Assessment of agreement and interchangeability between the TEG5000 and TEG6S thromboelastography haemostasis analysers: a prospective validation study.

BACKGROUND: TEG6S® and TEG5000® (Haemonetics Corp, USA) are haemostasis analysers that measure viscoelasticity properties of whole blood. Both use different mechanisms to assess similar components of the coagulation process. The aim of this study was to assess agreement and interchangeability between the TEG6S and TEG5000 analysers. METHODS: 3.5 mL whole blood was collected from 25 adult patients in a tertiary intensive care unit (ICU). Analysis was performed using TEG6S and TEG5000 haemostatic platforms. Agreement between platforms was measured using Lin's concordance coefficient (Lin's CC), further validated using intraclass correlation coefficients and reduced major axis regression (RMAR). RESULTS: Sixteen (64%) patients were male; mean (range) age: 59yo (23-86). TEG6S and TEG5000 systems were broadly interchangeable. The majority of TEG variables demonstrated almost perfect or substantial agreement and minimal proportional bias (maximum amplitude demonstrated a fixed bias). LY30%, however, demonstrated poor agreement and a proportional bias. Lin's CC coefficients (95% CI, RMAR slope, intercept) between TEG6S and TEG5000 variables were: R time: 0.78 (0.64-0.92, 0.76, 0.92); K time: 0.82 (0.69-0.94, 1.30, - 0.93); alpha angle: 0.79 (0.64-0.95, 1.04, - 1.43); maximum amplitude (MA): 0.90 (0.83-0.96, 0.99, - 5.0); LY30%: 0.34 (0.1-0.58, 0.43, 0.04). CONCLUSIONS: Adult patients with critical illness demonstrate almost perfect agreement in the R time and MA, substantial agreement in K time and alpha angle, but poor agreement in LY30%, as measured by the TEG6S and TEG5000 analysers. With the exception of LY30%, the TEG6S and TEG5000 platforms appear interchangeable. This has important implications for use in clinical practice and multi-site research programs. TRIAL REGISTRATION: ANZCRT number: 12617000062325 , registered 12/Jan17. Retrospectively registered.

The epidemiology of bacteriuria and candiduria in critically ill patients.

An observational study was conducted to describe the epidemiology of bacteriuria and candiduria in the intensive care unit (ICU), and the occurrence of blood stream infection (BSI) associated with ICU-acquired positive urine culture. Between 2006 and 2011, 444 episodes of either bacteriuria or candiduria defined by positive urine culture (microorganisms ⩾105 c.f.u./ml) occurred in 406 patients. Three hundred and seventy-seven (85%) were hospital-acquired including 221 which were ICU-acquired (6·4 ± 0·8 episodes/1000 ICU days). Escherichia coli was the most common bacteria of both community- and ICU-acquired bacteriuria/candiduria (49·2% and 29%, respectively). Candida spp. represented 55% (129/236) of pathogens responsible for ICU-acquired positive urine cultures. Patients with ICU-acquired candiduria had greater illness severity at ICU admission than those with ICU-acquired bacteriuria (APACHE III score 79 ± 25 vs. 66 ± 31, P = 0·0015). BSI associated with ICU-acquired positive urine culture occurred in 0·15/1000 ICU days and was more often due to Candida. In this study, Candida was the most common pathogen responsible for ICU-acquired positive urine cultures and illness severity was a risk factor for candiduria in the study population.

A pilot study of the relationship between Doppler-estimated carotid and brachial artery flow and cardiac index.

