Critical Care - Research Publications

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    Renal haemodynamics and oxygenation during and after cardiac surgery and cardiopulmonary bypass
    Evans, RG ; Lankadeva, YR ; Cochrane, AD ; Marino, B ; Iguchi, N ; Zhu, MZL ; Hood, SG ; Smith, JA ; Bellomo, R ; Gardiner, BS ; Lee, C-J ; Smith, DW ; May, CN (WILEY, 2018-03)
    Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac surgery-associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra-operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi-disciplinary pathway for translation comprising three components. Firstly, large-animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non-invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts.
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    Review article: Sepsis in the emergency department - Part 1: Definitions and outcomes
    Macdonald, SPJ ; Williams, JM ; Shetty, A ; Bellomo, R ; Finfer, S ; Shapiro, N ; Keijzers, G (WILEY, 2017-12)
    Sepsis has recently been redefined as acute organ dysfunction due to infection. The ED plays a critical role in identifying patients with sepsis. This is challenging due to the heterogeneity of the syndrome, and the lack of an objective standard diagnostic test. While overall mortality rates from sepsis appear to be falling, there is an increasing burden of morbidity among survivors. This largely reflects the growing proportion of older patients with comorbid illnesses among those treated for sepsis.
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    Risk factors for unfavourable postoperative outcome in patients with Crohn's disease undergoing right hemicolectomy or ileocaecal resection An international audit by ESCP and S-ECCO.
    2015 European Society of Coloproctology collaborating group, (Wiley, 2017-09-15)
    BACKGROUND: Patient and disease-related factors, as well as operation technique all have the potential to impact on postoperative outcome in Crohn's disease. The available evidence is based on small series and often displays conflicting results. AIM: To investigate the effect of pre- and intra-operative risk factors on 30-day postoperative outcome in patients undergoing surgery for Crohn's disease. METHOD: International prospective snapshot audit including consecutive patients undergoing right hemicolectomy or ileocaecal resection. This study analysed a subset of patients who underwent surgery for Crohn's disease. The primary outcome measure was the overall Clavien-Dindo postoperative complication rate. The key secondary outcomes were anastomotic leak, re-operation, surgical site infection and length of stay at hospital. Multivariable binary logistic regression analyses were used to produce odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Three hundred and seventy five resections in 375 patients were included. The median age was 37 and 57.1% were female. In multivariate analyses, postoperative complications were associated with preoperative parenteral nutrition (OR 2.36 95% CI 1.10-4.97)], urgent/expedited surgical intervention (OR 2.00, 95% CI 1.13-3.55) and unplanned intraoperative adverse events (OR 2.30, 95% CI 1.20-4.45). The postoperative length of stay in hospital was prolonged in patients who received preoperative parenteral nutrition (OR 31, CI [1.08-1.61]) and those who had urgent/expedited operations (OR 1.21, CI [1.07-1.37]). CONCLUSION: Preoperative parenteral nutritional support, urgent/expedited operation and unplanned intraoperative adverse events were associated with unfavourable postoperative outcome. Enhanced preoperative optimization and improved planning of operation pathways and timings may improve outcomes for patients. This article is protected by copyright. All rights reserved.
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    Renal effects of an emergency department chloride-restrictive intravenous fluid strategy in patients admitted to hospital for more than 48 hours
    Yunos, NM ; Bellomo, R ; Taylor, DM ; Judkins, S ; Kerr, F ; Sutcliffe, H ; Hegarty, C ; Bailey, M (WILEY, 2017-12)
    OBJECTIVE: Patients commonly receive i.v. fluids in the ED. It is still unclear whether the choice of i.v. fluids in this setting influences renal or patient outcomes. We aimed to assess the effects of restricting i.v. chloride administration in the ED on the incidence of acute kidney injury (AKI). METHODS: We conducted a before-and-after trial with 5008 consecutive ED-treated hospital admissions in the control period and 5146 consecutive admissions in the intervention period. During the control period (18 February 2008 to 17 August 2008), patients received standard i.v. fluids. During the intervention period (18 February 2009 to 17 August 2009), we restricted all chloride-rich fluids. We used the Kidney Disease: Improving Global Outcomes (KDIGO) staging to define AKI. RESULTS: Stage 3 of KDIGO-defined AKI decreased from 54 (1.1%; 95% confidence interval [CI] 0.8-1.4) to 30 (0.6%; 95% CI 0.4-0.8) (P = 0.006). The rate of renal replacement therapy did not change, from 13 (0.3%; 95% CI 0.2-0.4) to 8 (0.2%; 95% CI 0.1-0.3) (P = 0.25). After adjustment for relevant covariates, liberal chloride therapy remained associated with a greater risk of KDIGO stage 3 (hazard ratio 1.82; 95% CI 1.13-2.95; P = 0.01). On sensitivity assessment after removing repeat admissions, KDIGO stage 3 remained significantly lower in the intervention period compared with the control period (P = 0.01). CONCLUSION: In a before-and-after trial, a chloride-restrictive strategy in an ED was associated with a significant decrease in the incidence of stage 3 of KDIGO-defined AKI.
