Endothelial Cell Toxicity of Vancomycin Infusion Combined with Other Antibiotics

French guidelines recommend central intravenous (i.v.) infusion for high concentrations of vancomycin, but peripheral intravenous (p.i.v.) infusion is often preferred in intensive care units. Vancomycin infusion has been implicated in cases of phlebitis, with endothelial toxicity depending on the drug concentration and the duration of the infusion. Vancomycin is frequently infused in combination with other i.v. antibiotics through the same administrative Y site, but the local toxicity of such combinations has been poorly evaluated. Such an assessment could improve vancomycin infusion procedures in hospitals. Human umbilical vein endothelial cells (HUVEC) were challenged with clinical doses of vancomycin over 24 h with or without other i.v. antibiotics. Cell death was measured with the alamarBlue test. We observed an excess cellular death rate without any synergistic effect but dependent on the numbers of combined infusions when vancomycin and erythromycin or gentamicin were infused through the same Y site. Incompatibility between vancomycin and piperacillin-tazobactam was not observed in our study, and rinsing the cells between the two antibiotic infusions did not reduce endothelial toxicity. No endothelial toxicity of imipenem-cilastatin was observed when combined with vancomycin. p.i.v. vancomycin infusion in combination with other medications requires new recommendations to prevent phlebitis, including limiting coinfusion on the same line, reducing the infusion rate, and choosing an intermittent infusion method. Further studies need to be carried out to explore other drug combinations in long-term vancomycin p.i.v. therapy so as to gain insight into the mechanisms of drug incompatibility under multidrug infusion conditions.     

Continuous intravenous versus intermittent ampicillin therapy of experimental endocarditis caused by aminoglycoside-resistant enterococci.

We studied the efficacy of continuous intravenous infusion of ampicillin compared with that of intermittent administration of ampicillin alone or in combination with gentamicin for the therapy of highly aminoglycoside-resistant enterococcal experimental endocarditis. Rabbits were infected with a gentamicin-susceptible (MIC, 256 micrograms/ml) strain of Enterococcus faecalis or a strain of E. faecalis which was highly resistant to gentamicin in vitro (MIC, greater than 2,000 micrograms/ml). Administration of ampicillin by continuous intravenous infusion did not significantly enhance the killing of enterococci in vivo compared with that by intermittent administration of ampicillin for either the aminoglycoside-susceptible or the aminoglycoside-resistant strain. In combination with gentamicin, there were no significant differences in efficacies obtained with intermittent versus continuous intravenous infusion of ampicillin therapy for experimental endocarditis caused by either strain of E. faecalis.     

乳腺癌患者化疗期间不同静脉输液途径的选择与血管保护的关系

目的探讨乳腺癌患者术后行多周期化疗期间血管的保护。方法选择90位乳腺癌术后需行多周期化疗的患者入组,由患者根据自己的经济情况、接受能力和认识程度决定治疗期间所选择的输液途径入组观察,三组患者分别采用外周静脉化疗、外周静脉加PICC化疗、PICC化疗。结果三种输液途径穿刺次数比较有明显差别;三种输液途径所致静脉炎情况比较:外周静脉化疗组与外周静脉加PICC化疗组比较P<0．01,差异有显著意义;外周静脉化疗组与PICC化疗组比较P<0．01,差异有极显著意义;外周静脉加PICC化疗组与PICC化疗组比较P<0．05,差异有显著意义。三种输液途径在化疗期间药物外渗情况比较有明显差异,P<0．01。结论乳腺癌患者行多周期化疗期间早期置入PICC导管,可以减少反复穿刺带给病人的痛苦,避免了化学性静脉炎和化疗药物外渗的发生,能够最大限度地保护病人的血管免受损害。     

Level of evidence for therapeutic drug monitoring of vancomycin

Vancomycin is an antibiotic for exclusive hospital use administrated in intravenous infusion to treat systemic infections. It is mainly eliminated by kidneys and potentially nephrotoxic. Data available show that Therapeutic Drug Monitoring (TDM) of vancomycin is highly recommended. It aims to ensure efficacy and avoid resistance by maintaining trough plasma concentrations above the MIC. Secondary, vancomycine TDM may be indicated to prevent nephrotoxicity in high risk patients. TDM is often underwent at steady state (48 to 72 h after the treatment initiation) unless in case of renal impairment (24 h). While compared with intermittent administration, continuous infusion did not result in prognosis improvement; however it resulted in lower pharmacokinetic variability and better cost-efficiency. Targeted trough concentrations for intermittent infusion are between 15 and 20 mg/L (up to 25-30 mg/L for GISA). In case of continuous infusion, targets are higher (25 to 40 mg/L).     