We measured carotid and brachial artery blood flow by Doppler ultrasound in 11 human volunteers, and related these to cardiac index and to each other. The median (IQR [range]) carotid arterial blood flow was 0.334 (0.223-0.381 [0.052-0.563]) l.min(-1) on the right and 0.315 (0.223-0.369 [0.061-0.690]) l.min(-1) on the left. The brachial arterial blood flow was 0.049 (0.033-0.062 [0.015-0.204]) l.min(-1) on the right and 0.039 (0.027-0.054 [0.011-0.116]) on the left. Cardiac index was 3.2 (2.8-3.5 [1.9-5.4]) l.min(-1) .m(-2) . There was a moderate to good correlation between right-and left-sided flows (brachial: ρ = 0.45; carotid: ρ = 0.567). Brachial and carotid flow had no or a negative correlation with cardiac index (right brachial: ρ = -0.145, left brachial: ρ = -0.349; right carotid: ρ = -0.376, left carotid: ρ = -0.285). In contrast to some previous studies, we found that Doppler-estimated peripheral arterial blood flows only show a weak correlation with cardiac index and cannot be used to provide non-invasive estimates of cardiac index in man.

D-dimer assays--a help or hindrance in suspected pulmonary thromboembolism assessment?

BACKGROUND: Suspected pulmonary thromboembolism (PTE) is a common presentation to acute medical units and can cause diagnostic difficulty. National guidelines on PTE management highlight the need for clinical probability assessment and D-dimer assays to ensure appropriate use of diagnostic imaging. D-dimers are used widely in UK hospitals, yet concern exists regarding their misuse. AIMS: In this study we aimed to assess the impact of the introduction of D-dimer assays, combined with clinical probability assessment, for evaluation of suspected PTE in our unit. MATERIALS AND METHODS: This was a prospective audit of all patients presenting with suspected PTE over two 12-week periods, exactly 1 year apart. D-dimers were introduced into our unit between these two periods. We recorded the clinical probability score, potential causes of false-positive D-dimer assay, diagnostic imaging result, patient outcome, admission rates, and length of inpatient stay. STATISTICAL ANALYSIS: Categorical variables were compared using a 2 x 2 chi-square test or Fisher's exact test. Groups were compared utilizing the two-sample t-test or Mann-Whitney U test. RESULTS: A total of 190 patients were included in the study; 65% were female. PTE was confirmed in 8.4%. Patients in both audit periods were comparable with regard to suitability for D-dimer measurement. Following D-dimer introduction, 40 out of 110 patients in period 2 could be discharged directly from the emergency department. Of those admitted to hospital, the median length of stay was significantly reduced in period 2 (3 days in period 1 vs 1 day in period 2; P=0.0007). Use of diagnostic imaging was significantly reduced following the introduction of D-dimers (90% in period 1 vs 40% in period 2; P<0.0001). The positive diagnostic yield for PTE on CT pulmonary angiogram (CTPA) increased significantly from 10% in period 1 to 23% in period 2 (P=0.039). CONCLUSION: D-dimers must be used judiciously in the assessment of suspected PTE. Appropriate use of D-dimers can provide many benefits, including reductions in diagnostic imaging (and thus radiation exposure), admission rates, and length of inpatient stay.

Non-invasive estimation of cardiac index in healthy volunteers.

The primary objective was to non-invasively measure the cardiac index (CI) and associated haemodynamic parameters of healthy volunteers and their changes with age. This was a single centre, prospective, observational study of healthy volunteers aged between 20 and 59 years, using the ClearSight™ (Edwards Life Sciences, Irvine, CA, USA) device. We recorded 514 observations in 97 participants. The mean CI was 3.5 l/min/m2 (95% confidence interval [95% CI] 3.4 to 3.7 l/min/m2). The mean stroke volume index (SVI) was 47 ml/m2 (95% CI 45 to 49 ml/m2) and the mean systemic vascular resistance index was 2,242 dyne.s/cm5/m2 (95% CI 2,124 to 2,365 dyne.s/cm5/m2). There was an inverse linear relationship between increasing age and CI (P <0.0001), which decreased by 0.044 l/min/m2 (95% CI  -0.032 to -0.056 l/min/m2) per year. This change was mostly due to a decrease in SVI of 0.45 ml/m2 (95% CI 0.32 to 0.57 ml/m2) per year (P <0.0001). The mean CI of young healthy humans is approximately 3.5 l/min/m2 and declines by approximately 40 ml/min/m2 per year, mostly due to a decline in stroke volume (SV). These findings have significant implications regarding the clinical interpretation of haemodynamic parameters and the application of these results to individual patients.

