Role of aprotinin in the management of patients during and after cardiac surgery

Management of patients undergoing cardiac surgery has evolved in recent years as more is understood about the physiological changes and responses that occur during and after cardiopulmonary bypass (CPB). In particular, our understanding of the mechanisms involved in haemostasis and in the inflammatory response to bypass surgery, has allowed significant refinements in patient management. Improvements in the pharmacological conservation of blood loss have been striking, particularly with the development of the serine protease inhibitor, aprotinin (Trasylol^®, Bayer). Aprotinin represents a significant improvement, especially for patients at high risk, since it reduces the need for allogeneic and (sometimes scarce) blood products. However, in view of its cost, making an appropriate selection of patients most at risk of serious blood loss is a major consideration in the use of aprotinin. While its mechanisms of action are not well understood, the use of aprotinin also appears to reduce inflammatory response to CPB.     

Benefits and risks of aprotinin use during cardiac surgery

Aprotinin is a serine protease inhibitor with antithrombotic, antifibrinolytic, and antiinflammatory effects. It is effective in reducing bleeding and the need for blood transfusions after cardiac surgery with cardiopulmonary bypass. Additional benefits, such as cerebral protection, are hypothesized but not yet thoroughly substantiated. The safety of aprotinin has been questioned based on a phase IV analysis of large data sets, including patients undergoing cardiac surgery. Potential risks including increased occurrences of stroke, myocardial infarction, renal failure, and death are implied by these analyses; however, adequate study group matching is lacking from these nonrandomized, retrospective studies. In October 2007, a large randomized controlled trial comparing antifibrinolytics in patients undergoing cardiac surgery was stopped after a preliminary analysis suggested a trend toward an increase in all-cause 30-day mortality associated with aprotinin. Subsequently, the manufacturer of aprotinin temporarily suspended marketing and halted all shipment of aprotinin on a worldwide basis. Pending a complete analysis of this study, the use of aprotinin could be considered as one component of a blood conservation strategy. After contemplating the benefits and risks of this controversial drug, clinicians should reserve its use for patients at high risk for postoperative blood loss.     

Safety aspects of aprotinin therapy in cardiac surgery patients

Aprotinin is the only agent with Class A Level 1 evidence for reduction in rates of transfusion and return to operating theatre to control bleeding after heart surgery. Principal on the list of safety issues raised over the years are increased risk for: a) thrombosis; and b) renal dysfunction. With multiple administrations, hypersensitivity reactions have emerged as a further safety concern. This review discusses these issues, based on the examination of > 500 published articles. The article also specifically places in context the data presented recently from the observational McSPI database analysis. This report suggested that aprotinin should be withdrawn from human use as serious safety issues have been ignored or missed, an inference not in agreement with the majority of the human safety literature.     

Is there still a role for aprotinin in cardiac surgery?

Cardiac surgery is associated with a systemic inflammatory response and systemic coagulopathy, which can result in significant organ dysfunction and bleeding. Aprotinin, a serine protease inhibitor, can limit systemic inflammation, and has been associated with myocardial, pulmonary and cerebral protection in addition to its proven haemostatic efficacy. Data are currently conflicting regarding the haemostatic efficacy of aprotinin relative to alternative agents including tranexamic acid. Recent studies have demonstrated aprotinin usage is associated with increased rates of thrombotic and renal complications, but these findings are at odds with the majority of studies relating to aprotinin safety to date. The lack of adequately powered, randomised studies evaluating aprotinin and alternative agents limits drawing conclusions about the complete use or disuse of aprotinin presently and requires individualised patient selection based on bleeding risk and co-morbidities for its usage.     

Heart rate variability in patients after cardiac valve surgery

The aim of study was to analyze heart rate variability (HRV) after different cardiac valve surgery procedures and the prognostic values of these findings. This study included 101 consecutive patients who underwent surgical implantation for an artificial valve. The mean age of the patients was 62 ± 10 years. An aortic valve was implanted in 65 patients. A mitral valve was implanted in 36 patients. HRV was analyzed from 24 hours Holter electrocardiographic (ECG) records. The time from the operation to the recording of Holter ECG and measuring HRV was 3.8 ± 1.4 months. After discharged from stationary cardiac rehabilitation, all involved patients were contacted to provide data on their health in the follow-up period (33 ± 21 months). A total of 46 patients with an implanted artificial valve had decreased overall HRV or standard deviation of all normal R-R intervals (SDNN) < 93 ms. Patients with an implanted artificial mitral valve had a shorter RR interval (817 ± 122 vs. 863 ± 122ms, p=0.03) and lower values of total power (1166 ± 1888 vs. 2802 ± 3601 ms², p<0.001) compared to patients with an implanted artificial aortic valve. The results of study show that several months after cardiac surgery, almost half of the patients with an implanted artificial valve have decreased HRV. However, postoperative decreased HRV in those patients have no importance in long-term prediction of mortality rate.     

