A Comparison of the Commonly Used Surrogate Markers for Citrate Accumulation and Toxicity during Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation.

INTRODUCTION: Continuous renal replacement therapy using regional citrate anticoagulation is commonly used as a modality of organ support in the critically ill population. Currently, citrate accumulation or toxicity is assessed using surrogate markers, notably the uncorrected total-to-ionized calcium ration. The accuracy and utility of this method have been questioned. OBJECTIVES/AIMS: The aim of this study was to compare the surrogate markers used for assessing citrate accumulation or toxicity using the measurement of plasma citrate as the gold standard. METHODS: Blood was sampled from 20 patients before, during, and after episodes of filtration with citrate concentration measured using spectrophotometry. Demographic and other clinical and biochemical data were also collected. According to protocol, a 15 mmol/L solution of trisodium citrate was used as the prefilter anticoagulant. Results were analyzed using STATA (v16.0) and presented as mean (SD), median (IQR), or simple proportion. Univariate linear regression using citrate concentration as the dependent variable was performed with all surrogate markers. RESULTS: Twenty patients (17 males) were enrolled in the study with a mean (SD) age of 62.7 (9.9) years. The uncorrected calcium ratio had the best fit to the citrate data with an R2 value of 0.39. The albumin-corrected calcium ratio, pH, anion gap (AG), albumin-corrected AG, standard base excess, and strong ion gap all had R2 values less than 0.05. CONCLUSION(S): In the absence of direct measurement of citrate concentration, uncorrected total-to-ionized calcium ratio is superior to other surrogate markers, though not ideal, in assessing citrate accumulation or toxicity.

Impact of fasting on the gastric volume of critically ill patients before extubation: a prospective observational study using gastric ultrasound.

Background: A period of fasting before tracheal extubation of ventilated patients in the ICU is common practice, aiming to reduce gastric volume and aspiration risk. As the volume of gastric content is unknown at the time of extubation, the efficacy of this practice is uncertain. Methods: A prospective, observational study using gastric ultrasound was undertaken. Images were obtained at four time points: (i) at baseline, with gastric feeds running; (ii) after suctioning of gastric contents through a gastric tube; (iii) after a 4 h period with no gastric feed running; and (iv) after both a 4 h fasting period and gastric tube suctioning. The primary outcome was the proportion of patients classed as low risk of aspiration with each intervention, using qualitative and quantitative gastric ultrasound. Results: Fifty-four patients in the ICU were enrolled. Forty-four (81%) subjects had images that were suitable for analysis. Suctioning of stomach content through a gastric tube and fasting were equivalent with 39/44 (88.6%) and 5/44 (11.4%) subjects classified as low risk and at risk of aspiration, respectively. A period of fasting followed by suction resulted in 41/44 (93.2%) patients being at low risk. Conclusions: Suctioning of stomach contents through the gastric tube and a 4 h fasting period appear equivalent at reducing gastric volume below a safe threshold. A small percentage did not reach the threshold despite all interventions.

Measurement of the Concentration of Citrate in Human Biofluids in Patients Undergoing Continuous Renal Replacement Therapy Using Regional Citrate Anticoagulation: Application of a Two-Step Enzymatic Assay.

BACKGROUND: Continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) is now commonly used to treat acute kidney injury in critically ill patients. The concentration of citrate is not routinely measured, with citrate accumulation and/or toxicity primarily assessed using surrogate measures. OBJECTIVES: The aim of this study was to measure the concentration of citrate in plasma and ultrafiltrate in patients receiving CRRT with RCA using a modified commercial enzymatic assay. METHODS: After meeting inclusion criteria, blood was sampled from 20 patients before, during, and after episodes of filtration. Using spectrophotometry, samples were tested for citrate concentration. Demographic and other clinical and biochemical data were also collected. Throughout, a 15 mmol/L solution of trisodium citrate was used as the prefilter anticoagulant. Results were analysed using STATA (v15.0) and presented as mean (SD), median (IQR), or simple proportion. Comparisons were made using either the Student t test or the Wilcoxon rank-sum test. Correlation was assessed using Pearson's r. RESULTS: Twenty patients (17 males) were enrolled in the study. Mean (SD) age was 63.7 years (9.9). Median (IQR) ICU length of stay was 281 h (199, 422) with 85% undergoing intermittent positive pressure ventilation. Median APACHE 3 score was 95 (87, 117) with an overall 30% mortality rate. Median filtration time was 85 h (46, 149). No difference was found between pre- and post-filtration plasma citrate concentrations (79 µmol/L [50] vs. 71 µmol/L [42], p = 0.65). Mean citrate concentration during filtration was 508 µmol/L (221) with a maximum of 1,070 µmol/L. This was significantly higher than the pre/post levels (p < 0.001). CONCLUSIONS: Plasma concentrations of citrate rose significantly during episodes of CRRT using RCA returning back to normal after cessation of treatment.

