Correction to: Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

Following publication of the original article [1], we were notified that the collaborators' names part of the "The TBI Collaborative" group has not been indexed in Pubmed. Below the collaborators names full list.

Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

BACKGROUND: In traumatic brain injury (TBI) patients desmopressin administration may induce rapid decreases in serum sodium and increase intracranial pressure (ICP). AIM: In an international multi-centre study, we aimed to report changes in serum sodium and ICP after desmopressin administration in TBI patients. METHODS: We obtained data from 14 neurotrauma ICUs in Europe, Australia and UK for severe TBI patients (GCS ≤ 8) requiring ICP monitoring. We identified patients who received any desmopressin and recorded daily dose, 6-hourly serum sodium, and 6-hourly ICP. RESULTS: We studied 262 severe TBI patients. Of these, 39 patients (14.9%) received desmopressin. Median length of treatment with desmopressin was 1 [1-3] day and daily intravenous dose varied between centres from 0.125 to 10 mcg. The median hourly rate of decrease in serum sodium was low (- 0.1 [- 0.2 to 0.0] mmol/L/h) with a median period of decrease of 36 h. The proportion of 6-h periods in which the rate of natremia correction exceeded 0.5 mmol/L/h or 1 mmol/L/h was low, at 8% and 3%, respectively, and ICPs remained stable. After adjusting for IMPACT score and injury severity score, desmopressin administration was independently associated with increased 60-day mortality [HR of 1.83 (1.05-3.24) (p = 0.03)]. CONCLUSIONS: In severe TBI, desmopressin administration, potentially representing instances of diabetes insipidus is common and is independently associated with increased mortality. Desmopressin doses vary markedly among ICUs; however, the associated decrease in natremia rarely exceeds recommended rates and median ICP values remain unchanged. These findings support the notion that desmopressin therapy is safe.

Prevalence of augmented renal clearance and performance of glomerular filtration estimates in Indigenous Australian patients requiring intensive care admission.

Augmented renal clearance (ARC) refers to the enhanced renal excretion of circulating solute commonly demonstrated in numerous critically ill subgroups. This study aimed to describe the prevalence of ARC in critically ill Indigenous Australian patients and explore the accuracy of commonly employed mathematical estimates of glomerular filtration. We completed a single-centre, prospective, observational study in the intensive care unit (ICU), Alice Springs Hospital, Central Australia. Participants were critically ill adult Indigenous and non-Indigenous Australian patients with a urinary catheter in situ. Exclusion criteria were anuria, pregnancy or the requirement for renal replacement therapy. Daily eight-hour measured creatinine clearances (CrCLm) were collected throughout the ICU stay. ARC was defined by a CrCLm ≥130 ml/min/1.73 m2. The Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations were also used to calculate mathematical estimates for comparison. In total, 131 patients were recruited (97 Indigenous, 34 non-Indigenous) and 445 samples were collected. The median (range) CrCLm was 93.0 (5.14 to 205.2) and 90.4 (18.7 to 206.8) ml/min/1.73 m2 in Indigenous and non-Indigenous patients, respectively. Thirty-one of 97 (32%) Indigenous patients manifested ARC, compared to 7 of 34 (21%) non-Indigenous patients (P=0.21). Younger age, major surgery, higher baseline renal function and an absence of diabetes were all associated with ARC. Both mathematical estimates manifest limited accuracy. ARC was prevalent in critically ill Indigenous patients, which places them at significant risk of underdosing with renally excreted drugs. CrCLm should be obtained wherever possible to ensure accurate dosing.

The influence of intensive care unit-acquired central line-associated bloodstream infection on in-hospital mortality: A single-center risk-adjusted analysis.

