Leonard Ebah

A Randomized Double-Blind Controlled Trial of Taurolidine-Citrate Catheter Locks for the Prevention of Bacteremia in Patients Treated With Hemodialysis

BACKGROUND Bacteremia is a major cause of morbidity in patients using intravascular catheters. Interdialytic locking with antibiotics decreases the incidence of bacteremia, but risks antibiotic resistance. Taurolidine is a nontoxic broad-spectrum antimicrobial agent that has not been associated with resistance. Preliminary evidence suggests that taurolidine-citrate locks decrease bacteremia, but cause flow problems in established catheters. STUDY DESIGN Double-blind randomized controlled trial. INTERVENTION Interdialytic locking with taurolidine and citrate (1.35% taurolidine and 4% citrate) compared with heparin (5,000 U/mL) started at catheter insertion. SETTING & PARTICIPANTS 110 adult hemodialysis patients with tunneled cuffed intravascular catheters inserted at 3 centers in Northwest England. OUTCOMES & MEASUREMENTS Primary end points were time to first bacteremia episode from any cause and time to first use of thrombolytic therapy. RESULTS There were 11 bacteremic episodes in the taurolidine-citrate group and 23 in the heparin group (1.4 and 2.4 episodes/1,000 patient-days, respectively; P = 0.1). There was no significant benefit of taurolidine-citrate versus heparin for time to first bacteremia (hazard ratio, 0.66; 95% CI, 0.2-1.6: P = 0.4). Taurolidine-citrate was associated with fewer infections caused by Gram-negative organisms than heparin (0.2 vs 1.1 infections/1,000 patient-days; P = 0.02); however, there was no difference for Gram-positive organisms (1.1 vs 1.2 infections/1,000 patient-days; P = 0.8). There was a greater need for thrombolytic therapy in the taurolidine-citrate versus heparin group (hazard ratio, 2.5; 95% CI, 1.3-5.2; P = 0.008). LIMITATIONS Small sample size. The study included bacteremia from all causes and was not specific for catheter-related bacteremia. CONCLUSIONS Taurolidine-citrate use did not decrease all-cause bacteremia and was associated with a greater need for thrombolytic treatment. There was a decrease in infections caused by Gram-negative organisms and a trend to a lower frequency of bacteremia, which warrants further study.

Subcutaneous interstitial pressure and volume characteristics in renal impairment associated with edema.

The kidneys and the interstitial compartment play a vital role in body fluid regulation. The latter may be significantly altered in renal dysfunction, but experimental studies are lacking. To help define this we measured the subcutaneous interstitial pressure, bioimpedance volumes, and edema characteristics in 10 healthy subjects and 21 patients with obvious edema and chronic kidney disease (CKD). Interstitial edema was quantified by the time taken for a medial malleolar thumb pit to refill and termed the edema refill time. Interstitial pressure was significantly raised in CKD compared to healthy subjects. Total body water (TBW), extracellular fluid volume (ECFV), interstitial fluid volume, the ratio of the ECFV to the TBW, and segmental extracellular fluid volume were raised in CKD. The ratio of the ECFV to the TBW and the interstitial fluid volume were the best predictors of interstitial pressure. Significantly higher interstitial pressures were noted in edema of 2 weeks or less duration. A significant nonlinear relationship defined interstitial pressure and interstitial fluid volume. Edema refill time was significantly inversely related to interstitial pressure, interstitial compartment volumes, and edema vintage. Elevated interstitial pressure in CKD with obvious edema is a combined function of accumulated interstitial compartment fluid volumes, edema vintage, and tissue mechanical properties. The edema refill time may represent an important parameter in the clinical assessment of edema, providing additional information about interstitial pathophysiology in patients with CKD and fluid retention.

Neuropathic diabetic foot ulcers - evidence-to-practice.

