Preoperative statins and infectious complications following cardiac surgery

ABSTRACT

Purpose: Recent observational studies have suggested that statins can decrease the incidence and severity of various infections including pneumonia and bacteremia. However, the effect of statins on post-cardiac surgery infection has not been adequately evaluated. Therefore we sought to determine whether preoperative statin use resulted in a reduction in infection following cardiac surgery.

Methods: This was a cohort evaluation of all consecutive patients who underwent coronary artery bypass graft (CABG) and/or valve surgery at our institution between January 1, 2004 and August 31, 2006. Our primary outcome measure was the occurrence of at least one of the following postoperative infectious complications (pneumonia, bacteremia, sternal wound, leg vein harvest site infection, urinary tract infection, or tracheotomy site infection). We used multivariable logistic regression to control for potential confounding and to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs).

Results: A total of 1934 patients were included in this evaluation of which 1248 received a statin preoperatively and 686 did not. Our study population was 66.3 ± 11.6 years of age, 71.3% male; 37.2% underwent complex surgery, 3.6% were morbidly obese, and 32.0% were diabetic (each being previously identified as an independent predictor of infection following cardiac surgery). Patients receiving a statin preoperatively and not receiving a statin preoperatively varied in respect to a number of important pre- and peri- operative character­istics. Patients receiving preoperative statin therapy were more likely to have had a history of diabetes, chronic obstructive pulmonary disease or high cholesterol and to be smokers, but less likely to be undergoing urgent/emergent surgery or surgery utilizing a cardiopul­monary bypass pump (?p < 0.05 for all comparisons). In total, 151 (7.8%) patients developed an infectious complication. Upon multivariable logistic regression, preoperative statin use was associated with a significant reduction in the development of infection (AOR; 0.67 (95% CI 0.46–0.99), p = 0.04). The use of a statin was not associated with a statistically significant reduction in any individual infection on its own (?p > 0.08 for all).

Limitations: Patients were not randomized to receive statins or not. We did not have adequate power to evaluate individual infections.

Conclusions: Preoperative statin use is associated with a reduction in patients’ odds of developing a postoperative infection following cardiac surgery.     

Famotidine. Pharmacokinetic properties and suppression of acid secretion in paediatric patients following cardiac surgery

The pharmacokinetic and pharmacodynamic properties of the H2-receptor antagonist famotidine have been well described in adult subjects. However, similar data for children are not available. Therefore, this study looked at the disposition of the drug (given to prevent aspiration following cardiac surgery) in 10 paediatric patients with normal kidney function (age range 2 to 7 years, bodyweight 14 to 25 kg) after a single intravenous dose of famotidine 0.3 mg/kg. Plasma concentrations of the drug and gastric pH values were both monitored for 20 hours by high performance liquid chromatography and aspiration of gastric juice, respectively. Plasma famotidine concentrations declined with an elimination half-life of 3.3 +/- 1.8 h (mean +/- SD) and the drug was effective in elevating the gastric pH above 3.5 for about 9 hours in 6 patients. The variable volume of distribution and total plasma clearance of famotidine averaged 1.4 +/- 1.0 L/kg and 0.3 +/- 0.17 L/h/kg, respectively. In 4 patients unchanged famotidine could also be measured in a 12-hour urine fraction. The amount excreted (21 to 79%) correlated with clearance (r = 0.97). All these data are comparable to those obtained in healthy adults, indicating that paediatric patients receiving intensive medical treatment after cardiac surgery can handle famotidine in a way very similar to healthy adult subjects. A dosage of 0.3 mg/kg every 8 hours appears to be advisable.     

Serum anticholinergic activity in patients following cardiac surgery and healthy individuals following amitriptyline application

The serum anticholinergic activity (SAA) is used as a marker for cognitive impairment. Here, two studies have been performed characterizing the SAA profile. In Study 1 the endogenous SAA in relation to the total serum protein concentration was monitored for 24 h in five healthy individuals and compared with that in four inpatients following cardiac surgery. In Study 2 the SAA of seven healthy individuals was assessed following a single amitriptyline dose. In both studies SAA was assessed by an ex vivo assay. In Study 1, the absolute SAA varied in a wide range of 1.2 and 14.5 atropine equivalents (AEs) over 24 h. A circadian pattern was not observed. The mean total serum protein concentration, but not the SAA, was significantly lower in inpatients than in healthy individuals. In Study 2, the SAA increased following amitriptyline to a maximum. The mean SAA increased by 6.39 AE at the amitriptyline peak concentration. High SAA variability showed a low statistical relation to amitriptyline concentrations. Both studies characterize the SAA as an individual parameter not affected per se by surgery or clinical care and poorly correlated with the total serum protein concentration. The relation with amitriptyline concentration helps to quantify SAA values towards a better understanding of the clinical implications and limitations of SAA changes.     