OBJECTIVE: To explore the risk-adjusted association between intensive care unit (ICU)-acquired central line-associated bloodstream infection (CLABSI) and in-hospital mortality. DESIGN: Retrospective observational study. SETTING: Forty-five-bed adult ICU. PATIENTS: All non-extracorporeal membrane oxygenation ICU admissions between July 1, 2008, and April 30, 2014, requiring a central venous catheter (CVC), with a length of stay > 48 hours, were included. METHODS: Data were extracted from our infection prevention and ICU databases. A multivariable logistic regression model was constructed to identify independent risk factors for ICU-acquired CLABSI. The propensity toward developing CLABSI was then included in a logistic regression of in-hospital mortality. RESULTS: Six thousand three hundred fifty-three admissions were included. Forty-six cases of ICU-acquired CLABSI were identified. The overall CLABSI rate was 1.12 per 1,000 ICU CVC-days. Significant independent risk factors for ICU-acquired CLABSI included: double lumen catheter insertion (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.16-5.77), CVC exposure > 7 days (OR, 2.07; 95% CI, 1.06-4.04), and CVC insertion before 2011 (OR, 2.20; 95% CI, 1.22-3.97). ICU-acquired CLABSI was crudely associated with greater in-hospital mortality, although this was attenuated once the propensity to develop CLABSI was adjusted for (OR, 1.20; 95% CI, 0.54-2.68). CONCLUSIONS: A greater propensity toward ICU-acquired CLABSI was independently associated with higher in-hospital mortality, although line infection itself was not. The requirement for prolonged specialized central venous access appears to be a key risk factor for ICU-acquired CLABSI, and likely informs mortality as a marker of persistent organ dysfunction.

Select critically ill patients at risk of augmented renal clearance: experience in a Malaysian intensive care unit.

Augmented renal clearance (ARC) refers to increased solute elimination by the kidneys. ARC has considerable implications for altered drug concentrations. The aims of this study were to describe the prevalence of ARC in a select cohort of patients admitted to a Malaysian intensive care unit (ICU) and to compare measured and calculated creatinine clearances in this group. Patients with an expected ICU stay of <24 hours plus an admission serum creatinine concentration <120 µmol/l, were enrolled from May to July 2013. Twenty-four hour urinary collections and serum creatinine concentrations were used to measure creatinine clearance. A total of 49 patients were included, with a median age of 34 years. Most study participants were male and admitted after trauma. Thirty-nine percent were found to have ARC. These patients were more commonly admitted in emergency (P=0.03), although no other covariants were identified as predicting ARC, likely due to the inclusion criteria and the study being under-powered. Significant imprecision was demonstrated when comparing calculated Cockcroft-Gault creatinine clearance (Crcl) and measured Crcl. Bias was larger in ARC patients, with Cockcroft-Gault Crcl being significantly lower than measured Crcl (P <0.01) and demonstrating poor correlation (rs=-0.04). In conclusion, critically ill patients with 'normal' serum creatinine concentrations have varied Crcl. Many are at risk of ARC, which may necessitate individualised drug dosing. Furthermore, significant bias and imprecision between calculated and measured Crcl exists, suggesting clinicians should carefully consider which method they employ in assessing renal function.

Tracheal cuff pressure monitoring in the ICU: a literature review and survey of current practice in Queensland.

The application of tracheal cuff pressure monitoring is likely to vary between institutions. The aim of this study was therefore to review current evidence concerning this intervention in the intensive care unit (ICU) and to appraise regional practice by performing a state-wide survey. Publications for review were identified through searches of PubMed, EMBASE and Cochrane (1977 to 2014). All studies in English relevant to critical care and with complete data were included. Survey questions were developed by small-group consensus. Public and private ICUs across Queensland were contacted, with responses obtained from a representative member of the medical or nursing staff. Existing literature suggests significant variability in tracheal cuff pressure monitoring in the ICU, particularly in the applied technique, frequency of assessment and optimal intra-cuff pressures. Twenty-nine respondents completed the survey, representing 80.5% (29/36) of ICUs in Queensland. Twenty-eight out of twenty-nine respondents reported routinely monitoring tracheal cuff function, primarily employing cuff pressure measurement (26/28). Target cuff pressures varied, with 3/26 respondents aiming for 10 to 20 cmH2O, 10/26 for 21 to 25 cmH2O, and 13/26 for 26 to 30 cmH2O. Fifteen out of twenty-nine reported they had no current guideline or protocol for tracheal cuff management and only 16/29 indicated there was a dedicated area in the clinical record for reporting cuff intervention. Our results indicate that many ICUs across Queensland routinely measure tracheal cuff function, with most utilising pressure monitoring devices. Consistent with existing literature, the optimum cuff pressure remains uncertain. Most, however, considered that this should be a routine part of ICU care.