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    Duration of platelet storage and outcomes of critically ill patients
    Flint, A ; Aubron, C ; Bailey, M ; Bellomo, R ; Pilcher, D ; Cheng, AC ; Hegarty, C ; Reade, MC ; McQuilten, Z (WILEY, 2017-03)
    BACKGROUND: The storage duration of platelet (PLT) units is limited to 5 to 7 days. This study investigates whether PLT storage duration is associated with patient outcomes in critically ill patients. STUDY DESIGN AND METHODS: This study was a retrospective analysis of critically ill patients admitted to the intensive care unit (ICU) of two hospitals in Australia who received one or more PLT transfusions from 2008 to 2014. Storage duration was approached in several different ways. Outcome variables were hospital mortality and ICU-acquired infection. Associations between PLT storage duration and outcomes were evaluated using multiple logistic regression and also by Cox regression. RESULTS: Among 2250 patients who received one or more PLT transfusions while in the ICU, the storage duration of PLTs was available for 64% of patients (1430). In-hospital mortality was 22.1% and ICU infection rate 7.2%. When comparing patients who received PLTs of a maximum storage duration of not more than 3, 4, or 5 days, there were no significant differences in baseline characteristics. After confounders were adjusted for, the storage duration of PLTs was not independently associated with mortality (4 days vs. ≤3 days, odds ratio [OR] 0.88, 95% confidence interval [CI] 0.59-1.30; 5 days vs. ≤3 days, OR 0.97, 95% CI 0.68-1.37) or infection (4 days vs. ≤3 days, OR 0.71, 95% CI 0.39-1.29; 5 days vs. ≤3 days, OR 1.11, 95% CI 0.67-1.83). Similar results were obtained regardless of how storage duration of PLTs was approached. CONCLUSIONS: In this large observational study in a heterogeneous ICU population, storage duration of PLTs was not associated with an increased risk of mortality or infection.
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    Fluid bolus therapy in emergency department patients: Indications and physiological changes
    Bihari, S ; Teubner, DJ ; Prakash, S ; Beatty, T ; Morphett, M ; Bellomo, R ; Bersten, A (WILEY, 2016-10)
    OBJECTIVE: The aim of the present paper is to study the indications for fluid bolus therapy (FBT) and its associated physiological changes in ED patients. METHODS: Prospective observational study of FBT in a tertiary ED, we recorded indications, number, types and volumes, resuscitation goals and perceived success rates of FBT. Moreover, we studied key physiological variables before, 10 min, 1 h and 2 h after FBT. RESULTS: We studied 500 FBT episodes (750 [500-1250] mL). Median age was 59 (36-76) years and 57% were male. Shock was deemed present in 135 (27%) patients, septic shock in 80 (16%), and cardiogenic shock in 30 (6%). Overall, 0.9% saline (84%) was the most common fluid and hypotension the most common indication (70%). 'Avoidance of hospital/ICU admission' was the goal perceived to have the greatest success rate (85%). However, although mean arterial pressure (MAP) increased (P < 0.01) and heart rate (HR) decreased (P = 0.04) at 10 min (P = 0.01), both returned to baseline at 1 and 2 h. In contrast, respiratory rate (RR) increased at 1 (P < 0.01) and 2 h (P = 0.03) and temperature decreased at 1 and 2 h (both P < 0.001). In patients with shock, 1 h after FBT, there was a median 3 mmHg increase in MAP (P = 0.01) but no change in HR (P = 0.44), while RR increased (P < 0.01) and temperature decreased (P = 0.01). CONCLUSIONS: In ED, FBT is used mostly in patients without shock. However, after an immediate haemodynamic effect, FBT is associated with absent or limited physiological changes at 1 or 2 h. Even in shocked patients, the changes in MAP at 1 or 2 h after FBT are small.