Nosocomial infection prevalence in patients undergoing extracorporeal membrane oxygenation (ECMO): protocol for a point prevalence study across Australia and New Zealand.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) provides cardiac and/or respiratory support when other therapies fail. Nosocomial infection is reported in up to 64% of patients receiving ECMO and increases morbidity and mortality. These patients are at high risk of infection due, in part, to the multiple invasive devices required in their management, the largest being the cannulae through which ECMO is delivered. Prevalence of nosocomial infection in ECMO patients, including ECMO cannula-related infection, is not well described across Australia and New Zealand. METHODS AND ANALYSIS: This is a prospective, observational point prevalence study of 12 months duration conducted at 11 ECMO centres across Australia and New Zealand. Data will be collected for every patient receiving ECMO during 12 predetermined data collection weeks. The primary outcome is the prevalence of laboratory-confirmed bloodstream infection, and suspected or probable nosocomial infections; and the secondary outcomes include describing ECMO cannula dressing and securement practices, and adherence to local dressing and securement guidelines. Data collection will be finalised by March 2019. ETHICS AND DISSEMINATION: Relevant ethical and governance approvals have been received. Study results will describe the prevalence of suspected and confirmed nosocomial infection in adult, paediatric and neonatal patients receiving ECMO across Australia and New Zealand. It is expected that the results will be hypothesis generating and lead to interventional trials aimed at reducing the high infection rates seen in this cohort. Results will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ANZCTRN12618001109291; Pre-results.

Pre-clinical study protocol: Blood transfusion in endotoxaemic shock.

The Surviving Sepsis Campaign (SCC) and the American College of Critical Care Medicine (ACCM) guidelines recommend blood transfusion in sepsis when the haemoglobin concentration drops below 7.0 g/dL and 10.0 g/dL respectively, while the World Health Organisation (WHO) guideline recommends transfusion in septic shock 'if intravenous (IV) fluids do not maintain adequate circulation', as a supportive measure of last resort. Volume expansion using crystalloid and colloid fluid boluses for haemodynamic resuscitation in severe illness/sepsis, has been associated with adverse outcomes in recent literature. However, the volume expansion effect(s) following blood transfusion for haemodynamic circulatory support, in severe illness remain unclear with most previous studies having focused on evaluating effects of either different RBC storage durations (short versus long duration) or haemoglobin thresholds (low versus high threshold) pre-transfusion. •We describe the protocol for a pre-clinical randomised controlled trial designed to examine haemodynamic effect(s) of early volume expansion using packed RBCs (PRBCs) transfusion (before any crystalloids or colloids) in a validated ovine-model of hyperdynamic endotoxaemic shock.•Additional exploration of mechanisms underlying any physiological, haemodynamic, haematological, immunologic and tissue specific-effects of blood transfusion will be undertaken including comparison of effects of short (≤5 days) versus long (≥30 days) storage duration of PRBCs prior to transfusion.

Impacts of Aging on Anemia Tolerance, Transfusion Thresholds, and Patient Blood Management.