Foot ulcers and their attendant complications are disquietingly high in people with diabetes, a majority of whom have underlying neuropathy. This review examines the evidence base underpinning the prevention and management of neuropathic diabetic foot ulcers in order to inform best clinical practice. Since it may be impractical to ask patients not to weight-bear at all, relief of pressure through the use of offloading casting devices remains the mainstay for management of neuropathic ulcers, whilst provision of appropriate footwear is essential in ulcer prevention. Simple non-surgical debridement and application of hydrogels are both effective in preparing the wound bed for healthy granulation and therefore enhancing healing. Initial empirical antibiotic therapy for infected ulcers should cover the most common bacterial flora. There is limited evidence supporting the use of adjunctive therapies such as hyperbaric oxygen and cytokines or growth factors. In selected cases, recombinant human platelet-derived growth factor has been shown to enhance healing; however, its widespread use cannot be advised due to the availability of more cost-effective approaches. While patient education may be beneficial, the evidence base remains thin and conflicting. In conclusion, best management of foot ulcers is achieved by what is taken out of the foot (pressure, callus, infection, and slough) rather than what is put on the foot (adjuvant treatment).

Genomic Structure of Capsular Determinants

The production of an extracellular polysaccharide capsule is a common feature of many bacteria (Whitfield and Valvano 1993). The capsule, which often constitutes the outermost layer of the cell, mediates the interaction between the bacterium and its immediate environment and plays a crucial role in the survival of bacteria in hostile environments. One such environment is the human host, where interactions between the capsule and the host’s immune system may be vital in deciding the outcome of an infection (Moxon and Kroll 1990). In the absence of specific antibody, a capsule offers protection against the nonspecific arm of the host’s immune system by conferring increased resistance to complement-mediated killing and complement-mediated opsonophagocytosis (Michalek et al. 1988; Moxon and Kroll 1990). A small set of capsular polysaccharides which resemble polysaccharide moieties present in host tissue are poorly immunogenic (Finne 1982; Lindahl et al. 1994). The Escherichia coli K1 and Neisseria meningitidis serogroup B capsules, both of which contain N-acetyl-neuraminic acid and the heparin-like E. coli K5 capsule, all elicit a poor antibody response in infected individuals (Jennings 1990) and confer some measure of resistance to the host’s adaptive humoral response. Aside from direct interactions with the host’s immune system, capsules may promote the formation of biofilms and the colonisation of a variety of ecological niches, including indwelling catheters, prostheses and the formation of alginate-rich biofilms in the lungs of cystic fibrosis patients (Roberts 1995). In such instances the polysaccharide may present a permeability barrier to antibiotics and hinder the effective eradication of the bacteria (Costerton et al. 1999).

Acute arteriovenous access failure: long-term outcomes of endovascular salvage and assessment of co-variates affecting patency.

Aims: This study reports long-term outcomes after endovascular salvage (EVS) for acute dialysis fistula/graft dysfunction. Methods: All patients presenting with acute fistula or graft dysfunction, excluding primary failures, referred for endovascular salvage were included in this single-centre prospective study. Results: Altogether, 410 procedures were carried out in 232 patients. Overall, the incidence of thrombosis/occlusion (per patient-year) was 0.12 for fistulae and 0.9 for grafts. The anatomical success rate for EVS was 94% for fistulae and 92% for grafts. Primary patency rates for fistulae at 1, 6, 12, 24 and 36 months were 82, 64, 44, 34 and 26%, respectively, whereas secondary patency rates were 88, 84, 74, 69 and 61%, respectively. Primary patency rates for grafts at 1, 6 and 12 months were 50, 14 and 8%. The overall rate of complications was 6% with no incidence of symptomatic pulmonary embolism. In a Cox regression model, upper-arm location of fistula (HR 1.9, p = 0.04, n = 144) was associated with lower primary patency, whereas the presence of thrombosis was associated lower primary (HR 1.9, p = 0.004, n = 144) and secondary patency (HR 3.7, p < 0.001, n = 144). Aspirin therapy was associated with longer primary patency (HR 0.6, p = 0.02, n = 144) and secondary patency (HR 0.58, p = 0.08, n = 144). Conclusion: EVS is effective but longer-term outcomes are poor. Presence of thrombosis portends poor fistula survival and strategies for prevention need attention. Balloon maceration, our preferred declotting technique, is safe and the most cost-effective method. Aspirin therapy for patients presenting with failure of fistulae deserves further investigation.