Risk factors for target non-attainment during empirical treatment with ß-lactam antibiotics in critically ill patients.

PURPOSE: Risk factors for ß-lactam antibiotic underdosing in critically ill patients have not been described in large-scale studies. The objective of this study was to describe pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment envisioning empirical dosing in critically ill patients and considering a worst-case scenario as well as to identify patient characteristics that are associated with target non-attainment. METHODS: This analysis uses data from the DALI study, a prospective, multi-centre pharmacokinetic point-prevalence study. For this analysis, we assumed that these were the concentrations that would be reached during empirical dosing, and calculated target attainment using a hypothetical target minimum inhibitory concentration (MIC), namely the susceptibility breakpoint of the least susceptible organism for which that antibiotic is commonly used. PK/PD targets were free drug concentration maintained above the MIC of the suspected pathogen for at least 50 % and 100 % of the dosing interval respectively (50 % and 100 % f T (>MIC)). Multivariable analysis was performed to identify factors associated with inadequate antibiotic exposure. RESULTS: A total of 343 critically ill patients receiving eight different ß-lactam antibiotics were included. The median (interquartile range) age was 60 (47-73) years, APACHE II score was 18 (13-24). In the hypothetical situation of empirical dosing, antibiotic concentrations remained below the MIC during 50 % and 100 % of the dosing interval in 66 (19.2 %) and 142 (41.4 %) patients respectively. The use of intermittent infusion was significantly associated with increased risk of non-attainment for both targets; creatinine clearance was independently associated with not reaching the 100 % f T( >MIC) target. CONCLUSIONS: This study found that-in empirical dosing and considering a worst--case scenario--19 % and 41 % of the patients would not achieve antibiotic concentrations above the MIC during 50 % and 100 % of the dosing interval. The use of intermittent infusion (compared to extended and continuous infusion) was the main determinant of non-attainment for both targets; increasing creatinine clearance was also associated with not attaining concentrations above the MIC for the whole dosing interval. In the light of this study from 68 ICUs across ten countries, we believe current empiric dosing recommendations for ICU patients are inadequate to effectively cover a broad range of susceptible organisms and need to be reconsidered.

Phenytoin loading doses in adult critical care patients: does current practice achieve adequate drug levels?

Phenytoin is regularly employed in the critically ill for prophylaxis against or treatment of seizure disorders. No prior studies have examined current dosing practices in an Australasian intensive care unit (ICU) setting. The aims of this study were to: a) describe the adequacy of contemporary dosing in respect to free and total serum phenytoin concentrations; b) identify factors associated with therapeutic drug concentrations; and c) examine the accuracy of predictive equations that estimate free concentrations in this setting. All patients receiving a loading dose of phenytoin in a tertiary-level ICU were eligible for enrolment; 53 patients were enrolled in the study. Serum samples to determine free and total phenytoin concentrations (measured by high performance liquid chromatography) were then drawn prior to the following dose. Free concentrations below the recommended target (<1 mg/l) were considered as suboptimal. The most common indication for phenytoin loading was traumatic brain injury (49%) and the mean administered dose was 14.5 (3.66) mg/kg. Twenty-six patients (49%) had suboptimal trough free concentrations, although this subgroup was significantly heavier and therefore received a lower per kilogram dose (12.8 [3.1] vs 16.3 [3.4] mg/kg, P=0.001). In multivariate analysis, larger weight adjusted doses (P=0.018), higher albumin concentration (P=0.034) and receiving phenytoin for an indication other than seizure (P=0.035), were associated with a greater likelihood of adequate concentrations. In conclusion, phenytoin dosing remains complex in critically ill patients, although lower per kilogram loading doses are strongly associated with free concentrations below the desired target.