Evidence-based patient blood management guidelines commonly recommend restrictive hemoglobin thresholds of 70 to 80 g/L for asymptomatic adults. However, most transfusion trials have enrolled adults across a broad age span, with few exclusive to older adults. Our recent meta-analysis of transfusion trials that focused on older adults paradoxically found lower mortality and fewer cardiac complications when these patients were managed using higher hemoglobin thresholds. We postulate that declining cardiac output with age contributes to deteriorating oxygen delivery capacity which impacts anemia-associated outcomes in older adults and propose a model to explain this age-related difference. We reviewed evidence concerning the pathophysiology of aging to explore the disparity in transfusion trial outcomes related to hemoglobin thresholds in different age groups. The literature was searched for normative cardiac output values at different ages in healthy adults. Using normative peak cardiac output data, we modeled oxygen delivery capacity in young, middle-aged, and older adults at a range of hemoglobin levels. Cardiovascular and pulmonary systems are impacted by age-related pathophysiological changes. Diminishing peak cardiac output associated with aging reduces the maximal oxygen delivery achievable under metabolic stress. Hence, at low hemoglobin levels, older adults are more susceptible to tissue hypoxia than younger adults. Our model predicts that an older adult with a hemoglobin of 100 g/L has a similar peak oxygen delivery capacity to a young adult with a hemoglobin of 70 g/L. Age-related pathophysiological changes provide some explanation as to why older adults have a lower tolerance for anemia than younger adults. This indicates the need for patient blood management hemoglobin thresholds specific to older as distinct from younger adults. The primary application of this model is in the consideration of patients rehabilitating to life outside hospital. It is important to note that pathophysiological changes associated with critical illness and major surgery are more complex than can be described in a simple model based on cardiac output and hemoglobin concentration. However, our review of oxygen transport and delivery in health and disease states allows the model to be considered in the context of treatment decisions for anemic adults in a range of hospital and community settings.

Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock.

INTRODUCTION: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock. MATERIALS AND METHODS: Twenty-one adult female sheep were randomly divided into no endotoxemia (n = 5) or endotoxemia groups (n = 16) with an escalating dose of lipopolysaccharide (LPS) up to 4 µg/kg/h administered to achieve a mean arterial pressure below 60 mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n = 8) or a 0.9% saline bolus (40 mL/kg over 60 min) (n = 8). No endotoxemia, saline only animals (n = 5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65 mm Hg in all the groups. RESULTS: Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001). CONCLUSIONS: Endotoxemia impairs secondary haemostasis and induces changes in the intrinsic, extrinsic and anti-coagulant pathways. These changes to haemostasis are exacerbated following resuscitation with 0.9% saline, a commonly used crystalloid in clinical settings.

Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock.

BACKGROUND: Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process. METHODS: Endotoxemic shock was induced in sheep by administration of an escalating dose of lipopolysaccharide, after which they subsequently received either no fluid bolus resuscitation or a 0.9% saline bolus. Lung tissue, bronchoalveolar fluid (BAL) and plasma were analysed by real-time PCR, ELISA, flow cytometry and immunohistochemical staining to assess inflammatory cells, cytokines, hyaluronan and matrix metalloproteinases. RESULTS: Endotoxemia was associated with decreased serum albumin and total protein levels, with activated neutrophils, while the glycocalyx glycosaminoglycan hyaluronan was significantly increased in BAL. Quantitative real-time PCR studies showed higher expression of IL-6 and IL-8 with saline resuscitation but no difference in matrix metalloproteinase expression. BAL and tissue homogenate levels of IL-6, IL-8 and IL-1ß were elevated. CONCLUSIONS: This data shows that the inflammatory response is enhanced when a host with endotoxemia is resuscitated with saline, with a comparatively higher release of inflammatory cytokines and endothelial/glycocalyx damage, but no change in matrix metalloproteinase levels.

Urine and serum midkine levels in an Australian chronic kidney disease clinic population: an observational study.