Elimination of amrinone during continuous veno-venous haemofiltration after cardiac surgery

We studied the elimination of amrinone during continuous veno-venous haemofiltration (CVVHF) in three anuric patients after cardiac surgery. The patients had developed low cardiac output followed by acute prerenal failure. Plasma amrinone levels measured by HPLC were fitted to a two-compartment model.We found significant amrinone clearance, with a mean sieving coefficient (S) of 0.44%, which correlates with the protein-unbound, pharmacologically effective fraction of amrinone. The AUC of the arterial plasma concentration-time curve was decreased by 49.8%. All pharmacokinetic parameters showed wide interindividual variation.To ensure the therapeutic effect of amrinone and to avoid toxic adverse effects monitoring of plasma amrinone levels is necessary.     

心脏直视手术应用不同血浆代用品对机体的影响

目的比较新一代中分子羟乙基淀粉与琥珀酰明胶用于体外循环心脏手术时对机体的影响,探讨二药在心血管手术中容量治疗的有效性和安全性。方法选择54例行瓣膜置换术的患者,完全随机分为羟乙基淀粉组和琥珀酰明胶组,各27例。羟乙基淀粉组在体外循环前、体外循环中及术后住ICU期间应用羟乙基淀粉作为体外循环预充液和补充血容量的血浆代用品;琥珀酰明胶组同期应用琥珀酰明胶作为体外循环预充液和补充血容量的血浆代用品。观察并比较2组患者围术期生命体征、血浆胶体渗透压、液体出入量。结果2组患者均痊愈出院。2组患者各时间血压差异均无统计学意义（P〉0．05）。羟乙基淀粉组诱导后、术毕、ICU2h、ICU6h和ICU20h的胶体渗透压分别为（19．2±2．0）、（19．3±4．6）、（17．0±2．1）、（20．7±2．2）、（20．5±2．2）ITIITIHg,琥珀酰明胶组分别为（18．1±2．3）、（16．9±2．0）、（16．9±2．3）、（19．3±4．5）、（20．0±2．1）mmHg,2组差异无统计学意义。结论羟乙基淀粉与琥珀酰明胶可安全用于心脏直视手术围术期的容量治疗。     

基于加速康复外科理念的围手术期吸烟管理

吸烟和二手烟暴露严重危害人类健康,吸烟管理也是围手术期一个重要的公共卫生问题。吸烟患者术后呼吸系统、心血管系统并发症的发生率显著升高,烟草对术后疼痛控制、伤口愈合及术后康复指标均有不利影响。加速康复外科（enhanced recovery after surgery,ERAS）提倡通过充分的循征医学证据来优化围术期处理措施,减轻患者手术的应激反应,减少术后并发症,达到快速康复的目的。本文遵从加速康复外科理念,通过检索各国文献指南证据,对围手术期戒烟策略、戒烟时间及二手烟暴露处理和戒烟方法作一综述,为临床围手术期吸烟管理提供参考。     

利钠肽对老年人非心脏手术心血管事件的预测价值

目的探讨B型利钠肽(BNP)预测老年非心脏手术心血管事件的价值。方法依据术前血浆BNP浓度将62例择期行非心脏手术患者分为两组,A组(42例):BNP浓度≤100ng/L;B组(20例):BNP浓度>100ng/L。比较两组患者术后心脏事件并计算敏感性、特异性、假阳性率、假阴性率、阳性预测值、阴性预测值、准确率等指标。结果A组无心脏事件发生,B组中有14例(70%)发生心脏事件,两组比较差异有统计学意义(P<0.05),BNP浓度>100ng/L预测心脏事件敏感性100%、特异性87.5%、假阳性率12.5%、假阴性率0、阳性预测值70%、阴性预测值100%、准确率90.3%。结论术前血浆BNP浓度>100ng/L对老年非心脏手术心血管事件有较好的预测价值。     