Postoperative epidural analgesia following elective major abdominal surgery in high risk patients: a retrospective cohort study

AIM: To describe the effect of post-operative epidural analgesia on morbidity and mortality rates in a group of high-risk patients undergoing elective major abdominal surgery. METHODS: Retrospective chart review of patients in American Society of Anaesthetists Physical Status (ASA) category III or IV, who underwent elective major I or II general surgical procedures between 01/01/1996 and 01/09/1998. Patients were identified from a prospective audit database. Patients who had epidural analgesia or conventional parenteral opioids were compared for outcome measures. RESULTS: There were 167 patients identified (72 epidural, 95 non-epidural group). There was no significant difference in demographic data, inpatient stay, intensive care unit stay, or mortality rates (11% epidural v 17% non-epidural, p>0.05). There was no significant difference in morbidity rates, however there was a non-significant trend towards a lower morbidity in the epidural group. CONCLUSIONS: This study does not show any benefit from post-operative epidural analgesia on morbidity and mortality rates in high risk patients undergoing major abdominal surgery. It does illustrate that ASA 3 and 4 patients undergoing major abdominal surgery have a high morbidity and mortality.     

术中iv维生素C对心脏手术患者术后肺部并发症的影响

目的 观察术中iv维生素C对心肺转流下行心脏手术患者术后肺部并发症的影响。方法 选取2018年12月—2019年8月在徐州医科大学附属医院择期在心肺转流下行心脏手术最终的70例患者为研究对象,采用随机序列法将患者分为对照组（37例）和维生素C组（33例）。维生素C组患者分别在麻醉诱导后10 min、体外循环后并行开始前10 min、胸骨完全闭合后予iv维生素C注射液,1 g用生理盐水稀释至10 mL,总量3 g。对照组患者在同等时间静脉注射10 mL生理盐水。记录患者术后肺部并发症发生率、严重度评分及种类。分别于插管后10 min（T₀）、胸骨完全闭合后（T₁）、术后第1天（T₃）、术后第3天（T₃）记录患者氧合指数（PaO₂/FiO₂）、肺泡动脉血氧分压差（A-aDO₂）。并于T₀、T₁记录肺动态顺应性（Cd）、肺静态顺应性（Cs）。观察患者术后其他并发症发生情况。结果 与T₀时刻比较,两组T₁~T₃时刻PaO₂/FiO₂、A-aDO₂明显降低（P<0.01）;两组T₁时刻Cd、Cs明显升高（P<0.05）。维生素C组术后肺部并发症发生率为12.12%,显著低于对照组的29.73%（P<0.05）。与对照组相比,维生素C组患者术后肺部评分显著降低（P<0.01）。术后患者其他并发症以房颤最常见,但两组间差异无统计学意义。结论 术中iv维生素C能够降低心脏手术患者术后肺部并发症评分,减少术后肺部并发症发生率,改善患者的肺功能。     

Risk of worsening renal function with nesiritide following cardiac surgery.

PURPOSE: The relationship between the perioperative use of nesiritide and the development of postoperative renal insufficiency in open-heart surgery (OHS) patients is discussed. SUMMARY: Postoperative renal dysfunction occurs in about 8% of patients who undergo elective coronary bypass surgery. The worsening of renal function is associated with increased length of stay and mortality. Nesiritide, a vasodilator, improves the hemodynamic profile and symptoms in patients with acute decompensated heart failure (ADHF). Because patients undergoing OHS have physiological characteristics similar to ADHF, it is theorized that nesiritide could preserve renal function by opposing the neurohormonal response to OHS. However, there has been recent attention on the potential nephrotoxic effects of nesiritide in patients with heart failure, although the association between these effects and nesiritide is unclear. There is little clinical evidence supporting the use of nesiritide in OHS patients. Three small studies have demonstrated beneficial hemodynamic effects of nesiritide; one prospective, controlled trial evaluated the effect of nesiritide on renal function and found no significant difference between nesiritide and placebo; and two small studies demonstrated renal-protective effects of nesiritide in cardiac surgery patients. CONCLUSION: Evidence of the clinical benefit of nesiritide on renal function in patients undergoing OHS is controversial. A prospective, controlled trial is needed to determine the effect of nesiritide on renal function. Regardless, it is recommended that patients at risk for worsening renal function after OHS should be identified and targeted for interventions aimed at preserving renal function and improving outcomes.     