BACKGROUND AND OBJECTIVES: The cytokine midkine (MK) is pathologically implicated in progressive chronic kidney disease (CKD) and its systemic consequences and has potential as both a biomarker and therapeutic target. To date, there are no published data on MK levels in patients with different stages of CKD. This study aims to quantify MK levels in patients with CKD and to identify any correlation with CKD stage, cause, progression, comorbid disease or prescribed medication. METHODS: In this observational, single-centre study, demographic data were collected, and serum and urine assayed from 197 patients with CKD and 19 healthy volunteers in an outpatient setting. RESULTS: The median serum and urine MK level in volunteers was 754 pg/mL (IQR: 554-1025) and 239 pg/mL (IQR: 154-568), respectively. Compared with serum MK in stage 1 CKD (660 pg/mL, IQR: 417-893), serum MK increased in stage 3 (1878 pg/mL, IQR: 1188-2756; p<0.001), 4 (2768 pg/mL, IQR: 2065-4735; p<0.001) and 5 (4816 pg/mL, IQ: 37477807; p<0.001). Urine MK levels increased from stage 1 CKD (343 pg/mL, IQR: 147-437) to stage 3 (1007 pg/mL, IQR: 465-2766; p=0.07), 4 (2961 pg/mL, IQR: 1368-5686; p=0.005) and 5 (6722 pg/mL, IQR: 3796-10 060; p=0.001). Fractional MK excretion (FeMK) increased from stage 1 CKD (0.159, IQR: 0.145-0.299) to stage 3 (1.024, IQR: 0.451-1.886, p=0.047), 4 (3.39, IQR: 2.10-5.82, p=0.004) and 5 (11.95, IQR: 5.36-24.41, p<0.001). When adjusted for estimated glomerular filtration rate, neither serum nor urine MK correlated with primary CKD diagnosis or CKD progression (small sample). There was a positive correlation between protein:creatinine ratio and FeMK (p=0.003). Angiotensin blockade (adjusted for proteinuria) was associated with lower urine MK (p=0.018) and FeMK (p=0.025). CONCLUSION: MK levels sequentially rise with CKD stage beyond stage 2, and our data support existing animal evidence for an MK/renin angiotensin-system/proteinuria relationship. To what extent this is related to renal clearance versus pathology, or the consequences of chronically elevated MK levels requires further exploration.

Ventilation distribution and lung recruitment with speaking valve use in tracheostomised patient weaning from mechanical ventilation in intensive care.

PURPOSE: Speaking valves (SV) are used infrequently in tracheostomised ICU patients due to concerns regarding their putative effect on lung recruitment. A recent study in cardio-thoracic population demonstrated increased end-expiratory lung volumes during and post SV use without examining if the increase in end-expiratory lung impedance (EELI) resulted in alveolar recruitment or potential hyperinflation in discrete loci. MATERIALS AND METHODS: A secondary analysis of Electrical Impedance Tomography (EIT) data from a previous study was conducted. EELI distribution and tidal variation (TV) were assessed with a previously validated tool. A new tool was used to investigate ventilated surface area (VSA) and regional ventilation delay (RVD) as indicators of alveolar recruitment. RESULTS: The increase in EELI was found to be uniform with significant increase across all lung sections (p<0.001). TV showed an initial non-significant decrease (p=0.94) with subsequent increase significantly above baseline (p<0.001). VSA and RVD showed non-significant changes during and post SV use. CONCLUSIONS: These findings indicate that hyperinflation did not occur with SV use, which is supported by previously published data on respiratory parameters. These data along with obvious psychological benefits to patients are encouraging towards safe use of SVs in this critically ill cardio-thoracic patient population. TRIAL REGISTRATION: Anna-Liisa Sutt, Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN: ACTRN12615000589583. 4/6/2015.

A head to head evaluation of 8 biochemical scanning tools for unmeasured ions.

We aimed to evaluate the sensitivity and specificity of 8 biochemical scanning tools in signalling the presence of unmeasured anions. We used blood gas and biochemical data from 15 patients during and after cardio-pulmonary bypass. Sampling time-points were pre-bypass (T1), 2 min post equilibration with priming fluid containing acetate and gluconate anions (T2), late bypass (T3) and 4 h after surgery (T4). We calculated the anion gap (AG), albumin-corrected anion gap (AGc), whole blood base excess (BE) gap, plasma BE gap, standard BE gap and the strong ion gap (SIG), plus 2 new indices-the unmeasured ion index (UIX) and unmeasured plasma anions according to the interstitial, plasma and erythrocyte acid-base model (IPEua). Total measured plasma concentrations of acetate and gluconate [XA] were proxies for unmeasured plasma anions. [XA] values (mmol/L) were 1.41 (0.87) at T1, 11.73 (3.28) at T2, 4.80 (1.49) at T3 and 1.36 (0.73) at T4. Corresponding [albumin] values (g/L) were 32.3 (2.0), 19.8 (2.6), 21.3 (2.5) and 29.1 (2.3) respectively. Only the AG failed to increase significantly at T2 in response to a mean [XA] surge of >10 mEq/L. At an [XA] threshold of 6 mEq/L, areas under receiver -operator characteristic curves in rank order were IPEua and UIX (0.88 and 0.87 respectively), SIG (0.81), AGc (0.79), standard BE gap (0.77), plasma BE gap (0.71), BE gap (0.70) and AG (0.59). Similar ranking hierarchies applied to positive and negative predictive values. We conclude that during acute hemodilution UIX and IPEua are superior to the anion gap (with and without albumin correction) and 4 other indices as scanning tools for unmeasured anions.