Coming full circle: thirty years of paediatric fluid resuscitation.

Fluid bolus therapy (FBT) is a cornerstone of the management of the septic child, but clinical research in this field is challenging to perform, and hard to interpret. The evidence base for independent benefit from liberal FBT in the developed world is limited, and the Fluid Expansion as Supportive Therapy (FEAST) trial has led to conservative changes in the World Health Organization-recommended approach to FBT in resource-poor settings. Trials in the intensive care unit (ICU) and emergency department settings post-FEAST have continued to explore liberal FBT strategies as the norm, despite a strong signal associating fluid accumulation with pulmonary pathology in the paediatric population. Modern clinical trial methodology may ameliorate the traditional challenges of performing randomised interventional trials in critically ill children. Such trials could examine differing strategies of fluid resuscitation, or compare early FBT to early vasoactive agent use. Given the ubiquity of FBT and the potential for harm, appropriately powered examinations of the efficacy of FBT compared to alternative interventions in the paediatric emergency and ICU settings in the developed world appear justified and warranted.

Intravenous fluid bolus therapy: a bi-national survey of critical care nurses' self-reported practice.

Knowledge of critical care nurses' intravenous fluid bolus therapy (FBT) practice remains underexplored. Using a multi-choice online survey conducted between September and October 2014, we sought to describe the self-reported practice of critical care nurses located in Australia and New Zealand. Two hundred and ninety-five critical care nurses responded to the survey with most practising in adult ICUs. Overall, 0.9% saline solution was the preferred solution for FBT. However, more Australian than New Zealand respondents preferred 'albumin 4%' (31% versus 3.6%, P <0.01) for FBT. In contrast, more New Zealand respondents preferred 'Plasma-Lyte®' (33.3% versus 6.4%, P <0.01). Half of the respondents defined FBT as 250 ml administered as quickly as possible. However, FBT volumes ranged from 100 ml to >1000 ml and administration duration from as quickly as possible to 60 minutes. In response to FBT, almost half of the respondents expected an increase in mean arterial pressure of between 11 to 20 mmHg. Similarly, >40% expected a central venous pressure increase >3 mmHg, >70% expected a urinary output increase of 0.5 to 1.0 ml/kg/hr, and >60% expected a decrease in heart rate of >11 /min. Overall, 0.9% saline remains the most common solution for FBT, but there are significant national differences in the preference for albumin and Plasma-Lyte. A volume of 250 ml defines a fluid bolus, with a range from 100 ml to >1000 ml, and speed of delivery from stat to 60 minutes. Most nurses expect substantial physiological effects with FBT.

Predicting intensive care and hospital outcome with the Dalhousie Clinical Frailty Scale: a pilot assessment.

Frailty may help to predict intensive care unit (ICU) patient outcome. The Dalhousie Clinical Frailty Scale (DCFS) is validated to assess frailty in ambulatory settings but has not been investigated in Australian ICUs. We conducted a prospective three-month study of patients admitted to a tertiary level ICU. Within 24 hours of ICU admission, the next of kin or nurse in charge assigned a DCFS score to the patient. Data were obtained to assess the association between frailty and patient outcome. The DCFS score was completed in 205 of 348 (59%) of eligible patient admissions. The mean DCFS score was 3.2 (±1.6). Overall frailty (DCFS>4) occurred in 28 of 205 patients (13%, confidence interval 9% to 17%), 13 of 93 (15%, confidence interval 10% to 25%) in patients aged >65 years and 5 of 11 (45%, confidence interval 21% to 71%) in those>85 years. Patients with chronic liver disease (P<0.001) and end-stage renal failure (P=0.009) were more likely to be frail. The DCFS score was not significantly associated with ICU or hospital mortality: odds ratio 0.98 (95% confidence interval 0.6 to 1.6) and odds ratio 1.07 (95% confidence interval 0.8 to 1.4), respectively. However, after adjustment for illness severity and requirement for palliative care, the DCFS score was significantly associated with increased (log) hospital length-of-stay (P=0.04) and age (P=0.001). Approximately 1 in 10 ICU patients were frail and this frequency increased with age. The DCFS was associated with patient age and comorbidities and potentially predicts increased hospital length-of-stay but not other outcomes. Strategies to improve compliance with DCFS completion are needed.