聚焦解决模式在社区膀胱癌术后患者随访管理中的运用效果分析

目的 分析聚焦解决模式在社区膀胱癌术后患者随访管理中的运用价值.方法 将79例社区膀胱癌术后康复期患者进行随机分组,其中对照组40例采取传统随访管理方案,观察组39例采取聚焦解决模式随访管理方案,观察期为3个月,比较干预前后两组患者的生存质量、自我护理能力和自我效能方面的差异.结果 干预前两组患者生存质量、自我护理能力及自我效能评分差异无统计学意义(P＞0.05),干预后观察组上述指标均明显高于对照组.结论 聚焦解决模式可提升社区膀胱癌术后康复期患者的自我护理能力,提升患者的自我效能感,对改善术后生存质量有促进意义.     

Theophylline metabolism after cardiac surgery

The effect and metabolism of theophylline administration after cardiac surgery has never been reported. Two series of 2-hour intravenous aminophylline administrations (3 mg/kg/h) were conducted in 10 adult patients on the operative day (acute phase) and on the 4th or 5th postoperative day (recovery phase). Both blood and urine samples were collected for 24 hours after dosing. Heart rate increased in both phases, but the cardiac index increased with the decrease of diastolic blood pressure only in the acute phase (p < 0.05). Plasma concentration levels of theophylline tended to be slightly higher in the acute phase, and renal clearance increased in the recovery phase (p < 0.05). The urinary ratio of 3-methylxanthine to theophylline was significantly higher in the acute phase (p < 0.05). This suggests that cytochrome P4501A2 is partially activated rather than depressed and that N-demethylation is promoted more than hydroxylation immediately after surgery.     

抑肽酶与赖氨酸类药物在心脏手术中疗效比较的Meta分析

目的:比较抑肽酶与赖氨酸类药物对心脏手术疗效的影响。方法:检索电子数据库,检索时限为1990年1月—2015年8月,全面搜集比较抑肽酶与赖氨酸类药物对心脏手术疗效的研究,并用Rev Man 5.0.2软件对其进行Meta分析。结果:纳入31项研究共33 501例患者。在低风险组和中级风险组中,抑肽酶均可显著增加心脏手术的早期病死率[RR=1.86,95%CI(1.53~2.25),P<0.000 01;RR=1.40,95%(1.18~1.66),P=0.000 1]。而在高危组,抑肽酶和赖氨酸类药物相比较,死亡风险比较差异无统计学意义[RR=1.03,95%(0.67~1.58),P=0.90],但抑肽酶能够减少高等风险心脏手术后的输血和出血并发症的风险[RR=0.79,95%CI(0.70~0.89),P<0.01]。结论:抑肽酶与赖氨酸类药物比较,会增加低危和中等风险的心脏手术病死率的风险,但可减少高危组的心脏手术输血和出血并发症的风险,而对其早期病死率没有影响。     

右美托咪定在心脏术后肺部感染患者纤维支气管镜检查中的麻醉效果

目的探讨心脏术后肺部感染的清醒患者行纤维支气管镜检查(纤支镜检查)时使用右美托咪定的麻醉效果。方法 98例确诊肺部感染需行纤支镜检查的心脏术后清醒患者随机分为两组。右美托咪定组50例,以右美托咪定0.5μg·kg-1为首剂量,0.5~1.0μg·kg-1·h-1为维持剂量;丙泊酚组48例,以丙泊酚1~1.5 mg·kg-1为首剂量,2~4 mg·kg-1·h-1为维持剂量实施静脉麻醉。比较两组患者给药前(T0)、检查开始时(T1)、检查开始后5 min(T2)、检查结束时(T3)平均动脉压(MAP)、心率(HR)、脉搏血氧饱和度(Sp O2)、呼吸频率(RR)和心率收缩压乘积(HPP)的变化,同时记录各时点ST段及T波变化,观察患者不良反应发生情况。结果两组患者基线资料无显著差异(P>0.05)。丙泊酚组T2、T3时MAP和HR均高于T0时,T2、T3、T4时HPP均高于T0时(P<0.05);T3时丙泊酚组MAP、HR、HPP水平均高于右美托咪定组(P<0.05)。T1时右美托咪定组心电图ST段阳性变化发生率为25%,高于丙泊酚组(4%,P<0.05)。右美托咪定组发生呛咳14例、体动12例、喉痉挛4例,丙泊酚组分别为26例、23例、10例,右美托咪定组呛咳、体动、喉痉挛的发生率低于丙泊酚组(P<0.05)。结论对于心脏术后肺部感染的清醒患者,与丙泊酚相比,以右美托咪定镇静实施纤支镜检查,患者血流动力学更平稳,麻醉效果提高。     