Inflammation and lung injury in an ovine model of extracorporeal membrane oxygenation support.

Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for patients with severe refractory cardiorespiratory failure. Exposure to the ECMO circuit is thought to trigger/exacerbate inflammation. Determining whether inflammation is the result of the patients' underlying pathologies or the ECMO circuit is difficult. To discern how different insults contribute to the inflammatory response, we developed an ovine model of lung injury and ECMO to investigate the impact of smoke-induced lung injury and ECMO in isolation and cumulatively on pulmonary and circulating inflammatory cells, cytokines, and tissue remodeling. Sheep receiving either smoke-induced acute lung injury (S-ALI) or sham injury were placed on veno-venous (VV) ECMO lasting either 2 or 24 h, with controls receiving conventional ventilation only. Lung tissue, bronchoalveolar fluid, and plasma were analyzed by RT-PCR, immunohistochemical staining, and zymography to assess inflammatory cells, cytokines, and matrix metalloproteinases. Pulmonary compliance decreased in sheep with S-ALI placed on ECMO with increased numbers of infiltrating neutrophils, monocytes, and alveolar macrophages compared with controls. Infiltration of neutrophils was also observed with S-ALI alone. RT-PCR studies showed higher expression of matrix metalloproteinases 2 and 9 in S-ALI plus ECMO, whereas IL-6 was elevated at 2 h. Zymography revealed higher levels of matrix metalloproteinase 2. Circulating plasma levels of IL-6 were elevated 1-2 h after commencement of ECMO alone. These data show that the inflammatory response is enhanced when a host with preexisting pulmonary injury is placed on ECMO, with increased infiltration of neutrophils and macrophages, the release of inflammatory cytokines, and upregulation of matrix metalloproteinases.

Complementary and alternative medicine use by patients receiving curative-intent chemotherapy.

AIM: To determine which types of complementary and alternative medicine (CAM) are being used by cancer patients commencing curative-intent chemotherapy, whether the CAM taken has the potential to affect treatment efficacy, the reasons for patients' decisions to use CAM and whether these patients would like information on CAM safety with chemotherapy. METHODS: Seventy-five solid tumor malignancy patients receiving curative-intent treatment attending a cancer care day unit were interviewed about their CAM use on the day of receiving their first dose of chemotherapy. RESULTS: Sixty percent of study participants were using CAM at the start of chemotherapy treatment. Biologically active CAM assessed as having potential to interact with prescribed chemotherapy was ingested by 27% of patients, all of whom had routinely used CAM prior to cancer diagnosis. CAM was used by 51% of patients for supportive care reasons and by 28% of patients with the intention of treating their cancer. Patients' CAM decision-making was influenced by advice from family and friends, practitioners and casual acquaintances. Thirteen percent of patients were told by a CAM advice-giver not to have chemotherapy. The majority of patients (84%) would have liked to receive information on which CAM is safe to use with chemotherapy before treatment commenced. CONCLUSIONS: Patients being treated with curative intent, particularly those with a history of CAM use, may be taking biologically active CAM with potential to compromise their chemotherapy treatment. These patients want cancer-care health professionals to provide them evidence-based information on safe CAM use with chemotherapy and may be contending with alternative health advice to not have chemotherapy.

Speaking valves in tracheostomised ICU patients weaning off mechanical ventilation--do they facilitate lung recruitment?