Reverse iontophoresis of urea in health and chronic kidney disease: a potential diagnostic and monitoring tool?

Eur J Clin Invest 2012;

Phosphate enrichment of dialysate for use in standard and extended haemodialysis.

Background/Aims: Intensive haemodialysis (HD) sometimes causes hypophosphataemia, but phosphate-containing dialysate is not readily available. We examined the effectiveness of extemporaneously producing a phosphate-rich dialysate for use in HD. Methods: Incremental volumes of Fleet® were added to acid concentrate and predicted to deliver dialysate phosphate concentrations of 0.19–1.1 mmol/l, following mixture with ultrapure water and base concentrate by the HD machine. Results: The achieved concentrations were close to predicted values (p = 0.77) and remained stable throughout an 8-hour ‘treatment’ time (p = 0.99). The dialysate phosphate concentration had a linear relationship with the Fleet® volume added, defined by the regression equation y = 172.79 x – 1.47 (R2 = 0.99, r = 0.99, p = 0.003). The dialysate pH, calcium, magnesium and bicarbonate concentrations did not change over the study period (p = 0.28–0.99). Microscopic analysis under polarised light showed no evidence of crystal formation. Conclusion: The study validates a simple, reliable and cost-effective protocol for phosphate supplementation in conventional and extended HD.

A Modified in vivo Flow Variation Technique of Microdialysis for Sampling Uremic Toxins in the Subcutaneous Interstitial Compartment

Background: Uremic toxins are typically measured in plasma and little is known of their interstitial concentrations. We undertook experiments to validate a microdialysis technique for simultaneous recovery of small and large uremic toxins in the subcutaneous interstitial fluid (ISF). Methods: Microdialysis catheters were inserted into the subcutaneous interstitium of 8 subjects (controls and uremic patients) and perfused using two different solutions at incremental flow rates to determine analyte recovery and ISF concentrations of urea and protein. Results: 10% dextran-40 perfusate allowed the determination of interstitial concentrations of urea and protein reliably, by virtue of the exponential decay of their concentrations in the microdialysate with incremental flow rates (R2 = 0.63–0.99). Interstitial and plasma urea correlated well (r = 0.95), as did interstitial urea from distant anatomical sites (r = 0.96). Conclusion: Cutaneous microdialysis with dextran-40 allows measurement of small and large molecule concentrations in ISF, creating an opportunity to characterize ISF in uremia.

Peritoneal Dialysis Solutions

Peritoneal dialysis (PD) solutions contribute to homeostasis in patients with end stage renal disease (ESRD) by removing accumulated electrolytes and toxins, maintaining acid-base balance, and removing excess fluid through ultrafiltration. To achieve these functions, current PD solutions are an electrolyte solution of sodium, calcium and magnesium to which an osmotic agent and a buffer are added. Glucose remains the most used osmolyte, although icodextrin and amino acid solutions are also available. Icodextrin is a glucose polymer that confers the advantage of sustained ultrafiltration and minimal metabolite absorption. Amino acid solutions are used in patients as a form of nutritional supplementation. Older PD solutions used lactate as the buffer, but lactate/bicarbonate and bicarbonate only buffered solutions are more physiological and increasingly used. Accumulated evidence of local and systemic effects of PD fluids due to low pH and glucose degradation products (GDPs) has led to a drive towards more biocompatible solutions. Thus, the wide variety of PD solutions can be tailored for a patient specific management approach.

Front & Back Matter

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