Critical Care - Research Publications

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    Rapid 500 mL albumin bolus versus rapid 200 mL bolus followed by slower continuous infusion in post-cardiac surgery patients: a pilot before-and-after study
    Yanase, F ; Naorungroj, T ; Cutuli, SL ; Eastwood, GM ; Bellomo, R (AUSTRALASIAN MED PUBL CO LTD, 2021-09)
    Objective: To evaluate the haemodynamic effects of rapid fluid bolus therapy (FBT) (500 mL of 4% albumin over several minutes) versus combined FBT (rapid 200 mL FBT followed by a 300 mL infusion over 30 minutes). Design: Single centre, prospective, before-and-after trial. Setting: A tertiary intensive care unit in Australia. Participants: Fifty mechanically ventilated post-cardiac surgery patients. Interventions: Rapid 4% albumin FBT versus combined FBT. Main outcome measures: We recorded haemodynamic parameters from before FBT to 30 minutes after FBT. A mean arterial pressure (MAP) response was defined by a MAP increase > 10%, and a cardiac index (CI) response was defined by a CI increase > 15%. Results: Immediately after rapid FBT versus combined FBT, there was a CI response in 13 patients (52%) compared with five patients (20%) respectively (P = 0.038), and a MAP response in 11 patients (44%) in each group. However, from FBT administration to 30 minutes, there was a time and group interaction such that MAP was higher in the rapid FBT group (P = 0.003), as was the case for central venous pressure (P = 0.002) and mean pulmonary artery pressure (P < 0.001). Body temperature fell immediately and was lower with rapid FBT but became warmer than with combined FBT later (P < 0.001). At 30 minutes, a MAP response was seen in ten patients (40%) compared with nine patients (36%) (P < 0.99) and a CI response was present in eight patients (32%) compared with 11 patients (44%) (P = 0.56) in the rapid versus combined FBT groups respectively. Conclusion: Rapid FBT was superior to combined FBT in terms of mean MAP levels and immediate CI response. However, the number of MAP responders or CI responders was similar at 30 minutes.
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    Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest
    Eastwood, G ; Nichol, AD ; Hodgson, C ; Parke, RL ; McGuinness, S ; Nielsen, N ; Bernard, S ; Skrifvars, MB ; Stub, D ; Taccone, FS ; Archer, J ; Kutsogiannis, D ; Dankiewicz, J ; Lilja, G ; Cronberg, T ; Kirkegaard, H ; Capellier, G ; Landoni, G ; Horn, J ; Olasveengen, T ; Arabi, Y ; Chia, YW ; Markota, A ; Haenggi, M ; Wise, MP ; Grejs, AM ; Christensen, S ; Munk-Andersen, H ; Granfeldt, A ; Andersen, GO ; Qvigstad, E ; Flaa, A ; Thomas, M ; Sweet, K ; Bewley, J ; Backlund, M ; Tiainen, M ; Iten, M ; Levis, A ; Peck, L ; Walsham, J ; Deane, A ; Ghosh, A ; Annoni, F ; Chen, Y ; Knight, D ; Lesona, E ; Tlayjeh, H ; Svensek, F ; McGuigan, PJ ; Cole, J ; Pogson, D ; Hilty, MP ; During, JP ; Bailey, MJ ; Paul, E ; Ady, B ; Ainscough, K ; Hunt, A ; Monahan, S ; Trapani, T ; Fahey, C ; Bellomo, R (MASSACHUSETTS MEDICAL SOC, 2023-07-06)
    BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).