BACKGROUND: Patients who require positive pressure ventilation through a tracheostomy are unable to phonate due to the inflated tracheostomy cuff. Whilst a speaking valve (SV) can be used on a tracheostomy tube, its use in ventilated ICU patients has been inhibited by concerns regarding potential deleterious effects to recovering lungs. The objective of this study was to assess end expiratory lung impedance (EELI) and standard bedside respiratory parameters before, during and after SV use in tracheostomised patients weaning from mechanical ventilation. METHODS: A prospective observational study was conducted in a cardio-thoracic adult ICU. 20 consecutive tracheostomised patients weaning from mechanical ventilation and using a SV were recruited. Electrical Impedance Tomography (EIT) was used to monitor patients' EELI. Changes in lung impedance and standard bedside respiratory data were analysed pre, during and post SV use. RESULTS: Use of in-line SVs resulted in significant increase of EELI. This effect grew and was maintained for at least 15 minutes after removal of the SV (p < 0.001). EtCO2 showed a significant drop during SV use (p = 0.01) whilst SpO2 remained unchanged. Respiratory rate (RR (breaths per minute)) decreased whilst the SV was in situ (p <0.001), and heart rate (HR (beats per minute)) was unchanged. All results were similar regardless of the patients' respiratory requirements at time of recruitment. CONCLUSIONS: In this cohort of critically ill ventilated patients, SVs did not cause derecruitment of the lungs when used in the ventilator weaning period. Deflating the tracheostomy cuff and restoring the airflow via the upper airway with a one-way valve may facilitate lung recruitment during and after SV use, as indicated by increased EELI. TRIAL REGISTRATION: Anna-Liisa Sutt, Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN: ACTRN12615000589583. 4/6/2015.

Nasal high flow oxygen therapy in patients with COPD reduces respiratory rate and tissue carbon dioxide while increasing tidal and end-expiratory lung volumes: a randomised crossover trial.

UNLABELLED: Patients with COPD using long-term oxygen therapy (LTOT) over 15 h per day have improved outcomes. As inhalation of dry cold gas is detrimental to mucociliary clearance, humidified nasal high flow (NHF) oxygen may reduce frequency of exacerbations, while improving lung function and quality of life in this cohort. In this randomised crossover study, we assessed short-term physiological responses to NHF therapy in 30 males chronically treated with LTOT. LTOT (2-4 L/min) through nasal cannula was compared with NHF at 30 L/min from an AIRVO through an Optiflow nasal interface with entrained supplemental oxygen. Comparing NHF with LTOT: transcutaneous carbon dioxide (TcCO2) (43.3 vs 46.7 mm Hg, p<0.001), transcutaneous oxygen (TcO2) (97.1 vs 101.2 mm Hg, p=0.01), I:E ratio (0.75 vs 0.86, p=0.02) and respiratory rate (RR) (15.4 vs 19.2 bpm, p<0.001) were lower; and tidal volume (Vt) (0.50 vs 0.40, p=0.003) and end-expiratory lung volume (EELV) (174% vs 113%, p<0.001) were higher. EELV is expressed as relative change from baseline (%Δ). Subjective dyspnoea and interface comfort favoured LTOT. NHF decreased TcCO2, I:E ratio and RR, with a concurrent increase in EELV and Vt compared with LTOT. This demonstrates a potential mechanistic rationale behind the improved outcomes observed in long-term treatment with NHF in oxygen-dependent patients. TRIAL REGISTRATION NUMBER: ACTRN12613000028707.

Data quality of the Australia and New Zealand Dialysis and Transplant Registry: a pilot audit.