Weight gain and changes in metabolic variables following olanzapine treatment in schizophrenia and bipolar disorder

Antipsychotic therapy forms the cornerstone of treatment for people with severe mental illness. Second-generation (atypical) antipsychotics are associated with a significantly lower incidence of extrapyramidal symptoms than the typical, first-generation agents; however, changes in metabolic variables -- including impaired glucose metabolism, diabetes mellitus, weight gain and dyslipidaemia -- have been reported during treatment with second-generation antipsychotics. Understanding any potential link between antipsychotic treatment and the incidence of these events is complicated by the increasing prevalence of obesity and diabetes occurring in the general population and the increased risk of diabetes and changes in metabolic variables in people with schizophrenia. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose level appears to fall on a continuum, with olanzapine appearing to have a greater association than some other atypical antipsychotics. The PubMed database was used to search for publications that included any information on measures of changes in weight, body mass index (BMI) and/or metabolic variables in randomized studies of olanzapine published between 1992 and 2010. In long-term (≥48 weeks) studies of olanzapine, the mean weight gain was 5.6?kg (last observation carried forward; median exposure 573 days). The proportions of patients who gained at least 7%, 15% or 25% of their baseline weight with long-term exposure were 64%, 32% and 12%, respectively. Some studies have suggested that weight gain early during the course of olanzapine treatment may predict clinically significant weight gain following long-term exposure to the drug. Changes in metabolic variables, such as elevated indices of glucose metabolism and triglyceride level, have also been observed during treatment with olanzapine. Consensus guidelines emphasize the importance of appropriate baseline screening and ongoing monitoring of weight gain and metabolic variables for people receiving all antipsychotic treatments. Long-term weight management programmes have been shown to reduce weight gain in some patients.     

体外循环心脏术后腹部并发症临床分析

目的探讨体外循环心脏术后腹部并发症的诊断、处理、相关危险因素和预后。方法回顾性分析1998-07～2008-08的1726例体外循环心脏术后出现腹部并发症的53例患者的临床资料,采用卡方检验和多因素logstie回归分析方法分析相关危险因素和发病率。结果多因素回归分析结果提示术前溃疡病史、体外循环时间、主动脉阻断时间、术后呼吸机辅助时间和术后肾功能不全是体外循环术后腹部并发症发生的高危因素。体外循环术后腹部并发症的临床表现各异,且发生时间分布在术后各个阶段,但以术后1周以内为高发时间。其中以上消化道出血（34．0％）、肝功能不全（30．2％）和麻痹性肠梗阻（26．4％）最为多见。在本组中,体外循环心脏手术后腹部并发症的总发生率为3．1％,总病死率为13．2％。结论体外循环心脏手术后腹部并发症病死率较高,对高危患者有必要采取预防措施;早期进行诊断、处理可取得较好的效果。     

Pharmacokinetics and effects of propofol 6% for short-term sedation in paediatric patients following cardiac surgery