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    Breaches of pre-medical emergency team call criteria in an Australian hospital
    Jones, D ; Kishore, K ; Eastwood, G ; Sprogis, SK ; Glassford, NJ (ELSEVIER, 2023-12)
    OBJECTIVES AND OUTCOMES: To evaluate the 24hrs before medical emergency team (MET) calls to examine: 1) the frequency, nature, and timing of pre-MET criteria breaches; 2) differences in characteristics and outcomes between patients who did and didn't experience pre-MET breaches. DESIGN: Retrospective observational study November 2020-June 2021. SETTING: Tertiary referral Australian hospital. PARTICIPANTS: Adults (≥18 years) experiencing MET calls. RESULTS: Breaches in pre-MET criteria occurred prior to 1886/2255 (83.6%) MET calls, and 1038/1281 (81.0%) of the first MET calls. Patients with pre-MET breaches were older (median [IQR] 72 [57-81] vs 66 [56-77] yrs), more likely to be admitted from home (87.8% vs 81.9%) and via the emergency department (73.0% vs 50.2%), but less likely to be for full resuscitation after (67.3% vs 76.5%) the MET. The three most common pre-MET breaches were low SpO2 (48.0%), high pulse rate (39.8%), and low systolic blood pressure (29.0%) which were present for a median (IQR) of 15.4 (7.5-20.8), 13.2 (4.3-21.0), and 12.6 (3.5-20.1) hrs before the MET call, respectively. Patients with pre-MET breaches were more likely to need intensive care admission within 24 h (15.6 vs 11.9%), have repeat MET calls (33.3 vs 24.7%), and die in hospital (15.8 vs 9.9%). CONCLUSIONS: Four-fifths of MET calls were preceded by pre-MET criteria breaches, which were present for many hours. Such patients were older, had more limits of treatment, and experienced worse outcomes. There is a need to improve goals of care documentation and pre-MET management of clinical deterioration.
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    Nature and impact of in-hospital complications associated with persistent critical illness
    Tseitkin, B ; Martensson, J ; Eastwood, GM ; Brown, A ; Ancona, P ; Lucchetta, L ; Iwashyna, TJ ; Robbins, R ; Bellomo, R (AUSTRALASIAN MED PUBL CO LTD, 2020-12)
    Background: Persistent critical illness (PerCI) is defined as an intensive care unit (ICU) admission lasting ≥ 10 days. The in-hospital complications associated with its development are poorly understood. Aims: To test whether PerCI is associated with a greater prevalence, rate and specific types of in-hospital complications. Methods: Single-centre, retrospective, observational case-control study. Results: We studied 1200 patients admitted to a tertiary ICU from 2010 to 2015. Median ICU length of stay was 16 days (interquartile range [IQR], 12-23) for PerCI patients v 2.3 days (IQR, 1.1-3.7) for controls, and median hospital length of stay was 41 days (IQR, 22-75) v 8 days (IQR, 4-17) respectively. A greater proportion of PerCI patients received acute renal replacement therapy (37% v 6.8%) or underwent reintubation (17% v 1%) and/or tracheostomy (36% v 0.6%); P < 0.0001. Despite these complications, PerCI patients had similar hospital mortality (29% v 27%; P = 0.53). PerCI patients experienced a greater absolute number of complications (12.1 v 4.0 complications per patient; P < 0.0001) but had fewer exposure-adjusted complications (202 v 272 complications per 1000 hospital bed-days; P < 0.001) and a particularly high overall prevalence of specific complications. Conclusions: PerCI patients experience a higher prevalence, but not a higher rate, of exposure-adjusted complications. Some of these complications appear amenable to prevention, helping to define intervention targets in patients at risk of PerCI. Funding: Austin Hospital Intensive Care Trust Fund.
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    Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial
    Poole, AP ; Finnis, ME ; Anstey, J ; Bellomo, R ; Bihari, S ; Biradar, V ; Doherty, S ; Eastwood, G ; Finfer, S ; French, CJ ; Ghosh, A ; Heller, S ; Horowitz, M ; Kar, P ; Kruger, PS ; Maiden, MJ ; Martensson, J ; McArthur, CJ ; McGuinness, SP ; Secombe, PJ ; Tobin, AE ; Udy, AA ; Young, PJ ; Deane, AM (AUSTRALASIAN MED PUBL CO LTD, 2020-06)
    BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial - the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial - which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0-14.0 mmol/L) or usual care (target 6.0-10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.
