perfused vessels and the microvascular flow index (MFI) were significantly increased; furthermore, the heterogeneity index of small vessels was markedly decreased in both the interventional groups with respect to the control group. Compared with the NE group, the MFI was significantly higher (P < 0.05) and the heterogeneity index was significantly lower (P < 0.05) in the TP group.

Conclusions

Both TP and NE improved hemodynamic and microcirculatory alterations in rats with endotoxic shock. Compared with NE, TP was more effective in promoting MFI and improving the heterogeneity of small bowel mesentery in rats.     

Alexithymia is linked to neurocognitive,psychological, neuroendocrine,and immune dysfunction in persons living with HIV

The neuropathological changes resulting from Human Immunodeficiency Virus (HIV) infection may manifest in alexithymia (AL), a multidimensional trait characterized by impairments in the cognitive assimilation of feelings and emotions. A sample of 93 HIV survivors scoring high, i.e., ⩾74 on the 26-item Toronto Alexithymia Scale (TAS-26), were compared to 79 low AL (TAS-26 ⩽ 54) survivors on measures of neurocognitive, psychological, neuroendocrine and immune function. Neurocognitive function was evinced by a standardized test of psychomotor speed, cognitive flexibility and task switching ability, HIV Dementia and general cognitive status. Patients were also screened for levels of depression, anxiety and psychological stress. A 24-h urinary norepinephrine (NE) and cortisol (CORT) collection was taken; blood was drawn for T lymphocyte subset counts (CD4+CD3+) and HIV-1 viral load. Alexithymic patients exhibited higher levels of executive dysfunction, psychological distress, norepinephrine-to-cortisol (NE/CORT) ratio and viral load. Linear regression models accounting for sociodemographic and disease-related variables revealed two AL subscales, difficulties identifying and describing feelings, predicted and explained a significant proportion of variance in the outcome measures. Specifically, poorer executive task-switching/cognitive flexibility was associated with greater difficulty describing feelings; dysregulated autonomic response (high NE/CORT ratio) and depressive symptoms were predicted by difficulty identifying feelings; higher levels of anxiety and psychological stress were both predicted by greater difficulty describing and identifying feelings. Overall, the psychoneuroimmunological profile of alexithymia in HIV positive persons at mid-stage of infection suggests a greater vulnerability for disease progression.     

胃镜下注射去甲肾上腺素联合奥美拉唑治疗消化性溃疡出血的疗效观察

目的探讨胃镜下注射去甲肾上腺素联合奥美拉唑治疗消化性溃疡出血的疗效及安全性。方法将82例消化性溃疡出血患者随机分为观察组和对照组,每组各4l例。观察组采用胃镜下注射去甲肾上腺素联合奥美拉唑治疗,对照组采用奥美拉唑联合立止血治疗。结果观察组总有效率明显高于对照组,两组比较差异有统计学意义（P〈0．05）;两组患者24h、48h及72h空腹胃液pH值逐渐升高,与治疗前相比有统计学意义（P〈0．05）,且观察组升高幅度明显优于对照组（P〈0．05）;观察组患者止血时间、输液时间、住院时间均明显低于对照组（P〈0．05）,输血量及住院费用较对照组明显减少（P〈0．05）,再出血发生率明显低于对照组（P〈0．05）。两组均未见明显不良反应。结论胃镜下注射去甲肾上腺素联合奥美拉唑治疗消化性溃疡出血疗效确切,安全可靠,值得临床推广应用。     

Norepinephrine provides short-term neuroprotection against Aβ1–42 by reducing oxidative stress independent of Nrf2 activation

Pathophysiological evidence correlating locus ceruleus neuron loss with increased Alzheimer's disease pathology suggests that norepinephrine (NE) is neuroprotective. Here, we evaluated the effects of NE on amyloid-β (Aβ)1-42–induced neurotoxicity and determined how NE exerts its actions in human SK-N-SH neurons. NE protected SK-N-SH cells against Aβ1-42–induced neurotoxicity only after a 4-hour treatment. The ability of NE to reduce Aβ1-42–induced neurotoxicity was independent of the adrenoceptor signaling pathway. Notably, NE downregulated Aβ1-42–mediated increases in intracellular reactive oxygen species (ROS) production. However, NE did not affect Aβ1-42–induced activation of the nuclear factor erythroid 2–related factor 2 (Nrf2) redox signaling pathway, known to be involved in oxidative stress. Among the antioxidants tested, N-acetyl cysteine and glutathione, which are not only ROS scavengers but also thiol-reducing agents, mimicked the protective effects of NE. Consistently, Kelch-like ECH-associating protein 1 inhibitors, which activated the Nrf2 pathway, failed to decrease Aβ1-42–induced ROS generation and elicited no protection against Aβ1–42. Taken together, these findings suggest that NE could exert neuroprotective function against Aβ1–42 via redox cycling and reduction of intracellular oxidative stress regardless of downstream activation of the Nrf2 pathway.