Characteristics and expectations of fluid bolus therapy: a bi-national survey of acute care physicians.

There is little consensus on the definition or optimal constituents of fluid bolus therapy (FBT), and there is uncertainty regarding its physiological effects. The aims of this study were to determine clinician-reported definitions of FBT and to explore the physiological responses clinicians expect from such FBT. In June and October 2014, intensive care and emergency physicians in Australia and New Zealand were asked to participate in an electronic questionnaire of the reported practice and expectations of FBT. Two hundred and fifty-one questionnaires were completed, 65.3% from intensivists. We identified the prototypical FBT given by intensivists is more than 250 ml of compound sodium lactate, saline or 4% albumin given in less than 30 minutes, while that given by emergency department physicians is a similar volume of saline delivered over a similar time frame. Intensive care and emergency physicians expected significantly different changes in mean arterial pressure (P=0.001) and heart rate (P=0.033) following FBT. Substantial variation was demonstrated in the magnitude of expected response within both specialties for each variable. Major variations exist in self-reported FBT practice, both within and between acute specialties, and wide variation can be demonstrated in the expected physiological responses to FBT. International explorations of practice and prospective quantification of the actual physiological response to FBT are warranted.

Urinary neutrophil gelatinase-associated lipocalin to hepcidin ratio as a biomarker of acute kidney injury in intensive care unit patients.

BACKGROUND: Labile iron is important in the pathogenesis of acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin control iron metabolism and are upregulated during renal stress. However, higher levels of urinary NGAL are associated with AKI severity whereas higher urinary hepcidin levels are associated with absence of AKI. We aimed to investigate the value of combining both biomarkers to estimate the severity and progression of AKI in intensive care unit (ICU) patients. METHODS: Urinary NGAL and hepcidin were quantified within 48 hours of ICU admission in patients with the systemic inflammatory response syndrome and early kidney dysfunction (oliguria for ≥ 2 hours and/or a 25 µmol/L creatinine rise from baseline). Diagnostic and prognostic characteristics were assessed by logistic regression and receiver operating characteristics (ROC) analysis. RESULTS: Of 102 patients, 26 had mild AKI and 28 patients had severe AKI on admission. Sepsis (21%), cardiac surgery (17%) and liver failure (9%) were primary admission diagnoses. NGAL increased (P=0.03) whereas hepcidin decreased (P=0.01) with increasing AKI severity. The value of NGAL/hepcidin ratio to detect severe AKI was higher than when NGAL and hepcidin were used individually and persisted after adjusting for potential confounders (adjusted OR 2.40, 95% CI 1.20-4.78). The ROC areas for predicting worsening AKI were 0.50, 0.52 and 0.48 for NGAL, 1/hepcidin and the NGAL/hepcidin ratio. CONCLUSION: The NGAL/hepcidin ratio is more strongly associated with severe AKI than the single biomarkers alone. NGAL and hepcidin, alone or combined as a ratio, were unable to predict progressive AKI in this selected ICU cohort.

Laryngeal rhabdomyosarcoma in adults.

Laryngeal rhabdomyosarcoma is a rare disease. Only nine of these tumours have been adequately described in world literature in the adult population. Adult patients with laryngeal rhabdomyosarcoma often present at a later stage than other laryngeal tumours, including squamous cell carcinoma. Diagnosis is made by identification of cross-striations histochemically or cytoplasmic myoglobin by immunohistological methods. We present a 66-year-old woman with pleomorphic rhabdomyosarcoma of her larynx. This is the first female in the adult age group to be presented. Surgical treatment with adjuvant radiotherapy is currently the treatment of choice for this disease. We provide a review of the literature on laryngeal rhabdomyosarcoma, including presentation, pathology and management of this rare disease.