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    Reduced urinary levels of angiotensin-converting enzyme 2 activity predict acute kidney injury in critically ill patients
    Bitker, L ; Patel, SK ; Bittar, I ; Eastwood, GM ; Bellomo, R ; Burrell, LM (AUSTRALASIAN MED PUBL CO LTD, 2020-12)
    Objective: Angiotensin-converting enzyme 2 activity reflects non-classical renin-angiotensin system upregulation. We assessed the association of urinary angiotensin-converting enzyme 2 (uACE2) activity with acute kidney injury (AKI). Design, setting and participants: A prospective observational study in which we measured uACE2 activity in 105 critically ill patients at risk of AKI. We report AKI stage 2 or 3 at 12 hours of urine collection (AKI12h) and AKI stage 2 or 3 at any time during intensive care unit stay in patients free from any stage of AKI at inclusion (AKIICU). AKI prediction was assessed using area under the receiver-operating characteristics curve (AUROC) and net reclassification indices (NRIs). Main outcome measure: AKI stage 2 or 3 at 12 hours of urine collection. Results: Within 12 hours of inclusion, 32 of 105 patients (30%) had developed AKI12h. Corrected uACE2 activity was significantly higher in patients without AKI12h compared with those with AKI12h (median [interquartile range], 13 [6-24] v 7 [4-10] pmol/min/mL per mmol/L of urine creatinine; P < 0.01). A 10-unit increase in uACE2 was associated with a 28% decrease in AKI12h risk (odds ratio [95% CI], 0.72 [0.46-0.97]). During intensive care unit admission, 39 of 76 patients (51%) developed AKIICU. uACE2 had an AUROC for the prediction of AKI12h of 0.68 (95% CI, 0.57-0.79), and correctly reclassified 28% of patients (positive NRI) to AKI12h. Patients with uACE2 > 8.7 pmol/min/mL per mmol/L of urine creatinine had a significantly lower risk of AKIICU on log-rank analysis (52% v 84%; P < 0.01). Conclusions: Higher uACE2 activity was associated with a decreased risk of AKI stage 2 or 3. Our findings support future evaluations of the role of the non-classical renin-angiotensin system during AKI.
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    The relationship between Nephrocheck® test values, outcomes, and urinary output in critically ill patients at risk of acute kidney injury.
    Naorungroj, T ; Yanase, F ; Bittar, I ; Eastwood, G ; Bellomo, R (Wiley, 2022-11)
    BACKGROUND: Nephrocheck® was approved for acute kidney injury (AKI) risk assessment in critically illness. However, new studies suggest that urinary concentration affects Nephrocheck® and previous studies did not provide data on urinary output (UO) at the time of measurement. METHODS: We performed a prospective cohort study of the Nephrocheck® in intensive care unit patients fulfilling standard inclusion criteria. The primary outcome was Stage 2 or 3 AKI defined by both UO and creatinine Kidney Disease Improving Global Outcomes (KDIGO) criteria in the subsequent 12 h. The secondary outcome was the relationship of UO with Nephrocheck® measurement. RESULTS: Among 98 patients, the primary outcome occurred in 53 (54.1%) overall, but in 23 (23.5%) by creatinine criteria alone. The median (interquartile range) Nephrocheck® in patients with subsequent Stage 2 or 3 AKI was greater than in Stage 1 or no-AKI patients (0.97 [0.48-1.99] vs. 0.46 [0.22-1.17]; p = .005). However, its area under the receiver characteristic curve was 0.66 (95% confidence interval [CI], 0.56-0.77). Moreover, Nephrocheck® was significantly and inversely correlated with UO (ρ = -.46, p < .001) at the time of measurement and, on a multivariable logistic regression, Nephrocheck® was not associated with subsequent Stage 2 or 3 AKI (OR 1.06 [95% CI, 0.74-1.53], p = .73). In contrast, the UO had an OR of 0.98 for each ml/h increase (95% CI, 0.97-1.00, p = .007). CONCLUSION: Nephrocheck®'s predictive performance was limited and its value was inversely correlated with UO. Nephrocheck® had no independent relationship with outcome once UO at measurement was considered.
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    Registrar triage, communication and moral distress during end-of-life care rapid response team calls in a teaching hospital
    Callahan, S ; Moran, J ; See, E ; Jones, D ; Eastwood, GM ; Warrillow, S (WILEY, 2022-12)
    BACKGROUND: Approximately one-third of rapid response teams (RRT) involve end-of-life care (EOLC) issues. Intensive care unit (ICU) registrar experience in such calls is underinvestigated. AIMS: To evaluate the proportion of RRT calls triaged as relating to EOLC issues, issues around communication regarding prognostication, registrar self-reported moral distress and associations between RRT EOLC classification and patient outcomes. METHODS: Prospective observational study of RRT calls in a tertiary referrals hospital between December 2016 and January 2017 using a standardised case report form and data from an electronic RRT database. RESULTS: There were 401 RRT calls in the study period, and data were available for 270 (67%) calls, of which 72%, 10% and 18% were triaged as 'obviously not EOLC call', 'obvious EOLC call' and 'uncertain EOLC call' respectively. Most discussions regarding prognostication occurred between registrars, and more than half (55%) were with a covering doctor. Consensus on prognostication was achieved in 93% cases. Registrars reported distress in 19% of calls that obviously related to EOLC and 22% of calls that were uncertain, compared with <1% of calls that were obviously not relating to EOLC. Inhospital mortality was 6%, 67% and 39% for obviously not EOLC, obvious EOLC and uncertain EOLC calls respectively. CONCLUSIONS: EOLC issues occur commonly in RRT calls and are often associated with moral distress to ICU registrars. Although consensus on prognostication is usually achieved, conversations often involve covering doctors. These issues impact on the ICU registrar experience of RRT calls and require further exploration.