Prostaglandin E1 in therapy of peripheral arterial occlusive disease]

The intraarterial and intravenous infusion of prostaglandin E1 (PGE1) today is well established in the therapy of peripheral arterial occlusive disease. This review summarizes the results of pharmacological-clinical studies and the influence of PGE1 on the pathomechanism of ischaemia due to its antithrombotic, leukocyte and endothelial stabilizing properties. Clinical data available on continuous and intermittent infusion for both modes of administration are critically appraised, taking into account more recent data on active metabolites.     

Pharmacokinetics of vancomycin in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of vancomycin were studied in four patients on continuous ambulatory peritoneal dialysis. After a single intravenous infusion of 10 mg/kg of total body weight, multiple blood, urine, and dialysate samples were collected during a 72-h evaluation period. The steady-state volume of distribution was 0.73 +/- 0.07 (mean +/- standard deviation) liters/kg with a beta half-life of 90.2 +/- 24.2 h. The continuous ambulatory peritoneal dialysis clearance of vancomycin was 1.35 +/- 0.35 ml/min, and the serum clearance was 6.4 +/- 1.1 ml/min. Peritoneal dialysate concentrations of vancomycin were rapidly attained after the intravenous infusion and averaged 2.2 +/- 0.7 mg/liter throughout the 72-h observation period. A loading dose of 23 mg/kg followed by a maintenance dose of 17 mg/kg every 7 days should attain and maintain therapeutic serum and dialysate concentrations. More frequent dosing may be necessary for less susceptible organisms.     

Dicloxacillin and erythromycin at high concentrations increase ICAM-1 expression by endothelial cells: a possible factor in the pathogenesis of infusion phlebitis

OBJECTIVES: Antimicrobial agents are important risk factors for infusion phlebitis, but the risk varies between different antibiotics. Erythromycin and dicloxacillin are known to induce phlebitis frequently, as well as to exert toxic effects on cultured endothelial cells. The pathogenesis of infusion phlebitis is unclear, but chemical toxicity is thought to lead to inflammation and subsequent thrombosis. In the present study, endothelial cells were exposed to antibiotics at the range of concentrations used for intravenous administration, followed by analysis of pro-inflammatory and pro-coagulant surface molecules. METHODS: Primary human umbilical vein endothelial cells (HUVEC) and the endothelial hybrid cell line EaHy926 were exposed to dicloxacillin, erythromycin, benzylpenicillin and cefuroxime (all at 6250 mg/L) for 60 min, followed by washing. After 5 or 24 h additional incubation, cells were analysed for E-selectin (CD62E), tissue factor (TF) or intercellular adhesion molecule 1 (ICAM-1, CD54) density by flow cytometry. RESULTS: Despite constitutive expression of ICAM-1 (34%) in HUVEC, 6250 mg/L of dicloxacillin or erythromycin significantly increased the number of cells with ICAM-1 expression by 37% and 30%, respectively. In contrast, cefuroxime and benzylpenicillin did not up-regulate ICAM-1 above background levels. A similar pattern was seen with the endothelial cell line EaHy926. The E-selectin and TF density were not affected by the antibiotics examined. CONCLUSIONS: The results of this study support the theory that endothelial cells that are affected by high concentrations of antibiotics may initiate an inflammatory response through expression of ICAM-1. This is a novel finding in the pathogenesis of infusion phlebitis.     

Transdermal nitroglycerin for the prevention of intravenous infusion failure due to phlebitis and extravasation

OBJECTIVE: To evaluate the clinical use of transdermal nitroglycerin for the prevention of intravenous infusion failures due to phlebitis or extravasation. DATA SOURCES: Clinical literature was accessed through a MEDLINE search (1966-May 2000). Key search terms included nitroglycerin, transdermal, phlebitis, extravasation, intravenous, and infusion. DATA SYNTHESIS: Common and serious consequences of intravenous therapy include the occurrence of postinfusion phlebitis and failure to maintain intravenous therapy due to intravenous fluid extravasation. Transdermal application of nitroglycerin has been evaluated as a treatment and preventive method for intravenous infusion failures related to phlebitis or extravasation. An evaluation of studies focusing on transdermal nitroglycerin in the prevention of infusion failures due to phlebitis or extravasation was conducted. CONCLUSIONS: Use of transdermal nitroglycerin as a prophylactic measure for intravenous infusion failures is a therapeutic option for patients requiring long-term intravenous therapy (i.e., > 50 h).     

