A randomised comparative crossover study to assess the affect on circuit life of varying pre-dilution volumes associated with continuous veno-venous haemofiltration (CVVH) and continuous veno-venous haemodiafiltration (CVVHDf)

Continuous renal replacement therapy (CRRT) is an established treatment option in Australia for critically ill patients with acute renal failure (ARF). Critical care nurses play a primary role in the set-up of equipment, monitoring and care of patients receiving CRRT. Although described as a continuous therapy, delays or interruptions in CRRT can interfere with treatment efficiency. A review of the literature identified how optimal circuit function is an important factor in determining the effectiveness of treatment and patient outcomes.The aim of this research was to evaluate treatment efficiency in terms of circuit life between two widely used forms of CRRT, continuous veno-venous haemofiltration (CVVH) versus continuous veno-venous haemodiafiltration (CVVHDf). The investigation focused attention on the influence higher pre-dilution volumes and convective clearance of CVVH may have on circuit life when compared to the lower pre-dilution volumes and diffusive clearance required for CVVHDf.This thesis describes how the impact of CVVH versus CVVHDf on circuit life was investigated using a randomised comparative crossover study design. Once institutional ethics committee approval had been received, 45 patients were recruited to the study who were 18 years or older and required the commencement of CRRT as part of their Intensive Care treatment. Of the 45 patients who were randomised to receive CVVH or CVVHDf, 31 patients achieved a successful crossover to the alternative technique. Failure to achieve a „natural‟ circuit life – that is one which terminated due to clotting, in a CVVH and CVVHDf circuit accounted for the large drop out rate. Blood flow rate, vascular access device and insertion site, haemofilter, anticoagulation and machine hardware were standardised. An ultrafiltrate dose 35 millilitres (ml) per kilogram (kg) per hour (hr) delivered pre-filter was used for CVVH and a fixed pre-dilution volume of 600ml per hr with a dialysate dose of 1litre (L) was used for CVVHDf. Patients were excluded if coagulopathic, thrombocytopenic or unable to receive heparin.Of the 31 paired comparisons there was a significant difference in circuit life measurements between CVVH and CVVHDf after a paired-sample t-test was performed following natural logarithm base-e (ln) dataset transformation (CVVH 6.101 versus CVVHDf 6.779, P-value = 0.001). A Wilcoxon signed ranks test used raw dataset values of circuit life measurements as an alternative non-parametric comparison (Z = -4.076, P-value 0.09 (coefficient of determination = 0.117) or a linear relationship which could be associated with circuit life (P-value = 0.228).The evaluation of treatment efficiency in terms of circuit life between the different techniques of CVVH and CVVHDF is of clinical importance, since each treatment mode depends upon a measure of circuit longevity to achieve adequate replacement of renal function. Numerous factors have been described which influence circuit life in the delivery of CRRT including circuit and filter design, anticoagulation and staff training and expertise. In this study a longer circuit life was reported using CVVHDf which incorporated lower pre-dilution volumes when compared with the higher pre-dilution volumes associated with CVVH. This could possibly be explained by the physical processes involved in fluid and solute transport across the filter membrane. The choice of CRRT mode is a factor which may be an important independent determinant of circuit life using the techniques of CVVH and CVVHDf. This information may influence intensive care nursing practice in respect of mode selection for CRRT in collaboration with medical colleagues

Progress in Hemodialysis

Hemodialysis (HD) represents the first successful long-term substitutive therapy with an artificial organ for severe failure of a vital organ. Because HD was started many decades ago, a book on HD may not appear to be up-to-date. Indeed, HD covers many basic and clinical aspects and this book reflects the rapid expansion of new and controversial aspects either in the biotechnological or in the clinical field. This book revises new technologies and therapeutic options to improve dialysis treatment of uremic patients. This book consists of three parts: modeling, methods and technique, prognosis and complications

Precision antimicrobial therapy: the application of therapeutic drug monitoring in critical illness