AIMS: This paper describes the pharmacokinetics and effects of propofol in short-term sedated paediatric patients. METHODS: Six mechanically ventilated children aged 1-5 years received a 6 h continuous infusion of propofol 6% at the rate of 2 or 3 mg kg-1 h-1 for sedation following cardiac surgery. A total of seven arterial blood samples was collected at various time points during and after the infusion in each patient. Pharmacokinetic modelling was performed using NONMEM. Effects were assessed on the basis of the Ramsay sedation score as well as a subjective sedation scale. RESULTS: The data were best described by a two-compartment pharmacokinetic model. In the model, body weight was a significant covariate for clearance. Pharmacokinetic parameters in the weight-proportional model were clearance (CL) = 35 ml kg-1 min-1, volume of central compartment (V1) = 12 l, intercompartmental clearance (Q) = 0.35 l min-1 and volume of peripheral compartment (V2) = 24 l. The interindividual variabilities for these parameters were 8%, < 1%, 11% and 35%, respectively. Compared with the population pharmacokinetics in adults following cardiac surgery and when normalized for body weight, statistically significant differences were observed the parameters CL and V1 (35 vs 29 ml kg-1 min-1 and 0.78 vs 0.26 l kg-1P < 0.05), whereas the values for Q and V2 were similar (23 vs 18 ml kg-1 min-1 and 1.6 vs 1.8 l kg-1, P > 0.05). In children, the percentage of adequately sedated patients was similar compared with adults (50% vs 67%) despite considerably higher propofol concentrations (1.3 +/- 0.10 vs 0.51 +/- 0.035 mg l-1, mean +/- s.e. mean), suggesting a lower pharmacodynamic sensitivity to propofol in children. CONCLUSIONS: In children aged 1-5 years, a pharmacokinetic model for propofol was described using sparse data. In contrast to adults, body weight was a significant covariate for clearance in children. The model may serve as a useful basis to study the role of covariates in the pharmacokinetics and pharmacodynamics of propofol in paediatric patients of different ages.     

A possible cardioprotective effect of heat shock proteins during cardiac surgery in pediatric patients.

BACKGROUND: Overexpression of heat shock proteins (Hsps) is associated to myocardial protection and it has been suggested that they could be a marker of cardiac preservation in conditions such as extracorporeal circulation. Aim of this study was to evaluate if cardioplegic arrest can modify the expression of Hsps in the heart and if this alteration is associated to cardiac preservation.METHOD: The levels of Hsp 27, Hsp 60, and both the constitutive and the inducible form of Hsp 70 were measured in the cardiac tissue from right atrium of pediatric patients before and after aortic cross-clamping (ACC) during cardiopulmonary bypass surgery for correction of congenital heart disease (n=20). The quantitative evaluation of Hsps was made by Western blotting analysis after tissue extraction and protein separation. Hsp 72 mRNA expression was also evaluated in pre- and post-ACC samples of eight subjects by semiquantitative RT-PCR. Peripheral levels of Troponin I, Myoglobin, LDH, CK, CK-MB were measured in basal conditions and at 12 and 24h after cardiosurgery as markers of heart damage.RESULTS: The cardioplegic arrest did not significantly modify the mean levels of all the Hsps measured. Hsp 72 levels increased after cardioplegia in the 40% of the patients and all Hsps in the 28% of subjects. The patients whose levels of Hsps are increased after cardioplegia are associated with lower post-surgery concentrations of all the markers of cardiac injury.CONCLUSIONS: This observation suggests a relationship between the increase of Hsps and the reduction of cardiac injury.     

类风湿关节炎与骨关节炎全膝关节置换术术后并发症比较

目的 比较类风湿关节炎(Rheumatoid arthritis,RA)和骨关节炎(Osteoarthritis,OA)患者行全膝关节置换术术后并发症的差别,以期指导临床决策及治疗.方法 回顾性分析安徽医科大学第一附属医院2009年1月至2014年1月因RA及OA行初次单侧全膝关节置换的患者,通过病例查阅,门诊随访及电话随访收集患者术后早期翻修率,假体周围骨折率,下肢深静脉血栓发生率,90 d感染率及90 d死亡率等数据并进行分析对比.结果 共收集221例行全膝关节置换术患者,其中RA患者64例,OA患者157例,RA组术后翻修率1.6％ (1/64),假体周围骨折率1.6％ (1/64),下肢深静脉血栓发生率6.3％ (4/64),切口感染率6.3％ (4/64)及术后90 d死亡率1.6％ (1/64).上述观察指标OA组依次为1.9％ (3/157),1.3％ (2/157),3.8％ (6/157),3.2％ (5/157)及0％ (0/157),两组均差异无统计学意义(均P＞0.05).结论 RA患者行全膝关节置换术较OA患者不增加术后并发症的发生率.     