Clinical evaluation of elastomeric hydrogel peripheral catheters during home infusion therapy

The use of elastomeric hydrogel (Aquavene, Menlo Care, Menlo Park, Calif.) peripheral catheters in home infusion therapy was prospectively evaluated. Elastomeric hydrogel catheter composition differs from that of conventional peripheral catheters made of Teflon or silicone in that it softens upon insertion and expands two gauge sizes within 30 minutes of insertion. Fifty-four test catheters were successfully placed in 44 home infusion therapy patients, for a total dwell time of 290 days. Average dwell time was 5.37 days, with a range of 1 to 20 days. The extension of dwell time beyond the accepted standard of 72 hours was not associated with an increased incidence of phlebitis when compared to the incidence of phlebitis reported in the scientific literature. The ability to extend peripheral catheter dwell time without increasing the incidence of catheter-related complications may have major clinical and economic advantages for the payors, providers, and consumers of home infusion therapy.     

3种外用药物预防静脉留置针输注营养液所致静脉炎的效果观察

目的对比3种不同外用药物对经外周静脉留置针输注营养液致静脉炎的预防效果。方法将应用静脉留置针且输注同比例静脉营养液的129位患者随机分成3组:维生素E乳膏组(n=44)、芝麻油组(n=43)、赛肤润组(n=42)。输液第一天开始,3组均在输液前在敷贴上方沿静脉走向外用相应药物,3次/d,直至拔除留置针。记录各组患者静脉炎发生率、留置针留置时间、静脉炎范围、疼痛分值。结果静脉炎发生率比较,维生素E乳膏组、芝麻油组较赛肤润组低(P<0.01)。疼痛分值比较,维生素E乳膏组、芝麻油组较赛肤润组低(P<0.01)。留置时间比较,维生素E乳膏组、芝麻油组较赛肤润组长(P<0.01)。结论芝麻油、维生素E乳膏可有效预防输注营养液所致静脉留置针静脉炎,尤其是芝麻油,具有经济成本低的优点,值得临床借鉴。     

姜醇联合紫花烧伤膏在预防化疗性静脉炎中的应用效果评价

目的 探讨姜醇联合紫花烧伤膏外涂预防化疗性静脉炎的疗效.方法 将200例外周静脉化疗患者随机分为实验组和对照组各100例.对照组按常规输注化疗药物,实验组采用姜醇联合紫花烧伤膏外涂静脉周围皮肤,预防化疗性静脉炎.化疗结束后观察并记录结果.结果 实验组与对照组相比,静脉炎的发生率明显降低.结论 姜醇联合紫花烧伤膏局部外涂预防化疗性静脉炎,操作简单,疗效显著.     

水胶体敷料预防长春瑞宾所致静脉炎的效果

目的观察局部外敷水胶体敷料预防长春瑞宾所致周围静脉炎的效果。方法选取192例接受了1～3个疗程NP方案化疗的非小细胞肺癌病人,随机分为观察组和对照组。两组均采取常规地塞米松加利多卡因静滴护理,在此基础上,观察组沿静脉走向局部外敷水胶体敷料,而对照组则于静脉穿刺处给予500g/L硫酸镁湿敷。结果观察组病人静脉炎发生率和静脉损伤程度显著低于对照组（χ2=40.72,u=3.71,P〈0.01）。结论局部外敷水胶体敷料能有效减少输注长春瑞宾所致静脉炎的发生,大大减轻病人痛苦。     

Relative Incidence of Phlebitis Caused by Continuous Intravenous Infusion of Cephapirin and Cephalothin

In a single-blinded study, two groups of 10 healthy subjects were given cephapirin or cephalothin by continuous intravenous infusion for 5 days, 0.5 g every 6 hr for the first day and then 1.0 g every 6 hr for 4 days. Eight of the cephalothin subjects and two of the cephapirin subjects developed phlebitis. Phlebitis was more severe in the cephalothin group and developed more rapidly, necessitating vein changes six times more often than in the cephapirin group. The less irritating properties of cephapirin demonstrated in this study indicate it may be the more useful cephalosporin analogue for intravenous therapy.     