AIM: Most clinical registries in Australia, including the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), do not audit submitted data. Inaccurate data can bias registry analysis. This study aimed to audit data submitted to ANZDATA from a single region. METHODS: A retrospective audit of individual haemodialysis patient data recorded by ANZDATA at 31 December 2009 was completed by nephrologists in a blinded fashion. Original data were recorded by nursing staff. Patients received treatment at a public hospital, two affiliated satellite haemodialysis units, and three private haemodialysis units. RESULTS: Fifty-one audits were completed of a total 175 patients (29.1%) undertaking haemodialysis in 2009. Primary renal disease was correct in 86.3% (95%CI: 74.3-93.2), although errors in type of glomerulonephritis were common. Date of first dialysis (± 1-month error margin) was correct for 93.6%. Creatinine at first dialysis (± 10% error margin) was correct in 74.4%. Baseline comorbidity accuracy included: peripheral vascular disease (sensitivity 36.4% (95%CI: 24.6-50.1), specificity 82.8% (95%CI: 70.2-90.7)), ischaemic heart disease (sensitivity 69.2% (95%CI: 55.6-80.2), specificity 88.0% (95%CI: 76.3-94.3)), chronic lung disease (sensitivity 25.0% (95%CI: 15.2-38.3), specificity 93.6% (95%CI: 83.4-97.7)), diabetes (sensitivity 86.4% (95%CI: 74.4-93.2), specificity 96.6% (95%CI: 87.5-99.1)), cerebrovascular disease (sensitivity 75.0% (95%CI: 61.7-84.8), specificity 95.3% (95%CI: 85.8-98.6)), and ever smoked (sensitivity 83.3% (95%CI: 70.3-91.4), specificity 71.4% (95%CI: 57.3-82.3)). Non-melanoma skin cancer was under-reported and inaccurate. CONCLUSION: Data accuracy was favourable compared with other renal registry validation studies. Data accuracy may be improved by education and training of collectors. A larger audit is necessary to validate ANZDATA.

Impact of non-traditional phosphate binders and cinacalcet on haemodialysis patient biochemistry, pill burden and cost.

AIM: The Australian Pharmaceutical Benefits Scheme (PBS) commenced cost subsidization for haemodialysis patients of sevelamer in December 2007, cinacalcet in July 2008 and lanthanum in May 2009. To determine the impact of PBS listing of these medications, we performed a single centre cross-sectional, longitudinal study. METHODS: Dialysis parameters and biochemistry were prospectively collected at 6 monthly intervals for all prevalent haemodialysis patients from October 2007 to April 2010. Medications prescribed to manage chronic kidney disease mineral and bone disorder were recorded. Univariate regression analysis was undertaken for each variable against time. RESULTS: Patient numbers ranged from 87 to 114 in each period. At baseline, mean age was 68.8 ± 14.3 years, 71% male, 15.1 ± 3.5 haemodialysis hours/week and urea reduction ratio 71.9 ± 9.8%. These variables were unchanged over time. The use of sevelamer, cinacalcet and lanthanum increased (P < 0.001). There was a decrease in the use of aluminium- and calcium-based phosphate binders (P < 0.001) but no change in the use of magnesium based phosphate binders (P = 0.09) or calcitriol (P = 0.11). Serum phosphate (P = 0.13) and parathyroid hormone (PTH) (P = 0.87) were unchanged. Mean 'bone pill' burden fell from 60.3/week to 51.9/week (P = 0.02). Mean pill cost increased from Australian dollars (AUD) 12.85/patient per week to AUD 59.85/patient per week (P < 0.001). CONCLUSION: The PBS subsidization of sevelamer, cinacalcet and lanthanum has changed prescribing patterns, although serum phosphate and PTH remain unchanged. These changes have been at an additional cost of AUD 2444/patient per year. Data to address clinical end-points of mortality and hospitalization is needed to determine if the cost of these newer agents is warranted.

Comparison of three strong ion models used for quantifying the acid-base status of human plasma with special emphasis on the plasma weak acids.

Currently, three strong ion models exist for the determination of plasma pH. Mathematically, they vary in their treatment of weak acids, and this study was designed to determine whether any significant differences exist in the simulated performance of these models. The models were subjected to a "metabolic" stress either in the form of variable strong ion difference and fixed weak acid effect, or vice versa, and compared over the range 25 < or = Pco(2) < or = 135 Torr. The predictive equations for each model were iteratively solved for pH at each Pco(2) step, and the results were plotted as a series of log(Pco(2))-pH titration curves. The results were analyzed for linearity by using ordinary least squares regression and for collinearity by using correlation. In every case, the results revealed a linear relationship between log(Pco(2)) and pH over the range 6.8 < or = pH < or = 7.8, and no significant difference between the curve predictions under metabolic stress. The curves were statistically collinear. Ultimately, their clinical utility will be determined both by acceptance of the strong ion framework for describing acid-base physiology and by the ease of measurement of the independent model parameters.