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    COMBED: Rapid non-invasive Cardiac Output Monitoring Baseline assessment in adult Emergency Department patients with haemodynamic instability
    Eyeington, CT ; Canet, E ; Cutuli, SL ; Ancona, P ; Brown, AJ ; Jenkins, E ; Taylor, DM ; Eastwood, GM ; Bellomo, R (WILEY, 2022-08)
    OBJECTIVE: The application of rapid, non-operator-dependent, non-invasive cardiac output monitoring (COM) may provide early physiological information in ED patients with haemodynamic instability (HI). Our primary objective was to assess the feasibility of measuring pre-intervention (baseline) cardiac index (CI) and associated haemodynamic parameters. METHODS: We performed a prospective observational study of adults shortly after presentation to the ED of a large university hospital with tachycardia or hypotension or both. We applied non-invasive COM for 5 min and recorded CI, mean arterial pressure (MAP), stroke volume index (SVI) and systemic vascular resistance index (SVRI). We assessed for differences between those presenting with hypotension or hypotension and tachycardia with tachycardia alone and between those with or without suspected infection. RESULTS: We obtained haemodynamic parameters in 46 of 49 patients. In patients with hypotension or hypotension and tachycardia (n = 15) rather than tachycardia alone (n = 31), we observed a lower MAP (60.8 vs 87.7, P < 0.0001), CI (2.8 vs 3.9, P = 0.0167) and heart rate (85.5 vs 115.4, P < 0.0001). There was no difference in SVI (33.7 vs 33.4, P = 0.93) or SVRI (1970 vs 2088, P = 0.67). Patients with suspected infection had similar haemodynamic values except for a lower SVRI (1706 vs 2237, P = 0.011). CONCLUSIONS: Rapid, non-operator-dependent, non-invasive COM was possible in >90% of ED patients presenting with HI. Compared with tachycardia alone, patients with hypotension had lower CI, MAP and heart rate, while those with suspected infection had a lower SVRI. This technology provides novel insights into the early state of the circulation in ED patients with HI.
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    Improving the quality of family meeting documentation in the ICU at the end of life
    Kennedy, AC ; Jones, DA ; Eastwood, GM ; Wellington, D ; See, E ; Lewis, JE (SAGE PUBLICATIONS INC, 2022)
    OBJECTIVE: Improve documentation quality of end-of-life family meetings in a tertiary intensive care unit (ICU). DESIGN: Before-and-after interventional quality improvement project between October 2018 and February 2020 utilising an electronic pro-forma record. SETTING: Australian, University affiliated, mixed medical-surgical 22 bed adult ICU. PARTICIPANTS: Patients who were admitted to the ICU for active management and subsequently died during that ICU admission. We enrolled 50 patients who died before and 50 patients after the introduction of the electronic family meeting pro-forma record. INTERVENTION: Through collaboration with ICU medical and nursing staff, End-of-life Special Interest Group and Clinical Documentation Committee we developed the ICU Family Meeting Discussion Note as an electronic pro-forma record with multiple key fields of entry. MAIN OUTCOME MEASURES: Patient records were examined for the presence of documented details around patient's admission, family meetings and specific elements surrounding the patient's death. RESULTS: The introduction of a pro-forma record markedly improved the quality of documentation of end-of-life care related family meetings. Documentation increased in recording hospital admission date/time (6% vs 84%), meeting location (14% vs 70%), the reason patients were absent from the meeting (34% vs 72%), the Medical Treatment Decision Maker (MTDM) (10% vs 44%), the patient's resuscitation status (22% vs 54%), and treatment options discussed (78% vs 94%) (p ⩽ 0.005 for all). CONCLUSION: Introducing an electronic pro-forma record to facilitate family meeting documentation increased the frequency of important recorded information. Further studies are required to assess whether documentation quality improvements are sustainable and whether they affect patient- or relative-centred outcomes.