连续性肾脏替代治疗对心脏术后患者不稳定血流动力学的作用

目的 观察连续性肾脏替代治疗（CRRT）对心脏术后患者不稳定血流动力学的治疗作用。方法 选取安徽医科大学第二附属医院2010年10月至2015年3月心脏术后血流动力学不稳定进行CRRT治疗的13例患者,分别记录患者术后入住ICU时、开始CRRT时、CRRT 24小时、48小时的左心射血分数（EF）、平均动脉压（MAP）、中心静脉压（CVP）、肾上腺素（E）、去甲肾上腺素（NE）的剂量及白细胞计数（WBC）、血乳酸（LAC）水平。结果 CRRT开始后,EF、MAP均呈上升趋势,且48小时水平显著高于CRRT开始时,差异有统计学意义（P<0.05）。LAC水平逐渐降低,且48小时的LAC水平显著低于CRRT开始时,差异有统计学意义（P<0.05）。结论 CRRT对稳定心脏术后患者血流动力学具有积极作用。     

Medical complications of cocaine: changes in pattern of use and spectrum of complications.

We sought to determine whether changes in patterns of cocaine use, characterized by widespread abuse of cocaine alkaloid, have altered the nature and severity of medical complications over the past decade. Infectious complications, almost invariably associated with intravenous use, accounted for nearly all hospital admissions in the early 1980s. Cardiovascular, neurologic and psychiatric complications rose dramatically after 1987 both in absolute number and as a proportion of total complications. This rise parallelled increases in the absolute number and proportion of hospitalized patients smoking cocaine alkaloid or using intranasal cocaine, both disproportionately associated with non-infectious complications. While infectious complications were often local in nature, serious neurologic and cardiovascular sequelae were observed. These data indicate that changes in patterns of cocaine use have altered the nature and increased the severity of medical complications with a shift from infectious to cardiovascular, neurologic and psychiatric complications which may be life-threatening and associated with substantial morbidity.     

颈椎手术96例早期并发症分析

目的：分析颈椎手术早期并发症的发生原因及处理方法。方法回顾性分析96例颈椎手术患者的临床资料,其中脊髓型颈椎病56、颈椎骨折脱位21例、颈椎肿瘤11例、寰枢椎脱位5例、Chiari 畸形3例;颈椎前路手术57例、后路手术24例,前后联合手术15例,分析早期并发症发生率、发生原因及其对策。结果96例颈椎手术中27例出现并发症,发生率为29．2％,其中死亡1例,切口血肿2例,切口感染4例,脊髓或神经损伤3例,脑脊液瘘3例,喉返神经损伤2例,喉上神经损伤2例,肺部感染5例,尿路感染4例,无食管瘘及椎动脉损伤病例。前路手术并发症发生率24．6％（14/57）,后路手术并发症发生率36．8％（7/19）,联合入路手术并发症发生率40．0％（6/15）。结论颈椎手术早期并发症较多,严格掌握手术适应证,提高手术技巧,准确进行术前评估,精心术后护理,是减少颈椎手术后并发症的重要措施。     

Subacute toxicity of alpha-ergocryptine in Sprague-Dawley rats. 2: metabolic and hormonal changes.

The present study describes the metabolic changes observed in a dietary subacute toxicity experiment with the ergot alkaloid alpha-ergocryptine in Sprague-Dawley rats. The observed effects on metabolic and hormonal parameters were described separately from the general toxicological effects, in view of the important role of dopamine agonists in metabolism (e.g. ergot alkaloids in fescue toxicosis). The rats were fed 0, 4, 20, 100 or 500 mg ergocryptine/kg diet for 28-32 days (equal to 0, 0.36, 1.7, 8.9 and 60 mg ergocryptine/kg body weight/day for females and 0, 0.34, 1.4, 6.6 and 44 mg ergocryptine/kg body weight/day for males). Total cholesterol and high-density lipoprotein (HDL)-cholesterol were decreased dose dependently in females but the ratio HDL-cholesterol/total cholesterol was only decreased at 20 mg/kg body weight. Triglycerides and glucose concentrations were decreased in the highest dose groups of both sexes. Serum urea concentrations were increased in the 20, 100 and 500 mg/kg dose groups. Insulin, glucagon and liver glycogen were increased in the highest dose group at the end of the study, when the animals were allowed to eat prior to blood sampling and necropsy. Prolactin, T4 and FT4 were decreased in the 20, 100 and 500 mg/kg dose groups of both sexes. Follicle-stimulating hormone (FSH) was decreased in the 20, 100 and 500 mg/kg female dose groups and luteinizing hormone (LH) was increased in the 20, 100 and 500 mg/kg male dose groups. It is postulated that the observed effects on food intake, metabolism (lipid and carbohydrate) and hormonal parameters are due to an interaction of ergocryptine with central dopaminergic activities, which comprise a major functional component of a central regulatory system for metabolism.