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    The epidemiology of in-hospital cardiac arrests in Australia and New Zealand
    Fennessy, G ; Hilton, A ; Radford, S ; Bellomo, R ; Jones, D (WILEY, 2016-10)
    BACKGROUND: The epidemiology of in-hospital cardiac arrests (IHCA) in Australia and New Zealand (ANZ) has not been systematically assessed. AIM: To conduct a systematic review of the frequency, characteristics and outcomes of adult IHCA in ANZ. METHODS: Medline search for studies published in 1964-2014 using MeSH terms 'arrest AND hospital AND Australia', 'arrest AND hospital AND New Zealand', 'inpatient AND arrest AND Australia' and 'inpatient AND arrest AND New Zealand'. RESULTS: We screened 934 studies, analysed 50 and included 30. Frequency of IHCA ranged from 1.31 to 6.11 per 1000 admissions in 4 population studies and 0.58 to 4.59 per 1000 in 16 cohort studies. The frequency was 4.11 versus 1.32 per 1000 admissions in hospitals with rapid response system (RRS) compared with those without (odds ratio: 0.32; 95% confidence interval 0.28-0.37; P < 0.001). On aggregate, the initial cardiac rhythm was ventricular tachycardia/fibrillation in 31.4% (range 19.0-48.8%) in 10 studies reporting such data. On aggregate, IHCA were witnessed in 80.2% cases (three studies) and monitored patients in 53.4% cases (four studies). Details of life support were poorly documented. On aggregate, return of spontaneous circulation occurred in 46.0% of patients. Overall, 74.6% (range 59.4-77.5%) died in-hospital but survival was higher among monitored or younger patients, in those with a shockable rhythm, or during working hours. CONCLUSION: IHCA are uncommon in ANZ and three quarters die in-hospital. However, their frequency varies markedly across institutions and may be affected by the presence of RRS. Where reported, the long-term outcomes survivors appear to have acceptable neurological outcomes.
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    Characteristics, incidence and outcome of patients admitted to intensive care because of pulmonary embolism
    Winterton, D ; Bailey, M ; Pilcher, D ; Landoni, G ; Bellomo, R (WILEY, 2017-02)
    BACKGROUND AND OBJECTIVE: Despite the clinical significance of major pulmonary embolism (PE), little is known about patients with a presentation severe enough to lead to intensive care unit (ICU) admission and nothing is known about PE requiring mechanical ventilation (MV). We aimed to examine the characteristics, incidence and outcome of patients with PE as their reason for ICU admission. METHODS: We performed a retrospective, cross-sectional study of patients admitted to Australia's and New Zealand's ICUs because of PE from 2005 to 2013. We compared survivors with non-survivors and mechanically ventilated with non-ventilated patients. We analysed variations in incidence and mortality over time. RESULTS: We studied 2797 patients. PE accounted for 0.3% of all ICU admissions and had a population incidence of 11 cases/million people/year, which increased significantly during the study period (P < 0.0001). Co-morbidities were common (24.1%) and the emergency department was the most common admission source (49.1%). However, patients who died were more commonly admitted from the wards (P < 0.0001). Overall mortality was 14.1% but reached 41.0% in patients requiring MV (P < 0.0001). Illness severity-adjusted mortality rate did not change during the study period. CONCLUSION: The incidence of PE requiring admission to ICU has increased over time; its mortality rate remains high, especially in mechanically ventilated patients, and its prognosis has not improved over time. Our findings imply the need for focused research in this high-risk patient group.
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    Sodium bicarbonate infusion in patients undergoing orthotopic liver transplantation: a single center randomized controlled pilot trial
    Weinberg, L ; Broad, J ; Pillai, P ; Chen, G ; Nguyen, M ; Eastwood, GM ; Scurrah, N ; Nikfarjam, M ; Story, D ; McNicol, L ; Bellomo, R (WILEY-BLACKWELL, 2016-05)
    BACKGROUND: Liver transplantation-associated acute kidney injury (AKI) carries significant morbidity and mortality. We hypothesized that sodium bicarbonate would reduce the incidence and/or severity of liver transplantation-associated AKI. METHODS: In this double-blinded pilot RCT, adult patients undergoing orthotopic liver transplantation were randomized to an infusion of either 8.4% sodium bicarbonate (0.5 mEq/kg/h for the first hour; 0.15 mEq/kg/h until completion of surgery); (n = 30) or 0.9% sodium chloride (n = 30). PRIMARY OUTCOME: AKI within the first 48 h post-operatively. RESULTS: There were no significant differences between the two treatment groups with regard to baseline characteristics, model for end-stage liver disease and acute physiology and chronic health evaluation (APACHE) II scores, and pre-transplantation renal function. Intra-operative factors were similar for duration of surgery, blood product requirements, crystalloid and colloid volumes infused and requirements for vasoactive therapy. Eleven patients (37%) in the bicarbonate group and 10 patients (33%) in the sodium chloride group developed a post-operative AKI (p = 0.79). Bicarbonate infusion attenuated the degree of immediate post-operative metabolic acidosis; however, this effect dissipated by 48 h. There were no significant differences in ventilation hours, ICU or hospital length of stay, or mortality. CONCLUSIONS: The intra-operative infusion of sodium bicarbonate did not decrease the incidence of AKI in patients following orthotopic liver transplantation.
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    The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial
    Chiam, E ; Weinberg, L ; Bailey, M ; McNicol, L ; Bellomo, R (WILEY, 2016-04)
    AIM: The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. METHODS: We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. RESULTS: Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). CONCLUSIONS: I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.