Despite advances in critical care medicine, severe infections and sepsis-related mortality remain a pressing problem. There is considerable evidence of under- and overexposure from standard dosing regimens across numerous antimicrobial classes in critically ill patients, a result of pharmacokinetic alterations arising from unique pathophysiologic changes. Timely initiation of adequately dosed antimicrobial therapy is recognised to be paramount in improving clinical outcomes in sepsis. Therapeutic drug monitoring (TDM), a tool traditionally used to minimise toxicity of glycopeptides and aminoglycosides, is increasingly being used to increase the precision of antimicrobial dose regimens in critical illness. ‘Emerging’ candidates for which TDM is recommended include β-lactam antibiotics, linezolid, ciprofloxacin, and antifungal, antiviral and antimycobacterial drugs. Little is known about the current uptake of TDM for these agents in Australian hospitals and the barriers to TDM implementation. Performing TDM also presents a learning opportunity whereby the probability of attaining therapeutic targets using empiric dosing strategies may be (re)evaluated. Chapter 1 presents an overview of the challenges facing clinicians prescribing antimicrobials for critically ill patients and potential ways TDM data can be used to overcome these challenges. Chapter 2 explores performance, clinician attitudes and barriers to implementation of TDM for emerging antimicrobial candidates, mapping out current unmet clinical need and providing a framework for TDM data driven precision antimicrobial dosing in subsequent chapters. Chapter 3 examines concentration–toxicity relationships in critically ill patients treated with β-lactam antibiotics and defines threshold concentrations associated with neuro- and nephrotoxicity. Chapter 3 also identifies factors that contribute to underexposure of antibiotics in critically ill patients. Chapter 4 investigates the pharmacokinetics and current dosing regimens of the antifungal drug fluconazole, another emerging TDM candidate. These findings are extended in Chapter 5 with an evaluation of a novel model-based dosing strategy for fluconazole. The findings from Chapters 3 and 4 leverage TDM data to provide insights into critically ill patients at risk of under- and overexposure of antimicrobials, and the use of novel antimicrobial dosing strategies. Chapter 6 discusses the clinical implications of this work and recommendations for future research

The conditioning of medical gases with hot water humidifiers

During invasive mechanical ventilation due to the dryness of medical gases is necessary to provide an adequate level of conditioning. The hot water humidifiers (HWH) heat the water, thus allowing the water vapor to heat and humidify the medical gases. In the common HWH there is a contact between the medical gases and the sterile water, thus increasing the risk of patient’s colonization and infection. Recently to avoid the condensation in the inspiratory limb of the ventilator circuit, new heated ventilator circuits have been developed. In this in vitro study we evaluated the efficiency (absolute/relative humidity) of three HWH: (1) a common HWH without a heated ventilator circuit (MR 730, Fisher&Paykel, New Zeland), (2) the same HWH with a heated ventilator circuit (Mallinckrodt Dar, Italy) and (3) a new HWH (DAR HC 2000, Mallinkckrodt Dar, Italy) with a heated ventilator circuit in which the water vapor reaches the medical gases through a gorotex membrane, avoiding any direct contact between the water and gases. At a temperature of 35°C and 37°C the HWH and heated tube were evaluated. The absolute humidity (AH) and relative humidity (RH) were measured by a psychometric method. The minute ventilation, tidal volume respiratory rate and oxygen fraction were: 5.8 ± 0.1 l/min, 740 ± 258 ml, 7.5 ± 2.6 bpm and 100%, respectively. Ventilator P2 Use of a bougie during percutaneous tracheostom

Clinical and pathophysiological aspects of severe falciparum malaria

Malaria is a major global public health problem. One-fifth of the world's population is at risk of malaria and drug resistance is spreading. Nearly five times as many cases of malaria were reported in 2000 as tuberculosis, AIDS, measles and leprosy cases combined. In the time it takes to say the word "malaria," ten children will contract the disease and begin fighting for their lives. Since the cinchona alkaloids were introduced as a specific treatment for agues 350 years ago, the treatment of severe malaria has changed little and therapy remains largely empirical. Quinine and quinidine remain the drugs of choice for severe chloroquine-resistant malaria due to Plasmodium falciparum, and with the spread of these resistant parasites, the usage of these drugs is increasing. In 1972 scientists in China discovered the antimalarial properties of a group of sesquiterpene lactone peroxides derived from the qinghao plant (Artemisia annua). The principal component, qinghaosu (artemisinin), and two derivatives - the water-soluble hemisuccinate artesunate and the oil-soluble artemether - are the most rapidly acting and potent of all antimalarial drugs. Although much research effort has been invested in optimizing antimalarial drug regimes, severe malaria remains a major cause of adult mortality in the Asiatic tropics. Despite many clinical trials reducing the mortality from severe malaria has proved difficult. Artemether has been shown to be as good as quinine but not better. This thesis set out to determine whether Artemether or Artesunate was the the better drug, how to manage acute renal failure in severe malaria, to design a severity score for malaria and assess whether there had been any change in the parasite clearance times in Viet Nam over a 18 year period. The results from a series of clinical trials and research from one hospital in Viet Nam are presented. This thesis undertook the following studies: 1. A randomised clinical trial of artesunate vs artemether in the treatment of severe malaria in adults in Viet Nam. 2. A randomized comparison of pumped venovenous haemofiltration and peritoneal dialysis in acute renal failure associated with severe infection. 3. Fluid management in severe malaria. 4. The stage of the development of the falciparum parasites at the time of clinical presentation with severe malaria is important in predicting outcome. 5. Development of a predictive score of outcome in adults with severe falciparum malaria. 6. Assessment of the efficacy of the artemisinin derivatives in the treatment of severe falciparum malaria in Viet Nam 1991-2008