主动静脉治疗模式在ICU中的应用

目的探讨主动静脉治疗模式在重症监护室(ICU)中应用效果。方法将120例危重患者随机分为主动静脉治疗组(试验组)和被动静脉治疗组(对照组)各60例。两组患者均在入院后立即建立外周浅静脉通道的情况下,主动静脉治疗组在24h内再进行评估,包括患者情况、治疗方案、穿刺工具选择及护理、维护、风险管理评估。结果与被动静脉治疗组相比,主动静脉治疗组静脉炎发生率较低(P<0.05),血管内导管相关性感染发生率较低(P<0.05)。结论在ICU主动静脉治疗模式能降低静脉炎发生率和血管内导管相关性血流感染发生率,进一步提高护理质量。     

Differential effects of oral, peripheral intravenous, and intraportal glucose on hepatic glucose uptake and insulin and glucagon extraction in conscious dogs.

The effect of equal (1.1 +/- 0.1 g/kg body wt) amounts of glucose administered orally, or by peripheral intravenous or intraportal infusion on hepatic glucose uptake and fractional hepatic extraction of insulin and glucagon was studied in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, carotid artery, and superior mesenteric vein. Portal vein and hepatic vein plasma flow increased only after oral glucose administration. Arterial plasma glucose increased equally to 150-160 mg/100 ml after all three routes of glucose administration. Portal vein glucose was similar after oral (195 +/- 15 mg/100 ml) and intraportal glucose infusion (215 +/- 11 mg/100 ml) and significantly higher than after peripheral intravenous glucose. Hepatic glucose uptake after oral (68 +/- 4%) and intraportal glucose administration (65 +/- 7%) significantly exceeded that after peripheral intravenous glucose infusion (23 +/- 5%). The amount of insulin above basal presented to the liver during the 180 min after oral glucose was 7.6 +/- 1.3 U, 4.3 +/- 0.6 U after intraportal glucose, and 4.1 +/- 0.6 U after peripheral intravenous glucose. Hepatic extraction of insulin increased significantly after oral glucose (42 +/- 3 to 61 +/- 4%), but was unchanged after intraportal and peripheral intravenous glucose administration. When the portal vein glucose levels achieved during peripheral intravenous glucose infusion for 90 min were maintained by a subsequent 90-min intraportal glucose infusion, hepatic glucose uptake was significantly greater during the intraportal glucose infusion. Glucagon secretion was suppressed equally after oral glucose, intraportal glucose, and peripheral intravenous glucose administration; fractional hepatic extraction of that hormone, which was significantly less than that of insulin, was unchanged. These results indicate that hepatic glucose uptake is significantly greater after oral and intraportal glucose administration than after peripheral intravenous glucose infusion. This difference is not simply related to the amount of glucose or insulin presented to the liver and the increased hepatic glucose uptake did not depend solely upon the augmented fractional hepatic extraction of insulin. Hepatic extraction of insulin and hepatic glucose uptake appear to be regulated independently.     

三七醇外敷治疗慢性肝病病人输液所致外周静脉炎

[目的 ]探讨三七醇外敷治疗慢性肝病病人输液所致外周静脉炎的疗效。 [方法 ]将 10 2例因输液致外周静脉炎病人随机分为实验组和对照组 ,每组 5 1例 ,实验组采用三七醇外敷 ,对照组采用硫酸镁外敷 ,观察受损静脉恢复情况。 [结果 ]经2个疗程治疗 ,实验组受损静脉恢复明显优于对照组 (P <0 .0 0 1)。[结论 ]三七醇外敷能有效地治疗慢性肝病病人输液引起的外周静脉炎     