Hemodynamic effects of levosimendan in patients with low-output heart failure after cardiac surgery

Following cardiac surgery, low-output syndrome is relatively common. Since this condition can lead to serious consequences, this postsurgical, low-output state should be reversed whenever possible. Patients with low-output syndrome need drug and fluid management aimed at enhancing cardiac contractility and at facilitating optimal myocardial loading. The objective of this pilot study was to evaluate whether benefits of levosimendan, a new calcium-sensitizing agent approved for treatment of patients with acute exacerbation of chronic heart failure, could be extended to patients with low-output syndrome following cardiac surgery. For this study, each patient was given levosimendan as a loading dose of 12 microg/kg over 10 minutes, followed by a continuous infusion of 0.1 microg/kg/min for 12 hours. Of 11 postsurgical patients with severely impaired cardiac output and hemodynamic compromise, 8 patients (73%) showed evidence of combined hemodynamic improvement (> 30% increase in cardiac index and PCWP corrected to < 18 mmHg) within 3 h after the start of levosimendan infusion. Specifically, cardiac index and stroke volume were significantly increased, while mean arterial pressure, indexed systemic vascular resistance, mean pulmonary pressure, right arterial pressure, and pulmonary capillary wedge pressure were all significantly lowered. Taken together, such changes showed enhanced cardiac output along with significantly decreased preload and afterload--conditions associated with recovery of cardiac function. Levosimendan is thus highly favorable for short-term treatment of patients with low cardiac output following cardiac surgery.     

Brain damage in cardiac surgery patients

Neuropsychological disorders and brain injury are still a serious problem in cardiac surgery patients. Owing to multifactorial mechanism of brain injury during extracorporeal circulation, the effective and safe protection is extremely difficult. Despite several studies, the ideal neuroprotective treatment has not been found. Based on literature we analysed the main mechanisms of brain injury and new methods of brain protection.     

Alteration of vancomycin pharmacokinetics during cardiopulmonary bypass in patients undergoing cardiac surgery.

The alteration of vancomycin pharmacokinetics during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery was studied. Eighteen patients were enrolled in the study. Vancomycin (1 g) was intravenously infused one to two hours before surgery. Blood samples were taken before, during, and after CPB. Serum drug concentrations were determined by an automated fluorescence polarization immunoassay and adjusted, with a bayesian analysis, to a bi-compartmental model implemented in a pharmacokinetic system program. Serum creatinine, hematocrit, and plasma proteins were also measured before, during, and after CPB. During CPB, serum creatinine, hematocrit, and plasma protein values all decreased significantly (p < 0.05). Serum vancomycin concentration also diminished abruptly with CPB (7.04 micrograms/mL; 95% confidence interval, 5.70-8.38 micrograms/mL) but increased moderately during the next 30 minutes, probably attributable to redistribution into plasma from tissue stores. Vancomycin's apparent volume of distribution showed an important increase during CPB (58.8%) (p < 0.0005), and its systemic clearance also increased significantly after CPB (19.7%) (p < 0.0005). The decrease in serum vancomycin concentration seems mediated by the hemodilution associated with the pump prime volume. Vancomycin's mean +/- S.D. nadir serum concentration before the next dose was 7.13 +/- 2.1 micrograms/mL. In patients undergoing cardiac surgery and treated prophylactically with a 1-g preoperative i.v. dose of vancomycin, the onset of CPB was associated with a drop in serum vancomycin concentration.     

围心脏手术期胺碘酮的静脉应用

目的：探讨围心脏手术期病人静脉应用胺碘酮的临床疗效和不良反应。方法：对1997年9月－1998年11月1360例心脏病人的临床资料进行回顾性分析，将115例术后心律失常病人分为治疗有效和无效两组，进行两组间统计学分析。结果：93例治疗有效，21例治疗无明显变化，1例恶化。治疗有效组中平均负荷剂量与平均体重之间相关系数为0.495，具有高度显著性（P＜0.01）。结论：临床证明术后心律失常的静脉胺碘酮治疗，安全有效，但也有一定不良反应。