Blood culture collection in patients with acute kidney injury receiving renal replacement therapy: an observational study.

Critically ill patients receiving renal replacement therapy (RRT) for acute kidney injury (AKI) have high reported intensive care unit (ICU) mortality. Blood culture (BC) collection practices in this population have to date been poorly characterised, specifically in regards to the influence of RRT on the clinical triggers for such an investigation. Utilising our electronic clinical information system, we conducted a retrospective observational study of patients admitted to a 30-bed tertiary level ICU and requiring RRT over a four-year period. Patients with a history of chronic kidney disease, prior RRT or ICU length-of-stay (LOS)<48 hours were excluded. Two hundred and thirty-one patients treated with RRT for AKI were identified. The observed median [interquartile range] BC collection rate in those having them drawn was 18 [11-32] per 100 patient days, although 42% of the cohort had no BC drawn during their ICU stay. Application of RRT in the 24 hours prior to initial BC collection was associated with lower body temperatures, higher white cell counts and greater use of vasopressor therapy. Bloodstream infection (identified from the first BC) was associated with greater ICU and in-hospital mortality. We also observed a predominance of candidaemia in this cohort, despite the absence of neutropenia. This study provides unique data describing BC collection rates in a cohort of critically ill patients receiving RRT for AKI and at high risk of dying. Further study of temperature alteration, detection of bloodstream infection and outcome in patients receiving RRT is now warranted.

A comparison of pulse contour wave analysis and ultrasonic cardiac output monitoring in the critically ill.

Cardiac output (CO) is a key determinant of major organ blood flow and solute delivery to drug eliminating organs. As such, CO assessment is a key covariate in understanding altered drug handling in the critically ill. Newer minimally-invasive devices are providing unique platforms for such an application, although comparison data are currently lacking. In this study we evaluated the Vigileo (Edwards Lifesciences, Irvine, CA, USA) and USCOM (USCOM Ltd, Sydney, NSW) devices in 62 critically ill patients requiring antibacterial therapy. The mean COVigileo and COUSCOM for the first paired measurements were 8.20±2.65 l/minute and 6.84±2.57 l/minute respectively (P <0.001). A significant correlation was evident in all patients (r=0.537, P <0.001) although the recorded bias was large (1.36±2.51 l/minute, limits of agreement -3.6 to±6.3 l/minute). The overall percentage error was 65%. There was an improved correlation in those admitted with sepsis (r=0.639, P <0.001), compared to trauma (r=0.373, P=0.066), although bias, precision and percentage error were similar in both subgroups. In 54 patients a second paired assessment was obtained at three hours. A weak, although significant correlation (r=0.377, P=0.005) was observed suggesting that gross trends over time were similar. In conclusion, our findings demonstrate poor agreement between these techniques suggesting that these devices are not simply interchangeable when assessing CO in a research or clinical setting.

Sensitivity to fungal allergens is a risk factor for life-threatening asthma.

BACKGROUND: Previous studies have suggested that sensitivity to Alternaria and Cladosporium may be risk factors for life-threatening asthma. We have investigated this by studying the relationship between skin tests for fungal spores and admission to an intensive care unit (ICU) for asthma. METHODS: Skin prick tests for fungal spores (Alternaria tenuis, Cladosporium cladosporoides, Helminthosporium maydis, and Epicoccum nigrum), cat dander, house-dust mite (Dermatophagoides pteronyssinus), and a seven-grass mix were performed in three groups of patients: patients admitted to an ICU with an attack of asthma; those who had received emergency treatment for asthma but had not been admitted to an ICU, and those who had never required emergency treatment for their asthma. RESULTS: Twenty of 37 patients (54%) admitted to the ICU had a positive skin test for one or more fungal allergens compared with 15/50 patients (30%) in each of the other groups (P=0.005). The ICU patients were no more likely to have positive skin tests for the grass mix, cat dander, or house-dust mite than the other patients. CONCLUSIONS: A positive skin test for fungal allergens is a risk factor for admission to an ICU with an acute attack of asthma.