山莨菪碱减轻化疗性静脉炎的临床观察

目的探讨局部涂擦自制2%山莨菪碱霜剂减轻刺激性化疗药物所致静脉炎及局部疼痛的疗效。方法采用自身对照方法,选择118例发生过外周静脉损伤的化疗病人为研究对象,于第1周期化疗或第2周期化疗前5～10min,将2%安慰剂或山莨菪碱霜剂沿静脉走向均匀地涂擦于静脉穿刺点血管近心端的皮肤上,长10cm左右,连续输注化疗药物的病人每隔12h同法外涂2%山莨菪碱霜剂或安慰剂1次,直至刺激性化疗药物输注完毕。观察病人输液过程中及输液后疼痛及静脉炎发生的情况及严重程度。结果第2周期化疗时,使用2%山莨菪碱霜剂后病人静脉炎的发生率明显低于第1周期涂擦安慰剂时(P<0.01);第2周期化疗时,使用2%山莨菪碱霜剂的病人局部疼痛的发生率明显低于第1周期涂擦安慰剂时(P<0.01)。结论2%山莨菪碱霜剂能明显减轻刺激性化疗药物输注时所致静脉炎及局部疼痛。     

In vivo efficacy of continuous infusion versus intermittent dosing of linezolid compared to vancomycin in a methicillin-resistant Staphylococcus aureus rabbit endocarditis model

Linezolid is the first drug issued from the oxazolidinones, a novel class of antimicrobial agents with potent activity against gram-positive pathogens. A rabbit endocarditis model was used to compare the in vivo activities of different linezolid regimens mimicking intermittent dosing of 10 mg/kg of body weight every 12 h for 5 days or continuous (constant-rate) infusion of a daily dose of 20 mg/kg (for 5 days) or 40 mg/kg (for 3 and 5 days) and the activities of intermittent dosing and continuous infusion of vancomycin (for 5 days). The in vivo activities of these regimens were tested against three strains of methicillin-resistant Staphylococcus aureus. A human-like pharmacokinetic simulation was used for linezolid in order to improve the extrapolation of the results to human therapy. All linezolid regimens significantly reduced the numbers of S. aureus cells in aortic valve vegetations compared to the numbers in the control groups. Linezolid intermittent dosing had an in vivo bacteriostatic effect. Switching from intermittent dosing to continuous infusion (at the same dose) led to in vivo bactericidal activity, with a decrease of at least 3 log(10) CFU/g of vegetation compared to the counts for the controls. After 5 days of treatment, continuous infusion of linezolid (corresponding to a daily dose of 40 mg/kg in humans) seemed to be at least as effective as vancomycin against the three strains. No resistant variant was isolated from the vegetations during any of the treatments. These data suggest that continuous infusion of linezolid could be an appropriate alternative to the use of glycopeptides for the treatment of severe methicillin-resistant S. aureus infections.     

老年急性下呼吸道感染患者抗生素序贯治疗与护理

目的探讨老年急性下呼吸道感染患者抗生素序贯治疗与护理。方法对老年急性下呼吸道感染患者的两种治疗方案:静脉-口服序贯治疗组、连续静脉治疗组进行了临床疗效对比,同时对两组患者的细菌清除率、静脉治疗时间、住院日、输液次数、静脉穿刺成功率以及抗生素医疗费用进行比较。结果两组临床疗效相同,但序贯组的静脉用药时间、输液次数、抗生素费用明显低于静脉组(P<0.01),静脉穿刺成功率明显高于静脉组(P<0.01),平均住院日亦少于静脉组(P<0.05)。结论对老年急性下呼吸道感染患者合理应用抗生素序贯治疗是安全有效的,而且有更加合理的成本-效果比。护理上要注意合理选择血管,指导老年患者正确服用抗生素,并密切观察药物疗效与不良反应。     

Clinical audit documenting insertion date of peripheral intravenous cannulae

The Royal College Of Nursing (RCN) have evidence-based guidelines with regard to optimal time for changing peripheral intravenous cannulae (PIC) and documentation post-insertion (patient and nursing notes). This clinical audit assesses the compliance with respect to the RCN and Eastbourne District General Hospital guidelines of documenting the date post-insertion of PIC, optimal time for changing cannulae and rates of superficial phlebitis on the surgical wards. All PIC, their dressings, sites and intravenous infusions were examined on all inpatients on the surgical wards on three random days. Staff awareness with regard to RCN and local guidelines for optimal time to change peripheral venous cannulae and documentation post-insertion was assessed. The majority of staff nurses correctly stated that the optimal time for changing an uncomplicated PIC was 72 hours, despite this 13.8% had a cannulae which had been inserted for more than 72 hours. Our study has found that despite medical and nursing staff being aware of RCN and local guidelines, there is still poor compliance with regards to documentation, optimal time for changing and thus increased levels of superficial phlebitis post insertion of PIC.